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Abstract Haploid induction (HI) holds great promise in expediting the breeding process in onion, a biennial cross-pollinated crop. We used the CENH3-based genome elimination technique in producing a HI line in onion. Here, we downregulated AcCENH3 using the RNAi approach without complementation in five independent lines. Out of five events, only three could produce seeds upon selfing. The progenies showed poor seed set and segregation distortion, and we were unable to recover homozygous knockdown lines. The knockdown lines showed a decrease in accumulation of AcCENH3 transcript and protein in leaf tissue. The decrease in protein content in transgenic plants was correlated with poor seed set. When the heterozygous knockdown lines were crossed with wild-type plants, progenies showed HI by genome elimination of the parental chromosomes from AcCENH3 knockdown lines. The HI efficiency observed was between 0 and 4.63% in the three events, and it was the highest (4.63%) when E1 line was crossed with wildtype. Given the importance of doubled haploids in breeding programmes, the findings from our study are poised to significantly impact onion breeding.

We present the results of the human genomic small variant calling benchmarking initiative of the German Research Foundation (DFG) funded Next Generation Sequencing Competence Network (NGS-CN) and the German Human Genome-Phenome Archive (GHGA). In this effort, we developed NCBench, a continuous benchmarking platform for the evaluation of small genomic variant callsets in terms of recall, precision, and false positive/negative error patterns. NCBench is implemented as a continuously re-evaluated open-source repository. We show that it is possible to entirely rely on public free infrastructure (Github, Github Actions, Zenodo) in combination with established open-source tools. NCBench is agnostic of the used dataset and can evaluate an arbitrary number of given callsets, while reporting the results in a visual and interactive way. We used NCBench to evaluate over 40 callsets generated by various variant calling pipelines available in the participating groups that were run on three exome datasets from different enrichment kits and at different coverages. While all pipelines achieve high overall quality, subtle systematic differences between callers and datasets exist and are made apparent by NCBench.These insights are useful to improve existing pipelines and develop new workflows. NCBench is meant to be open for the contribution of any given callset. Most importantly, for authors, it will enable the omission of repeated re-implementation of paper-specific variant calling benchmarks for the publication of new tools or pipelines, while readers will benefit from being able to (continuously) observe the performance of tools and pipelines at the time of reading instead of at the time of writing.

Abstract For people with respiratory disorders who need additional oxygen therapy, oxygen concentrators are vital medical equipment. By concentrating oxygen from the ambient air, they function to give the user a greater flow of oxygen-enriched air. The application of lithium zeolite for oxygen concentration in POCs is the most intense part of this work. One kind of zeolite material that may selectively absorb nitrogen from the air to increase oxygen concentration is lithium zeolite. The capacity, effectiveness, and dependability of a POC fitted with lithium zeolite are all examined in this study, along with its overall performance. The findings show that lithium zeolite, which has benefits including high oxygen purity and low energy consumption, is a potential material for use in POCs. The results of this study aid in the creation of POCs for oxygen therapy that are more effective and efficient. This study suggests utilizing an Arduino microcontroller and an HX710B air pressure sensor to measure the oxygen flow rate in a POC. The POC’s oxygen flow channel incorporates the HX710B sensor to monitor pressure variations, which the Arduino uses to translate into flow rate readings. To verify the accuracy and dependability of the system, its performance is assessed under different flow rate scenarios. Lithium zeolites are well-known for having a high selectivity for nitrogen adsorption, which can enhance the concentrator’s oxygen separation process’s effectiveness. Lithium-zeolite-based oxygen concentrators may have a lower environmental effect than standard concentrators.

Abstract Organophosphorus nerve agents are toxic compounds that disrupt neuromuscular transmission by inhibiting the neurotransmitter enzyme, acetylcholinesterase, leading to rapid death. A hybrid composite was synthesized using a hydrothermal process for the early detection of dimethyl methyl phosphonate (DMMP), a simulant of the G-series nerve agent, sarin. Quartz crystal microbalance (QCM) and surface acoustic wave (SAW) sensors were used as detectors. Nitrogen-doped multiwalled carbon nanotubes (N-MWCNTs), cobalt oxide (Co3O4), and N-MWCNT@Co3O4 were compared to detect DMMP concentrations of 25–150 ppm. At 25 ppm, the differential frequencies (Δf) of the N-MWCNT, Co3O4, and N-MWCNT@Co3O4 sensors were 5.8, 2.3, and 99.5 Hz, respectively. The selectivity results revealed a preference for the DMMP rather than potential interference. The coefficients of determination (R2) of the N-MWCNT, Co3O4, and N-MWCNT@Co3O4 sensors for detecting 25–150 ppm DMMP were 0.983, 0.986, and 0.999, respectively. The response times of the N-MWCNT, Co3O4, and N-MWCNT@Co3O4 sensors for detecting 100 ppm DMMP were 25, 27, and 34 s, respectively, while the corresponding recovery times were 85, 105, and 181 s. The repeatability results revealed the reversible adsorption and desorption phenomena for the fixed DMMP concentration of 100 ppm. These unique findings show that synthesized materials can be used to detect organophosphorus nerve agents.

Abstract Male-pattern hair loss (MPHL) is common and highly heritable. While genome-wide association studies (GWAS) have generated insights into the contribution of common variants to MPHL etiology, the relevance of rare variants remains unclear. To determine the contribution of rare variants to MPHL etiology, we perform gene-based and single-variant analyses in exome-sequencing data from 72,469 male UK Biobank participants. While our population-level risk prediction suggests that rare variants make only a minor contribution to general MPHL risk, our rare variant collapsing tests identified a total of five significant gene associations. These findings provide additional evidence for previously implicated genes (EDA2R, WNT10A) and highlight novel risk genes at and beyond GWAS loci (HEPH, CEPT1, EIF3F). Furthermore, MPHL-associated genes are enriched for genes considered causal for monogenic trichoses. Together, our findings broaden the MPHL-associated allelic spectrum and provide insights into MPHL pathobiology and a shared basis with monogenic hair loss disorders.

The current study deals with the extraction and characterization of natural cellulose fibers from Lycium ferocissimum plant stems. The fibers were retted using a manual retting process and were subjected to benzoylation treatment. The properties namely physio-chemical, thermal, crystalline, and morphological were measured for both untreated and chemical treated Lycium ferocissimum fibers. Then, the epoxy composites were fabricated using chemical treated and untreated Lycium ferocissimum fibers and analyzed for their mechanical performance. The cellulose content was 67.19%, with the crystalline index of 47.7% for the benzoyl chloride treated Lycium ferocissimum fibers, which were substantially higher than untreated Lycium ferocissimum fibers. While the epoxy composites containing benzoyl chloride treated Lycium ferocissimum fibers showed an increase in the ultimate flexural strength of 51.3 MPa, while it was 42 MPa for untreated Lycium ferocissimum fiber-based composite. Thus, the test results elucidated that benzoyl chloride treatment reduced Lycium ferocissimum fibers hydrophilicity that induced fiber wettability with the matrix to better mechanical properties compared to untreated Lycium ferocissimum fiber-based composites.

Performance of composites can be improved by adding a suitable fiber to the polymer matrix. Many natural fibers available are cost-effective and can be used as reinforcement. Mudar fiber is one among the natural fiber obtained from bark of Crown flower (Calotropis Gigantea) plant. The natural fiber, Mudar, is available in the southern parts of India. The Mudar fiber is primed in a sodium hydroxide solution and diced into 4 mm length. The fiber-reinforced composite is obtained by mixing the epoxy resin with Mudar fiber, and the roller is repeatedly used to reduce the inherent porosities. The mechanical behaviors like flexural, compression, tensile, and impact behaviors of untreated and NaOH-treated Mudar fiber composites are analyzed. The maximum tensile strength was accounted for 20% treated fiber composite,s which was 90% more than the untreated composites. The compressive strength and flexural strength of 30% treated composites was 31% and 83% more than that of the untreated composites, respectively. Similarly, the maximum flexural strength of 40% treated composites was 2.6 times higher than the untreated composites. The morphological characteristics of specimens after tensile and compressive tests for treated and untreated conditions are also investigated. Consequently, it is found that the structural characteristics of polymer composites reinforced with alkali-treated fiber are more superior than those of the untreated fiber.

Abstract Nitrogen-doped multiwalled carbon nanotubes (N-MWCNTs) have been used to fabricate nanostructured materials for various energy devices, such as supercapacitors, sensors, batteries, and electrocatalysts. Nitrogen-doped carbon-based electrodes have been widely used to improve supercapacitor applications via various chemical approaches. Based on previous studies, CuO@MnO2 and CuO@MnO2/N-MWCNT composites were synthesized using a sonication-supported hydrothermal reaction process to evaluate their supercapacitor properties. The structural and morphological properties of the synthesized composite materials were characterized via Raman spectroscopy, XRD, SEM, and SEM–EDX, and the morphological properties of the composite materials were confirmed by the nanostructured composite at the nanometer scale. The CuO@MnO2 and CuO@MnO2/N-MWCNT composite electrodes were fabricated in a three-electrode configuration, and electrochemical analysis was performed via CV, GCD, and EIS. The composite electrodes exhibited the specific capacitance of ~ 184 F g−1 at 0.5 A g−1 in the presence of a 5 M KOH electrolyte for the three-electrode supercapacitor application. Furthermore, it exhibited significantly improved specific capacitances and excellent cycling stability up to 5000 GCD cycles, with a 98.5% capacity retention.

This study analyzes the dynamics of surface melting in Antarctica, which are crucial for understanding glacier and ice sheet behavior and monitoring polar climate change. Specifically, we focus on the Nivlisen ice shelf in East Antarctica, examining melt ponds, supra glacial lakes (SGLs), seasonal surface melt extent, and surface ice flow velocity. Spatial and temporal analysis is based on Landsat and Sentinel-1 data from the austral summers of 2000 to 2023. Between 2000 and 2014, melt ponds and SGLs on the ice shelf covered roughly 1 km2. However, from 2015 to 2023, surface melting increased consistently, leading to more extensive melt ponds and SGLs. Significant SGL depths were observed in 2016, 2017, 2019, and 2020, with 2008, 2016, and 2020 showing the highest volumes and progressive SGL area growth. We also examined the relationship between seasonal surface melt extent and ice flow velocity. Validation efforts involved ground truth data from a melt pond in central Dronning Maud Land (cDML) during the 2022–2023 austral summer, along with model-based results. The observed increase in melt pond depth and volume may significantly impact ice shelf stability, potentially accelerating ice flow and ice shelf destabilization. Continuous monitoring is essential for accurately assessing climate change’s ongoing impact on Antarctic ice shelves.

Abstract The Co3O4@N-MWCNT composite was synthesized by a sonication-supported thermal reduction process for supercapacitor applications. The structural and morphological properties of the materials were characterized via Raman, XRD, XPS, SEM–EDX, and FE-TEM analysis. The composite electrode was constructed into a three-electrode configuration and examined by using CV, GCD and EIS analysis. The demonstrated electrochemical value of ~ 225 F/g at 0.5 A/g by the electrode made it appropriate for potential use in supercapacitor applications.

Abstract Substance abuse affects the central nervous system (CNS) and remains a global health problem. Psychostimulants, such as cocaine and methamphetamine (METH), and opioids affect neuronal function and lead to behavioral impairments via epigenetic modification. Epigenetic changes occur via classical pathways, especially the class III histone deacetylase (HDAC)-sirtuin (SIRT) family, that act as cellular sensors to regulate energy homeostasis and coordinate cellular responses to maintain genome integrity. However, SIRT family (1–7)-associated neurodegeneration has not been elucidated in the context of energy metabolism. The present study examined the effects of psychostimulants, such as cocaine and METH, and opioids, such as morphine, on SIRT family (1–7) [class I, II, III and IV] expression and cellular translocation-mediated dysfunction in astrocytes and microglial cells. The “nootropic” drug piracetam played a preventative role against psychostimulant- and opioid-induced SIRT (1–7) expression in astrocytes. These results indicate that cocaine, METH, and morphine affected deacetylation and cellular function, and these changes were prevented by piracetam in astrocytes.

Abstract Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.

Abstract In this study, a novel nanohybrid composite containing nitrogen-doped multiwalled carbon nanotubes/carboxymethylcellulose (N-MWCNT/CMC) was synthesized for supercapacitor applications. The synthesized composite materials were subjected to an ultrasonication-mediated solvothermal hydrothermal reaction. The synthesized nanohybrid composite electrode material was characterized using analytical methods to confirm its structure and morphology. The electrochemical properties of the composite electrode were investigated using cyclic voltammetry (CV), galvanic charge–discharge, and electrochemical impedance spectroscopy (EIS) using a 3 M KOH electrolyte. The fabricated composite material exhibited unique electrochemical properties by delivering a maximum specific capacitance of approximately 274 F g−1 at a current density of 2 A g−1. The composite electrode displayed high cycling stability of 96% after 4000 cycles at 2 A g−1, indicating that it is favorable for supercapacitor applications.

The additive manufacturing (AM) of products involves various processes, such as raising the temperature of a work-piece (part) and substrate to the melting point and subsequent solidification, using a movable source of heat. The work piece is subjected to repeated cycles of heating and cooling. The main objective of this work was to present an overview of the various methods used for prediction of the residual stresses and how their contributions can be used to improve current additive manufacturing methods. These novel methods of manufacturing have several merits, compared to conventional methods. Some of these merits include the lower costs, higher precision and accuracy of manufacturing, faster processing time and more eco-friendly approaches to processes involved.

Abstract Here, we developed a new approach to synthesize NiCo2S4 thin films for supercapacitor application using the successive ionic layer adsorption and reaction (SILAR) method on Ni mesh with different molar ratios of Ni and Co precursors. The five different NiCo2S4 electrodes affect the electrochemical performance of the supercapacitor. The NiCo2S4 thin films demonstrate superior supercapacitance performance with a significantly higher specific capacitance of 1427 F g−1 at a scan rate of 20 mV s−1. These results indicate that ternary NiCo2S4 thin films are more effective electrodes compared to binary metal oxides and metal sulfides.

The spectrum of somatic genetic variation in colorectal adenomas caused by biallelic pathogenic germline variants in the MSH3 gene, was comprehensively analysed to characterise mutational signatures and identify potential driver genes and pathways of MSH3-related tumourigenesis. Three patients from two families with MSH3-associated polyposis were included. Whole exome sequencing of nine adenomas and matched normal tissue was performed. The amount of somatic variants in the MSH3-deficient adenomas and the pattern of single nucleotide variants (SNVs) was similar to sporadic adenomas, whereas the fraction of small insertions/deletions (indels) (21-42% of all small variants) was significantly higher. Interestingly, pathogenic somatic APC variants were found in all but one adenoma. The vast majority (12/13) of these were di-, tetra-, or penta-base pair (bp) deletions. The fraction of APC indels was significantly higher than that reported in patients with familial adenomatous polyposis (FAP) (p < 0.01) or in sporadic adenomas (p < 0.0001). In MSH3-deficient adenomas, the occurrence of APC indels in a repetitive sequence context was significantly higher than in FAP patients (p < 0.01). In addition, the MSH3-deficient adenomas harboured one to five (recurrent) somatic variants in 13 established or candidate driver genes for early colorectal carcinogenesis, including ACVR2A and ARID genes. Our data suggest that MSH3-related colorectal carcinogenesis seems to follow the classical APC-driven pathway. In line with the specific function of MSH3 in the mismatch repair (MMR) system, we identified a characteristic APC mutational pattern in MSH3-deficient adenomas, and confirmed further driver genes for colorectal tumourigenesis.

BackgroundIndigenous Australians suffer a disproportionate burden of sepsis, however, the performance of scoring systems that predict mortality in Indigenous patients with critical illness is incompletely defined.Materials and methodsThe study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis. The ability of the ANZROD, APACHE-II, APACHE-III, SAPS-II, SOFA and qSOFA scores to predict death before ICU discharge in the two populations was compared.ResultsThere were 442 individuals enrolled in the study, 145 (33%) identified as Indigenous. Indigenous patients were younger than non-Indigenous patients (median (interquartile range (IQR) 53 (43-60) versus 65 (52-73) years, p = 0.0001) and comorbidity was more common (118/145 (81%) versus 204/297 (69%), p = 0.005). Comorbidities that were more common in the Indigenous patients included diabetes mellitus (84/145 (58%) versus 67/297 (23%), pConclusionsAlthough the crude case-fatality rates of Indigenous and non-Indigenous Australians admitted to ICU with sepsis is comparable, Indigenous patients die at a much younger age. Despite this, the ability of commonly used scoring systems to predict outcome in Indigenous Australians is similar to that of non-Indigenous Australians, supporting their use in ICUs with a significant Indigenous patient population and in clinical trials that enrol Indigenous Australians.

Abstract The present study investigates the fabrication of hierarchical 3D nanostructures with multi-component metal oxides in the presence of highly-porous graphene and characterized for its applications in high-performance supercapacitors. A hierarchical flowers like 3D nanostructure of Co3O4 @MnO2 on nitrogen-doped graphene oxide (NGO) hybrid composite was synthesized by thermal reduction process at 650 °C in the presence of ammonia and urea. The synthesized Co3O4@MnO2/NGO hybrid composites were studied via Raman, XRD, X-ray XPS, FE-SEM, FE-SEM with EDX, FE-TEM and BET analyses. The electrochemical analysis of Co3O4@MnO2/NGO hybrid composite electrode was investigated using cyclic voltammetry, chronopotentiometry and electrochemical impedance measurements. The hybrid composite electrode showed significant specific capacitance results of up to 347 F/g at 0.5 A/g and a corresponding energy density of 34.83 Wh kg−1 with better rate performance and excellent long-term cycling stability were achieved for 10,000 cycles. The obtained electrochemical results paved a way to utilize Co3O4@MnO2/NGO composite electrode as a promising electrode material in high performance supercapacitors.

Abstract Jumping spiders are proficient jumpers that use jumps in a variety of behavioural contexts. We use high speed, high resolution video to measure the kinematics of a single regal jumping spider for a total of 15 different tasks based on a horizontal gap of 2–5 body lengths and vertical gap of +/−2 body lengths. For short range jumps, we show that low angled trajectories are used that minimise flight time. For longer jumps, take-off angles are steeper and closer to the optimum for minimum energy cost of transport. Comparison of jump performance against other arthropods shows that Phidippus regius is firmly in the group of animals that use dynamic muscle contraction for actuation as opposed to a stored energy catapult system. We find that the jump power requirements can be met from the estimated mass of leg muscle; hydraulic augmentation may be present but appears not to be energetically essential.

Most SNPs are located in non-coding genomic regions and their function remains elusive. Here, the authors perform a genome-wide scan of expression and DNA methylation quantitative trait loci in human hippocampal tissue to provide a resource for the functional interpretation of SNPs in brain disorders.

Abstract Drought transcriptome analysis of finger millet (Eleusine coracana) by cDNA subtraction identified drought responsive genes that have a potential role in drought tolerance. Through virus-induced gene silencing (VIGS) in a related crop species, maize (Zea mays), several genes, including a G-BOX BINDING FACTOR 3 (GBF3) were identified as candidate drought stress response genes and the role of GBF3 in drought tolerance was studied in Arabidopsis thaliana. Overexpression of both EcGBF3 and AtGBF3 in A. thaliana resulted in improved tolerance to osmotic stress, salinity and drought stress in addition to conferring insensitivity to ABA. Conversely, loss of function of this gene increased the sensitivity of A. thaliana plants to drought stress. EcGBF3 transgenic A. thaliana results also suggest that drought tolerance of sensitive plants can be improved by transferring genes from far related crops like finger millet. Our results demonstrate the role of GBF3 in imparting drought tolerance in A. thaliana and indicate the conserved role of this gene in drought and other abiotic stress tolerance in several plant species.

Abstract Symbiotic effectiveness of rhizobitoxine (Rtx)-producing strains of Bradyrhizobium spp. in soybean (cultivar NRC-37/Ahilya-4) under limited soil moisture conditions was evaluated using phenomics tools such as infrared(IR) thermal and visible imaging. Red, green and blue (RGB) colour pixels were standardized to analyse a total of 1017 IR thermal and 692 visible images. Plants inoculated with the Rtx-producing strains B. elkanii USDA-61 and USDA-94 and successive inoculation by B. diazoefficiens USDA-110 resulted in cooler canopy temperatures and increased canopy greenness. The results of the image analysis of plants inoculated with Rtx-producing strains were correlated with effective nodulation, improved photosynthesis, plant nitrogen status and yield parameters. Principal component analysis (PCA) revealed the reliability of the phenomics approach over conventional destructive approaches in assessing the symbiotic effectiveness of Bradyrhizobium strains in soybean plants under watered (87.41–89.96%) and water-stressed (90.54–94.21%) conditions. Multivariate cluster analysis (MCA) revealed two distinct clusters denoting effective (Rtx) and ineffective (non-Rtx) Bradyrhizobium inoculation treatments in soybean. Furthermore, correlation analysis showed that this phenotyping approach is a dependable alternative for screening drought tolerant genotypes or drought resilience symbiosis. This is the first report on the application of non-invasive phenomics techniques, particularly RGB-based image analysis, in assessing plant-microbe symbiotic interactions to impart abiotic stress tolerance.

The gut microbial community structure of adult Thrips tabaci collected from 10 different agro-climatically diverse locations of India was characterized by using the Illumina MiSeq platform to amplify the V3 region of the 16S rRNA gene of bacteria present in the sampled insects. Analyses were performed to study the bacterial communities associated with Thrips tabaci in India. The complete bacterial metagenome of T. tabaci was comprised of 1662 OTUs of which 62.25% belong to known and 37.7% of unidentified/unknown bacteria. These OTUs constituted 21 bacterial phyla of 276 identified genera. Phylum Proteobacteria was predominant, followed by Actinobacteria, Firmicutes, Bacteroidetes and Cyanobacteria. Additionally, the occurrence of the reproductive endosymbiont, Wolbachia was detected at two locations (0.56%) of the total known OTUs. There is high variation in diversity and species richness among the different locations. Alpha-diversity metrics indicated the higher gut bacterial diversity at Bangalore and lowest at Rahuri whereas higher bacterial species richness at T. tabaci samples from Imphal and lowest at Jhalawar. Beta diversity analyses comparing bacterial communities between the samples showed distinct differences in bacterial community composition of T. tabaci samples from different locations. This paper also constitutes the first record of detailed bacterial communities associated with T. tabaci. The location-wise variation in microbial metagenome profile of T. tabaci suggests that bacterial diversity might be governed by its population genetic structure, environment and habitat.

Jumping take-off in birds is an explosive behaviour with the goal of providing a rapid transition from ground to airborne locomotion. An effective jump is predicated on the need to maintain dynamic stability through the acceleration phase. The present study concerns understanding how birds retain control of body attitude and trajectory during take-off. Cursory observation suggests that stability is achieved with relatively little cost. However, analysis of the problem shows that the stability margins during jumping are actually very small and that stability considerations play a significant role in the selection of appropriate jumping kinematics. We use theoretical models to understand stability in prehensile take-off (from a perch) and also in non-prehensile take-off (from the ground). The primary instability is tipping, defined as rotation of the centre of gravity about the ground contact point. Tipping occurs when the centre of pressure falls outside the functional foot. A contribution of the paper is the development of graphical tipping stability margins for both centre of gravity location and acceleration angle. We show that the nose-up angular acceleration extends stability bounds forward and is hence helpful in achieving shallow take-offs. The stability margins are used to interrogate simulated take-offs of real birds using published experimental kinematic data from a guinea fowl (ground take-off) and a diamond dove (perch take-off). For the guinea fowl, the initial part of the jump is stable; however, simulations exhibit a stuttering instability not observed experimentally that is probably due to the absence of compliance in the idealized joints. The diamond dove model confirms that the foot provides an active torque reaction during take-off, extending the range of stable jump angles by around 45°.

Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25-38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.

To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting.We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis.There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p

Foragers facilitate horizontal pathogen transmission in honey bee colonies, yet their systemic immune function wanes during transition to this life stage. In general, the insect immune system can be categorized into mechanisms operating at both the barrier epithelial surfaces and at the systemic level. As proposed by the intergenerational transfer theory of aging, such immunosenescence may result from changes in group resource allocation. Yet, the relative influence of pathogen transmission and resource allocation on immune function in bees from different stages has not been examined in the context of barrier immunity. We find that expression levels of antimicrobial peptides (AMPs) in honey bee barrier epithelia of the digestive tract do not follow a life stage-dependent decrease. In addition, correlation of AMP transcript abundance with microbe levels reveals a number of microbe-associated changes in AMPs levels that are equivalent between nurses and foragers. These results favor a model in which barrier effectors are maintained in foragers as a first line of defense, while systemic immune effectors are dismantled to optimize hive-level resources. These findings have important implications for our understanding of immunosenescence in honey bees and other social insects.

The arsenite oxidase (Aio) from the facultative autotrophic Alphaproteobacterium Rhizobium sp. NT-26 is a bioenergetic enzyme involved in the oxidation of arsenite to arsenate. The enzyme from the distantly related heterotroph, Alcaligenes faecalis, which is thought to oxidise arsenite for detoxification, consists of a large α subunit (AioA) with bis-molybdopterin guanine dinucleotide at its active site and a 3Fe-4S cluster, and a small β subunit (AioB) which contains a Rieske 2Fe-2S cluster. The successful heterologous expression of the NT-26 Aio in Escherichia coli has resulted in the solution of its crystal structure. The NT-26 Aio, a heterotetramer, shares high overall similarity to the heterodimeric arsenite oxidase from A. faecalis but there are striking differences in the structure surrounding the Rieske 2Fe-2S cluster which we demonstrate explains the difference in the observed redox potentials (+225 mV vs. +130/160 mV, respectively). A combination of site-directed mutagenesis and electron paramagnetic resonance was used to explore the differences observed in the structure and redox properties of the Rieske cluster. In the NT-26 AioB the substitution of a serine (S126 in NT-26) for a threonine as in the A. faecalis AioB explains a -20 mV decrease in redox potential. The disulphide bridge in the A. faecalis AioB which is conserved in other betaproteobacterial AioB subunits and the Rieske subunit of the cytochrome bc 1 complex is absent in the NT-26 AioB subunit. The introduction of a disulphide bridge had no effect on Aio activity or protein stability but resulted in a decrease in the redox potential of the cluster. These results are in conflict with previous data on the betaproteobacterial AioB subunit and the Rieske of the bc 1 complex where removal of the disulphide bridge had no effect on the redox potential of the former but a decrease in cluster stability was observed in the latter.

BACKGROUND:Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. METHODOLOGY AND PRINCIPAL FINDINGS:Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFalpha, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-kappaB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. CONCLUSIONS:Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection.

Functional annotation of protein sequences with low similarity to well characterized protein sequences is a major challenge of computational biology in the post genomic era. The cyclin protein family is once such important family of proteins which consists of sequences with low sequence similarity making discovery of novel cyclins and establishing orthologous relationships amongst the cyclins, a difficult task. The currently identified cyclin motifs and cyclin associated domains do not represent all of the identified and characterized cyclin sequences. We describe a Support Vector Machine (SVM) based classifier, CyclinPred, which can predict cyclin sequences with high efficiency. The SVM classifier was trained with features of selected cyclin and non cyclin protein sequences. The training features of the protein sequences include amino acid composition, dipeptide composition, secondary structure composition and PSI-BLAST generated Position Specific Scoring Matrix (PSSM) profiles. Results obtained from Leave-One-Out cross validation or jackknife test, self consistency and holdout tests prove that the SVM classifier trained with features of PSSM profile was more accurate than the classifiers based on either of the other features alone or hybrids of these features. A cyclin prediction server--CyclinPred has been setup based on SVM model trained with PSSM profiles. CyclinPred prediction results prove that the method may be used as a cyclin prediction tool, complementing conventional cyclin prediction methods.

BackgroundCurrent gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes.Methods and resultsIn a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta.ConclusionsWe demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical.

Forcibly displaced individuals typically encounter daily stressors, which can negatively impact mental health above and beyond direct exposure to war-related violence, trauma and loss. Understanding the perspectives of war affected communities regarding daily stressors can enhance the integration of mental health into local primary care. The aim of the current study was to explore how daily stressors are conceptualized in a post-conflict setting. Data collection was completed with 53 adult participants who were recruited from primary healthcare clinics in Northern Province, Sri Lanka. Individual interviews were conducted in Tamil, audio-recorded, translated from Tamil to English, and transcribed. Themes emerging from the data were organized into an analytical framework based on iterative coding and grounded in the daily stressors framework. Stressors were conceptualized as chronic stressors and systemic stressors. Findings indicate that chronic stressors, such as loss of property, permeate daily life and have a profound impact on psychological wellbeing. Interviewees additionally reported that systemic stressors stemmed from unresolved grief for missing family members and limited support from institutions. The results of the current study complement existing literature, suggesting the value of multipronged approaches which identify and address symptoms of complicated bereavement while simultaneously alleviating financial hardship. An understanding of stressors experienced by conflict-affected populations in times of chronic adversity can be informative for the design and implementation of culturally-tailored interventions.

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.