bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Impact of Electrode/Tissue Geometry on Electrical Stimulation in Stereo-EEG
Authors: Shindhelm Alexis C. , Thio Brandon J. , Sinha Saurabh R.
Published: September 2021

Purpose:

Electrical stimulation through depth electrodes is used to map function and seizure onset during stereoelectroencephalography in patients undergoing evaluation for epilepsy surgery. Factors such as electrode design, location, and orientation are expected to impact effects of electrical stimulation.

Methods:

We developed a steady-state finite element model of brain tissue including five layers (skull through white matter) and an implanted electrode to explore the impact of electrode design and placement on the activation of brain tissue by electrical stimulation. We calculated electric potentials, current densities, and volume of tissue activated (Vol

act
) in response to constant current bipolar stimulation. We modeled two depth electrode designs (3.5- and 4.43-mm intercontact spacing) and varied electrode location and orientation.

Results:

The electrode with greater intercontact spacing produced 8% to 23% larger Vol

act
(1% to 16% considering only gray matter). Vertical displacement of the electrodes by half intercontact space increased Vol

act
for upward displacement (6% to 83% for all brain tissue or −5% to 96% gray matter only) and decreased Vol

act
(1% to 16% or 24% to 49% gray matter only) for downward displacement. Rotating the electrode in the tissue by 30° to 60° with respect to the vertical axis increased Vol

act
by 30% to 90% (20%–48% gray matter only).

Conclusions:

Location and orientation of depth electrodes with respect to surrounding brain tissue have a large impact on the amount of tissue activated during electrical stimulation mapping in stereoelectroencephalography. Electrode design has an impact, although modest for commonly used designs. Individualization of stimulation intensity at each location remains critical, especially for avoiding false-negative results.
Disinfection to control African swine fever virus: a UK perspective
Authors: Wales Andrew D. , Davies Robert H.
Published: September 2021

A review of African swine fever (ASF) was conducted, including manifestations of disease, its transmission and environmental persistence of ASF virus. Findings on infectious doses of contemporary highly-pathogenic strains isolated from outbreaks in Eastern Europe were included. Published data on disinfectant susceptibility of ASF virus were then compared with similar findings for selected other infectious agents, principally those used in the UK disinfectant approvals tests relating to relevant Disease Orders for the control of notifiable and zoonotic diseases of livestock. These are: swine vesicular disease virus, foot and mouth disease virus, Newcastle disease virus and

Salmonella enterica

serovar Enteritidis. The comparative data thus obtained, presented in a series of charts, facilitated estimates of efficacy against ASF virus for some UK approved disinfectants when applied at their respective General Orders concentrations. Substantial data gaps were encountered for several disinfectant agents or classes, including peracetic acid, quaternary ammonium compounds and products based on phenols and cresols.
Prototheca bovis, a unicellular achlorophyllous trebouxiophyte green alga in the healthy human intestine
Authors: Jinatham Vasana , Cantoni Diego M. , Brown Ian R. , Vichaslip Thanakrit , Suwannahitatorn Picha , Popluechai Siam , Tsaousis Anastasios D. , Gentekaki Eleni
Published: September 2021

Introduction.
Prototheca species are non-photosynthetic trebouxiophyte algae ubiquitously distributed in nature and can be found in sewage and soil. This microbial eukaryote causes human protothecosis in immunocompromised individuals. Thus, Prototheca presence in the stool of individuals without gastrointestinal symptoms has been reported only rarely.

Hypothesis/Gap statement. There is an absence of detailed characterization of human Prototheca isolates.

Aim. The aim of this study was to perform morphological and molecular characterization of Prototheca isolates obtained from human stool.

Methodology.
Prototheca was isolated from faecal samples of four individuals living in a rural area in Thailand. A combination of bioimaging along with molecular and bioinformatics tools was used to characterize the four strains. The growth rate was tested using four media and three temperature conditions. Phylogenetic analysis using the small subunit ribosomal RNA (SSU rRNA) and cytochrome b (cytb) was also performed.

Results. Static and live microscopy demonstrated the various life stages of Prototheca and its major defining cellular characteristics. An optimized DNA extraction methodology that improves DNA yield is provided. Partial fragments of the SSU rRNA and cytb genes were obtained. Phylogenetic analysis placed all four strains in the clade with Prototheca bovis. More broadly, Prototheca was not monophyletic but split into at least two distinct clades instead.

Conclusion. The results represent the first molecular characterization of Prototheca in Thailand. The study provides insight into transmission dynamics of the organism and potential caveats in estimating the global prevalence of Prototheca. These will spearhead further investigations on Prototheca occurrence in rural areas of both industrialized and developing nations.
Mutations in the gdpP gene are a clinically relevant mechanism for β-lactam resistance in meticillin-resistant Staphylococcus aureus lacking mec determinants
Authors: Sommer Anna , Fuchs Stephan , Layer Franziska , Schaudinn Christoph , Weber Robert E. , Richard Hugues , Erdmann Mareike B. , Laue Michael , Schuster Christopher F. , Werner Guido , Strommenger Birgit
Published: September 2021

In

Staphylococcus aureus

, resistance to β-lactamase stable β-lactam antibiotics is mediated by the penicillinbinding protein 2a, encoded by mecA or by its homologues mecB or mecC. However, a substantial number of meticillin-resistant isolates lack known mec genes and, thus, are called meticillin resistant lacking mec (MRLM). This study aims to identify the genetic mechanisms underlying the MRLM phenotype. A total of 141 MRLM isolates and 142 meticillin-susceptible controls were included in this study. Oxacillin and cefoxitin minimum inhibitory concentrations were determined by broth microdilution and the presence of mec genes was excluded by PCR. Comparative genomics and a genome-wide association study (GWAS) approach were applied to identify genetic polymorphisms associated with the MRLM phenotype. The potential impact of such mutations on the expression of PBP4, as well as on cell morphology and biofilm formation, was investigated. GWAS revealed that mutations in gdpP were significantly associated with the MRLM phenotype. GdpP is a phosphodiesterase enzyme involved in the degradation of the second messenger cyclic-di-AMP in

S. aureus

. A total of 131 MRLM isolates carried truncations, insertions or deletions as well as amino acid substitutions, mainly located in the functional DHH-domain of GdpP. We experimentally verified the contribution of these gdpP mutations to the MRLM phenotype by heterologous complementation experiments. The mutations in gdpP had no effect on transcription levels of pbp4; however, cell sizes of MRLM strains were reduced. The impact on biofilm formation was highly strain dependent. We report mutations in gdpP as a clinically relevant mechanism for β-lactam resistance in MRLM isolates. This observation is of particular clinical relevance, since MRLM are easily misclassified as MSSA (meticillin-susceptible

S. aureus

), which may lead to unnoticed spread of β-lactam-resistant isolates and subsequent treatment failure.
Citation Analysis of the Journal of Bone Metabolism from Korean Citation Index, Web of Science, and Scopus
Authors: Yoon Byung-Ho , Hwang Bo Kwon , Jung Eun-Ae , Kim Deog-Yoon
Published: September 2021

Background: Nine years have passed since the Journal of Bone Metabolism (JBM) was launched as an English journal in 2012; it was finally included in Scopus in January 2019. Therefore, this study aimed to provide evidence of increased international recognition based on journal metrics and reflect on its efforts to be recognized as a top-notch journal.Methods: Databases, such as the Web of Science (WoS), Scopus, Korean Citation Index (KCI), and citation indicators, including the impact factor (IF) and SCImago journal rank (SJR) were reviewed and calculated according to years, and the results were drawn. Furthermore, country-wise contributions and top-cited articles were also investigated.Results: The JBM 2020 IF was 2.17 in the WoS. The 2020 SJR in Scopus was 0.334, with a ranking of 165/219 (75.3%) in the Endocrinology, Diabetes, and Metabolism category. The 2020 KCI was 0.42. Of 263 articles, 260 were citable (98.9%), and of 176 original articles, 15 (8.5%) were supported by research grants. The total citation of JBM has increased from 16 in 2014 to 141 in 2020; however, its KCI remained stationary from 0.29 in 2015 to 0.42 in 2020.Conclusions: Currently, JBM is increasingly cited by international researchers than Korean researchers, indicating that the journal’s content is valued at an international level. Its inclusion in PubMed Central appears to have increased its international relevance; however, publishing English-only articles may hinder its use domestically. Therefore, efforts should be made to increase citation rates and enhance domestic readership.
Specific Bioactive Collagen Peptides in Osteopenia and Osteoporosis: Long-Term Observation in Postmenopausal Women
Authors: Zdzieblik Denise , Oesser Steffen , König Daniel
Published: September 2021

Background: The effects of specific collagen peptides on bone mineral density (BMD) in subjects with osteoporosis or osteopenia have already been investigated in 131 postmenopausal women in a randomized controlled trial. The purpose of this follow-up observation was to determine the longer-term effects of the same specific bioactive collagen peptides after a total intervention time of 4 years.Methods: In this open-label follow-up observation, 31 postmenopausal women with reduced BMD (initial T-score lower than−1 of either the femoral neck or the lumbar spine) completed the follow-up. BMD was measured via dual energy X-ray absorptiometry. Absolute changes in BMD and T-scores in the spine and femoral neck were assessed. The number of fractures was also recorded. All participants received specific bioactive collagen peptides.Results: Supplementation with bioactive collagen peptides during follow-up led to a clinically relevant increase in BMD in the spine. These findings were consistent with the results for the femoral neck.Conclusions: Long-term supplementation with specific bioactive collagen peptides appears to be effective in counteracting losses in BMD. Moreover, significant increases in BMD could contribute to improved bone stability.
Anti-Müllerian Hormone Negatively Regulates Osteoclast Differentiation by Suppressing the Receptor Activator of Nuclear Factor-κB Ligand Pathway
Authors: Kim Jung Ha , Yang Yong Ryoul , Kwon Ki-Sun , Kim Nacksung
Published: September 2021

Background: Multiple members of the transforming growth factor-β (TGF-β) superfamily have well-established roles in bone homeostasis. Anti-Müllerian hormone (AMH) is a member of TGF-β superfamily of glycoproteins that is responsible for the regression of fetal Müllerian ducts and the transcription inhibition of gonadal steroidogenic enzymes. However, the involvement of AMH in bone remodeling is unknown. Therefore, we investigated whether AMH has an effect on bone cells as other TGF-β superfamily members do.Methods: To identify the roles of AMH in bone cells, we administered AMH during osteoblast and osteoclast differentiation, cultured the cells, and then stained the cultured cells with Alizarin red and tartrate-resistant acid phosphatase, respectively. We analyzed the expression of osteoblast- or osteoclast-related genes using real-time polymerase chain reaction and western blot.Results: AMH does not affect bone morphogenetic protein 2-mediated osteoblast differentiation but inhibits receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation. The inhibitory effect of AMH on osteoclast differentiation is mediated by IκB-NF-κB signaling.Conclusions: AMH negatively regulates osteoclast differentiation without affecting osteoblast differentiation.
Temporal irreversibility of neural dynamics as a signature of consciousness
Authors: de la Fuente Laura , Zamberlan Federico , Bocaccio Hernán , Kringelbach Morten , Deco Gustavo , Sanz Perl Yonatan , Tagliazucchi Enzo
Published: September 2021

Even though the fundamental laws of physics are the same when the direction of time is inverted, dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. Inspired by recent developments in stochastic thermodynamics, we implemented a data-driven and model-free deep learning framework to decode the temporal inversion of electrocorticography signals acquired from non-human primates. Brain activity time series recorded during conscious wakefulness could be distinguished from their inverted counterparts with high accuracy, both using frequency and phase information. However, classification accuracy was reduced for data acquired during deep sleep and under ketamine-induced anesthesia; moreover, the predictions obtained from multiple independent neural networks were less consistent for sleep and anesthesia than for conscious wakefulness. Finally, the analysis of feature importance scores highlighted transitions between slow (≈20 Hz) and fast frequencies (> 40 Hz) as the main contributors to the temporal asymmetry observed during conscious wakefulness. Our results show that a preferred temporal direction is simultaneously manifest in the neural activity evoked by conscious mentation and in the phenomenology of the passage of time, establishing common ground to tackle the relationship between brain and subjective experience.
HyperEx: A Tool to Extract Hypervariable Regions from 16S rRNA Sequencing Data
Authors: Ebou Anicet , Koua Dominique , Zeze Adolphe
Published: September 2021

The 16S ribosomal RNA gene is one of the most studied genes in biology. This 16S ribosomal RNA importance is due to its wide application in phylogenetics and taxonomic elucidation of bacteria and archaea. Indeed, 16S ribosomal RNA is present in almost all bacteria and archaea and has, among many other useful characteristics, a low mutation rate. The 16S ribosomal RNA is composed of nine hypervariable regions which are commonly targeted by high throughput sequencing technologies in identification or community studies like metabarcoding studies. Unfortunately, the hypervariable regions do not have the same taxonomic resolution among all bacteria taxa. This requires a preliminaryin silicoanalysis to determine the best hypervariable regions to target in a particular study. Nevertheless, to the best of our knowledge, no automated primer-based open-source tool exists to extract hypervariable regions from complete or near-complete 16S rRNA sequencing data. Here we present HyperEx which efficiently extracts the hypervariable region of interest based on embedded primers or user-given primers. HyperEx implements the Myers algorithm for the exact pairwise sequence alignment. HyperEx is freely available under the MIT license as an operating system independent Rust command-line tool athttps://github.com/Ebedthan/hyperexandhttps://crates.io.
Silencing of hippocampal synaptic transmission impairs spatial reward search on a head-fixed tactile treadmill task
Authors: Jordan Jake T. , Gonçalves J. Tiago
Published: September 2021

Head-fixed linear treadmill tasks have been used to study hippocampal physiology in mice. Although some hippocampal neurons establish place fields along linear treadmills, it is not clear if the hippocampus is required for spatial memory on this task. Using a Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) approach, we found that silencing hippocampal output on rewarded treadmill tasks impaired search for rewards signaled by spatial cues but did not impair search for rewards signaled by local cues, recapitulating findings from other behavior tasks. These findings serve to contextualize data on hippocampal physiology from mice performing this task.
Enhancer-priming in ageing human bone marrow mesenchymal stromal cells contributes to immune traits
Authors: Lai Mang Ching , Ruiz-Velasco Mariana , Arnold Christian , Sigalova Olga , Bunina Daria , Berest Ivan , Ding Ximing , Hennrich Marco L. , Poisa-Beiro Laura , Claringbould Annique , Mathioudaki Anna , Pabst Caroline , Ho Anthony D. , Gavin Anne-Claude , Zaugg Judith B.
Published: September 2021

Bone marrow mesenchymal stromal cells (BMSCs) can differentiate into adipocytes and osteoblasts, and are important regulators of the haematopoietic system. Ageing associates with an increased ratio of bone marrow adipocytes to osteoblasts and immune dysregulation. Here, we carried out an integrative multiomics analysis of ATAC-Seq, RNA-Seq and proteomics data from primary human BMSCs in a healthy cohort age between 20 - 60. We identified age-sensitive elements uniquely affecting each molecular level where transcription is mostly spared, and characterised the underlying biological pathways, revealing the interplay of age-related gene expression mechanism changes spanning multiple gene regulatory layers. Through data integration with enhancer-mediated gene regulatory network analysis, we discovered that enhancers and transcription factors influence cell differentiation potential in the ageing BMSCs. By combining our results with genome-wide association study data, we found that age-specific changes could contribute to common traits related to BMSC-derived tissues such as bone and adipose tissue, and to immune-related traits on a systemic level such as asthma. We demonstrate here that a multiomics approach is crucial for unravelling complex information, providing new insights on how ageing contributes to bone marrow- and immune-related disorders.
Quantifying the Effect of Anti-cancer Compound (Piperlongumine) on Cancer Cells Using Single-Cell Force Spectroscopy
Authors: de Alcântara-Contessoto Nayara Sousa , Cornélio Marinônio Lopes , Kiang Ching-Hwa
Published: September 2021

Natural compounds have shown a great potential in anti-cancer research by tumor growth inhibition and anti-metastatic properties. Piperlongumine (PL) is a natural compound derived from pepper species that has been demonstrated to have anti-cancer effect on HeLa cells. Here we focus on understanding the mechanical properties of HeLa cells under PL treatment, using Atomic Force Microscopy (AFM) based single-cell manipulation technique. We used AFM to pull single HeLa cells and acquired the force-distance curves that presented stepwise patterns. We analyzed the step force (SF) and observed that cells treated with PL exhibit higher force compared to control cells. This SF increase was also observed in experiments performed on substrates of different stiffness. Therefore, analyzing SF, it is possible to investigate the effect of PL on the mechanical properties of the HeLa cells. The understanding of the PL action on HeLa cells’ mechanical properties may help in the development of effective therapeutic drugs against cancers.
The Immunomodulatory Effects of Social Isolation in Mice are Linked to Temperature Control
Authors: Hamilton Alice , Rizzo Raffaella , Brod Samuel , Ono Masahiro , Perretti Mauro , Cooper Dianne , D’Acquisto Fulvio
Published: September 2021

Living in isolation is considered an emerging societal problem that negatively affects the physical wellbeing of its sufferers in ways that we are just starting to appreciate. This study investigates the immunomodulatory effects of social isolation in mice, utilising a two-week program of sole cage occupancy followed by the testing of immune-inflammatory resilience to bacterial sepsis. Our results revealed that mice housed in social isolation showed an increased ability to clear bacterial infection compared to control socially housed animals. These effects were associated with specific changes in whole blood gene expression profile and an increased production of classical pro-inflammatory cytokines. Interestingly, equipping socially isolated mice with artificial nests as a substitute for their natural huddling behaviour reversed the increased resistance to bacterial sepsis. These results further highlight the ability of the immune system to act as a sensor of our living conditions and to respond in a compensatory fashion to external challenges that might threaten the survival of the host.
Experimental evolution of insect resistance to two pesticide classes reveals mechanistic diversity and context-dependent fitness costs
Authors: Birnbaum Stephanie S.L. , Schulz Nora K.E. , Garrett Destane S. , Tate Ann T.
Published: September 2021

Does rapid adaptation to stressors evolve through similar underlying mechanisms among diverse populations, or are there many roads to a similar phenotype? The experimental evolution of pesticide resistance in insects provides a powerful model to study the diverse evolutionary signatures of adaptation and their associated costs. Here, we selected for resistance to two pesticides (organophosphates and pyrethroids) in six field-derived populations of the red flour beetle (Tribolium castaneum). After several generations of selection, we performed transcriptomic analyses and measured survival, development, and fecundity in the presence and absence of pesticides to detect fitness costs of resistance evolution. All pesticide-selected populations exhibited significantly improved survival after pesticide exposure without substantial fitness costs, compared to control populations. Populations that evolved to resist organophosphates had distinct gene expression in the presence and absence of organophosphates, supporting different detoxification mechanisms and cuticular modifications among populations. In contrast, pyrethroid resistant populations demonstrated common differential expression of cytochrome P450 transcripts. Furthermore, some populations evolved similar mechanisms against both pesticides while others showed little overlap in their evolved responses, suggesting variation in potential cross-resistance phenotypes. Overall, between populations, we observed both parallel and divergent patterns in gene expression associated with acquired pesticide resistance, without ubiquitous fitness costs.
Sexual signals persist over deep time: ancient co-option of bioluminescence for courtship displays in cypridinid ostracods
Authors: Ellis Emily A. , Goodheart Jessica A. , Hensley Nicholai M. , González Vanessa L. , Reda Nicholas J. , Rivers Trevor J. , Morin James G. , Torres Elizabeth , Gerrish Gretchen A. , Oakley Todd H.
Published: September 2021

Although the the diversity, beauty, and intricacy of sexually selected courtship displays command the attention of evolutionists, the longevity of these traits in deep time is poorly understood. Population-based theory suggests sexual selection could either lower or raise extinction risk, resulting in high or low persistence of lineages with sexually selected traits. Furthermore, empirical studies that directly estimate longevity of sexually selected traits are uncommon. Sexually selected signals - including bioluminescent courtship - originated multiple times during evolution, allowing empirical study of their longevity after careful phylogenetic and divergence time analyses. Here, we estimate the first transcriptome-based molecular phylogeny and divergence times of Cypridinidae. We report extreme longevity of bioluminescent courtship, a trait important in mate choice and probably under sexual selection. Our relaxed-clock estimates of divergence times coupled with stochastic character mapping show luminous courtship evolved only once in Cypridinidae in a Sub-Tribe we name Luxorina at least 151 Million Years Ago (Ma) from cypridinid ancestors that used bioluminescence only in anti-predator displays, defining a Tribe we name Luminini. This time-calibrated molecular phylogeny of cypridinids will serve as a foundation for integrative and comparative studies on the biochemistry, molecular evolution, courtship, diversification, and ecology of cypridinid bioluminescence. The persistence of luminous courtship for hundreds of millions of years indicates that rates of speciation within the group exceeded extinction risk, allowing for the persistence of a diverse clade of signalling species and that sexual selection did not cause rapid loss of associated traits.
Movement-Dependent Electrical Stimulation for Volitional Strengthening of Cortical Connections in Behaving Monkeys
Authors: Moorjani Samira , Walvekar Sarita , Fetz Eberhard E. , Perlmutter Steve I.
Published: September 2021

Correlated activity of neurons can lead to long-term strengthening or weakening of the connections between them. In addition, the behavioral context, imparted by execution of physical movements or the presence of a reward, can modulate the plasticity induced by Hebbian mechanisms. In the present study, we have combined behavior and induced neuronal correlations to strengthen connections in the motor cortex of adult behaving monkeys. Correlated activity was induced using an electrical-conditioning protocol in which stimuli gated by voluntary movements were used to produce co-activation of neurons at motor-cortical sites involved in those movements. Delivery of movement-dependent stimulation resulted in small increases in the strength of associated cortical connections immediately after conditioning. Remarkably, when paired with further repetition of the movements that gated the conditioning stimuli, there were substantially larger gains in the strength of cortical connections, that occurred in a use-dependent manner, without delivery of additional conditioning stimulation. In the absence of such movements, little change was observed in the strength of motor-cortical connections. Performance of the motor behavior in the absence of conditioning also did not produce any changes in connectivity. Our results show that combining movement-gated stimulation with further natural use of the “conditioned” pathways after stimulation ends can produce use-dependent strengthening of connections in adult primates, highlighting an important role for behavior in cortical plasticity. Our data also provide strong support for combining movement-gated stimulation with use-dependent physical rehabilitation for strengthening connections weakened by a stroke or spinal-cord injury.

Significance Statement

We describe an electrical-conditioning protocol in adult behaving monkeys in which stimuli gated by voluntary movements were used to strengthen connections between motor-cortical neurons involved in those movements. Movement-gated stimulation created a plastic landscape in which repetition of the movements that gated conditioning stimuli produced strengthening of cortical connections, in a use-dependent manner, long after stimulation had ended, a finding that is both novel and unique. In the absence of such behavior, little change was observed in the strength of connections. Similarly, movements alone did not produce any changes in connectivity. Our data highlight a critical role for behavior in plasticity and provide strong support for combining movement-gated stimulation with use-dependent rehabilitation for strengthening connections weakened by injury or disease.
When no answer is better than a wrong answer: a causal perspective on batch effects
Authors: Bridgeford Eric W. , Powell Michael , Kiar Gregory , Noble Stephanie , Chung Jaewon , Panda Sambit , Lawrence Ross , Xu Ting , Milham Michael , Caffo Brian , Vogelstein Joshua T.
Published: September 2021

Batch effects, undesirable sources of variability across multiple experiments, present significant challenges for scientific and clinical discoveries. Batch effects can (i) produce spurious signals and/or (ii) obscure genuine signals, contributing to the ongoing reproducibility crisis. Because batch effects are typically modeled as classical statistical effects, they often cannot differentiate between sources of variability due to confounding biases, which may lead them to erroneously conclude batch effects are present (or not). We formalize batch effects as causal effects, and introduce algorithms leveraging causal machinery, to address these concerns. Simulations illustrate that when non-causal methods provide the wrong answer, our methods either produce more accurate answers or “no answer”, meaning they assert the data are an inadequate to confidently conclude on the presence of a batch effect. Applying our causal methods to 27 neuroimaging datasets yields qualitatively similar results: in situations where it is unclear whether batch effects are present, non-causal methods confidently identify (or fail to identify) batch effects, whereas our causal methods assert that it is unclear whether there are batch effects or not. In instances where batch effects should be discernable, our techniques produce different results from prior art, each of which produce results more qualitatively similar to not applying any batch effect correction to the data at all. This work therefore provides a causal framework for understanding the potential capabilities and limitations of analysis of multi-site data.
Sex Chromosome Heteromorphism and the Fast-X Effect in Poeciliids
Authors: Darolti Iulia , Fong Lydia J. M. , Sandkam Benjamin A. , Metzger David C. H. , Mank Judith E.
Published: September 2021

Accelerated rates of sequence evolution on the X chromosome compared to autosomes, known as Fast-X evolution, have been observed in a range of heteromorphic sex chromosomes. However, it remains unclear how early in the process of sex chromosome differentiation the Fast-X effect becomes detectible. Recently, we uncovered an extreme variation in sex chromosome heteromorphism across Poeciliid fish species. The common guppy,Poecilia reticulata, Endler’s guppy,P. wingei, swamp guppy,P. picta, and para guppy,P. parae, appear to share the same XY system and exhibit a remarkable range of heteromorphism. This sex chromosome system is absent in recent outgroups. We combined analyses of sequence divergence and polymorphism data across Poeciliids to investigate X chromosome evolution as a function of hemizygosity and reveal the causes for Fast-X effects. Consistent with the extent of Y degeneration in each species, we detect higher rates of divergence on the X relative to autosomes, a signal of Fast-X evolution, inP. pictaandP. parae, while no change in the rate of evolution of X-linked relative to autosomal genes inP. reticulata. InP. wingei, the species with intermediate sex chromosome differentiation, we see an increase in the rate of nonsynonymous substitutions on the older stratum of divergence only. We also use our comparative approach to test different models for the origin of the sex chromosomes in this clade. Taken together, our study reveals an important role of hemizygosity in Fast-X and suggests a single, recent origin of the sex chromosome system in this clade.
Single-cell perturbation dissects transcription factor control of progression speed and trajectory choice in early T-cell development
Authors: Zhou Wen , Gao Fan , Romero-Wolf Maile , Jo Suin , Rothenberg Ellen V.
Published: September 2021

In early T-cell development, single cells dynamically shift expression of multiple transcription factors (TFs) during transition from multipotentiality to T-lineage commitment, but the functional roles of many TFs have been obscure. Here, synchronizedin vitrodifferentiation systems, scRNA-seq with batch indexing, and controlled gene-disruption strategies have unraveled single-cell impacts of perturbing individual TFs at two stages in early T-cell development. Single-cell CRISPR perturbation revealed that early-acting TFs Bcl11a, Erg, Spi1 (PU.1), Gata3, and Tcf7 (TCF1) each play individualized roles promoting or retarding T-lineage progression and suppressing alternative trajectories, collectively determining population dynamics and path topologies. Later, during T-lineage commitment, cells prevented from expressing TF Bcl11b ‘realized’ this abnormality not with a developmental block, but by shifting into a divergent path via bZIP and Sox TF activation as well as E protein antagonism, finally exiting the T-lineage trajectory. These TFs thus exert a network of impacts to control progression kinetics, trajectories, and differentiation outcomes of early pro-T cells.
Properties of Photosystem II lacking the PsbJ subunit
Authors: Boussac Alain , Sellés Julien , Hamon Marion , Sugiura Miwa
Published: September 2021

Photosystem II (PSII), the oxygen-evolving enzyme, consists of 17 trans-membrane and 3 extrinsic membrane proteins. Other subunits bind to PSII during assembly, like Psb27, Psb28, Tsl0063. The presence of Psb27 has been proposed (Zabret et al. 2021; Huang et al. 2021; Xiao et al. 2021) to prevent the binding of PsbJ, a single transmembrane α-helix close to the quinone QB binding site. Consequently, a PSII rid of Psb27, Psb28 and Tsl0034 prior to the binding of PsbJ would logically correspond to an assembly intermediate. The present work describes experiments aiming at further characterizing such a ΔPsbJ-PSII, purified from the thermophilic Thermosynechococcus elongatus, by means of MALDI-TOF spectroscopy, Thermoluminescence, EPR spectroscopy and UV-visible time-resolved spectroscopy. In the purified ΔPsbJ-PSII, an active Mn4CaO5 cluster is present in 60-70 % of the centers. In these centers, although the forward electron transfer seems not affected, the Em of the QB/QB- couple increases by ≥ 120 mV thus disfavoring the electron coming back on QA. The increase of the energy gap between QA/QA- and QB/QB- could contribute in a protection against the charge recombination between the donor side and QB-, identified at the origin of photoinhibition under low light (Keren et al. 1997), and possibly during the slow photoactivation process.
Highly specific chimeric DNA-RNA guided genome editing with enhanced CRISPR-Cas12a system
Authors: Kim Hanseop , Lee Wi-jae , Kim Chan Hyoung , Oh Yeounsun , Gwon Lee Wha , Lee Hyomin , Song WooJeung , Hur Junho K. , Lim Kyung-Seob , Jeong Kang Jin , Nam Ki-Hoan , Won Young-Suk , Lee Youngjeon , Kim Young-Hyun , Huh Jae-Won , Jun Bong-Hyun , Lee Dong-Seok , Lee Seung Hwan
Published: September 2021

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a system is composed of a Cas12a effector that acts as a deoxyribonucleic acid (DNA)-cleaving endonuclease and a crispr ribonucleic acid (crRNA) that guides the effector to the target DNA. It is considered a key molecule for inducing target-specific gene editing in various living systems. Here, we improved the efficiency and specificity of the CRISPR-Cas12a system through protein and crRNA engineering. In particular, to optimize the CRISPR-Cas12a system at the molecular level, we used a chimeric DNA-RNA guide chemically similar to crRNA to maximize target sequence specificity. Compared to the wild type (wt)-Cas12a system, when using enhanced Cas12a system (en-Cas12a), the efficiency and target specificity improved on average by 7.41 and 7.60 times respectively. In our study, when the chimeric DNA-RNA guided en-Cas12a effector was used, the gene editing efficiency and accuracy were simultaneously increased. These findings could contribute to highly accurate genome editing, such as human gene therapy, in the near future.
CluSem: Accurate Clustering-based Ensemble Method to Predict Motor Imagery Tasks from Multi-channel EEG Data
Authors: Miah Md. Ochiuddin , Muhammod Rafsanjani , Al Mamun Khondaker Abdullah , Farid Dewan Md. , Kumar Shiu , Sharma Alok , Dehzangi Abdollah
Published: September 2021

Background

The classification of motor imagery electroencephalogram (MI-EEG) is a pivotal task in the biosignal classification process in the brain-computer interface (BCI) applications. Currently, this bio-engineering-based technology is being employed by researchers in various fields to develop cuttingedge applications. The classification of real-time MI-EEG signals is the most challenging task in these applications. The prediction performance of the existing classification methods is still limited due to the high dimensionality and dynamic behaviors of the real-time EEG data.

Proposed Method

To enhance the classification performance of real-time BCI applications, this paper presents a new clustering-based ensemble technique called CluSem to mitigate this problem. We also develop a new brain game called CluGame using this method to evaluate the classification performance of real-time motor imagery movements. In this game, real-time EEG signal classification and prediction tabulation through animated balls are controlled via threads. By playing this game, users can control the movements of the balls via the brain signals of motor imagery movements without using any traditional input devices.

Results

Our results demonstrate that CluSem is able to improve the classification accuracy between 5% and 15% compared to the existing methods on our collected as well as the publicly available EEG datasets. The source codes used to implement CluSem and CluGame are publicly available at https://github.com/MdOchiuddinMiah/MI-BCI_ML.
Pilot identification of the Live-1/Prox-1 expressing lymphatic vessels and lymphatic elements in the unaffected and affected human brain
Authors: Semyachkina-Glushkovskaya O. , Fedosov I. , Navolokin N. , Shirokov A. , Maslyakova G. , Bucharskaya A. , Blokhina I. , Terskov A. , Khorovodov A. , Postnov D. , Kurths J.
Published: September 2021

We report here a pilot identification of the presence of the lumenized Lyve-1/Prox-1-expressing vessels with distinct walls composed of a single endothelial layer in the unaffected brain and with intraventricular hemorrhages. These lymphatic vessels (LVs) have valves and an undulating shape in the distal region that is the classical characteristic of lymphatic precollectors. Furthermore, we identified Lyve-1/Prox-1-expressing lymphatic elements in the enlarged perivascular spaces. These pioneering results might be a revolutionary step in our understanding of anatomy and physiology of the cerebral lymphatics and stimulate a reassessment of basic assumptions in the aetiology of brain diseases associated with lymphatic dysfunction. The discovery of the cerebral LVs is a crucial step in the development of breakthrough technologies of modulations of lymphatic removing of toxins and blood from the brain.

One Sentence Summary

Lyve1/Prox1-expressing lymphatic vessels and elements in the unaffected and affected human brain.
Hippocampal astroglial hypertrophy in mice subjected to early life maternal deprivation
Authors: Nandi Arnab , Virmani Garima , Marathe Swananda
Published: September 2021

Early-life stress (ELS), including chronic deprivation of maternal care, exerts persistent life-long effects on animal physiology and behavior, and is associated with several neurodevelopmental disorders. Long-lasting changes in neuronal plasticity and electrophysiology are documented extensively in the animal models of ELS. However, the role of astroglia in the lasting effects of ELS remains elusive. Astrocytes are intricately involved in the regulation of synaptic physiology and behavior. Moreover, astrocytes play a major role in the innate and adaptive immune responses in the central nervous system (CNS). The role of immune responses and neuroinflammation in the altered brain development and persistent adverse effects of ELS are beginning to be explored. Innate immune response in the CNS is characterized by a phenomenon called astrogliosis, a process in which astrocytes undergo hypertrophy, along with changes in gene expression and function. While the immune activation and neuroinflammatory changes concomitant with ELS, or in juveniles and young adults have been reported, it is unclear whether mice subjected to ELS exhibit astrogliosis-like alterations well into late-adulthood. Here, we subjected mice to maternal separation from postnatal day 2 to day 22 and performed comprehensive morphometric analysis of hippocampal astrocytes during late-adulthood. We found that the astrocytes in the stratum radiatum region of the CA1 hippocampal subfield from maternally separated mice exhibit significant hypertrophy as late as 8 months of age, revealing the crucial changes in astrocytes that manifest long after the cessation of ELS. This study highlights the persistence of neuroinflammatory changes in mice exposed to ELS.
Continuous tracking of gravistimulated roots in a chambered coverslip by confocal microscopy allows first glimpse on mechanoadaptation of cell files during curvature initiation
Authors: Retzer Katarzyna
Published: September 2021

Mechanical responses of individual cells to plant internal and external stimuli modulate organ movement and ensure plant survival as sessile organism in a constantly changing environment. The root is a complex, three-dimensional object, which continuously modifies its growth path. Autonomous and paratonic root movements are both orchestrated by different signaling pathways, whereby auxin modulated directional growth adaptations, including gravitropic response, were already subject of manifold studies. But we still know very little about how cells adapt upon gravitropic stimulus to initiate curvature establishment, which is required to align root tip growth again along the gravitropic vector. This manuscript shows first insights into cell file movements upon gravitropic stimulus of Arabidopsis thaliana roots that initiate curvature establishment. The roots were grown shaded from light and without exogenous sucrose supplementation, both growth conditions that are known to negatively interfere with directed root growth, which allowed a more uniform tracking of root bending by using a confocal microscope with vertical stage.
CROP: A Retromer-PROPPIN complex mediating membrane fission in the endo-lysosomal system
Authors: Courtellemont Thibault , De Leo Maria Giovanna , Gopaldass Navin , Mayer Andreas
Published: September 2021

Endo-lysosomal compartments exchange proteins by fusing, fissioning, and through endosomal transport carriers. Thereby, they sort many plasma membrane receptors and transporters and control cellular signaling and metabolism. How the membrane fission events are catalyzed is poorly understood. Here, we identify the novel CROP complex as a factor acting at this step. CROP joins members of two protein families: the peripheral subunits of retromer, a coat forming endosomal transport carriers, and membrane inserting PROPPINs. Integration into CROP potentiates the membrane fission activity of the PROPPIN Atg18 on synthetic liposomes and confers strong preference for binding PI(3,5)P2, a phosphoinositide required for membrane fission activity. Disrupting CROP blocks fragmentation of lysosome-like yeast vacuoles in vivo. CROP-deficient mammalian endosomes accumulate micrometer-long tubules and fail to export cargo, suggesting that carriers attempt to form but cannot separate from these organelles. PROPPINs compete for retromer binding with the SNX proteins, which recruit retromer to the membrane during the formation of endosomal carriers. Transition from retromer-SNX complexes to retromer-PROPPIN complexes might hence switch retromer activities from cargo capture to membrane fission.
Parallel evolution of phage resistance - virulence trade - offs duringin vitroand nasalPseudomonas aeruginosaphage treatment
Authors: Castledine Meaghan , Padfield Daniel , Sierocinski Pawel , Soria Pascual Jesica , Hughes Adam , Mäkinen Lotta , Friman Ville-Petri , Pirnay Jean-Paul , Merabishvili Maya , De Vos Daniel , Buckling Angus
Published: September 2021

With rising antibiotic resistance, there has been increasing interest in treating pathogenic bacteria with bacteriophages (phage therapy). One limitation of phage therapy is the ease at which bacteria can evolve resistance. Negative effects of resistance may be mitigated when resistance results in reduced bacterial growth and virulence, or when phage coevolve to overcome resistance. Resistance evolution and its consequences are contingent on the bacteria-phage combination and their environmental context, making therapeutic outcomes hard to predict. One solution might be to conduct “in vitroevolutionary simulations” using bacteria-phage combinations from the therapeutic context. Overall, our aim was to investigate parallels betweenin vitroexperiments andin vivodynamics in a human participant. Evolutionary dynamics were similar, with high levels of resistance evolving quickly with limited evidence of phage evolution. Resistant bacteria – evolvedin vitroandin vivo- had lower virulence.In vivo, this was linked to lower growth rates of resistant isolates, whereasin vitrophage resistant isolates evolved greater biofilm production. Population sequencing suggests resistance resulted from selection onde novomutations rather than sorting of existing variants. These results highlight the speed at which phage resistance can evolvein vivo, andin vitroexperiments may give useful insights for clinical evolutionary outcomes.
The transformation of corrosion products on 0Cu2Cr carbon steel in the marine
Authors: Liu Hongyu , Teng Yingxue , Guo Jing , Xiao Qinghe , Wang Miao , Pang QiHang , Li Shengli
Published: September 2021

Purpose

This paper aims to explore the transformation process and transformation mechanism of carbon steel under the marine environment.

Design/methodology/approach

In this paper, the transformation and rust layers corrosion products on 0Cu2Cr carbon steel with different cycles coupon test was investigated and deeply explored by scanning electron microscope, energy dispersive spectrometer, X-ray diffraction.

Findings

The results showed that the thickness of rust layers grew from 71.83 µm to 533.7 µm with increasing duration of corrosion. The initial corrosion product was γ-FeOOH, then part of the γ-FeOOH continued growing, and under the capillary action, the other part of the γ-FeOOH transformed to α-FeOOH.

Originality/value

To the best of the authors’ knowledge, this paper puts forward for the first time a new viewpoint of the development of corrosion products of low-carbon steel in two ways. This discovery provides a new idea for the future development of steel for marine engineering.