Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation.

As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces of the human body. Commensalism is tightly controlled by complex interactions of the fungus and the host to preclude fungal elimination but also fungal overgrowth and invasion, which can result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance of the oral mucosa. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. Using an experimental model of C. albicans oral colonization in mice we explored fungal determinants of commensalism in the oral cavity. Transcript profiling of the oral isolate 101 in the murine tongue tissue revealed a characteristic metabolic profile tailored to the nutrient poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. Here we show that these immune evasive properties of isolate 101 are explained by a strong attenuation of a number of virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of NRG1 abolished the commensal behaviour of isolate 101, thereby establishing a central role of this factor in the commensal lifestyle of C. albicans in the oral niche of the host.

MetaNetX/MNXref: unified namespace for metabolites and biochemical reactions in the context of metabolic models.

MetaNetX/MNXref is a reconciliation of metabolites and biochemical reactions providing cross-links between major public biochemistry and Genome-Scale Metabolic Network (GSMN) databases. The new release brings several improvements with respect to the quality of the reconciliation, with particular attention dedicated to preserving the intrinsic properties of GSMN models. The MetaNetX website (https://www.metanetx.org/) provides access to the full database and online services. A major improvement is for mapping of user-provided GSMNs to MXNref, which now provides diagnostic messages about model content. In addition to the website and flat files, the resource can now be accessed through a SPARQL endpoint (https://rdf.metanetx.org).

Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.

Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.

Condition-specific series of metabolic sub-networks and its application for gene set enrichment analysis.

MOTIVATION: Genome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organism's metabolism, yet their integration to achieve biological insight remains challenging. RESULTS: We investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set, i.e. a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data for Yarrowia lipolytica and mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO. AVAILABILITY AND IMPLEMENTATION: The metaboGSE R package is available at https://CRAN.R-project.org/package=metaboGSE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Three-Dimensional Printable Sodium Carbonate Composite Sorbents for Efficient Biogas Upgrading.

We have developed a new class of sodium carbonate/silicone composite sorbents that selectively capture carbon dioxide (CO2) and can purify biogas to natural gas pipeline-quality biomethane. These nontoxic composites can be three-dimensionally printed or extruded at low costs, can have high specific CO2 sorption rates (in excess of 5 µmol s-1 g-1 bar-1) and high selectivity due to their chemical mechanism, and can be regenerated with low-energy air stripping. Therefore, these composite sorbents combine the high selectivity of liquid sorbents with the high specific sorption rates and low regeneration energies found in many solid sorbents. We characterized these composite sorbents with X-ray computed tomography, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Furthermore, we measured composite sorption capacities of up to 0.62 mol CO2 kg-1 and recorded breakthrough curves in a flow-through, fixed-bed reactor using both simulated biogas and locally sourced industrial biogas. Additional tests of the composite sorbent were carried out with pure CO2 in a sealed pressure drop apparatus. This experimental data was used to validate a numerical model of the setup and to simulate an industrial-scale biogas upgrading process. Finally, we performed a preliminary technoeconomic analysis for this upgrading process and found that this composite sorbent can upgrade biogas at a lower cost (∼$0.97 per GJ) than other currently implemented techniques.

[Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza].

Objective: To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. Methods: This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups. Results: A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4(+)T, CD8(+)T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/µl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/µl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/µl respectively]. Meanwhile, the T cells and CD8(+)T counts in fatal patients [370 (260,537) cells/µl and 87 (74,105) cells/µl] were significantly lower than those in severe and alive patients [722 (390,990) cells/µl and 222 (154,404) cells/µl]. CD8(+)HLA-DR/CD8(+)and CD8(+)CD38(+)/CD8(+)T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8(+)HLA-DR/CD8(+)count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8(+)T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8(+)HLA-DR/CD8(+)T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions: All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8(+)T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

Research Progress of Metabolomics in Forensic Pathology.

ABSTRACT: Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.

Evaluating the Performance of Micro-Encapsulated CO2 Sorbents during CO2 Absorption and Regeneration Cycling.

We encapsulated six solvents with novel physical and chemical properties for CO2 sorption within gas-permeable polymer shells, creating Micro-Encapsulated CO2 Sorbents (MECS), to improve the CO2 absorption kinetics and handling of the solvents for postcombustion CO2 capture from flue gas. The solvents were sodium carbonate (Na2CO3) solution, uncatalyzed and with two different promoters, two ionic liquid (IL) solvents, and one CO2-binding organic liquid (CO2BOL). We subjected each of the six MECS to multiple CO2 absorption and regeneration cycles and measured the working CO2 absorption capacity as a function of time to identify promising candidate MECS for large-scale carbon capture. We discovered that the uncatalyzed Na2CO3 and Na2CO3-sarcosine MECS had lower CO2 absorption rates relative to Na2CO3-cyclen MECS over 30 min of absorption, while the CO2BOL Koechanol appeared to permeate through the capsule shell and is thus unsuitable. We rigorously tested the most promising three MECS (Na2CO3-cyclen, IL NDIL0309, and IL NDIL0230) by subjecting each of them to a series of 10 absorption/stripping cycles. The CO2 absorption curves were highly reproducible for these three MECS across 10 cycles, demonstrating successful absorption/regeneration without degradation. As the CO2 absorption rate is dynamic in time and the CO2 loading per mass varies among the three most promising MECS, the process design parameters will ultimately dictate the selection of MECS solvent.

Custom 3D Printable Silicones with Tunable Stiffness.

Silicone elastomers have broad versatility within a variety of potential advanced materials applications, such as soft robotics, biomedical devices, and metamaterials. A series of custom 3D printable silicone inks with tunable stiffness is developed, formulated, and characterized. The silicone inks exhibit excellent rheological behavior for 3D printing, as observed from the printing of porous structures with controlled architectures. Herein, the capability to tune the stiffness of printable silicone materials via careful control over the chemistry, network formation, and crosslink density of the ink formulations in order to overcome the challenging interplay between ink development, post-processing, material properties, and performance is demonstrated.

miRBoost: boosting support vector machines for microRNA precursor classification.

Identification of microRNAs (miRNAs) is an important step toward understanding post-transcriptional gene regulation and miRNA-related pathology. Difficulties in identifying miRNAs through experimental techniques combined with the huge amount of data from new sequencing technologies have made in silico discrimination of bona fide miRNA precursors from non-miRNA hairpin-like structures an important topic in bioinformatics. Among various techniques developed for this classification problem, machine learning approaches have proved to be the most promising. However these approaches require the use of training data, which is problematic due to an imbalance in the number of miRNAs (positive data) and non-miRNAs (negative data), which leads to a degradation of their performance. In order to address this issue, we present an ensemble method that uses a boosting technique with support vector machine components to deal with imbalanced training data. Classification is performed following a feature selection on 187 novel and existing features. The algorithm, miRBoost, performed better in comparison with state-of-the-art methods on imbalanced human and cross-species data. It also showed the highest ability among the tested methods for discovering novel miRNA precursors. In addition, miRBoost was over 1400 times faster than the second most accurate tool tested and was significantly faster than most of the other tools. miRBoost thus provides a good compromise between prediction efficiency and execution time, making it highly suitable for use in genome-wide miRNA precursor prediction. The software miRBoost is available on our web server http://EvryRNA.ibisc.univ-evry.fr.

Gastric emptying for liquids of different compositions in children.

BACKGROUND: Pre-operative fasting balances safety against patient discomfort. We compared the gastric emptying profiles of a novel clear, high protein drink against a "traditional" clear and a non-clear fluid. METHODS: We conducted a prospective cross-sectional study with 48 healthy volunteers, eight to 14 yr of age, fasted overnight and without risk factors for abnormal gastrointestinal motility. Subjects were randomized in equal ratio to ingest 296 ml of apple juice, 2% milk or Ensure Clear. The gastric antrum was seen by ultrasound in the right lateral decubitus position at baseline, after ingestion, then every 30 min thereafter until return to baseline or six h. Gastric antral cross-sectional area was measured independently by two anaesthetists, and compared between drinks. RESULTS: Gastric emptying differed between apple juice, 2% milk and Ensure Clear by analysis of co-variance (P<0.0001), and was faster in males than females (P<0.01). The terminal phase however was similar using interval-censored time to gastric emptying in a survival model (P=0.17) or by comparing proportions with empty stomach vs not empty at 90 min (P=1.0), 120 min (P=0.32), 150 min (P=0.11), 180 min (P=0.76) or 210 min (P=1.0). CONCLUSIONS: Despite early differences, clearance from the stomach of apple juice, 2% milk or Ensure Clear is similar at the terminal phase, which is the period of greatest relevance to preoperative fasting recommendations. The stomach is essentially clear by 3-3.5 h for all three drinks studied. The differentiation between liquids in current guidelines is not supported by this study. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT02938065 clinicaltrials.gov/ct2/show/NCT02938065.

Sex differences in the impact of nonalcoholic fatty liver disease on cardiovascular risk factors.

BACKGROUND AND AIMS: Information on sex differences in the association of nonalcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) risk factors is scarce. We examined whether men exhibit greater differences in established CVD risk factors between NAFLD and non-NAFLD than women. METHODS AND RESULTS: We conducted a cross-sectional analysis using a cohort of 10761 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. In the setting of NAFLD and non-NAFLD, although men had significantly higher levels of atherogenic lipids as indicated by higher levels of triglyceride, triglyceride/HDL-cholesterol, and lower levels of HDL-cholesterol and worsen renal function as indicated by higher levels of creatinine and lower levels of estimated glomerular filtration rate (eGFR) than female counterparts, men with NAFLD showed greater relative differences in atherogenic lipids and deteriorated renal function than women with NAFLD when compared with their non-NAFLD counterparts. The interactions between sex and NAFLD on triglyceride, HDL-cholesterol, triglyceride/HDL-cholesterol, creatinine, and eGFR were statistically significant (P < 0.05). In the multivariate Logistic regression analyses, we observed a stronger association of TG with NAFLD and comparable associations of eGFR or HDL-C with NAFLD in men compared with women. CONCLUSION: There was greater adverse influence of NAFLD per se on triglyceride, and triglyceride/HDL-cholesterol in men compared with women. The greater adverse influence of NAFLD per se on HDL-C and eGFR in men compared with women probably related to the gender differences in TG levels.

Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models.

Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from a number of different solid tumors recently, although the isolation of CSCs in colon cancer is still challenging. We cultured colon cancer cells in stem cell medium to obtain colonosphere cells. These cells possessed the characteristics of CSCs, with a high capacity of tumorigenicity, migration and invasion in vitro and in vivo. The isolation and identification of CSCs have provided new targets for the therapeutics. Oncolytic herpes simplex viruses (oHSV) are an effective strategy for killing colon cancer cells in preclinical models. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). oHSV2 was found to be highly cytotoxic to the adherent and sphere cells in vitro, and oHSV2 treatment in vivo significantly inhibited tumor growth. This study demonstrates that oHSV2 is effective against colon cancer cells and colon CSLCs and could be a promising strategy for treating colon cancer patients.

Microencapsulation of advanced solvents for carbon capture.

Purpose-designed, water-lean solvents have been developed to improve the energy efficiency of CO2 capture from power plants, including CO2-binding organic liquids (CO2BOLs) and ionic liquids (ILs). Many of these solvents are highly viscous or change phases, posing challenges for conventional process equipment. Such problems can be overcome by encapsulation. Micro-Encapsulated CO2 Sorbents (MECS) consist of a CO2-absorbing solvent or slurry encased in spherical, CO2-permeable polymer shells. The resulting capsules have diameters in the range of 100-600 µm, greatly increasing the surface area and CO2 absorption rate of the encapsulated solvent. Encapsulating these new solvents requires careful selection of shell materials and fabrication techniques. We find several common classes of polymers are not compatible with MECS production, but we develop two custom formulations, a silicone and an acrylate, that show promise for encapsulating water-lean solvents. We make the first demonstration of an encapsulated IL for CO2 capture. The rate of CO2 absorption is enhanced by a factor of 3.5 compared to a liquid film, a value that can be improved by further development of shell materials and fabrication techniques.

Detection of generic differential RNA processing events from RNA-seq data.

RNA-seq data analysis has revealed abundant alternative splicing in eukaryotic mRNAs. However, splicing is only one of many processing events that transcripts may undergo during their lifetime. We present here RNAprof (RNA profile analysis), a program for the detection of differential processing events from the comparison of RNA-seq experiments. RNAprof implements a specific gene-level normalization procedure and compares RNA-seq coverage profiles at nucleotide resolution to detect regions of significant coverage differences, independently of splice sites or other gene features. We used RNAprof to analyze the effect of alternative-splicing regulators NSRa and NSRb on the Arabidopsis thaliana transcriptome. A number of intron retention events and alternative transcript structures were specifically detected by RNAprof and confirmed by qRT-PCR. Further tests using a public Mus musculus RNA-seq dataset and comparisons with other RNA isoform predictors showed that RNAprof uniquely identified sets of highly significant processing events as well as other relevant library-specific differences in RNA-seq profiles. This highlights an important layer of variation that remains undetected by current protocols for RNA-seq analysis.

Multilayer photo-aligned thin-film structure for polarizing photonics.

In this Letter, an advanced multilayer photo-aligned liquid crystal polymer (LCP) thin-film structure with multiple optical functions is introduced. Within each LCP layer, a spatially distribution of local optical axes can be controlled by a patterned photo-alignment layer. As an embodiment of the proposed structure, a two-layer structure with pixelated controlled light-propagation directions and polarizations has been studied, which has shown the potential to be used as a photomask for generating multi-domain photo-alignment structures with a single exposure step. The combination of the multilayer structure with patterned photo-alignment technology provides a new perspective of designing optical structures for polarizing photonics applications.

Nontraditional risk factors for cardiovascular disease and visceral adiposity index among different body size phenotypes.

BACKGROUND AND AIMS: Increased cardiovascular disease and mortality risk in metabolically healthy obese (MHO) individuals remain highly controversial. Several studies suggested risk while others do not. The traditional cardiovascular risk factors may be insufficient to demonstrate the complete range of metabolic abnormalities in MHO individuals. Hence, we aimed to compare the prevalence of elevated lipoprotein (a), apolipoprotein B, and uric acid (UA) levels, apolipoprotein B/apolipoprotein A1 ratio, and visceral adiposity index (VAI) scores, and low apolipoprotein A1 levels among 6 body size phenotypes (normal weight with and without metabolic abnormalities, overweight with and without metabolic abnormalities, and obese with or without metabolic abnormalities). METHODS AND RESULTS: We conducted a cross-sectional analysis of 7765 Chinese adults using data from the nationwide China Health and Nutrition Survey 2009. MHO persons had intermediate prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low apolipoprotein A1 levels between metabolically healthy normal-weight (MHNW) and metabolically abnormal obese individuals (P < 0.001 for all comparisons). Elevated apolipoprotein B and UA concentrations, apolipoprotein B/apolipoprotein A1 ratio, and VAI scores were all strongly associated with the MHO phenotype (all P < 0.01). CONCLUSIONS: Prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low levels of apolipoprotein A1 was higher among MHO persons than among MHNW individuals. The elevated levels of the nontraditional risk factors and VAI scores in MHO persons could contribute to the increased cardiovascular disease risk observed in long-term studies.

Association of alcohol consumption with specific biomarkers: a cross-sectional study in South Africa.

Alcohol consumption plays an important role in the health transition associated with urbanization in developing countries. Thus, reliable tools for assessing alcohol intake levels are necessary. We compared two biological markers of alcohol consumption and self-reported alcohol intakes in participants from urban and rural South African communities. This cross-sectional epidemiological survey was part of the North West Province, South African leg of the 12-year International Prospective Urban and Rural Epidemiology (PURE) study which investigates the health transition in urban and rural subjects. A total of 2,010 apparently healthy African volunteers (35 years and older) were recruited from a sample of 6,000 randomly-selected households. Alcohol consumption was assessed through self-reports (24-hour recalls and quantitative food frequency questionnaire) and by two biological markers: percentage carbohydrate-deficient transferrin (%CDT) and gamma-glutamyl transferase (GGT). Of the 716 men and 1,192 women volunteers, 64% and 33% respectively reported regular alcohol consumption. Reported mean habitual intakes of drinker men and women were 29.9 (± 30.0) and 23.3 (± 29.1) g of pure alcohol per day. Reported habitual intake of the whole group correlated positively and significantly with both %CDT (R=0.32; p ≤ 0.01) and GGT (R=0.43; p ≤ 0.01). The correlation between the two biomarkers was low (0.211; p ≤ 0.01). GGT and %CDT values should be interpreted with care in Africans as self-reported non-drinker men and women had elevated levels of GGT (19% and 26%) and %CDT (48% and 38%). A need exists for a more specific biological marker for alcohol consumption in black Africans.