ALBERT

Description: Ultrasound-assisted extraction (UAE) is an effective tool for the extraction of natural antioxidants. Thus, differentially roasted Arabica-coffee beans known as light (LC), medium (MC), and dark coffee (DC) were prepared and extracted under the influence of UAE. Following that, they were examined specifically on theirs physicochemical and biological characteristics: nutritional values, pH, °Brix, antioxidant activities, polyphenol content, caffeine, and chlorogenic-acid levels. Various parameters, such as extraction temperatures (20, 40, and 80°C) and extraction time periods (5, 10, and 20 min), were examined. DC extract was less acidic than those on MC and LC extracts. LC showed higher moisture content than the MC and DC (1.56, 1.3, and 0.92%, respectively). MC displayed the highest polyphenol content and potent antioxidant activity. Caffeine and chlorogenic acid contents trend to decrease during roasting. The maximum caffeine level was found in MC at 80°C for 5 min (27.65 mg/g extract). The highest chlorogenic acid content was in LC at 80°C for 10 min (16.67 mg/g extract). The caffeine and chlorogenic acid contents were related to the polyphenol content and depended on the roasting and extraction conditions. These results suggest that the UAE at various temperature and extraction time period may alter the physicochemical and biological characteristics of different coffee roasts.

Description: A series of neurological manifestations such as intellectual disability and epilepsy are closely related to hypomagnesemia. Cyclin M2 (CNNM2) proteins, as a member of magnesium (Mg2+) transporters, were found along the basolateral membrane of distal renal tubules and involved in the reabsorption of Mg2+. Homozygous and heterozygous variants in CNNM2 reported so far were responsible for a variable degree of hypomagnesemia, several of which also showed varying degrees of neurological phenotypes such as intellectual disability and epilepsy. Here, we report a de novo heterozygous CNNM2 variant (c.2228C 〉 T, p.Ser743Phe) in a Chinese patient, which is the variant located in the cyclic nucleotide monophosphate-binding homology (CNBH) domain of CNNM2 proteins. The patient presented with mild intellectual disability and refractory epilepsy but without hypomagnesemia. Thus, we reviewed the literature and analyzed the phenotypes related to CNNM2 variants, and then concluded that the number of variant alleles and the changed protein domains correlates with the severity of the disease, and speculated that the CNBH domain of CNNM2 possibly plays a limited role in Mg2+ transport but a significant role in brain development. Furthermore, it can be speculated that neurological phenotypes such as intellectual disability and seizures can be purely caused by CNNM2 variants.

Description: In 2019, the Nosology Committee of the International Skeletal Dysplasia Society provided an updated version of the Nosology and Classification of Genetic Skeletal Disorders. This is a reference list of recognized diseases in humans and their causal genes published to help clinician diagnosis and scientific research advances. Complementary to mammalian models, zebrafish has emerged as an interesting species to evaluate chemical treatments against these human skeletal disorders. Due to its versatility and the low cost of experiments, more than 80 models are currently available. In this article, we review the state-of-art of this “aquarium to bedside” approach describing the models according to the list provided by the Nosology Committee. With this, we intend to stimulate research in the appropriate direction to efficiently meet the actual needs of clinicians under the scope of the Nosology Committee.

Description: Colorectal cancer (CRC) is a common cancer worldwide with complex etiology. Fusobacterium nucleatum (F. nucleatum), an oral symbiotic bacterium, has been linked with CRC in the past decade. A series of gut microbiota studies show that CRC patients carry a high abundance of F. nucleatum in the tumor tissue and fecal, and etiological studies have clarified the role of F. nucleatum as a pro-carcinogenic bacterium in various stages of CRC. In this review, we summarize the biological characteristics of F. nucleatum and the epidemiological associations between F. nucleatum and CRC, and then highlight the mechanisms by which F. nucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment (TME). We also discuss the research gap in this field and give our perspective for future studies. These findings will pave the way for manipulating gut F. nucleatum to deal with CRC in the future.

Description: Pseudomonas aeruginosa is one of the most critical opportunistic pathogens in humans, able to cause both lethal acute and chronic lung infections. In previous work, we indicated that the small RNA ErsA plays a role in the regulatory network of P. aeruginosa pathogenicity in airways infection. To give further insight into the lifestyle functions that could be either directly or indirectly regulated by ErsA during infection, we reanalyzed the categories of genes whose transcription appeared dysregulated in an ersA knock-out mutant of the P. aeruginosa PAO1 reference strain. This preliminary analysis indicated ErsA as a candidate co-modulator of denitrification and in general, the anaerobiosis response, a characteristic physiologic state of P. aeruginosa during chronic infection of the lung of cystic fibrosis (CF) patients. To explain the pattern of dysregulation of the anaerobic-lifestyle genes in the lack of ErsA, we postulated that ErsA regulation could target the expression of Anr, a well-known transcription factor that modulates a broad regulon of anoxia-responsive genes, and also Dnr, required for the transcription activation of the denitrification machinery. Our results show that ErsA positively regulates Anr expression at the post-transcriptional level while no direct ErsA-mediated regulatory effect on Dnr was observed. However, Dnr is transcriptionally downregulated in the absence of ErsA and this is consistent with the well-characterized regulatory link between Anr and Dnr. Anr regulatory function is critical for P. aeruginosa anaerobic growth, both through denitrification and fermentation of arginine. Interestingly, we found that, differently from the laboratory strain PAO1, ErsA deletion strongly impairs the anaerobic growth by both denitrification and arginine fermentation of the RP73 clinical isolate, a multi-drug resistant P. aeruginosa CF-adapted strain. This suggests that P. aeruginosa adaptation to CF lung might result in a higher dependence on ErsA for the transduction of the multiple signals to the regulatory network of key functions for survivance in such a complex environment. Together, our results suggest that ErsA takes an upper place in the regulatory network of airways infection, transducing host inputs to biofilm-related factors, as underlined in our previous reports, and to functions that allow P. aeruginosa to thrive in low-oxygen conditions.

Description: Increased global production of animal-based protein results in high greenhouse gas (GHG) emissions and other adverse consequences for human and planetary health. Recently, commercial insect rearing has been claimed a more sustainable source of animal protein. However, this system also leaves residues called frass, which—depending on the insect diet—is rich in carbon (C) and nitrogen (N), and could thus be used as fertilizer in agriculture. The impact of this kind of fertilizer on soil GHG emissions is yet unknown. Therefore, we investigated the effect of black soldier fly (Hermetia illucens L.) frass derived from a carbohydrate (Carb-) or a protein (Prot-) based diet applied at two different application rates to an arable soil on C and N fluxes and microbial properties in a 40-day incubation experiment. CO2, N2O, NO, N2, CH4, water extractable organic C (WEOC), and inorganic N were continuously measured quantitatively. At the end of the incubation, microbial biomass (MB), stoichiometry, community composition, and abundance of functional genes were assessed. Along with a strong increase in WEOC and CO2, Carb-frass caused strong initial N2O emissions associated with high N and C availability. In contrast, Prot-frass showed lower CO2 emissions and N2O release, although soil nitrate levels were higher. At the end of incubation, MB was significantly increased, which was more pronounced following Carb-frass as compared to Prot-frass application, and at higher amendment rates. Fungal abundance increased most from both frass types with an even stronger response at higher application rates, whereas bacterial abundance rose following Carb-frass as compared to Prot-application. Abundance of functional genes related to ammonia-oxidizing bacteria and archaea were enhanced by high frass application but did not clearly differ between frass types. C use efficiency of microorganisms, as revealed by the metabolic quotient, was most strongly reduced in the high Prot-frass application rate. Overall, insect diet influenced available C and N in frass and thus affected mineralization dynamics, GHG emissions, and microbial growth. Overall, emissions were very high undermining the potential environmental benefit of insect based protein production and calling for more detailed analyses before frass is widely applied in agriculture.

Description: The COVID-19 pandemic has now strengthened its hold on human health and coronavirus’ lethal existence does not seem to be going away soon. In this regard, the optimization of reported information for understanding the mechanistic insights that facilitate the discovery towards new therapeutics is an unmet need. Remdesivir (RDV) is established to inhibit RNA-dependent RNA polymerase (RdRp) in distinct viral families including Ebola and SARS-CoV-2. Therefore, its derivatives have the potential to become a broad-spectrum antiviral agent effective against many other RNA viruses. In this study, we performed comparative analysis of RDV, RMP (RDV monophosphate), and RTP (RDV triphosphate) to undermine the inhibition mechanism caused by RTP as it is a metabolically active form of RDV. The MD results indicated that RTP rearranges itself from its initial RMP-pose at the catalytic site towards NTP entry site, however, RMP stays at the catalytic site. The thermodynamic profiling and free-energy analysis revealed that a stable pose of RTP at NTP entrance site seems critical to modulate the inhibition as its binding strength improved more than its initial RMP-pose obtained from docking at the catalytic site. We found that RTP not only occupies the residues K545, R553, and R555, essential to escorting NTP towards the catalytic site, but also interacts with other residues D618, P620, K621, R624, K798, and R836 that contribute significantly to its stability. From the interaction fingerprinting it is revealed that the RTP interact with basic and conserved residues that are detrimental for the RdRp activity, therefore it possibly perturbed the catalytic site and blocked the NTP entrance site considerably. Overall, we are highlighting the RTP binding pose and key residues that render the SARS-CoV-2 RdRp inactive, paving crucial insights towards the discovery of potent inhibitors.

Description: The synonymous codons usage shows a characteristic pattern of preference in each organism. This codon usage bias is thought to have evolved for efficient protein synthesis. Synonymous codon usage was studied in genes of the hexaploid wheat Triticum aestivum (AABBDD) and its progenitor species, Triticum urartu (AA), Aegilops tauschii (DD), and Triticum turgidum (AABB). Triticum aestivum exhibited stronger usage bias for G/C-ending codons than did the three progenitor species, and this bias was especially higher compared to T. turgidum and Ae. tauschii. High GC content is a primary factor influencing codon usage in T. aestivum. Neutrality analysis showed a significant positive correlation (p

Description: Background: There is growing interest in the connection between the gut microbiome and human health and disease. Conventional approaches to analyse microbiome data typically entail dimensionality reduction and assume linearity of the observed relationships, however, the microbiome is a highly complex ecosystem marked by non-linear relationships. In this study, we use topological data analysis (TDA) to explore differences and similarities between the gut microbiome across several countries.Methods: We used curated adult microbiome data at the genus level from the GMrepo database. The dataset contains OTU and demographical data of over 4,400 samples from 19 studies, spanning 12 countries. We analysed the data with tmap, an integrative framework for TDA specifically designed for stratification and enrichment analysis of population-based gut microbiome datasets.Results: We find associations between specific microbial genera and groups of countries. Specifically, both the USA and UK were significantly co-enriched with the proinflammatory genera Lachnoclostridium and Ruminiclostridium, while France and New Zealand were co-enriched with other, butyrate-producing, taxa of the order Clostridiales.Conclusion: The TDA approach demonstrates the overlap and distinctions of microbiome composition between and within countries. This yields unique insights into complex associations in the dataset, a finding not possible with conventional approaches. It highlights the potential utility of TDA as a complementary tool in microbiome research, particularly for large population-scale datasets, and suggests further analysis on the effects of diet and other regionally varying factors.

Description: From the observed datasets, we should be able to produce curve surfaces that have the same characteristics as the original datasets. For instance, if the given data are positive, then the resulting curve or surface must be positive on entire given intervals, i.e., everywhere. In this study, a new partial blended rational bi-quartic spline with C1 continuity is constructed through the partially blended scheme. This rational spline is defined on four corners of the rectangular meshes. The sufficient condition for the positivity of rational bi-quartic spline is derived on four boundary curve networks. There are eight free parameters that can be used for shape modification. The first-order partial derivatives are estimated by using numerical techniques. We also show that the proposed scheme is local quadratic reproducing such that it can exactly reproduce the quadratic surface. We test the proposed scheme to interpolate various types of positive surface data. Based on statistical indicators such as the root mean square error (RMSE) and coefficient of determination (R2), we found that the proposed scheme is on par with some established schemes. In fact, it requires less CPU times (in seconds) to generate the interpolating surface on rectangular meshes. Furthermore, by combining the statistical indicators’ result and graphically visualizing the test functions, the proposed method has the capability to reconstruct very comparable smoothing interpolating positive surfaces compared to some existing schemes. This finding is significant in producing a better interpolating surface for computer graphics applications since the proposed scheme has a smaller error compared with existing schemes.

Description: Whole body plethysmography (WBP) monitors respiratory rate and depth but conventional analysis fails to capture the diversity of waveforms. Our first purpose was to develop a waveform cluster analysis method for quantifying dynamic changes in respiratory waveforms. WBP data, from adult Sprague-Dawley rats, were sorted into time domains and principle component analysis was used for hierarchical clustering. The clustering method effectively sorted waveforms into categories including sniffing, tidal breaths of varying duration, and augmented breaths (sighs). We next used this clustering method to quantify breathing after opioid (fentanyl) overdose and treatment with ampakine CX1942, an allosteric modulator of AMPA receptors. Fentanyl caused the expected decrease in breathing, but our cluster analysis revealed changes in the temporal appearance of inspiratory efforts. Ampakine CX1942 treatment shifted respiratory waveforms toward baseline values. We conclude that this method allows for rapid assessment of breathing patterns across extended data recordings. Expanding analyses to include larger portions of recorded WBP data may provide insight on how breathing is affected by disease or therapy.

Description: Inflammation is considered one of the possible mechanisms behind long-term cognitive dysfunction persistent after chemotherapy treatment. The chemotherapy combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) was one of the older methods of treating breast cancer patients. Decades later, these patients still report experiencing cognitive side effects. In this present bibliometric review, we applied the VOSviewer tool to describe the existing landscape on literature concerning inflammation as it relates to CMF and cognitive dysfunctions. As time progressed, we saw an increase in interest in the topic. By the mid-2010s there were approximately 1,000 publications per year. Terms related to the brain and CNS did not appear until the later years, and terms related to inflammation and breast cancer were very prevalent throughout the three decades. Also, in more recent years, inflammatory markers and plant-derived compounds used to alleviate side effects of the inflammatory response appeared in the search results. The USA remained the most prolific producer of CMF-, inflammation-, and cognitive dysfunction-related papers throughout the three decades followed by Asia and Europe. As research of cognitive dysfunction caused by inflammation due to chemotherapy treatment progresses, more opportunities emerge for therapeutic methods to improve the quality of life for long-term survivors.

Description: In an immersion incident, a person may be required to tread water for extended periods of time in order to survive. Treading water, or maintaining a stable head position above the water surface, can be achieved in several different ways. Determining which treading water techniques are economic (energetically and cognitively) is an important first step in approaching evidence-based water safety instruction. The present study investigated the cognitive and metabolic demands associated with four main techniques for treading water in experienced water treaders. Skilled water treaders (n=21) performed four common treading techniques for 3min each: “running” in the water, “flutter kick” with hands sculling, “upright breaststroke,” and “egg-beater.” Self-reported rate of perceived exertion (RPE) and task load index (TLX) score, as well as objective measures of probe reaction time (PRT; i.e., response to auditory cues while treading), oxygen consumption and heart rate were assessed. The “egg-beater” technique and the “upright breaststroke” technique were linked to significantly lower cognitive and energetic demands compared to the other techniques (VO2: p

Description: Acid fracturing is an effective method to develop ultra-low permeability reservoirs. However, the fast reaction rate reduces the effect of the acid fracturing and increases the near-well collapse risk. Therefore, it is necessary to retard the acid–rock reaction rate. In this work, we synthesized an acid-resistant Gemini zwitterionic viscoelastic surfactant (named VES-c), which has good performances such as temperature resistance, salt resistance, and shear resistance. Besides, a low concentration of VES-c increases the viscosity of the acid solution. The CO2 drainage method was used to measure the reaction rate between the dibasic acid and dolomite/broken core. We find that the dibasic acid containing 0.3% VES-c retards the dolomite reaction rate of 3.22 times compared with only dibasic acid. Furthermore, the dibasic acid containing 0.3% VES-c exhibits uniform distribution and is not easy to adhere to the solid surface. The VES-c also is favorable to reduce the formation of amorphous calcium carbonate. Retarding the rate of acid–rock reaction and enhancing the acidification are mainly attributed to VES-c's salt-tolerance, anti-adsorption, and the property of increasing the viscosity of the solution. Hopefully, this kind of surfactant retarding reaction rate is applied to other acid–rock reactions.

Description: BackgroundDiagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management.ObjectivesTo determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB.MethodsRetrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500’000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation.ResultsAmong 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ vs AFB- samples, and samples from cavitary vs non cavitary or extra-thoracic disease.ConclusionsIn Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.

Description: The accuracy of biosensor ratio imaging is limited by signal/noise. Signals can be weak when biosensor concentrations must be limited to avoid cell perturbation. This can be especially problematic in imaging of low volume regions, e.g., along the cell edge. The cell edge is an important imaging target in studies of cell motility. We show how the division of fluorescence intensities with low signal-to-noise at the cell edge creates specific artifacts due to background subtraction and division by small numbers, and that simply improving the accuracy of background subtraction cannot address these issues. We propose a new approach where, rather than simply subtracting background from the numerator and denominator, we subtract a noise correction factor (NCF) from the numerator only. This NCF can be derived from the analysis of noise distribution in the background near the cell edge or from ratio measurements in the cell regions where signal-to-noise is high. We test the performance of the method first by examining two noninteracting fluorophores distributed evenly in cells. This generated a uniform ratio that could provide a ground truth. We then analyzed actual protein activities reported by a single chain biosensor for the guanine exchange factor (GEF) Asef, and a dual chain biosensor for the GTPase Cdc42. The reduction of edge artifacts revealed persistent Asef activity in a narrow band (∼640 nm wide) immediately adjacent to the cell edge. For Cdc42, the NCF method revealed an artifact that would have been obscured by traditional background subtraction approaches.

Description: Acetaminophen (APAP) is a mild analgesic and antipyretic used commonly worldwide. Although considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), to proteins. The aim of this study was to identify APAP-protein targets in both rat and mouse liver, and to compare the results from both species, using bottom-up proteomics with data-dependent high resolution mass spectrometry and targeted multiple reaction monitoring (MRM) experiments. Livers from rats and mice, treated with APAP, were homogenized and digested by trypsin. Digests were then fractionated by mixed-mode solid-phase extraction prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS). Targeted LC-MRM assays were optimized based on high-resolution MS/MS data from information-dependent acquisition (IDA) using control liver homogenates treated with a custom alkylating reagent yielding an isomeric modification to APAP on cysteine residues, to build a modified peptide database. A list of putative in vivo targets of APAP were screened from data-dependent high-resolution MS/MS analyses of liver digests, previous in vitro studies, as well as selected proteins from the target protein database (TPDB), an online resource compiling previous reports of APAP targets. Multiple protein targets in each species were found, while confirming modification sites. Several proteins were modified in both species, including ATP-citrate synthase, betaine-homocysteine S-methyltransferase 1, cytochrome P450 2C6/29, mitochondrial glutamine amidotransferase-like protein/ES1 protein homolog, glutamine synthetase, microsomal glutathione S-transferase 1, mitochondrial-processing peptidase, methanethiol oxidase, protein/nucleic acid deglycase DJ-1, triosephosphate isomerase and thioredoxin. The targeted method afforded better reproducibility for analysing these low-abundant modified peptides in highly complex samples compared to traditional data-dependent experiments.

Description: Many shallow coastal systems experience diel fluctuations in dissolved oxygen (DO) and pH that can intensify throughout the summer season and expose estuarine organisms to repeated episodes of coastal hypoxia and acidification. In temperate regions, larval release of the economically important blue crab Callinectes sapidus occurs in the summer, and while the earliest stage (zoea I) larvae are susceptible to persistent low DO and low pH conditions, their sensitivity to diel fluctuations is unknown. Here, a series of short-term (≤96 h) experiments were conducted to investigate the survival of C. sapidus zoea I larvae exposed to a range of diel cycling hypoxic and acidified conditions and durations. Two experiments comparing a diel cycling DO/pH treatment (fluctuating from ∼30% air saturation to ∼103% averaging ∼66%/and from pH ∼7.26 to ∼7.80 averaging ∼7.53) to a static low DO/pH treatment (∼43%/∼7.35), a static moderate DO/pH treatment (∼68%/∼7.59), and a static control treatment (∼106%/∼7.94) indicated that survival in the diel cycling treatment was significantly lower than the moderate treatment (p 〈 0.05) by 75 and 48% over 96 and 48 h, respectively, despite comparable mean experimental DO/pH values. Three other experiments aimed at identifying the effective minimum duration of low DO/low pH to significantly depress larval survival under diel cycling conditions revealed that 8 h of low DO/low pH (∼28%/∼7.43) over a 24-h diel cycle consistently decreased survival (p 〈 0.05) relative to control conditions by at least 55% regardless of experimental duration (72-, 48-, and 24-h experiments). An increase in DO beyond saturation to supersaturation (160%) and pH beyond normocapnic to highly basified (8.34) conditions during the day phase of the diel cycle did not improve survival of larvae exposed to nocturnal hypoxia and acidification. Collectively, these experiments demonstrate that diel cycling does not provide newly hatched C. sapidus larvae a temporal refuge capable of ameliorating low DO/pH stress, but rather is more lethal than chronic exposure to comparable average DO/pH conditions. Given that larvae exposed to a single nocturnal episode of moderate hypoxia and acidification experience significantly reduced survival, such occurrences may depress larval recruitment.

Description: The west coast of South Korea is characterized by a wide macrotidal area with a maximum tidal range of ∼10 m. The sea surface elevation varies with the tidal phase, which leads to significant changes in the vertical structure of the physical, chemical, and biological properties of the water column, especially when the interaction by waves and/or the freshwater and sediment input from the river increases. Under such conditions, it is difficult to carry out continuous and consistent measurements of the vertical structures of the water qualities using a conventional observation system that is fixed to the seabed or sea surface because the thickness of the water column constantly changes. Based on the demand for long-term observations of the vertical structures of the water properties in macrotidal environments, the Intelligent Buoy System (INBUS) was developed by the Korea Institute of Ocean Science and Technology (KIOST). INBUS is a buoy equipped with an instrument frame, which is similar to other buoys that are fixed to the sea surface. During every measurement, INBUS detects the water depth and sends the frame down to the seabed to measure the water quality at every vertical level set up in the system. For example, if N levels are set in INBUS, the water depth of each measurement is divided by N layers and the instruments in the lifting frame measure the water properties of each of the N layers while they are descending to the bottom. Based on this procedure, the vertical structure of the water column is consistently measured in N layers regardless of changes of the water depth due to tides and waves. The lifting and measuring process is automatically controlled by INBUS once it is set up in the system. In addition, because INBUS allows bidirectional communication through code division multiple access (CDMA), the system can be controlled by stations on land. If the CDMA communication becomes inoperable owing to extreme wave conditions or the buoy is lost because of incidents such as a collision with a ship, the location of INBUS can be tracked by low-earth-orbit satellites.

Description: Long non-coding RNAs (lncRNAs) play an important role in many diseases and are involved in the post-transcriptional regulatory network of tumors. The purpose of this study is to mine new lncRNA–mRNA regulatory pairs and analyze the new mechanism of lncRNA involvement in breast cancer progression. Using breast cancer miRNA and mRNA expression profiling from The Cancer Genome Atlas (TCGA), we identified 59 differentially expressed lncRNAs, 88 differentially expressed miRNAs, and 1,465 differentially expressed mRNAs between breast cancer tissue and adjacent normal breast cancer. Whereafter, four candidate lncRNAs (FGF14-AS2, LINC01235, AC055854.1, and AC124798.1) were identified by the Kaplan–Meier (K–M) plotter. Furthermore, we screened the hub lncRNA (LINC01235) through univariate Cox analysis, multivariate Cox analysis, and qPCR validation, which was significantly correlated with breast cancer stage, ER status, and pathological N. Subsequently, 107 LINC01235-related mRNAs were obtained by combining differentially expressed miRNAs, differentially expressed mRNAs, and LINC01235 targeting miRNAs and mRNAs. The protein–protein interaction (PPI) network was established by Cytoscape software, and 53 key genes were screened. Function and pathway enrichment showed that LINC01235-related key genes might be involved in the process of cell differentiation, cell proliferation, and p53 signal pathway. In addition, LINC01235 has been confirmed to regulate the proliferation, migration, and invasion of MCF-7 cells in in vitro experiments. Furthermore, we screened three mRNAs (ESR1, ADRA2A, and DTL) associated with breast cancer drug resistance from key genes. Through RNA interference experiments in vitro and correlation analysis, we found that there was a negative feedback mechanism between LINC01235 and ESR1/ADRA2A. In conclusion, our results suggest that LINC01235-ESR1 and LINC01235-ADRA2A could serve as important co-expression pairs in the progression of breast cancer, and LINC01235 plays a key role as an independent prognostic factor in patients with breast cancer. The findings of this work greatly increase our understanding of the molecular regulatory mechanisms of lncRNA in breast cancer.

Description: A new robust method for optimal damper placement is presented for building structures under the critical double impulse. Oil dampers are treated here as representative supplemental dampers to control the seismic response of high-rise buildings. Such oil dampers usually obey a bi-linear force-velocity relation in controlling the maximum damping force through a relief mechanism to avoid the occurrence of excessive design forces in surrounding frames. The influence of uncertainty in characteristics of those bi-linear oil dampers on building structural safety is investigated. For the efficient evaluation of dynamic performance, the resonant critical double impulse is used as the base input instead of actual earthquake ground motions. Since the critical double impulse is determined to maximize the input energy to the objective building by changing the second impulse timing, uncertainties in input ground motions can be taken into account in a robust manner. To consider these various uncertainties, the robustness function based on the Info-Gap model is used in the robust optimization to assess structural performance variations caused by various uncertainties in the structural design phase. In this paper, a new innovative objective function in the robust optimal damper placement problem is proposed to enhance the robustness of structural performance under the variation of structural parameters by comparing the robustness function of the robust design with that of an ordinary optimal damper placement without considering uncertainties. Numerical examples of the robust optimal design of linear and bi-linear oil damper placements are shown for 10-story and 20-story planar building frame models. Structural performances of the robust optimal design to the conventional design earthquake ground motions are examined to investigate the validity of using the critical double impulse in the structural design under uncertainties.

Description: We study theoretically the properties of local heat originated from energy exchange between electrons passing through a quantum dot (QD) coupled to a phonon bath. The dot is sandwiched between two normal metal leads and also side-coupled to Majorana bound states (MBSs) formed at opposite ends of a topological superconductor nanowire. We find that in addition to the negative differential of heat generation (NDHG) in the Coulomb blockade regime, another NDHG emerges near the leads’ Fermi level due to the dot-MBS coupling. This dual NDHG effect is robust against the variation of intradot Coulomb interaction strength, and disappears if the QD is coupled to regular Fermions. Direct hybridization between the MBSs reduces their impacts on the electronic transport processes, and eliminates the dual NDHG effect. Our results show that the dual NDHG effect is quite efficient for inferring the existence of MBSs, and may remedy some limitations of the detection schemes relying on tunneling spectroscopy technique.

Description: Novel human coronavirus disease (COVID-19), an infectious respiratory disease, has affected more than 50 million people around the world up to November 2020, thereby becoming the fifth documented pandemic since the Spanish flu in 1918. SARS-CoV-2 virus originated in China and evolved for 4 months within the country before becoming a global threat. There is currently no drug approved by the Food and Drug Administration (FDA) for which efficacy on the virus has been proved. Therefore, the only strategy against this virus is to apply measures that are capable of reducing its spread, such as isolation and quarantine, social distancing, community-wide containment, and strict enforcement of hygiene. Quarantine has proved to be effective in combating the spread of the virus; however, it has inevitably led to a radical change in the lives of people. Studies have been conducted in Italy and some European countries to highlight the role that quarantine has played in determining the lifestyle changes both in eating habits and physical activity and their possible correlation with increase in weight. The selection criteria involved answering a questionnaire that included information on the weight status and at least one of the other two aspects: changes in eating habits and/or physical activity during the quarantine period. The results obtained indicate, in general, that the negative effect of quarantine was on eating habits and physical activity. This was based on the observation that there has been an increase in food consumption and a reduction in physical activity with a consequent increase in weight.

Description: Eutrophic coastal regions are highly productive and greatly influenced by human activities. Primary production supporting the coastal ecosystems is supposed to be affected by progressive ocean acidification driven by increasing CO2 emissions. In order to investigate the effects of high pCO2 (HC) on eutrophic plankton community structure and ecological functions, we employed 9 mesocosms and carried out an experiment under ambient (∼410 ppmv) and future high (1000 ppmv) atmospheric pCO2 conditions, using in situ plankton community in Wuyuan Bay, East China Sea. Our results showed that HC along with natural seawater temperature rise significantly boosted biomass of diatoms with decreased abundance of dinoflagellates in the late stage of the experiment, demonstrating that HC repressed the succession from diatoms to dinoflagellates, a phenomenon observed during algal blooms in the East China Sea. HC did not significantly influence the primary production or biogenic silica contents of the phytoplankton assemblages. However, the HC treatments increased the abundance of viruses and heterotrophic bacteria, reflecting a refueling of nutrients for phytoplankton growth from virus-mediated cell lysis and bacterial degradation of organic matters. Conclusively, our results suggest that increasing CO2 concentrations can modulate plankton structure including the succession of phytoplankton community and the abundance of viruses and bacteria in eutrophic coastal waters, which may lead to altered biogeochemical cycles of carbon and nutrients.

Description: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide with very limited treatment options. Cold-inducible RNA binding protein (CIRBP) plays promoting roles in several types of cancers, but its function remains unclear in PDAC. Here, we found that the expression of CIRBP was upregulated in PDAC tumor tissues and was significantly associated with poor prognosis. Knockdown of CIRBP in PANC-1 and SW1990 cells inhibited proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Moreover, CIRBP knockdown enhanced the antitumour effects of gemcitabine treatment in PANC-1 and SW1990 cells, whereas CIRBP overexpression exerted the opposite effects. Mechanistically, CIRBP promoted PDAC malignancy and chemoresistance via upregulation of dual-specificity tyrosine-Y-phosphorylation regulated kinase 1B (DYRK1B). Indeed, knockdown of CIRBP sensitized pancreatic tumors to gemcitabine treatment by diminishing DYRK1B expression and increasing the ratio of ERK/p38 activity. Our findings suggest that CIRBP overexpression facilitates PDAC progression and gemcitabine resistance by upregulating DYRK1B expression and inhibiting the ERK/p38 signaling pathway, highlighting CIRBP as a potential new therapeutic target for PDAC.

Description: We numerically calculate the quasinormal frequencies of the Klein-Gordon and Dirac fields propagating in a two-dimensional asymptotically anti-de Sitter black hole of the dilaton gravity theory. For the Klein-Gordon field we use the Horowitz-Hubeny method and the asymptotic iteration method for second order differential equations. For the Dirac field we first exploit the Horowitz-Hubeny method. As a second method, instead of using the asymptotic iteration method for second order differential equations, we propose to take as a basis its formulation for coupled systems of first order differential equations. For the two fields we find that the results that produce the two numerical methods are consistent. Furthermore for both fields we obtain that their quasinormal modes are stable and we compare their quasinormal frequencies to analyze whether their spectra are isospectral. Finally we discuss the main results.

Description: Background: Pancreatic adenocarcinoma (PAAD) has a considerably bad prognosis, and its pathophysiologic mechanism remains unclear. Thus, we aimed to identify real hub genes to better explore the pathophysiology of PAAD and construct a prognostic panel to better predict the prognosis of PAAD using the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithms.Methods: WGCNA identified the modules most closely related to the PAAD stage and grade based on the Gene Expression Omnibus. The module genes significantly associated with PAAD progression and prognosis were considered as the real hub genes. Eligible genes in the most significant module were selected for construction and validation of a multigene prognostic signature based on the LASSO-Cox regression analysis in The Cancer Genome Atlas and the International Cancer Genome Consortium databases, respectively.Results: The brown module identified by WGCNA was most closely associated with the clinical characteristics of PAAD. Scaffold attachment factor B (SAFB) was significantly associated with PAAD progression and prognosis, and was identified as the real hub gene of PAAD. Moreover, both transcriptional and translational levels of SAFB were significantly lower in PAAD tissues compared with normal pancreatic tissues. In addition, a novel multigene-independent prognostic signature consisting of SAFB, SP1, and SERTAD3 was identified and verified. The predictive accuracy of our signature was superior to that of previous studies, especially for predicting 3- and 5-year survival probabilities. Furthermore, a prognostic nomogram based on independent prognostic variables was developed and validated using calibration curves. The predictive ability of this nomogram was also superior to the well-established AJCC stage and histological grade. The potential mechanisms of different prognoses between the high- and low-risk subgroups were also investigated using functional enrichment analysis, GSEA, ssGSEA, immune checkpoint analysis, and mutation profile analysis.Conclusion: SAFB was identified as the real hub gene of PAAD. A novel multigene-independent prognostic signature was successfully identified and validated to better predict PAAD prognosis. An accurate nomogram was also developed and verified to aid in the accurate treatment of tumors, as well as in early intervention.

Description: The ongoing urbanization requires enhanced understanding of the local meteorological and climatological conditions within the urban environment for multiple applications, concerning energy demand, human health, and spatial planning. Identifying areas with harmful meteorological conditions enables citizens and local authorities to take actions to optimize quality of life for urban dwellers. At the moment cities have (in general) limited networks of meteorological monitoring stations. To overcome this lack of observations, the use of non-traditional data sources is rapidly increasing. However, the use of such data sources without enough prior verification has become a controversial topic in the scientific community. This study aims to verify and assess one of the main non-traditional data sources, i.e. smartphones. The goal is to research the potential of smartphones (using the Samsung Galaxy S4 as an example phone model) to correctly sense air temperature, relative humidity, and solar radiation, and to determine to what extent environmental conditions negatively affect their performance. The smartphone readings were evaluated against observations from reference instrumentation at a weather station and a mobile measurement platform. We test the response time of the smartphone thermometer and hygrometer, and the light sensor’s cosine response. In a lab setting, we find that a smartphone can provide reliable temperature information when it is not exposed to direct solar radiation. The smartphone’s hygrometer performs better at low relative humidity levels while it can over-saturate at higher levels. The light sensor records show substantial correlation with global radiation observations, and short response times. Measurements along an urban transect of 10 km show the smartphone’s ability to react to fast changes of temperature in the field, both in time and space. However, a bias correction (dependent on wind speed and radiation) is required to represent the reference temperature. Finally we show that after such a bias correction, a smartphone record can successfully capture spatial variability over a transect as well.

Description: In this review, we report on recent progress in the generation and application of multichromatic polarization-tailored pulse sequences for the coherent control of multiphoton ionization (MPI) dynamics and present unpublished experimental results that complement our previous findings. Specifically, we utilize single-color, bichromatic, and trichromatic polarization-controlled pulse sequences generated by spectral amplitude, phase and polarization modulation of a carrier-envelope phase (CEP)-stable white light supercontinuum for MPI. The analysis of the number of ionization pathways and the number of distinct final free electron states shows that both increase significantly, but scale differently with the number of absorbed photons and the number of pulses in the sequence. In our experiments, ultrafast polarization shaping is combined with high-resolution photoelectron tomography to generate, control, and reconstruct three-dimensional photoelectron momentum distributions from atomic and molecular MPI. We discuss the use of polarization-controlled single-color and bichromatic pulse sequences in perturbative and non-perturbative coherent control of coupled electron-nuclear dynamics in molecules, atomic spin-orbit wave packet dynamics and the directional photoemission from atoms and chiral molecules. We compare the coherent control of CEP-insensitive intraband multipath interference in the MPI with a fixed number of photons with CEP-sensitive interband multipath interference in the ionization with a different number of photons. The generation and control of free electron vortices with even-numbered rotational symmetry by MPI with single-color pulse sequences is contrasted with the bichromatic control of CEP-sensitive electron vortices with odd-numbered rotational symmetry. To illustrate the potential of multichromatic pulse sequences for coherent control, we present a trichromatic scheme for shaper-based quantum state holography.

Description: Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity. Microbial communities residing in the host's airways have immunomodulatory effects, but it is unclear if the inter-individual variability of these microbial communities is associated with the heterogeneity of pulmonary TB. Here, we investigated this possibility by characterizing the microbial composition in the sputum of 334 TB patients from Tanzania, and by assessing its association with three aspects of disease manifestations: sputum mycobacterial load, severe clinical findings, and chest x-ray (CXR) findings. Compositional data analysis of taxonomic profiles based on 16S-rRNA gene amplicon sequencing and on whole metagenome shotgun sequencing, and graph-based inference of microbial associations revealed that the airway microbiome of TB patients was shaped by inverse relationships between Streptococcus and two anaerobes: Selenomonas and Fusobacterium. Specifically, the strength of these microbial associations was negatively correlated with Faith's phylogenetic diversity (PD) and with the accumulation of transient genera. Furthermore, low body mass index (BMI) determined the association between abnormal CXRs and community diversity and composition. These associations were mediated by increased abundance of Selenomonas and Fusobacterium, relative to the abundance of Streptococcus, in underweight patients with lung parenchymal infiltrates and in comparison to those with normal chest x-rays. And last, the detection of herpesviruses and anelloviruses in sputum microbial assemblage was linked to co-infection with HIV. Given the anaerobic metabolism of Selenomonas and Fusobacterium, and the hypoxic environment of lung infiltrates, our results suggest that in underweight TB patients, lung tissue remodeling toward anaerobic conditions favors the growth of Selenomonas and Fusobacterium at the expense of Streptococcus. These new insights into the interplay among particular members of the airway microbiome, BMI, and lung parenchymal lesions in TB patients, add a new dimension to the long-known association between low BMI and pulmonary TB. Our results also drive attention to the airways virome in the context of HIV-TB coinfection.

Description: This study was undertaken to evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae in selected shrimp aquaculture farms (n = 37) in Kerala, South India and to characterize the isolates using molecular tools. Overall, a low prevalence of ESBL-producers was found in the farms, most likely due to the reduced antibiotic usage in the shrimp farming sector. Out of the 261 samples (77 shrimp and 92 each of water and sediment), 14 (5.4%) tested positive for ESBL-E. coli or ESBL-K. pneumoniae. A total of 32 ESBL-E. coli and 15 ESBL- K. pneumoniae were recovered from these samples. All ESBL isolates were cefotaxime-resistant with minimal inhibitory concentration (MIC) ≥32 μg/ml. Of all isolates, 9 (28.1%) E. coli and 13 (86.7%) K. pneumoniae showed simultaneous resistance to tetracycline, ciprofloxacin, and trimethoprim-sulfamethoxazole. PCR analysis identified CTX-M group 1 (blaCTX–M–15) as the predominant ESBL genotype in both E. coli (23, 71.9%) and K. pneumoniae (15, 100%). Other beta-lactamase genes detected were as follows: blaTEM and blaSHV (11 K. pneumoniae), blaCTX–M group 9 (9 E. coli), and blaCMY–2 (2 E. coli). Further screening for AMR genes identified tetA and tetB (13, 40.6%), sul1 (11, 34.4%), sul2 (9, 28.1%), catA and cmlA (11, 34.4%), qepA and aac(6′)-Ib-cr (9, 28.1%) and strAB and aadA1 (2, 6.3%) in E. coli, and qnrB (13, 86.7%), qnrS (3, 20%), oqxB (13, 86.7%), tetA (13, 86.7%), and sul2 (13, 86.7%) in K. pneumoniae isolates. Phylogenetic groups identified among E. coli isolates included B1 (4, 12.5%), B2 (6, 18.8%), C (10, 31.3%), D (3, 9.4%), and E (9, 28.1%). PCR-based replicon typing (PBRT) showed the predominance of IncFIA and IncFIB plasmids in E. coli; however, in K. pneumoniae, the major replicon type detected was IncHI1. Invariably, all isolates of K. pneumoniae harbored virulence-associated genes viz., iutA, entB, and mrkD. Epidemiological typing by pulsed-field gel electrophoresis (PFGE) revealed that E. coli isolates recovered from different farms were genetically unrelated, whereas isolates of K. pneumoniae showed considerable genetic relatedness. In conclusion, our findings provide evidence that shrimp aquaculture environments can act as reservoirs of multi-drug resistant E. coli and K. pneumoniae.

Description: Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.

Description: Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI

Description: Global food and water insecurity could be serious problems in the upcoming decades with growing demands from the increasing global population and more frequent effect of climatic extremes. As the available water resources are diminishing and facing continuous stress, it is crucial to monitor water demand and water availability to understand the associated water stresses. This study assessed the water stress by applying the water supply stress index (WaSSI) in relation to green (WaSSIG) and blue (WaSSIB) water resources across six major cropland basins including the Mississippi (North America), San Francisco (South America), Nile (Africa), Danube (Europe), Ganges-Brahmaputra (Asia), and Murray-Darling (Australia) for the past 17-years (2003–2019). The WaSSIG and WaSSIB results indicated that the Murray-Darling Basin experienced the most severe (maximum WaSSIG and WaSSIB anomalies) green and blue water stresses and the Mississippi Basin had the least. All basins had both green and blue water stresses for at least 35% (6 out of 17 years) of the study period. The interannual variations in green water stress were driven by both crop water demand and green water supply, whereas the blue water stress variations were primarily driven by blue water supply. The WaSSIG and WaSSIB provided a better understanding of water stress (blue or green) and their drivers (demand or supply driven) across cropland basins. This information can be useful for basin-specific resource mobilization and interventions to ensure food and water security.

Description: In this paper, a biological template method is introduced and investigated to fabricate ionic polymer-metal composite (IPMC) strain sensor with bionic hierarchical structures. We utilized the multi-level structure of reed leaf surface, which can improve the contact area between the substrate and the electrode layers. Hierarchical structures were observed on the IPMC samples, including pyramid strips with the width in the range of 60–80 μm as well as synaptic scatters with diameter around 10 μm. In addition, five kinds of sensors with different interface structures were obtained by combining the traditional microneedle roller roughening and chemical plating processes. It was found that the IPMC sensor with reed-leaf and microneedle structure on each side presented the best performance, along with a high linearity, a sensitivity of 62.5 mV/1% and a large generated voltage peak under given mechanical stimuli, which is 3.7 times that of the sample fabricated without roughening.

Description: Increased basal low-grade inflammation is observed with advancing age, which is augmented by physical inactivity. However, data regarding the influence of lifelong exercise training and particularly high-intensity interval training (HIIT) on inflammatory mediators in older men are scarce. Therefore, we examined effects of 6weeks of aerobic preconditioning followed by 6weeks of HIIT on inflammatory mediators [interleukin (IL)-6, homocysteine, and high-sensitivity C-reactive protein (hsCRP)] in previously sedentary older men (SED) and masters athletes (LEX). Further, we investigated whether SED exhibited greater basal inflammatory biomarkers compared to LEX. Twenty-two men (aged 62±2years) participated in the SED group, while 17 age-matched LEX men (aged 60±5years) also participated as a positive comparison group. In SED, preconditioning (P=0.030, d=0.34) and HIIT (P=0.030, d=0.48) caused a reduction in IL-6 compared to enrollment. SED homocysteine did not change throughout (P〉0.57; d0.42; d0.131; d

Description: Appropriately responding to stressful events is essential for maintaining health and well-being of any organism. Concerning social stress, the response is not always as straightforward as reacting to physical stressors, e.g., extreme heat, and thus has to be balanced subtly. Particularly, regulatory mechanisms contributing to gaining resilience in the face of mild social stress are not fully deciphered yet. We employed an intrinsic social hierarchy stress paradigm in mice of both sexes to identify critical factors for potential coping strategies. While global transcriptomic changes could not be observed in male mice, several genes previously reported to be involved in synaptic plasticity, learning, and anxiety-like behavior were differentially regulated in female mice. Moreover, changes in N6-methyladenosine (m6A)-modification of mRNA occurred associated with corticosterone level in both sexes with, e.g., increased global amount in submissive female mice. In accordance with this, METTL14 and WTAP, subunits of the methyltransferase complex, showed elevated levels in submissive female mice. N6-adenosyl-methylation is the most prominent type of mRNA methylation and plays a crucial role in processes such as metabolism, but also response to physical stress. Our findings underpin its essential role by also providing a link to social stress evoked by hierarchy building within same-sex groups. As recently, search for small molecule modifiers for the respective class of RNA modifying enzymes has started, this might even lead to new therapeutic approaches against stress disorders.

Description: Mooring observations in the eastern Eurasian Basin of the Arctic Ocean showed that mean 2013–2018 along-slope volume and heat (calculated relative to the freezing temperature) transports in the upper 800 m were 4.8 ± 0.1 Sv (1 Sv = 106 m3/s) and 34.8 ± 0.6 TW, respectively. Volume and heat transports within the Atlantic Water (AW) layer (∼150–800 m) in 2013–2018 lacked significant temporal shifts at annual and longer time scales: averaged over the two periods of mooring deployment in 2013–2015 and 2015–2018, volume transports were 3.1 ± 0.1 Sv, while AW heat transports were 31.3 ± 1.0 TW and 34.8 ± 0.8 TW. Moreover, the reconstructed AW volume transports over longer, 2003–2018, period of time showed strong interannual variations but lacked a statistically significant trend. However, we found a weak positive trend of 0.08 ± 0.07 Sv/year in the barotropic AW volume transport estimated using dynamic ocean topography (DOT) measurements in 2003–2014 – the longest period spanned by the DOT dataset. Vertical coherence of 2013–2018 transports in the halocline (70–140 m) and AW (∼150–800 m) layers was high, suggesting the essential role of the barotropic forcing in constraining along-slope transports. Quantitative estimates of transports and their variability discussed in this study help identify the role of atlantification in critical changes of the eastern Arctic Ocean.

Description: Head and neck squamous cell carcinomas (HNSCC) are still one of the most common malignant tumors in China, with a high metastasis rate and poor prognosis. The tumor immune microenvironment can affect the occurrence, development and prognosis of tumors, but the underlying mechanism is still unclear. In this study, we tried to describe the correlation between the recurrence of HNSCC and the tumor microenvironment (TME). The expression data [estimate the level of tumor stromal and immune infiltration, expression data (ESTIMATE)] algorithm was used to identify and estimate highly correlated stromal cells, immune cells, and prognostic scores in 116 samples of head and neck cancer patients from The Cancer Genome Atlas (TCGA) dataset. The functional enrichment analysis and protein-protein interaction (PPI) networks of differential expressed genes (DEGs) were constructed. Subsequently, the abundance of various infiltrating immune cells was estimated with the tumor immune estimation resource (TIMER) and the infiltration pattern of immune cells were explored in HNSCC. A total of 407 immune-related genes were identified to involve in the TME. We found that CCR5, CD3E, CD4, and HLA -DRB1 were the most obvious DEGs and the dendritic cells (DCs) showed the highest abundance in the TME of HNSCC. In addition, the unsupervised cluster analysis determined 10 clusters of immune infiltration patterns, and indicated that immune infiltrated CD4 + T and B cells may be related to the prognosis of HNSCC. In conclusion, our research determined the list of immune genes and immune infiltrating cells related to the prognosis of HNSCC, and provided a perspective for HNSCC evolution, anti-tumor drugs selection, and drug resistance research.

Description: This study evaluated the agricultural eco-efficiency (AEE) of 77 counties and districts in Jiangsu Province from 1999 to 2018 using the slack-based measure (SBM) of efficiency in data envelopment analysis (DEA) (SBM-DEA) and analyzed its spatiotemporal evolution characteristics and influencing factors. We found that 1) the overall AEE, pure technology efficiency (PTE), and scale efficiency (SE) exhibited a fluctuating downward trend. AEE exhibited a significantly positive spatial association and an increasingly widening regional inequality. 2) AEE featured the “high south” and “low north” spatial pattern, with the high-value regions concentrated around the Taihu Lake plain region in southern Jiangsu Province (Sunan) and low-value regions scattered across most of the northern Jiangsu Province (Subei) cities. The high-high and low-low spatial association types further confirmed the existence of the north–south agglomeration pattern. 3) PTE and SE exhibited a similar “high south” and “low north” spatial pattern to that of AEE. The areas with the growth trends of AEE, PTE, and SE were clustered in Xuzhou and Nanjing city and in the bordering regions between Yangzhou and the Huai’an city, and also between Changzhou and the Wuxi city. 4) Excessive redundant input and use of pesticides, chemical fertilizers, agricultural diesel, labor, land, and agricultural carbon emissions, all have been the primary factors affecting Jiangsu’s AEE. Irrigation also considerably affected AEE, while mechanical power and agricultural film have minimal effects. The majority of counties and districts in the Subei, central Jiangsu Province (Suzhong), and Ningzhen Yang Hilly region experienced excessive usage of chemical fertilizers, pesticides, chemical fertilizers, agricultural diesel, labor, and land. The findings can improve understanding of the spatial association effect and underlying impediment of AEE and can further help policymakers promoting agricultural eco-efficiency.

Description: The interaction between the serine protease urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) focalizes plasminogen activation to cell surfaces, thereby regulating extravascular fibrinolysis, cell adhesion, and migration. uPAR belongs to the Ly6/uPAR (LU) gene superfamily and the high-affinity binding site for uPA is assembled by a dynamic association of its three consecutive LU domains. In most human solid cancers, uPAR is expressed at the invasive areas of the tumor-stromal microenvironment. High levels of uPAR in resected tumors or shed to the plasma of cancer patients are robustly associated with poor prognosis and increased risk of relapse and metastasis. Over the years, a plethora of different strategies to inhibit uPA and uPAR function have been designed and investigated in vitro and in vivo in mouse models, but so far none have been implemented in the clinics. In recent years, uPAR-targeting with the intent of cytotoxic eradication of uPAR-expressing cells have nonetheless gained increasing momentum. Another avenue that is currently being explored is non-invasive imaging with specific uPAR-targeted reporter-molecules containing positron emitting radionuclides or near-infrared (NIR) florescence probes with the overarching aim of being able to: (i) localize disease dissemination using positron emission tomography (PET) and (ii) assist fluorescence guided surgery using optical imaging. In this review, we will discuss these advancements with special emphasis on applications using a small 9-mer peptide antagonist that targets uPAR with high affinity.

Description: Managed and wild bee populations contribute over $15 billion in pollination services to US agriculture, yet both are declining or becoming increasingly vulnerable to parasites and disease. The loss of healthy and diverse forage is a key driver in bee declines, so incentivizing land managers to adopt diversified bee-friendly management practices such as forage plantings and reduced pesticide use can directly increase food security, pollinator health, and farmer adaptive capacity. To better understand what might incentivize growers to adopt bee-friendly practices, we conducted a survey of California almond growers, whose orchards are entirely dependent on bee pollination and draw nearly 88% of US bee colonies each February to pollinate almond bloom. We asked 329 respondents across all major almond growing regions of CA about their adoption rate and incentives for planting cover crops, pollinator habitat, and practicing the recommended and legally required bee-friendly best management practices, as well as their interest in bee-friendly certification programs. Using a model selection framework, we evaluated which geographic, social, operational, and pollination-service related factors were predictive of bee-friendly practice adoption. We found that no single factor was a statistically significant predictor of adoption across all models, suggesting there is no silver bullet determining bee-friendly practice adoption. However, we discovered that region and concerns about future pollination services consistently emerged as important factors related to all the practices we investigated, except the adoption of legally required BMPs. These findings suggest that a regionally flexible pollinator conservation strategy focused on supporting honey bee colonies might have the highest likelihood of grower participation and adoption.

Description: Treatment of leishmaniasis is a challenging subject. Although available, chemotherapy is limited, presenting toxicity and adverse effects. New drugs with antileishmanial activity are being investigated, such as antiparasitic compounds derived from plants. In this work, we investigated the antileishmanial activity of the biflavonoid amentoflavone on the protozoan Leishmania amazonensis. Although the antileishmanial activity of amentoflavone has already been reported in vitro, the mechanisms involved in the parasite death, as well as its action in vivo, remain unknown. Amentoflavone demonstrated activity on intracellular amastigotes in macrophages obtained from BALB/c mice (IC50 2.3 ± 0.93 μM). No cytotoxicity was observed and the selectivity index was estimated as greater than 10. Using BALB/c mice infected with L. amazonensis we verified the effect of an intralesional treatment with amentoflavone (0.05 mg/kg/dose, in a total of 5 doses every 4 days). Parasite quantification demonstrated that amentoflavone reduced the parasite load in treated footpads (46.3% reduction by limiting dilution assay and 56.5% reduction by Real Time Polymerase Chain Reaction). Amentoflavone decreased the nitric oxide production in peritoneal macrophages obtained from treated animals. The treatment also increased the expression of ferritin and decreased iNOS expression at the site of infection. Furthemore, it increased the production of ROS in peritoneal macrophages infected in vitro. The increase of ROS in vitro, associated with the reduction of NO and iNOS expression in vivo, points to the antioxidant/prooxidant potential of amentoflavone, which may play an important role in the balance between inflammatory and anti-inflammatory patterns at the infection site. Taken together these results suggest that amentoflavone has the potential to be used in the treatment of cutaneous leishmaniasis, working as an ally in the control and development of the lesion.

Description: We investigated the effects of principal instructional leadership (IL) on the frequency of two forms of teacher collaboration (TC) namely exchange and coordination of teaching (EXCHT) and professional collaboration (PROFCOLT) and their influence on student achievement (SA). Using data from the representative German PISA 2015 sample, we carry out structural equation modeling analysis to estimate the direct effects of IL on TC and of TC on SA, as well as the indirect effects of IL on SA. The analyses were conducted at the school level and only teachers belonging to the non-science group in PISA 2015 were included. After testing for the factorial validity of the instrument, only the collaboration form (EXCHT) could be retained. Our analysis suggests that principal instructional leadership can positively influence teachers’ collaboration frequency and that the remaining form of teacher collaboration is not positively related to student achievement. Our study builds on and extends research on student achievement by adding evidence about the relations between principal leadership and teacher collaboration in Germany.

Description: Water-soluble species constitute a significant fraction (up to 60–70%) of the total aerosol loading in the marine atmospheric boundary layer (MABL). The “indirect” effects, that is, climate forcing due to modification of cloud properties depend on the water-soluble composition of aerosols. Thus, the characterization of aerosols over the MABL is of greater relevance. Here, we present 1-year long aerosol chemical composition data of PM10 and PM2.5 at a costal location in the northeastern Arabian Sea (Goa; 15.45°N, 73.20°E, 56 m above the sea level). Average water-soluble ionic concentration (sum of anion and cation) is highest (25.5 ± 6.9 and 19.6 ± 5.8 μg·m−3 for PM10 and PM2.5, respectively) during winter season and lowest during post-monsoon (17.3 ± 9.1 and 14.4 ± 8.1 μg·m−3 for PM10 and PM2.5, respectively). Among water-soluble ionic spices, SO42- ion was found to be dominant species in anions and NH4+ is dominant in cations, for both PM10 and PM2.5 during all the seasons. These observations clearly hint to the contribution from anthropogenic emission and significant secondary inorganic species formation. Sea-salt (calculated based on Na+ and Cl−) concentration shows significant temporal variability with highest contribution during summer seasons in both fractions. Sea-salt corrected Ca2+, an indicator of mineral dust is found mostly during summer months, particularly in PM10 samples, indicates contribution from mineral dust emissions from arid/semiarid regions located in the north/northwestern India and southwest Asia. These observations are corroborated with back-trajectory analyses, wherein air parcels were found to derive from the desert area in summer and Indo-Gangetic Plains (a hot spot for anthropogenic emissions) during winter. In addition, we also observe the presence of nss-K+ (sea-salt corrected), for PM2.5, particularly during winter months, indicating influence of biomass burning emissions. The impact on aerosol chemistry is further assessed based on chloride depletion. Chloride depletion is observed very significant during post-monsoon months (October and November), wherein more than 80 up to 100% depletion is found, mediated by excess sulfates highlighting the role of secondary species in atmospheric chemistry. Regional scale characterization of atmospheric aerosols is important for their better parameterization in chemical transport model and estimation of radiative forcing.

Description: Teachers’ diagnostic competences are regarded as highly important for classroom assessment and teacher decision making. Prior conceptualizations of diagnostic competences as judgement accuracy have been extended to include a wider understanding of what constitutes a diagnosis; novel models of teachers’ diagnostic competences explicitly include the diagnostic process as the core of diagnosing. In this context, domain-general and mathematics-specific research emphasizes the importance of tasks used to elicit student cognition. However, the role of (mathematical) tasks in diagnostic processes has not yet attracted much systematic empirical research interest. In particular, it is currently unclear whether teachers consider diagnostic task potential when selecting tasks for diagnostic interviews and how this relationship is shaped by their professional knowledge. This study focuses on pre-service mathematics teachers’ selection of tasks during one-to-one diagnostic interviews in live simulations. Each participant worked on two 30 mins interviews in the role of a teacher, diagnosing a student’s mathematical understanding of decimal fractions. The participants’ professional knowledge was measured afterward. Trained assistants played simulated students, who portrayed one of four student case profiles, each having different mathematical (mis-)conceptions of decimal fractions. For the interview, participants could select tasks from a set of 45 tasks with different diagnostic task potentials. Two aspects of task selection during the diagnostic processes were analyzed: participants’ sensitivity to the diagnostic potential, which was reflected in higher odds for selecting tasks with high potential than tasks with low potential, and the adaptive use of diagnostic task potential, which was reflected in task selection influenced by a task’s diagnostic potential in combination with previously collected information about the student’s understanding. The results show that participants vary in their sensitivity to diagnostic task potential, but not in their adaptive use. Moreover, participants’ content knowledge had a significant effect on their sensitivity. However, the effects of pedagogical content and pedagogical knowledge did not reach significance. The results highlight that pre-service teachers require further support to effectively attend to diagnostic task potential. Simulations were used for assessment purposes in this study, and they appear promising for this purpose because they allow for the creation of authentic yet controlled situations.

Description: Edible insects are proposed as a nutritious and environmentally sustainable alternative source to animal proteins, due to their numerous advantages in terms of reduced ecological impact and high nutritional value. However, the novelty for edible insects relies on the content of bioactive ingredients potentially able to induce a functional effect in the body. The present review summarizes the main findings on the antioxidant properties of edible insects available in the literature. A total of 30 studies involving animals, cell cultures, or in vitro experimental studies evaluating the antioxidant effect of edible insects are presented in this work. When the antioxidant activity was investigated, using a wide variety of in vitro tests and in cellular models, positive results were shown. Dietary supplementation with edible insects was also able to counteract dietary oxidative stress in animal models, restoring the balance of antioxidant enzymes and reducing the formation of oxidation damage markers. On the basis of the reviewed evidences, edible insects might represent a source of novel redox ingredients at low ecological impact able to modulate oxidative stress. However, due to the fact that majority of these evidences have been obtained in vitro and in cellular and animal models, dietary intervention trials are needed to assess the efficacy of edible insect consumption to modulate redox status in humans.

Description: Of the seven currently known botulinum neurotoxin-producing species of Clostridium, C. parabotulinum, or C. botulinum Group I, is the species associated with the majority of human botulism cases worldwide. Phylogenetic analysis of these bacteria reveals a diverse species with multiple genomic clades. The neurotoxins they produce are also diverse, with over 20 subtypes currently represented. The existence of different bont genes within very similar genomes and of the same bont genes/gene clusters within different bacterial variants/species indicates that they have evolved independently. The neurotoxin genes are associated with one of two toxin gene cluster types containing either hemagglutinin (ha) genes or orfX genes. These genes may be located within the chromosome or extrachromosomal elements such as large plasmids. Although BoNT-producing C parabotulinum bacteria are distributed globally, they are more ubiquitous in certain specific geographic regions. Notably, northern hemisphere strains primarily contain ha gene clusters while southern hemisphere strains have a preponderance of orfX gene clusters. OrfX C. parabotulinum strains constitute a subset of this species that contain highly conserved bont gene clusters having a diverse range of bont genes. While much has been written about strains with ha gene clusters, less attention has been devoted to those with orfX gene clusters. The recent sequencing of 28 orfX C. parabotulinum strains and the availability of an additional 91 strains for analysis provides an opportunity to compare genomic relationships and identify unique toxin gene cluster characteristics and locations within this species subset in depth. The mechanisms behind the independent processes of bacteria evolution and generation of toxin diversity are explored through the examination of bacterial relationships relating to source locations and evidence of horizontal transfer of genetic material among different bacterial variants, particularly concerning bont gene clusters. Analysis of the content and locations of the bont gene clusters offers insights into common mechanisms of genetic transfer, chromosomal integration, and development of diversity among these genes.

Description: In this work we present results of the magnetic properties characterization of sediment samples from a brownfield site that is generating methane biogas in São Paulo–Brazil. We applied interpretation procedures (frequency dependent susceptibility and time-dependent Isothermal Remanent Magnetization) appropriate to study the ultrafine magnetic fraction response of the samples. The higher content of superparamagnetic (SP) particles correlates well with the detected biogas pockets, suggesting that the methanogens activity produces these ultrafine particles, different from the magnetic particles at other depth levels. We propose the use of two simple measurement and interpretation techniques to identify such magnetic particles fingerprints. The results presented here support the use of environmental magnetism techniques to investigate biogeochemical processes of anaerobic microbial activity.

Description: Distributional shifts driven by Quaternary climatic oscillations have been suggested to cause interspecific hybridization and introgression. In this study, we aimed to test this hypothesis by using population transcriptomes and coalescent modeling of two alpine none-sister gentians. Previous studies suggested that historical hybridizations occurred between Gentiana siphonantha and G. straminea in the high-altitude Qinghai-Tibet Plateau although both species are not sister to each other with the most recent divergence. In the present study, we sequenced transcriptomes of 33 individuals from multiple populations of G. siphonantha and G. straminea. The two species are well delimited by nuclear genomic SNPs while phylogenetic analyses of plastomes clustered one G. straminea individual into the G. siphonantha group. Further population structure analyses of the nuclear SNPs suggested that two populations of G. siphonantha were admixed with around 15% ancestry from G. straminea. These analyses suggested genetic introgressions from G. straminea to G. siphonantha. In addition, our coalescent-based modeling results revealed that gene flow occurred between the two species since Last Glacier Maximum after their initial divergence, which might have leaded to the observed introgressions. Our results underscore the significance of transcriptome population data in determining timescale of interspecific gene flow and direction of the resulting introgression.

Description: Infants hospitalized for critical illnesses are at a high risk of undernutrition because of increased nutrient requirements (due to increased metabolism) and decreased nutrient intake (due to disease-related problems such as anorexia or feeding difficulties). This can result in a slowing down of their normal growth, referred to as “growth faltering.” Appropriate nutritional management of these infants is extremely important to avoid long-term adverse outcomes. Administration of energy- and nutrient-dense formula (ENDF; 100 kcal energy and 2.6 g protein per 100 mL, with added micronutrients) can be an effective means of increasing the nutrient and energy intake of these children. Despite the high prevalence of undernutrition and growth faltering among pediatric patients in India, there is a paucity of literature on the use of ENDF in Indian infants. Herein, we report the successful use of ENDF for the nutritional management of two infants hospitalized for growth faltering because of severe upper airway obstruction. The aim of nutritional management was to achieve satisfactory weight gain, which can lead to spontaneous resolution of upper airway obstruction. ENDF was initially administered to provide 50–100 kcal/kg/day, and the dose was gradually increased to 160–185 kcal/kg/day. Both infants tolerated the formula well and showed satisfactory weight gain. These cases clearly demonstrate that early administration of ENDF is an effective means of increasing nutrient and energy intake of critically ill infants, thereby facilitating catchup growth, without any notable adverse effects.

Description: Insulin resistance in obesity coincides with abnormalities in lipid profile and lipoprotein subclass distribution and size even before abnormalities in glucose homeostasis manifest. We aimed to assess this relationship in the absence of obesity. Insulin sensitivity (3-h intravenous glucose tolerance test and minimal modeling) and lipoprotein particle concentrations and sizes (proton nuclear magnetic resonance spectroscopy) were evaluated in 15 insulin-resistant and 15 insulin-sensitive lean Asians of Chinese descent with normal glucose tolerance, matched on age, sex, and body mass index. Despite a ~50% lower insulin sensitivity index (Si) in insulin-resistant than in insulin-sensitive subjects, which was accompanied by significantly greater acute insulin response to glucose (AIRg) and fasting insulin concentration but not different fasting glucose concentration, there were no significant differences between groups in the blood lipid profile (p ≥ 0.44) or the lipoprotein subclass concentrations (p ≥ 0.30) and particle sizes (p ≥ 0.43). We conclude that, contrary to observations in subjects with obesity, insulin resistance is not accompanied by unfavorable changes in the plasma lipid profile and lipoprotein particle concentrations and sizes in lean Asians with normal glucose tolerance. Therefore, insulin resistance at the level of glucose metabolism is mechanistically or temporally dissociated from lipid and lipoprotein metabolism.Trial Registration:clinicaltrials.gov, NCT03264001.

Description: Acute myeloid leukemia (AML) is a malignant disease of hematopoietic stem/progenitor cells, and most AML patients are in a severe state. Internal tandem duplication mutations in FLT3 gene (FLT3-ITD) detected in AML stem cells account for 20–30 percent of AML patients. In this study, we attempted to study the impact of the interaction of FLT3-ITD mutation and the CXCL12/CXCR4 axis in AML, and the possible mechanisms caused by the impact by bioinformatics. Gene set variation analysis (GSVA) revealed that the PI3K-Akt-mTOR pathway positively correlated with the status of FLT3-ITD mutation. Multiple survival analyses were performed on TCGA-AML to screen the prognostic-related genes, and RPS6KA1 and AP2M1 are powerful prognostic candidates for overall survival in AML. WGCNA, KEGG/GO analysis, and the functional roles of RPS6KA1 and AP2M1 in AML were clarified by correlation analysis. We found that the expression levels of RPS6KA1 and AP2M1 were significantly associated with chemoresistance of AML, and the CXCL12/CXCR4 axis would regulate RPS6KA1/AP2M1 expression. Besides, miR-138-5p, regulated by the CXCL12/CXCR4 axis, was the common miRNA target of RPS6KA1 and AP2M1. Taken together, the interaction of FLT3-ITD mutation and the CXCL12/CXCR4 axis activated the PI3K-Akt-mTOR pathway, and the increased expression of RPS6KA1 and AP2M1 caused by hsa-miR-138-5p downregulation regulates the multi-resistance gene expression leading to drug indications.

Description: Lysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. Target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo via its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. More recently, it was found that TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, this review illustrates how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.

Description: High-throughput sequencing of 16S rRNA amplicon has been extensively employed to perform microbiome characterization worldwide. As a culture-independent methodology, it has allowed high-level profiling of sample bacterial composition directly from samples. However, most studies are limited to information regarding relative bacterial abundances (sample proportions), ignoring scenarios in which sample microbe biomass can vary widely. Here, we use an equivolumetric protocol for 16S rRNA amplicon library preparation capable of generating Illumina sequencing data responsive to input DNA, recovering proportionality between observed read counts and absolute bacterial abundances within each sample. Under specified conditions, we show that the estimation of colony-forming units (CFU), the most common unit of bacterial abundance in classical microbiology, is challenged mostly by resolution and taxon-to-taxon variation. We propose Bayesian cumulative probability models to address such issues. Our results indicate that predictive errors vary consistently below one order of magnitude for total microbial load and abundance of observed bacteria. We also demonstrate our approach has the potential to generalize to previously unseen bacteria, but predictive performance is hampered by specific taxa of uncommon profile. Finally, it remains clear that high-throughput sequencing data are not inherently restricted to sample proportions only, and such technologies bear the potential to meet the working scales of traditional microbiology.

Description: IFT20 is a subunit of the intraflagellar transport (IFT) system essential for the formation and function of cilia. Besides predominant research in the cilia field, some IFT subunits perform extraciliary roles in non-ciliated cancer cells. However, the specific roles of IFT subunits in tumorigenesis remain unknown. Here, we found that knockout of IFT20 in mouse breast cancer cells lacking primary cilia promoted epithelial mesenchymal transitions (EMTs), active lamellipodia formation, and cell migration. IFT20 localized at the trans-Golgi and trans-Golgi network (TGN), and displayed vesicular co-distributions with Rab8a, the marker of TGN-to-plasma membrane vesicular trafficking. Proximity-dependent biotin identification (BioID) and colocalization analyzes showed that Numb and Ctnnal1, whose depletion promoted cell migration, co-localized with IFT20 at the trans-Golgi/TGN or intracellular transport vesicles. Furthermore, Strep-Tactin pulldown assays revealed an interaction between IFT20 and Ctnnal1 or Numb. Loss of IFT20 lowered the expression of actin-associated Tagln2, whose knockdown promoted cell migration. Thus, the extraciliary function of ITF20 in breast cancer cell was associated with the negative regulation of migration.

Description: Tropical theileriosis is the disease caused by tick-transmitted apicomplexan parasite Theileria annulata, which has ability to transform bovine leukocytes, including B cells, macrophage cells, and dendritic cells. The T. annulata transformed cells are characterized as uncontrolled proliferation and shared some cancer-like phenotypes. The mechanism of the transformation by T. annulata is still not understood well. In previous reports, the subtelomere-encoded variable secreted proteins (SVSP) of T. parva were considered to contribute to phenotypic changes of the host cell, but the role of SVSP of T. annulata in host-pathogen relationship remains unknown. In the present study, a member of SVSP family, TA05575 of T. annulata was selected as the target molecule to analyze its expression profiles in different life cycle stages of T. annulata by qPCR and investigate its subcellular distribution of different passages of T. annulata transformed cells using confocal experiments. From the results, the transcription level of TA05575 at schizont stage was significantly higher than the other two life stages of T. annulata, and the protein of TA05575 was mainly distributed in nucleus of T. annulata infected cells. In addition, the potential proteins of host cells interacting with TA05575 were screened by Yeast-two hybrid system. The results of Co-IP experiment confirmed that TA05575 interacted with RBMX2-like protein that participated in transcription regulation of cells. In addition, a novel BiFC assay and flow cytometry were carried out, and the results further revealed that TA05575-RBMX2-like pair was directly interacted in cell context. Moreover, this interacting pair was found to distribute in intracellular compartments of HEK293T cells by using confocal microscopy. The results of the present study suggest that TA05575 may contribute for cells transformation due its distribution. According to the function of RBMX2, the interaction of TA05575 and RMMX2-like will provide a new information to further understand the mechanisms of cells transformation by T. annulata.

Description: Biocide use is essential and ubiquitous, exposing microbes to sub-inhibitory concentrations of antiseptics, disinfectants, and preservatives. This can lead to the emergence of biocide resistance, and more importantly, potential cross-resistance to antibiotics, although the degree, frequency, and mechanisms that give rise to this phenomenon are still unclear. Here, we systematically performed adaptive laboratory evolution of the gut bacteria Escherichia coli in the presence of sub-inhibitory, constant concentrations of ten widespread biocides. Our results show that 17 out of 40 evolved strains (43%) also decreased the susceptibility to medically relevant antibiotics. Through whole-genome sequencing, we identified mutations related to multidrug efflux proteins (mdfA and acrR), porins (envZ and ompR), and RNA polymerase (rpoA and rpoBC), as mechanisms behind the resulting (cross)resistance. We also report an association of several genes (yeaW, pyrE, yqhC, aes, pgpA, and yeeP-isrC) and specific mutations that induce cross-resistance, verified through mutation repairs. A greater capacity for biofilm formation with respect to the parent strain was also a common feature in 11 out of 17 (65%) cross-resistant strains. Evolution in the biocides chlorophene, benzalkonium chloride, glutaraldehyde, and chlorhexidine had the most impact in antibiotic susceptibility, while hydrogen peroxide and povidone-iodine the least. No cross-resistance to antibiotics was observed for isopropanol, ethanol, sodium hypochlorite, and peracetic acid. This work reinforces the link between exposure to biocides and the potential for cross-resistance to antibiotics, presents evidence on the underlying mechanisms of action, and provides a prioritized list of biocides that are of greater concern for public safety from the perspective of antibiotic resistance.Significance StatementBacterial resistance and decreased susceptibility to antimicrobials is of utmost concern. There is evidence that improper biocide (antiseptic and disinfectant) use and discard may select for bacteria cross-resistant to antibiotics. Understanding the cross-resistance emergence and the risks associated with each of those chemicals is relevant for proper applications and recommendations. Our work establishes that not all biocides are equal when it comes to their risk of inducing antibiotic resistance; it provides evidence on the mechanisms of cross-resistance and a risk assessment of the biocides concerning antibiotic resistance under residual sub-inhibitory concentrations.

Description: During primary tumorigenesis isolated cancer cells may undergo genetic or epigenetic changes that render them responsive to additional intrinsic or extrinsic cues, so that they enter a transitional state and eventually acquire an aggressive, metastatic phenotype. Among these changes is the alteration of the cell metabolic/catabolic machinery that creates the most permissive conditions for invasion, dissemination, and survival. The lysosomal system has emerged as a crucial player in this malignant transformation, making this system a potential therapeutic target in cancer. By virtue of their ubiquitous distribution in mammalian cells, their multifaced activities that control catabolic and anabolic processes, and their interplay with other organelles and the plasma membrane (PM), lysosomes function as platforms for inter- and intracellular communication. This is due to their capacity to adapt and sense nutrient availability, to spatially segregate specific functions depending on their position, to fuse with other compartments and with the PM, and to engage in membrane contact sites (MCS) with other organelles. Here we review the latest advances in our understanding of the role of the lysosomal system in cancer progression. We focus on how changes in lysosomal nutrient sensing, as well as lysosomal positioning, exocytosis, and fusion perturb the communication between tumor cells themselves and between tumor cells and their microenvironment. Finally, we describe the potential impact of MCS between lysosomes and other organelles in propelling cancer growth and spread.

Description: During bone resorption, the osteoclast must sustain an extraordinarily low pH environment, withstand immense ionic pressures, and coordinate nutrient and waste exchange across its membrane to sustain its unique structural and functional polarity. To achieve this, osteoclasts are equipped with an elaborate set of membrane transport proteins (pumps, transporters and channels) that serve as molecular ‘gatekeepers’ to regulate the bilateral exchange of ions, amino acids, metabolites and macromolecules across the ruffled border and basolateral domains. Whereas the importance of the vacuolar-ATPase proton pump and chloride voltage-gated channel 7 in osteoclasts has long been established, comparatively little is known about the contributions of other membrane transport proteins, including those categorized as secondary active transporters. In this Special Issue review, we provide a contemporary update on the ‘ins and outs’ of membrane transport proteins implicated in osteoclast differentiation, function and bone homeostasis and discuss their therapeutic potential for the treatment of metabolic bone diseases.

Description: The records of maintenance activities are required for modeling the track irregularity deterioration process. However, it is hard to guarantee the completeness and accuracy of the maintenance records. To tackle this problem, an adaptive piecewise modeling framework for the rail track deterioration process driven by historical measurement data from the comprehensive inspection train (referred to as CIT) is proposed. The identification of when maintenance activities occurred is reformulated as a model selection optimization problem based on Bayesian Information Criterion. An efficient solution algorithm utilizing adaptive thresholding and dynamic programming is proposed for solving this optimization problem. This framework’s validity and practicability are illustrated by the measurement data from the CIT inspection of the mileage section of K21 + 184 to K220 + 308 on the Nanchang-Fuzhou railway track from 2014 to 2019. The results indicate that this framework can overcome the disturbance of contaminated measurement data and accurately estimate when maintenance activities were undertaken without any historical maintenance records. What is more, the adaptive piecewise fitting model provided by this framework can describe the irregular deterioration process of corresponding rail track sections.

Description: Tubular Aggregate Myopathy (TAM) is a hereditary ultra-rare muscle disorder characterized by muscle weakness and cramps or myasthenic features. Biopsies from TAM patients show the presence of tubular aggregates originated from sarcoplasmic reticulum due to altered Ca2+ homeostasis. TAM is caused by gain-of-function mutations in STIM1 or ORAI1, proteins responsible for Store-Operated-Calcium-Entry (SOCE), a pivotal mechanism in Ca2+ signaling. So far there is no cure for TAM and the mechanisms through which STIM1 or ORAI1 gene mutation lead to muscle dysfunction remain to be clarified. It has been established that post-natal myogenesis critically relies on Ca2+ influx through SOCE. To explore how Ca2+ homeostasis dysregulation associated with TAM impacts on muscle differentiation cascade, we here performed a functional characterization of myoblasts and myotubes deriving from patients carrying STIM1 L96V mutation by using fura-2 cytofluorimetry, high content imaging and real-time PCR. We demonstrated a higher resting Ca2+ concentration and an increased SOCE in STIM1 mutant compared with control, together with a compensatory down-regulation of genes involved in Ca2+ handling (RyR1, Atp2a1, Trpc1). Differentiating STIM1 L96V myoblasts persisted in a mononuclear state and the fewer multinucleated myotubes had distinct morphology and geometry of mitochondrial network compared to controls, indicating a defect in the late differentiation phase. The alteration in myogenic pathway was confirmed by gene expression analysis regarding early (Myf5, Mef2D) and late (DMD, Tnnt3) differentiation markers together with mitochondrial markers (IDH3A, OGDH). We provided evidences of mechanisms responsible for a defective myogenesis associated to TAM mutant and validated a reliable cellular model usefull for TAM preclinical studies.

Description: Scaffold-free cartilage-sheet technology can stably regenerate high-quality cartilage tissue in vivo. However, uncontrolled shape maintenance and mechanical strength greatly hinder its clinical translation. Decalcified bone matrix (DBM) has high porosity, a suitable pore structure, and good biocompatibility, as well as controlled shape and mechanical strength. In this study, cartilage sheet was prepared into engineered cartilage gel (ECG) and combined with DBM to explore the feasibility of regenerating 3D cartilage with controlled shape and mechanical strength. The results indicated that ECG cultured in vitro for 3 days (3 d) and 15 days (15 d) showed good biocompatibility with DBM, and the ECG–DBM constructs successfully regenerated viable 3D cartilage with typical mature cartilage features in both nude mice and autologous goats. Additionally, the regenerated cartilage had comparable mechanical properties to native cartilage and maintained its original shape. To further determine the optimal seeding parameters for ECG, the 3 d ECG regenerated using human chondrocytes was diluted in different concentrations (1:3, 1:2, and 1:1) for seeding and in vivo implantation. The results showed that the regenerated cartilage in the 1:2 group exhibited better shape maintenance and homogeneity than the other groups. The current study established a novel mode of 3D cartilage regeneration based on the design concept of steel (DBM)-reinforced concrete (ECG) and successfully regenerated homogenous and mature 3D cartilage with controlled shape and mechanical strength, which hopefully provides an ideal cartilage graft for the repair of various cartilage defects.

Description: As ecosystem-based fisheries management becomes more ingrained into the way fisheries agencies do business, a need for ecosystem and multispecies models arises. Yet ecosystems are complex, and model uncertainty can be large. Model ensembles have historically been used in other disciplines to address model uncertainty. To understand the benefits and limitations of multispecies model ensembles (MMEs), cases where they have been used in the United States to address fisheries management issues are reviewed. The cases include: (1) development of ecological reference points for Atlantic Menhaden, (2) the creation of time series to relate harmful algal blooms to grouper mortality in the Gulf of Mexico, and (3) fostering understanding of the role of forage fish in the California Current. Each case study briefly reviews the management issue, the models used and model synthesis approach taken, and the outcomes and lessons learned from the application of MMEs. Major conclusions drawn from these studies highlight how the act of developing an ensemble model suite can improve the credibility of multispecies models, how qualitative synthesis of projections can advance system understanding and build confidence in the absence of quantitative treatments, and how involving a diverse set of stakeholders early is useful for ensuring the utility of the models and ensemble. Procedures for review and uptake of information from single-species stock assessment models are well established, but the absence of well-defined procedures for MMEs in many fishery management decision-making bodies poses a major obstacle. The benefits and issues identified here should help accelerate the design, implementation, and utility of MMEs in applied fisheries contexts.

Description: Nowadays, most of the preimplantation genetic testing (PGT) is performed with a strategy of comprehensive chromosome screening and trophectoderm biopsy. Nevertheless, patients with ovarian insufficiency may not have competent blastocysts. In the present study, we aimed to establish the value of multiple annealing and looping-based amplification cycle (MALBAC)-based next-generation sequencing (NGS) for PGT in day-3 embryos. A total of 94.3% (1168/1239) of embryos yielded informative results, and the overall embryo euploid rate was 21.9% (256/1168). Overall, 225 embryos were transferred in 169 cycles with a clinical pregnancy rate of 49.1% (83/169). The live birth and implantation rates were 47.3% (80/169) and 44.4% (100/225), respectively. Double embryos transfer showed higher clinical pregnancy and live birth rates compared with single embryo transfer, but the implantation rates were similar (44.2% vs. 44.6%, P 〉 0.05). The euploid rate for reciprocal translocations (16.1%) was significantly lower than that for Robertsonian translocations (28.0%, P 〈 0.01) and inversions (28.0%, P 〈 0.01). However, higher percentages of embryos with de novo abnormalities were observed with Robertsonian translocations (23.3%, P 〈 0.01) and inversions (30.5%, P 〈 0.01) than with reciprocal translocations (11.6%). We demonstrated that NGS for PGT on day-3 embryos is an effective clinical application, particularly for patients with a diminished ovarian reserve and limited embryos.

Description: Micro and nanoplastics are fragments with dimensions less than a millimeter invading all terrestrial and marine environments. They have become a major global environmental issue in recent decades and, indeed, recent scientific studies have highlighted the presence of these fragments all over the world even in environments that were thought to be unspoiled. Analysis of micro/nanoplastics in isolated samples from abiotic and biotic environmental matrices has become increasingly common. Hence, the need to find valid techniques to identify these micro and nano-sized particles. In this review, we discuss the current and potential identification methods used in microplastic analyses along with their advantages and limitations. We discuss the most suitable techniques currently available, from physical to chemical ones, as well as the challenges to enhance the existing methods and develop new ones. Microscopical techniques (i.e., dissect, polarized, fluorescence, scanning electron, and atomic force microscopy) are one of the most used identification methods for micro/nanoplastics, but they have the limitation to produce incomplete results in analyses of small particles. At present, the combination with chemical analysis (i.e., spectroscopy) overcome this limit together with recently introduced alternative approaches. For example, holographic imaging in microscope configuration images microplastics directly in unfiltered water, thus discriminating microplastics from diatoms and differentiates different sizes, shapes, and plastic types. The development of new analytical instruments coupled with each other or with conventional and innovative microscopy could solve the current problems in the identification of micro/nanoplastics.

Description: Achieving goals for conservation and sustainability using nature, decision-making, and policy planning requires accurate modes of description to understand the relationship between society and the environment. Despite most planning strategies being constrained by policy objectives, planning is expected to be more participatory and inclusive of the plurality of values and all types of socio-spatial relationships. Based on Lefebvre's social theory, the objectives of this work are to propose a triad of spaces as a helpful framework to analyse nature's contributions to people (NCP), describe different spaces socially constructed by coffee and potato farmer communities in Colombia, and explore the implications for various kinds of decision-making. Using qualitative research methods, this manuscript describes three spaces: lived spaces as intangible spaces based on local, religious, and ceremonial values of NCP; perceived spaces include farmer spatial organization according to the ties of kinship and the downward course of streams, the incidence of negative NCP, such as plant diseases, and types of management crops; and conceived spaces as the overlapping of different spatial views of territorial planning. Given that NCP has great potential to integrate diversity of values about nature and cultural contexts into decision-making, the triad of social spaces offers a spatial dimension to the analyses of NCP. Lived spaces make non-material NCP and non-instrumental values more visible. Perceived spaces highlight material NCP and regulating NCP with the view that maintenance of NCP in the future is essential for relational and instrumental values, e.g., how material NCP and regulating NCP of landscapes are perceived and by whom. Conceived spaces emphasize the predominance of the intrinsic biophysical values of NCP. Thus, the triad of social spaces as a conceptual framework can be useful in the operationalization of NCP in environmental management, the governance of schemes, and the implementation of land-use plans at the local scale. By thinking of these spaces relationally, such insight can inform and enhance decisions and policymaking about the value of places toward the priorities of meeting management. The results of the study emphasize the important policy implications of recognizing lived and perceived spaces in decision-making and highlight the role of NCP in facilitating the communication of these spaces to support spatial management of land use.

Description: Drug repurposing is also termed as drug repositioning or therapeutic switching. This method is applied to identify the novel therapeutic agents from the existing FDA approved clinically used drug molecules. It is considered as an efficient approach to develop drug candidates with new pharmacological activities or therapeutic properties. As the drug discovery is a costly, time-consuming, laborious, and highly risk process, the novel approach of drug repositioning is employed to increases the success rate of drug development. This strategy is more advantageous over traditional drug discovery process in terms of reducing duration of drug development, low-cost, highly efficient and minimum risk of failure. In addition to this, World health organization declared Coronavirus disease (COVID-19) as pandemic globally on February 11, 2020. Currently, there is an urgent need to develop suitable therapeutic agents for the prevention of the outbreak of COVID-19. So, various investigations were carried out to design novel drug molecules by utilizing different approaches of drug repurposing to identify drug substances for treatment of COVID-19, which can act as significant inhibitors against viral proteins. It has been reported that COVID-19 can infect human respiratory system by entering into the alveoli of lung via respiratory tract. So, the infection occurs due to specific interaction or binding of spike protein with angiotensin converting enzyme-2 (ACE-2) receptor. Hence, drug repurposing strategy is utilized to identify suitable drugs by virtual screening of drug libraries. This approach helps to determine the binding interaction of drug candidates with target protein of coronavirus by using computational tools such as molecular similarity and homology modeling etc. For predicting the drug-receptor interactions and binding affinity, molecular docking study and binding free energy calculations are also performed. The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19.

Description: During pepper and tomato production seasons in 2013–2017, large-scale virus disease surveys were conducted in different regions of Yunnan Province, China. A total of 1,267 pepper and tomato samples with various virus-like symptoms were collected and analyzed for virus infections through dot enzyme-linked immunosorbent assay (dot-ELISA), polymerase chain reaction (PCR), and reverse-transcription (RT)-PCR. The detection results showed that 19 different viruses were present in about 50.9% of the assayed samples, and among these viruses, seven viruses were found in both pepper and tomato samples. Mixed infections with two to three of the 15 identified mixed infection types were found in the pepper samples and 10 identified mixed infection types were found in the tomato samples. Among the infected samples, Tomato spotted wilt orthotospovirus (TSWV) was the most common virus, with a detection rate of about 20.0% followed by Pepper vein yellows virus (PeVYV, 13.0%). This survey revealed for the first time that pepper is a natural host of Tobacco vein distorting virus (TVDV) worldwide and tomato is a natural host of Potato leafroll virus (PLRV) in China. PeVYV, Tobacco mild green mosaic virus (TMGMV) and Wild tomato mosaic virus (WTMV) were first time found in pepper and Tomato mottle mosaic virus (ToMMV) and Chilli veinal mottle virus (ChiVMV) were first time found in tomato in Yunnan Province. Finally, the virus incidences were higher in Kunming, Yuxi, Chuxiong, and Honghe region than other regions.

Description: Real-time, nondestructive, and accurate estimation of plant water status is important to the precision irrigation of winter wheat. The objective of this study was to develop a method to estimate plant water content (PWC) by using canopy spectral proximal sensing data. Two experiments under different water stresses were conducted in 2014–2015 and 2015–2016. The PWC and canopy reflectance of winter wheat were collected at different growth stages (the jointing, booting, heading, flowering, and filling stages in 2015 and the jointing, booting, flowering, and filling stages in 2016). The performance of different spectral transformation approaches was further compared. Based on the optimal pretreatment, partial least squares regression (PLSR) and four combination methods [i.e., PLSR-stepwise regression (SR), PLSR-successive projections algorithm (SPA), PLSR-random frog (RF), and PLSR-uninformative variables elimination (UVE)] were used to extract the sensitive bands of PWC. The results showed that all transformed spectra were closely correlated to PWC. The PLSR models based on the first derivative transformation method exhibited the best performance (coefficient of determination in calibration, R2C = 0.96; root mean square error in calibration, RMSEC = 20.49%; ratio of performance to interquartile distance in calibration, RPIQC = 9.19; and coefficient of determination in validation, R2V = 0.86; root mean square error in validation, RMSEV = 46.27%; ratio of performance to interquartile distance in validation, RPIQV = 4.34). Among the combination models, the PLSR model established with the sensitive bands from PLSR-RF demonstrated a good performance for calibration and validation (R2C = 0.99, RMSEC = 11.53%, and RPIQC = 16.34; and R2V = 0.84, RMSEV = 44.40%, and RPIQV = 4.52, respectively). This study provides a theoretical basis and a reference for estimating PWC of winter wheat by using canopy spectral proximal sensing data.

Description: Spikelet number is an important target trait for wheat yield improvement. Thus, the identification and verification of novel quantitative trait locus (QTL)/genes controlling spikelet number are essential for dissecting the underlying molecular mechanisms and hence for improving grain yield. In the present study, we constructed a high-density genetic map for the Kechengmai1/Chuanmai42 doubled haploid (DH) population using 13,068 single-nucleotide polymorphism (SNP) markers from the Wheat 55K SNP array. A comparison between the genetic and physical maps indicated high consistence of the marker orders. Based on this genetic map, a total of 27 QTLs associated with total spikelet number per spike (TSN) and fertile spikelet number per spike (FSN) were detected on chromosomes 1B, 1D, 2B, 2D, 3D, 4A, 4D, 5A, 5B, 5D, 6A, 6B, and 7D in five environments. Among them, five QTLs on chromosome 2D, 3D, 5A, and 7D were detected in multiple environments and combined QTL analysis, explaining the phenotypic variance ranging from 3.64% to 23.28%. Particularly, QTsn/Fsn.cib-3D for TSN and FSN [phenotypic variation explained (PVE) = 5.97–23.28%, limit of detection (LOD) = 3.73–18.51] is probably a novel locus and located in a 4.5-cM interval on chromosome arm 3DL flanking by the markers AX-110914105 and AX-109429351. This QTL was further validated in other two populations with different genetic backgrounds using the closely linked Kompetitive Allele-Specific PCR (KASP) marker KASP_AX-110914105. The results indicated that QTsn/Fsn.cib-3D significantly increased the TSN (5.56–7.96%) and FSN (5.13–9.35%), which were significantly correlated with grain number per spike (GNS). We also preliminary analyzed the candidate genes within this locus by sequence similarity, spatial expression patterns, and collinearity analysis. These results provide solid foundation for future fine mapping and cloning of QTsn/Fsn.cib-3D. The developed and validated KASP markers could be utilized in molecular breeding aiming to increase the grain yield in wheat.

Description: Clonal plants in heterogeneous environments can benefit from their habitat selection behavior, which enables them to utilize patchily distributed resources efficiently. It has been shown that such behavior can be strongly influenced by their memories on past environmental interactions. Epigenetic variation such as DNA methylation was proposed to be one of the mechanisms involved in the memory. Here, we explored whether the experience with Ultraviolet B (UV-B) radiation triggers epigenetic memory and affects clonal plants’ foraging behavior in an UV-B heterogeneous environment. Parental ramets of Glechoma longituba were exposed to UV-B radiation for 15 days or not (controls), and their offspring ramets were allowed to choose light environment enriched with UV-B or not (the species is monopodial and can only choose one environment). Sizes and epigenetic profiles (based on methylation-sensitive amplification polymorphism analysis) of parental and offspring plants from different environments were also analyzed. Parental ramets that have been exposed to UV-B radiation were smaller than ramets from control environment and produced less and smaller offspring ramets. Offspring ramets were placed more often into the control light environment (88.46% ramets) than to the UV-B light environment (11.54% ramets) when parental ramets were exposed to UV-B radiation, which is a manifestation of “escape strategy.” Offspring of control parental ramets show similar preference to the two light environments. Parental ramets exposed to UV-B had lower levels of overall DNA methylation and had different epigenetic profiles than control parental ramets. The methylation of UV-B-stressed parental ramets was maintained among their offspring ramets, although the epigenetic differentiation was reduced after several asexual generations. The parental experience with the UV-B radiation strongly influenced foraging behavior. The memory on the previous environmental interaction enables clonal plants to better interact with a heterogeneous environment and the memory is at least partly based on heritable epigenetic variation.

Description: Working nonstandard work schedules is often associated with increased sedentary behavior and risk of sleep disorders. Night shift workers are prone to accumulating sleep debt, which they recover by sleeping during the day. The effect on daytime activity levels is unknown. The present study aims to objectively assess whether daytime sleep could affect daytime activity levels of shift worker nurses, resulting in an accumulation of their activity debt differently between working and rest periods. The study population (N = 37; mean age 41.7 ± 9.1 years) was composed of orthopedic nurses working on a rotating schedule, including either a night shift (NS) or only day/afternoon shift (DS). Actigraph monitoring lasted both on the working and the rest period. For the NS nurses, the working period recorded higher daytime activity levels than the rest period, while daytime sleep during the working and rest periods was similar. Conversely, DS nurses showed higher daytime activity levels and shorter daytime sleep during the working period. NS nurses were less active than DS nurses during the working period, probably because NS tended to have a longer daytime sleep. During the rest period, daytime activity levels for both groups were decreased. For NS nurses, sleep recorded the better sleep parameters during the rest period, while sleep parameters did not show significant differences between the working and the rest periods in DS. During the working period, NS nurses slept worse than the DS nurses. Both groups tended to accumulate a debt in daytime activity levels during the rest period. While daytime sleep may be an excellent way to counteract sleep debt and increase sleep duration over 24 h period, on the other hand, it makes nurses less active.

Description: The Arctic is experiencing dramatic changes including increases in precipitation, glacial melt, and permafrost thaw, resulting in increasing freshwater runoff to coastal waters. During the melt season, terrestrial runoff delivers carbon- and nutrient-rich freshwater to Arctic coastal waters, with unknown consequences for the microbial communities that play a key role in determining the cycling and fate of terrestrial matter at the land-ocean interface. To determine the impacts of runoff on coastal microbial (bacteria and archaea) communities, we investigated changes in pelagic microbial community structure between the early (June) and late (August) melt season in 2018 in the Isfjorden system (Svalbard). Amplicon sequences of the 16S rRNA gene were generated from water column, river and sediment samples collected in Isfjorden along fjord transects from shallow river estuaries and glacier fronts to the outer fjord. Community shifts were investigated in relation to environmental gradients, and compared to river and marine sediment microbial communities. We identified strong temporal and spatial reorganizations in the structure and composition of microbial communities during the summer months in relation to environmental conditions. Microbial diversity patterns highlighted a reorganization from rich communities in June toward more even and less rich communities in August. In June, waters enriched in dissolved organic carbon (DOC) provided a niche for copiotrophic taxa including Sulfitobacter and Octadecabacter. In August, lower DOC concentrations and Atlantic water inflow coincided with a shift toward more cosmopolitan taxa usually associated with summer stratified periods (e.g., SAR11 Clade Ia), and prevalent oligotrophic marine clades (OM60, SAR92). Higher riverine inputs of dissolved inorganic nutrients and suspended particulate matter also contributed to spatial reorganizations of communities in August. Sentinel taxa of this late summer fjord environment included taxa from the class Verrucomicrobiae (Roseibacillus, Luteolibacter), potentially indicative of a higher fraction of particle-attached bacteria. This study highlights the ecological relevance of terrestrial runoff for Arctic coastal microbial communities and how its impacts on biogeochemical conditions may make these communities susceptible to climate change.

Description: Polyploids play an important role in the breeding of plant for superior characteristics, and many reports have focused on the effects upon photosynthesis from polyploidization in some plant species recently, yet surprisingly little of this is known for barley. In this study, homozygous diploid and tetraploid plants, derived from microspore culturing of the barley cultivar “H30,” were used to assess differences between them in their cellular, photosynthetic, and transcriptomic characteristics. Our results showed that tetraploid barley has the distinct characteristics of polyploids, namely thicker and heavier leaves, enlarged stomata size or stomatal guard cell size, and more photosynthetic pigments and improved photosynthesis (especially under high light intensity). This enhanced photosynthesis of tetraploid barley was confirmed by several photosynthetic parameters, including net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr), maximum net photosynthetic rate (Pmax), light saturation point (LSP), maximum RuBP saturated rate carboxylation (Vcmax), and maximum rate of electron transport (Jmax). Transcriptomic analyses revealed that just ~2.3% of all detected genes exhibited differential expression patterns [i.e., differentially expressed genes (DEGs)], and that most of these – 580 of 793 DEGs in total – were upregulated in the tetraploid barley. The follow-up KEGG analysis indicated that the most enriched pathway was related to photosynthesis-antenna proteins, while the downregulation of DEGs was related mainly to the light-harvesting cholorophyII a/b-binding protein (Lhcb1) component, both validated by quantitative PCR (qPCR). Taken together, our integrated analysis of morphology, photosynthetic physiology, and transcriptome provides evidences for understanding of how polyploidization enhances the photosynthetic capacity in tetraploids of barley.

Description: The two-spotted spider mite (TSSM; Tetranychus urticae) is a ubiquitous polyphagous arthropod pest that has a major economic impact on the tomato (Solanum lycopersicum) industry. Tomato plants have evolved broad defense mechanisms regulated by the expression of defense genes, phytohormones, and secondary metabolites present constitutively and/or induced upon infestation. Although tomato defense mechanisms have been studied for more than three decades, only a few studies have compared domesticated cultivars' natural mite resistance at the molecular level. The main goal of our research was to reveal the molecular differences between two tomato cultivars with similar physical (trichome morphology and density) and agronomic traits (fruit size, shape, color, cluster architecture), but with contrasting TSSM susceptibility. A net house experiment indicated a mite-resistance difference between the cultivars, and a climate-controlled performance and oviposition bioassay supported these findings. A transcriptome analysis of the two cultivars after 3 days of TSSM infestation, revealed changes in the genes associated with primary and secondary metabolism, including salicylic acid and volatile biosynthesis (volatile benzenoid ester and monoterpenes). The Terpene synthase genes, TPS5, TPS7, and TPS19/20, encoding enzymes that synthesize the monoterpenes linalool, β-myrcene, limonene, and β-phellandrene were highly expressed in the resistant cultivar. The volatile profile of these cultivars upon mite infestation for 1, 3, 5, and 7 days, revealed substantial differences in monoterpenoid and phenylpropanoid volatiles, results consistent with the transcriptomic data. Comparing the metabolic changes that occurred in each cultivar and upon mite-infestation indicated that monoterpenes are the main metabolites that differ between cultivars (constitutive levels), while only minor changes occurred upon TSSM attack. To test the effect of these volatile variations on mites, we subjected both the TSSM and its corresponding predator, Phytoseiulus persimilis, to an olfactory choice bioassay. The predator mites were only significantly attracted to the TSSM pre-infested resistant cultivar and not to the susceptible cultivar, while the TSSM itself showed no preference. Overall, our findings revealed the contribution of constitutive and inducible levels of volatiles on mite performance. This study highlights monoterpenoids' function in plant resistance to pests and may inform the development of new resistant tomato cultivars.

Description: An increasing number of web services providing convenient access to seismological data have become available in recent years. A huge effort at multiple levels was required to achieve this goal and the seismological community was engaged in the standardization of both data formats and web services. Although access to seismological data is much easier than in the past, users encounter problems because of the large number of web services, and due to the complexity of the discipline-specific data encodings. In addition, instead of adopting cross-disciplinary standards such as those by the Open Geospatial Consortium (OGC), most seismological web services created their own standards, primarily those by the International Federation of Digital Seismograph Networks (FDSN). This article introduces “QQuake,” a plugin for QGIS—the Open Source Geographic Information System—that aims at making access to seismological data easier. The plugin is based on an Open Source code available on GitHub, and it is designed in a modular and customizable way, allowing users to easily include new web services.

Description: Fuel cell technology is continuously gaining ground in E-mobility applications. Fuel cells require a constant supply of pressurized air, for which high-speed turbo compressors with air bearings are an optimal choice to reduce size, guarantee oil-free operation required for the lifetime of the fuel cell, and increase efficiency. However, the inverter driving the electric motor of the turbo compressor does not scale down with increasing speed; therefore, other technology advances are required to achieve an overall compressor system with low weight. New power electronic topologies (double-bridge voltage sources inverter), cutting edge power semiconductor technology (gallium nitride), and multiobjective optimization techniques allow reducing the inverter size, increasing inverter efficiency, and improving the output current quality and in return lowering the losses in the electric motor. This enables the electrical, mechanical, and thermal integration of the inverter into the compressor housing of very high-speed and compact turbo compressors, thereby reducing the size and weight of the overall compressor system by a factor of two. Furthermore, a turbo compressor with an integrated inverter reduces complexity and cost for operators with savings in casing, cables, coolant piping, and connectors and reduces EMI noise by shielding the high-frequency motor currents with one housing. Beside its main application for fuel cell air supply, the advantages gained by an integrated inverter can also be used in other boosting and air handling applications such as advanced air and exhaust handling in combustion engines. The proposed integration concept is verified with a 280,000 rpm, 1 kW turbo compressor, targeted for the Balance of Plant (BoP) of a 5–15 kW fuel cell. The experimental results show that the temperature limits on the power electronics parts can be kept below the limit of 90 °C up to a coolant temperature of 55 °C, and beside the advantage of lower cabling effort, the efficiency of the compressor system (turbo compressor and integrated inverter) is increased by 5.5% compared to a turbo compressor without an integrated inverter.

Description: Hypertension is one predictive factor for stroke and heart ischemic disease. Nowadays, it is considered an inflammatory disease with elevated cytokine levels, oxidative stress, and infiltration of immune cells in several organs including heart, kidney, and vessels, which contribute to the hypertension-associated cardiovascular damage. Macrophages, the most abundant immune cells in tissues, have a high degree of plasticity that is manifested by polarization in different phenotypes, with the most well-known being M1 (proinflammatory) and M2 (anti-inflammatory). In hypertension, M1 phenotype predominates, producing inflammatory cytokines and oxidative stress, and mediating many mechanisms involved in the pathogenesis of this disease. The increase in the renin–angiotensin system and sympathetic activity contributes to the macrophage mobilization and to its polarization to the pro-inflammatory phenotype. Heme oxygenase-1 (HO-1), a phase II detoxification enzyme responsible for heme catabolism, is induced by oxidative stress, among others. HO-1 has been shown to protect against oxidative and inflammatory insults in hypertension, reducing end organ damage and blood pressure, not only by its expression at the vascular level, but also by shifting macrophages toward the anti-inflammatory phenotype. The regulatory role of heme availability for the synthesis of enzymes involved in hypertension development, such as cyclooxygenase or nitric oxide synthase, seems to be responsible for many of the beneficial HO-1 effects; additionally, the antioxidant, anti-inflammatory, antiapoptotic, and antiproliferative effects of the end products of its reaction, carbon monoxide, biliverdin/bilirubin, and Fe2+, would also contribute. In this review, we analyze the role of HO-1 in hypertensive pathology, focusing on its expression in macrophages.

Description: Volcanic activity at the Santiaguito dome complex (Guatemala) is characterized by lava extrusion interspersed with small, regular, gas-and-ash explosions that are believed to result from shallow magma fragmentation; yet, their triggering mechanisms remain debated. Given that the understanding of source processes at volcanoes is essential to risk assessments of future eruptions, this study seeks to shed light on those processes. We use data from a permanent seismic and infrasound network at Santiaguito volcano, Guatemala, established in 2018 and additional temporary stations, including a seismic array deployed during a 13-day field investigation in January 2019 to analyze and resolve the source characteristics of fragmentation leading to gas-and-ash explosions. Seismic data gathered within a distance of 4.5 km from the vent show a weak seismic signal 2–6 s prior to the explosions and associated main seismic signal. To resolve the source location and origin of the seismic signals, we first used ambient noise analysis to assess seismic velocities in the subsurface and then used two-dimensional spectral element modeling (SPECFEM2D) to simulate seismic waveforms. The analyzed data revealed a two-layer structure beneath the array, with a shallow, low-velocity layer (vs = 650 m/s) above deeper, high-velocity rocks (vs = 2,650 m/s). Using this velocity structure, possible source mechanisms and depths were constrained using array and particle motion analyses. The comparison of simulated and observed seismic data indicated that the precursory signal is associated with particle motion in the RZ-plane, pointing toward the opening of tensile cracks at a depth of ∼600 m below the summit; in contrast, the main signal is accompanied by a vertical single force, originating at a shallow depth of about ∼200 m. This suggests that the volcanic explosions at Santiaguito are following a bottom-up process in which tensile fractures develop at depth and enable rapid gas rise which leads to the subsequent explosion. The result indicates that explosions at Santiaguito do not occur from a single source location, but from a series of processes possibly associated with magma rupture, gas channeling and accumulation, and fragmentation. Our study provides a good foundation for further investigations at Santiaguito and shows the value of comparing seismic observations with synthetic data calculated for complex media to investigate in detail the processes leading up to gas-ash-rich explosions found at various other volcanoes worldwide.

Description: Chlamydia psittaci is an important zoonotic factor associated with human and animal atypical pneumonia. Resisting host cell apoptosis is central to sustaining Chlamydia infection in vivo. Chlamydia can secrete inclusion membrane proteins (Incs) that play important roles in their development cycle and pathogenesis. CPSIT_0846 is an Inc protein in C. psittaci identified by our team in previous work. In the current study, we investigated the regulatory role of CPSIT_0846 in HeLa cell apoptosis, and explored potential mechanisms. The results showed that HeLa cells treated with CPSIT_0846 contained fewer apoptotic bodies and exhibited a lower apoptotic rate than untreated cells either with Hoechst 33258 fluorescence staining or flow cytometry with or without induction by staurosporine (STS). CPSIT_0846 could increase the phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) or stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathways, and the Bcl-2 associated X protein (Bax)/B cell lymphoma 2 (Bcl-2) ratio, levels of cleaved caspase-3/9 and cleaved Poly-ADP-ribose polymerase (PARP) were significantly up-regulated following inhibition of ERK1/2 or SAPK/JNK pathways with U0126 or SP600125. After carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment, the mitochondrial membrane potential (MMP) of cells was significantly decreased in control group, but stable in the CPSIT_0846 treated one, and less cytochrome c (Cyt.c) was released into the cytoplasm. Inhibition of the ERK1/2 or SAPK/JNK pathway significantly decreased the JC-1 red-green fluorescence signal, and promoted Cyt.c discharge into the cytoplasm in HeLa cells treated with CPSIT_0846. In conclusion, CPSIT_0846 can regulate mitochondrial pathway-mediated apoptosis in HeLa cells by activating the ERK/JNK signaling pathway.

Description: Although belong to the same genus, Aspergillus fumigatus is primarily involved in invasive pulmonary infection, whereas Aspergillus flavus is a common cause of superficial infection. In this study, we compared conidia (the infective propagules) of these two Aspergillus species. In immunocompetent mice, intranasal inoculation with conidia of A. flavus resulted in significantly higher inflammatory responses in the lungs compared to mice inoculated with A. fumigatus conidia. In vitro assays revealed that the dormant conidia of A. flavus, unlike A. fumigatus dormant conidia, are immunostimulatory. The conidial surface of A. fumigatus was covered by a rodlet-layer, while that of A. flavus were presented with exposed polysaccharides. A. flavus harbored significantly higher number of proteins in its conidial cell wall compared to A. fumigatus conidia. Notably, β-1,3-glucan in the A. flavus conidial cell-wall showed significantly higher percentage of branching compared to that of A. fumigatus. The polysaccharides ensemble of A. flavus conidial cell wall stimulated the secretion of proinflammatory cytokines, and conidial cell wall associated proteins specifically stimulated IL-8 secretion from the host immune cells. Furthermore, the two species exhibited different sensitivities to antifungal drugs targeting cell wall polysaccharides, proposing the efficacy of species-specific treatment strategies. Overall, the species-specific organization of the conidial cell wall could be important in establishing infection by the two Aspergillus species.

Description: More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.

Description: Atmospheric gravity waves (GWs) are generated in the lower atmosphere by various weather phenomena. They propagate upward, carry energy and momentum to higher altitudes, and appreciably influence the general circulation upon depositing them in the middle and upper atmosphere. We use a three-dimensional first-principle general circulation model (GCM) with implemented nonlinear whole atmosphere GW parameterization to study the global climatology of wave activity and produced effects at altitudes up to the upper thermosphere. The numerical experiments were guided by the GW momentum fluxes and temperature variances as measured in 2010 by the SABER (Sounding of the Atmosphere using Broadband Emission Radiometry) instrument onboard NASA’s TIMED (Thermosphere Ionosphere Mesosphere Energetics Dynamics) satellite. This includes the latitudinal dependence and magnitude of GW activity in the lower stratosphere for the boreal summer season. The modeling results were compared to the SABER temperature and total absolute momentum flux and Upper Atmosphere Research Satellite (UARS) data in the mesosphere and lower thermosphere. Simulations suggest that, in order to reproduce the observed circulation and wave activity in the middle atmosphere, GW fluxes that are smaller than observed fluxes have to be used at the source level in the lower atmosphere. This is because observations contain a broader spectrum of GWs, while parameterizations capture only a portion relevant to the middle and upper atmosphere dynamics. Accounting for the latitudinal variations of the source appreciably improves simulations.

Description: This study investigated the interface morphology, microstructure composition and connection strength of 7A52 aluminum alloy-Al2O3 ceramic brazed joints under heat treatment conditions. Alumina ceramics were first treated with electroless nickel plating, followed by vacuum heat treatment at different temperatures. Then an Al-Si-Mg intermediate layer was placed between the treated alumina ceramic and 7A52 aluminum alloy for brazing under the conditions of welding temperature 590, holding time 1h, pressure 2 MPa. Results showed that when heat treatment was performed at 350°C and below, the nickel-plated metal had an amorphous structure, and when performed at 400°C, the nickel-plated layer had a crystalline structure and the brittle phase Ni3P was precipitated. When the heat treatment temperature was 350°C, the joint shear strength reached the maximum, which was 68.7 MPa.

Description: Larval aquatic insects are used to assess water quality, but less attention is paid to their adult, terrestrial life stage, which is an important food resource for declining aerial insectivorous birds. We used open-access water-quality, aquatic-invertebrate, and bird-survey data to study how impaired water quality can emanate from streams and lakes through changes in aquatic insect communities across the contiguous United States. Emergent insect relative abundance was highest across the West, in northern New England, and the Carolinas in streams, and highest near the Great Lakes, parts of the Southwest, and northern New England for lakes. Emergent insects declined with sedimentation, roads, and elevated ammonium concentrations in streams, but not lakes. The odds that a given taxon would be non-emergent increased by up to 2.0× as a function of pollution tolerance, underscoring the sensitivity of emergent aquatic insects to water-quality impairment. However, relationships between bird populations and emergent insects were generally weak for both streams and lakes. For streams, we observed the strongest positive relationships for a mixture of upland and riparian aerial insectivorous birds such as Western Wood-Pewee, Olive-sided Flycatcher, and Acadian Flycatcher and the strongest negative association for Purple Martin. Different avian insectivores responded to emergent insect abundances in lakes (e.g., Barn Swallow, Chimney Swift, Eastern Wood-Pewee, Common Nighthawk). In both streams and lakes, we observed stronger, but opposing, relationships between several aerial insectivores and the relative abundance of sensitive insect orders (E)phemeroptera, (P)lecoptera, and (T)richoptera (positive), and pollution tolerant individuals (negative). Overall, our findings indicate that emergent insects are negatively correlated with pollution tolerance, suggesting a large-scale loss of this nutritional subsidy to terrestrial environments from impaired aquatic ecosystems. While some bird populations tracked scarcities of emergent aquatic insects, especially EPT taxa, responses varied among species, suggesting that unique habitat and foraging behaviors likely complicated these relationships. Strengthening spatial and temporal concordance between emergent-insect and bird-survey data will improve our ability to interpret species-level responses over time. Thus, our analysis highlights the need for developing conservation and biomonitoring strategies that consider the cross-ecosystem effects of water quality declines for threatened insectivorous avifauna and other terrestrial wildlife.

Description: Antibiotic misuse is greatly contributing to an increase in antimicrobial resistance (AMR) in humans and animals. Natural and synthetic alternative strategies are being investigated in human and veterinary medicine, but little attention is paid to the antimicrobial effects of edible lipids, such as medium-chain fatty acids (MCFAs) and monoglycerides. Among MCFAs, lauric acid (LA) and its monoglyceride derivative, glycerol monolaurate (GML), exhibit the strongest antimicrobial activity. Coconut and palm kernel oils are considered the main sources of LA. On the other hand, some edible insects (e.g., Hermetia illucens) are gaining interest as novel feed ingredients, due to the high amount of LA they contain as well as their numerous bioactive components, which provide many additional benefits to animal health. Although the beneficial effect of both MCFAs and LA is gradually being recognized, their high content within insects and, consequently, their possible role as antimicrobials, has not been well-reported. This mini review focuses on the anti-infective effects of the insect-derived MCFAs LA and its derivatives. We emphasize the potential of insect lipids, compared to the other vegetable sources, in the current global scenario where a sustainable and circular economy is required. Finally, we critically discuss the use and the benefits of edible insects such as favorable options as feed and food from the perspective of animal and human nutrition.

Description: BackgroundElectroanatomic mapping systems are used to support electrophysiology research. Data exported from these systems is stored in proprietary formats which are challenging to access and storage-space inefficient. No previous work has made available an open-source platform for parsing and interrogating this data in a standardized format. We therefore sought to develop a standardized, open-source data structure and associated computer code to store electroanatomic mapping data in a space-efficient and easily accessible manner.MethodsA data structure was defined capturing the available anatomic and electrical data. OpenEP, implemented in MATLAB, was developed to parse and interrogate this data. Functions are provided for analysis of chamber geometry, activation mapping, conduction velocity mapping, voltage mapping, ablation sites, and electrograms as well as visualization and input/output functions. Performance benchmarking for data import and storage was performed. Data import and analysis validation was performed for chamber geometry, activation mapping, voltage mapping and ablation representation. Finally, systematic analysis of electrophysiology literature was performed to determine the suitability of OpenEP for contemporary electrophysiology research.ResultsThe average time to parse clinical datasets was 400 ± 162 s per patient. OpenEP data was two orders of magnitude smaller than compressed clinical data (OpenEP: 20.5 ± 8.7 Mb, vs clinical: 1.46 ± 0.77 Gb). OpenEP-derived geometry metrics were correlated with the same clinical metrics (Area: R2 = 0.7726, P 〈 0.0001; Volume: R2 = 0.5179, P 〈 0.0001). Investigating the cause of systematic bias in these correlations revealed OpenEP to outperform the clinical platform in recovering accurate values. Both activation and voltage mapping data created with OpenEP were correlated with clinical values (mean voltage R2 = 0.8708, P 〈 0.001; local activation time R2 = 0.8892, P 〈 0.0001). OpenEP provides the processing necessary for 87 of 92 qualitatively assessed analysis techniques (95%) and 119 of 136 quantitatively assessed analysis techniques (88%) in a contemporary cohort of mapping studies.ConclusionsWe present the OpenEP framework for evaluating electroanatomic mapping data. OpenEP provides the core functionality necessary to conduct electroanatomic mapping research. We demonstrate that OpenEP is both space-efficient and accurately representative of the original data. We show that OpenEP captures the majority of data required for contemporary electroanatomic mapping-based electrophysiology research and propose a roadmap for future development.

Description: The immune response type organized against viral infection is determinant in the prognosis of some infections. This work has aimed to study Th polarization in acute COVID-19 and its possible association with the outcome through an observational prospective study. Fifty-eight COVID-19 patients were recruited in the Medicine Department of the hospital “12 de Octubre,” 55 patients remaining after losses to follow-up. Four groups were established according to maximum degree of disease progression. T-helper cell percentages and phenotypes, analyzed by flow cytometer, and serum cytokines levels, analyzed by Luminex, were evaluated when the microbiological diagnosis (acute phase) of the disease was obtained. Our study found a significant reduction of %Th1 and %Th17 cells with higher activated %Th2 cells in the COVID-19 patients compared with reference population. A higher percent of senescent Th2 cells was found in the patients who died than in those who survived. Senescent Th2 cell percentage was an independent risk factor for death (OR: 13.88) accompanied by the numbers of total lymphocytes (OR: 0.15) with an AUC of 0.879. COVID-19 patients showed a profile of pro-inflammatory serum cytokines compared to controls, with higher levels of IL-2, IL-6, IL-15, and IP-10. IL-10 and IL-13 were also elevated in patients compared to controls. Patients who did not survive presented significantly higher levels of IL-15 than those who recovered. No significant differences were observed according to disease progression groups. The study has shown that increased levels of IL-15 and a high Th2 response are associated with a fatal outcome of the disease.

Description: RAD17, a replication factor C (RFC)-like DNA damage sensor protein, is involved in DNA checkpoint control and required for both meiosis and mitosis in yeast and mammals. In plant, the meiotic function of RAD17 was only reported in rice so far. Here, we identified and characterized the RAD17 homolog in maize. The Zmrad17 mutants exhibited normal vegetative growth but male was partially sterile. In Zmrad17 pollen mother cells, non-homologous chromosome entanglement and chromosome fragmentation were frequently observed. Immunofluorescence analysis manifested that DSB formation occurred as normal and the loading pattern of RAD51 signals was similar to wild-type at the early stage of prophase I in the mutants. The localization of the axial element ASY1 was normal, while the assembly of the central element ZYP1 was severely disrupted in Zmrad17 meiocytes. Surprisingly, no obvious defect in female sterility was observed in Zmrad17 mutants. Taken together, our results suggest that ZmRAD17 is involved in DSB repair likely by promoting synaptonemal complex assembly in maize male meiosis. These phenomena highlight a high extent of divergence from its counterpart in rice, indicating that the RAD17 dysfunction can result in a drastic dissimilarity in meiotic outcome in different plant species.