bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of Mutation in ATP7B gene and its correlation with clinical phenotype and radiological features in Wilson Disease patients
Authors: Chaudhuri Jasodhara , Biswas Samar , Gangopadhyay Goutam , Biswas Tamoghna , Datta Jyotishka , Biswas Atanu , Datta Amlan K , Mukherjee Adreesh , Datta Atanu K , Hazra Avijit
Published: January 2021

Introduction

Wilson Disease (WD) is an autosomal recessive disease caused by mutations in the ATP7B gene. Clinical manifestations of WD are variable. Identification of prevalent mutations in a given population is necessary to provide mutation-based molecular diagnosis. Previous studies have detected common mutations in this part of the world and our study aimed to correlate genotype with clinical and radiological features.

Methods

A descriptive cross-sectional observational study was conducted over a period of two years in a tertiary care hospital and neurology referral unit of Kolkata, India. All WD patients within the study period and meeting the inclusion criteria were included. Demographic data collection, clinical examination and relevant laboratory investigations were done. Magnetic resonance imaging of brain and cognitive assessment by Mini Mental Score Exam (MMSE) were also performed. Blood was collected for genetic analyses. PCR-Sanger sequencing of exons 2,4,6,8,10,14,16,18 of ATP7B gene was done based on previous reports of mutation hotspots of ATP7B gene for WD in Eastern India. Genotype phenotype correlation was attempted using two supervised machine learning methods, viz. logistic regression with an elastic-net penalty and the random forest.

Results

Of 52 WD patients were included in the study, 57.7% were males. The mean age at diagnosis was 13.96 years. Majority (61.8%) of the patients had dystonia on presentation, followed by dysarthria (41.2%), tremor (17.6%) and ataxia (11.8%). The mean MMSE and Frontal Assessment Battery score were 23.74 and 10.63 respectively and both were lower than the normal baseline values.Out of the total cohort of 52 patients,15(28.8%) harbored previously reported common mutations from this part of the country. Of the 15, 12 had the same mutation of c.813C>A(p.cys271Ter).The presence of common mutationswas associated with several distinct clinical phenotypes in the mathematical models but larger sample sizes are needed to corroborate the correlation.

Conclusions

WD patients in eastern India have significant genotypic and phenotypic diversity. Further studies with larger samples and screening of remaining exons are warranted.
Quantitative Analysis of Drug Efficacy onC. elegansModels for Neuromuscular Diseases
Authors: Sofela Samuel , Sahloul Sarah , Song Yong-Ak
Published: January 2021

Caenorhabditis eleganshas emerged as a powerful model organism for drug screening due to its cellular simplicity, genetic amenability and homology to humans combined with its small size and low cost. Currently, high-throughput drug screening assays are mostly based on image-based phenotyping not exploiting key locomotory parameters of this multicellular model with muscles such as its thrashing force, a critical parameter when screening drugs for muscle-related diseases. In this study, we demonstrated the use of a micropillar-based force assay chip in combination with an imaging assay to evaluate the efficacy of various drugs currently used in treatment of neuromuscular diseases. Using this two-dimensional approach, we showed that the force assay was generally more sensitive in measuring efficacy of drug treatment in Duchenne Muscular Dystrophy and Parkinson’s Disease mutant worms as well as partly in Amyotrophic Lateral Sclerosis model. These results underline the potential of our force assay chip in screening of potential drug candidates for the treatment of neuromuscular diseases when combined with an imaging assay in a two-dimensional analysis approach.
Laterally biased diffusion of males of the water fleaDaphnia magna
Authors: Toyota Kenji , Yasugi Masaki , Tatarazako Norihisa , Iguchi Taisen , Watanabe Eiji
Published: January 2021

The water fleaDaphnia magnais a representative example of zooplankton living in freshwater environments. They primarily propagate via asexual reproduction under normal and healthy environmental conditions. Environmental stimuli that signal a shift to disadvantageous conditions induceD. magnato change their mode of reproduction from asexual to sexual reproduction. During the sexual reproduction phase, they produce special tough eggs (resting eggs), which can survive severe environmental conditions. Despite our increased understanding of their mating behaviours, the sex-specific characteristics of swimming behaviours among daphnid species are poorly understood. In this study, we analysed the swimming patterns and dynamics of female and male adultD. magna. First, we found laterally biased diffusion of males in contrast to the homogeneous, nondirectional diffusion of females. Second, computer modelling analysis using a discrete-time Markov chain simulation, in which the frequencies of turning behaviour were evaluated as probability distributions, explained the greater diffusion of males in the horizontal direction. Under the presumption that high diffusion in the horizontal direction increases the probability of encountering a distant mate, these findings led us to hypothesise that maleD. magnaincrease genotype heterogeneity by effectively selecting the probability distributions of certain motion parameters.

Summary statements

We analysed the swimming behaviours of adult water fleaDaphnia magna, and found apparent sexual differences: laterally biased diffusion of males in contrast to the nondirectional diffusion of females.
MMpred: a distance-assisted multimodal conformation sampling for de novo protein structure prediction
Authors: Zhao Kai-Long , Liu Jun , Zhou Xiao-Gen , Su Jian-Zhong , Zhang Yang , Zhang Gui-Jun
Published: January 2021

Motivation

The mathematically optimal solution in computational protein folding simulations does not always correspond to the native structure, due to the imperfection of the energy force fields. There is therefore a need to search for more diverse suboptimal solutions in order to identify the states close to the native. We propose a novel multimodal optimization protocol to improve the conformation sampling efficiency and modeling accuracy of de novo protein structure folding simulations.

Results

A distance-assisted multimodal optimization sampling algorithm, MMpred, is proposed for de novo protein structure prediction. The protocol consists of three stages: The first is a modal exploration stage, in which a structural similarity evaluation model DMscore is designed to control the diversity of conformations, generating a population of diverse structures in different low-energy basins. The second is a modal maintaining stage, where an adaptive clustering algorithm MNDcluster is proposed to divide the populations and merge the modal by adjusting the annealing temperature to locate the promising basins. In the last stage of modal exploitation, a greedy search strategy is used to accelerate the convergence of the modal. Distance constraint information is used to construct the conformation scoring model to guide sampling. MMpred is tested on a large set of 320 non-redundant proteins, where MMpred obtains models with TM-score≥0.5 on 268 cases, which is 20.3% higher than that of Rosetta guided with the same set of distance constraints. The results showed that MMpred can help significantly improve the model accuracy of protein assembly simulations through the sampling of multiple promising energy basins with enhanced structural diversity.

Availability

The source code and executable versions are freely available athttps://github.com/iobio-zjut/MMpred.

Contact

zgj@zjut.edu.cnorzhng@umich.eduorsujz@wmu.edu.cn
Indian genetic heritage in Southeast Asian populations
Authors: Changmai Piya , Jaisamut Kitipong , Kampuansai Jatupol , Kutanan Wibhu , Altınışık N. Ezgi , Flegontova Olga , Inta Angkhana , Yüncü Eren , Boonthai Worrawit , Pamjav Horolma , Reich David , Flegontov Pavel
Published: January 2021

The great ethnolinguistic diversity found today in mainland Southeast Asia (MSEA) reflects multiple migration waves of people in the past. Deeply divergent East Eurasian hunter-gatherers were the first anatomically modern human population known to migrate to the region. Agriculturalists from South China migrated to the region and admixed with the local hunter-gatherers during the Neolithic period. During the Bronze and Iron Ages, the genetic makeup of people in MSEA changed again, indicating an additional influx of populations from South China. Maritime trading between MSEA and India was established at the latest 300 BCE, and the formation of early states in Southeast Asia during the first millennium CE was strongly influenced by Indian culture, and this cultural influence is still prominent today. Several ancient Indian-influenced states were located in present-day Thailand, and various populations in the country are likely to be descendants of people from those states. To systematically explore Indian genetic heritage in MSEA, we generated genome-wide SNP data (the HumanOrigins array) for 119 present-day individuals belonging to 10 ethnic groups from Thailand and co-analyzed them with published data from MSEA using the PCA, ADMIXTURE,f3-statistics, qpAdm, and qpGraph methods. We found South Asian low-level admixture in various MSEA populations which are probably descendants of people from the ancient Indian-influenced states, but failed to find a South Asian genetic component in present-day hunter-gatherer groups and relatively isolated groups from highlands in Northern Thailand. Our results also support close genetic affinity between Kra-Dai-speaking (also known as Tai-Kadai) and Austronesian-speaking populations, which fits a linguistic hypothesis suggesting cladality of the two language families.

Author Summary

Mainland Southeast Asia is a region with great ethnolinguistic diversity and complex population history. We studied genetic population history of present-day mainland Southeast Asian populations using genome-wide SNP data (the HumanOrigins array). We generated new data for 10 present-day ethnic groups from Thailand, which we further combined with published data from mainland and island Southeast Asians and worldwide populations. We revealed South Asian genetic admixture in various mainland Southeast Asian ethnic groups which are highly influenced by Indian culture, but failed to find it in groups who remained culturally isolated until recently. Our finding suggests that a massive migration of Indian people in the past was responsible for the spread of Indian culture in mainland Southeast Asia. We also found support for a close genetic affinity between Kra-Dai- and Austronesianspeaking populations, which fits a linguistic hypothesis suggesting cladality of the two language families.
Asymmetric Binomial Statistics Explains Organelle Partitioning Variance in Cancer Cell Proliferation
Authors: Peruzzi Giovanna , Miotto Mattia , Maggio Roberta , Ruocco Giancarlo , Gosti Giorgio
Published: January 2021

Asymmetric inheritance of organelle and cellular compounds between daughter cells impacts on the phenotypic variability and was found to be a hallmark for differentiation and rejuvenation in stem-like cells as much as a mechanism for enhancing resistance in bacteria populations. Whether the same processes take place in the context of cancer cell lines is still poorly investigated. Here, we present a method that allows the measurement of asymmetric organelle partitioning, and we use it to simultaneously measure the partitioning of three kinds of cellular elements, i.e. cytoplasm, membrane, and mitochondria in a proliferating population of human Jurkat T-cells. For this porpoise, we use multiple live cell markers which permit us both to follow the partitioning process for multiple generations and to investigate the correlations between the partitioning of different cellular constituents. Assuming a minimal model of asymmetric partitioning where cell sub-components are divided according to a biased binomial statistics, we derived exact analytical relationships for the average fluorescence intensity and its fluctuations as a function of the generation, obtaining an excellent agreement with the experimental measurements.

We found that although cell cytoplasm is divided symmetrically, mitochondria and membrane lipids are asymmetrically distributed between the two daughter cells and present a stable positive correlation with cytoplasm apportioning, which is incompatible with an independent division mechanism. Therefore, our findings show that asymmetric segregation mechanisms can also arise in cancer cell populations, and that, in this case, membrane lipids and mitochondria do not respectively segregate independently from the cytoplasm. This helps us understand the high phenotypic variability reported in these cancer cell lines. In perspective, this could be particularly relevant in the case of tumor micro-environment diversity, where comprehension of the non-genetic cell heterogeneity could pave the way to novel and more targeted therapies. Moreover, the developed experimental and theoretical apparatus can be easily generalized to different cell kinds and different cell sub-components providing a powerful tool for understanding partitioning-driven heterogeneity.
A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus
Authors: Rutherford Holly A. , Clarke Amy , Chambers Emily V. , Petts Jessica J. , Carson Euan G. , Isles Hannah M. , Duque-Jaramillo Alejandra , Renshaw Stephen A , Levraud Jean-Pierre , Hamilton Noémie
Published: January 2021

Endogenous retroviruses (ERVs) are fossils left in our genome from retrovirus infections of the past. Their sequences are part of every vertebrate genome and their random integrations are thought to have contributed to evolution. Although ERVs are mainly kept silenced by the host genome, they are found activated in multiple disease states such as auto-inflammatory disorders and neurological diseases. What makes defining their role in health and diseases challenging is the numerous copies in mammalian genomes and the lack of tools to study them. In this study, we identified 8 copies of the zebrafish endogenous retrovirus (zferv). We created and characterised the firstin vivoERV reporter line in any species. Using a combination of live imaging, flow cytometry and single cell RNA sequencing, we mappedzfervexpression to early T cells and neurons. Thus, this new tool identified tissues expressing ERV in zebrafish, highlighting a potential role of ERV during brain development and strengthening the hypothesis that ERV play a role in immunity and neurological diseases. This transgenic line is therefore a suitable tool to study the function of ERV in health and diseases.
Slow oscillation-spindle coupling strength predicts real-life gross-motor learning in adolescents and adults
Authors: Hahn Michael A. , Bothe Kathrin , Heib Dominik P. J. , Schabus Manuel , Helfrich Randolph F. , Hoedlmoser Kerstin
Published: January 2021

Previously, we demonstrated that precise temporal coordination between slow oscillations (SO) and sleep spindles indexes declarative memory network development (Hahn et al., 2020). However, it is unclear whether these findings in the declarative memory domain also apply in the motor memory domain. Here, we compared adolescents and adults learning juggling, a real-life gross-motor task. We found that improved task proficiency after sleep lead to an attenuation of the learning curve, suggesting a dynamic juggling learning process. We employed individualized cross-frequency coupling analyses to reduce inter and intra-group variability of oscillatory features. Advancing our previous findings, we identified a more precise SO-spindle coupling in adults compared to adolescents. Importantly, coupling precision over motor areas predicted overnight changes in task proficiency and learning curve, indicating that SO-spindle coupling is sensitive to the dynamic motor learning process. Our results provide first evidence that regionally specific precisely coupled sleep oscillations support gross-motor learning.
Emergence of XDR high-riskPseudomonas aeruginosaST309 in South America: a global comparative genomic analysis
Authors: Fonseca Érica L. , Morgado Sérgio M. , Caldart Raquel V. , Freitas Fernanda , Vicente Ana Carolina P.
Published: January 2021

Pseudomonas aeruginosahas been considered one of the major nosocomial pathogens associated with elevated morbidity and mortality worldwide. Outbreaks have been associated with few high-risk pandemicP. aeruginosalineages, presenting a remarkable antimicrobial resistance. However, the biological features involved with the persistence and spread of such lineages among clinical settings remain to be unravel. This study reports the emergence of the ST309P. aeruginosalineage in South America/Brazil, more precisely, in the Amazon region. Global genomic analyses were performed with the Brazilian strain (PA834) and more 41 complete and draft ST309 genomes publicly available, giving insights about ST309 epidemiology and its resistome and mobilome. Antimicrobial susceptibility tests revealed that the Brazilian PA834 strain presented the XDR phenotype, which was mainly due to intrinsic resistance mechanisms. Genomic analyses revealed a heterogeneous distribution of acquired antimicrobial resistance genes among ST309 genomes, which includedblaVIM-2,blaIMP-15andqnrVC1, all of them associated with class 1 integrons. The mobilome mining showed the presence of Integrative and Conjugative Elements, transposons and genomic islands harbouring a huge arsenal of hevy metal resistance genes. Moreover, these elements also carried genes involved with virulence and adaptive traits. Therefore, the presence of such genes in ST309 lineage possibly accounted for the global spread and persistence of this emerging clone, and for its establishment as a pandemic lineage of clinical importance.
An activating mutation inPdgfrbcauses skeletal stem cell defects with osteopenia and overgrowth in mice
Authors: Kwon Hae Ryong , Kim Jang H. , Woods John P. , Olson Lorin E.
Published: January 2021

Autosomal dominant PDGFRβgain-of-function mutations in mice and humans cause a spectrum of wasting and overgrowth disorders afflicting the skeleton and other connective tissues, but the cellular origin of these disorders remains unknown. We demonstrate that skeletal stem cells (SSCs) isolated from mice with a gain-of-function D849V point mutation in PDGFRβexhibit SSC colony formation defects that parallel the wasting or overgrowth phenotypes of the mice. Single-cell RNA transcriptomics with the SSC colonies demonstrates alterations in osteoblast and chondrocyte precursors caused by PDGFRβD849V. Mutant SSC colonies undergo poor osteogenesisin vitroand mice with PDGFRβD849Vexhibit osteopenia. Increased expression ofSox9and other chondrogenic markers occurs in SSC colonies from mice with PDGFRβD849V. Increased STAT5 phosphorylation and overexpression ofIgf1andSocs2in PDGFRβD849VSSCs suggests that overgrowth in mice involves PDGFRβD849Vactivating the STAT5-IGF1 axis locally in the skeleton. Our study establishes that PDGFRβD849Vcauses osteopenic skeletal phenotypes that are associated with intrinsic changes in SSCs, promoting chondrogenesis over osteogenesis.
miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to affect muscle contractility upon proteotoxic challenge during ageing
Authors: Schiffer Isabelle , Gerisch Birgit , Kawamura Kazuto , Laboy Raymond , Hewitt Jennifer , Denzel Martin S. , Mori Marcelo A. , Vanapalli Siva , Shen Yidong , Symmons Orsolya , Antebi Adam
Published: January 2021

Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also highly plastic, and remodelled in response to stress, growth, neural and metabolic inputs. The evolutionarily conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle biology during development, but whether it plays a role during ageing is unknown. Here we investigated the role ofC. elegansmiR-1 in muscle function in response to proteostatic stress during adulthood.mir-1deletion results in improved mid-life muscle motility, pharyngeal pumping, and organismal longevity under conditions of polyglutamine repeat proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunitvha-13/ATP6VIA as a direct target downregulated via its 3’UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. In summary, our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during ageing.
Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species sweeps and geographical clustering
Authors: García-Bayona Leonor , Coyne Michael J. , Comstock Laurie E.
Published: January 2021

The human gut microbiota is a dense microbial ecosystem with extensive opportunities for bacterial contact-dependent processes such as conjugation and type VI secretion system (T6SS)-dependent antagonism. In the gut Bacteroidales, two distinct genetic architectures of T6SS loci, GA1 and GA2, are contained on integrative and conjugative elements (ICE). Despite intense interest in the T6SSs of the gut Bacteroidales, there is only a superficial understanding of their evolutionary patterns, and of their dissemination among Bacteroidales species in human gut communities. Here, we combine extensive genomic and metagenomic analyses to better understand their ecological and evolutionary dynamics. We identify new genetic subtypes, document extensive intrapersonal transfer of these ICE to Bacteroidales species within human gut microbiomes, and most importantly, reveal frequent population sweeps of these newly armed strains in multiple species within a person. We further show the distribution of each of the distinct T6SSs in human populations and show there is geographical clustering. We reveal that the GA1 T6SS ICE integrates at a minimal recombination site leading to their integration throughout genomes and their frequent interruption of genes, whereas the GA2 T6SS ICE integrate at one of three different tRNA genes. The exclusion of concurrent GA1 and GA2 T6SSs in individual strains is associated with intact T6SS loci and with an ICE-encoded gene. By performing a comprehensive analysis of mobile genetic elements (MGE) in co-resident Bacteroidales species in numerous human gut communities, we identify 177 MGE that sweep through multiple Bacteroidales species within individual gut microbiomes. We further show that only eight MGE demonstrate multi-species population sweeps in as many human gut microbiomes as the GA1 and GA2 ICE. These data underscore the ubiquity and rapid dissemination of mobile T6SS loci within Bacteroidales communities and across human populations.
Ketogenesis Impact on Liver Metabolism Revealed by Proteomics of Lysine β-hydroxybutyrylation
Authors: Koronowski Kevin B. , Greco Carolina M. , Huang He , Kim Jin-Kwang , Fribourgh Jennifer L. , Crosby Priya , Partch Carrie L. , Qiao Feng , Zhao Yingming , Sassone-Corsi Paolo
Published: January 2021

Ketone bodies are evolutionarily conserved metabolites that function as energy substrates, signaling molecules and epigenetic regulators. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, which associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Global protein Kbhb is induced in a tissue-specific manner by a variety of interventions that evoke β-OHB. Mass spectrometry analysis of the β-hydroxybutyrylome in mouse liver revealed 891 sites of Kbhb within 267 proteins enriched for fatty acid, amino acid, detoxification and 1-carbon metabolic pathways. Kbhb of S-adenosyl-L-homocysteine hydrolase (AHCY), a rate-limiting enzyme of the methionine cycle, results in inhibition of enzymatic activity. Our results illuminate the role of Kbhb on hepatic metabolism under ketogenic conditions and demonstrate the functional consequence of this modification on a central metabolic enzyme.
BMP-treated human embryonic stem cells transcriptionally resemble amnion cells in the monkey embryo
Authors: Chhabra Sapna , Warmflash Aryeh
Published: January 2021

Human embryonic stem cells (hESCs) possess an immense potential to generate clinically relevant cell types and unveil mechanisms underlying early human development. However, using hESCs for discovery or translation requires accurately identifying differentiated cell types through comparison with their in vivo counterparts. Here, we set out to determine the identity of much debated BMP-treated hESCs by comparing their transcriptome to the recently published single cell transcriptomes of early human embryos in the study Xiang et al 2019. Our analyses reveal several discrepancies in the published human embryo dataset, including misclassification of putative amnion, intermediate and inner cell mass cells. These misclassifications primarily resulted from similarities in pseudogene expression, highlighting the need to carefully consider gene lists when making comparisons between cell types. In the absence of a relevant human dataset, we utilized the recently published single cell transcriptome of the early post implantation monkey embryo to discern the identity of BMP-treated hESCs. Our results suggest that BMP-treated hESCs are transcriptionally more similar to amnion cells than trophectoderm cells in the monkey embryo. Together with prior studies, this result indicates that hESCs possess a unique ability to form mature trophectoderm subtypes via an amnion-like transcriptional state.
Simulation of sugar kelp (Saccharina latissima) breeding guided by practices to prioritize accelerated research gains
Authors: Huang Mao , Robbins Kelly R , Li Yaoguang , Umanzor Schery , Marty-Rivera Michael , Bailey David , Yarish Charles , Lindell Scott , Jannink Jean-Luc
Published: January 2021

The domestication process of sugar kelp in the Northeast U.S. was initiated by selective breeding two years ago. In this study, we will demonstrate how obstacles for accelerated genetic gain can be assessed using simulation approaches that inform resource allocation decisions in our research. Thus far, we have used 140 wild sporophytes (SPs) that were sampled from the northern Gulf of Maine (GOM) to southern New England (SNE). From these SPs, we sampled gametophytes (GPs) and made and evaluated over 600 progeny SPs from crosses among the GPs. The biphasic life cycle of kelp gives a great advantage in selective breeding as we can potentially select both on the SPs and GPs. However, several obstacles exist, such as the amount of time it takes to complete a breeding cycle, the number of GPs that can be maintained in the lab, and whether positive selection can be conducted on farm tested SPs. Using the GOM population characteristics for heritability and effective population size, we simulated a founder population of 1000 individuals and evaluated the impact of overcoming these obstacles on genetic gain. Our results showed that key factors to improve current genetic gain rely mainly on our ability to induce reproduction of the best farm-tested SPs, and to accelerate the clonal vegetative growth of released GPs so that enough GP biomass is ready for making crosses by the next growing season. Overcoming these challenges could improve rates of genetic gain more than two-fold. Future research should focus on conditions favorable for inducing spring and early summer reproduction, and increasing the amount of GP tissue available in time to make fall crosses.
CloudBrain: Online neural computation in the cloud
Authors: Larsen Leon Bonde , Karnøe Stagsted Rasmus , Strohmer Beck , Christensen Anders Lyhne
Published: January 2021

Neuromorphic computing currently relies heavily on complicated hardware design to implement asynchronous, parallel and very large-scale brain simulations. This dependency slows down the migration of biological insights into technology. It typically takes several years from idea to finished hardware and once developed the hardware is not broadly available to the community. In this contribution, we present the CloudBrain research platform, an alternative based on modern cloud computing and event stream processing technology. Typical neuromorphic design goals, such as small form factor and low power consumption, are traded for 1) no constraints on the model elements, 2) access to all events and parameters during and after the simulation, 3) online reconfiguration of the network, and 4) real-time simulation. We explain principles for how neuron, synapse and network models can be implemented and we demonstrate that our implementation can be used to control a physical robot in real-time. CloudBrain is open source and can run on commodity hardware or in the cloud, thus providing the community a new platform with a different set of features supporting research into, for example, neuron models, structural plasticity and three-factor learning.
Mechanisms of far-red light-mediated dampening of defense againstBotrytis cinereain tomato leaves
Authors: Courbier Sarah , Snoek Basten L. , Kajala Kaisa , Van Wees Saskia C.M. , Pierik Ronald
Published: January 2021

Plants detect neighboring competitors through a decrease in the ratio between red and far-red light (R:FR). This decreased R:FR is perceived by phytochrome photoreceptors and triggers shade avoidance responses such as shoot elongation and upward leaf movement (hyponasty). In addition to promoting elongation growth, low R:FR perception enhances plant susceptibility to pathogens: the growth-defense trade-off. Although increased susceptibility in low R:FR has been studied for over a decade, the associated timing of molecular events is still unknown. Here, we studied the chronology of FR-induced susceptibility events in tomato plants pre-exposed to either white light (WL) or WL supplemented with FR light (WL+FR) prior to inoculation with the necrotrophic fungusBotrytis cinerea(B.c.). We monitored the leaf transcriptional changes over a 30-hr time course upon infection and followed up with functional studies to identify mechanisms. We found that FR-induced susceptibility in tomato is linked to a general dampening ofB.c.-responsive gene expression, and a delay in both pathogen recognition and jasmonic acid-mediated defense gene expression. In addition, we found that the supplemental FR-induced ethylene emissions affect plant immune responses under WL+FR conditions. This study increases our understanding of the growth-immunity trade-off, while simultaneously providing leads to improve tomato resistance against pathogens in dense cropping systems.

One-sentence summary

Low Red:Far-red ratio enhances tomato susceptibility towards the necrotrophic fungusBotrytis cinereavia delayed early pathogen detection and dampening of jasmonic acid-mediated defense activation.
A structural basis for inhibition of the complement initiator protease C1r by Lyme disease spirochetes
Authors: Garrigues Ryan J. , Powell Pierce Alexandra D. , Hammel Michal , Skare Jon T. , Garcia Brandon L.
Published: January 2021

Complement evasion is a hallmark of extracellular microbial pathogens such asBorreliella burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed co-crystallography and size exclusion chromatography-coupled small angle x-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. The studies reported here, for the first time, provide a structural basis for classical pathway-specific inhibition by a human pathogen.
One-dimensional ledges and migration mechanism of incoherent interphase boundaries
Authors: Huang Yunhao , Wang Jincheng , Wang Zhijun , Li Junjie
Published: January 2021

Since the edge-to-edge matching relationship of close-packed planes on an incoherent interphase boundary was found, the one-dimensional ledge migration mechanism has been put forward. However, owing to the lack of direct experimental evidence, the existence of the one-dimensional ledge is still questioned and it is thus usually treated as just an assumption. In this study, focusing on the existence of one-dimensional ledges and the migration mechanism of incoherent interphase boundaries, an atomic scale investigation on the migration of incoherent interphase boundaries in a body- to face-centered cubic transformation has been carried out using the phase-field crystal model. Simulation results demonstrated the presence of one-dimensional ledges on incoherent interphase boundaries, but only on those boundaries with high atomic densities. The simulation results further showed that the interphase boundaries with one-dimensional ledges migrate as a result of the nucleation and extension of the one-dimensional ledge, similar to the mechanism for two-dimensional ledges; meanwhile the interphase boundaries without one-dimensional ledges migrate according to a continuous mechanism by random atomic jumping. Because it is difficult for one-dimensional ledges to nucleate under low driving forces, interphase boundary migration based on the one-dimensional ledge mechanism is slower than that based on the continuous mechanism. This study reveals the structures and mechanisms of complex transitions of incoherent interphase boundaries and can aid a deeper understanding of solid phase transformations.
Honeycomb molecular network based upon a hydrate of 4,6-dichlororesorcinol and the photoproduct rtct-tetrakis(pyridin-4-yl)cyclobutane
Authors: Santana Carlos L. , Battle Jessica D. , Unruh Daniel K. , Groeneman Ryan H.
Published: January 2021

The formation of a self-interpenetrated honeycomb molecular network based upon 4,6-dichlororesorcinol (4,6-diCl res), a water molecule, and the photoproduct rtct-tetrakis(pyridin-4-yl)cyclobutane (
rtct

-TPCB) is reported. Interestingly, only three of the four pyridine rings on the central cyclobutane ring are found to engage in O—H...N hydrogen bonds with either the 4,6-diCl res or an included water molecule, resulting in a three-connected net. Notably, the solid (4,6-diCl res)·(
rtct

-TPCB)·(H2O), C6H4Cl2O2·C24H20N4·H2O, contains channels that run along the crystallographic b axis, which are found to be interpenetrated. Although
rtct

-TPCB has been employed as a bridging ligand in the formation of numerous metal–organic materials, surprisingly neither the single-component X-ray structure nor any multi-component molecular solids based upon this stereoisomer have been reported previously. Lastly, the single-crystal X-ray structure of the photoproduct
rtct

-TPCB is also reported.
Rapid Identification of Water‐Conducting Fractures Using a Trace Methane Gas Measurement
Authors: Niwa Ph.D Masakazu , Amano Ph.D Kenji , Takeuchi Ph.D Ryuji , Shimada Ph.D Koji
Published: January 2021

Identification of water‐conducting fractures is important for the safety assessment of underground projects in crystalline rocks at geological disposal sites. We applied a portable methane gas analyzer by wavelength‐scanned cavity ring‐down spectroscopy to detect the water‐conducting fractures in the underground tunnel of the Mizunami Underground Research Laboratory, central Japan. The tunnel is excavated in granite with CH4‐rich groundwater. Two approaches were taken to obtain the profile of CH4 concentration along the gallery walls: (1) “Scan by walking” at the speed of 0.5 m/s and (2) monitoring for 30 s at 0.5 or 1 m intervals. In the Scan by walking approach, the peaks of the CH4 concentration corresponded well with the occurrence of high water flow rate fractures. Thus, this method is useful for rapid identification of major water‐conducting fractures. Monitoring at constant intervals takes more time than the Scan by walking approach; however, this method can largely detect occurrences of fractures with low fluid fluxes.
Exploring the effects of for‐profit and nonprofit size congruency: An exchange perspective on cause‐related marketing
Authors: Hamby Anne , Jones Niusha , Yu Guohong
Published: January 2021

Prior research on cause‐related marketing (CM) shows that congruencies between for‐profit and nonprofit organizational missions and target markets affect consumers' perceptions of the partnership fit, and their subsequent response to CM promotions. The current work explores how congruencies between for‐profit and nonprofit sizes influence consumers' perceptions of the partnership fit, and subsequently, their attitudes toward CM efforts. Study 1 shows that consumers perceive a low degree of organizational partnership fit between a small for‐profit and large nonprofit (relative to other partnership configurations). Study 2 shows the nature of donated resources can affect organizational partnership fit perceptions, such that donations of needed goods (vs. money) can improve consumers' perceptions of partnership fit between a small for‐profit and large nonprofit. Study 3 shows that organizational cause congruency and organizational size both independently contribute to perceptions of organizational partnership fit.
Five decades of the Journal of Consumer Affairs: A bibliometric analysis
Authors: Baker H. Kent , Kumar Satish , Pandey Nitesh
Published: January 2021

This study presents a retrospective of the Journal of Consumer Affairs (JCA) using bibliographic analysis between 1967 and 2019. The results indicate that both the number of JCA's publications and citations grew markedly over time. The dominant contributors to the journal are authors affiliated with U.S. institutions. Trends show increasing organizational diversity and collaboration among authors. The journal's central themes are consumer perception, consumer behavior, financial behavior, consumer spending patterns, financial literacy, consumer decision‐making processes, and marketing practices. Statistically significant relationships exist between the following article attributes and citations based on our negative binomial regression analysis. Age has a negative association with citations, but the direction of association turns positive when considering non‐linearity. A positive association exists between the number of authors, references, and U.S. affiliation. A negative relationship exists with article order, non‐academic author, top institution affiliation (FT100), funding, lead article, title length, and conceptual article.
Inhibition of persimmon tannin extract on guinea pig skin pigmentation
Authors: Sun Wanting , Chen Xuanhong , Nan Xijun , Zhang Jun , Dong Leichao , Ji Wei , Sheng Guihua , Zhou Quancheng
Published: January 2021

Background

In daily life, excessive exposure to ultraviolet light can lead to pigmentation.

Aims

This study is to determine the mechanism of persimmon tannin extract in inhibiting pigmentation, to investigate whether the effect of persimmon tannin extract is superior to that of arbutin, and to detect the optimal concentration.

Methods

In this study, the guinea pig pigmentation model was established by ultraviolet B (UVB) irradiation. With arbutin as a positive control, Masson‐Fontana silver staining was used to observe the effects of persimmon tannin extract on melanin distribution in guinea pigs' skin tissue. Then, the tyrosinase activity was measured, and an Enzyme‐linked immunosorbent assay was used to investigate the contents of antioxidant enzymes, inflammatory factors, and signaling pathway inhibitors in guinea pigs' skin tissue.

Results

The results showed that compared with the model group, superoxide dismutase, catalase, glutathione peroxidase, DKK1 content of Wnt/‐catenin signaling pathway inhibitors levels, and inhibitory tyrosinase activity were increased by 24.3%, 33.3%, 59.3%, 36.81%, and 17.16%, respectively. Meanwhile, the interleukin‐6 and interleukin‐8 expression were reduced by approximately 22.2% and 54%. The results also showed that persimmon tannin extract could significantly reduce melanin density. The differences in experimental results were statistically significant (P < .01).

Conclusions

Compared with the arbutin group, the medium‐dose group (persimmon tannin extract of 20%) had a more significant effect on inhibiting pigmentation. Persimmon tannin could serve as a promising agent for preventing skin pigmentation. It is expected to provide ideas for the development of deep‐processed persimmon products related to functional foods and cosmetics.
Nanomedicine: towards innovative solutions in the clinic
Authors: Fadeel B.
Published: January 2021

Click here to view the Review by Sindhwani S and Chan WCW
Effects of dietary cellobiose on the intestinal microbiota and excretion of nitrogen metabolites in healthy adult dogs
Authors: Paßlack Nadine , Kohn Barbara , Vahjen Wilfried , Zentek Jürgen
Published: January 2021

In order to evaluate the potential prebiotic effects of cellobiose, 10 healthy adult research beagle dogs received a complete diet containing 0, 0.5 and 1 g cellobiose/kg bodyweight (BW)/day. At the end of each feeding period, faeces, urine and blood of the dogs were collected. The results demonstrated a significant increase of faecal lactate concentrations, indicating a bacterial fermentation of cellobiose in the canine intestine. Along with this, a dose‐dependent linear increase of the relative abundance of Lactobacillaceae in the faeces of the dogs was observed (p = 0.014). In addition, a dose‐dependent increase (p < 0.05) of Alloprevotella, Bacteroides and Prevotella, and a linear decrease for unidentified Lachnospiraceae (p = 0.011) was observed when cellobiose was added to the diet, although the relative abundance of these genera was low (<1%) among all groups. The faecal pH was not affected by dietary cellobiose. Cellobiose seemed to modulate the excretion of nitrogen metabolites, as lower concentrations of phenol (p = 0.034) and 4‐ethylphenol (p = 0.002) in the plasma of the dogs were measured during the supplementation periods. Urinary phenols and indoles, however, were not affected by the dietary supplementation of cellobiose. In conclusion, cellobiose seems to be fermented by the intestinal microbiota of dogs. Although no effect on the faecal pH was detected, the observed increase of microbial lactate production might lower the pH in the large intestine and consecutively modulate the intestinal absorption of nitrogen metabolites. Also, the observed changes of some bacterial genera might have been mediated by increased intestinal lactate concentrations or a higher relative abundance of lactobacilli. Whether these results could be considered as a prebiotic effect and used as a dietetic strategy in diseased animals to improve gut function or hepatic and renal nitrogen metabolism should be evaluated in future studies.
Evaluation of origanum oil, hydrolysable tannins and tea saponin in mitigating ruminant methane: In vitro and in vivo methods
Authors: Zhang Fangyu , Li Baihao , Ban Zhibin , Liang Hao , Li Lijia , Zhao Wei , Yan Xiaogang
Published: January 2021

The objective of this study was to investigate the effects of origanum oil (ORO), hydrolysable tannins (HYT) and tea saponin (TES) on methane (CH4) emission, rumen fermentation, productive performance and gas exchange in sheep by using in vitro and in vivo methods. The ORO, HYT and TES additive levels were normalized per kg dry matter (DM) in both in vitro and in vivo experiments: ORO‐0, 10, 20 and 40 ml/kg; HYT‐0, 15, 30 and 60 g/kg; and TES‐0, 15, 30 and 60 g/kg, respectively. During in vitro incubation, 40 ml/kg ORO linearly decreased CH4 emission (p < 0.05); 20 and 40 ml/kg ORO cubically decreased carbon dioxide (CO2) production (p < 0.05), and rumen pH was cubically raised with the increasing ORO additive level (p < 0.01). The 60 g/kg HYT cubically decreased CH4 production (p < 0.05). The pH of 60 g/kg HYT was higher than that of 15 and 30 g/kg (p < 0.01); the pH of 20 g/kg TES was higher than that of 5 g/kg (p < 0.05). In the in vivo experiments, 40 ml/kg ORO inhibited dry matter intake (p < 0.01) cubically and reduced average daily gain (ADG) and feed conversion ratio (FCR) cubically (p < 0.05), and 20 or 40 ml/kg ORO linearly decreased CH4 production based on per day or metabolic weight (W0.75) (p < 0.05). Both 30 and 60 g/kg HYT linearly inhibited CH4 emission on the bases of per day and W0.75 (p < 0.05). The 20 g/kg TES improved the apparent digestibility of crude protein (p < 0.05), 10 and 20 g/kg of TES decreased CH4 emission (p < 0.05), and 5 g/kg of TES reduced O2 consumption and CO2 production (p < 0.05). In conclusion, these three plant extracts all showed the abilities on mitigating CH4 emission of sheep with appropriate additive ranges.
Antibiofilm activity of chitosan/epsilon‐poly‐L‐lysine hydrogels in a porcine ex vivo skin wound polymicrobial biofilm model
Authors: Pati Brooke A. , Kurata Wendy E. , Horseman Timothy S. , Pierce Lisa M.
Published: January 2021

As antibiotic resistance continues to increase globally, there is an urgency for novel, non‐antibiotic approaches to control chronic drug‐resistant infections, particularly those associated with polymicrobial biofilm formation in chronic wounds. Also needed are clinically relevant polymicrobial biofilm models that can be utilized to assess the efficacy of innovative therapeutics against mature biofilms. We successfully developed a highly reproducible porcine ex vivo skin wound polymicrobial biofilm model using clinical isolates of multidrug‐resistant Pseudomonas aeruginosa, methicillin‐resistant Staphylococcus aureus, and Candida albicans. This ex vivo biofilm model was then used to assess the antimicrobial and antibiofilm properties of an easily fabricated chitosan hydrogel incorporating the natural antimicrobial peptide epsilon‐poly‐L‐lysine. Antimicrobial activity was evaluated against planktonic cultures in vitro and against mature biofilms ex vivo. The antibiofilm efficiency of the hydrogels was especially pronounced against Pseudomonas aeruginosa, whose counts were reduced by 99.98% after 2 hours in vitro and by 99.94% after treatment for 24 hours when applied to 24 hour ex vivo polymicrobial wound biofilms. The activity of the hydrogels was lower against Staphylococcus aureus and ineffective against Candida albicans. Gram, Hucker‐Twort staining of paraffin sections revealed balanced polymicrobial communities in mature 48 hour untreated biofilms. Treatment of 48 or 72 hour biofilms for 2 or 3 days with hydrogels that were applied within 5 hours after inoculation resulted in an impressive 96% and 97% reduction in biofilm thickness compared to untreated biofilms, respectively (P < .001). Likewise, topical gel treatment for 24 hours reduced biofilm thickness by 84% and 70%, respectively, when applied to mature biofilms at 24 and 48 hours after inoculation (P < .001). Thus, this ex vivo wound biofilm model provides a useful means to assess the efficacy of novel treatments to prevent and eradicate polymicrobial biofilms consisting of multidrug‐resistant Pseudomonas aeruginosa, methicillin‐resistant Staphylococcus aureus, and Candida albicans.