bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying interactions in omics data for clinical biomarker discovery using symbolic regression
Authors: Christensen Niels Johan , Demharter Samuel , Machado Meera , Pedersen Lykke , Salvatore Marco , Stentoft-Hansen Valdemar , Iglesias Miquel Triana
Published: January 2022

The identification of predictive biomarker signatures from omics data for clinical applications is an active area of research. Recent developments in assay technologies and machine learning (ML) methods have led to significant improvements in predictive performance. However, most high-performing ML methods suffer from complex architectures and lack interpretability. Here, we present the application of a novel symbolic-regression-based algorithm, the QLattice, on a selection of clinical omics data sets. This approach generates parsimonious high-performing models that can both predict disease outcomes and reveal putative disease mechanisms. Due to their high performance, simplicity and explicit functional form, these biomarker signatures can be readily explained, thereby making them attractive tools for high-stakes applications in primary care, clinical decision making and patient stratification.
Transposable elements contribute to the spatiotemporal microRNA landscape in human brain development
Authors: Playfoot Christopher J. , Sheppard Shaoline , Planet Evarist , Trono Didier
Published: January 2022

Transposable elements (TEs) contribute to the evolution of gene regulatory networks and are dynamically expressed throughout human brain development and disease. One gene regulatory mechanism influenced by TEs is the miRNA system of post-transcriptional control. miRNA sequences frequently overlap TE loci and this miRNA expression landscape is crucial for control of gene expression in adult brain and different cellular contexts. Despite this, a thorough investigation of the spatiotemporal expression of TE-embedded miRNAs in human brain development is lacking. Here, we identify a spatiotemporally dynamic TE-embedded miRNA expression landscape between childhood and adolescent stages of human brain development. These miRNAs sometimes arise from two apposed TEs of the same subfamily, such as for L2 or MIR elements, but in the majority of cases stem from solo TEs. They give rise to in silico predicted high-confidence pre-miRNA hairpin structures, likely represent functional miRNAs and have predicted genic targets associated with neurogenesis. TE-embedded miRNA expression is distinct in the cerebellum when compared to other brain regions, as has previously been described for gene and TE expression. Furthermore, we detect expression of previously non-annotated TE-embedded miRNAs throughout human brain development, suggestive of a previously undetected miRNA control network. Together, as with non-TE-embedded miRNAs, TE-embedded sequences give rise to spatiotemporally dynamic miRNA expression networks, the implications of which for human brain development constitute extensive avenues of future experimental research. To facilitate interactive exploration of these spatiotemporal miRNA expression dynamics, we provide the “Brain miRTExplorer” web application freely accessible for the community.
Region Selective Cortical Control Of The Thalamic Reticular Nucleus
Authors: Hádinger Nóra , Bősz Emília , Tóth Boglárka , Vantomme Gil , Lüthi Anita , Acsády László
Published: January 2022

Corticothalamic pathways, responsible for the top-down control of the thalamus display a classical, canonical organization in that every cortical region sends dual, layer 6 (L6) and layer 5 (L5) output to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of corticothalamic pathways. We show that L5 pyramidal cells of the frontal, but not other cortical regions establish monosynaptic connection with the inhibitory thalamic reticular nucleus (TRN). The frontal L5-TRN pathway paralleled the L6-TRN projection but displayed distinct morphological and physiological features. The exact spike output of the L5 contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5-TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated all thalamic nuclei involved in the control of frontal cortical activity. Our data show that frontal cortical functions require a highly specialized cortical control over intrathalamic inhibitory processes.
Scale Bar of Aging Trajectories for Screening Personal Rejuvenation Treatments
Authors: Shen Xilin , Wu Bingbing , Jiang Wei , Li Yu , Zhang Yuping , Zhao Kun , Nie Nanfang , Gong Lin , Liu Yixiao , Zou Xiaohui , Liu Jian , Jin Jingfen , Ouyang HongWei
Published: January 2022

Although aging is an increasingly severe healthy, economic, and social global problem, it is far from well-modeling aging due to the aging process’s complexity. To promote the aging modeling, here we did the quantitative measurement based on aging blood transcriptome. Specifically, the aging blood transcriptome landscape was constructed through ensemble modeling in a cohort of 505 people, and 1138 age-related genes were identified. To assess the aging rate in the linear dimension of aging, we constructed a simplified linear aging clock, which distinguished fast-aging and slow-aging populations and showed the differences in the composition of immune cells. Meanwhile, the non-linear dimension of aging revealed the transcriptome fluctuations with a crest around the age of 40 and showed that this crest came earlier and was more vigorous in the fast-aging population. Moreover, the aging clock was applied to evaluate the rejuvenation effect of molecules in vitro, such as Nicotinamide Mononucleotide (NMN) and Metformin. In sum, this study developed a de novo aging clock to evaluate agedependent precise medicine by revealing its fluctuation nature based on comprehensively mining the aging blood transcriptome, promoting the development of personal aging monitoring and anti-aging therapies.
Phenotypic deconvolution in heterogeneous cancer cell populations using drug screening data
Authors: Köhn-Luque Alvaro , Myklebust Even Moa , Tadele Dagim Shiferaw , Giliberto Mariaserena , Schmiester Leonard , Noory Jasmine , Harivel Elise , Arsenteva Polina , Mumenthaler Shannon M. , Schjesvold Fredrik , Taskén Kjetil , Enserink Jorrit M. , Leder Kevin , Frigessi Arnoldo , Foo Jasmine
Published: January 2022

Tumor heterogeneity is an important driver of treatment failure in cancer since therapies often select for drug-tolerant or drug-resistant cellular subpopulations that drive tumor growth and recurrence. Profiling the drug-response heterogeneity of tumor samples using traditional genomic deconvolution methods has yielded limited results, due in part to the imperfect mapping between genomic variation and functional characteristics. Here, we leverage mechanistic population modeling to develop a statistical framework for profiling phenotypic heterogeneity from standard drug screen data on bulk tumor samples. This method, called PhenoPop, reliably identifies tumor subpopulations exhibiting differential drug responses, and estimates their drug-sensitivities and frequencies within the bulk. We apply PhenoPop to synthetically-generated cell populations, mixed cell-line experiments, and multiple myeloma patient samples, and demonstrate how it can provide individualized predictions of tumor growth under candidate therapies. This methodology can also be applied to deconvolution problems in a variety of biological settings beyond cancer drug response.

Motivation

Tumors are typically comprised of heterogeneous cell populations exhibiting diverse phenotypes. This heterogeneity, which is correlated with tumor aggressiveness and treatment failure, confounds current drug screening efforts aimed at informing therapy selection. In order to optimally select treatments, understanding the frequency and drug-response profile of individual subpopulations within a tumor is critical. Furthermore, quantitative profiles of tumor drug-response heterogeneity, in combination with predictive mathematical modeling of tumor dynamics, can be used to design effective temporal drug-sequencing strategies for tumor reduction.

Here, we present a method that enables the deconvolution of tumor samples into individual sub-components exhibiting differential drug-response. This method relies on standard bulk drug-screen measurements and outputs the frequencies and drug-sensitivities of tumor subpopulations. This framework can also be applied more broadly to deconvolve cellular populations with heterogeneous responses to a variety of external stimuli and environmental factors.
The formal demography of kinship IV: Two-sex models
Authors: Caswell Hal
Published: January 2022

Background

Previous kinship models analyze female kin through female lines of descent, neglecting male kin and male lines of descent. Because males and females differ in mortality and fertility, including both sexes in kinship models is an important unsolved problem.

Objectives

The objectives are to develop a kinship model including female and male kin through all lines of descent, to explore approximations when full sex-specific rates are unavailable, and to apply the model to several populations as an example.

Methods

The kin of a focal individual form an age×sex-classified population and are projected as Focal ages using matrix methods, providing expected age-sex structures for every type of kin at every age of Focal. Initial conditions are based on the distribution of ages at maternity and paternity.

Results

The equations for two-sex kinship dynamics are presented. As an example, the model is applied to populations with large (Senegal), medium (Haiti), and small (France) differences between female and male fertility. Results include numbers and sex ratios of kin as Focal ages. An approximation treating female and male rates as identical provides some insight into kin numbers, even when male and female rates are very different.

Contribution

Many demographic and sociological parameters (e.g., aspects of health, bereavement, labor force participation) differ markedly between the sexes. This model permits analysis of such parameters in the context of kinship networks. The matrix formulation makes it possible to extend the two-sex analysis to include kin loss, multistate kin demography, and time varying rates.
Impact of ionizing radiation on the environmental microbiomes of Chernobyl wetlands
Authors: Videvall Elin , Burraco Pablo , Orizaola Germán
Published: January 2022

Radioactive contamination in the form of ionizing radiation can be a devastating pollutant because it has the potential to cause damage to DNA and other biomolecules. Anthropogenic sources of ionizing radiation include accidents in nuclear power plants, such as the one in Chernobyl 1986, which caused long-term radioactive pollution. Studies on animals within radioactive zones have provided us with a greater understanding of how wildlife can persevere despite chronic radiation exposure, however, we still know very little about the effects of radiation on the microbial communities in the environment. Here, we examined the impact of ionizing radiation and other environmental factors on the diversity and composition of environmental microbiomes in the wetlands of Chernobyl. We combined extensive field sampling along a gradient of radiation together with 16S rRNA high-throughput metabarcoding (Illumina NovaSeq). While radiation did not affect the alpha diversity of the microbiomes in sediment, soil, or water, it had a strong effect on the beta diversity, indicating that the microbial composition was affected by ionizing radiation. Specifically, we detected several microbial taxa that were more abundant in areas with high radiation levels within the Chernobyl Exclusion Zone, including bacteria and archaea known to be radioresistant. Overall, our results reveal the existence of rich and diverse microbiomes in Chernobyl wetlands, with multiple taxonomic groups that are able to thrive despite the radioactive contamination. Further field and laboratory-based approaches will help to forecast the functionality and re-naturalization dynamics of radiocontaminated environments.
Integration of heterogeneous biological data in multiscale mechanistic model calibration: application to lung adenocarcinoma
Authors: Palgen Jean-Louis , Perrillat-Mercerot Angélique , Ceres Nicoletta , Peyronnet Emmanuel , Coudron Matthieu , Tixier Eliott , Illigens Ben M.W. , Bosley Jim , L’Hostis Adèle , Monteiro Claudio
Published: January 2022

Mechanistic models are built using knowledge as the primary information source, with well-established biological and physical laws determining the causal relationships within the model. Once the causal structure of the model is determined, parameters must be defined in order to accurately reproduce relevant data. Determining parameters and their values is particularly challenging in the case of models of pathophysiology, for which data for calibration is sparse. Multiple data sources might be required, and data may not be in a uniform or desirable format. We describe a calibration strategy to address the challenges of scarcity and heterogeneity of calibration data. Our strategy focuses on parameters whose initial values cannot be easily derived from the literature, and our goal is to determine the values of these parameters via calibration with constraints set by relevant data. When combined with a covariance matrix adaptation evolution strategy (CMA-ES), this step-by-step approach can be applied to a wide range of biological models. We describe a stepwise, integrative and iterative approach to multiscale mechanistic model calibration, and provide an example of calibrating a pathophysiological lung adenocarcinoma model. Using the approach described here we illustrate the successful calibration of a complex knowledge-based mechanistic model using only the limited heterogeneous datasets publicly available in the literature.
A deep CNN framework for neural drive estimation from HD-EMG across contraction intensities and joint angles
Authors: Wen Yue , Kim Sangjoon J. , Avrillon Simon , Levine Jackson T. , Hug François , Pons José L.
Published: January 2022

Objective

Previous studies have demonstrated promising results in estimating the neural drive to muscles, the net output of all motoneurons that innervate the muscle, using high-density electromyography (HD-EMG) for the purpose of interfacing with assistive technologies. Despite the high estimation accuracy, current methods based on neural networks need to be trained with specific motor unit action potential (MUAP) shapes updated for each condition (i.e., varying muscle contraction intensities or joint angles). This preliminary step dramatically limits the potential generalization of these algorithms across tasks. We propose a novel approach to estimate the neural drive using a deep convolutional neural network (CNN), which can identify the cumulative spike train (CST) through general features of MUAPs from a pool of motor units.

Methods

We recorded HD-EMG signals from the gastrocnemius medialis muscle under three isometric contraction scenarios: 1) trapezoidal contraction tasks with different intensities, 2) contraction tasks with a trapezoidal or sinusoidal torque target, and 3) trapezoidal contraction tasks at different ankle angles. We applied a convolutive blind source separation (BSS) method to decompose HD-EMG signals to CST and segmented both signals into windows to train and validate the deep CNN. Then, we optimized the structure of the deep CNN and validated its generalizability across contraction tasks within each scenario.

Results

With the optimal configuration for the HD-EMG data window (overlap of 20 data points and window length of 40 data points), the deep CNN estimated the CST close to that from BSS, with a correlation coefficient higher than 0.96 and normalized root-mean-square-error lower than 7% with respect to the BSS (golden standard) within each scenario.

Conclusion

The proposed deep CNN framework can utilize data from different contraction tasks (e.g., different intensities), learn general features of MUAP variants, and estimate the neural drive for other contraction tasks.

Significance

With the proposed deep CNN, we could potentially build a neuraldrive-based human-machine interface that is generalizable to different contraction tasks without retraining.
Differences in environmental stability among SARS-CoV-2 variants of concern: Omicron has higher stability
Authors: Hirose Ryohei , Itoh Yoshito , Ikegaya Hiroshi , Miyazaki Hajime , Watanabe Naoto , Yoshida Takuma , Bandou Risa , Daidoji Tomo , Nakaya Takaaki
Published: January 2022

SARS-CoV-2 variants of concern (VOCs) could cause significant human and economic damage owing to increased infectivity and transmissibility, and understanding their characteristics is crucial for infection control. Here, we analyzed differences in viral stability and disinfection efficacy between the Wuhan strain and all VOCs. On plastic and skin surfaces, Alpha, Beta, Delta, and Omicron variants exhibited more than two-fold longer survival than the Wuhan strain, and the Omicron variant had the longest survival time. Specifically, survival times of the Wuhan strain, Alpha variant, Beta variant, Gamma variant, Delta variant, and Omicron variant on skin surfaces were 8.6 h (95% CI, 6.5–10.9 h), 19.6 h (95% CI, 14.8–25.3 h), 19.1 h (95% CI, 13.9– 25.3 h), 11.0 h (95% CI, 8.1–14.7 h), 16.8 h (95% CI, 13.1–21.1 h), and 21.1 h (95% CI, 15.8– 27.6 h), respectively. In vitro, disinfectant effectiveness evaluations showed that Alpha, Beta, Delta, and Omicron were slightly more resistant to ethanol than the Wuhan strain. However, ex vivo evaluation showed that on human skin, all viruses were completely inactivated by exposure to 35 w/w % ethanol for 15 s. The high environmental stability of these VOCs could increase transmission risk and contribute to spread. Additionally, the Omicron variant might have been replaced by the Delta variant due to its increased environmental stability and rapid spread. To prevent VOC spread, it is highly recommended that current infection control practices use disinfectants with appropriate ethanol concentrations.
Reconstructing the spatiotemporal patterns of admixture during the European Holocene using a novel genomic dating method
Authors: Chintalapati Manjusha , Patterson Nick , Moorjani Priya
Published: January 2022

Recent studies have shown that gene flow or admixture has been pervasive throughout human history. While several methods exist for dating admixture in contemporary populations, they are not suitable for sparse, low coverage data available from ancient specimens. To overcome this limitation, we developed DATES that leverages ancestry covariance patterns across the genome of a single individual to infer the timing of admixture. By performing simulations, we show that DATES provides reliable results under a range of demographic scenarios and outperforms available methods for ancient DNA applications. We apply DATES to ~1,100 ancient genomes to reconstruct gene flow events during the European Holocene. Present-day Europeans derive ancestry from three distinct groups, local Mesolithic hunter-gatherers, Anatolian farmers, and Yamnaya Steppe pastoralists. These ancestral groups were themselves admixed. By studying the formation of Anatolian farmers, we infer that the gene flow related to Iranian Neolithic farmers occurred no later than 9,600 BCE, predating agriculture in Anatolia. We estimate the early Steppe pastoralist groups genetically formed more than a millennium before the start of steppe pastoralism, providing new insights about the history of proto-Yamnaya cultures and the origin of Indo-European languages. Using ancient genomes across sixteen regions in Europe, we provide a detailed chronology of the Neolithization across Europe that occurred from ~6,400–4,300 BCE. This movement was followed by a rapid spread of steppe ancestry from ~3,200–2,500 BCE. Our analyses highlight the power of genomic dating methods to elucidate the legacy of human migrations, providing insights complementary to archaeological and linguistic evidence.

Significance

The European continent was subject to two major migrations during the Holocene: the movement of Near Eastern farmers during the Neolithic and the migration of Steppe pastoralists during the Bronze Age. To understand the timing and dynamics of these movements, we developed DATES that leverages ancestry covariance patterns across the genome of a single individual to infer the timing of admixture. Using ~1,100 ancient genomes spanning ~8,000–350 BCE, we reconstruct the chronology of the formation of the ancestral populations and the fine-scale details of the spread of Neolithic farming and Steppe pastoralist-related ancestry to Europe. Our analysis demonstrates the power of genomic dating methods to provide an independent and complementary timeline of population origins and movements using genetic data.
Evolutionary PTEN gene divergence underpins the remodeling of plant vacuolar compartments
Authors: Gujas Bojan , Champeyroux Chloe , Hunkeler Anna , Robinson Emilija , Blanco-Touriñán Noel , Dias Cruz Tiago Miguel , Durme Matthias Van , Nowack Moritz K. , Rodriguez-Villalon Antia
Published: January 2022

Membrane fusion and fission are fundamental processes in sustaining cellular compartmentalization. Fission of a lipid bilayer requires a furrow formation that brings membranes in close proximity prior to a contiguous membrane cleavage. Although plant ancestors abandoned cleavage furrow-mediated cytokinesis more than 500 million years ago, here we show that plants still employ this mechanical principle to divide embryonic vacuoles. The evolutionary divergence in PHOSPHATASE AND TENSIN HOMOLOG DELETED ON CHROMOSOME TEN (PTEN) enzymes was required to coordinate this process, as Arabidopsis loss-of-function pten2a pten2b mutants contain hyper compartmentalized embryonic vacuoles. In contrast, PTEN2 overexpression hinders lytic and secretion cellular pathways downstream of TGN in xylem cells. These processes are critical for the formation of secondary cell walls in xylem cells and depend on a poorly characterized and evolutionarily novel N-terminal domain in PTEN2s. The PTEN2 subfamily appeared with the emergence of the Phragmoplastophyta clade, when vacuolar compartments enlarged and cleavage furrow-mediated cytokinesis became extinct. Together, our work suggests that the evolutionary innovation of the PTEN family is conserved across terrestrial plants and central to vacuolar remodelling.
Elucidating gene expression patterns across multiple biological contexts through a large-scale investigation of transcriptomic datasets
Authors: Figueiredo Rebeca Queiroz , del Ser Sara Díaz , Raschka Tamara , Hofmann-Apitius Martin , Kodamullil Alpha Tom , Mubeen Sarah , Domingo-Fernández Daniel
Published: January 2022

Distinct gene expression patterns within cells are foundational for the diversity of functions and unique characteristics observed in specific contexts, such as human tissues and cell types. Though some biological processes commonly occur across contexts, by harnessing the vast amounts of available gene expression data, we can decipher the processes that are unique to a specific context. Therefore, with the goal of developing a portrait of context-specific patterns to better elucidate how they govern distinct biological processes, this work presents a large-scale exploration of transcriptomic signatures across three different contexts (i.e., tissues, cell types, and cell lines) by leveraging over 600 gene expression datasets categorized into 98 subcontexts. The strongest pairwise correlations between genes from these subcontexts are used for the construction of co-expression networks. Using a network-based approach, we then pinpoint patterns that are unique and common across these subcontexts. First, we focused on patterns at the level of individual nodes and evaluated their functional roles using a human protein-protein interactome as a referential network. Next, within each context, we systematically overlaid the co-expression networks to identify specific and shared correlations as well as relations already described in scientific literature. Additionally, in a pathway-level analysis, we overlaid node and edge sets from co-expression networks against pathway knowledge to identify biological processes that are related to specific subcontexts or groups of them. Finally, we have released our data and scripts athttps://zenodo.org/record/5831786andhttps://github.com/ContNeXt/, respectively and developed ContNeXt (https://contnext.scai.fraunhofer.de/), a web application to explore the networks generated in this work.
Validity and reliability of Kinect v2 for quantifying upper body kinematics during seated reaching
Authors: Faity Germain , Mottet Denis , Froger Jérôme
Published: January 2022

Background

Kinematic analysis of the upper limbs is a good way to assess and monitor recovery in individuals with stroke, but remains little used in clinical routine due to its low feasibility. The aim of this study is to assess the validity and reliability of the Kinect v2 for the assessment of 17 kinematic variables commonly used in the analysis of upper limb reaching in stroke.

Methods

26 healthy participants performed seated hand-reaching tasks while holding a dumbbell to induce a behaviour similar to that of a person with a stroke. 3D upper limb and trunk motion were simultaneously recorded with the Kinect v2 (Microsoft, USA) and with the VICON (OxfordMetrics, UK), the latter being the reference system. For each kinematic outcome, the validity of the Kinect was assessed with ICC, linear regression and Bland & Altman plots.

Results

The Kinect assesses trunk compensations, hand range of motion, movement time and mean velocity with a moderate to excellent reliability. In contrast, elbow and shoulder range of motion, time to peak velocity and path length ratio have a poor to moderate reliability, indicating that these variables should be interpreted with caution. Finally, instantaneous hand and elbow tracking are not precise enough to reliably assess Cartesian and angular kinematics over time, rendering variables such as the number of velocity peaks and the peak hand velocity unusable.

Conclusions

Thanks to its ease of use and markerless properties, the Kinect can be used in clinical routine for semi-automated quantitative diagnostics guiding individualised rehabilitation of the upper limb. However, engineers and therapists must bear in mind the limitations of the Kinect for the instantaneous tracking of the hand and elbow.
The cross-domain functional organisation of posterior lateral temporal cortex: Insights from ALE meta-analyses of seven cognitive domains spanning 9515 participants
Authors: Hodgson Victoria J. , Lambon Ralph Matthew A. , Jackson Rebecca L.
Published: January 2022

The posterior lateral temporal cortex is implicated in many verbal, nonverbal and social cognitive domains and processes. Yet without directly comparing these disparate domains, the region’s organisation remains unclear; do distinct processes engage discrete subregions, or could different domains engage shared neural correlates and processes? Here, using activation likelihood estimation meta-analyses, the bilateral posterior lateral temporal cortex subregions engaged in seven domains were directly compared. These domains comprised semantics, semantic control, phonology, biological motion, face processing, theory of mind, and representation of tools. Whilst phonology and biological motion were predominantly associated with distinct regions, other domains implicated overlapping areas, perhaps due to shared underlying processes. Theory of mind recruited regions implicated in semantic representation in the left hemisphere, tools engaged semantic control areas, and faces engaged subregions for biological motion and theory of mind. This cross-domain approach provides insight into how posterior lateral temporal cortex is organised and why.
High-Throughput Screening for Myelination Promoting Compounds Using Human Stem Cell-derived Oligodendrocyte Progenitor Cells Identifies Novel Targets
Authors: Li Weifeng , Berlinicke Cynthia , Huang Yinyin , Fang Weixiang , Chen Celeste , Takaesu Felipe , Chang Xiaoli , Duan Yukan , Chang Calvin , Mao Hai-Quan , Sheng Guoqing , Giera Stefanie , Dodge James C. , Ji Hongkai , Madden Stephen , Zack Donald J. , Chamling Xitiz
Published: January 2022

Promoting myelination capacity of endogenous oligodendrocyte precursor cells (OPCs) is a promising therapeutic approach for central nervous system demyelinating disorders such as Multiple Sclerosis (MS). To aid in the discovery of myelination promoting compounds, we generated an advanced, genome engineered, human pluripotent stem cell (hPSC) line that consist of three reporters (identification-and-purification tag, GFP, and secreted NanoLuc) driven by the endogenous PDGFRα, PLP1 and MBP genes, respectively. Based upon this line, we established a high-throughput drug screening platform and performed a small molecule screen with 2500 bioactive molecules. In addition to a number of previously known pathways, our screening effort identified new pathways whose inhibition enhance oligodendrocyte maturation and myelination. Although further genetic and molecular validation is required, the identified inhibitors could potentially be repurposed to develop remyelination therapy for MS and other demyelinating disorders.
Genomic diversity ofHelicobacter pyloripopulations from different regions of the human stomach
Authors: Wilkinson D.J. , Dickins B. , Robinson K. , Winter J.
Published: January 2022

Individuals infected withHelicobacter pyloriharbour unique and diverse populations of quasispecies, but diversity between and within different regions of the human stomach and the process of bacterial adaptation to each location are not yet well understood.

We applied whole-genome deep sequencing to characterise the within- and between- stomach region genetic diversityof H. pyloripopulations from paired antrum and corpus biopsies of 15 patients, along with single biopsies from one region of 3 patients, by scanning allelic diversity. We combined population deep sequencing with more conventional sequencing of multipleH. pylorisingle colony isolates from individual biopsies to generate a unique dataset. Single colony isolates were used to validate the scanning allelic diversity pipelines.

We detected extensive population allelic diversity within the different regions of each patient’s stomach. Diversity was most commonly found within non-coding, hypothetical, outer membrane, restriction modification system, virulence, lipopolysaccharide biosynthesis, efflux systems and chemotaxis-associated genes. Antrum and corpus populations from the same patient grouped together phylogenetically, indicating that most patients were initially infected with a single strain, which then diversified. Single colonies from the antrum and corpus of the same patients grouped into distinct clades, suggesting mechanisms for within-location adaptation across multipleH. pyloriisolates from different patients. Recombination was observed both within and between different regions of the same stomach.

The comparisons made available by combined sequencing and analysis of isolates and populations enabled comprehensive analysis of the genetic changes associated withH. pyloridiversification and stomach region adaptation.
Metagenomics revealing molecular profiling of microbial community structure and metabolic capacity in Bamucuo, Tibet
Authors: Wei Cai , Sun Dan , Yuan Wenliang , Li Lei , Dai Chaoxu , Chen Zuozhou , Zeng Xiaomin , Wang Shihang , Zhang Yuyang , Jiang Shouwen , Wu Zhichao , Liu Dong , Jiang Linhua , Peng Sihua
Published: January 2022

We performed a survey of the microorganisms in Bamucuo, Tibet, resulting in 160,212 (soil) and 135,994 (water) contigs by shotgun metagenomic methods. We discovered 74 new bacterial species and reconstructed their draft genomes, which were obtained from the 75 reconstructed almost complete metagenomic assembly genomes (MAG) in the soil and water samples. Proteobacteria and Actinobacteria were found to be the most dominant bacterial phyla, while Euryarchaeota was the most dominant archaeal phylum. To our surprise,Pandoravirus salinuswas found in the soil microbial community. We concluded that the microorganisms in Bamucuo fix carbon mainly through the 3-hydroxypropionic bi-cycle pathway.

IMPORTANCE

The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and the microorganisms there play vital ecological roles in the global biogeochemical cycle; however, detailed information on the microbial communities in QTP is still lacking, especially in high altitude areas above 4500 meters. This study, for the first time, characterized the microbial community composition and metabolic capacity in QTP high-altitude areas (with an altitude of 4,555 meters), confirmed that QTP is a huge and valuable resource bank in which more new non-resistant antibiotics and many other bioactive substances could be developed. In addition, the discovery ofPandoravirus salinusin the soil provides important information for further exploring this unique microorganism, and many draft genomes and the genome annotation information obtained in this study have laid the foundation for further in-depth study of the microbial ecology in Qinghai-Tibet Plateau.
Mechanisms linking physical activity with psychiatric symptoms: a protocol for a systematic review
Authors: Nguyen Ho Phuong Thuy , Pham Bich Tram Ha , Tong Thao , Bramer Wichor M , Hofman Amy , Lubans David R , Vernooij Meike W , Rodriguez-Ayllon María
Published: January 2022

Introduction

Persistent psychiatric symptomatology during childhood and adolescence predicts vulnerability to experience mental illness in adulthood. Physical activity is well-known to provide mental health benefits across the lifespan. However, the underlying mechanisms linking physical activity and psychiatric symptoms remain underexplored. In this context, we aim to systematically synthesize evidence focused on the mechanisms through which physical activity might reduce psychiatric symptoms across all ages.

Methods and analysis

With the aid of a biomedical information specialist, we will develop a systematic search strategy based on the predetermined research question in the following electronic databases: MEDLINE, Embase, Web of Science, Cochrane, and PsycINFO. Two independent reviewers will screen and select studies, extract data, and assess the risk of bias. In case of inability to reach a consensus, a third person will be consulted. We will not apply any language restriction, and we will perform a qualitative synthesis of our findings as we anticipate that studies are scarce and heterogeneous.

Ethics and dissemination

Only data that has already been published will be included. Then, ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at conferences. Additionally, we will communicate our findings to healthcare providers and other sections of society (e.g., through regular channels, including social media).

PROSPERO registration number

CRD42021239440

Strengths and limitations of this study

This protocol has been designed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses for Protocols (PRISMA-P) guidelines and guidelines of the Cochrane Effective Practice and Organisation of Care.

This protocol presents a cautiously designed search strategy, inclusion and exclusion criteria, and timespan and age-range coverage.

A possible limitation is that included studies might be heterogeneous in the study design, data collection methods, and data analysis which might limit the ability to synthesize the results using a meta-analysis.

The value of this systematic review depends on the quality and availability of the evidence on the topic.
Discovery and characterization of the first known biological lanthanide chelator
Authors: Zytnick Alexa M. , Gutenthaler-Tietze Sophie M. , Aron Allegra T. , Reitz Zachary L. , Phi Manh Tri , Good Nathan M. , Petras Daniel , Daumann Lena J. , Martinez-Gomez N. Cecilia
Published: January 2022

Many bacteria secrete metallophores, low-molecular weight organic compounds that bind ions with high selectivity and affinity, in order to access essential metals from the environment.1Previous work has elucidated the structures and biosynthetic machinery of metallophores specific for iron, zinc, nickel, molybdenum, and copper.1No lanthanide-specific metallophore has been discovered despite the knowledge that lanthanide metals (Ln) have been revealed to be essential cofactors for certain alcohol dehydrogenases across a diverse range of phyla.2Here, we report the biosynthetic machinery, the structure, and the physiological relevance of the first known lanthanophore, methylolanthanin. The structure of methylolanthanin exhibits a unique 4-hydroxybenzoate moiety which has not previously been described in other metallophores. We find that production of methylolanthanin is required for normal levels of Ln accumulation in the methylotrophic bacteriumMethylobacterium extorquensAM1, while overexpression of the molecule greatly increases bioaccumulation. Our results provide a clearer understanding of how Ln-utilizing bacteria sense, scavenge, and store Ln; essential processes in the environment where Ln are poorly bioavailable. Beyond Ln, we anticipate our study to be a starting point for understanding how organisms acquire otherf-block metals, the actinides.3More broadly, the discovery of a lanthanophore opens doors for study of how biosynthetic gene clusters are repurposed for new functions, how metallophores acquire their metal specificity, and the complex relationship between metal homeostasis and fitness.
HuR-dependent expression of Wisp1 is necessary for TGFβ-induced cardiac myofibroblast activity
Authors: Green Lisa C , Slone Samuel , Anthony Sarah R , Aube Jeffrey , Wu Xiaoqing , Xu Liang , Kanisicak Onur , Tranter Michael
Published: January 2022

Cardiac fibrosis is regulated by the activation and phenotypic switching of quiescent cardiac fibroblasts to active myofibroblasts, which have extracellular matrix (ECM) remodeling and contractile functions which play a central role in cardiac remodeling in response to injury. Here, we show that expression and activity of the RNA binding protein HuR is increased in cardiac fibroblasts upon transformation to an active myofibroblast. Pharmacological inhibition of HuR significantly blunts the TGFβ-dependent increase in ECM remodeling genes, total collagen secretion, in vitro scratch closure, and collagen gel contraction in isolated primary cardiac fibroblasts, suggesting a suppression of TGFβ-induced myofibroblast activation upon HuR inhibition. To delineate HuR-dependent mechanisms, we used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify eleven mRNA transcripts that showed enriched HuR binding following TGFβ treatment as well as significant co-expression correlation with HuR, αSMA, and periostin using single-cell RNA-sequencing from ischemic-zone isolated fibroblasts. Of these, Wnt1-inducible signaling pathway protein-1 (Wisp1; Ccn4), was the most significantly associated with HuR expression in fibroblasts. Accordingly, we found Wisp1 expression to be increased in cardiac fibroblasts isolated from the ischemic-zone of mouse hearts following ischemia/reperfusion, and confirmed Wisp1 expression to be HuR-dependent in isolated fibroblasts. Finally, addition of exogenous recombinant Wisp1 is able to partially rescue myofibroblast contractile function following HuR inhibition, demonstrating that HuR-dependent Wisp1 expression plays a functional role in HuR-dependent MF activity downstream of TGFβ. In conclusion, HuR activity is necessary for the functional activation of primary cardiac fibroblasts in response to TGFβ, in part through post-transcriptional regulation of Wisp1.

HIGHLIGHTS

The RNA binding protein HuR is highly expressed in cardiac fibroblasts and its expression strongly correlates with markers of active myofibroblasts

HuR inhibition reduces migration, contraction, and ECM production activity of cardiac fibroblasts

Expression of the secreted matricellular protein, Wisp1, is increased in a HuR-dependent manner following TGFβ treatment

Recombinant Wisp1 rescues myofibroblast contractile function following HuR inhibition

HuR-dependent expression of Wisp1 is necessary for myofibroblast activation
Foreign competition and corporate social responsibility: the role of the firm–government relationships
Authors: Meng Shuang , Sima Yueling
Published: January 2022

Purpose

This study aims to investigate how and why corporate social responsibility (CSR) among domestic firms in emerging countries is affected by foreign competition.

Design/methodology/approach

The paper combines the resource-based view with the institution-based view to explain how different levels of firm–government relationships prompt firms to enact CSR when facing foreign competition. First, this paper examines how domestic firms engage in CSR in the presence of foreign competition, followed by the consideration of how different firm–government relationships affect CSR strategies for firms faced with foreign competition. Using a database of 1,665 publicly listed Chinese firms between 2011 and 2017, this paper tests four hypotheses regarding CSR behaviors, foreign competition and firm–government relationships, and the findings of this paper generally support all four hypotheses.

Findings

This study contributes to the literature by demonstrating that domestic firms in China respond to foreign competition by increased engagement in CSR, and this positive relationship is heterogeneous among different firm–government relationships. CSR is attenuated by state ownership but enhanced by high industry competition and high regional marketization.

Practical implications

The findings of this research have implications for managers regarding the integration of internal and external resources to enhance CSR as a nonmarket strategy to help maintain firms’ competitive advantages. For the government, policymakers should establish and maintain a fair and market-oriented environment that encourages firms to increase CSR engagement.

Originality/value

The paper contributes to the literature exploring the mechanisms that motivate firms’ pursuit of CSR as a nonmarket strategy under the impact of intensified foreign competition.
Mediation effect of product diversification on the relationship between top management team heterogeneity and firm value in China
Authors: Shen Ning , Zhuo Zhiyi
Published: January 2022

Purpose

Based on upper echelons (UE) theory, the purpose of this study is to investigate a conceptualized moderated mediation model for examining the effects of top management team (TMT) heterogeneity and firm value in China through the mediating effect of product diversification, the moderating effect of ownership type between TMT heterogeneity and product diversification and the moderating effect of executive shareholding between product diversification and firm value.

Design/methodology/approach

Unbalanced panel data were collected over 5 years with a total of 6,597 observations, organized through the WIND (Wind Economic Database) and CSMAR (China Stock Market and Accounting Research) Database. The hypotheses were tested using structural equation modeling and analyzed with stata15.0 software.

Findings

The results indicated that product diversification plays a mediating role between TMT heterogeneity and firm value. In China, TMT heterogeneity of non–state-owned enterprises plays a more significant role in promoting product diversification than that of state-owned enterprises; executive shareholding strengthens the relationship between product diversification and firm value.

Research limitations/implications

The characteristic dimension of TMT is seen as a relatively static factor, and it is worth looking at whether a more dynamic system of evaluation and measurement can be established.

Originality/value

This study enriches theoretical research on TMT and contributes to UE theory in several ways. First, we studied the mediation effect of product diversification between TMT heterogeneity and firm value. This extends research on UE theory to possible process variables. Second, considering the influence of the unique institutional environment in China on corporate strategic decisions, the study investigates state-owned and non–state-owned enterprises. Specifically, it looks at the influence of ownership type as a moderating variable between TMT heterogeneity and product diversification. Third, the paper discusses the moderating effect of executive shareholding on the product diversification–firm value relationship. The research contributes to agency theory and expands research on different economic systems by implementing agency theory.
Mitigation of contractual breaches in international construction joint ventures under conditions of absent legal recourse: case studies from Iran
Authors: Mirzaee Ali Mohammad , Hosseini M. Reza , Martek Igor , Rahnamayiezekavat Payam , Arashpour Mehrdad
Published: January 2022

Purpose

Legal remedies are incorporated into international construction joint ventures (ICJVs) to mitigate contractual breaches. The effectiveness of remedies is predicated on two conditions; the comprehensiveness of the contract and its enforceability within the jurisdiction of interpretation. Relational-related weaknesses contribute to contracting parties placing a premium on the contract's capacity for mediating the relationship. However, contracts are not always enforceable. This study aims to examine means by which joint venture relational governance can be maintained under conditions of minimal legal recourse.

Design/methodology/approach

A relational contracting (RC) theory was used as the theoretical underpinning of the paper. Data were collected and analyzed following a multiple-case study approach from case projects in which ICJVs' was used.

Findings

The findings reveal (1) 17 relational and contractual governance problems; the main six being contractual flexibility, contractual joint venture system, contract reviewing, project conflict, national culture and leader–follower transgressions; (2) relational and contractual governance problems are managed differently, depending on financing sources and partners' national culture; and (3) that a developed RC-based framework comprising four stages is able to facilitate relational and contractual governance in ICJVs.

Originality/value

This study is novel in providing a guided approach to developing non-legal remedies for the mitigation of contractual breaches in ICJVs, grounded in theory and contextualized for the construction sector.