bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric dimethylarginine positively modulates Calcium-Sensing Receptor signalling to promote lipid accumulation and adiposity
Authors: Dowsett Laura , Duluc Lucie , Higgins Erin , Alghamdi Fatmah , Fast Walter , Salt Ian P. , Leiper James
Published: July 2022

Irreversible methylation of arginine residues generates asymmetric dimethylarginine (ADMA). ADMA is a competitive inhibitor of nitric oxide (NO) synthase and an independent risk factor for cardiovascular disease. Plasma ADMA concentrations increase with obesity and fall following weight loss. Here, we demonstrate that ADMA drives lipid accumulation through a newly identified NO-independent pathway via the amino-acid sensitive calcium-sensing receptor (CaSR). ADMA treatment of 3T3-L1 and HepG2 cells activates mTOR signalling and upregulates a suite of lipogenic genes with an associated increase in triglyceride content. Pharmacological blockade of CaSR inhibits ADMA driven lipid accumulation and ADMA treatment potentiates CaSR signalling via both Gq and Gi/o pathways. Impairment of ADMA metabolism in adipocytes in vivo, by dimethylamine dimethylaminohydrolase-1 (DDAH1) deletion, increases visceral adiposity and adipocyte hypertrophy. This study identifies a signalling mechanism for ADMA as an endogenous ligand of the G protein-coupled receptor CaSR that potentially contributes to the impact of ADMA in cardiometabolic disease.
DNAffinity: A Machine-Learning Approach to Predict DNA Binding Affinities of Transcription Factors
Authors: Barissi Sandro , Sala Alba , Wieczor Milosz , Battistini Federica , Orozco Modesto
Published: July 2022

We present a physics-based machine learning approach to predict in vitro transcription factor binding affinities from structural and mechanical DNA properties directly derived from atomistic molecular dynamics simulations. The method is able to predict affinities obtained with techniques as different as uPBM, gcPBM and HT-SELEX with an excellent performance, much better than existing algorithms. Due to its nature, the method can be extended to epigenetic variants, mismatches, mutations, or any non-coding nucleobases. When complemented with chromatin structure information, our in vitro trained method provides also good estimates of in vivo binding sites in yeast.
Significance of two transmembrane ion gradients for human erythrocyte volume stabilization
Authors: Ataullakhanov F.I. , Martinov M.V. , Shi Qiang , Vitvitsky V.M.
Published: July 2022

Functional completeness of erythrocytes depends on high deformability of these cells, that allows them to pass through narrow tissue capillaries. The erythrocytes high deformability is provided due to maintenance of discoid shape with an optimal cell surface area to volume ratio. This ratio can be maintained due to cell volume stabilization at a given cell surface area. We studied role of Na/K-ATPase and transmembrane Na+and K+gradients in human erythrocyte volume stabilization at non-selective increase in cell membrane permeability to cations by using mathematical simulation. The simulation took into account a contribution of glycolytic metabolites and adenine nucleotides to cytoplasm osmotic pressure in the cells. It was shown that in the presence of Na/K-ATPase activated by intracellular sodium ions and two oppositely directed gradients of Na+and K+ions in the cell, the volume of the erythrocyte deviates from the optimal value by no more than 10% with a change in the non-selective permeability of the cell membrane to cations from 50 to 200% of the normal value. The transport Na/K-ATPase, which sets the ratio of transmembrane fluxes of sodium and potassium ions equal to 3:2, provides the best stabilization of the erythrocyte volume exactly at a non-selective increase in the permeability of the cell membrane, when the permeability for sodium and potassium ions increases equally. Such increase in erythrocyte membrane permeability is caused by oxidation of the membrane components and by mechanical stress during circulation. In the case of only one transmembrane ion gradient (Na+), the cell loses the ability to stabilize the volume when the cell membrane is damaged. In this case even small variations of cell membrane permeability cause dramatic changes in the cell volume. Our results reveal that the presence of two oppositely directed transmembrane ion gradients (Na+and K+) and the transport Na/K-ATPase activated by intracellular sodium are fundamentally important conditions for the stabilization of cellular volume in human erythrocytes.
Glucose lowering effects by sago (Metroxylon sagu Rottb) resistant starches Type 2 and 4 in spontaneously type 2 diabetes, Goto kakizaki rat
Authors: Lokman Ezarul Faradianna , Bugam Sal Hazreen , Ibrahim Aina Shafiza , Yunus Nurleyna , Mansor Fazliana , Balasubramaniam Vimala , Mohamad Khairul Mirza , Lazim Rabizah Md , Seruji Awang Zulfikar Rizal Awang
Published: July 2022

The beneficial effects of resistant starch (RS) consumption on health in terms of reducing postprandial hyperglycemia are evident. However, the potential of local Sarawak sago RS in regulating glucose has not been extensively studied. This study aims to identify glucose lowering effects of Sarawak sago RS namely, native unmodified (RS2) and chemically modified (RS4). An oral glucose tolerance test was performed before and after one-month treatment with sago RS2 and RS4 in spontaneously type 2 diabetes, goto kakizaki rat. The mechanisms involved were further explored by screening the in vitro inhibitory activities of α-Glucosidase and DPP-IV. Histopathology examination for pancreas, kidney and liver tissues was performed in response to sago RS treatment using hematoxylin and eosin (H&E) staining.The blood glucose area under the curve (AUC) in RS-treated groups was decreased and significant in RS2-treated group (p<0.05). Improved insulin AUC and higher glucagon like peptide (GLP-1) levels were observed in all RS-treated groups (p<0.05). Sago RS2 and RS4 might have potential roles in regulating glucose via α-Glucosidase and DPP-IV inhibitory activities by reducing glucose absorption in the intestine. For histopathology study, although insignificant, sago RS2 and RS4 attenuated lesion scores of pancreatic tissue whereas the liver and kidney tissues significantly showed lesser lesion scores as compared to the control diabetic group suggesting the potential of RS in reducing cell degeneration which indeed requires further validation.Findings of this study suggests the therapeutic potential of sago RS in the T2D management which may justify further investigation to be done.
Network analysis of the human structural connectome including the brainstem: a new perspective on consciousness
Authors: Salhi Salma , Kora Youssef , Ham Gisu , Haghighi Hadi Zadeh , Simon Christoph
Published: July 2022

The underlying anatomical structure is fundamental to the study of brain networks and is likely to play a key role in the generation of conscious experience. We conduct a computational and graph-theoretical study of the human structural connectome incorporating a variety of subcortical structures including the brainstem, which is typically not considered in similar studies. Our computational scheme involves the use of Python DIPY and Nibabel libraries to develop an averaged structural connectome comprised of 100 healthy adult subjects. We then compute degree, eigenvector, and betweenness centralities to identify several highly connected structures and find that the brainstem ranks highest across all examined metrics. Our results highlight the importance of including the brainstem in structural network analyses. We suggest that structural network-based methods can inform theories of consciousness, such as global workspace theory (GWT), integrated information theory (IIT), and the thalamocortical loop theory.
Inspecting the interaction between HIV and the immune system through genetic turnover
Authors: Mazzolini Andrea , Mora Thierry , Walczak Aleksandra M
Published: July 2022

Chronic infections of the human immunodeficiency virus (HIV) create a very complex co-evolutionary process, where the virus tries to escape the continuously adapting host immune system. Quantitative details of this process are largely unknown and could help in disease treatment and vaccine development. Here we study a longitudinal dataset of ten HIV-infected people, where both the B-cell receptors and the virus are deeply sequenced. We focus on simple measures of turnover, which quantify how much the composition of the viral strains and the immune repertoire change between time points. At the single-patient level, the viral-host turnover rates do not show any statistically significant correlation, however they correlate if the information is aggregated across patients. In particular, we identify an anti-correlation: large changes in the viral pool composition come with small changes in the B-cell receptor repertoire. This result seems to contradict the naive expectation that when the virus mutates quickly, the immune repertoire needs to change to keep up. However, we show that the observed anti-correlation naturally emerges and can be understood in terms of simple population-genetics models.
Generation and propagation of network bursts in the basal ganglia exhibit dynamic changes during early postnatal development
Authors: Klavinskis-Whiting Sebastian , Bitzenhofer Sebastian , Hanganu-Opatz Ileana , Ellender Tommas
Published: July 2022

The neonatal brain is characterised by intermittent bursts of oscillatory activity interspersed by relative silence. While these bursts of activity are well characterised for many cortical areas much less is known whether and how these propagate and interact with subcortical regions. Here, early network activity was recorded using silicon probes from the developing basal ganglia, including the motor/somatosensory cortex, dorsal striatum and intralaminar thalamus, during the first two postnatal weeks in mice. Using an unsupervised detection and classification method, two main classes of bursting activity were found, consisting of spindle bursts (SB) and nested gamma spindle bursts (NGB), which were characterised by oscillatory activity at respectively ∼10 Hz and ∼30 Hz. These bursts were reliably identified across all three brain structures but differed in their structural, spectral, and developmental characteristics. Coherence and cross-correlation analyses revealed that burst events often occur synchronously across different brain regions and were mostly of a similar type, especially between cortex and striatum, which also exhibited the strongest interactions as compared to other brain regions. Interestingly, the preferred frequency for these interactions suggested a developmental shift from initial lower frequencies to higher frequencies across development. Together, these results provide the first detailed description of early network activity within the developing basal ganglia and suggests that distinct brain regions drive and coordinate burst activity at different developmental stages.
Connectome spectrum electromagnetic tomography: a method to reconstruct electrical brain source-networks at high-spatial resolution
Authors: Rué-Queralt Joan , Fluhr Hugo , Tourbier Sebastien , Aleman-Gómez Yasser , Pascucci David , Yerly Jérôme , Glomb Katharina , Plomp Gijs , Hagmann Patric
Published: July 2022

Connectome Spectrum Electromagnetic Tomography (CSET) combines diffusion MRI-derived structural connectivity data with well-established graph signal processing tools to solve the M/EEG inverse problem. Using simulated EEG signals from fMRI responses, and two EEG datasets on visual-evoked potentials, we provide evidence supporting that (i) CSET captures realistic neurophysiological patterns with better accuracy than state-of-the-art methods, (ii) CSET can reconstruct brain responses more accurately and with more robustness to intrinsic noise in the EEG signal. These results demonstrate that CSET offers high spatio-temporal accuracy, enabling neuroscientists to extend their research beyond the current limitations of low sampling frequency in functional MRI and the poor spatial resolution of M/EEG.
Transcriptional response of the xerotolerant Arthrobacter sp. Helios strain to PEG-induced drought stress
Authors: Hernández-Fernández G , Galán B , Carmona M , Castro L , García JL
Published: July 2022

A new bacterial strain highly tolerant to desiccation and to UV radiation has been isolated from the microbiome of solar panels. This strain showed a high xerotolerance in the exponential and the stationary phase of growth and it has been classified as Arthrobacter sp. Helios according to its 16S rDNA, positioning this new strain in the ‘Arthrobacter citreus group’. The complete genome of Arthrobacter sp. Helios consists in a single circular chromosome of 3,895,998 bp, with a 66% GC content and no plasmids. A total of 3,586 genes were predicted, of which 2,275 protein-encoding genes were functionally assigned. The genome analysis suggests that it is motile, ecologically versatile, capable of growing in a variety of carbon sources and well poised to respond to environmental stresses. Using PEG6000 to mimic arid stress conditions, we have studied the transcriptional response of this strain to matric stress when cells are cultured on media containing 10% (PEG10) and 35% PEG (PEG35). The transcriptomic analysis revealed that cells can be easily adapted to moderate matric stress (PEG10) by modifying the expression of a small number of genes to maintain a high growth rate, while a higher matric stress (PEG35) altered the expression of many more genes. Remarkably, these metabolic changes do not confer the cells a higher tolerance to desiccation, suggesting that mechanisms to support matric stress and desiccation tolerance are different. The peculiar observation that Arthrobacter sp. Helios seems to be permanently prepared to handle the desiccation stress makes it an exciting chassis for biotechnological applications.
A simple thermodynamic description of phase separation of Nup98 FG domains
Authors: Ng Sheung Chun , Görlich Dirk
Published: July 2022

The permeability barrier of nuclear pore complexes (NPCs) controls nucleocytoplasmic transport. It retains inert macromolecules but allows facilitated passage of nuclear transport receptors that shuttle cargoes into or out of nuclei. The barrier can be described as a condensed phase assembled from cohesive FG repeat domains, including foremost the charge-depleted FG domain of Nup98. We found that Nup98 FG domains show an LCST-type phase separation, and we provide comprehensive and orthogonal experimental datasets for a quantitative description of this behaviour. A derived thermodynamic model correlates saturation concentration with repeat number, temperature, and ionic strength. It allows estimating the enthalpy, entropy, and ΔG (∼0.2 kJ/mol, 0.1 kB·T) contributions per repeat to phase separation and inter-repeat cohesion. While changing the cohesion strength strongly impacts the strictness of barrier, these numbers provide boundary conditions for in-depth modelling not only of barrier assembly but also of NPC passage.
Robust Harmonization of Microbiome Studies by Phylogenetic Scaffolding with MaLiAmPi
Authors: Minot Samuel S , Garb Bailey , Roldan Alennie , Tang Alice , Oskotsky Tomiko , Rosenthal Christopher , Hoffman Noah G , Sirota Marina , Golob Jonathan L
Published: July 2022

Microbiome science is difficult to translate back to patients due to an inability to harmonize 16S rRNA gene-based microbiome data, as differences in the technique will result in different amplicon sequence variants (ASV) from the same microbe. Here we demonstrate that placement of ASV onto a common phylogenetic tree of full-length 16S rRNA alleles can harmonize microbiome studies. Using in silico data approximating 100 healthy human stool microbiomes we demonstrated that phylogenetic placement of ASV can recapitulate the true relationships between communities as compared closed-OTU based approaches (Spearman R 0.8 vs 0.2). Using real data from thousands of human gut and vaginal microbiota, we demonstrate phylogenetic placement, but not closed OTUs, were able to group communities by origin (stool vs vaginal) without being confounded by technique and integrate new data into existing ordination/clustering models for precision medicine. This enables meta-analysis of microbiome studies and the microbiome as a biomarker.
Hepatic lipid overload potentiates biliary epithelial cell activation via E2Fs
Authors: Yildiz Ece , Alam Gaby El , Perino Alessia , Jalil Antoine , Denechaud Pierre-Damien , Huber Katharina , Fajas Lluis , Auwerx Johan , Sorrentino Giovanni , Schoonjans Kristina
Published: July 2022

During severe or chronic hepatic injury, biliary epithelial cells (BECs), also known as cholangiocytes, undergo rapid reprogramming and proliferation, a process known as ductular reaction (DR), and allow liver regeneration by differentiating into both functional cholangiocytes and hepatocytes. While DR is a hallmark of chronic liver diseases, including advanced stages of non-alcoholic fatty liver disease (NAFLD), the early events underlying BEC activation are largely unknown. Here, we demonstrate that BECs readily accumulate lipids upon fatty acid (FA) treatment in BEC-derived organoids, and during high-fat diet feeding in mice. Lipid overload induces a metabolic rewiring to support the conversion of adult cholangiocytes into active BECs. Mechanistically, we found that lipid overload unleashes the activation of the E2F transcription factors in BECs, which drives cell cycle progression while promoting glycolytic metabolism. These findings demonstrate that fat overload is sufficient to initiate a DR, without epithelial damage, and provide new insights into the mechanistic basis of BEC activation, revealing unexpected connections between lipid metabolism, stemness, and regeneration.
Dysfunction of the Polycomb protein RYBP and of 5-methylcytosine oxidases leads to widespread CpG island hypermethylation and cell transformation
Authors: Cui Wei , Huang Zhijun , Jin Seung-Gi , Johnson Jennifer , Hostetter Galen , Pfeifer Gerd P.
Published: July 2022

DNA hypermethylation is a hallmark of cancer and predominantly affects CpG island regions. Although this phenomenon was first described more than three decades ago, its mechanisms have remained unknown. Since CpG island hypermethylation is strongly biased towards Polycomb target genes, we reasoned that dysfunction of Polycomb repression complexes (PRCs) may underlie CpG island hypermethylation. We observed that a few genes coding for components of the PRC1 complex are downregulated in many cancer types. We focused on RYBP, a key activator of variant PRC1 complexes responsible for H2AK119 monoubiquitylation. We inactivated RYBP in nontumorigenic bronchial epithelial cells and observed a limited extent of DNA hypermethylation. Considering that tumors are deficient in 5-methylcytosine oxidase (TET protein) function as documented by substantially reduced levels of 5-hydroxymethylcytosine in all solid tumors, we then inactivated TET1, TET2, and TET3 in bronchial cells, individually and in combination. Using quadruple knockouts of RYBP and all three TET proteins, we observed widespread hypermethylation of H2AK119Ub1-marked CpG islands affecting almost 4,000 target genes. This hypermethylation closely mirrored the DNA hypermethylation landscape observed in human lung tumors. These cells showed aberrant methylation and dysregulation of several cancer-relevant pathways including cell cycle control genes, defects in the Hippo pathway and overexpression of AP-1 transcription factor genes. As a result, the quadruple knockout bronchial cells acquired properties of a transformed phenotype, including efficient growth in soft agar and formation of squamous cell carcinomas in immune-compromised mice. Our data provide a long- sought mechanism for DNA hypermethylation in cancer and explain how such hypermethylation leads to cell transformation. Cancer formation, therefore, is achievable by misregulation of two epigenetic pathways without introduction of cancer driver mutations.
Sunscreen redox status in a multicellular cyanobacterium visualized by Raman scattering spectral microscope
Authors: Tamamizu Kouto , Sakamoto Toshio , Kurashige Yuki , Nozue Shuho , Kumazaki Shigeichi
Published: July 2022

UV radiation, desiccation, and starvation induce some cyanobacteria to produce a UVA-absorbing pigment, scytonemin, at extracellular sheaths. Although the accumulation of scytonemin is recognizable as dark sheaths through optical microscopes, it has been nontrivial to identify its redox status and obtain its subcellular distribution in response to physiological conditions. Here, we show that a spontaneous Raman scattering spectral microscopy based on an excitation-laser-line-scanning method unveil 3D subcellular distributions of non-UV-induced scytonemins with distinct redox statuses in a filamentous cyanobacterium with a single nitrogen-fixing cell at the basal end. Cellular differentiations and scytonemin redox conditions were simultaneously visualized with an excitation wavelength at 1064 nm that is virtually free from the optical screening by the dark sheaths. The molecular imaging results give insights into not only secretion mechanisms of the sunscreen pigment but also interdependence between photosynthesis, nitrogen fixation, and redox homeostasis in one of the simplest forms of multicellular organisms.
Brain structural covariances in the ageing brain in the UK Biobank
Authors: Dong Chao , Thalamuthu Anbupalam , Jiang Jiyang , Mather Karen A. , Sachdev Perminder S. , Wen Wei
Published: July 2022

Brain structural covariances or pairwise correlations describe how morphologic properties of brain regions are related to one another across individuals. Although it is reported that brain structural covariance changes during brain development, it is not clear how structural covariance relates to the ageing process. Here we investigated the human brain structural covariances of cortical thickness and subcortical volumes in the ageing brain and their associations with age, cognition, and longevity polygenic risk score (longevity-PRS) by using cross-sectional data from the UK Biobank (N = 42075, aged 45-83 years, M/F=19752 /22323). The sample of participants was divided into 84 non-overlapping groups based on their age. The older the age group, the greater the variability in the whole brain structural covariance. However, there was a differential rate of age-related increase of variance between males and females. The variance of females started lower than those of males and then increased with age with a greater gradient than that of males. There was a consistent and significant enrichment of pairwise correlations within the occipital lobe in ageing process. The cortical thickness and subcortical covariances in older groups were significantly different from those in the youngest group. Sixty-two of the total 528 pairs of cortical thickness correlations and 10 of the total 21 pairs of subcortical volume correlations were significantly associated with age after Bonferroni correction. Specifically, with an increasing age, most decreased cortical thickness correlations were found between the regions within the frontal lobe as well as between the frontal lobe regions and regions in other lobes, while pairwise correlations within occipital lobe regions were all strengthening. Most of these correlations were also associated with global cognition and weakly associated with longevity-PRS. These findings revealed that the structural covariance was not stable during ageing. Given the thinning of the cortex and the volumetric reduction of subcortical structures seen in the ageing process, an increased pairwise correlation between the brain regions in the older brain suggested a strengthened coordinated decline between the brain regions involved. However, some of the brain regions demonstrated a differentiated rate of decline which was shown as the inversed or reduced pairwise correlations between these regions.
Effect of Single Nucleotide Polymorphisms on the structure of long noncoding RNAs and their interaction with RNA Binding Proteins
Authors: Singh Mandakini , Kumar Santosh
Published: July 2022

Long non-coding RNAs (lncRNA) are emerging as a new class of regulatory RNAs with remarkable potential to be utilized as therapeutic targets against many human diseases. Several genome-wide association studies (GWAS) have catalogued Single Nucleotide Polymorphisms (SNPs) present in the noncoding regions of the genome, transcribing lncRNAs. In this study, we have selected 67 lncRNAs with GWAS-tagged SNPs and have also investigated their role in affecting the local secondary structures. The majority of the SNPs lead to changes in the secondary structure of lncRNA to a different extent by altering the base pairing patterns. These structural changes in lncRNA are also manifested in form of alteration in the binding site for RNA binding proteins (RBPs) along with affecting their binding efficacies. Ultimately, these structural modifications may influence the transcriptional and post-transcriptional pathways of these RNAs, leading to the causation of diseases. Hence, it is important to understand the possible underlying mechanism of RBPs in association with GWAS-tagged SNPs in human diseases.
Environmental Stability of Enveloped Viruses is Impacted by the Initial Volume and Evaporation Kinetics of Droplets
Authors: French Andrea J. , Longest Alexandra K. , Pan Jin , Vikesland Peter J. , Duggal Nisha K. , Lakdawala Seema S. , Marr Linsey C.
Published: July 2022

Efficient spread of respiratory viruses requires the virus to maintain infectivity in the environment. Environmental stability of viruses can be influenced by many factors, including temperature and humidity. Our study measured the impact of initial droplet volume (50, 5, and 1 µL) and relative humidity (RH: 40%, 65%, and 85%) on the stability of influenza A virus, bacteriophage, Phi6, a common surrogate for enveloped viruses, and SARS-CoV-2 under a limited set of conditions. Our data suggest that the drying time required for the droplets to reach quasi-equilibrium (i.e. a plateau in mass) varied with RH and initial droplet volume. The macroscale physical characteristics of the droplets at quasi-equilibrium varied with RH but not with initial droplet volume. We observed more rapid virus decay when the droplets were still wet and undergoing evaporation, and slower decay after the droplets had dried. Initial droplet volume had a major effect on virus viability over the first few hours; whereby the decay rate of influenza virus was faster in smaller droplets. In general, influenza virus and SARS-CoV-2 decayed similarly. Overall, this study suggests that virus decay in media is closely correlated with the extent of droplet evaporation, which is controlled by RH. Taken together, these data suggest that decay of different viruses is more similar at higher RH and in smaller droplets and is distinct at lower RH and in larger droplets. Importantly, accurate assessment of transmission risk requires use of physiologically relevant droplet volumes and careful consideration of the use of surrogates.

Funding

National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health; Department of Health and Human Services; Flu Lab.

Importance

During the COVID-19 pandemic, policy decisions were being driven by virus stability experiments involving SARS-CoV-2 applied to surfaces in large droplets at various humidity conditions. The results of our study indicate that determination of half-lives for emerging pathogens in large droplets likely over-estimates transmission risk for contaminated surfaces, as occurred during the COVID-19 pandemic. Our study implicates the need for the use of physiologically relevant droplet sizes with use of relevant surrogates in addition to what is already known about the importance of physiologically relevant media for risk assessment of future emerging pathogens.
Long-term effects of early postnatal stress on Sertoli cells functions
Authors: Thumfart Kristina M. , Lazzeri Samuel , Manuella Francesca , Mansuy Isabelle M.
Published: July 2022

Sertoli cells are somatic cells in testes essential for spermatogenesis, as they support the development, maturation, and differentiation of germ cells. Sertoli cells are metabolically highly active and physiologically regulated by external signals, particularly factors in the blood stream. In disease conditions, circulating pathological signals may affect Sertoli cells and consequentially, alter germ cells and fertility. While the effects of stress on reproductive cells have been well studied, how Sertoli cells respond to stress remains poorly characterized. Therefore, we used a mouse model of early postnatal stress to assess the effects of stress on Sertoli cells. We developed an improved enrichment strategy based on intracellular stainings and obtained enriched preparations of adult Sertoli cells from exposed males. We show that adult Sertoli cells have impaired electron transport chain (ETC) pathways and that several components of ETC complexes I, III, and IV are persistently affected. We identify the circulation as a potential mediator of the effects of stress, since treatment of primary Sertoli cells with serum from stressed males induces similar ETC alterations. These results newly highlight Sertoli cells as cellular targets of early life stress, and suggest that they may contribute to the negative effects of stress on fertility.

Highlights

We present an improved method to obtain enriched preparations of Sertoli cells from adult mouse testis for molecular analyses

Sertoli cells from adult males exposed to stress during early postnatal life have altered electron transport chain (ETC) expression, suggesting persistent effects of early life stress on Sertoli cells physiology

Serum from adult males exposed to early postnatal stress reproduces ETC gene dysregulation in cultured Sertoli cells.

Graphical abstract
Segmented MS/MS acquisition of a1 ion-based strategy for in-depth proteome quantitation
Authors: Wang Zhiting , Liu Chao , Wang Songduo , Hou Xinhang , Gong Pengyun , Li Xiao , Liang Zhen , Liu Jianhui , Zhang Lihua , Zhang Yukui
Published: July 2022

In-depth proteome quantitation is of great significance for understanding protein functions, advancing biological, medical, environmental and metabolic engineering research. Herein, benefiting from the high formation efficiencies and intensities of dimethyl-labeled a1 ions for accurate quantitation, we developed an in-depth a1 ion-based proteome quantitation method, named deep-APQ, by a sequential MS/MS acquisition of the high mass range for identification and the low mass range for a1 ion intensity extraction to increase quantitative protein number and sequence coverage. By the analysis of HeLa protein digests, our developed method showed deeper quantitative coverage than our previously reported a1 ion-based quantitation method without mass range segmentation and lower missing values than widely-used label-free quantitation method. It also exhibited excellent accuracy and precision within a 20-fold dynamic range. We further integrated a workflow combining the deep-APQ method with highly efficient sample preparation, high-pH and low-pH reversed-phase separation and high-field asymmetric waveform ion mobility spectrometry (FAIMS) to study E. coli proteome responses under the nutritional conditions of glucose and acetate. A total of 3447 proteins were quantified, representing 82% of protein-coding genes, with the average sequence coverage up to 40%, demonstrating the high coverage of quantitation results. We found that most of the quantified proteins related to chemotaxis were differentially expressed, including the low-abundance proteins such as trg, fliL, and cheA, indicating that chemotaxis would play an important role for E. coli cell to survive from acetate toxicity. The above results demonstrated that the deep-APQ method is of great promising to achieve the deep-coverage proteome quantitation with high confidence.

GRAPHICAL ABSTRACT
TCR-pMHC complex formation triggers CD3 dynamics
Authors: van Eerden Floris J. , Sherif Aalaa Alrahman , Llamas-Covarrubias Mara Anais , Millius Arthur , Lu Xiuyuan , Ishizuka Shigenari , Yamasaki Sho , Standley Daron M.
Published: July 2022

In this study, we present an allosteric mechanism for T cell receptor (TCR) triggering upon binding a peptide-MHC complex (pMHC), in which a conformational change in the TCR upon pMHC binding controls the mobility of the CD3 proteins. We found that the TCRβ FG loop serves as a gatekeeper, preventing accidental triggering, while the connecting peptide acts as a hinge for essential conformational changes in the TCR. Atomistic simulations and cell-based experiments with genetically modified connecting peptides demonstrate that rigidified hinge residues result in excessive CD3 dynamics and hypersensitivity to pMHC binding. Our model thus provides a clear connection between extracellular TCR-pMHC binding and changes in CD3 dynamic that propagate from outside to inside the cell.
COVID19-vaccination affects breath methane dynamics
Authors: Polag Daniela , Keppler Frank
Published: July 2022

Methane (CH4) is well known as a component in the exhaled breath of humans. It has been assumed for a long time that formation of CH4 in humans occurs exclusively by anaerobic microbial activity (methanogenesis) in the gastrointestinal tract. A fraction of the produced CH4 is excreted via the lungs and can then be detected in the breath. However, recent studies challenge this view by showing that CH4 might also be produced endogenously in cells by oxidative-reductive stress reactions. Thus, an increased and fluctuating level of breath CH4 compared to the base level of an individual might also indicate enhanced oxidative stress levels. Thus, monitoring breath CH4 levels might have great potential for ‘in vivo’ diagnostics.

Generally, vaccines generate a strong immune response including the production of pro-inflammatory cytokines. To evaluate the effect from current vaccines against COVID-19 on breath CH4 dynamics, breath CH4 was monitored from 12 subjects prior and after the injection of several COVID-vaccines. Prior to COVID-19 vaccination the concentration of breath CH4 was frequently measured by gas chromatograph flame ionization detection (GC-FID, with analytical precision better than 10 parts per billion, ppbv) to obtain the individual variation range of breath CH4 for each subject. Following vaccination, CH4 breath samples were collected at high frequency for a period of 14 days.

All subjects monitored showed a strong response in breath CH4 release within 1 to 72 hours after vaccination including shifts and high fluctuations with maximum peaks showing a factor of up to ±100 compared to base values. Thus, it is highly likely that the observed changes in breath CH4 are coupled to immune responses following Covid-19 vaccination. These preliminary results strongly support the hypothesis that non-microbial methane liberation and utilisation in the human body might be also linked to cellular processes and stress responses independent of classical microbial methanogenesis. Thus, CH4 might be used as a breath biomarker for specific immune responses and individual immune states.
Phenotypic extremes or extreme phenotypes? On the use of large and small-bodied “phenocopied” Drosophila melanogaster males in studies of sexual selection and conflict
Authors: Schang Kyle , Garant Renée , Long Tristan A.F.
Published: July 2022

In the fruit fly, Drosophila melanogaster, variation in body size is influenced by a number of different factors and may be strongly associated with individual condition, performance and success in reproductive competitions. Consequently, intra-sexual variation in size in this model species has been frequently explored in order to better understand how sexual selection and sexual conflict may operate and shape evolutionary trajectories. However, measuring individual flies can often be logistically complicated and inefficient, which can result in limited sample sizes. Instead, many experiments use large and/or small body sizes that are created by manipulating the developmental conditions experienced during the larval stages, resulting in “phenocopied” flies whose phenotypes resemble what is seen at the extremes of a population’s size distribution. While this practice is fairly common, there has been remarkedly few direct tests to empirically compare the behaviour or performance of phenocopied flies to similarly-sized individuals that grew up under typical developmental conditions. Contrary to assumptions that phenocopied flies are reasonable approximations, we found that both large and small-bodied phenocopied males frequently differed from their standard development equivalents in their mating frequencies, their lifetime reproductive successes, and in their effects on the fecundity of the females they interacted with. Our results highlight the complicated contributions of environment and genotype to the expression of body size phenotypes and lead us to strongly urge caution in the interpretation of studies solely replying upon phenocopied individuals.
Global fMRI signal topography differs systematically across the lifespan
Authors: Nomi Jason S. , Bzdok Danilo , Li Jingwei , Bolt Taylor , Chang Catie , Kornfeld Salome , Goodman Zachary T. , Yeo B.T. Thomas , Spreng R. Nathan , Uddin Lucina Q.
Published: July 2022

The global signal (GS) in resting-state fMRI, known to contain artifacts and non-neuronal physiological signals, also contains important neural information related to individual state and trait characteristics. Here we show distinct linear and curvilinear lifespan patterns of GS topography in a cross-sectional lifespan sample, demonstrating its importance for consideration in studies of development and aging. Subcortical brain regions such as the thalamus and putamen show linear associations with the GS across the lifespan. The thalamus has stronger coupling in older-age individuals compared with younger-aged individuals, while the putamen has stronger coupling in younger individuals compared with older individuals. The subcortical nucleus basalis shows a u-shaped pattern similar to cortical regions within the lateral frontoparietal network and dorsal attention network, where coupling with the GS is stronger at early and old age, with weaker coupling in middle age. This differentiation in coupling strength between subcortical and cortical brain activity across the lifespan supports a dual-layer model of GS composition, where subcortical aspects of the GS are differentiated from cortical aspects of the GS. We find that these subcortical-cortical contributions to the GS depend strongly on the lifespan stage of individuals. Our findings demonstrate how neurobiological information within the GS differs across development and highlight the need to carefully consider whether or not to remove this signal when investigating age-related functional differences in the brain.
Assembler artifacts include misassembly because of unsafe unitigs and underassembly because of bidirected graphs
Authors: Rahman Amatur , Medvedev Paul
Published: July 2022

Recent assemblies by the T2T and VGP consortia have achieved significant accuracy but required a tremendous amount of effort and resources. More typical assembly efforts, on the other hand, still suffer both from misassemblies (joining sequences that should not be adjacent) and from underassemblies (not joining sequences that should be adjacent). To better understand the common algorithm-driven causes of these limitations, we investigated the unitig algorithm, which is a core algorithm at the heart of most assemblers. We prove that, contrary to popular belief, even when there are no sequencing errors, unitigs are not always safe (i.e., they are not guaranteed to be substrings of the sequenced genome). We also prove that the unitigs of a bidirected de Bruijn graph are different from those of a doubled de Bruijn graph and, contrary to our expectations, result in underassembly. Using experimental simulations, we then confirm that these two artifacts exist not only in theory but also in the output of widely used assemblers. In particular, when coverage is low, then even error-free data result in unsafe unitigs; also, unitigs may unnecessarily split palindromes in half if special care is not taken. To the best of our knowledge, this paper is the first to theoretically predict the existence of these assembler artifacts and confirm and measure the extent of their occurrence in practice.
Orientation evaluation of ultra-high molecular weight polyethylene fibers: previous studies and an improved method
Authors: Zhang Hao , Li Jianrong , Guo Yuihai , Tian Feng , Qiao Yongna , Tang Zheng , Zhu Caizhen , Xu Jian
Published: July 2022

Determination of the orientation of microfibrils within ultra-high molecular weight polyethylene (UHMWPE) fibers is considered to be an important method in evaluating the mechanical properties of the fibers. Four commonly used orientation evaluation methods are summarized and used to evaluate UHMWPE fibers at different drawing stages in the industrial line, and the results exhibit certain limitations. To overcome these limitations, a new evaluation method for quantitive characterization of UHMWPE fiber properties is proposed. Meanwhile, in situ small-angle X-ray scattering data of an UHMWPE fiber drawn at 100°C were used to perform a Pearson correlation coefficient test, and the results show a very strong correlation between the strain ratio and the evaluated coefficient.
Voltage sag compensation at load side in armor fighting vehicles using ultra capacitor
Authors: N. Saravanan , S. Hosimin Thilagar
Published: July 2022

Purpose

The purpose of this paper rapid development of various voltage sag compensation techniques in DC bus using ultra-capacitors (UCs) provides satisfactory results when compared with required peak power demand for shorter duration. Later, UCs have been used as floating capacitors [1] [2]. Various UCs are available based on internal resistances which also rely on its manufacturing materials, similar to double layer capacitors.

Design/methodology/approach

This paper demonstrates UCs based voltage sag compensation at load side under different working modes of hydraulic pack (HP) in an armored fighting vehicle (AFV). The main sources to supply the HP are 24 V, 400 Ahr battery bank and 20 kW main generator. HP is considered to be the highest power load of a system. 2,500 A inrush current was drawn by HP during initial conditions, and also, this system works in both elevation and azimuth mode. Voltage sag has been varied from 15 to 24 V for different modes. But as per the military standard, electrical systems should operate between 18 and 32 V DC. Because of insufficient terminal voltage, required energy cannot be attained and supplied to the loads. The proposed topology compensated the voltage sag and maintains nominal voltage on a DC bus. The devised circuit has been verified under all possible operating loads such as continuous, intermittent and momentary. The same has been simulated using MATLAB/Simulink and was experimentally verified. The minimum voltage maintained in a DC bus is 22.2 V in simulation, while experimentally, it was 24.2 V.

Findings

For getting higher percentage of efficiency, secondary energy system configuration, mainly designed for electrical vehicles, is needed. It was implemented and same was tested with the fighting vehicle system[1]. The proposed configuration comprises of bank of an UC and a battery bank. The system was finally implemented in AFVs.

Originality/value

The goods vehicles made of UCs can hold very minimum energy because of minimum density of energy. The modified AFV can have minimum charging as well as discharging of rate of energy and, thus, power[3][4]. Thus, the proposed idea of modified vehicle system has influence over significant change in the state of charge.
Emotional & technological impact on managerial competencies: outlining the development agenda
Authors: Agnihotri Amit , Misra Rajnish Kumar
Published: July 2022

Purpose

The purpose of this article is to examine the Emotional, Behavioural and Psychological impact, and impact of explosion of Technology-led complexity on Managerial Competencies. The article offers a new training and development agenda that can mitigate these impacts, and improve employee productivity and well-being.

Design/methodology/approach

After exploring the theoretical underpinning of management competencies, and dimensions that could impact them, discussions with senior industry experts from different sectors were carried out to understand the impact and suggest ways to mitigate them.

Findings

COVID-19 shock and experiences may have impacted the Intrapersonal skills, Interpersonal skill and Leadership skills. Technology explosion may have impacted all these and Business skills as well. A new Learning and Development agenda is suggested to mitigate the emotional and technology impact on each of the managerial competencies, thus improving on-job productivity.

Practical implications

A strategic development program can be created to mitigate the recent emotional, psychological and technology impact on different managerial competencies. This granular training program that understands the cause, and offers a specific solution will greatly benefit the organizations and employees.

Originality/value

The paper combines the understanding of managerial competencies with recent social and workplace developments, and draws on the learnings from industry experts to make practical suggestions for talent development.
Flood hazards and housing prices: a spatial regression analysis for Hat Yai, Songkhla, Thailand
Authors: Chongwilaikasaem Sukampon , Chalermyanont Tanit
Published: July 2022

Purpose

Global warming exacerbates sea level rise and extreme weather events that cause severe flooding, resulting in lost productivity and property damage. To reduce the impact of flooding, residents are avoiding purchasing homes in high-risk areas. There are numerous studies on the relationship between flood hazards and housing prices in developed countries, but few in developing countries. Therefore, this study aims to investigate the relationship between flood hazards and housing prices in Hat Yai, Songkhla, Thailand.

Design/methodology/approach

This study uses spatial-lag, spatial error and spatial autoregressive lag and error (SARAR) models to analyze the effect of flood risk on property prices. The main analysis examines the degree of flood risk and housing rental prices from our survey of 380 residences. To test the robustness of the results, the authors examine a different data set of the same samples by using the official property valuation from the Ministry of Finance and the flood risk estimated by the Southern Natural Disaster Research Center.

Findings

The SARAR model was chosen for this study because of the occurrence of spatial dependence in both dependent variable and the error term. The authors find that flood risk has a negative impact on property prices in Hat Yai, which is consistent with both models.

Originality/value

This study is one of the first to use spatial econometrics to analyze the impact of flood risk on property prices in Thailand. The results of this study are valuable to policymakers for benefit assessment in cost–benefit analysis of flood risk avoidance or reduction strategies and to the insurance market for pricing flood risk insurance.