ALBERT

Description: Sustainable food systems education (SFSE) is rapidly advancing to meet the need for developing future professionals who are capable of effective decision-making regarding agriculture, food, nutrition, consumption, and waste in a complex world. Equity, particularly racial equity and its intersectional links with other inequities, should play a central role in efforts to advance SFSE given the harmful social and environmental externalities of food systems and ongoing oppression and systemic inequities such as lack of food access faced by racialized and/or marginalized populations. However, few institutional and intra-disciplinary resources exist on how to engage students in discussion about equity and related topics in SFSE. We present perspectives based on our multi-institutional collaborations to develop and apply pedagogical materials that center equity while building students' skills in systems thinking, critical reflection, and affective engagement. Examples are provided of how to develop undergraduate and graduate sustainable food systems curricula that embrace complexity and recognize the affective layers, or underlying experiences of feelings and emotions, when engaging with topics of equity, justice, oppression, and privilege.

Description: The industrial microbe Corynebacterium glutamicum is gaining substantial importance as a platform host for recombinant protein secretion. We recently developed a fluorescence-based (eYFP) C. glutamicum reporter strain for the quantification of Sec-dependent protein secretion by monitoring the secretion-related stress response and now demonstrate its applicability in optimizing the secretion of the heterologous enzyme cutinase from Fusarium solani pisi. To drive secretion, either the poor-performing PelSP or the potent NprESP Sec signal peptide from Bacillus subtilis was used. To enable easy detection and quantification of the secreted cutinase we implemented the split green fluorescent protein (GFP) assay, which relies on the GFP11-tag fused to the C-terminus of the cutinase, which can complement a truncated GFP thereby reconstituting its fluorescence. The reporter strain was transformed with different mutant libraries created by error-prone PCR, which covered the region of the signal peptide and the N-terminus of the cutinase. Fluorescence-activated cell sorting (FACS) was performed to isolate cells that show increased fluorescence in response to increased protein secretion stress. Five PelSP variants were identified that showed a 4- to 6-fold increase in the amount and activity of the secreted cutinase (up to 4,100 U/L), whereas two improved NprESP variants were identified that showed a ∼35% increase in secretion, achieving ∼5,500 U/L. Most of the isolated variants carried mutations in the h-region of the signal peptide that increased its overall hydrophobicity. Using site-directed mutagenesis it was shown that the combined mutations F11I and P16S within the hydrophobic core of the PelSP are sufficient to boost cutinase secretion in batch cultivations to the same level as achieved by the NprESP. Screening of a PelSP mutant library in addition resulted in the identification of a cutinase variant with an increased specific activity, which was attributed to the mutation A85V located within the substrate-binding region. Taken together the biosensor-based optimization approach resulted in a substantial improvement of cutinase secretion by C. glutamicum, and therefore represents a valuable tool that can be applied to any secretory protein of interest.

Description: Internal seawater systems (ISS) are critical to the proper functioning of maritime vessels. Sea water is pumped on board ships for a broad array of uses, primarily for temperature control (e.g., engine and electrical systems), cooling capacity (e.g., air conditioners and refrigeration), and water provision (e.g., drinking, firefighting, steam, and ballast). Although sea water may spend only a brief period within ISS of a vessel, it can carry microorganisms and larval stages of macroorganisms throughout the system leading to biofouling accumulation that can impair system function or integrity. ISS can also act as a sub-vector of species translocations, potentially facilitating biological invasions. This review describes ships’ ISS with a focus on operational impacts of biofouling and current drivers and barriers associated with ISS biofouling management. As ISS internal components are difficult to access, reports and studies of ISS biofouling are uncommon and much of the dedicated literature is decades old. The impact of biofouling on ISS and vessel operations is based on increased surface roughness of pipework and equipment, restricted water flow, corrosion and subsequent component impingement, reduced surface functional efficiency, and potential contamination by pathogens that can affect human and aquatic animal health. Biofouling management is primarily achieved using antifouling coatings and marine growth prevention systems, but independent and accessible data on their efficacy in ISS remain limited. Further research is required to resolve the extent to which biofouling occurs in ISS of the modern commercial fleet and the efficacy of preventive systems. Such information can ultimately inform decisions to improve operational efficiency for vessel operators and ensure any biosecurity risks are appropriately managed.

Description: Single-cell assays have transformed our ability to model heterogeneity within cell populations. As these assays have advanced in their ability to measure various aspects of molecular processes in cells, computational methods to analyze and meaningfully visualize such data have required matched innovation. Independently, Virtual Reality (VR) has recently emerged as a powerful technology to dynamically explore complex data and shows promise for adaptation to challenges in single-cell data visualization. However, adopting VR for single-cell data visualization has thus far been hindered by expensive prerequisite hardware or advanced data preprocessing skills. To address current shortcomings, we present singlecellVR, a user-friendly web application for visualizing single-cell data, designed for cheap and easily available virtual reality hardware (e.g., Google Cardboard, ∼$8). singlecellVR can visualize data from a variety of sequencing-based technologies including transcriptomic, epigenomic, and proteomic data as well as combinations thereof. Analysis modalities supported include approaches to clustering as well as trajectory inference and visualization of dynamical changes discovered through modelling RNA velocity. We provide a companion software package, scvr to streamline data conversion from the most widely-adopted single-cell analysis tools as well as a growing database of pre-analyzed datasets to which users can contribute.

Description: Sustainable development and reducing environmental pressure are major issues that concern developed as well as developing countries. Although researchers widely use carbon dioxide emissions and ecological footprint within the scope of environmental degradation, a more comprehensive ecological indicator is needed to assess environmental sustainability. In this context, the load capacity factor enables a comprehensive environmental sustainability assessment through the simultaneous analysis of biocapacity and ecological footprint. However, there are few studies analyzing the determinants of load capacity factor and this study aims to fill this gap for Indonesia. Using the recently developed Fourier quantile causality test, this study investigates the impact of income, export diversification, non-renewable and renewable energy consumption on the load capacity factor for Indonesia during 1965Q1–2014Q4. The results show unidirectional causality from non-renewable energy consumption to the load capacity factor at all quantiles, while income, export diversification, and renewable energy are the causes of environmental quality at middle and higher quantiles (within 0.5, 0.7, and 0.9). Most importantly, renewable energy and export diversification increase the load capacity factor and thus support environmental quality. In contrast, an increase in income and consumption of non-renewable energy reduces the load capacity factor. These results highlight the importance of renewable energy and export diversification for the sustainable development of Indonesia.

Description: In this review, we introduce microbially-mediated soil processes, players, their functional traits, and their links to processes at biogeochemical interfaces [e.g., rhizosphere, detritusphere, (bio)-pores, and aggregate surfaces]. A conceptual view emphasizes the central role of the rhizosphere in interactions with other biogeochemical interfaces, considering biotic and abiotic dynamic drivers. We discuss the applicability of three groups of traits based on microbial physiology, activity state, and genomic functional traits to reflect microbial growth in soil. The sensitivity and credibility of modern molecular approaches to estimate microbial-specific growth rates require further development. A link between functional traits determined by physiological (e.g., respiration, biomarkers) and genomic (e.g., genome size, number of ribosomal gene copies per genome, expression of catabolic versus biosynthetic genes) approaches is strongly affected by environmental conditions such as carbon, nutrient availability, and ecosystem type. Therefore, we address the role of soil physico-chemical conditions and trophic interactions as drivers of microbially-mediated soil processes at relevant scales for process localization. The strengths and weaknesses of current approaches (destructive, non-destructive, and predictive) for assessing process localization and the corresponding estimates of process rates are linked to the challenges for modeling microbially-mediated processes in heterogeneous soil microhabitats. Finally, we introduce a conceptual self-regulatory mechanism based on the flexible structure of active microbial communities. Microbial taxa best suited to each successional stage of substrate decomposition become dominant and alter the community structure. The rates of decomposition of organic compounds, therefore, are dependent on the functional traits of dominant taxa and microbial strategies, which are selected and driven by the local environment.

Description: Hybrid sedimentary rocks (HSR) are a major reservoir type in unconventional oil exploration. The reservoir characteristics and controlling factors of the oil content of HSR are not clear, restricting the understanding of the storage mechanism and sweet spots within HSR. The Lucaogou Formation in the western Jimusar Sag is taken as a case study. Starting with the classification of the lithofacies system, differences in the microscopic pore structure, oil content and controlling factors of HSR reservoirs are revealed. The results show that seven lithofacies are recognized based on mineral composition, sedimentary structure, and organic matter characteristics, exhibiting rapid vertical and horizontal changes affected by the sedimentary environment. Layered mudstone lithofacies of the shallow lake mud and massive dolomitic mudstone lithofacies of dolomitic mud flats have the worst physical properties and oil content properties. However, they do have high organic matter contents and are the main source rocks of the Lucaogou Formation. The massive argillaceous siltstone and massive argillaceous dolomite lithofacies interbed frequently. Although their physical properties are moderate, “source-reservoir integrated” unconventional oil reservoirs can be formed, due to the adjacent to the source rock. Massive dolomitic siltstone, massive siltstone, and massive silty dolomite lithofacies are developed in the middle of the Lucaogou Formation, with the highest proportion of mesopores and macropores, which is indicative of good storage properties. When these lithofacies are filled with crude oil generated from source rocks at the top and bottom of the formation, “source storage adjacent” unconventional oil reservoirs be formed. The oil content is also controlled by the pore structure and specific surface area. The proportion of macropores and mesopores is positively correlated with oil content. The oil content of the samples is very low, when the specific surface area exceeds 2 m2/g. This manuscript provides a geological basis for evaluating and establishing reasonable interpretation models of HSR sweet spots.

Description: This paper is proposed for modelling concrete beams reinforced with fiber reinforced polymer (FRP) bars in a simplified way. In order to appropriately model the FRP-reinforced concrete beams the stiffness matrix is developed in the frequency domain using fast Fourier Transform. Numerical results with the proposed spectral model for the load-displacement response and the shear stress distribution between FRP reinforcement and surrounding concrete are obtained for beams statically tested. Tens of elements are deployed in this work due to the simplicity of the proposed model. Using the same spectral model the natural frequency and mode shapes are evaluated since the frequency-dependent stiffness matrix enables it to apply for dynamic study, e.g. modal analysis. The feasibility of the proposed numerical approach for performing dynamic analysis especially for high frequency excitations in an efficient way makes it a promising tool for use in the field of structural health monitoring according to the changes in dynamic characteristics.

Description: Background: Colorectal cancer (CRC) is a leading cause of cancer death, and early diagnosis of CRC could significantly reduce its mortality rate. Previous studies suggest that the DNA methylation status of zinc finger genes (ZFGs) could be of potential in CRC early diagnosis. However, the comprehensive evaluation of ZFGs in CRC is still lacking.Methods: We first collected 1,426 public samples on genome-wide DNA methylation, including 1,104 cases of CRC tumors, 54 adenomas, and 268 para-tumors. Next, the most differentially methylated ZFGs were identified and validated in two replication cohorts comprising 218 CRC patients. Finally, we compared the prediction capabilities between the ZFGs and the SEPT9 in all CRC patients and the KRAS + and KRAS- subgroup.Results: Five candidate ZFGs were selected: ESR1, ZNF132, ZNF229, ZNF542, and ZNF677. In particular, ESR1 [area under the curve (AUC) = 0.91] and ZNF132 (AUC = 0.93) showed equivalent or better diagnostic capability for CRC than SEPT9 (AUC = 0.91) in the validation dataset, suggesting that these two ZFGs might be of potential for CRC diagnosis in the future. Furthermore, we performed subgroup analysis and found a significantly higher diagnostic capability in KRAS + (AUC ranged from 0.97 to 1) than that in KRAS- patients (AUC ranged from 0.74 to 0.86) for all these five ZFGs, suggesting that these ZFGs could be ideal diagnostic markers for KRAS mutated CRC patients.Conclusion: The methylation profiles of the candidate ZFGs could be potential biomarkers for the early diagnosis of CRC, especially for patients carrying KRAS mutations.

Description: Predicting the ambient environmental conditions in the coming several years to one decade is of key relevance for elucidating how deep-sea habitats, like for example sponge habitats, in the North Atlantic will evolve under near-future climate change. However, it is still not well known to what extent the deep-sea environmental properties can be predicted in advance. A regional downscaling prediction system is developed to assess the potential predictability of the North Atlantic deep-sea environmental factors. The large-scale climate variability predicted with the coupled Max Planck Institute Earth System Model with low-resolution configuration (MPI-ESM-LR) is dynamically downscaled to the North Atlantic by providing surface and lateral boundary conditions to the regional coupled physical-ecosystem model HYCOM-ECOSMO. Model results of two physical fields (temperature and salinity) and two biogeochemical fields (concentrations of silicate and oxygen) over 21 sponge habitats are taken as an example to assess the ability of the downscaling system to predict the interannual to decadal variations of the environmental properties based on ensembles of retrospective predictions over the period from 1985 to 2014. The ensemble simulations reveal skillful predictions of the environmental conditions several years in advance with distinct regional differences. In areas closely tied to large-scale climate variability and ice dynamics, both the physical and biogeochemical fields can be skillfully predicted more than 4 years ahead, while in areas under strong influence of upper oceans or open boundaries, the predictive skill for both fields is limited to a maximum of 2 years. The simulations suggest higher predictability for the biogeochemical fields than for the physical fields, which can be partly attributed to the longer persistence of the former fields. Predictability is improved by initialization in areas away from the influence of Mediterranean outflow and areas with weak coupling between the upper and deep oceans. Our study highlights the ability of the downscaling regional system to predict the environmental variations at deep-sea benthic habitats on time scales of management relevance. The downscaling system therefore will be an important part of an integrated approach towards the preservation and sustainable exploitation of the North Atlantic benthic habitats.

Description: Chemoresistance is an impending challenge in cancer treatment. In recent years, exosomes, a subtype of extracellular vesicles with a diameter of 40–150 nm in bloodstream and other bio-fluids, have attracted increasing interest. Exosomes contain proteins, nucleic acids, and lipids, which act as important signaling molecules. Many reports indicate that exosomes play critical roles in chemoresistance through intercellular interactions, including drug removal from cells, transfer of drug resistance phenotypes to other cancer cells, and the increase in plastic stem cell subsets. Exosomes can reflect the physiological and pathological state of parent cells. Owing to their elevated stability, specificity, and sensitivity, exosomes are served as biomarkers in liquid biopsies to monitor cancer chemoresistance, progression, and recurrence. This review summarizes the exosome-mediated mechanisms of cancer chemoresistance, as well as its role in reversing and monitoring chemoresistance. The scientific and technological challenges and future applications of exosomes are also explored.

Description: European beech is one of the most important deciduous tree species in natural forest ecosystems in Central Europe. Its dominance is now being questioned by the emerging drought damages due to the increased incidence of severe summer droughts. In Switzerland, Fagus sylvatica have been observed in the Intercantonal Forest Observation Program since 1984. The dataset presented here includes 179176 annual observations of beech trees on 102 plots during 37 years. The plots cover gradients in drought, nitrogen deposition, ozone, age, altitude, and soil chemistry. In dry regions of Switzerland, the dry and hot summer of 2018 caused a serious branch dieback, increased mortality in Fagus sylvatica and increased yellowing of leaves. Beech trees recovered less after 2018 than after the dry summer 2003 which had been similar in drought intensity except that the drought in 2018 started earlier in spring. Our data analyses suggest the importance of drought in subsequent years for crown transparency and mortality in beech. The drought in 2018 followed previous dry years of 2015 and 2017 which pre-weakened the trees. Our long-term data indicate that the drought from up to three previous years were significant predictors for both tree mortality and for the proportion of trees with serious (〉60%) crown transparency. The delay in mortality after the weakening event suggests also the importance of weakness parasites. The staining of active vessels with safranine revealed that the cavitation caused by the low tree water potentials in 2018 persisted at least partially in 2019. Thus, the ability of the branches to conduct water was reduced and the branches dried out. Furthermore, photooxidation in light-exposed leaves has increased strongly since 2011. This phenomenon was related to low concentrations of foliar phosphorus (P) and hot temperatures before leaf harvest. The observed drought effects can be categorized as (i) hydraulic failure (branch dieback), (ii) energy starvation as a consequence of closed stomata and P deficiency (photooxidation) and (iii) infestation with weakness parasites (beech bark disease and root rots).

Description: Nucleoid-associated proteins (NAPs) or histone-like proteins (HLPs) are DNA-binding proteins present in bacteria that play an important role in nucleoid architecture and gene regulation. NAPs affect bacterial nucleoid organization via DNA bending, bridging, or forming aggregates. EbfC is a nucleoid-associated protein identified first in Borrelia burgdorferi, belonging to YbaB/EbfC family of NAPs capable of binding and altering DNA conformation. YbaB, an ortholog of EbfC found in Escherichia coli and Haemophilus influenzae, also acts as a transcriptional regulator. YbaB has a novel tweezer-like structure and binds DNA as homodimers. The homologs of YbaB are found in almost all bacterial species, suggesting a conserved function, yet the physiological role of YbaB protein in many bacteria is not well understood. In this study, we characterized the YbaB/EbfC family DNA-binding protein in Caulobacter crescentus. C. crescentus has one YbaB/EbfC family gene annotated in the genome (YbaBCc) and it shares 41% sequence identity with YbaB/EbfC family NAPs. Computational modeling revealed tweezer-like structure of YbaBCc, a characteristic of YbaB/EbfC family of NAPs. N-terminal–CFP tagged YbaBCc localized with the nucleoid and is able to compact DNA. Unlike B. burgdorferi EbfC protein, YbaBCc protein is a non-specific DNA-binding protein in C. crescentus. Moreover, YbaBCc shields DNA against enzymatic degradation. Collectively, our findings reveal that YbaBCc is a small histone-like protein and may play a role in bacterial chromosome structuring and gene regulation in C. crescentus.

Description: Traditional reinforced concrete piles have high strength and low cost in slope engineering, but the slow forming and long maintenance period make it difficult to meet the needs of emergency and disaster relief tasks, such as landslides caused by rainfall. In this paper, the influence of a new type of polymer anti-slide pile on slope stability under rainfall conditions is studied. With the advantages of fast forming, high strength, simple construction technology, and small disturbance to slope, the new type of anti-slide pile can meet the requirements of emergency and disaster relief tasks. The influence of different rainfall duration, rainfall form, location, and spacing of pile laying on the stability of rainfall slope is explored with fluid-solid coupling analysis. The results show that the slope stability gradually deteriorates with the increase of the peak duration of rainfall intensity. Without rainfall conditions, the reinforcement effect is optimal when the position of pile cloth is 1/2–3/4 L away from the foot of the slope (L is the horizontal length of the slope); with rainfall conditions, when the position of pile cloth is 1/4–1/2 L away from the foot of the slope, the reinforcement effect is optimal. Without rainfall conditions, the reduction of pile spacing can improve the reinforcement effect; with rainfall conditions, the reduction of pile spacing will affect the flow and discharge of seepage rainwater and reduce the reinforcement effect.

Description: Numerous flavoring chemicals are added to e-cigarette liquids to create various flavors. Flavorings provide sensory experience to users and increase product appeal; however, concerns have been raised about their potential inhalation toxicity. Estimating potential health risk of inhaling these chemicals has been challenging since little is known about their actual concentrations in e-cigarette products. To date, a limited number of analytical methods exist to measure the concentrations of flavoring chemicals in e-cigarette products. We have developed an analytical method that accurately and precisely measures the concentrations of 20 flavoring chemicals of potential inhalation risk concerns: 2,3,5-trimethylpyrazine, acetoin, benzaldehyde, benzyl alcohol, butanoic acid, dl-limonene, ethyl maltol, ethyl salicylate, ethyl vanillin, eucalyptol, eugenol, furaneol, isovanillin, l-menthol, maltol, methyl salicylate, pulegone, trans-cinnamaldehyde, triacetin, and vanillin. Calibration and QC solutions were prepared in 50:50 propylene glycol (PG):vegetable glycerin (VG) and 5% H2O and flavoring concentrations ranging from 0.02 to 10.00 mg/ml. Samples of commercial e-cigarette liquids, calibration and QC solutions were combined with 30 µL of an internal standard mix (benzene-d6, pyridine-d5, chlorobenzene-d5, naphthalene-d8 and acenaphthene-d10; 1 mg/ml each) and were diluted 100-fold into methanol. Analysis was performed on an Agilent 7890B/7250 GC/Q-TOF using a DB-624UI column (30 m x 0.25 mmID x 1.4 μm film thickness), with a total runtime of 13.5 min. Calibration curves were fit using a weighted quadratic model and correlations of determination (r2) values exceeded 0.990 for all chemicals. Bias and precision tests yielded values less than 20% and lower limits of quantitation (LLOQ) ranged from 0.02 to 0.63 mg/ml. Over 200 commercially available products, purchased or collected from adult e-cigarette users and spanning a range of flavor categories, were evaluated with this method. Concentrations of pulegone, a suspected carcinogen, varied from below limit of quantitation (BLOQ) to 0.32 mg/ml, while acetoin and vanillin, known precursors to more cytotoxic byproducts, ranged from BLOQ to 1.52 mg/ml and from BLOQ to 16.22 mg/ml, respectively. This method features a wide dynamic working range and allows for a rapid routine analysis of flavoring additives in commercial e-cigarette liquids.

Description: Invasive species pose one of the greatest threats to global biodiversity. Early detection of invasive species is critical in order to prevent or manage their spread before they exceed the ability of land management groups to control them. Optical remote sensing has been established as a useful technology for the early detection and mapping of invasive vegetation populations. Through the use of airborne hyperspectral imagery (HSI), this study establishes a target detection methodology used to identify and map the invasive reed Phragmites australis subsp. australis within the entire extent of Îles-de-Boucherville National Park (Quebec, ON, Canada). We applied the Spectral Angle Mapper (SAM) target detection algorithm trained with a high accuracy GNSS ground truth data set to produce a park-wide map illustrating the extent of detected Phragmites. The total coverage of detected Phragmites was 26.74 ha (0.267 km2), which represents 3.28% of the total park area of 814 ha (8.14 km2). The inherent spatial uncertainty of the airborne HSI (∼2.25 m) was accounted for with uncertainty buffers, which, when included in the measurement of detected Phragmites, lead to a total area of 59.17 ha (0.591 km2), or 7.26% of the park. The overall accuracy of the Phragmites map was 84.28%, with a sensitivity of 76.32% and a specificity of 91.57%. Additionally, visual interpretation of the validation ground truth dataset was performed by 10 individuals, in order to compare their performance to that of the target detection algorithm. The overall accuracy of the visual interpretation was lower than the target detection (i.e., 69.18%, with a sensitivity of 59.21% and a specificity of 78.31%). Overall, this study is one of the first to utilize airborne HSI and target detection to map the extent of Phragmites over a moderately large extent. The uses and limitations of such an approach are established, and the methodology described here in detail could be adapted for future remote sensing studies of Phragmites or other vegetation species, native or invasive, at study sites around the world.

Description: Ultraviolet radiation (UVR) is a major environmental stressor for terrestrial plants. Here we investigated genetic responses to acute broadband UVR exposure in the highly desiccation-tolerant mosses Syntrichia caninervis and Syntrichia ruralis, using a comparative transcriptomics approach. We explored whether UVR protection is physiologically plastic and induced by UVR exposure, addressing the following questions: (1) What is the timeline of changes in the transcriptome with acute UVR exposure in these two species? (2) What genes are involved in the UVR response? and (3) How do the two species differ in their transcriptomic response to UVR? There were remarkable differences between the two species after 10 and 30 min of UVR exposure, including no overlap in significantly differentially abundant transcripts (DATs) after 10 min of UVR exposure and more than twice as many DATs for S. caninervis as there were for S. ruralis. Photosynthesis-related transcripts were involved in the response of S. ruralis to UVR, while membrane-related transcripts were indicated in the response of S. caninervis. In both species, transcripts involved in oxidative stress and those important for desiccation tolerance (such as late embryogenesis abundant genes and early light-inducible protein genes) were involved in response to UVR, suggesting possible roles in UVR tolerance and cross-talk with desiccation tolerance in these species. The results of this study suggest potential UVR-induced responses that may have roles outside of UVR tolerance, and that the response to URV is different in these two species, perhaps a reflection of adaptation to different environmental conditions.

Description: Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Description: The objective of this study was to compare the accuracies of genomic prediction for milk yield, fat yield, and protein yield from Philippine dairy buffaloes using genomic best linear unbiased prediction (GBLUP) and single-step GBLUP (ssGBLUP) with the accuracies based on pedigree BLUP (pBLUP). To also assess the bias of the prediction, the regression coefficient (slope) of the adjusted phenotypes on the predicted breeding values (BVs) was also calculated. Two data sets were analyzed. The GENO data consisting of all female buffaloes that have both phenotypes and genotypes (n = 904 with 1,773,305-days lactation records) were analyzed using pBLUP and GBLUP. The ALL data, consisting of the GENO data plus females with phenotypes but not genotyped (n = 1,975 with 3,821,305-days lactation records), were analyzed using pBLUP and ssGBLUP. Animals were genotyped with the Affymetrix 90k buffalo genotyping array. After quality control, 60,827 single-nucleotide polymorphisms were used for downward analysis. A pedigree file containing 2,642 animals was used for pBLUP and ssGBLUP. Accuracy of prediction was calculated as the correlation between the predicted BVs of the test set and adjusted phenotypes, which were corrected for fixed effects, divided by the square root of the heritability of the trait, corrected for the number of lactations used in the test set. To assess the bias of the prediction, the regression coefficient (slope) of the adjusted phenotypes on the predicted BVs was also calculated. Results showed that genomic methods (GBLUP and ssGBLUP) provide more accurate predictions compared to pBLUP. Average GBLUP and ssGBLUP accuracies were 0.24 and 0.29, respectively, whereas average pBLUP accuracies (for GENO and ALL data) were 0.21 and 0.22, respectively. Slopes of the two genomic methods were also closer to one, indicating lesser bias, compared to pBLUP. Average GBLUP and ssGBLUP slopes were 0.89 and 0.84, respectively, whereas the average pBLUP (for GENO and ALL data) slopes were 0.80 and 0.54, respectively.

Description: Here, we report on the symbiotic N2 fixation and water use efficiency (δ13C) of Kersting's groundnut, an important but underutilized grain legume in Africa, in response to inoculation with Bradyrhizobium strains 3267 and CB756. The 15N natural abundance and xylem ureide techniques were used to quantify N2 fixation. The landraces in this study derived variable levels of their N requirements from symbiosis, which translated into marked differences in the amounts of N-fixed by the landrace–inoculant combinations across the test locations. In most instances, the landrace-strain combinations that elicited higher shoot biomass also recorded greater N-fixed and/or ureide-N in xylem sap as well as grain yield. Although some landraces coupled increased grain yield with higher water use efficiency (shoot δ13C), a trait that could be tapped for crop improvement, others recorded lower yields despite eliciting relatively high shoot δ13C values, indicating genotypic variations in adaptation to the different environments. Grain yield of the test landraces showed marked variation and ranged from 131 to 1349.8 kg ha−1 depending on the landrace–strain combination used and the planting location. The high symbiotic dependence by landraces in this study could explain why Kersting's groundnut thrives in the low nutrient soils that are prevalent in its cultivation areas. These results provide more insights into the literature regarding the Kersting's groundnut–rhizobia symbiosis as well as the crop's water use efficiency.

Description: One of the major challenges in the understanding of the crater lakes dynamics and their connection with magmatic/hydrothermal processes is the continuous tracking of the physical behavior of lakes, especially in cases of remote and poorly accessible volcanoes. Peteroa volcano (Chile–Argentina border) is part of the Planchón–Peteroa–Azufre Volcanic Complex, one of the three volcanoes in the Southern Volcanic Zone of the Andes with crater lakes. Peteroa volcano is formed by a ∼5 km diameter caldera-type crater, which hosts four crater lakes and several fumarolic fields. Peteroa volcano has a large history of eruptive activity including phreatic-and-phreatomagmatic explosions and several episodes of strong degassing from its crater lakes. Here, we used TIR and SWIR bands from Landsat TM, ETM+, and OLI images available from October 1984 to December 2020 to obtain thermal parameters such as thermal radiance, brightness temperature, and heat fluxes, and Planet Labs Inc. images (RapidEye and PlanetScope) available between May 2009 and December 2020 to obtain physical parameters such as area, color, and state (liquid or frozen) of the crater lakes. We reviewed the historical eruptive activity and compared it with thermal and physical data obtained from satellite images. We determined the occurrence of two eruptive/thermal cycles: 1) Cycle 1 includes the formation of a new fumarolic field and two active craters during a short eruptive period, which includes thermal activity in three of the four crater lakes, and a strong degassing process between October 1998 and February 2001, coincident with a peak of volcanic heat flux (Qvolc) in two craters. The cycle finished with an eruptive episode (September 2010–July 2011). 2) Cycle 2 is represented by the thermal reactivation of two crater lakes, formation and detection of thermal activity in a new nested crater, and occurrence of a new eruptive episode (October 2018–April 2019). We observed a migration of the thermal and eruptive activity between the crater lakes and the interconnection of the pathways that feed the lakes, in both cases, partially related to the presence of two deep magma bodies. The Qvolc in Peteroa volcano crater lakes is primarily controlled by volcanic activity, and seasonal effects affect it at short-term, whilst at long-term, seasonal effects do not show clear influences in the volcanic heat fluxes. The maximum Qvolc measured between all crater lakes during quiescent periods was 59 MW, whereas during unrest episodes Qvolc in single crater lakes varied from 7.1 to 38 MW, with Peteroa volcano being classified as a low volcanic heat flux system. The detection of new thermal activity and increase of Qvolc in Peteroa volcano previous to explosive unrest can be considered as a good example of how thermal information from satellite images can be used to detect possible precursors to eruptive activity in volcanoes which host crater lakes.

Description: Middle bias has been reported for responses to multiple-choice test items used in educational assessment. It has been claimed that this response bias probably occurs because test developers tend to place correct responses among middle options, tests thus presenting a middle-biased distribution of answer keys. However, this response bias could be driven by strong distractors being more frequently located among middle options. In this study, the frequency of responses to a Chilean national examination used to rank students wanting to access higher education was used to categorize distractors based on attractiveness level. The distribution of different distractor types (best distractor, non-functioning distractors…) was analyzed across 110 tests of 80 five-option items administered to assess several disciplines in five consecutive years. Results showed that the strongest distractors were more frequently found among middle options, most commonly at option C. In contrast, the weakest distractors were more frequently found at the last option (E). This pattern did not substantially vary across disciplines or years. Supplementary analyses revealed that a similar position bias for distractors could be observed in tests administered in countries other than Chile. Thus, the location of different types of distractors might provide an alternative explanation for the middle bias reported in literature for tests’ responses. Implications for test developers, test takers, and researchers in the field are discussed.

Description: The Leishmania developmental cycle comprises three main life forms in two hosts, indicating that the parasite is continually challenged due to drastic environmental changes. The disruption of this cycle is critical for discovering new therapies to eradicate leishmaniasis, a neglected disease that affects millions worldwide. Telomeres, the physical ends of chromosomes, maintain genome stability and cell proliferation and are potential antiparasitic drug targets. Therefore, understanding how telomere length is regulated during parasite development is vital. Here, we show that telomeres form clusters spread in the nucleoplasm of the three parasite life forms. We also observed that amastigotes telomeres are shorter than metacyclic and procyclic promastigotes and that in parasites with continuous in vitro passages, telomere length increases over time. These observed differences in telomere length among parasite’s life stages were not due to lack/inhibition of telomerase since enzyme activity was detected in all parasite life stages, although the catalysis was temperature-dependent. These data led us to test if, similar to other eukaryotes, parasite telomere length maintenance could be regulated by Hsp83, the ortholog of Hsp90 in trypanosomatids, and Leishmania (LHsp90). Parasites were then treated with the Hsp90 inhibitor 17AAG. The results showed that 17AAG disturbed parasite growth, induced accumulation into G2/M phases, and telomere shortening in a time-dependent manner. It has also inhibited procyclic promastigote’s telomerase activity. Besides, LHsp90 interacts with the telomerase TERT component as shown by immunoprecipitation, strongly suggesting a new role for LHsp90 as a parasite telomerase component involved in controlling telomere length maintenance and parasite life span.

Description: The coronavirus disease 2019 (COVID-19) has caused a serious disease burden and poses a tremendous public health challenge worldwide. Here, we report a comprehensive epidemiological and genomic analysis of SARS-CoV-2 from 63 patients in Niigata City, a medium-sized Japanese city, during the early phase of the pandemic, between February and May 2020. Among the 63 patients, 32 (51%) were female, with a mean (±standard deviation) age of 47.9 ± 22.3 years. Fever (65%, 41/63), malaise (51%, 32/63), and cough (35%, 22/63) were the most common clinical symptoms. The median Ct value after the onset of symptoms lowered within 9 days at 20.9 cycles (interquartile range, 17–26 cycles), but after 10 days, the median Ct value exceeded 30 cycles (p 〈 0.001). Of the 63 cases, 27 were distributed in the first epidemic wave and 33 in the second, and between the two waves, three cases from abroad were identified. The first wave was epidemiologically characterized by a single cluster related to indoor sports activity spread in closed settings, which included mixing indoors with families, relatives, and colleagues. The second wave showed more epidemiologically diversified events, with most index cases not related to each other. Almost all secondary cases were infected by droplets or aerosols from closed indoor settings, but at least two cases in the first wave were suspected to be contact infections. Results of the genomic analysis identified two possible clusters in Niigata City, the first of which was attributed to clade S (19B by Nexstrain clade) with a monophyletic group derived from the Wuhan prototype strain but that of the second wave was polyphyletic suggesting multiple introductions, and the clade was changed to GR (20B), which mainly spread in Europe in early 2020. These findings depict characteristics of SARS-CoV-2 transmission in the early stages in local community settings during February to May 2020 in Japan, and this integrated approach of epidemiological and genomic analysis may provide valuable information for public health policy decision-making for successful containment of chains of infection.

Description: Mountains are rich in pastures and water for agro-pastoral resources and supports rain-fed farming that sustain the livelihoods of many indigenous communities. This work seeks to examine the implications of climatic variability on agro-pastoral resources (pasture land, water) and food security within the Mbororo communities. To ascertain this, 350 household questionnaires were randomly administered in four Mbororo Ardorates and in-depth interviews conducted with local authorities. Quantitative and qualitative analysis of data collected revealed that the link between climate, land and water is paramount in animal rearing and crop farming in mountains. Cattle rearing and crop farming have been the main source of livelihoods for about 90% of the Mbororos as they depend on it for food and income. Climatic perturbations characterized by frequent dry spells, rainfall anomalies and other environmental stressors predicted degrading pastoral resources and the independent variable explained the outcome variable at R = 0.787; R2 = 0. 623; ΔR2 = 0.622; p 〈 0.01. This implies that 62.3% of degradation is accounted for by environmental stressors. As such, the carrying capacity of grazing have gone above the authorized number of two cattle per hectare, leading to overgrazing and degradation. Encroachments into grazing lands by crop farmers, invasion by unproductive grass species and farmer-grazer conflicts are aggravated by climatic stressors. The Fundong council and traditional authorities of the Kom Fondom have been working together to demarcate grazing land and provide water for cattle rearing. Mbororo communities are equally diversifying their activities to ensure food availability.

Description: In order to determine the atmospheric input of 210Pb and seawater-dissolvable Pb in the East Sea (Japan Sea), we measured the concentrations of total 210Pb and dissolved Pb (

Description: We studied the expression profile and ontogeny (from the egg stage through the larval stages and pupal stages, to the elderly adult age) of four OBPs from the silkworm moth Bombyx mori. We first showed that male responsiveness to female sex pheromone in the silkworm moth B. mori does not depend on age variation; whereas the expression of BmorPBP1, BmorPBP2, BmorGOBP1, and BmorGOBP2 varies with age. The expression profile analysis revealed that the studied OBPs are expressed in non-olfactory tissues at different developmental stages. In addition, we tested the effect of insecticide exposure on the expression of the four OBPs studied. Exposure to a toxic macrolide insecticide endectocide molecule (abamectin) led to the modulated expression of all four genes in different tissues. The higher expression of OBPs was detected in metabolic tissues, such as the thorax, gut, and fat body. All these data strongly suggest some alternative functions for these proteins other than olfaction. Finally, we carried out ligand docking studies and reported that PBP1 and GOBP2 have the capacity of binding vitamin K1 and multiple different vitamins.

Description: Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG.Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson’s correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs.Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p 〈 0.001; FOXG1-AS1: Cor = 0.288, p 〈 0.01; AC004943.1: Cor = -0.236, p 〈 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance.Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.

Description: We study theoretical and operational issues of geodesic tractography, a geometric methodology for retrieving biologically plausible neural fibers in the brain from diffusion weighted magnetic resonance imaging. The premise is that true positives are geodesics in a suitably constructed metric space, but unlike traditional first order methods these are not a priori constrained to connect nongeneric points on subdimensional manifolds, such as the characteristics in traditional streamline methods. By virtue of the Hopf-Rinow theorem geodesic tractography furnishes a huge amount of redundancy, ensuring the a priori existence of at least one tentative fiber between any two points and permitting additional tractometric and data-extrinsic constraints for (fuzzy or crisp) classification of true and false positives. In our feasibility study we consider a hybrid paradigm that unifies existing ideas on tractography, combining deterministic and probabilistic elements in a way naturally supported by metric geometry. Particular attention is paid to an analytical prediction of geodesic deviation on numerically computed geodesics, a ‘tidal’ effect induced by small perturbations resulting from data noise. Taking these effects into account clarifies the inherent uncertainty of geodesics, while simultaneosuly offering a dimensionality reduction of the tractography problem.

Description: The importance of phosphorus in the regulation of plant growth function is well studied. However, the role of the inorganic phosphate (Pi) molecule in the mitigation of abiotic stresses such as drought, salinity, heavy metal, heat, and acid stresses are poorly understood. We revisited peer-reviewed articles on plant growth characteristics that are phosphorus (P)-dependently regulated under the sufficient-P and low/no-P starvation alone or either combined with one of the mentioned stress. We found that the photosynthesis rate and stomatal conductance decreased under Pi-starved conditions. The total chlorophyll contents were increased in the P-deficient plants, owing to the lack of Pi molecules to sustain the photosynthesis functioning, particularly, the Rubisco and fructose-1,6-bisphosphatase function. The dry biomass of shoots, roots, and P concentrations were significantly reduced under Pi starvation with marketable effects in the cereal than in the legumes. To mitigate P stress, plants activate alternative regulatory pathways, the Pi-dependent glycolysis, and mitochondrial respiration in the cytoplasm. Plants grown under well-Pi supplementation of drought stress exhibited higher dry biomass of shoots than the no-P treated ones. The Pi supply to plants grown under heavy metals stress reduced the metal concentrations in the leaves for the cadmium (Cd) and lead (Pb), but could not prevent them from absorbing heavy metals from soils. To detoxify from heavy metal stress, plants enhance the catalase and ascorbate peroxidase activity that prevents lipid peroxidation in the leaves. The HvPIP and PHO1 genes were over-expressed under both Pi starvation alone and Pi plus drought, or Pi plus salinity stress combination, implying their key roles to mediate the stress mitigations. Agronomy Pi-based interventions to increase Pi at the on-farm levels were discussed. Revisiting the roles of P in growth and its better management in agricultural lands or where P is supplemented as fertilizer could help the plants to survive under abiotic stresses.

Description: There is a growing body of literature that examines the role of affect and emotions in climate change risk perception and risk communication. Conceptions of affect and emotions have differed according to theoretical perspectives and disciplinary orientations (e.g., sociology of risk, psychology of risk, climate science communication), but little has been done to map these differences. This perspective article provides an in-depth analysis of the study of affect and emotions in climate change risk research through a literature review of studies published in the last 20 years. In this perspective, we examined how affect is conceived, what emotions have been considered, and their role in climate change risk perception and risk communication. Early studies in climate risk perception and risk communication included vaguely defined emotions (e.g., negative and positive) in climate risk perception and risk communication studies, more recently turning attention to how different affective dimensions interact with other factors, such as personal experience, knowledge, culture and worldviews, gender, and social norms. Using this review as a mapping exercise of the research landscape on affect and emotions in climate risk perception and communication, we suggest that future research could benefit from more interdisciplinary work that explores the role of different affective responses and their intensities before, during, and after climate-related events.

Description: Sambhar Salt Lake, situated in the state of Rajasthan, India is a unique temperate hypersaline ecosystem. Exploration of the salt lake microbiome will enable us to understand microbiome functioning in nutrient-deprived extreme conditions, as well as enrich our understanding of the environment-specific microbiome evolution. The current study has been designed to explore the Sambhar Salt Lake microbiome with a culture-independent multi-omics approach to define its metagenomic features and prevalent metabolic functionaries. The rRNA feature and protein feature-based phylogenetic reconstruction synchronously (R = 0.908) indicated the dominance of the archaea (Euryarchaeota) and bacteria (Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria). Metabolic reconstruction identified selective enrichment of the protein features associated with energy harvesting and stress tolerance (osmotic, oxidative, metal/metalloid, heat/cold, antibiotic, and desiccation). Metabolites identified with metabolome analysis confirmed physiological adaptation of the lake microbiome within a hypersaline and nutrient-deprived environment. Comparative metagenomics of the 212 metagenomes representing freshwater, alkaline, and saline ecosystem microbiome indicated the selective enrichment of the microbial groups and genetic features. The current study elucidates microbiome functioning within the nutrient-deprived harsh ecosystems. In summary, the current study harnessing the strength of multi-omics and comparative metagenomics indicates the environment-specific microbiome evolution.

Description: Background: Motilin increases left gastric artery (LGA) blood flow in dogs via the endothelial motilin receptor (MLNR). This article investigates the signaling pathways of endothelial MLNR.Methods: Motilin-induced relaxation of LGA rings was assessed using wire myography. Nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) levels were measured using an NO assay kit and cGMP ELISA kit, respectively.Results: Motilin concentration-dependently (EC50=9.1±1.2×10−8M) relaxed LGA rings precontracted with U46619 (thromboxane A2 receptor agonist). GM-109 (MLNR antagonist) significantly inhibited motilin-induced LGA relaxation and the production of NO and cGMP. N-ethylmaleimide (NEM; G-protein antagonist), U73122 [phospholipase C (PLC) inhibitor], and 2-aminoethyl diphenylborinate [2-APB; inositol trisphosphate (IP3) blocker] partially or completely blocked vasorelaxation. In contrast, chelerythrine [protein kinase C (PKC) inhibitor] and H89 [protein kinase A (PKA) inhibitor] had no such effect. Low-calcium or calcium-free Krebs solutions also reduced vasorelaxation. N-nitro-L-arginine methyl ester [L-NAME; nitric oxide synthase (NOS) inhibitor] and ODQ [soluble guanylyl cyclase (sGC) inhibitor] completely abolished vasodilation and synthesis of NO and cGMP. Indomethacin (cyclooxygenase inhibitor), 18α-glycyrrhetinic acid [18α-GA; myoendothelial gap junction (MEGJ) inhibitor], and K+ channel inhibition through high K+ concentrations or tetraethylammonium (TEA-Cl; KCa channel blocker) partially decreased vasorelaxation, whereas glibenclamide (KATP channel blocker) had no such effect.Conclusion: The current study suggests that motilin-induced LGA relaxation is dependent on endothelial MLNR through the G protein-PLC-IP3 pathway and Ca2+ influx. The NOS-NO-sGC-cGMP pathway, prostacyclin, MEGJ, and K+ channels (especially KCa) are involved in endothelial-dependent relaxation of vascular smooth muscle (VSM) cells.

Description: A review of 35 peer reviewed articles dated from 2016 to February, 2021 was conducted to identify and describe the types of wayfinding devices that people who are blind, visually impaired or deafblind use while navigating indoors and/or outdoors in dynamic travel contexts. Within this investigation, we discovered some characteristics of participants with visual impairments, routes traveled, and real-world environments that have been included in recent wayfinding research as well as information regarding the institutions, agencies, and funding sources that enable these investigations. Results showed that 33 out of the 35 studies which met inclusionary criteria integrated the use of smart device technology. Many of these devices were supplemented by bluetooth low-energy beacons, and other sensors with more recent studies integrating LIDAR scanning. Identified studies included scant information about participant’s visual acuities or etiologies with a few exceptions, which limits the usability of the findings for this highly heterogeneous population. Themes derived from this study are categorized around the individual traveler’s needs; the wayfinding technologies identified and their perceived efficacy; the contexts and routes for wayfinding tasks; and the institutional support offered for sustaining wayfinding research.

Description: Coastal regions globally have experienced widespread anthropogenic eutrophication in recent decades. Loading of autochthonous carbon to coastal sediments enhances the demand for electron acceptors for microbial remineralization, often leading to rearrangement of the sediment diagenetic zonation and potentially enhancing fluxes of methane and hydrogen sulfide from the seafloor. However, the role of anthropogenic inputs of terrestrial organic matter (OMterr.) in modulating diagenesis in coastal sediments is often overlooked, despite being of potential importance in regions of land-use and industrial change. Here we present a dated 4-m sediment and porewater geochemistry record from a eutrophic coastal location in the northern Baltic Sea, to investigate sources of recent carbon loading and their impact on modern diagenetic processes. Based on an end-member mixing model of sediment N/C ratios, we observe that a significant fraction of the late-20th century carbon loading at this location was contributed by OMterr.. Furthermore, analysis of lignin in this material shows depleted ratios of syringyl/vanillyl (S/V) and cinnamyl/vanillyl (C/V) phenols, indicative of enhanced inputs of woody gymnosperm tissue likely from forest industries. The rapid loading of organic matter from combined terrestrial and autochthonous sources during the late 20th century has stimulated methanogenesis in the sediment column, and shoaled the sulfate-methane transition zone (SMTZ) to a depth of 5–20 cm. Optical parameters of colored dissolved organic matter confirm that OMterr. is actively degrading in the methanogenic layer, implying a role for this material in diagenetic processes. Porewater CH4, SO42− δ13C-DIC, and ∑S2− data suggest that the modern SMTZ is a broad zone in which organoclastic sulfate reduction, methanogenesis and anaerobic oxidation of methane (AOM) co-occur. However, fluxes of CH4 and SO42− show that rates of these processes are similar to other marine locations with a comparably shallow SMTZ. We suggest that the shallow depth of the modern SMTZ is the principal reason for high observed diffusive and ebullitive methane fluxes from sediments in this area. Our results highlight that anthropogenic activities lead to multiple pathways of carbon loading to coastal sediments, and that forest industry impacts on sedimentation in the northern Baltic Sea may be more widespread than previously acknowledged.

Description: In this paper, a numerical model based on the mass flow rate of seal leakage is presented, and a 3D numerical method of a multistage axial compressor with good engineering practicability is established. Validation consists of modeling a nine-stage axial compressor in all operating rotation speeds and calculating results of the performance characteristic curves in good agreement with test data. Comparisons are made against different cases of seal leakage mass flow rate for analyzing the impact of increasing seal leakage on the aerodynamic performance of the multistage axial compressor. The results indicate that the performance of the nine-stage axial compressor is degenerated faster and faster with seal leakage increasing in all operating working points, and the degeneration of performance of this compressor can be evaluated by the relationships of main performance parameters with the mass flow rate of seal leakage. Comparisons of flow distribution in the compressor for different cases of seal leakage also show that stators located in front stages of the multistage axial compressor are affected more seriously by the increasing seal leakage, and it can be confirmed that relatively larger flow losses in front stages bring significant impact on the decay of aerodynamic performance of a multistage axial compressor.

Description: Background: Current biomarkers for nasopharyngeal carcinoma (NPC) are less effective for early diagnosis and prognosis. The basic leucine zipper ATF-like transcription factor 2 (BATF2) gene has been shown to have a tight association with the pathogenesis of various malignancies but received scant attention in NPC research. We aimed to assess the performances of circulating and tissue BATF2 in the diagnosis and prognosis of NPC.Materials and Methods: Immunohistochemistry (IHC) microarrays were performed to quantitate the BATF2 protein expression in NPC tissues. The relationships of BATF2 protein expression with clinicopathological characteristics and NPC prognosis were assessed. BATF2 mRNA expressions in serum and serum-derived exosomes were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay.Results: The IHC microarrays revealed a predominant nuclear expression of BATF2 in NPC cells. The Kaplan-Meier survival analysis showed that BATF2-positive NPC patients enjoyed longer overall survival than BATF2-negative patients. NPC patients with serum and exosomal BATF2 mRNA expressions made up 51.47 and 48.52% of all patients, respectively. The AUCs of serum and exosomal BATF2 mRNA expressions in discriminating NPC from healthy controls were 0.9409 and 0.8983. Patients who had received radiochemotherapy exhibited higher serum and exosomal BATF2 mRNA expressions versus the levels at baseline as well as those detected in recurrent patients.Conclusion: BATF2 is expressed cancerous tissues, serum, and serum-derived exosomes in NPC patients. Circulating and tissue BATF2 can serve as a multipurpose biomarker capable of the diagnosis, prognosis prediction, efficacy evaluation, and recurrence monitoring in NPC.

Description: Protons may have contributed to the evolution of plants as a major component of cosmic-rays and also have been used for mutagenesis in plants. Although the mutagenic effect of protons has been well-characterized in animals, no comprehensive phenotypic and genomic analyses has been reported in plants. Here, we investigated the phenotypes and whole genome sequences of Arabidopsis M2 lines derived by irradiation with proton beams and gamma-rays, to determine unique characteristics of proton beams in mutagenesis. We found that mutation frequency was dependent on the irradiation doses of both proton beams and gamma-rays. On the basis of the relationship between survival and mutation rates, we hypothesized that there may be a mutation rate threshold for survived individuals after irradiation. There were no significant differences between the total mutation rates in groups derived using proton beam or gamma-ray irradiation at doses that had similar impacts on survival rate. However, proton beam irradiation resulted in a broader mutant phenotype spectrum than gamma-ray irradiation, and proton beams generated more DNA structural variations (SVs) than gamma-rays. The most frequent SV was inversion. Most of the inversion junctions contained sequences with microhomology and were associated with the deletion of only a few nucleotides, which implies that preferential use of microhomology in non-homologous end joining was likely to be responsible for the SVs. These results show that protons, as particles with low linear energy transfer (LET), have unique characteristics in mutagenesis that partially overlap with those of low-LET gamma-rays and high-LET heavy ions in different respects.

Description: In this study, a new adhesive contact model is built upon a boundary element method (BEM) model developed by Pohrt and Popov (2015). The strain energy release rate (SERR) on the edge of the bonding interface is evaluated using Virtual Crack Closure Technique (VCCT) which is shown to have better accuracy and weaker mesh-size dependency than the closed-form SERR formula derived by Pohrt and Popov. A composite delamination criterion is proposed for crack nucleation and propagation. Numerical results predicted by the present model are in good agreement with the analytical solutions of two classic problems, namely, the axisymmetric parabolic contact and the sinusoidal waviness contact in the plane strain condition. The model of Pohrt and Popov can achieve a similar accuracy for the axisymmetric parabolic contact where the mesh grid is non-conforming to the crack front. Once the conforming mesh grid is used, the accuracy of their model is significantly deteriorated, especially at high work of adhesion and high mesh density. In both BEM models, however, the crack nucleation is found to be mesh-dependent which may be solved by introducing an upper limit for the tensile normal traction.

Description: Monte Carlo simulation of particle tracking in matter is the reference simulation method in the field of medical physics. It is heavily used in various applications such as 1) patient dose distribution estimation in different therapy modalities (radiotherapy, protontherapy or ion therapy) or for radio-protection investigations of ionizing radiation-based imaging systems (CT, nuclear imaging), 2) development of numerous imaging detectors, in X-ray imaging (conventional CT, dual-energy, multi-spectral, phase contrast … ), nuclear imaging (PET, SPECT, Compton Camera) or even advanced specific imaging methods such as proton/ion imaging, or prompt-gamma emission distribution estimation in hadrontherapy monitoring. Monte Carlo simulation is a key tool both in academic research labs as well as industrial research and development services. Because of the very nature of the Monte Carlo method, involving iterative and stochastic estimation of numerous probability density functions, the computation time is high. Despite the continuous and significant progress on computer hardware and the (relative) easiness of using code parallelisms, the computation time is still an issue for highly demanding and complex simulations. Hence, since decades, Variance Reduction Techniques have been proposed to accelerate the processes in a specific configuration. In this article, we review the recent use of Artificial Intelligence methods for Monte Carlo simulation in medical physics and their main associated challenges. In the first section, the main principles of some neural networks architectures such as Convolutional Neural Networks or Generative Adversarial Network are briefly described together with a literature review of their applications in the domain of medical physics Monte Carlo simulations. In particular, we will focus on dose estimation with convolutional neural networks, dose denoising from low statistics Monte Carlo simulations, detector modelling and event selection with neural networks, generative networks for source and phase space modelling. The expected interests of those approaches are discussed. In the second section, we focus on the current challenges that still arise in this promising field.

Description: The untranslated region (UTRs) of viral genome are important for viral replication and immune modulation. Japanese encephalitis virus (JEV) is the most significant cause of epidemic encephalitis worldwide. However, little is known regarding the characterization of the JEV UTRs. Here, systematic analyses of the UTRs of JEVs isolated from a variety of hosts worldwide spanning about 80 years were made. All the important cis-acting elements and structures were compared with other mosquito-borne Flaviviruses [West Nile virus (WNV), Yellow fever virus (YFV), Zika virus (ZIKV), Dengue virus (DENV)] and annotated in detail in the UTRs of different JEV genotypes. Our findings identified the JEV-specific structure and the sequence motif with unique JEV feature. (i) The 3’ dbsHP was identified as a small hairpin located in the DB region in the 3′ UTR of JEV, with the structure highly conserved among the JEV genotypes. (ii) The spacer sequence UARs of JEV consist of four discrete spacer sequences, whereas the UARs of other mosquito-borne Flaviviruses are continuous sequences. In addition, repetitive elements have been discovered in the UTRs of mosquito-borne Flaviviruses. The lengths, locations, and numbers of the repetitive elements of JEV also differed from other Flaviviruses (WNV, YFV, ZIKV, DENV). A 300 nt-length region located at the beginning of the 3′ UTR exhibited significant genotypic specificity. This study lays the basis for future research on the relationships between the JEV specific structures and elements in the UTRs, and their important biological function.

Description: Fibroblast growth factor (FGF) 23 is elevated in chronic kidney disease (CKD) to maintain phosphate homeostasis. FGF23 is associated with left ventricular hypertrophy (LVH) in CKD and induces LVH via klotho-independent FGFR4-mediated activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling in animal models, displaying systemic alterations possibly contributing to heart injury. Whether elevated FGF23 per se causes LVH in healthy animals is unknown. By generating a mouse model with high intra-cardiac Fgf23 synthesis using an adeno-associated virus (AAV) expressing murine Fgf23 (AAV-Fgf23) under the control of the cardiac troponin T promoter, we investigated how cardiac Fgf23 affects cardiac remodeling and function in C57BL/6 wild-type mice. We report that AAV-Fgf23 mice showed increased cardiac-specific Fgf23 mRNA expression and synthesis of full-length intact Fgf23 (iFgf23) protein. Circulating total and iFgf23 levels were significantly elevated in AAV-Fgf23 mice compared to controls with no difference in bone Fgf23 expression, suggesting a cardiac origin. Serum of AAV-Fgf23 mice stimulated hypertrophic growth of neonatal rat ventricular myocytes (NRVM) and induced pro-hypertrophic NFAT target genes in klotho-free culture conditions in vitro. Further analysis revealed that renal Fgfr1/klotho/extracellular signal-regulated kinases 1/2 signaling was activated in AAV-Fgf23 mice, resulting in downregulation of sodium-phosphate cotransporter NaPi2a and NaPi2c and suppression of Cyp27b1, further supporting the bioactivity of cardiac-derived iFgf23. Of interest, no LVH, LV fibrosis, or impaired cardiac function was observed in klotho sufficient AAV-Fgf23 mice. Verified in NRVM, we show that co-stimulation with soluble klotho prevented Fgf23-induced cellular hypertrophy, supporting the hypothesis that high cardiac Fgf23 does not act cardiotoxic in the presence of its physiological cofactor klotho. In conclusion, chronic exposure to elevated cardiac iFgf23 does not induce LVH in healthy mice, suggesting that Fgf23 excess per se does not tackle the heart.

Description: BackgroundVisceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani (L. donovani), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance. Therefore, it is time to search for cheap and effective antileishmanial agents. In the present work, we evaluated the antileishmanial potential of sesamol against promastigotes as well as intracellular amastigotes. Further, we tried to work out its mechanism of antileishmanial action on parasites through different assays.MethodologyIn vitro and ex vivo antileishmanial assays were performed to evaluate the antileishmanial potential of sesamol on L. donovani. Cytotoxicity was determined by MTT assay on human THP-1-derived macrophages. Sesamol-induced morphological and ultrastructural changes were determined by electron microscopy. H2DCFDA staining, JC-1dye staining, and MitoSOX red staining were performed for reactive oxygen assay (ROS), mitochondrial membrane potential, and mitochondrial superoxide, respectively. Annexin V/PI staining for apoptosis, TUNEL assay, and DNA laddering for studying sesamol-induced DNA fragmentation were performed.ConclusionsSesamol inhibited the growth and proliferation of L. donovani promastigotes in a dose-dependent manner. It also reduced the intracellular parasite load without causing significant toxicity on host-macrophages. Overall, it showed antileishmanial effects through induction of ROS, mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death to parasites. Our results suggested the possible use of sesamol for the treatment of leishmaniasis after further in vivo validations.

Description: Background: Colorectal cancer (CRC) ranks as the third most common malignancy worldwide but a reliable prognostic biomarker of CRC is still lack. Thus, the purpose of our study was to explore whether ferroptosis - related lncRNAs could predict the prognosis of CRC.Methods: The mRNA expression profiling of colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients in The Cancer Genome Atlas (TCGA) database were downloaded. Univariate Cox and multivariate Cox regression analyses was used to obtain prognostic differently expressed ferroptosis-related lncRNAs (DE-FLs) and a risk signature was developed. Quantitative polymerase chain reaction (q-PCR) was used to validated the different expressions of DE-FLs. The calibration curves, C-index and the receiver operating characteristic (ROC) curves were applied to evaluate the accuracy of nomogram. Gene set enrichment analyses (GSEA) were carried out to explore the biological mechanism between high- and low-risk group and the potential regulated pathway of prognostic DE-FLs in CRC.Results: Forty-nine DE-FLs were identified between CRC and normal tissue. Then, a 4-DE-FLs (AC016027.1, AC099850.3, ELFN1-AS1, and VPS9D1-AS1) prognostic signature model was generated. AC016027.1 was downregulated in CRC tissue; VPS9D1-AS1 and ELFN1-AS1 were upregulated by q-PCR. The model had a better accuracy presenting by 1-, 3-, and 5-years ROC curve (AUC ≥0.6), and identified survival probability (p 〈 0.05) well. Moreover, the risk signature could play as an independent factor of CRC (p 〈 0.05). Further, a nomogram including age, pathologic stage, T stage, and risk score with good prognostic capability (C-index = 0.789) was constructed. In addition, we found biological pathways mainly related to metabolism and apoptosis were down-regulated in high-risk group who with poor outcome. Finally, the functional enrichment showed prognostic DE-FLs may significantly impact bile secretion in CRC.Conclusion: A risk model and nomogram based on ferroptosis-related lncRNAs were created to predict 1-, 3-, and 5-years survival probability of CRC patients. Our data suggested that the prognostic lncRNAs could serve as valuable prognostic marker.

Description: Mitochondria-derived peptides (MDPs) are a new class of bioactive peptides encoded by small open reading frames (sORFs) within known mitochondrial DNA (mtDNA) genes. MDPs may affect the expression of nuclear genes and play cytoprotective roles against chronic and age-related diseases by maintaining mitochondrial function and cell viability in the face of metabolic stress and cytotoxic insults. In this review, we summarize clinical and experimental findings indicating that MDPs act as local and systemic regulators of glucose homeostasis, immune and inflammatory responses, mitochondrial function, and adaptive stress responses, and focus on evidence supporting the protective effects of MDPs against myocardial infarction. These insights into MDPs actions suggest their potential in the treatment of cardiovascular diseases and should encourage further research in this field.

Description: Watermelon (Citrullus lanatus) is a valuable horticultural crop with nutritional benefits grown worldwide. It is almost exclusively cultivated as grafted scions onto interspecific squash rootstock (Cucurbita maxima × Cucurbita moschata) to improve the growth and yield and to address the problems of soilborne diseases and abiotic stress factors. This study aimed to examine the effect of grafting (homo- and hetero-grafting) on the transcriptome level of the seedlings. Therefore, we compared homo-grafted watermelon (WW) with non-grafted watermelon control (W), homo-grafted squash (SS) with non-grafted squash control (S), hetero-grafted watermelon onto squash (WS) with SS, and WS with WW. Different numbers of differentially expressed genes (DEGs) were identified in each comparison. In total, 318 significant DEGs were detected between the transcriptomes of hetero-grafts and homo-grafts at 16 h after grafting. Overall, a significantly higher number of downregulated transcripts was detected among the DEGs. Only one gene showing increased expression related to the cytokinin synthesis was common in three out of four comparisons involving WS, SS, and S. The highest number of differentially expressed (DE) transcripts (433) was detected in the comparison between SS and S, followed by the 127 transcripts between WW and W. The study provides a description of the transcriptomic nature of homo- and hetero-grafted early responses, while the results provide a start point for the elucidation of the molecular mechanisms and candidate genes for the functional analyses of hetero-graft and homo-graft systems in Cucurbitaceae and generally in the plants.

Description: Ribosomal RNA genes (rDNAs) are located in large domains of hundreds of rDNA units organized in a head-to-tail manner. The proper and stable inheritance of rDNA clusters is of paramount importance for survival. Yet, these highly repetitive elements pose a potential risk to the genome since they can undergo non-allelic exchanges. Here, we review the current knowledge of the organization of the rDNA clusters in Arabidopsis thaliana and their stability during meiosis. Recent findings suggest that during meiosis, all rDNA loci are embedded within the nucleolus favoring non-homologous end joining (NHEJ) as a repair mechanism, while DNA repair via homologous recombination (HR) appears to be a rare event. We propose a model where (1) frequent meiotic NHEJ events generate abundant single nucleotide polymorphisms and insertions/deletions within the rDNA, resulting in a heterogeneous population of rDNA units and (2) rare HR events dynamically change rDNA unit numbers, only to be observed in large populations over many generations. Based on the latest efforts to delineate the entire rDNA sequence in A. thaliana, we discuss evidence supporting this model. The results compiled so far draw a surprising picture of rDNA sequence heterogeneity between individual units. Furthermore, rDNA cluster sizes have been recognized as relatively stable when observing less than 10 generations, yet emerged as major determinant of genome size variation between different A. thaliana ecotypes. The sequencing efforts also revealed that transcripts from the diverse rDNA units yield heterogenous ribosome populations with potential functional implications. These findings strongly motivate further research to understand the mechanisms that maintain the metastable state of rDNA loci.

Description: Soil salinity is important abiotic stress affecting various ecosystems worldwide such as grassland. Distinct ecotypes often evolve within species by natural selection to facilitate adaptation to different types of environmental stress. Leymus chinensis is a perennial rhizomatous grass that is widely distributed in the eastern Eurasian steppe; it has two main ecotypes, namely, yellow-green (YG) and gray-green (GG), which differ in their strategy for coping with salinity stress. Few studies have examined the seed germination of the two ecotypes under salinity stress. In this study, the seed germination and seedling growth of two ecotypes of L. chinensis in response to different levels of salinity (NaCl) stress [0 (control), 20, 50, 100, and 200 mM] were examined. Then, ungerminated seeds were placed under normal conditions to evaluate seedling growth following exposure to salt stress (i.e., regermination). The germination percentage was significantly higher, and the mean germination time was significantly shorter in the GG ecotype than in the YG ecotype at all NaCl concentrations. As the salinity level increased, the radicle length of the two ecotypes decreased; however, GG had longer radicles and a higher number of radicles, even at 200 mM NaCl when no radicle protruding from the seed coat was detected in YG. The shoot length of GG was significantly longer than that of YG at all NaCl levels. After salinity stress was removed, the seed germination percentage increased as the original concentration of NaCl applied increased, but the total germination percentage did not significantly differ among NaCl concentrations. The total seed germination percentage of GG was approximately 80%, whereas that of the YG was approximately 20%. The seedling length of regerminated seeds for both GG and YG was similar. The thousand-grain weight of GG was significantly higher than that of YG. GG was more salt-tolerant than YG and might be better capable of surviving in harsher environments, suggesting that GG might be particularly useful for saline grassland restoration.

Description: There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota, glucose, and lipid. However, the function of water-electrolyte metabolism remains undefined in children with NAFLD. Therefore, the aim of this case-control study was to better understand these interactions. The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without NAFLD. These groups were matched by age, sex, and body mass index. Data were collected between June, 2019 and December, 2019 at the Hunan Children’s Hospital, in China. Microbiome composition in fecal samples was assessed using 16S ribosomal RNA amplicon sequencing. In the clinical indices, 12 glucose and lipid metabolism indices were included, and six water-electrolyte metabolism indices were included. The results indicated that microbiomes of NAFLD children had lower alpha diversity but higher beta diversity index than the other two groups. Specifically, anti-inflammatory and probiotics abundance (e.g., Faecalibacterium, Akkermansia, and Bifidobacterium_adolescentis) was significantly decreased in NAFLD, whereas the abundance of harmful bacteria (e.g., Staphylococcaceae) was increased. Moreover, the abundance of butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia_inulinivorans, Roseburia_intestinalis, and Coprococcus_comes) was significantly decreased in NASH. The abundance of these bacteria were associated with glucose, lipid, and water-electrolyte metabolism (e.g., glucose, triglyceride, cholesterol, inorganic salt, total body water, etc.), implying that the NAFLD and its severity were associated with glucose, lipid, and water-electrolyte metabolism dysbiosis. Therefore, these findings suggest that the gut microbiome, especially butyrate-producing bacteria, play an important role in the development of NAFLD in children.

Description: Enshrined in different conventions nationally and internationally, education is a fundamental right of every child irrespective of identity and location worldwide. Despite the Universal Declaration of Human Rights (UDHR) 1948 and the United Nations (UN) Convention on the Rights of the Child 1989, education is not accessible and affordable for every child globally due to several entwined factors. Focusing on Pakistan’s Sindh Province, this article identifies the numerous factors that lead to school dropouts and illustrates their interconnectedness. Employing Sen’s Capabilities Approach, we show a relation between freedom and function, whereby a capability can only be a function if there is an opportunity. We conclude and suggest that since the basic right of education is denied in Pakistan owing to sociocultural, economic, and political factors, there is a need to make necessary efforts at the parental as well as national policy level to address it. We also ask for ethnographically rich studies that should comparatively and thoroughly bring this dropout problem to the center stage for generating a comprehensive understanding so that this basic right is given to every child of this country.

Description: Infectious diseases are the disorders caused by organisms such as bacteria, viruses, fungi, or parasites. Although many of them are permentantly hazardous, a number of them live in and on our bodies and they are normally harmless or even helpful. Under certain circumstances, some organisms may cause diseases and these infectious diseases may be passed directly from person to person or via intermediate vectors including insects and other animals. Dengue virus and Streptococcus pneumoniae are the critical and common sources of infectious diseases. So, it is critical to understand the gene expression profiling and their inferred functions in comparison to the normal and virus infected conditions. Here, we have analyzed the gene expression profiling for dengue hemorrhagic fever, dengue fever, and normal human dataset. Similar to it, streptococcus pneumoniae infectious data were analyzed and both the outcomes were compared. Our study leads to the conclusion that the dengue hemorrhagic fever arises in result to potential change in the gene expression pattern, and the inferred functions obviously belong to the immune system, but also there are some additional potential pathways which are critical signaling pathways. In the case of pneumoniae infection, 19 pathways were enriched, almost all these pathways are associated with the immune system and 17 of the enriched pathways were common with dengue infection except platelet activation and antigen processing and presentation. In terms of the comparative study between dengue virus and Streptococcus pneumoniae infection, we conclude that cell adhesion molecules (CAMs), MAPK signaling pathway, natural killer cell mediated cytotoxicity, regulation of actin cytoskeleton, and cytokine-cytokine receptor interaction are commonly enriched in all the three cases of dengue infection and Streptococcus pneumoniae infection, focal adhesion was enriched between classical dengue fever — dengue hemorrhagic fever, dengue hemorrhagic fever—normal samples, and SP, and antigen processing and presentation and Leukocyte transendothelial migration were enriched in classical dengue fever —normal samples, dengue hemorrhagic fever—normal samples, and Streptococcus pneumoniae infection.

Description: Tau35 is a truncated form of tau found in human brain in a subset of tauopathies. Tau35 expression in mice recapitulates key features of human disease, including progressive increase in tau phosphorylation, along with cognitive and motor dysfunction. The appearance of aggregated tau suggests that Tau35 may have structural properties distinct from those of other tau species that could account for its pathological role in disease. To address this hypothesis, we performed a structural characterization of monomeric and aggregated Tau35 and compared the results to those of two longer isoforms, 2N3R and 2N4R tau. We used small angle X-ray scattering to show that Tau35, 2N3R and 2N4R tau all behave as disordered monomeric species but Tau35 exhibits higher rigidity. In the presence of the poly-anion heparin, Tau35 increases thioflavin T fluorescence significantly faster and to a greater extent than full-length tau, demonstrating a higher propensity to aggregate. By using atomic force microscopy, circular dichroism, transmission electron microscopy and X-ray fiber diffraction, we provide evidence that Tau35 aggregation is mechanistically and morphologically similar to previously reported tau fibrils but they are more densely packed. These data increase our understanding of the aggregation inducing properties of clinically relevant tau fragments and their potentially damaging role in the pathogenesis of human tauopathies.

Description: The Leaf-Area-Index (LAI) is commonly used to characterize the plant canopy and is a fundamental indication of plant vitality and photosynthetic activity. The forest health status is not only vital for economical reasons, but also has a significant impact on global carbon sequestration. The LAI has a highly dynamic character among deciduous forests and is prone to significant seasonal fluctuations. Accurate continuous LAI measurements do provide valuable information on growth characteristics, but they require considerable measurement effort. In this study, we tested a novel method that would allow for continuous low-effort LAI parameterizations. For our study we used temperature measurements from 2011 to 2019 obtained at two meteorological stations: Station one is an open land station, station two is located inside a forest stand characterized by European beech (measurements were undertaken as part of the ICP Forests program), both are located in Klausen Leopoldsdorf (Austria). We chose the difference in daily maximum temperature between the two sites for our LAI parametrization (LAIpar) since the forest canopy has a significant impact on local radiation conditions. We were able to identify phenological events such as leaf unfolding, the end of leaf growth, and the beginning and end of defoliation by examining at the average course of the year for LAIpar. The resultant LAIpar values were compared to annual values derived from hemispheric photographs taken near the stand temperature sensor. For the years 2011–2017, we found a strong correlation of 0.93 between LAI measures and LAIpar, which dropped to 0.69 after adding the year 2018 and 0.32 after adding 2019. We further compared the phenological events obtained from LAIpar to phenological observations. The impact of forests on their site climate, according to our findings, can be utilized to identify phenological and growth characteristics. The proposed method, however, is not a replacement for conventional LAI measurements.

Description: Chagas disease is a major public health problem, especially in the South and Central America region. Its incidence is related to poverty and presents a high rate of morbidity and mortality. The pathogenesis of Chagas disease is complex and involves many interactive pathways between the hosts and the Trypanosoma cruzi. Several factors have been implicated in parasite-host interactions, including molecules secreted by infected cells, lipid mediators and most recent, extracellular vesicles (EVs). The EVs of T. cruzi (EVsT) were reported for the first time in the epimastigote forms about 42 years ago. The EVsT are involved in paracrine communication during the infection and can have an important role in the inflammatory modulation and parasite escape mechanism. However, the mechanisms by which EVs employ their pathological effects are not yet understood. The EVsT seem to participate in the activation of macrophages via TLR2 triggering the production of cytokines and a range of other molecules, thus modulating the host immune response which promotes the parasite survival. Moreover, new insights have demonstrated that EVsT induce lipid body formation and PGE2 synthesis in macrophages. This phenomenon is followed by the inhibition of the synthesis of pro-inflammatory cytokines and antigen presentation, causing decreased parasitic molecules and allowing intracellular parasite survival. Therefore, this mini review aims to discuss the role of the EVs from T. cruzi as well as its involvement in the mechanisms that regulate the host immune response in the lipid metabolism and its significance for the Chagas disease pathophysiology.

Description: The ecological success of corals depends on their association with microalgae and a diverse bacterial assemblage. Ocean acidification (OA), among other stressors, threatens to impair host-microbial metabolic interactions that underlie coral holobiont functioning. Volcanic CO2 seeps offer a unique opportunity to study the effects of OA in natural reef settings and provide insight into the long-term adaptations under a low pH environment. Here we compared nitrogen-fixing bacteria (diazotrophs) associated with four coral species (Pocillopora damicornis, Galaxea fascicularis, Acropora secale, and Porites rus) collected from CO2 seeps at Tutum Bay (Papua New Guinea) with those from a nearby ambient CO2 site using nifH amplicon sequencing to characterize the effects of seawater pH on bacterial communities and nitrogen cycling. Diazotroph communities were of generally low diversity across all coral species and for both sampling sites. Out of a total of 25 identified diazotroph taxa, 14 were associated with P. damicornis, of which 9 were shared across coral species. None of the diazotroph taxa, however, were consistently found across all coral species or across all samples within a species pointing to a high degree of diazotroph community variability. Rather, the majority of sampled colonies were dominated by one or two diazotroph taxa of high relative abundance. Pocillopora damicornis and Galaxea fascicularis that were sampled in both environments showed contrasting community assemblages between sites. In P. damicornis, Gammaproteobacteria and Cyanobacteria were prevalent under ambient pCO2, while a single member of the family Rhodobacteraceae was present at high relative abundance at the high pCO2 site. Conversely, in G. fascicularis diazotroph communities were indifferent between both sites. Diazotroph community changes in response to OA seem thus variable within as well as between host species, potentially arguing for haphazard diazotroph community assembly. This warrants further research into the underlying factors structuring diazotroph community assemblages and their functional role in the coral holobiont.

Description: Anthocyanins represent the major red, purple, and blue pigments in many flowers, fruits, vegetables, and cereals. They are also recognized as important health-promoting components in the human diet with protective effects against many chronic diseases, including cardiovascular diseases, obesity, and cancer. Anthocyanin biosynthesis has been studied extensively, and both biosynthetic and key regulatory genes have been isolated in many plant species. Here, we will provide an overview of recent progress in understanding the anthocyanin biosynthetic pathway in plants, focusing on the transcription factors controlling activation or repression of anthocyanin accumulation in cereals and fruits of different plant species, with special emphasis on the differences in molecular mechanisms between monocot and dicot plants. Recently, new insight into the transcriptional regulation of the anthocyanin biosynthesis, including positive and negative feedback control as well as epigenetic and post-translational regulation of MYB-bHLH-WD40 complexes, has been gained. We will consider how knowledge of regulatory mechanisms has helped to produce anthocyanin-enriched foods through conventional breeding and metabolic engineering. Additionally, we will briefly discuss the biological activities of anthocyanins as components of the human diet and recent findings demonstrating the important health benefits of anthocyanin-rich foods against chronic diseases.

Description: The study was conducted to compare peak oxygen uptake (VO2peak) measured with the incremental graded test (GXT) (VO2peak) and two tests to verify maximum oxygen uptake, performed 15 min after the incremental test (VO2peak1) and on a separate day (VO2peak2). The aim was to determine which of the verification tests is more accurate and, more generally, to validate the VO2max obtained in the incremental graded test on cycle ergometer. The study involved 23 participants with varying levels of physical activity. Analysis of variance showed no statistically significant differences for repeated measurements (F = 2.28, p = 0.118, η2 = 0.12). Bland–Altman analysis revealed a small bias of the VO2peak1 results compared to the VO2peak (0.4 ml⋅min–1⋅kg–1) and VO2peak2 results compared to the VO2peak (−0.76 ml⋅min–1⋅kg–1). In isolated cases, it was observed that VO2peak1 and VO2peak2 differed by more than 5% from VO2peak. Considering the above, it can be stated that among young people, there are no statistically significant differences between the values of VO2peak measured in the following tests. However, in individual cases, the need to verify the maximum oxygen uptake is stated, but performing a second verification test on a separate day has no additional benefit.

Description: Saccharomyces cerevisiae, commonly known as baker’s yeast, is one of the most comprehensively studied model organisms in science. Yeast has been used to study a wide variety of human diseases, and the yeast model system has proved to be an especially amenable tool for the study of lipids and lipid-related pathophysiologies, a topic that has gained considerable attention in recent years. This review focuses on how yeast has contributed to our understanding of the mitochondrial phospholipid cardiolipin (CL) and its role in Barth syndrome (BTHS), a genetic disorder characterized by partial or complete loss of function of the CL remodeling enzyme tafazzin. Defective tafazzin causes perturbation of CL metabolism, resulting in many downstream cellular consequences and clinical pathologies that are discussed herein. The influence of yeast research in the lipid-related pathophysiologies of Alzheimer’s and Parkinson’s diseases is also summarized.

Description: This study examines the direct and indirect effects of home numeracy and literacy environment, and parental factors (parental reading and math difficulties, and parental education) on the development of several early numeracy and literacy skills. The 265 participating Finnish children were assessed four times between ages 2.5 and 6.5. Children’s skills in counting objects, number production, number sequence knowledge, number symbol knowledge, number naming, vocabulary, print knowledge, and letter knowledge were assessed individually. Parents (N = 202) reported on their education level, learning difficulties in math and reading (familial risk, FR), and home learning environment separately for numeracy (HNE) and literacy (HLE) while their children were 2.5 years old and again while they were 5.5 years old. The results revealed both within-domain and cross-domain associations. Parents’ mathematical difficulties (MD) and reading difficulties (RD) and home numeracy environment predicted children’s numeracy and literacy skill development within and across domains. An evocative effect was found as well; children’s skills in counting, number sequence knowledge, number symbol identification, and letter knowledge negatively predicted later home numeracy and literacy activities. There were no significant indirect effects from parents’ RD, MD, or educational level on children’s skills via HLE or HNE. Our study highlights that parental RD and MD, parental education, and the home learning environment form a complex pattern of associations with children’s numeracy and literacy skills starting already in toddlerhood.

Description: In the current study the ability of four previously characterized bifidobacterial β-galactosidases (designated here as BgaA, BgaC, BgaD, and BgaE) to produce galacto-oligosaccharides (GOS) was optimized. Of these enzymes, BgaA and BgaE were found to be promising candidates for GOS production (and the corresponding GOS mixtures were called GOS-A and GOS-E, respectively) with a GOS concentration of 19.0 and 40.3% (of the initial lactose), respectively. GOS-A and GOS-E were partially purified and structurally characterized. NMR analysis revealed that the predominant (non-lactose) disaccharide was allo-lactose in both purified GOS preparations. The predominant trisaccharide in GOS-A and GOS-E was shown to be 3′-galactosyllactose, with lower levels of 6′-galactosyllactose and 4′-galactosyllactose. These three oligosaccharides have also been reported to occur in human milk. Purified GOS-A and GOS-E were shown to be able to support bifidobacterial growth similar to a commercially available GOS. In addition, GOS-E and the commercially available GOS were shown to be capable of reducing Escherichia coli adhesion to a C2BBe1 cell line. Both in vitro bifidogenic activity and reduced E. coli adhesion support the prebiotic potential of GOS-E and GOS-A.

Description: New miRNAs are evolutionarily important but their functional evolution remains unclear. Here we report that the evolution of a microRNA cluster, mir-972C rewires its downstream regulatory networks in Drosophila. Genomic analysis reveals that mir-972C originated in the common ancestor of Drosophila where it comprises six old miRNAs. It has subsequently recruited six new members in the melanogaster subgroup after evolving for at least 50 million years. Both the young and the old mir-972C members evolved rapidly in seed and non-seed regions. Combining target prediction and cell transfection experiments, we found that the seed and non-seed changes in individual mir-972C members cause extensive target divergence among D. melanogaster, D. simulans, and D. virilis, consistent with the functional evolution of mir-972C reported recently. Intriguingly, the target pool of the cluster as a whole remains relatively conserved. Our results suggest that clustering of young and old miRNAs broadens the target repertoires by acquiring new targets without losing many old ones. This may facilitate the establishment of new miRNAs in existing regulatory networks.

Description: In the modern era, rapid anthropogenic activities in the vicinity of the Himalayas disturb the carbon sequestration potential resulting in climate change. For the first time, this study estimates the biomass and carbon storage potential of Northeast India’s diverse land uses through a biomass estimation model developed for this region. The mean tree density in tropical, subtropical, and temperate forests was 539, 554, and 638 trees ha−1, respectively. The mean vegetation carbon stock was the highest for temperate forests (122.09 Mg C ha−1), followed by subtropical plantations (115.45 Mg C ha−1), subtropical forests (106.01 Mg C ha−1), tropical forests (105.33 Mg C ha−1), tropical plantations (93.00 Mg C ha−1), and temperate plantations (50.10 Mg C ha−1). Among the forests, the mean soil organic carbon (SOC) stock up to 45 cm depth was the highest for tropical forests (72.54 Mg C ha−1), followed by temperate forests (63.4 Mg C ha−1) and subtropical forests (42.58 Mg C ha−1). A strong relationship between the tree basal area and biomass carbon storage was found for all land-use types. The land-use transformation from agriculture to agroforestry, and grassland to plantations increased both vegetation carbon (VC) and SOC stocks. The corresponding increase in VC and SOC was 40.80 and 43.34 Mg C ha−1, respectively, in the former, and 83.18 and 97.64 Mg C ha−1 in the latter. In general, the landscape-level estimates were drawn from site-level estimates in a given land-use type, and therefore, the corresponding values might be overestimated. Nevertheless, the results provide baseline information on carbon stock which may serve as a reference for devising appropriate land-use change policies in the region.

Description: Background: Currently, the incidence of gastrointestinal stromal tumors (GIST) is increasing rapidly worldwide. Malnutrition may increase the risk of perioperative complications and affect the prognosis of patients. However, previous studies on the nutritional status of GIST patients and its impact on prognosis are limited. Therefore, this study aims to explore the incidence of malnutrition in newly diagnosed GIST patients, the proportion of participants in need of nutritional intervention, and the relationship between nutritional status and overall survival (OS).Methods: We retrospectively analyzed the clinical data of GIST patients treated in our hospital from January 2014 to January 2018. Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess the nutritional status of all patients. This study was to investigate the clinical significance of PG-SGA by analyzing the relationship between PG-SGA score and OS.Results: A total of 1,268 newly diagnosed GIST patients were included in this study, of which 77.76% were at risk of malnutrition (NRS2002 score ≥ 3), and the incidence of malnutrition was 10.09% (PG-SGA score ≥ 4). Meanwhile, we found 2.29% of the patients required urgent nutritional support (PG-SGA score ≥ 9). Multivariate analysis showed that age (p = 0.013), BMI (p = 0.001), weight loss (p = 0.001), anemia (p = 0.005), pre-albumin (p = 0.010), albumin (p = 0.002), tumor location (p = 0.001), tumor size (p = 0.002), and NIH classification (p = 0.001) were risk factors for nutritional status. The prognosis was significantly in GIST patients with different PG-SGA score at admission (p 〈 0.05).Conclusion: This study suggested that malnutrition is common in newly diagnosed GIST patients, and the higher the PG-SGA score, the worse the clinical outcome.

Description: Based on the newly released China Merged Surface Temperature (China-MST) dataset, we diagnose the leading mode of covariation between surface temperature and the summer precipitation in Eastern China (EC). A possible connection between the surface temperature in East Asia and EC summer precipitation since the last century (1901–2016) is analyzed. Results indicate that there exists a remarkable meridional dipole pattern of surface temperature, defined as the meridional temperature difference index (MTDI). Meanwhile, there is a tripolar pattern of summer precipitation, which coincides with the first principal component of summer precipitation in EC. Further analyses show that when the MTDI is high in summer, an anomalous anticyclonic/cyclonic circulation is in East Asia’s mid/low latitude. The water vapor is down in the Yangtze and Huaihe River basins, and the ascending motion is weak, resulting in reduced precipitation over this region. At the same time, more water vapor and intensified ascending motion in North and South China tend to produce more summer precipitation. The opposite situations are found when the MTDI is low. Moreover, the MTDI closely relates with the Pacific Decadal Oscillation and the Atlantic Multidecadal Oscillation at interdecadal and multi-decadal scales. These results have been substantiated in the application of information flow analysis, a recently developed method in physics for the inference of causality between dynamical events.

Description: Autophagy is an evolutionary conserved degradative process contributing to cytoplasm quality control, metabolic recycling and cell defense. Aging is a universal phenomenon characterized by the progressive accumulation of impaired molecular and reduced turnover of cellular components. Recent evidence suggests a unique role for autophagy in aging and age-related disease. Indeed, autophagic activity declines with age and enhanced autophagy may prevent the progression of many age-related diseases and prolong life span. All tissues experience changes during aging, while the role of autophagy in different tissues varies. This review summarizes the links between autophagy and aging in the whole organism and discusses the physiological and pathological roles of autophagy in the aging process in tissues such as skeletal muscle, eye, brain, and liver.

Description: A growing trend of interest for the cultivation of kelp is driven by predictions for high global demands of important commodities, which require the development of alternative supplies of natural resources. In this study the dynamics of loss of biomass from cultivated Saccharina latissima were studied from February to August 2018 at two kelp farms in Northern (69°45.26′N/019°02.18′E) and in Mid-Norway (63°42.28′N/08°52.23′E). Kelp fronds at each farm were individually followed throughout the growing season. Sectional regression was applied for conversion of measured frond lengths to estimated dry weights. The study shows that between 40 and 100% of all individuals in the studied kelp population constantly eroded slightly from their distal ends. However, until June the accumulated loss was only 8% of produced dry weight. Due to dislodgement of whole sporophytes this picture changed in July and August to heavy losses in Mid-Norway. Thus, the overall losses of kelp in terms of accumulated dry weight were only 8–13% of the gross growth until harvest in June in Mid-Norway and August in Northern Norway. Losses increased significantly in Mid-Norway during July and reached 49.4% of the annual production in August. The rates of losses were separated into specific erosion and dislodgement rates. Erosion rates over the whole experimental period for the two sites were not significantly different, while differences in dislodgement rates between farm sites proved to be highly significant. The exported annual amount of carbon was estimated on the basis of lost and measured carbon content in the tissue. From these data a scenario was built for a commercial Norwegian kelp farm growing S. latissima showing a carbon export of 63–88 g C m–2y–1. This is eight times less than has been reported from scenarios for kelp farms in China. This study confirms that optimal timing of harvest is the most important management tool for avoidance of heavy losses from kelp farms. In conclusion, an industry with early harvest will likely have a low carbon export, while a late-harvested bulk production could export four to six times as much carbon with an increased potential for carbon sequestration.

Description: The genus of Plasmodium parasites can cause malaria, which is a prevalent infectious disease worldwide, especially in tropical and subtropical regions. C57BL/6 mice infected with P. berghei ANKA (PbA) will suffer from experimental cerebral malaria (ECM). However, the gut microbiota in C57BL/6 mice has rarely been investigated, especially regarding changes in the intestinal environment caused by infectious parasites. P. berghei ANKA-infected (PbA group) and uninfected C57BL/6 (Ctrl group) mice were used in this study. C57BL/6 mice were infected with PbA via intraperitoneal injection of 1 × 106 infected red blood cells. Fecal samples of two groups were collected. The microbiota of feces obtained from both uninfected and infected mice was characterized by targeting the V4 region of the 16S rRNA through the Illumina MiSeq platform. The variations in the total gut microbiota composition were determined based on alpha and beta diversity analyses of 16S rRNA sequencing. The raw sequences from all samples were generated and clustered using ≥ 97% sequence identity into many microbial operational taxonomic units (OTUs). The typical microbiota composition in the gut was dominated by Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia at the phylum level. Bacteroidetes and Verrucomicrobia were considerably decreased after PbA infection compared with the control group (Ctrl), while Firmicutes and Proteobacteria were increased substantially after PbA infection compared with Ctrl. The alpha diversity index showed that the observed OTU number was increased in the PbA group compared with the Ctrl group. Moreover, the discreteness of the beta diversity revealed that the PbA group samples had a higher number of OTUs than the Ctrl group. LEfSe analysis revealed that several potential bacterial biomarkers were clearly related to the PbA-infected mice at the phylogenetic level. Several bacterial genera, such as Acinetobacter, Lactobacillus, and Lachnospiraceae_NK4A136_group, were overrepresented in the PbA-infected fecal microbiota. Meanwhile, a method similar to gene coexpression network construction was used to generate the OTU co-abundance units. These results indicated that P. berghei ANKA infection could alter the gut microbiota composition of C57BL/6 mice. In addition, potential biomarkers should offer insight into malaria pathogenesis and antimalarial drug and malaria vaccine studies.

Description: 5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to cause cognitive impairment, the synergistic effect of 5-Fu with LV has not been fully explored. The present investigation was designed to assess how the combination of 5-Fu and LV affect cognition in a murine model. Six-month-old male mice were used in this study; 15 mice received saline injections and 15 mice received 5-Fu/LV injections. One month after treatment, the elevated plus maze, Y-maze, and Morris water maze behavioral tasks were performed. Brains were then extracted, cryosectioned, and stained for CD68 to assay microglial activation and with tomato lectin to assay the vasculature. All animals were able to locate the visible and hidden platform locations in the water maze. However, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received 5-Fu/LV, but these animals showed spatial memory retention by day 5. There were no significant increases in inflammation as measured by CD68, but 5-Fu/LV treatment did modulate blood vessel morphology. Tandem mass tag proteomics analysis identified 6,049 proteins, 7 of which were differentially expressed with a p-value of 1.5. The present data demonstrate that 5-Fu/LV increases anxiety and significantly impairs spatial memory retention.

Description: The petiole–lamina relationship is central to the functional tradeoff between photosynthetic efficiency and the support/protection cost. Understanding environmental gradients in the relationship and its underlying mechanisms remains a critical challenge for ecologists. We investigated the possible scaling of the petiole–lamina relationships in three dimensions, i.e., petiole length (PL) vs. lamina length (LL), petiole cross sectional area (PCA) vs. lamina area (LA), and petiole mass (PM) vs. lamina mass (LM), for 325 Qinghai–Tibetan woody species, and examined their relation to leaf form, altitude, climate, and vegetation types. Both crossspecies analysis and meta-analysis showed significantly isometric, negatively allometric, and positively allometric scaling of the petiole–lamina relationships in the length, area, and mass dimensions, respectively, reflecting an equal, slower, and faster variation in the petiole than in the lamina in these trait dimensions. Along altitudinal gradients, the effect size of the petiole–lamina relationship decreased in the length and mass dimensions but increased in the area dimension, suggesting the importance of enhancing leaf light-interception and nutrient transport efficiency in the warm zones in petiole development, but enhancing leaf support/protection in the cold zones. The significant additional influences of LA, LM, and LA were observed on the PL–LL, PCA–LA, and PM–LM relationships, respectively, implying that the single-dimension petiole trait is affected simultaneously by multidimensional lamina traits. Relative to simple-leaved species, the presence of petiolule in compound-leaved species can increase both leaf light interception and static gravity loads or dynamic drag forces on the petiole, leading to lower dependence of PL variation on LL variation, but higher biomass allocation to the petiole. Our study highlights the need for multidimension analyses of the petiole–lamina relationships and illustrates the importance of plant functional tradeoffs and the change in the tradeoffs along environmental gradients in determining the relationships.

Description: Thread blight disease has recently been described as an emerging disease on cacao (Theobroma cacao) in Ghana. In Ghana, thread blight disease is caused by multiple species of the Marasmiaceae family: Marasmius tenuissimus, M. crinis-equi, M. palmivorus, and Marasmiellus scandens. Interestingly, two additional members of the Marasmiaceae; Moniliophthora roreri (frosty pod rot) and Moniliophthora perniciosa (witches’ broom disease), are major pathogens of cacao in the Western hemisphere. It is important to accurately characterize the genetic relationships among these economically important species in support of their disease management. We used data from Illumina NGS-based genome sequencing efforts to study the mitochondrial genomes (mitogenomes) of the four cacao thread blight associated pathogens from Ghana and compared them with published mitogenomes of Mon. roreri and Mon. perniciosa. There is a remarkable interspecies variation in mitogenome size within the six cacao-associated Marasmiaceae species, ranging from 43,121 to 109,103 bp. The differences in genome lengths are primarily due to the number and lengths of introns, differences in intergenic space, and differences in the size and numbers of unidentified ORFs (uORF). Among seven M. tenuissimus mitogenomes sequenced, there is variation in size and sequence pointing to divergent evolution patterns within the species. The intronic regions show a high degree of sequence variation compared to the conserved sequences of the 14 core genes. The intronic ORFs identified, regardless of species, encode GIY-YIG or LAGLIDADG domain-containing homing endonuclease genes. Phylogenetic relationships using the 14 core proteins largely mimic the phylogenetic relationships observed in gene order patterns, grouping M. tenuissimus with M. crinis-equi, and M. palmivorus with Mon. roreri and Mon. perniciosa, leaving Mar. scandens as an outlier. The results from this study provide evidence of independent expansion/contraction events and sequence diversification in each species and establish a foundation for further exploration of the evolutionary trajectory of the fungi in Marasmiaceae family.

Description: There is converging and increasing evidence, but also uncertainty, for the role of abnormal intestinal epithelial barrier function in the origin and development of a growing number of human gastrointestinal and extraintestinal inflammatory disorders, and their related complaints. Despite a vast literature addressing factors and mechanisms underlying changes in intestinal permeability in humans, and its connection to the appearance and severity of clinical symptoms, the ultimate link remains to be established in many cases. Accordingly, there are no directives or clinical guidelines related to the therapeutic management of intestinal permeability disorders that allow health professionals involved in the management of these patients to carry out a consensus treatment based on clinical evidence. Instead, there are multiple pseudoscientific approaches and commercial propaganda scattered on the internet that confuse those affected and health professionals and that often lack scientific rigor. Therefore, in this review we aim to shed light on the different therapeutic options, which include, among others, dietary management, nutraceuticals and medical devices, microbiota and drugs, and epigenetic and exosomes-manipulation, through an objective evaluation of the scientific publications in this field. Advances in the knowledge and management of intestinal permeability will sure enable better options of dealing with this group of common disorders to enhance quality of life of those affected.

Description: E-cigarette or vaping use-associated lung injury (EVALI) was identified with the incidents of a multi-state outbreak of acute lung injuries associated with the use of electronic cigarettes (e-cigs) and attributed to vitamin E acetate in off-market cannabis-based e-liquids. Aside from EVALI, hypersecretion of mucus, irritated nasal passages, and watery, red eyes have been defined as complaints associated with vaping standard nicotine-based e-liquids. The chemical composition of e-liquids varies between manufacturers and robust oversight of ingredients is lacking. Manufacturers use chemicals deemed “generally recognized as safe” (GRAS) by the FDA, a designation for chemicals used in foodstuffs to be ingested. Most “GRAS” chemicals are associated with at least one Global Harmonization System (GHS) warning class, ranging from irritant to toxic. Untargeted chemical analysis is critical to evaluate e-liquid products to determine chemical composition; equally important is the quantitation of components to help elucidate the potential harms from exceeding recommended exposure limits. Untargeted screening of e-liquids was accomplished using gas chromatography-mass spectrometry (GC-MS) and Direct Analysis in Real Time-AccuTOF™ mass spectrometry (DART-ToF-MS) and has identified 350 chemical constituents from 241 products analyzed. Nicotine, caffeine, menthol, and vitamin E were confirmed and quantitated by GC-MS, ethanol was confirmed and quantitated by headspace-gas chromatography-dual flame ionization detection (HS-GC-FID), and olivetol and cannabinoids were confirmed and quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maximum identified concentrations of nicotine, caffeine, menthol, vitamin E, ethanol, olivetol, Δ9-tetrahydrocannabinol, and cannabidiol were 56.4, 26.9, 4.28, 307.9, 217.2, 399.6, 497.7, and 332.6 mg/ml, respectively. Evaluation of untargeted analysis and quantitation of unlabeled chemical components of e-liquids is essential to improving etiology of acute lung injury and less severe impacts of vaping, both short-term and long-term. The historical documentation of unlabeled ingredients can provide some insight for a retrospective analysis of health consequences and inform policy discussions.

Description: Building on the considerable momentum from the commencement of the Decade of Ocean Science, the Ocean-climate nexus will be center stage at COP26. Many countries are including blue carbon Ocean commitments in their second round of nationally determined contributions (NDCs), and there is a need to harmonize the science, law, and economics of Ocean-based climate mitigation and adaptation strategies to enable implementation of Ocean commitments under the Paris Agreement. In addition, consistent with the Paris Agreement preamble's focus on human rights, the rights and empowerment of vulnerable and marginalized communities, and intergenerational equity, the design and implementation of Ocean commitments in NDCs should be centered on considerations of climate justice (“climate-just Ocean commitments”). The challenges and opportunities inherent in implementing climate-just Ocean commitments require a comprehensive review of the latest innovations in blue carbon scientific research, the enabling conditions necessary for uptake of this science into policies and decision making, and the financial structures needed to equitably finance Ocean nature-based solutions. Responding to this need, we propose that a framework is needed to support the inclusion of blue carbon sequestration potential in ambitious national and subnational action. The proposed framework should center on the intersectionality of climate justice with the three key layers essential to implementation of Ocean commitments—science, law, and economics—where traditional and local ecological knowledge is valued on par with western science, law and policy centers on vulnerable communities, and financial mechanisms respect national sovereignty, value local cultures, and support sustainable economic development.

Description: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory airflow limitation and symptoms such as shortness of breath. Although many studies have demonstrated dysregulated microRNA (miRNA) and gene (mRNA) expression in the pathogenesis of COPD, how miRNAs and mRNAs systematically interact and contribute to COPD development is still not clear. To gain a deeper understanding of the gene regulatory network underlying COPD pathogenesis, we used Sparse Multiple Canonical Correlation Network (SmCCNet) to integrate whole blood miRNA and RNA-sequencing data from 404 participants in the COPDGene study to identify novel miRNA–mRNA networks associated with COPD-related phenotypes including lung function and emphysema. We hypothesized that phenotype-directed interpretable miRNA–mRNA networks from SmCCNet would assist in the discovery of novel biomarkers that traditional single biomarker discovery methods (such as differential expression) might fail to discover. Additionally, we investigated whether adjusting -omics and clinical phenotypes data for covariates prior to integration would increase the statistical power for network identification. Our study demonstrated that partial covariate adjustment for age, sex, race, and CT scanner model (in the quantitative emphysema networks) improved network identification when compared with no covariate adjustment. However, further adjustment for current smoking status and relative white blood cell (WBC) proportions sometimes weakened the power for identifying lung function and emphysema networks, a phenomenon which may be due to the correlation of smoking status and WBC counts with the COPD-related phenotypes. With partial covariate adjustment, we found six miRNA–mRNA networks associated with COPD-related phenotypes. One network consists of 2 miRNAs and 28 mRNAs which had a 0.33 correlation (p = 5.40E-12) to forced expiratory volume in 1 s (FEV1) percent predicted. We also found a network of 5 miRNAs and 81 mRNAs that had a 0.45 correlation (p = 8.80E-22) to percent emphysema. The miRNA–mRNA networks associated with COPD traits provide a systems view of COPD pathogenesis and complements biomarker identification with individual miRNA or mRNA expression data.

Description: Injuries to menisci are the most common disease among knee joint-related morbidities and cover a widespread population ranging from children and the general population to the old and athletes. Repair of the injuries in the meniscal avascular zone remains a significant challenge due to the limited intrinsic healing capacity compared to the peripheral vascularized zone. The current surgical strategies for avascular zone injuries remain insufficient to prevent the development of cartilage degeneration and the ultimate emergence of osteoarthritis (OA). Due to the drawbacks of current surgical methods, the research interest has been transferred toward facilitating meniscal avascular zone repair, where it is expected to maintain meniscal tissue integrity, prevent secondary cartilage degeneration and improve knee joint function, which is consistent with the current prevailing management idea to maintain the integrity of meniscal tissue whenever possible. Biological augmentations have emerged as an alternative to current surgical methods for meniscal avascular zone repair. However, understanding the specific biological mechanisms that affect meniscal avascular zone repair is critical for the development of novel and comprehensive biological augmentations. For this reason, this review firstly summarized the current surgical techniques, including meniscectomies and meniscal substitution. We then discuss the state-of-the-art biological mechanisms, including vascularization, inflammation, extracellular matrix degradation and cellular component that were associated with meniscal avascular zone healing and the advances in therapeutic strategies. Finally, perspectives for the future biological augmentations for meniscal avascular zone injuries will be given.

Description: Blindness and deafness are the most frequent sensory disorders in humans. Whatever their cause — genetic, environmental, or due to toxic agents, or aging — the deterioration of these senses is often linked to irreversible damage to the light-sensing photoreceptor cells (blindness) and/or the mechanosensitive hair cells (deafness). Efforts are increasingly focused on preventing disease progression by correcting or replacing the blindness and deafness-causal pathogenic alleles. In recent years, gene replacement therapies for rare monogenic disorders of the retina have given positive results, leading to the marketing of the first gene therapy product for a form of childhood hereditary blindness. Promising results, with a partial restoration of auditory function, have also been reported in preclinical models of human deafness. Silencing approaches, including antisense oligonucleotides, adeno-associated virus (AAV)–mediated microRNA delivery, and genome-editing approaches have also been applied to various genetic forms of blindness and deafness The discovery of new DNA- and RNA-based CRISPR/Cas nucleases, and the new generations of base, prime, and RNA editors offers new possibilities for directly repairing point mutations and therapeutically restoring gene function. Thanks to easy access and immune-privilege status of self-contained compartments, the eye and the ear continue to be at the forefront of developing therapies for genetic diseases. Here, we review the ongoing applications and achievements of this new class of emerging therapeutics in the sensory organs of vision and hearing, highlighting the challenges ahead and the solutions to be overcome for their successful therapeutic application in vivo.

Description: Clubroot disease, which is caused by the soil-borne pathogen Plasmodiophora brassicae War (P. brassicae), is one of the oldest and most destructive diseases of Brassica and cruciferous crops in the world. Plant microRNAs [micro ribonucleic acids (miRNAs)] play important regulatory roles in several developmental processes. Although the role of plant miRNAs in plant-microbe interaction has been extensively studied, there are only few reports on the specific functions of miRNAs in response to P. brassicae. This study investigated the roles of miRNAs and their targets during P. brassicae infection in a pair of Brassica napus near-isogenic lines (NILs), namely clubroot-resistant line 409R and clubroot-susceptible line 409S. Small RNA sequencing (sRNA-seq) and degradome-seq were performed on root samples of 409R and 409S with or without P. brassicae inoculation. sRNA-seq identified a total of 48 conserved and 72 novel miRNAs, among which 18 had a significant differential expression in the root of 409R, while only one miRNA was differentially expressed in the root of 409S after P. brassicae inoculation. The degradome-seq analysis identified 938 miRNA target transcripts, which are transcription factors, enzymes, and proteins involved in multiple biological processes and most significantly enriched in the plant hormone signal transduction pathway. Between 409R and 409S, we found eight different degradation pathways in response to P. brassicae infection, such as those related to fatty acids. By combining published transcriptome data, we identified a total of six antagonistic miRNA-target pairs in 409R that are responsive to P. brassicae infection and involved in pathways associated with root development, hypersensitive cell death, and chloroplast metabolic synthesis. Our results reveal that P. brassicae infection leads to great changes in miRNA pool and target transcripts. More interestingly, these changes are different between 409R and 409S. Clarification of the crosstalk between miRNAs and their targets may shed new light on the possible mechanisms underlying the pathogen resistance against P. brassicae.

Description: Electrification of transportation using electric vehicles has a large potential to reduce transport related emissions but could potentially cause issues in generation and distribution of electricity. This study uses GPS measured driving patterns from conventional gasoline and diesel cars in western Sweden and Seattle, United States, to estimate and analyze expected charging coincidence assuming these driving patterns were the same for electric vehicles. The results show that the electric vehicle charging power demand in western Sweden and Seattle is 50–183% higher compared to studies that were relying on national household travel surveys in Sweden and United States. The after-coincidence charging power demand from GPS measured driving behavior converges at 1.8 kW or lower for Sweden and at 2.1 kW or lower for the United States The results show that nominal charging power has the largest impact on after-coincidence charging power demand, followed by the vehicle’s electricity consumption and lastly the charging location. We also find that the reduction in charging demand, when charging is moved in time, is largest for few vehicles and reduces as the number of vehicles increase. Our results are important when analyzing the impact from large scale introduction of electric vehicles on electricity distribution and generation.

Description: Leprosy is an infectious disease caused by Mycobacterium leprae with tropism for skin and peripheral nerves. Incessant transmission in endemic areas is still impeding elimination of leprosy. Although detection of M. leprae infection remains a challenge in asymptomatic individuals, the presence of antibodies specific for phenolglycolipid-I (PGL-I) correlate with bacterial load. Therefore, serosurveillance utilizing field-friendly tests detecting anti-PGL-I antibodies, can be applied to identify those who may transmit bacteria and to study (reduction of) M. leprae transmission. However, serology based on antibody detection cannot discriminate between past and present M. leprae infection in humans, nor can it detect individuals carrying low bacillary loads. In humans, anti-PGL-I IgM levels are long-lasting and usually detected in more individuals than anti-PGL-I IgG levels. Inherent to the characteristically long incubation time of leprosy, IgM/IgG relations (antibody kinetics) in leprosy patients and infected individuals are not completely clear. To investigate the antibody response directly after infection, we have measured antibody levels by ELISA, in longitudinal samples of experimentally M. leprae infected, susceptible nine-banded armadillos (Dasypus novemcinctus). In addition, we assessed the user- and field-friendly, low-cost lateral flow assay (LFA) utilizing upconverting reporter particles (UCP), developed for quantitative detection of human anti-PGL-I IgM (UCP-LFA), to detect treatment- or vaccination-induced changes in viable bacterial load. Our results show that serum levels of anti-PGL-I IgM, and to a lesser extent IgG, significantly increase soon after experimental M. leprae infection in armadillos. In view of leprosy phenotypes in armadillos, this animal model can provide useful insight into antibody kinetics in early infection in the various spectral forms of human leprosy. The UCP-LFA for quantitative detection of anti-PGL-I IgM allows monitoring the efficacy of vaccination and rifampin-treatment in the armadillo leprosy model, thereby providing a convenient tool to evaluate the effects of drugs and vaccines and new diagnostics.

Description: The existence of a coevolutionary process between avian brood parasites and their hosts predicts a lower intra-clutch variation in egg appearance of host eggs among rejecters as this would favor egg discrimination of parasite eggs by hosts once parasitic egg mimicry had evolved. So far empirical tests of this prediction have ignored the fact that different aspects of host egg phenotypes may differ in the relative role of environmental vs. genetic determination, and hence that the role of intra-clutch variation in egg rejection within a population cannot be invariant. Here, we estimated whether the intra-clutch variation in several aspects of host eggshell features is consistently associated to rejection of parasitic foreign eggs across years in a magpie host population parasitized by great spotted cuckoos. We innovatively estimated spottiness by means of the fractal dimension of eggs, which considers the homogeneity of spot pattern complexity in eggshells. Our results show that low intra-clutch variation in the blue-green coloration at the middle area of the eggs associated with a high chance of rejection, but only in one of the 3 years we conducted the study. In addition, females that rejected foreign eggs presented more homogenous spot patterns in their clutches as estimated by their fractal dimension than females that accepted experimental eggs, independently of the year of study. Finally, intra-clutch variation in egg volume of host eggs was not associated to rejection. Analyses at the individual level revealed that the relative role of genetic vs. environmental factors that determine egg phenotype would be feature-specific in magpies, females having a characteristic spottiness, but not color or volume, pattern. Our work stresses the importance of considering a holistic approach including several aspects of variation in host egg phenotype (size, color, and homogeneity of spot pattern), as some aspects might be more susceptible to selection through egg rejection than others, presumably because they are less influenced by variation in the environmental conditions. Moreover, our study highlights the importance of replication in studies on the adaptive value of host traits in egg rejection.

Description: Trophic contributions of diverse OM sources to estuarine and coastal food webs differ substantially across systems around the world, particularly for nekton (fish, cephalopods, and crustaceans), which utilize basal resources from multiple sources over space and time because of their mobility and feeding behaviors at multiple trophic levels. We investigated the contributions of putative OM sources to fish food webs and assessed the spatiotemporal patterns, structures, and trophic connectivity in fish food webs across four seasons from three closely spaced (10–15 km) sites: an estuarine channel (EC), a deep bay (DB), and an offshore (OS) region in Gwangyang Bay, a high-productivity, low-turbidity estuarine embayment off the Republic of Korea. While nearly all previous studies have focused on few representative species, we examined δ13C and δ15N values of whole nekton communities along with dominant benthic macro-invertebrates, zooplankton, and their putative primary food sources. The δ13C and δ15N values coupled with MixSIAR, a Bayesian mixing model, revealed that these communities utilized multiple primary producers, but phytoplankton comprised the primary trophic contributor (46.6–69.1%). Microphytobenthos (15.8–20.4%) and the seagrass Zostera marina (8.6–19.8%) made substantial contributions, but the role of river-borne terrestrial organic matter was negligible. Spatially different species composition and stable isotope values, but higher utilization of coastal phytoplankton by estuarine fish, indicated disparate food webs structures between the EC and DB/OS coastal areas, with considerable trophic connectivity. Greater overlaps in fish and cephalopod isotopic niches than among other consumers and a higher estimated carbon trophic enrichment factor for EC nekton confirmed feeding migration-mediated biological transport of coastal OM sources to the estuary. Further, the seasonally consistent structures and resource utilization patterns indicate that fish food webs are resilient to changes at lower trophic levels. Our results contrast with those for other highly turbid coastal systems depending highly on diversified basal sources, including exported terrestrial and wetland detritus alongside autochthonous phytoplankton. Finally, this study provides a novel perspective on the role of OM sources in such low turbidity and highly productive coastal embayments and enhances our understanding of marine ecosystems.

Description: The Salar de Atacama in the Chilean Central Andes harbors unique microbial ecosystems due to extreme environmental conditions, such as high altitude, low oxygen pressure, high solar radiation, and high salinity. Combining X-ray diffraction analyses, scanning electron microscopy and molecular diversity studies, we have characterized twenty previously unexplored Andean microbial ecosystems in eight different lakes and wetlands from the middle-east and south-east regions of this salt flat. The mats and microbialites studied are mainly formed by calcium carbonate (aragonite and calcite) and halite, whereas the endoevaporites are composed predominantly of gypsum and halite. The carbonate-rich mats and microbialites are dominated by Bacteroidetes and Proteobacteria phyla. Within the phylum Proteobacteria, the most abundant classes are Alphaproteobacteria, Gammaproteobacteria and Deltaproteobacteria. While in the phylum Bacteroidetes, the most abundant classes are Bacteroidia and Rhodothermia. Cyanobacteria, Chloroflexi, Planctomycetes, and Verrucomicrobia phyla are also well-represented in the majority of these systems. Gypsum endoevaporites, on the contrary, are dominated by Proteobacteria, Bacteroidetes, and Euryarchaeota phyla. The Cyanobacteria phylum is also abundant in these systems, but it is less represented in comparison to mats and microbialites. Regarding the eukaryotic taxa, diatoms are key structural components in most of the microbial ecosystems studied. The genera of diatoms identified were Achnanthes, Fallacia, Halamphora, Mastogloia, Navicula, Nitzschia, and Surirella. Normally, in the mats and microbialites, diatoms form nano-globular carbonate aggregates with filamentous cyanobacteria and other prokaryotic cells, suggesting their participation in the mineral precipitation process. This work expands our knowledge of the microbial ecosystems inhabiting the extreme environments from the Central Andes region, which is important to ensure their protection and conservation.

Description: Environmental flow programs aim to protect aquatic habitats and species while recognizing competing water demands. Often this is done at the local or watershed level because it is relatively easier to address technical and implementation challenges at these scales. However, a consequence of this approach is that ecological flow criteria are developed for only a few areas as dictated by funding and interest with many streams neglected. Here we discuss the collaborative development of the California Environmental Flows Framework (CEFF) as an example process for developing environmental flow recommendations at a statewide scale. CEFF uses a functional flows approach, which focuses on protecting a broad suite of ecological, geomorphic, and biogeochemical functions instead of specific species or habitats, and can be applied consistently across diverse stream types and spatial scales. CEFF adopts a tiered approach in which statewide models are used to estimate ecological flow needs based on natural functional flow ranges, i.e., metrics that quantify the required magnitude, timing, duration, frequency, and/or rate-of-change of functional flow components under reference hydrologic conditions, for every stream reach in the state. Initial flow needs can then be revised at regional, or watershed, scales based on local constraints, management objectives, and available data and resources. The third tier of CEFF provides a process for considering non-ecological flow needs to produce a final set of environmental flow recommendations that aim to balance of all desired water uses. CEFF was developed via a broad inclusive process that included technical experts across multiple disciplines, representatives from federal and state agencies, and stakeholders and potential end-users from across the state. The resulting framework is therefore not associated with any single agency or regulatory program but can be applied under different contexts, mandates and end-user priorities. The inclusive development of CEFF also allowed us to achieve consensus on the technical foundations and commitment to applying this approach in the future.