bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classic articles in Apoptotic Research: A Bibliometric Analysis
Authors: Jallow Amadou W. , Lee Shin-Da , Ho Yuh-Shan 
Published: August 2020

AbstractBackgroundClassic articles are defined as research papers with a total citation of one thousand or more. The present study is to identify and analyse the characteristics of the classic articles in apoptosis research.MethodClassic articles with total of 1,000 or more citations from Web of Science Core Collection since year of publication to the end of 2017 were basically assessed regarding their document types, languages, journals, and Web of Science categories within 1900 to 2017.ResultThe study showed 418 classic documents in apoptotic research including 260 articles published between 1972 and 2012. The most productive Web of Science category was multidisciplinary sciences.Naturepublished most of these classic articles followed byCell, andScience. The most productive country and institution were United States and Harvard University respectively. The author S.J. Korsmeyer from Harvard University was the most productive in apoptosis field and published 13 classic apoptosis articles while the author J.C Reed had more potential to publish classic apoptosis articles in future. The author J.C. Reed and V.A. Fadok had equal potential to publish the same number of classic articles as first- and corresponding-author. Article of Kerr et al. in 1972 was the most popular and cited apoptosis article. The most impact article in 2017 was article entitled “Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion” by Dong et al. in 2002.ConclusionThis study seems to identify the most industrious authors, institutions, and countries in the field of apoptosis research. It also tends to reveal the historical and discoveries related to the pathophysiology of apoptosis as well as the most impact publications on apoptosis studies.
Single amino acid mutations effect Zika virus replicationin vitroand virulencein vivo
Authors: Collette Nicole M. , Lao Victoria H.I. , Weilhammer Dina R. , Zingg Barbara , Cohen Shoshana D. , Hwang Mona , Coffey Lark L. , Grady Sarah L. , Zemla Adam T. , Borucki Monica K. 
Published: August 2020

AbstractThe 2014-2016 Zika virus (ZIKV) epidemic in the Americas resulted in large deposits of next-generation sequencing data from clinical samples. This resource was mined to identify emerging mutations and trends in mutations as the outbreak progressed over time. Information on transmission dynamics, prevalence and persistence of intra-host mutants, and the position of a mutation on a protein were then used to prioritize 544 reported mutations based on their ability to impact ZIKV phenotype. Using this criteria, six mutants (representing naturally occurring mutations) were generated as synthetic infectious clones using a 2015 Puerto Rican epidemic strain PRVABC59 as the parental backbone. The phenotypes of these naturally occurring variants were examined using both cell culture and murine model systems. Mutants had distinct phenotypes, including changes in replication rate, embryo death, and decreased head size. In particular, a NS2B mutant previously detected duringin vivostudies in rhesus macaques was found to cause lethal infections in adult mice, abortions in pregnant females, and increased viral genome copies in both brain tissue and blood of female mice. Additionally, mutants with changes in the region of NS3 that interfaces with NS5 during replication displayed reduced replication in the blood of adult mice. This analytical pathway, integrating both bioinformatic and wet lab experiments, provides a foundation for understanding how naturally occurring single mutations affect disease outcome and can be used to predict the of severity of future ZIKV outbreaks.Author summaryTo determine if naturally occurring individual mutations in the Zika virus epidemic genotype effect viral virulence or replication ratein vitroorin vivo, we generated an infectious clone representing the epidemic genotype of stain Puerto Rico, 2015. Using this clone, six mutants were created by changing nucleotides in the genome to cause one to two amino acid substitutions in the encoded proteins. The six mutants we generated represent mutations that differentiated the early epidemic genotype from genotypes that were either ancestral or that occurred later in the epidemic. We assayed each mutant for changes in growth rate, and for virulence in adult mice and pregnant mice. Three of the mutants caused catastrophic embryo effects including increased embryonic death or significant decrease in head diameter. Three other mutants that had mutations in a genome region associated with replication resulted in changes inin vitroandin vivoreplication rates. These results illustrate the potential impact of individual mutations in viral phenotype.
Genetic Disruption of WASHC4 Drives Endo-lysosomal Dysfunction and Cognitive-Movement Impairments in Mice and Humans
Authors: Courtland Jamie L. , Bradshaw Tyler W. A. , Waitt Greg , Soderblom Erik J. , Ho Tricia , Rajab Anna , Vancini Ricardo , Kim Hwan , Soderling Scott H. 
Published: August 2020

ABSTRACTMutation of the WASH complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH complex proteome, revealing a network of endosomal proteins. To uncover how dysfunction of endosomal SWIP leads to disease, we generate a mouse model of the humanWASHC4c.3056C>Gmutation. Quantitative spatial proteomics analysis of SWIPP1019Rmouse brain reveals that this mutation destabilizes the WASH complex and uncovers significant perturbations in both endosomal and lysosomal pathways. Cellular and histological analyses confirm that SWIPP1019Rresults in endo-lysosomal disruption and uncover indicators of neurodegeneration. We find that SWIPP1019Rnot only impacts cognition, but also causes significant progressive motor deficits in mice. Remarkably, a retrospective analysis of SWIPP1019Rpatients confirms motor deficits in humans. Combined, these findings support the model that WASH complex destabilization, resulting from SWIPP1019R, drives cognitive and motor impairments via endo-lysosomal dysfunction in the brain.
Confidence-controlled Hebbian learning efficiently extracts category membership from stimuli encoded in view of a categorization task
Authors: Berlemont Kevin , Nadal Jean-Pierre 
Published: August 2020

AbstractIn experiments on perceptual decision-making, individuals learn a categorization task through trial-and-error protocols. We explore the capacity of a decision-making attractor network to learn a categorization task through reward-based, Hebbian type, modifications of the weights incoming from the stimulus encoding layer. For the latter, we assume a standard layer of a large number of stimulus specific neurons. Within the general framework of Hebbian learning, authors have hypothesized that the learning rate is modulated by the reward at each trial. Surprisingly, we find that, when the coding layer has been optimized in view of the categorization task, such reward-modulated Hebbian learning (RMHL) fails to extract efficiently the category membership. In a previous work we showed that the attractor neural networks nonlinear dynamics accounts for behavioral confidence in sequences of decision trials. Taking advantage of these findings, we propose that learning is controlled by confidence, as computed from the neural activity of the decision-making attractor network. Here we show that this confidence-controlled, reward-based, Hebbian learning efficiently extracts categorical information from the optimized coding layer. The proposed learning rule is local, and, in contrast to RMHL, does not require to store the average rewards obtained on previous trials. In addition, we find that the confidence-controlled learning rule achieves near optimal performance.
Similarities and dissimilarities between psychiatric cluster disorders
Authors: Smail Marissa A. , Wu Xiaojun , Henkel Nicholas D. , Eby Hunter M. , Herman James P. , McCullumsmith Robert E. , Shukla Rammohan 
Published: August 2020

ABSTRACTThe common molecular mechanisms underlying psychiatric disorders are not well understood. Prior attempts to assess the pathological mechanisms responsible for psychiatric disorders have been limited by biased selection of comparable disorders, datasets as well as challenges associated with data normalization. However, publicly available databases offer a unique opportunity to expand such investigations both in terms of the number and types of diseases. Here, we used DisGeNET, a database of over 24,000 gene-disease associations to investigate the similarities and dissimilarities associated with enrichment of pathways, cell-types, drug targets, and human chromosomes within an unbiased cluster of psychiatric disorders. We show that cognition and neurotransmission related pathways are involved across all disorders, whereas those associated with immune system and signal-response coupling (cell-surface receptors, signal-transduction, gene-expression, and metabolic process) are associated with few disorders of the cluster. The drug-target based enrichment confirms the involvement of neurotransmission related changes across these disorders. At cell-type level, dendrite targeting interneurons, across all layers, are most involved across all disorders. Finally, using a clustering-based similarity index, we showed that the similarity between the disorders are influenced most at chromosomal level and to some extent at cellular level. Collectively, the results provide a comprehensive comparison of many psychiatric diseases in an unbiased manner and expand our understanding of the cellular and molecular pathologies associated with similar and comorbid psychiatric disorders.
Somatosensory versus cerebellar contributions to proprioceptive changes associated with motor skill learning: A theta burst stimulation study
Authors: Mirdamadi Jasmine L. , Block Hannah J. 
Published: August 2020

AbstractBackgroundIt is well established that proprioception (position sense) is important for motor control, yet its role in motor learning and associated plasticity is not well understood. We previously demonstrated that motor skill learning is associated with enhanced proprioception and changes in sensorimotor neurophysiology. However, the neural substrates mediating these effects are unclear.ObjectiveTo determine whether suppressing activity in the cerebellum and somatosensory cortex (S1) affects proprioceptive changes associated with motor skill learning.Methods54 healthy young adults practiced a skill involving visually-guided 2D reaching movements through an irregular-shaped track using a robotic manipulandum with their right hand. Proprioception was measured using a passive two-alternative choice task before and after motor practice. Continuous theta burst stimulation (cTBS), was delivered over S1 or the cerebellum (CB) at the end of training for two consecutive days. We compared group differences (S1, CB, Sham) in proprioception and motor skill, quantified by a speed-accuracy function, measured on a third consecutive day (retention).ResultsAs shown previously, the Sham group demonstrated enhanced proprioceptive sensitivity after training and at retention. The S1 group had impaired proprioceptive function at retention through online changes during practice, whereas the CB group demonstrated offline decrements in proprioceptive function. All groups demonstrated motor skill learning, however, the magnitude of learning differed between the CB and Sham groups, consistent with a role for the cerebellum in motor learning.ConclusionOverall, these findings suggest that the cerebellum and S1 are important for distinct aspects of proprioceptive changes during skill learning.
Nutrient dominance governs the assembly of microbial communities in mixed nutrient environments
Authors: Estrela Sylvie , Sanchez-Gorostiaga Alicia , Vila Jean C.C. , Sanchez Alvaro 
Published: August 2020

AbstractA major open question in microbial community ecology is whether we can predict how the components of a diet collectively determine the taxonomic composition of microbial communities. Motivated by this challenge, we investigate whether communities assembled in pairs of nutrients can be predicted from those assembled in every single nutrient alone. We first find that although the null, naturally additive model generally predicts well the family-level community composition, there exist systematic deviations from the additive predictions that reflect generic patterns of nutrient dominance at the family-level. Pairs of more similar nutrients (e.g. two sugars) are on average more additive than pairs of more dissimilar nutrients (one sugar-one organic acid). Second, a simple dominance rule emerges: sugars generally dominate organic acids. These findings may be explained by family-level asymmetries in nutrient benefits. Overall, our results suggest that regularities in how nutrients interact may help predict communities responses to dietary changes.
Cutting across structural and transcriptomic scales translates time across the lifespan and resolves frontal cortex development in human evolution
Authors: Charvet Christine J. 
Published: August 2020

AbstractHow the unique capacities of human cognition arose in evolution is a question of enduring interest. It is still unclear which developmental programs are responsible for the emergence of the human brain. The inability to determine corresponding ages between humans and apes has hampered progress in detecting developmental programs leading to the emergence of the human brain. I harness temporal variation in anatomical, behavioral, and transcriptional variation to determine corresponding ages from fetal to postnatal development and aging, between humans and chimpanzees. This multi-dimensional approach results in 137 corresponding time points across the lifespan, from embryonic day 44 to ∼55 years of age, in humans and their equivalent ages in chimpanzees. I used these data to test whether developmental programs, such as the timeline of prefrontal cortex maturation, previously claimed to differ between humans and chimpanzees, do so once variation in developmental schedules is controlled for. I compared the maturation of frontal cortex projections from structural magnetic resonance (MR) scans and from temporal variation in the expression of genes used to track long-range projecting neurons (i.e., supragranular-enirhced genes) in chimpanzees and humans. Contrary to what has been suggested, the timetable of prefrontal cortex maturation is not unusually extended in humans. This dataset, which is the largest with which to determine corresponding ages across humans and chimpanzees, provides a rigorous approach to control for variation in developmental schedules and to identify developmental programs responsible for unique features of the human brain.
An Organotypic Mammary Duct Model Capturing Distinct Events of DCIS Progression
Authors: Kulwatno Jonathan , Gong Xiangyu , DeVaux Rebecca , Herschkowitz Jason I. , Mills Kristen Lynn 
Published: August 2020

ABSTRACTDuctal carcinomain situ(DCIS) is a pre-cancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30-40% of DCIS cases are likely to progress into an invasive ductal carcinoma (IDC), while the remainder are innocuous. Since little is known about what contributes to the transition from DCIS to IDC, clinicians and patients tend to opt for treatment, leading to concerns of overdiagnosis and overtreatment.In vitromodels are currently being used to probe how DCIS transitions into IDC, but many models do not take into consideration the macroscopic tissue architecture and the biomechanical properties of the microenvironment. Here, we developed an organotypic mammary duct model by molding a channel within a collagen matrix and lining it with a basement membrane. By adjusting the concentration of collagen, we effectively modulated the stiffness and morphological properties of the matrix and examined how an assortment of breast cells responded to changing density and stiffness of the matrix. We first validated the model using two established, phenotypically divergent breast cancer cell lines by demonstrating the ability of the cells to either invade (MDA-MB-231) or cluster (MCF7). We then examined how cells of the isogenic MCF10 series—spanning the range from healthy to aggressive—behaved within our model and observed distinct characteristics of breast cancer progression such as hyperplasia and invasion, in response to collagen concentration. Our results show that the model can recapitulate different stages of breast cancer progression and that the MCF10 series is adaptable to physiologically relevantin vitrostudies, demonstrating the potential of both the model and cell lines to elucidate key factors that may contribute to understanding the transition from DCIS to IDC.IMPACT STATEMENTThe success of early preventative measures for breast cancer has left patients susceptible to overdiagnosis and overtreatment. Limited knowledge of factors driving an invasive transition has inspired the development ofin vitromodels that accurately capture this phenomenon. However, current models tend to neglect the macroscopic architecture and biomechanical properties of the mammary duct. Here, we introduce an organotypic model that recapitulates the cylindrical geometry of the tissue and the altered stroma seen in tumor microenvironments. Our model was able to capture distinct features associated with breast cancer progression, demonstrating its potential to uncover novel insights into disease progression.
Inhibition of SARS-CoV-2 polymerase by nucleotide analogs: a single molecule perspective
Authors: Seifert Mona , Bera Subhas Chandra , van Nies Pauline , Kirchdoerfer Robert N. , Shannon Ashleigh , Le Thi-Tuyet-Nhung , Meng Xiangzhi , Xia Hongjie , Wood James M. , Harris Lawrence D. , Papini Flávia S. , Arnold Jamie J. , Almo Steven C. , Grove Tyler L. , Shi Pei-Yong , Xiang Yan , Canard Bruno , Depken Martin , Cameron Craig E. , Dulin David 
Published: August 2020

AbstractThe nucleotide analog Remdesivir (RDV) is the only FDA-approved antiviral therapy to treat infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The physical basis for efficient utilization of RDV by SARS-CoV-2 polymerase is unknown. Here, we characterize the impact of RDV and other nucleotide analogs on RNA synthesis by the polymerase using a high-throughput, single-molecule, magnetic-tweezers platform. The location of the modification in the ribose or in the base dictates the catalytic pathway(s) used for its incorporation. We reveal that RDV incorporation does not terminate viral RNA synthesis, but leads the polymerase into deep backtrack, which may appear as termination in traditional ensemble assays. SARS-CoV-2 is able to evade the endogenously synthesized product of the viperin antiviral protein, ddhCTP, though the polymerase incorporates this nucleotide analog well. This experimental paradigm is essential to the discovery and development of therapeutics targeting viral polymerases.TeaserWe revise Remdesivir’s mechanism of action and reveal SARS-CoV-2 ability to evade interferon-induced antiviral ddhCTP
Ubiquitous selfish toxin-antidote elements inCaenorhabditisspecies
Authors: Ben-David Eyal , Pliota Pinelopi , Widen Sonya A. , Koreshova Alevtina , Lemus-Vergara Tzitziki , Verpukhovskiy Philipp , Mandali Sridhar , Braendle Christian , Burga Alejandro , Kruglyak Leonid 
Published: August 2020

AbstractToxin-antidote elements (TAs) are selfish genetic dyads that spread in populations by selectively killing non-carriers. TAs are common in prokaryotes, but few examples are known in animals. We discovered five maternal-effect TAs in the nematodeCaenorhabditis tropicalisand one inC. briggsae. Unlike previously reported TAs, five of these novel toxins do not kill embryos but instead cause larval arrest or developmental delay. We identified the genes underlying a TA causing developmental delay,slow-1/grow-1, and found that the toxin,slow-1,is homologous to nuclear hormone receptors. Last, we found that balancing selection of conflicting TAs hampers their ability to drive in populations, leading to more stable genetic incompatibilities. Our results show that TAs are common inCaenorhabditisspecies, target a wide range of developmental processes, and may act as barriers preventing gene flow.
Prevalence of SARS-CoV-2 among high-risk populations in Lomé (Togo) in 2020
Authors: Halatoko Wemboo Afiwa , Konu Yao Rodion , Gbeasor-Komlanvi Fifonsi Adjidossi , Sadio Arnold Junior , Tchankoni Martin Kouame , Komlanvi Koffi Segbeaya , Salou Mounerou , Dorkenoo Ameyo Monique , Maman Issaka , Agbobli Amétépé , Wateba Majesté Ihou , Adjoh Komi Séraphin , Akue Edem Goeh , Kao Yem-bla , Kpeto Innocent , Pana Paul , Kinde-Sossou Rebecca , Tamekloe Agbeko , Nayo-Apetsianyi Josée , Assane Simon-Pierre Hamadi , Prince-David Mireille , Awoussi Sossinou Marcel , Djibril Mohaman , Mijiyawa Moustafa , Dagnra Anoumou Claver , Ekouevi Didier Koumavi 
Published: August 2020

SummaryObjectiveThis survey aims at estimating the prevalence of SARS-CoV-2 in high risk populations in Lomé.MethodsFrom April 23rd to May 8th 2020, we recruited a random sample of participants from five sectors: healthcare, air transport, police, road transport and informal. We collected oropharyngeal swab for direct detection through real time reverse transcription polymerase chain reaction (rRT-PCR), and blood for antibodies detection by serological tests. The overall prevalence (current and past) of infection was defined by positivity for both tests.ResultsA total of 955 participants with a median age of 36 (IQR 32-43) were included and 71.6% (n=684) were men. Around 22.1% (n=212) were from the air transport sector, 20.5% (n=196) in the police, and 38.7% (n=370) in the health sector. Seven participants (0.7%, 95% CI: 0.3-1.6%) had a positive rRT-PCR at the time of recruitment and nine (0.9%, 95% CI: 0.4-1.8%) were seropositive for IgM or IgG against SARS-CoV-2. We found an overall prevalence of 1.6% (n=15), 95% CI: 0.9-2.6%.ConclusionThe prevalence of the SARS-CoV-2 infection among high-risk populations in Lomé was relatively low and could be explained by the various measures taken by the Togolese government. Therefore, we recommend targeted screening.