ALBERT

Description: In recent years, the rapid increase in CO2 concentration has accelerated global warming. As a result, sea levels rise, glaciers melt, extreme weather occurs, and species become extinct. As the world’s largest CO2 emission rights trading market, EU Emissions Trading System (EU-ETS) has reached 1.855 billion tons of quotas by 2019, influencing the development of the global carbon emission market. Crude oil, as one of the major fossil energy sources in the world, its price fluctuation is bound to affect the price of carbon emission rights. Therefore, this paper aims to reveal the correlation between crude oil futures prices and carbon emission rights futures prices by studying the price fluctuation. In this paper, the linkage between West Texas Intermediate (WTI) crude oil futures prices and European carbon futures prices was investigated. In addition, this paper selects continuous data of WTI crude oil futures prices and spot prices with European carbon futures prices from January 8, 2018 to November 27, 2020, and builds a smooth transformation regression (STR) model. The relationship between crude oil futures and carbon futures prices is studied in both forward and reversal linkage through empirical analysis. The results show that crude oil futures prices and carbon futures prices have a mutual effect on each other, and both linear and nonlinear correlations between the two prices exist. Based on the results of this research, some suggestions are provided.

Description: We present a high-efficiency method for simulating seawater intrusion (SWI), with mixing, in confined coastal aquifers based on uncoupled equations in the through-flow region of the aquifer. The flow field is calculated analytically and the tracer transport numerically, via spatial splitting along the principal directions (PD) of transport. Advection-dispersion processes along streamlines are simulated with the very efficient matched artificial dispersivity (MAD) method of Syriopoulou and Koussis and the system of discretized transverse-dispersion equations is solved with the Thomas algorithm. These concepts are embedded in the 2D-MADPD-SWI model, yielding comparable solutions to those of the uncoupled SWI equations with the state-of-the-art FEFLOW code, but faster, while 2D-MADPD-SWI achieves an at least hundredfold faster solution than a variable-density flow model. We demonstrate the utility of the 2D-MADPD-SWI model in stochastic Monte Carlo simulations by assessing the uncertainty on the advance of the 1,500 ppm TDS line (limit of tolerable salinity for irrigation) due to randomly variable hydraulic conductivity and freshwater flow rate.

Description: Wastewater stabilization ponds (WSPs) are commonly used to treat municipal wastewater in the Canadian Arctic. Bacterial community structure and functionality remain mostly uncharacterized for arctic WSPs, yet are presumed important for treatment outcomes during the 3-month summer treatment season with open water in the WSPs. The objective of this study was to investigate treatment performance and related temporal and spatial changes in the structure and putative function of bacterial communities during treatment of municipal wastewater in the WSPs of Pond Inlet and Clyde River, Nunavut over two consecutive summer treatment seasons. Influent raw wastewater contained a high organic load and large bacterial communities (~9 log 16S rRNA copies/mL) belonging mainly to Proteobacteria. Although designed to be facultative ponds, both WSPs remained anaerobic with neutral pH values (7.5–7.8) throughout the summer treatment season. Water quality data showed that nutrients [measured as carbonaceous biological oxygen demand (CBOD5)], total suspended solids, and total ammonia nitrogen were progressively reduced during treatment in the ponds as the summer progressed. The pond bacterial population size and species richness depended on the pond temperature (2–18°C), with 8.5 log 16S rRNA copies/mL and the largest alpha diversities (Shannon-Wiener index of 4-4.5) observed mid-season (late July). While the phylogenetic beta diversity in raw wastewater from the two locations remained similar, pond bacterial communities underwent significant (p 〈 0.05) changes to dominance of Comamonadaceae, Geobacteracea, and Porphyromonadaceae. Multivariate distance based redundancy analysis and predicted gene functionalities in the microbiota agreed with water quality results that microbial removal of nutrients (e.g., CBOD5) peaked in the middle of the summer coinciding with the treatment period with the highest pond temperatures. Information from this study will be useful for further development of models to predict biological treatment outcomes, which could be used to size and assess the feasibility of WSPs in extreme climates. Higher pond temperatures resulted in optimal biological processes and nutrient removal in the middle of the summer. While it is challenging to control environmental factors in a passive wastewater treatment system there are some design considerations that could be used to optimize temperature regimes, such as the depth of the pond.

Description: Metafounders are pseudo-individuals that act as proxies for animals in base populations. When metafounders are used, individuals from different breeds can be related through pedigree, improving the compatibility between genomic and pedigree relationships. The aim of this study was to investigate the use of metafounders and unknown parent groups (UPGs) for the genomic evaluation of a composite beef cattle population. Phenotypes were available for scrotal circumference at 14 months of age (SC14), post weaning gain (PWG), weaning weight (WW), and birth weight (BW). The pedigree included 680,551 animals, of which 1,899 were genotyped for or imputed to around 30,000 single-nucleotide polymorphisms (SNPs). Evaluations were performed based on pedigree (BLUP), pedigree with UPGs (BLUP_UPG), pedigree with metafounders (BLUP_MF), single-step genomic BLUP (ssGBLUP), ssGBLUP with UPGs for genomic and pedigree relationship matrices (ssGBLUP_UPG) or only for the pedigree relationship matrix (ssGBLUP_UPGA), and ssGBLUP with metafounders (ssGBLUP_MF). Each evaluation considered either four or 10 groups that were assigned based on breed of founders and intermediate crosses. To evaluate model performance, we used a validation method based on linear regression statistics to obtain accuracy, stability, dispersion, and bias of (genomic) estimated breeding value [(G)EBV]. Overall, relationships within and among metafounders were stronger in the scenario with 10 metafounders. Accuracy was greater for models with genomic information than for BLUP. Also, the stability of (G)EBVs was greater when genomic information was taken into account. Overall, pedigree-based methods showed lower inflation/deflation (regression coefficients close to 1.0) for SC14, WWM, and BWD traits. The level of inflation/deflation for genomic models was small and trait-dependent. Compared with regular ssGBLUP, ssGBLUP_MF4 displayed regression coefficient closer to one SC14, PWG, WWM, and BWD. Genomic models with metafounders seemed to be slightly more stable than models with UPGs based on higher similarity of results with different numbers of groups. Further, metafounders can help to reduce bias in genomic evaluations of composite beef cattle populations without reducing the stability of GEBVs.

Description: Large-scale transcriptome data, such as single-cell RNA-sequencing data, have provided unprecedented resources for studying biological processes at the systems level. Numerous dimensionality reduction methods have been developed to visualize and analyze these transcriptome data. In addition, several existing methods allow inference of functional variations among samples using gene sets with known biological functions. However, it remains challenging to analyze transcriptomes with reduced dimensions that are interpretable in terms of dimensions’ directionalities, transferrable to new data, and directly expose the contribution or association of individual genes. In this study, we used gene set non-negative principal component analysis (gsPCA) and non-negative matrix factorization (gsNMF) to analyze large-scale transcriptome datasets. We found that these methods provide low-dimensional information about the progression of biological processes in a quantitative manner, and their performances are comparable to existing functional variation analysis methods in terms of distinguishing multiple cell states and samples from multiple conditions. Remarkably, upon training with a subset of data, these methods allow predictions of locations in the functional space using data from experimental conditions that are not exposed to the models. Specifically, our models predicted the extent of progression and reversion for cells in the epithelial-mesenchymal transition (EMT) continuum. These methods revealed conserved EMT program among multiple types of single cells and tumor samples. Finally, we demonstrate this approach is broadly applicable to data and gene sets beyond EMT and provide several recommendations on the choice between the two linear methods and the optimal algorithmic parameters. Our methods show that simple constrained matrix decomposition can produce to low-dimensional information in functionally interpretable and transferrable space, and can be widely useful for analyzing large-scale transcriptome data.

Description: In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as well as gene set enrichment analyses (GSEA) and protein–protein interaction (PPI) network construction of top association hits genome-wide (p 〈 0.01; n = 441 genes). The maximum likelihood estimate of heritability for epileptic seizure in the pedigreed baboon sample is 0.76 (SE = 0.77; p = 0.07). Among candidate genes for GGE, a significant association was detected for an intronic SNP in RBFOX1 (p = 5.92 × 10–6; adjusted p = 0.016). For protein-altering variants, no genome-wide significant results were observed for epilepsy status. However, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR = 0.0072) and collagen formation (FDR = 0.017), which was reflected in a major PPI network cluster. This preliminary study highlights the potential role of RBFOX1 in the epileptic baboon, a protein involved in transcriptomic regulation of multiple epilepsy candidate genes in humans and itself previously implicated in human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the genome exhibit a pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE and lay the foundation for follow-up research.

Description: Occurrences and exposure to high levels of microbial bioaerosols such as pathogenic bacteria, fungi, fungal spores, and viruses can be linked to the deterioration of the environment and public health. This study aimed to review the results available for the unusual bioaerosol distribution scenario in the Asian regions. The amount of bioaerosol load and their environmental behavior in the atmosphere is heavily influenced by air pollution such as haze, fog, dust, and particulate matter (PM) and thus strongly affect the air quality index (AQI). Human factors such as heavy traffic, overcrowds, and biomass burning also affected the prevalence or occurrences of bioaerosols in the atmosphere. Seasonal/temporal and diurnal variation was significantly observed from these studies and in the case of South Asia, post-monsoon and winter months were incredibly concentrated with pathogenic bioaerosols. Many human infections, for example, pneumonia, tuberculosis, brucellosis, anthrax, and query fever (Q-fever), are linked to pathogenic bacterial bioaerosols. Respiratory diseases such as asthma and chronic pulmonary obstructiveness are related to fungal bioaerosols, spores, and viral infections. To facilitate the testing and monitoring appraisal of airborne bioaerosols, artificial intelligence, deep neural networks, and machine learning can be used to develop real-time PCR-based bioaerosol sensors. Moreover, mobile apps and compatible electronic gadgets can be developed for the city dwellers to real-time monitor the concentration of bioaerosols in the air they are breathing.

Description: In the context of the energy crisis and environmental deterioration, the integrated energy system (IES) based on multi-energy complementarity and cascaded utilization of energy is considered as an effective way to solve these problems. Due to the different energy forms and the various characteristics in the IES, the coupling relationships among various energy forms are complicated which enlarges the difficulty of energy efficiency evaluation of the IES. In order to flexibly analyze the energy efficiency of the IES, an operation efficiency evaluation model for the IES is established. First, energy utilization efficiency (EUE) and exergy efficiency (EXE) are proposed based on the first/second law of thermodynamics. Second, the energy efficiency models for five processes and four subsystems of the IES are formed. Lastly, an actual commercial-industrial park with integrated energy is employed to validate the proposed method.

Description: Understanding the etiology of cerebrospinal fluid (CSF) shunt infections and reinfections requires detailed characterization of associated microorganisms. Traditionally, identification of bacteria present in the CSF has relied on culture methods, but recent studies have used high throughput sequencing of 16S rRNA genes. Here we evaluated the method of shotgun DNA sequencing for its potential to provide additional genomic information. CSF samples were collected from 3 patients near the beginning and end of each of 2 infection episodes. Extracted total DNA was sequenced by: (1) whole genome amplification followed by shotgun sequencing (WGA) and (2) high-throughput sequencing of the 16S rRNA V4 region (16S). Taxonomic assignments of sequences from WGA and 16S were compared with one another and with conventional microbiological cultures. While classification of bacteria was consistent among the 3 approaches, WGA provided additional insights into sample microbiological composition, such as showing relative abundances of microbial versus human DNA, identifying samples of questionable quality, and detecting significant viral load in some samples. One sample yielded sufficient non-human reads to allow assembly of a high-quality Staphylococcus epidermidis genome, denoted CLIMB1, which we characterized in terms of its MLST profile, gene complement (including putative antimicrobial resistance genes), and similarity to other annotated S. epidermidis genomes. Our results demonstrate that WGA directly applied to CSF is a valuable tool for the identification and genomic characterization of dominant microorganisms in CSF shunt infections, which can facilitate molecular approaches for the development of better diagnostic and treatment methods.

Description: This paper investigates the thermophysical properties and heat transfer performance of graphene nanoplatelet (GNP) and alumina hybrid nanofluids at different mixing ratios. The electrical conductivity and viscosity of the nanofluids were obtained at temperatures between 15–55°C. The thermal conductivity was measured at temperatures between 20–40°C. The natural convection properties, including Nusselt number, Rayleigh number, and heat transfer coefficient, were experimentally obtained at different temperature gradients (20, 25, 30, and 35°C) in a rectangular cavity. The Mouromtseff number was used to theoretically estimate all the nanofluids’ forced convective performance at temperatures between 20–40°C. The results indicated that the thermal conductivity and viscosity of water are increased with the hybrid nanomaterial. On the other hand, the viscosity and thermal conductivity of the hybrid nanofluids are lesser than that of mono-GNP nanofluids. Notwithstanding, of all the hybrid nanofluids, GNP-alumina hybrid nanofluid with a mixing ratio of 50:50 and 75:25 were found to have the highest thermal conductivity and viscosity, enhancing thermal conductivity by 4.23% and increasing viscosity by 15.79%, compared to water. Further, the addition of the hybrid nanomaterials improved the natural convective performance of water while it deteriorates with mono-GNP. The maximum augmentation of 6.44 and 10.48% were obtained for Nuaverage and haverage of GNP-Alumina (50:50) hybrid nanofluid compared to water, respectively. This study shows that hybrid nanofluids are more effective for heat transfer than water and mono-GNP nanofluid.

Description: Postpartum depression (PPD) is a mental disorder that affects pregnant women around the world, with serious consequences for mothers, families, and children. Its pathogenesis remains unclear, and medications for treating PPD that can be used during lactation remain to be identified. 919 syrup (919 TJ) is a Chinese herbal medicine that has been shown to be beneficial in the treatment of postpartum depression in both clinical and experimental studies. The mechanism of action of 919 TJ is unclear. 919 syrup is ingested orally, making the potential interaction between the drug and the gut microbiome impossible to ignore. We therefore hypothesized that 919 syrup could improve the symptoms of postpartum depression by affecting the structure and function of the intestinal flora, thereby altering hippocampal metabolism. We compared changes in hippocampal metabolism, fecal metabolism, and intestinal microflora of control BALB/c mice, mice with induced untreated PPD, and mice with induced PPD treated with 919 TJ, and found that 4-aminobutyric acid (GABA) in the hippocampus corresponded with PPD behaviors. Based on changes in GABA levels, multiple key gut bacterial species (Mucispirillum schaedleri, Bifidobacterium pseudolongum, Desulfovibrio piger, Alloprevotella tannerae, Bacteroides sp.2.1.33B and Prevotella sp. CAG:755) were associated with PPD. Metabolic markers that may represent the function of the intestinal microbiota in mice with PPD were identified (Met-Arg, urocanic acid, thioetheramide-PC, L-pipecolic acid, and linoleoyl ethanolamide). The relationship between these factors is not a simple one-to-one correspondence, but more likely a network of staggered functions. We therefore believe that the composition and function of the entire intestinal flora should be emphasized in research studying the gut and PPD, rather than changes in the abundance of individual bacterial species. The introduction of this concept of “GutBalance” may help clarify the relationship between gut bacteria and systemic disease.

Description: Pepper is an important vegetable in the world. In this work, mRNA and ncRNA transcriptome profiles were applied to understand the heterosis effect on the alteration in the gene expression at the seedling and flowering stages between the hybrid and its parents in Capsicum chinense. Our phenotypic data indicated that the hybrid has dominance in leaf area, plant scope, plant height, and fruit-related traits. Kyoto Encyclopedia of Genes and Genomes analysis showed that nine members of the plant hormone signal transduction pathway were upregulated in the seedling and flowering stages of the hybrid, which was supported by weighted gene coexpression network analysis and that BC332_23046 (auxin response factor 8), BC332_18317 (auxin-responsive protein IAA20), BC332_13398 (ethylene-responsive transcription factor), and BC332_27606 (ethylene-responsive transcription factor WIN1) were candidate hub genes, suggesting the important potential role of the plant hormone signal transduction in pepper heterosis. Furthermore, some transcription factor families, including bHLH, MYB, and HSF were greatly over-dominant. We also identified 2,525 long ncRNAs (lncRNAs), 47 micro RNAs (miRNAs), and 71 circle RNAs (circRNAs) in the hybrid. In particular, downregulation of miR156, miR169, and miR369 in the hybrid suggested their relationship with pepper growth vigor. Moreover, we constructed some lncRNA–miRNA–mRNA regulatory networks that showed a multi-dimension to understand the ncRNA relationship with heterosis. These results will provide guidance for a better understanding of the molecular mechanism involved in pepper heterosis.

Description: Accurate survival prediction of breast cancer holds significant meaning for improving patient care. Approaches using multiple heterogeneous modalities such as gene expression, copy number alteration, and clinical data have showed significant advantages over those with only one modality for patient survival prediction. However, existing survival prediction methods tend to ignore the structured information between patients and multimodal data. We propose a multimodal data fusion model based on a novel multimodal affinity fusion network (MAFN) for survival prediction of breast cancer by integrating gene expression, copy number alteration, and clinical data. First, a stack-based shallow self-attention network is utilized to guide the amplification of tiny lesion regions on the original data, which locates and enhances the survival-related features. Then, an affinity fusion module is proposed to map the structured information between patients and multimodal data. The module endows the network with a stronger fusion feature representation and discrimination capability. Finally, the fusion feature embedding and a specific feature embedding from a triple modal network are fused to make the classification of long-term survival or short-term survival for each patient. As expected, the evaluation results on comprehensive performance indicate that MAFN achieves better predictive performance than existing methods. Additionally, our method can be extended to the survival prediction of other cancer diseases, providing a new strategy for other diseases prognosis.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Description: Large-scale disturbances such as ice storms may increase in frequency and intensity as climate changes. While disturbances are a natural component of forest ecosystems, climatically driven alteration to historical patterns may impart fundamental change to ecosystem function. At Hubbard Brook Experimental Forest, NH, experimental ice storms of varying severity were applied to replicate plots of mature northern hardwoods to quantify their effects on forested ecosystems. We assessed ice storm treatment effects on insectivorous foliage-gleaning birds and evaluated insectivore predation on model caterpillars in the understory vegetation. These birds are charismatic, of conservation concern, and are major predators of caterpillars. In turn, lepidopterans are the dominant herbivores in temperate forests and are integral to ecosystem function. We predicted that avian abundance would increase due to additional structural heterogeneity caused by ice treatments, with a concomitant increase in caterpillar predation. Point counts were used to measure insectivorous bird activity in the ice storm experiment plots and additional control plots before and after treatments. We deployed and retrieved plasticine model caterpillars and estimated predation from characteristic marks to these surrogates. Abundance of foliage-gleaning birds was higher in the ice storm plots and birds responded to treatments as a single diffuse disturbance rather than on an individual plot level. All species except one were observed both before and after the ice treatments. Surprisingly, predation on caterpillar models was unaffected by ice storm treatments but rather was a function of caterpillar density. The increase in avian abundance in the ice storm treatment plots corroborates other studies of bird responses to relatively small-scale disturbances in forests and the limited change in species composition was expected given the plot size. We conclude that ice storms may provide beneficial changes for foliage-gleaning birds in the growing season following the disturbance.

Description: Q fever is a zoonotic disease caused by the bacteria Coxiella burnetii. Domestic ruminants are the primary source for human infection, and the identification of likely contamination routes from the reservoir animals the critical point to implement control programs. This study shows that Q fever is detected in Belgium in abortion of cattle, goat and sheep at a different degree of apparent prevalence (1.93%, 9.19%, and 5.50%, respectively). In addition, and for the first time, it is detected in abortion of alpaca (Vicugna pacos), raising questions on the role of these animals as reservoirs. To determine the relationship between animal and human strains, Multiple Locus Variable-number Tandem Repeat Analysis (MLVA) (n=146), Single-Nucleotide Polymorphism (SNP) (n=92) and Whole Genome Sequencing (WGS) (n=4) methods were used to characterize samples/strains during 2009-2019. Three MLVA clusters (A, B, C) subdivided in 23 subclusters (A1-A12, B1-B8, C1-C3) and 3 SNP types (SNP1, SNP2, SNP6) were identified. The SNP2 type/MLVA cluster A was the most abundant and dispersed genotype over the entire territory, but it seemed not responsible for human cases, as it was only present in animal samples. The SNP1/MLVA B and SNP6/MLVA C clusters were mostly found in small ruminant and human samples, with the rare possibility of spillovers in cattle. SNP1/MLVA B cluster was present in all Belgian areas, while the SNP6/MLVA C cluster appeared more concentrated in the Western provinces. A broad analysis of European MLVA profiles confirmed the host-species distribution described for Belgian samples. In silico genotyping (WGS) further identified the spacer types and the genomic groups of C. burnetii Belgian strains: cattle and goat SNP2/MLVA A isolates belonged to ST61 and genomic group III, while the goat SNP1/MLVA B strain was classified as ST33 and genomic group II. In conclusion, Q fever is widespread in all Belgian domestic ruminants and in alpaca. We determined that the public health risk in Belgium is likely linked to specific genomic groups (SNP1/MLVA B and SNP6/MLVA C) mostly found in small ruminant strains. Considering the concordance between Belgian and European results, these considerations could be extended to other European countries.

Description: Overuse of antibiotics in clinical medicine has contributed to the global spread of multidrug-resistant bacterial pathogens, including Acinetobacter baumannii. We present a case of an 88-year-old Chinese man who developed hospital-acquired pneumonia caused by carbapenem-resistant A. baumannii (CRAB). A personalized lytic pathogen-specific single-phage preparation was nebulized to the patient continuously for 16 days in combination with tigecycline and polymyxin E. The treatment was well tolerated and resulted in clearance of the pathogen and clinical improvement of the patient’s lung function.

Description: BackgroundCircular RNAs (circRNAs) are now under hot discussion as novel promising biomarkers for patients with hepatocellular carcinoma (HCC). The purpose of our study is to identify several competing endogenous RNA (ceRNA) networks related to the prognosis and progression of HCC and to further investigate the mechanism of their influence on tumor progression.MethodsFirst, we obtained gene expression data related to liver cancer from The Cancer Genome Atlas (TCGA) database (http://www.portal.gdc.cancer.gov/), including microRNA (miRNA) sequence, RNA sequence, and clinical information. A co-expression network was constructed through the Weighted Correlation Network Analysis (WGCNA) software package in R software. The differentially expressed messenger RNAs (DEmRNAs) in the key module were analyzed with the Database for Annotation Visualization and Integrated Discovery (DAVID) (https://david.ncifcrf.gov/summary.jsp) to perform functional enrichment analysis including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The data of miRNA expression and clinical information downloaded from TCGA were utilized for survival analysis to detach the prognostic value of the DEmiRNAs of the key module.ResultsThe 201 differentially expressed miRNAs (DEmiRNAs) and 3,783 DEmRNAs were preliminarily identified through differential expression analysis. The co-expression networks of DEmiRNAs and DEmRNAs were constructed with WGCNA. Further analysis confirmed four miRNAs in the most significant module (blue module) were associated with the overall survival (OS) of patients with liver cancer, including hsa-miR-92b-3p, hsa-miR-122-3p, hsa-miR-139-5p, and hsa-miR-7850-5p. DAVID was used for functional enrichment analysis of 286 co-expressed mRNAs. The GO analysis results showed that the top enriched GO terms were oxidation–reduction process, extracellular exosome, and iron ion binding. In KEGG pathway analysis, the top three enriched terms included metabolic pathways, fatty acid degradation, and valine, leucine, and isoleucine degradation. In addition, we intersected the miRNA–mRNA interaction prediction results with the differentially expressed and prognostic mRNAs. We found that hsa-miR-92b-3p can be related to CPEB3 and ACADL. By overlapping the data of predicted circRNAs by circBank and differentially expressed circRNAs of GSE94508, we screened has_circ_0077210 as the upstream regulatory molecule of hsa-miR-92b-3p. Hsa_circ_0077210/hsa-miR-92b-3p/cytoplasmic polyadenylation element binding protein-3 (CPEB3) and acyl-Coenzyme A dehydrogenase, long chain (ACADL) were validated in HCC tissue.ConclusionOur research provides a mechanistic elucidation of the unknown ceRNA regulatory network in HCC. Hsa_circ_0077210 might serve a momentous therapeutic role to restrain the occurrence and development of HCC.

Description: Background:ODAD3 encodes a protein of 595 amino acids and contain three highly conserved coiled-coil domains, which is essential for cilia axoneme dynein arm assembly and docking. Primary ciliary dyskinesia (PCD) of ODAD3 deficiency are rarely reported. Female infertility in PCD related to ODAD3 variants has not been reported.Methods: Whole-exome and Sanger sequencing were used to identify the disease-related gene of the patient with PCD in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ODAD3 protein.Results: The 35 year-old female patient exhibited chronic sinusitis, diffuse bronchiectasis, dextrocardia and infertility. We identified a novel homozygous variant in ODAD3, c.1166_1169dupAGAC, p.(Leu391Aspfs*105) in the PCD patient by exome sequencing and Sanger sequencing. This frameshift variant was predicted to be disease causing by bioinformatics analysis and was also not presented in the current authorized large genetic databases.Conclusions: Our study enriches the genetic spectrum and clinical phenotypes of ODAD3 variants in PCD and provide more evidence for future genetic counseling and gene-targeted therapy for this disease.

Description: ObjectivesSeveral reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.MaterialsWe collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.ResultsThe bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.

Description: Exploring the molecular mechanisms of breast cancer is essential for the early prediction, diagnosis, and treatment of cancer patients. The large scale of data obtained from the high-throughput sequencing technology makes it difficult to identify the driver mutations and a minimal optimal set of genes that are critical to the classification of cancer. In this study, we propose a novel method without any prior information to identify mutated genes associated with breast cancer. For the somatic mutation data, it is processed to a mutated matrix, from which the mutation frequency of each gene can be obtained. By setting a reasonable threshold for the mutation frequency, a mutated gene set is filtered from the mutated matrix. For the gene expression data, it is used to generate the gene expression matrix, while the mutated gene set is mapped onto the matrix to construct a co-expression profile. In the stage of feature selection, we propose a staged feature selection algorithm, using fold change, false discovery rate to select differentially expressed genes, mutual information to remove the irrelevant and redundant features, and the embedded method based on gradient boosting decision tree with Bayesian optimization to obtain an optimal model. In the stage of evaluation, we propose a weighted metric to modify the traditional accuracy to solve the sample imbalance problem. We apply the proposed method to The Cancer Genome Atlas breast cancer data and identify a mutated gene set, among which the implicated genes are oncogenes or tumor suppressors previously reported to be associated with carcinogenesis. As a comparison with the integrative network, we also perform the optimal model on the individual gene expression and the gold standard PMA50. The results show that the integrative network outperforms the gene expression and PMA50 in the average of most metrics, which indicate the effectiveness of our proposed method by integrating multiple data sources, and can discover the associated mutated genes in breast cancer.

Description: Vibrio vulnificus is a deadly human pathogen for which infections occur via seafood consumption (foodborne) or direct contact with wounds. Virulence is not fully characterized for this organism; however, there is evidence of biochemical and genotypic correlations with virulence potential. In this study, biochemical profiles and virulence genotype, based on 16S rRNA gene (rrn) and virulence correlated gene (vcg) types, were determined for 30 clinical and 39 oyster isolates. Oyster isolates were more biochemically diverse than the clinical isolates, with four of the 20 tests producing variable (defined as 20–80% of isolates) results. Whereas, for clinical isolates only mannitol fermentation, which has previously been associated with virulence potential, varied among the isolates. Nearly half (43%) of clinical isolates were the more virulent genotype (rrnB/vcgC); this trend was consistent when only looking at clinical isolates from blood. The majority (64%) of oyster isolates were the less virulent genotype (rrnA or AB/vcgE). These data were used to select a sub-set of 27 isolates for virulence testing with a subcutaneously inoculated, iron-dextran treated mouse model. Based on the mouse model data, 11 isolates were non-lethal, whereas 16 isolates were lethal, indicating a potential for human infection. Within the non-lethal group there were eight oyster and three clinical isolates. Six of the non-lethal isolates were the less virulent genotype (rrnA/vcgE or rrnAB/vcgE) and two were rrnB/vcgC with the remaining two of mixed genotype (rrnAB/vcgC and rrnB/vcgE). Of the lethal isolates, five were oysters and 11 were clinical. Eight of the lethal isolates were the less virulent genotype and seven the more virulent genotype, with the remaining isolate a mixed genotype (rrnA/vcgC). A discordance between virulence genotype and individual mouse virulence parameters (liver infection, skin infection, skin lesion score, and body temperature) was observed; the variable most strongly associated with mouse virulence parameters was season (warm or cold conditions at time of strain isolation), with more virulent strains isolated from cold conditions. These results indicate that biochemical profiles and genotype are not significantly associated with virulence potential, as determined by a mouse model. However, a relationship with virulence potential and seasonality was observed.

Description: Infection with Mycobacterium tuberculosis (Mtb) leading to tuberculosis (TB) disease continues to be a major global health challenge. Critical barriers, including but not limited to the development of multi-drug resistance, lack of diagnostic assays that detect patients with latent TB, an effective vaccine that prevents Mtb infection, and infectious and non-infectious comorbidities that complicate active TB, continue to hinder progress toward a TB cure. To complement the ongoing development of new antimicrobial drugs, investigators in the field are exploring the value of host-directed therapies (HDTs). This therapeutic strategy targets the host, rather than Mtb, and is intended to augment host responses to infection such that the host is better equipped to prevent or clear infection and resolve chronic inflammation. Metabolic pathways of immune cells have been identified as promising HDT targets as more metabolites and metabolic pathways have shown to play a role in TB pathogenesis and disease progression. Specifically, this review highlights the potential role of lactate as both an immunomodulatory metabolite and a potentially important signaling molecule during the host response to Mtb infection. While long thought to be an inert end product of primarily glucose metabolism, the cancer research field has discovered the importance of lactate in carcinogenesis and resistance to chemotherapeutic drug treatment. Herein, we discuss similarities between the TB granuloma and tumor microenvironments in the context of lactate metabolism and identify key metabolic and signaling pathways that have been shown to play a role in tumor progression but have yet to be explored within the context of TB. Ultimately, lactate metabolism and signaling could be viable HDT targets for TB; however, critical additional research is needed to better understand the role of lactate at the host-pathogen interface during Mtb infection before adopting this HDT strategy.

Description: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates from an intensive care unit from one hospital in China collected over six years. All strains carried blaOXA-23, blaOXA-66 genes for carbapenem resistance, also had high resistance gene, virulence factor, and insertion sequence burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates were dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only existed in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences appeared among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in the hospital ICU environment demonstrating potential clone outbreak in the hospital.

Description: Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.

Description: Protein–protein interaction (PPI) is the basis of the whole molecular mechanisms of living cells. Although traditional experiments are able to detect PPIs accurately, they often encounter high cost and require more time. As a result, computational methods have been used to predict PPIs to avoid these problems. Graph structure, as the important and pervasive data carriers, is considered as the most suitable structure to present biomedical entities and relationships. Although graph embedding is the most popular approach for graph representation learning, it usually suffers from high computational and space cost, especially in large-scale graphs. Therefore, developing a framework, which can accelerate graph embedding and improve the accuracy of embedding results, is important to large-scale PPIs prediction. In this paper, we propose a multi-level model LPPI to improve both the quality and speed of large-scale PPIs prediction. Firstly, protein basic information is collected as its attribute, including positional gene sets, motif gene sets, and immunological signatures. Secondly, we construct a weighted graph by using protein attributes to calculate node similarity. Then GraphZoom is used to accelerate the embedding process by reducing the size of the weighted graph. Next, graph embedding methods are used to learn graph topology features from the reconstructed graph. Finally, the linear Logistic Regression (LR) model is used to predict the probability of interactions of two proteins. LPPI achieved a high accuracy of 0.99997 and 0.9979 on the PPI network dataset and GraphSAGE-PPI dataset, respectively. Our further results show that the LPPI is promising for large-scale PPI prediction in both accuracy and efficiency, which is beneficial to other large-scale biomedical molecules interactions detection.

Description: Microsatellite or simple sequence repeat (SSR) instability within genes can induce genetic variation. The SSR signatures remain largely unknown in different clades within Euarchontoglires, one of the most successful mammalian radiations. Here, we conducted a genome-wide characterization of microsatellite distribution patterns at different taxonomic levels in 153 Euarchontoglires genomes. Our results showed that the abundance and density of the SSRs were significantly positively correlated with primate genome size, but no significant relationship with the genome size of rodents was found. Furthermore, a higher level of complexity for perfect SSR (P-SSR) attributes was observed in rodents than in primates. The most frequent type of P-SSR was the mononucleotide P-SSR in the genomes of primates, tree shrews, and colugos, while mononucleotide or dinucleotide motif types were dominant in the genomes of rodents and lagomorphs. Furthermore, (A)n was the most abundant motif in primate genomes, but (A)n, (AC)n, or (AG)n was the most abundant motif in rodent genomes which even varied within the same genus. The GC content and the repeat copy numbers of P-SSRs varied in different species when compared at different taxonomic levels, reflecting underlying differences in SSR mutation processes. Notably, the CDSs containing P-SSRs were categorized by functions and pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations, highlighting their roles in transcription regulation. Generally, this work will aid future studies of the functional roles of the taxonomic features of microsatellites during the evolution of mammals in Euarchontoglires.

Description: Glutamine synthetase (GS) is one of the most important metabolic enzymes which catalyzes ligation of glutamate and ammonia to form glutamine. Previous studies from our lab had revealed significant differences in parasite and host GS enzyme which warranted us to further work on its relevance in parasite. To analyze glutamine synthetase function in Leishmania, we generated GS overexpressors and knockout mutants and evaluated their ability to grow in vitro in monocyte differentiated macrophage and in vivo by infections in BALB/c mice. GS knocked out strain showed significant growth retardation with delayed cell cycle progression and morphological alteration. Null mutants exhibited attenuated infectivity both in in vitro and in vivo experiments and the effect was reverted back when infected with GS complemented parasites. This indicated that the alterations in phenotype observed were indeed due to GS knockout. GS knockout also made the parasite increasingly sensitive to Miltefosine. Detailed investigation of mode of parasite death upon Miltefosine treatment by dual staining with Annexin-V conjugated FITC and propidium iodide, pointed towards apoptotic or necrotic mode of cell death. This is the first report to confirm that GS is essential for the survivability and infectivity of Leishmania donovani, and can be exploited as a potential drug-target.

Description: Strategies for the use of amendments on agricultural soils are needed to help build resilience against potential soil threats. Gypsum is commonly applied to improve soil quality and nutrient supply. However, the sustainability and environmental safety of some gypsum sources is uncertain. This study aims to i. characterize a new by-product, lacto-gypsum, derived from a dairy whey side stream over a 1 year pilot production cycle and ii. assess the temporal variability of the raw form of lacto-gypsum and the stability of its physico-chemical and compositional properties when stored under three potential storage regimes. Results showed that lacto-gypsum compares favorably with conventional equivalents in terms of nutrient and trace element concentrations and represents an environmentally safe material free of contaminants. Storage form did not affect its main physico-chemical characteristics over time and the raw lacto-gypsum remained stable up to 20 days when stored at 4°C. In contrast to conventional gypsum, the lacto-gypsum had very low pH. In general this new lacto-gypsum shows potential as a suitable product for use as a soil amendment or as an acidification agent for animal slurry to reduce ammonia gas emissions during storage. However, further evaluation of this by-product in real life scenarios is required.

Description: BackgroundThe emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed.MethodsTargeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively.ResultsThe limit of detection was 1 copies/μl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples.ConclusionThis work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.

Description: Non-obstructive azoospermia (NOA) denotes a severe form of male infertility, whose etiology is still poorly understood. This is mainly due to limited knowledge on the molecular mechanisms that lead to spermatogenesis failure. In this study, we acquired microarray data from GEO DataSets and identified differentially expressed genes using the limma package in R. We identified 1,261 differentially expressed genes between non-obstructive and obstructive azoospermia. Analysis of their possible biological functions and related signaling pathways using the cluster profiler package revealed an enrichment of genes involved in germ cell development, cilium organization, and oocyte meiosis. Immune infiltration analysis indicated that macrophages were the most significant immune component of NOA, cooperating with mast cells and natural killer cells. The weighted gene coexpression network analysis algorithm generated three related functional modules, which correlated closely with clinical parameters derived from histopathological subtypes of NOA. The resulting data enabled the construction of a protein–protein interaction network of these three modules, with CDK1, CDC20, CCNB1, CCNB2, and MAD2L1 identified as hub genes. This study provides the basis for further investigation of the molecular mechanism underlying NOA, as well as indications about potential biomarkers and therapeutic targets of NOA. Finally, using tissues containing different tissue types for differential expression analysis can reflect the expression differences in different tissues to a certain extent. But this difference in expression is only related and not causal. The specific causality needs to be verified later.

Description: Mutually exclusive splicing is an important mechanism for expanding protein diversity. An extreme example is the Down syndrome cell adhesion molecular (Dscam1) gene of insects, containing four clusters of variable exons (exons 4, 6, 9, and 17), which potentially generates tens of thousands of protein isoforms through mutually exclusive splicing, of which regulatory mechanisms are still elusive. Here, we systematically analyzed the variable exon 4, 6, and 9 clusters of Dscam1 in Coleoptera species. Through comparative genomics and RNA secondary structure prediction, we found apparent evidence that the evolutionarily conserved RNA base pairing mediates mutually exclusive splicing in the Dscam1 exon 4 cluster. In contrast to the fly exon 6, most exon 6 selector sequences in Coleoptera species are partially located in the variable exon region. Besides, bidirectional RNA–RNA interactions are predicted to regulate the mutually exclusive splicing of variable exon 9 of Dscam1. Although the docking sites in exon 4 and 9 clusters are clade specific, the docking sites-selector base pairing is conserved in secondary structure level. In short, our result provided a mechanistic framework for the application of long-range RNA base pairings in regulating the mutually exclusive splicing of Coleoptera Dscam1.

Description: Inadequate sleep prevails in modern society and it impairs the circadian transcriptome. However, to what extent acute sleep deprivation (SD) has impact on the circadian rhythms of peripheral tissues is not clear. Here, we show that in mouse lung, a 10-h acute sleep deprivation can alter the circadian expression of approximately 3,000 genes. We found that circadian rhythm disappears in genes related to metabolism and signaling pathways regulating protein phosphorylation after acute sleep deprivation, while the core circadian regulators do not change much in rhythmicity. Importantly, the strong positive correlation between mean expression and amplitude (E-A correlation) of cycling genes has been validated in both control and sleep deprivation conditions, supporting the energetic cost optimization model of circadian gene expression. Thus, we reveal that acute sleep deprivation leads to a profound change in the circadian gene transcription that influences the biological functions in lung.

Description: Parkinson’s disease (PD) exhibits the second-highest rate of mortality among neurodegenerative diseases. PD is difficult to diagnose and treat due to its polygenic nature. In recent years, numerous studies have established a correlation between this disease and miRNA expression; however, it remains necessary to determine the quantitative characteristics of the interactions between miRNAs and their target genes. In this study, using novel bioinformatics approaches, the quantitative characteristics of the interactions between miRNAs and the mRNAs of candidate PD genes were established. Of the 6,756 miRNAs studied, more than one hundred efficiently bound to mRNA of 61 candidate PD genes. The miRNA binding sites (BS) were located in the 5′-untranslated region (5′UTR), coding sequence (CDS) and 3′-untranslated region (3′UTR) of the mRNAs. In the mRNAs of many genes, the locations of miRNA BS with overlapping nucleotide sequences (clusters) were identified. Such clusters substantially reduced the proportion of nucleotide sequences of miRNA BS in the 5′UTRs, CDSs, and 3′UTRs. The organization of miRNA BS into clusters leads to competition among miRNAs to bind mRNAs. Differences in the binding characteristics of miRNAs to the mRNAs of genes expressed at different rates were identified. Single miRNA BS, polysites for the binding for one miRNA, and multiple BS for two or more miRNAs in one mRNA were identified. Evolutionary changes in the BS of miRNAs and their clusters in 5′UTRs, CDSs and 3′UTRs of mRNA of orthologous candidate PD genes were established. Based on the quantitative characteristics of the interactions between miRNAs and mRNAs candidate PD genes, several associations recommended as markers for the diagnosis of PD.

Description: BackgroundCarcass traits are crucial characteristics of broilers. However, the underlying genetic mechanisms are not well understood. In the current study, significant loci and major-effect candidate genes affecting nine carcass traits related to meat production were analyzed in 873 purebred broilers using an imputation-based genome-wide association study.ResultsThe heritability estimates of nine carcass traits, including carcass weight, thigh muscle weight, and thigh muscle percentage, were moderate to high and ranged from 0.21 to 0.39. Twelve genome-wide significant SNPs and 118 suggestively significant SNPs of 546,656 autosomal variants were associated with carcass traits. All SNPs for six weight traits (body weight at 42 days of age, carcass weight, eviscerated weight, whole thigh weight, thigh weight, and thigh muscle weight) were clustered around the 24.08 Kb region (GGA24: 5.73–5.75 Mb) and contained only one candidate gene (DRD2). The most significant SNP, rs15226023, accounted for 4.85–7.71% of the estimated genetic variance of the six weight traits. The remaining SNPs for carcass composition traits (whole thigh percentage and thigh percentage) were clustered around the 42.52 Kb region (GGA3: 53.03–53.08 Mb) and contained only one candidate gene (ADGRG6). The most significant SNP in this region, rs13571431, accounted for 11.89–13.56% of the estimated genetic variance of two carcass composition traits. Some degree of genetic differentiation in ADGRG6 between large and small breeds was observed.ConclusionWe identified one 24.08 Kb region for weight traits and one 42.52 Kb region for thigh-related carcass traits. DRD2 was the major-effect candidate gene for weight traits, and ADGRG6 was the major-effect candidate gene for carcass composition traits. Our results supply essential information for causative mutation identification of carcass traits in broilers.

Description: With the fossil energy crisis and environmental pollution, wind energy and other renewable energy have been booming. However, the strong intermittence and volatility of wind power make difficult of its integration into grid. To solve this problem, this study proposes a complementary power generation model of wind-hydropower-pumped storage systems, which uses hydropower and pumped storage to adjust the fluctuation of wind power. How to consider the uncertainty and unpredictability of wind power output and make more reliable hydropower generation plan and pumped storage generation plan is the key problem to be solved in the grid with the high proportion of renewable energy. The martingale model of forecast evolution is used to describe the uncertainty evolution of wind power in different regions. According to the flexible load in the region, the flexibility index is used to quantify flexibility, and the transaction price is set to be proportional to flexibility. The two-stage framework of day-ahead and real-time dispatching model is then developed. In the day-ahead stage, different regions trade with each other. If the power after trading is imbalanced, it will be supplemented by hydropower and the grid to meet the power demand. In the real-time stage, the pumped storage is added to quickly balance the deviation of wind power and load between the real-time and day-ahead stages. Finally, considering the positive effect of hydropower on wind power consumption in the grid, a benefit allocation method based on improved Shapley value method is proposed. Test cases are simulated to verify the rationality of the proposed dispatching model and the benefit allocation method. After the cooperation of hydropower and pumped storage, the average revenue growth is 3.02%. The improved benefit allocation scheme makes more benefit of hydropower and pumped storage and promotes the cooperation of multi-participants.

Description: The development of efficient and cost-effective solar photocatalysts capable of producing hydrogen from formic acid as a hydrogen storage medium is still a challenging issue. Herein, we report that iron minerals, ferric iron hydroxy sulfates (FHS), immobilized on a natural layered silicate, magadiite, can be used as a photocatalyst to produce hydrogen from formic acid under irradiation with solar simulator. The material exhibits the hydrogen production rate of 470 μmol g−1 h−1, which is considerably higher than that obtained on other iron minerals and comparable to that obtained on precious metal-based photocatalyst ever reported. The present result may open a way to design efficient photocatalyst for hydrogen production from formic acid in an economically and environmentally friendly way.

Description: Our research aims to analyze how the uncertainties and risks of the overseas oil & gas investment environment change over time and reveal the specific occurrence probabilities of risk on different levels. In the process of long-drawn overseas oil & gas investment that can last for 30 years or longer, it is difficult for investment decision-makers to grasp the occurrence probabilities and trends of some specific risks accurately and in a timely manner. The overseas risk assessment system has made great progress; however, it has remained elusive due to the challenge of too many complex and interweaved factors. With the advent of big data and artificial intelligence, more precise and specific risk evaluations can be conducted. Our research selects 25 indicators from six dimensions and applies a Cloud parameter Bayesian network algorithm to dynamically assess the oil and gas overseas investment risk of 10 countries. The results reveal how risk dynamics have changed over the past two decades. Our research may serve as a reference in future overseas oil & gas investment risk decision-making, and is also significant to outbound investing, engineering, and service projects. The proper use of risk assessment results can be conducive to potential investors who may invest in potential countries in the future.

Description: Primary cardiomyopathies (CMPs) are monogenic but multi-allelic disorders with dozens of genes involved in pathogenesis. The implementation of next-generation sequencing (NGS) approaches has resulted in more time- and cost-efficient DNA diagnostics of cardiomyopathies. However, the diagnostic yield of genetic testing for each subtype of CMP fails to exceed 60%. The aim of this study was to demonstrate that allelic dropout (ADO) is a common phenomenon that reduces the diagnostic yield in primary cardiomyopathy genetic testing based on targeted gene panels assayed on the Ion Torrent platform. We performed mutational screening with three custom targeted gene panels based on sets of oligoprimers designed automatically using AmpliSeq Designer® containing 1049 primer pairs for 37 genes with a total length of 153 kb. DNA samples from 232 patients were screened with at least one of these targeted gene panels. We detected six ADO events in both IonTorrent PGM (three cases) and capillary Sanger sequencing (three cases) data, identifying ADO-causing variants in all cases. All ADO events occurred due to common or rare single nucleotide variants (SNVs) in the oligoprimer binding sites and were detected because of the presence of “marker” SNVs in the target DNA fragment. We ultimately identified that PCR-based NGS involves a risk of ADO that necessitates the use of Sanger sequencing to validate NGS results. We assume that oligoprimer design without ADO data affects the amplification efficiency of up to 0.77% of amplicons.

Description: A 78 years old Chinese woman with five different cancer types and a family history of malignancy was the subject of this study. Pancreatic adenocarcinoma and gingival squamous cell carcinoma tissues were obtained from the patient and sequenced using Whole Exome Sequencing. Whole exome sequencing identified 20 mutation sites in six candidate genes. Sanger Sequencing was used for further validation. The results verified six mutations in three genes, OBSCN, TTN, and RPGRIP1L, in at least one cancer type. Immunohistochemistry was used to verify protein expression. mRNA expression analysis using The Cancer Genome Atlas database revealed that RPGRIP1L was highly expressed in several cancer types, especially in pancreatic adenocarcinoma, and correlated with patient survival and sensitivity to paclitaxel, probably through the TGF-β signaling pathway. The newly identified somatic mutations in RPGRIP1L might contribute to pathogenesis in the patients. Protein conformation simulation demonstrated that the alterations had caused the binding pocket at position 708 to change from concave to convex, which could restrict contraction and extension, and interfere with the physiological function of the protein. Further studies are required to determine the implication of RPGRIP1L in this family and in multiple primary tumors.

Description: AimImmune cells that infiltrate the tumor microenvironment (TME) are associated with cancer prognosis. The aim of the current study was to identify TME related gene signatures related to the prognosis of sarcoma (SARC) by using the data from The Cancer Genome Atlas (TCGA).MethodsImmune and stromal scores were calculated by estimation of stromal and immune cells in malignant tumor tissues using expression data algorithms. The least absolute shrinkage and selection operator (lasso) based cox model was then used to select hub survival genes. A risk score model and nomogram were used to predict the overall survival of patients with SARC.ResultsWe selected 255 patients with SARC for our analysis. The Kaplan–Meier method found that higher immune (p = 0.0018) or stromal scores (p = 0.0022) were associated with better prognosis of SARC. The estimated levels of CD4+ (p = 0.0012) and CD8+ T cells (p = 0.017) via the tumor immune estimation resource were higher in patients with SARC with better overall survival. We identified 393 upregulated genes and 108 downregulated genes (p 〈 0.05, fold change 〉4) intersecting between the immune and stromal scores based on differentially expressed gene (DEG) analysis. The univariate Cox analysis of each intersecting DEG and subsequent lasso-based Cox model identified 11 hub survival genes (MYOC, NNAT, MEDAG, TNFSF14, MYH11, NRXN1, P2RY13, CXCR3, IGLV3-25, IGHV1-46, and IGLV2-8). Then, a hub survival gene-based risk score gene signature was constructed; higher risk scores predicted worse SARC prognosis (p 〈 0.0001). A nomogram including the risk scores, immune/stromal scores and clinical factors showed a good prediction value for SARC overall survival (C-index = 0.716). Finally, connectivity mapping analysis identified that the histone deacetylase inhibitors trichostatin A and vorinostat might have the potential to reverse the harmful TME for patients with SARC.ConclusionThe current study provided new indications for the association between the TME and SARC. Lists of TME related survival genes and potential therapeutic drugs were identified for SARC.

Description: This study constructed a comprehensive index system and employed a coupling coordination degree model, global spatial autocorrelation models, and local spatial autocorrelation models to quantitatively investigate the spatiotemporal characteristics and dynamic mechanism of the coupling coordination relationship between green urbanization and green finance in China during 2010–2017. The results showed that the level of green urbanization and green finance improved over the study period, but the development of green finance lagged behind the pace of green urbanization and the comprehensive score was still low. The coupling coordination degree presented a trend of continuous optimization, with coordination in eastern China being clearly higher than in central, western, and northeastern China. Furthermore, there was both spatial dependency and spatial heterogeneity in the coupling coordination degree between green urbanization and green finance. Provinces with a high-high clustering mode were mainly distributed in the eastern region, while provinces in western and northeastern China mainly had a low-low clustering mode in 2010. The high-high clustering mode gradually expanded from eastern to central China, while most provinces in western and northeastern China still exhibited low-low clustering in 2017. This indicates that the coupling coordination degree between green urbanization and green finance had strong spatial agglomeration and spatial spillover effects in central and eastern China, while in western and northeastern China its development was still poor.

Description: The AP2/ERF is a large protein family of transcription factors, playing an important role in signal transduction, plant growth, development, and response to various stresses. AP2/ERF super-family is identified and functionalized in a different plant but no comprehensive and systematic analysis in wheat (Triticum aestivum L.) has been reported. However, a genome-wide and functional analysis was performed and identified 322 TaAP2/ERF putative genes from the wheat genome. According to the phylogenetic and structural analysis, TaAP2/ERF genes were divided into 12 subfamilies (Ia, Ib, Ic, IIa, IIb, IIc, IIIa, IIIb, IIIc, IVa, IVb, and IVc). Furthermore, conserved motifs and introns/exons analysis revealed may lead to functional divergence within clades. Cis-Acting analysis indicated that many elements were involved in stress-related and plant development. Chromosomal location showed that 320 AP2/ERF genes were distributed among 21 chromosomes and 2 genes were present in a scaffold. Interspecies microsynteny analysis revealed that maximum orthologous between Arabidopsis, rice followed by wheat. Segment duplication events have contributed to the expansion of the AP2/ERF family and made this family larger than rice and Arabidopsis. Additionally, AP2/ERF genes were differentially expressed in wheat seedlings under the stress treatments of heat, salt, and drought, and expression profiles were verified by qRT-PCR. Remarkably, the RNA-seq data exposed that AP2/ERF gene family might play a vital role in stress-related. Taken together, our findings provided useful and helpful information to understand the molecular mechanism and evolution of the AP2/ERF gene family in wheat.

Description: The observable phenotype is the manifestation of information that is passed along different organization levels (transcriptional, translational, and metabolic) of a biological system. The widespread use of various omic technologies (RNA-sequencing, metabolomics, etc.) has provided plant genetics and breeders with a wealth of information on pertinent intermediate molecular processes that may help explain variation in conventional traits such as yield, seed quality, and fitness, among others. A major challenge is effectively using these data to help predict the genetic merit of new, unobserved individuals for conventional agronomic traits. Trait-specific genomic relationship matrices (TGRMs) model the relationships between individuals using genome-wide markers (SNPs) and place greater emphasis on markers that most relevant to the trait compared to conventional genomic relationship matrices. Given that these approaches define relationships based on putative causal loci, it is expected that these approaches should improve predictions for related traits. In this study we evaluated the use of TGRMs to accommodate information on intermediate molecular phenotypes (referred to as endophenotypes) and to predict an agronomic trait, total lipid content, in oat seed. Nine fatty acids were quantified in a panel of 336 oat lines. Marker effects were estimated for each endophenotype, and were used to construct TGRMs. A multikernel TRGM model (MK-TRGM-BLUP) was used to predict total seed lipid content in an independent panel of 210 oat lines. The MK-TRGM-BLUP approach significantly improved predictions for total lipid content when compared to a conventional genomic BLUP (gBLUP) approach. Given that the MK-TGRM-BLUP approach leverages information on the nine fatty acids to predict genetic values for total lipid content in unobserved individuals, we compared the MK-TGRM-BLUP approach to a multi-trait gBLUP (MT-gBLUP) approach that jointly fits phenotypes for fatty acids and total lipid content. The MK-TGRM-BLUP approach significantly outperformed MT-gBLUP. Collectively, these results highlight the utility of using TGRM to accommodate information on endophenotypes and improve genomic prediction for a conventional agronomic trait.

Description: MotivationDNA N4-methylcytosine (4mC) and N6-methyladenine (6mA) are two important DNA modifications and play crucial roles in a variety of biological processes. Accurate identification of the modifications is essential to better understand their biological functions and mechanisms. However, existing methods to identify 4mA or 6mC sites are all single tasks, which demonstrates that they can identify only a certain modification in one species. Therefore, it is desirable to develop a novel computational method to identify the modification sites in multiple species simultaneously.ResultsIn this study, we proposed a computational method, called iDNA-MT, to identify 4mC sites and 6mA sites in multiple species, respectively. The proposed iDNA-MT mainly employed multi-task learning coupled with the bidirectional gated recurrent units (BGRU) to capture the sharing information among different species directly from DNA primary sequences. Experimental comparative results on two benchmark datasets, containing different species respectively, show that either for identifying 4mA or for 6mC site in multiple species, the proposed iDNA-MT outperforms other state-of-the-art single-task methods. The promising results have demonstrated that iDNA-MT has great potential to be a powerful and practically useful tool to accurately identify DNA modifications.

Description: Biomolecules specifically aggregate in the cytoplasm and nucleus, driving liquid-liquid phase separation (LLPS) formation and diverse biological processes. Extensive studies have focused on revealing multiple functional membraneless organelles in both the nucleus and cytoplasm. Condensation compositions of LLPS, such as proteins and RNAs affecting the formation of phase separation, have been gradually unveiled. LncRNAs possessing abundant second structures usually promote phase separation formation by providing architectural scaffolds for diverse RNAs and proteins interaction in both the nucleus and cytoplasm. Beyond scaffolds, lncRNAs may possess more diverse functions, such as functioning as enhancer RNAs or buffers. In this review, we summarized current studies on the function of phase separation and its related lncRNAs, mainly in the nucleus. This review will facilitate our understanding of the formation and function of phase separation and the role of lncRNAs in these processes and related biological activities. A deeper understanding of the formation and maintaining of phase separation will be beneficial for disease diagnosis and treatment.

Description: This work presents an optimized probabilistic modeling methodology that facilitates the modeling of photovoltaic (PV) modules with measured data over a range of environmental conditions. The method applies cuckoo search to optimize kernel parameters, followed by electrical characteristics estimation via relevance vector machine. Unlike analytical modeling techniques, the proposed cuckoo search-relevance vector machine (CS-RVM) takes advantages of no required knowledge of internal PV parameters, more accurate estimation capability and less computational effort. A comparative study has been done among the electrical characteristics predicted by back-propagation neural network (BPNN), radial basis function neural network (RBFNN), support vector machine (SVM), Villalva's model, relevance vector machine (RVM), and the CS-RVM. Experimental results show that the proposed CS-RVM provides the best prediction in most scenarios.

Description: Tuberculosis still remains a concerning health problem worldwide. Its etiologic agent, Mycobacterium tuberculosis, continues to be the focus of research to unravel new prophylactic and therapeutic strategies against this disease. The only vaccine in use against tuberculosis is based on the in vitro attenuated strain, M. bovis BCG. Dodecin is a dodecameric complex important for flavin homeostasis in Archea and Eubacteria, and the M. tuberculosis protein is described as thermo- and halostable. M. bovis BCG Moreau, the Brazilian vaccine strain, has a single nucleotide polymorphism in the dodecin start codon, leading to a predicted loss of seven amino acids at the protein N-terminal end. In this work we aimed to characterize the effect of this mutation in the BCG Moreau protein features. Our recombinant protein assays show that the predicted BCG homolog is less thermostable than M.tb’s but maintains its dodecamerization ability, although with a lower riboflavin-binding capacity. These data are corroborated by structural analysis after comparative modeling, showing that the predicted BCG dodecin complex has a lower interaction energy among its monomers and also a distinct electrostatic surface near the flavin binding pocket. However, western blotting assays with the native proteins were unable to detect significant differences between the BCG Moreau and M.tb orthologs, indicating that other factors may be modulating protein structure/function in the bacterial context.

Description: Multilayer networks provide an efficient tool for studying complex systems, and with current, dramatic development of bioinformatics tools and accumulation of data, researchers have applied network concepts to all aspects of research problems in the field of biology. Addressing the combination of multilayer networks and bioinformatics, through summarizing the applications of multilayer network models in bioinformatics, this review classifies applications and presents a summary of the latest results. Among them, we classify the applications of multilayer networks according to the object of study. Furthermore, because of the systemic nature of biology, we classify the subjects into several hierarchical categories, such as cells, tissues, organs, and groups, according to the hierarchical nature of biological composition. On the basis of the complexity of biological systems, we selected brain research for a detailed explanation. We describe the application of multilayer networks and chronological networks in brain research to demonstrate the primary ideas associated with the application of multilayer networks in biological studies. Finally, we mention a quality assessment method focusing on multilayer and single-layer networks as an evaluation method emphasizing network studies.

Description: Children with rare and common diseases now undergo whole genome sequencing (WGS) in clinical and research contexts. Parents sometimes request access to their child's raw genomic data, to pursue their own analyses or for onward sharing with health professionals and researchers. These requests raise legal, ethical, and practical issues for professionals and parents alike. The advent of widespread WGS in pediatrics occurs in a context where privacy and data protection law remains focused on giving individuals control-oriented rights with respect to their personal information. Acting in their child's stead and in their best interests, parents are generally the ones who will be exercising these informational rights on behalf of the child. In this paper, we map the contours of parental authority to access their child's raw genomic data. We consider three use cases: hospital-based researchers, healthcare professionals acting in a clinical-diagnostic capacity, and “pure” academic researchers at a public institution. Our research seeks to answer two principal questions: Do parents have a right of access to their child's raw WGS data? If so, what are the limits of this right? Primarily focused on the laws of Ontario, Canada's most populous province, with a secondary focus on Canada's three other most populous provinces (Quebec, British Columbia, and Alberta) and the European Union, our principal findings include (1) parents have a general right of access to information about their children, but that the access right is more capacious in the clinical context than in the research context; (2) the right of access extends to personal data in raw form; (3) a consideration of the best interests of the child may materially limit the legal rights of parents to access data about their child; (4) the ability to exercise rights of access are transferred from parents to children when they gain decision-making capacity in both the clinical and research contexts, but with more nuance in the former. With these findings in mind, we argue that professional guidelines, which are concerned with obligations to interpret and return results, may assist in furthering a child's best interests in the context of legal access rights. We conclude by crafting recommendations for healthcare professionals in the clinical and research contexts when faced with a parental request for a child's raw genomic data.

Description: Tea (Camellia sinensis) is an important economic beverage crop. Its flowers and leaves could be used as healthcare tea for its medicinal value. SWEET proteins were recently identified in plants as sugar transporters, which participate in diverse physiological processes, including pathogen nutrition, seed filling, nectar secretion, and phloem loading. Although SWEET genes have been characterized and identified in model plants, such as Arabidopsis thaliana and Oryza sativa, there is very little knowledge of these genes in C. sinensis. In this study, 28 CsSWEETs were identified in C. sinensis and further phylogenetically divided into four subfamilies with A. thaliana. These identified CsSWEETs contained seven transmembrane helixes (TMHs) which were generated by an ancestral three-TMH unit with an internal duplication experience. Microsynteny analysis revealed that the large-scale duplication events were the main driving forces for members from CsSWEET family expansion in C. sinensis. The expression profiles of the 28 CsSWEETs revealed that some genes were highly expressed in reproductive tissues. Among them, CsSWEET1a might play crucial roles in the efflux of sucrose, and CsSWEET17b could control fructose content as a hexose transporter in C. sinensis. Remarkably, CsSWEET12 and CsSWEET17c were specifically expressed in flowers, indicating that these two genes might be involved in sugar transport during flower development. The expression patterns of all CsSWEETs were differentially regulated under cold and drought treatments. This work provided a systematic understanding of the members from the CsSWEET gene family, which would be helpful for further functional studies of CsSWEETs in C. sinensis.

Description: The mixed linear model (MLM) has been widely used in genome-wide association study (GWAS) to dissect quantitative traits in human, animal, and plant genetics. Most methodologies consider all single nucleotide polymorphism (SNP) effects as random effects under the MLM framework, which fail to detect the joint minor effect of multiple genetic markers on a trait. Therefore, polygenes with minor effects remain largely unexplored in today’s big data era. In this study, we developed a new algorithm under the MLM framework, which is called the fast multi-locus ridge regression (FastRR) algorithm. The FastRR algorithm first whitens the covariance matrix of the polygenic matrix K and environmental noise, then selects potentially related SNPs among large scale markers, which have a high correlation with the target trait, and finally analyzes the subset variables using a multi-locus deshrinking ridge regression for true quantitative trait nucleotide (QTN) detection. Results from the analyses of both simulated and real data show that the FastRR algorithm is more powerful for both large and small QTN detection, more accurate in QTN effect estimation, and has more stable results under various polygenic backgrounds. Moreover, compared with existing methods, the FastRR algorithm has the advantage of high computing speed. In conclusion, the FastRR algorithm provides an alternative algorithm for multi-locus GWAS in high dimensional genomic datasets.

Description: LixFePO4 orthophosphates and fluorite- and pyrochlore-type zirconate materials are widely considered as functional compounds in energy storage devices, either as electrode or solid state electrolyte. These ceramic materials show enhanced cation exchange and anion conductivity properties that makes them attractive for various energy applications. In this contribution we discuss thermodynamic properties of LixFePO4 and yttria-stabilized zirconia compounds, including formation enthalpies, stability, and solubility limits. We found that at ambient conditions LixFePO4 has a large miscibility gap, which is consistent with existing experimental evidence. We show that cubic zirconia becomes stabilized with Y content of ~8%, which is in line with experimental observations. The computed activation energy of 0.92eV and ionic conductivity for oxygen diffusion in yttria-stabilized zirconia are also in line with the measured data, which shows that atomistic modeling can be applied for accurate prediction of key materials properties. We discuss these results with the existing simulation-based data on these materials produced by our group over the last decade. Last, but not least, we discuss similarities of the considered compounds in considering them as materials for energy storage and radiation damage resistant matrices for immobilization of radionuclides.

Description: Tandem repeats are important parts of eukaryotic genomes being crucial e.g., for centromere and telomere function and chromatin modulation. In Lepidoptera, knowledge of tandem repeats is very limited despite the growing number of sequenced genomes. Here we introduce seven new satellite DNAs (satDNAs), which more than doubles the number of currently known lepidopteran satDNAs. The satDNAs were identified in genomes of three species of Crambidae moths, namely Ostrinia nubilalis, Cydalima perspectalis, and Diatraea postlineella, using graph-based computational pipeline RepeatExplorer. These repeats varied in their abundance and showed high variability within and between species, although some degree of conservation was noted. The satDNAs showed a scattered distribution, often on both autosomes and sex chromosomes, with the exception of both satellites in D. postlineella, in which the satDNAs were located at a single autosomal locus. Three satDNAs were abundant on the W chromosomes of O. nubilalis and C. perspectalis, thus contributing to their differentiation from the Z chromosomes. To provide background for the in situ localization of the satDNAs, we performed a detailed cytogenetic analysis of the karyotypes of all three species. This comparative analysis revealed differences in chromosome number, number and location of rDNA clusters, and molecular differentiation of sex chromosomes.

Description: BackgroundGrowth arrest–specific 2 like 3 (GAS2L3) is a cytoskeleton-associated protein that interacts with actin filaments and tubulin. Abnormal GAS2L3 expression has been reported to be associated with carcinogenesis. However, the biological role of GAS2L3 in glioma remains to be determined.MethodsThe transcriptome level of GAS2L3 and its relationship with clinicopathological characteristics were analyzed among multiple public databases and clinical specimens. Bioinformatics analyses were conducted to explore biological functions and prognostic value of GAS2L3 in glioma.ResultsGAS2L3 was substantially expressed in glioma, and high GAS2L3 expression correlated with shorter overall survival time and poor clinical variables. Gene set enrichment analysis (GSEA), single-sample gene-set enrichment analysis, and CIBERSORT algorithm analyses showed that GAS2L3 expression was closely linked to immune-related pathways, inflammatory activities, and immune cell infiltration. Moreover, GAS2L3 was synergistic with T cell–inflamed gene signature, immune checkpoints, T-cell receptor diversities, and neoantigen numbers.ConclusionThis study suggests that GAS2L3 is a prognostic biomarker for glioma, providing a reference for further study of the potential role of GAS2L3 in the immunomodulation of glioma.

Description: Finding the underlying principles of social attention in humans seems to be essential for the design of the interaction between natural and artificial agents. Here, we focus on the computational modeling of gaze dynamics as exhibited by humans when perceiving socially relevant multimodal information. The audio-visual landscape of social interactions is distilled into a number of multimodal patches that convey different social value, and we work under the general frame of foraging as a tradeoff between local patch exploitation and landscape exploration. We show that the spatio-temporal dynamics of gaze shifts can be parsimoniously described by Langevin-type stochastic differential equations triggering a decision equation over time. In particular, value-based patch choice and handling is reduced to a simple multi-alternative perceptual decision making that relies on a race-to-threshold between independent continuous-time perceptual evidence integrators, each integrator being associated with a patch.

Description: Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (CDK6), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of CDK6 were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, CDK6 expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of CDK6 was tightly correlated with peripheral blood blasts, French–American–British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of CDK6 expression on the prognosis of non-APL AML patients remain uncertain. We found that CDK6 expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan–Meier analysis. CDK6 was also found to be positively associated with genes identified to contribute to the development of leukemia, including CCND2, DNMT3B, SOX4, and IKZF2, as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that CDK6 might be a potential diagnostic and prognostic biomarker in non-APL AML patients.

Description: The Characidae family contains the largest number of tropical fish species. Morphological similarities make species identification difficult within this family. Here, the complete mitogenomes of two Characidae fish were determined and comparatively analyzed with those of nine other Characidae fish species. The two newly sequenced complete mitogenomes are circular DNA molecules with sizes of 16,701 bp (Hyphessobrycon amandae; MT484069) and 16,710 bp (Hemigrammus erythrozonus; MT484070); both have a highly conserved structure typical of Characidae, with the start codon ATN (ATG/ATT) and stop codon TAR (TAA/TAG) or an incomplete T−−/TA−. Most protein-coding genes of the 11 Characidae mitogenomes showed significant codon usage bias, and the protein-coding gene cox1 was found to be a comparatively slow-evolving gene. Phylogenetic analyses via the maximum likelihood and Bayesian inference methods confirmed that H. amandae and H. erythrozonus belong to the family Characidae. In all Characidae species studied, one genus was well supported; whereas other two genera showed marked differentiation. These findings provide a phylogenetic basis for improved classification of the family Characidae. Determining the mitogenomes of H. erythrozonus and H. amandae improves our understanding of the phylogeny and evolution of fish species.

Description: Gastric cancer (GC) is one of the leading causes of cancer-associated deaths worldwide. Due to the lack of typical symptoms and effective biomarkers for non-invasive screening, most patients develop advanced-stage GC by the time of diagnosis. Circulating microRNA (miRNA)-based panels have been reported as a promising tool for the screening of certain types of cancers. In this study, we performed differential expression analysis of miRNA profiles of plasma samples obtained from gastric cancer and non-cancer patients using two independent Gene Expression Omnibus (GEO) datasets: GSE113486 and GSE124158. We identified three miRNAs, hsa-miR-320a, hsa-miR-1260b, and hsa-miR-6515-5p, to distinguish gastric cancer cases from non-cancer controls. The three miRNAs showed an area under the curve (AUC) over 0.95 with high specificity (〉93.0%) and sensitivity (〉85.0%) in both the discovery datasets. In addition, we further validated these three miRNAs in two external datasets: GSE106817 [sensitivity: hsa-miR-320a (99.1%), hsa-miR-1260b (97.4%), and hsa-miR-6515-5p (92.2%); specificity: hsa-miR-320a (88.8%), hsa-miR-1260b (89.6%), and hsa-miR-6515-5p (88.7%); and AUC: hsa-miR-320a (96.3%), hsa-miR-1260b (97.4%), and hsa-miR-6515-5p (94.6%)] and GSE112264 [sensitivity: hsa-miR-320a (100.0%), hsa-miR-1260b (98.0%), and hsa-miR-6515.5p (98.0%); specificity: hsa-miR-320a (100.0%), hsa-miR-1260b (100.0%), and hsa-miR-6515.5p (92.7%); and AUC: hsa-miR-320a (1.000), hsa-miR-1260b (1.000), and hsa-miR-6515-5p (0.988)]. On the basis of these findings, the three miRNAs can be used as potential biomarkers for gastric cancer screening, which can provide patients with a higher chance of curative resection and longer survival.

Description: Revegetation is regarded as an effective means to improve the ecological environment in deserts and profoundly influences the potential ecological functions of the soil fungal community. Therefore, Illumina high-throughput sequencing was performed to characterize the soil fungal diversity and community composition at two soil depths (0–10 cm and 10–20 cm) with four revegetation durations (natural grassland, half-mature, nearly mature, and mature Pinus. sylvestris var. mongolica plantations) in the Mu Us Sandy Land, China. The effects of soil properties on soil fungal communities were also examined to reveal the connection between fungal function and soil environment. The results indicated that 1) soil nutrient content and enzyme activity showed significant differences through the restoration durations, 2) there was no significant effect of soil depth on soil fungal diversity, while the Shannon diversity index of all fungal communities was significantly different among different revegetation durations, 3) compared with grassland, ectomycorrhizal fungi (notably, Inocybe, Tuber, and Calostoma) were abundant in plantations. The endophyte fungus Mortierella was among the top 10 genera in all soil samples and arbuscular mycorrhizal fungus Diversispora was the indicator genus of the grassland, and 4) catalase and total nitrogen were the main factors affecting fungal community composition and were closely related to saprotrophs and pathotrophs, respectively. This new information indicates the variation of soil fungal communities along revegetation durations and highlights the interaction between fungal functions and desert ecosystems.

Description: Combination therapies proved to be a valuable strategy in the fight against cancer, thanks to their increased efficacy in inducing tumor cell death and in reducing tumor growth, metastatic potential, and the risk of developing drug resistance. The identification of effective combinations of drug targets generally relies on costly and time consuming processes based on in vitro experiments. Here, we present a novel computational approach that, by integrating dynamic fuzzy modeling with multi-objective optimization, allows to efficiently identify novel combination cancer therapies, with a relevant saving in working time and costs. We tested this approach on a model of oncogenic K-ras cancer cells characterized by a marked Warburg effect. The computational approach was validated by its capability in finding out therapies already known in the literature for this type of cancer cell. More importantly, our results show that this method can suggest potential therapies consisting in a small number of molecular targets. In the model of oncogenic K-ras cancer cells, for instance, we identified combination of up to three targets, which affect different cellular pathways that are crucial for cancer proliferation and survival.

Description: Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.

Description: Osseointegration is a well-established concept used in applications including the percutaneous Bone-Anchored Hearing System (BAHS) and auricular rehabilitation. To date, few retrieved implants have been described. A systematic review including cases where percutaneous bone-anchored implants inserted in the temporal bone were retrieved and analyzed was performed. We also present the case of a patient who received a BAHS for mixed hearing loss. After the initial surgery, several episodes of soft tissue inflammation accompanied by pain were observed, leading to elective abutment removal 14 months post-surgery. Two years post-implantation, the implant was removed due to pain and subjected to a multiscale and multimodal analysis: microbial DNA using molecular fingerprinting, gene expression using quantitative real-time polymerase chain reaction (qPCR), X-ray microcomputed tomography (micro-CT), histology, histomorphometry, backscattered scanning electron microscopy (BSE-SEM), Raman spectroscopy, and fluorescence in situ hybridization (FISH). Evidence of osseointegration was provided via micro-CT, histology, BSE-SEM, and Raman spectroscopy. Polymicrobial colonization in the periabutment area and on the implant, including that with Staphylococcus aureus and Staphylococcus epidermidis, was determined using a molecular analysis via a 16S-23S rDNA interspace [IS]-region-based profiling method (IS-Pro). The histology suggested bacterial colonization in the skin and in the peri-implant bone. FISH confirmed the localization of S. aureus and coagulase-negative staphylococci in the skin. Ten articles (54 implants, 47 patients) met the inclusion criteria for the literature search. The analyzed samples were either BAHS (35 implants) or bone-anchored aural epitheses (19 implants) in situ between 2 weeks and 8 years. The main reasons for elective removal were nonuse/changes in treatment, pain, or skin reactions. Most samples were evaluated using histology, demonstrating osseointegration, but with the absence of bone under the implants’ proximal flange. Taken together, the literature and this case report show clear evidence of osseointegration, despite prominent complications. Nevertheless, despite implant osseointegration, chronic pain related to the BAHS may be associated with a chronic bacterial infection and raised inflammatory response in the absence of macroscopic signs of infection. It is suggested that a multimodal analysis of peri-implant health provides possibilities for device improvements and to guide diagnostic and therapeutic strategies to alleviate the impact of complications.

Description: Eukaryotic genomes are wrapped around nucleosomes and organized into different levels of chromatin structure. Chromatin organization has a crucial role in regulating all cellular processes involving DNA-protein interactions, such as DNA transcription, replication, recombination and repair. Histone post-translational modifications (HPTMs) have a prominent role in chromatin regulation, acting as a sophisticated molecular code, which is interpreted by HPTM-specific effectors. Here, we review the role of histone lysine methylation changes in regulating the response to radiation-induced genotoxic damage in mammalian cells. We also discuss the role of histone methyltransferases (HMTs) and histone demethylases (HDMs) and the effects of the modulation of their expression and/or the pharmacological inhibition of their activity on the radio-sensitivity of different cell lines. Finally, we provide a bioinformatic analysis of published datasets showing how the mRNA levels of known HMTs and HDMs are modulated in different cell lines by exposure to different irradiation conditions.

Description: Background: Traumatic brain injury (TBI) is a brain function change caused by external forces, which is one of the main causes of death and disability worldwide. The aim of this study was to identify early diagnostic markers and potential therapeutic targets for TBI.Methods: Differences between TBI and controls in GSE89866 and GSE104687 were analyzed. The two groups of differentially expressed genes (DEGs) were combined for coexpression analysis, and the modules of interest were performed using enrichment analysis. Hub genes were identified by calculating area under curve (AUC) values of module genes, PPI network analysis, and functional similarity. Finally, the difference in immune cell infiltration between TBI and control was calculated by ssGSEA.Results: A total of 4,817 DEGs were identified in GSE89866 and 1,329 DEGs in GSE104687. They were clustered into nine modules. The genes of modules 1, 4, and 7 had the most crosstalk and were identified as important modules. Enrichment analysis revealed that they were mainly associated with neurodevelopment and immune inflammation. In the PPI network constructed by genes with top 50 AUC values in module genes, we identified the top 10 genes with the greatest connectivity. Among them, down-regulated RPL27, RPS4X, RPL23A, RPS15A, and RPL7A had similar functions and were identified as hub genes. In addition, DC and Tem were significantly up-regulated and down-regulated between TBI and control, respectively.Conclusion: We found that hub genes may have a diagnostic role for TBI. Molecular dysregulation mechanisms of TBI are associated with neurological and immune inflammation. These results may provide new ideas for the diagnosis and treatment of TBI.

Description: Sexually transmitted infections (STIs) are one of the significant causes of morbidity and mortality among adolescents and adults across the globe and encompass all the infections transmitted via person-to-person sexual contact. In spite of the widespread approach being used, STIs remain under-reported and many infections have taken an epidemic turn. The biggest roadblock in this is the unraveled basis of immunopathology of these infections, hindering the discovery of potential targets for immunization. Thereby, it is of utmost significance to decipher the hidden basis of these STIs to control the increasing epidemic of less commonly studied STIs. A complex interplay between innate immune defenses, with resident microbiota and mucosal immune response serves as the basis of therapeutic approaches, by targeting the vital steps of this dynamic interaction. The characterization of pathogen-specific antibodies to significant immunogenic molecules may divulge the conceivable protective effects.

Description: Classification is widely used in gene expression data analysis. Feature selection is usually performed before classification because of the large number of genes and the small sample size in gene expression data. In this article, a novel feature selection algorithm using approximate conditional entropy based on fuzzy information granule is proposed, and the correctness of the method is proved by the monotonicity of entropy. Firstly, the fuzzy relation matrix is established by Laplacian kernel. Secondly, the approximately equal relation on fuzzy sets is defined. And then, the approximate conditional entropy based on fuzzy information granule and the importance of internal attributes are defined. Approximate conditional entropy can measure the uncertainty of knowledge from two different perspectives of information and algebra theory. Finally, the greedy algorithm based on the approximate conditional entropy is designed for feature selection. Experimental results for six large-scale gene datasets show that our algorithm not only greatly reduces the dimension of the gene datasets, but also is superior to five state-of-the-art algorithms in terms of classification accuracy.

Description: In semi-arid to arid regions, both anthropogenic sources (urban and agriculture) and deeper Critical Zone (groundwater with long flow paths and water residence times) may play an important role in controlling chemical exports to rivers. Here, we combined two anthropogenic isotope tracers: uranium isotope ratios (234U/238U) and boron isotope ratios (δ11B), with the 87Sr/86Sr ratios to identify and quantify multiple solute (salinity) sources in the Rio Grande river in southern New Mexico and western Texas. The Rio Grande river is a major source of freshwater for irrigation and municipal uses in southwestern United States. There has been a large disagreement about the dominant salinity sources to the Rio Grande and particularly significant sources are of anthropogenic (agriculture practices and shallow groundwater flows, groundwater pumping, and urban developments) and/or geological (natural groundwater upwelling) origins. Between 2014 and 2016, we collected monthly river samples at 15 locations along a 200-km stretch of the Rio Grande river from Elephant Butte Reservoir, New Mexico to El Paso, Texas, as well as water samples from agricultural canals and drains, urban effluents and drains, and groundwater wells. Our study shows that due to the presence of localized and multiple salinity inputs, total dissolved solids (TDS) and isotope ratios of U, B, and Sr in the Rio Grande river show high spatial and temporal variability. Several agricultural, urban, and geological sources of salinity in the Rio Grande watershed have characteristic and distinguishable U, Sr, and B isotope signatures. However, due to the common issue of overlapping signatures as identified by previous tracer studies (such as δ18O, δD, δ34S), no single isotope tracer of U, Sr, or B isotopes was powerful enough to distinguish multiple salinity sources. Here, combining the multiple U, Sr, and B isotope and elemental signatures, we applied a multi-tracer mass balance approach to quantify the relative contributions of water mass from the identified various salinity end members along the 200-km stretch of the Rio Grande during different river flow seasons. Our results show that during irrigation (high river flow) seasons, the Rio Grande had uniform chemical and isotopic compositions, similar to the Elephant Butte reservoir where water is stored and well-mixed, reflecting the dominant contribution from shallow Critical Zone in headwater regions in temperate southern Colorado and northern New Mexico. In non-irrigation (low flow) seasons when the river water is stored at Elephant Butte reservoir, the Rio Grande river at many downstream locations showed heterogeneous chemical and isotopic compositions, reflecting variable inputs from upwelling of groundwater (deeper CZ), displacement of shallow groundwater, agricultural return flows, and urban effluents. Our study highlights the needs of using multi-tracer approach to investigate multiple solutes and salinity sources in rivers with complex geology and human impacts.

Description: The constitutive expression of Speckled-100 (Sp100) is known to restrict the replication of many clinically important DNA viruses. This pre-existing (intrinsic) immune defense to virus infection can be further upregulated upon interferon (IFN) stimulation as a component of the innate immune response. In humans, Sp100 is encoded by a single gene locus, which can produce alternatively spliced isoforms. The widely studied Sp100A, Sp100B, Sp100C and Sp100HMG have functions associated with the transcriptional regulation of viral and cellular chromatin, either directly through their characteristic DNA-binding domains, or indirectly through post-translational modification (PTM) and associated protein interaction networks. Sp100 isoforms are resident component proteins of promyelocytic leukemia-nuclear bodies (PML-NBs), dynamic nuclear sub-structures which regulate host immune defenses against many pathogens. In the case of human herpesviruses, multiple protein antagonists are expressed to relieve viral DNA genome transcriptional silencing imposed by PML-NB and Sp100-derived proteinaceous structures, thereby stimulating viral propagation, pathogenesis, and transmission to new hosts. This review details how different Sp100 isoforms are manipulated during herpesviruses HSV1, VZV, HCMV, EBV, and KSHV infection, identifying gaps in our current knowledge, and highlighting future areas of research.

Description: The development of single-cell sequencing technologies has allowed researchers to gain important new knowledge about the expression profile of genes in thousands of individual cells of a model organism or tissue. A common disadvantage of this technology is the loss of the three-dimensional (3-D) structure of the cells. Consequently, the Dialogue on Reverse Engineering Assessment and Methods (DREAM) organized the Single-Cell Transcriptomics Challenge, in which we participated, with the aim to address the following two problems: (a) to identify the top 60, 40, and 20 genes of the Drosophila melanogaster embryo that contain the most spatial information and (b) to reconstruct the 3-D arrangement of the embryo using information from those genes. We developed two independent techniques, leveraging machine learning models from least absolute shrinkage and selection operator (Lasso) and deep neural networks (NNs), which are applied to high-dimensional single-cell sequencing data in order to accurately identify genes that contain spatial information. Our first technique, Lasso.TopX, utilizes the Lasso and ranking statistics and allows a user to define a specific number of features they are interested in. The NN approach utilizes weak supervision for linear regression to accommodate for uncertain or probabilistic training labels. We show, individually for both techniques, that we are able to identify important, stable, and a user-defined number of genes containing the most spatial information. The results from both techniques achieve high performance when reconstructing spatial information in D. melanogaster and also generalize to zebrafish (Danio rerio). Furthermore, we identified novel D. melanogaster genes that carry important positional information and were not previously suspected. We also show how the indirect use of the full datasets’ information can lead to data leakage and generate bias in overestimating the model’s performance. Lastly, we discuss the applicability of our approaches to other feature selection problems outside the realm of single-cell sequencing and the importance of being able to handle probabilistic training labels. Our source code and detailed documentation are available at https://github.com/TJU-CMC-Org/SingleCell-DREAM/.

Description: Ossification of the posterior longitudinal ligament (OPLL) is a hyperostonic condition in which the posterior longitudinal ligament becomes thick and loses its flexibility, resulting in ectopic ossification and severe neurologic deficit (Matsunaga and Sakou, 2012). It commonly presents with myelopathy and radiculopathy and with myelopathy progression motor disorders and balance disorders can appear. Even after appropriate surgical decompression, some motor impairments often remain. The Hybrid Assistive Limb (HAL) is a wearable powered suit designed to assist and support the user's voluntary control of hip and knee joint motion by detecting bioelectric signals from the skin surface and force/pressure sensors in the shoes during movement. In the current study, the HAL intervention was applied to 15 patients diagnosed with OPLL who presented with myelopathy after decompression surgery (6 acute and 9 chronic stage). Following the HAL intervention, there were significant improvements in gait speed, cadence, stride length, in both acute and chronic groups. Joint angle analysis of the lower limbs showed that range of motion (ROM) of hip and knee joints in acute group, and also ROM of hip joint and toe-lift during swing in chronic group increased significantly. ROM of knee joint became closer to healthy gait in both groups. Electromyography analysis showed that hamstrings activity in the late swing phase increased significantly for acute patients. Immidiate effect from HAL session was also observed. EMG of vastus medialis were decreased except chronic 7th session and EMG of gastrocnemius were decreased except acute 7th session, which suggests the patients were learning to walk with lesser knee-hypertension during the sessions. After all, double knee action appeared in both acute and chronic groups after the HAL intervention, rather than knee hyper-extension which is a common gait impairment in OPLL. We consider that these improvements lead to a smoother and healthier gait motion.

Description: The study on the fast-growing traits of trees, mainly valued by tree height (TH) and diameter at breast height (DBH), is of great significance to promote the development of the forest industry. Quantitative trait locus (QTL) mapping based on high-density genetic maps is an efficient approach to identify genetic regions for fast-growing traits. In our study, a high-density genetic map for the F1 population was constructed. The genetic map had a total size of 5,484.07 centimorgan (cM), containing 5,956 single nucleotide polymorphisms (SNPs) based on Specific Length Amplified Fragment sequencing. Six fast-growing related stable QTL were identified on six chromosomes, and five stable QTL were identified by a principal component analysis (PCA). By combining the RNA-seq analysis for the two parents and two progenies with the qRT-PCR analysis, four candidate genes, annotated as DnaJ, 1-aminocyclopropane-1-carboxylate oxidase 1 (ACO1), Caffeic acid 3-O-methyltransferase 1 (COMT1), and Dirigent protein 6 (DIR6), that may regulate height growth were identified. Several lignin biosynthesis-related genes that may take part in height growth were detected. In addition, 21 hotspots in this population were found. The results of this study will provide an important foundation for further studies on the molecular and genetic regulation of TH and DBH.