bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic changes in spatial representation within the posterior parietal cortex in response to visuomotor adaptation
Authors: Schintu S , Kravitz DJ , Silson EH , Cunningham CA , Wassermann EM , Shomstein S 
Published: October 2021

ABSTRACTRecent studies used fMRI population receptive field (pRF) mapping to demonstrate that retinotopic organization extends from primary visual cortex to ventral and dorsal visual pathways by quantifying visual field maps, receptive field size, and laterality throughout multiple areas. Visuospatial representation in the posterior parietal cortex (PPC) is modulated by attentional deployment, raising the question of whether spatial representation in the PPC is dynamic and flexible and that this flexibility contributes to visuospatial learning. To answer this question, changes in spatial representation within PPC, as measured with pRF mapping, were recorded before and after visuomotor adaptation. Visuospatial input was laterally manipulated, rightward or leftward, via prism adaptation, a well-established visuomotor technique that modulates visuospatial performance. Based on existing models of prism adaptation mechanism of action, we predicted left prism adaptation to produce a right visuospatial bias via an increasing pRF size in the left parietal cortex. However, our hypothesis was agnostic as to whether right PPC will show an opposite effect given the bilateral bias to right visual field. Findings show that adaptation to left-shifting prisms increases pRF size in both PPCs, while leaving space representation in early visual cortex unchanged. This is the first evidence that prism adaptation drives a dynamic reorganization of response profiles in the PPC. Our results show that spatial representation in the PPC not only reflects changes driven by attentional deployment but dynamically changes in response to visuomotor adaptation. Furthermore, our results provide support for using prism adaptation as a tool to rehabilitate visuospatial deficits.SIGNIFICANCE STATEMENTRepresentation of space in the posterior parietal cortex (PPC) is reflective of attentional selection. Deploying attention to a certain spatial location modulates response profiles of a corresponding set of neurons with receptive fields in the corresponding spatial location. Here, we show that visuomotor adaptation accomplished through left-shifting prism adaptation dynamically changes the representation of space in the PPC while preserving early visual representations. This is the first evidence that visuomotor adaptation drives an instant reorganization of spatial representation in PPC. This result has implications for understanding the dynamic organization of spatial representation in the PPC and for the rehabilitation of patients with neglect syndrome, whose spatial attention is compromised.
Hiding in the yolk: a unique feature ofLegionella pneumophilainfection of zebrafish
Authors: Viana Flávia , Boucontet Laurent , Laghi Valerio , Schator Daniel , Ibranosyan Marine , Jarraud Sophie , Colucci-Guyon Emma , Buchrieser Carmen 
Published: October 2021

AbstractThe zebrafish has become a powerful model organism to study host-pathogen interactions. Here, we developed a zebrafish model ofLegionella pneumophilainfection to dissect innate immune responses. We show thatL. pneumophilacause zebrafish larvae death in a dose dependent manner, and that macrophages are the first line of defence, with neutrophils cooperating to clear the infection. When either macrophages or neutrophils are depleted, these “immunocompromised” larvae become lethally sensitive toL. pneumophilasimilar to what is known for humans that develop pneumonia. Also as observed in human infections, the adaptor signalling molecule Myd88 is not required to control disease in the larvae. Furthermore, proinflammatory cytokine genesil1ßandtnfαwere upregulated during infection, recapitulating key immune responses seen in human infection. Strikingly, we uncovered a previously undescribed infection phenotype in zebrafish larvae, whereby bloodborne, wild typeL. pneumophilainvade and grow in the larval yolk region, a phenotype not observed with a type IV secretion system deficient mutant that cannot translocate effectors into its host cell. Thus, zebrafish larva represents an innovativeL. pneumophilainfection model that that on one hand mimics important aspects of the human immune response toL. pneumophilainfection and that on the other hand will allow to elucidate the mechanisms by which type IV secretion effectors allowL. pneumophilato cross membranes and to obtain nutrients from nutrient rich environments.
Detecting cell-of-origin and cancer-specific methylation features of cell-free DNA from Nanopore sequencing
Authors: Katsman Efrat , Orlanski Shari , Martignano Filippo , Fox-Fisher Ilana , Shemer Ruth , Dor Yuval , Zick Aviad , Eden Amir , Petrini Iacopo , Conticello Silvestro G. , Berman Benjamin P. 
Published: October 2021

AbstractThe Oxford Nanopore (ONT) platform provides portable and rapid genome sequencing, and its ability to natively profile DNA methylation without complex sample processing is attractive for clinical sequencing. We recently demonstrated ONT shallow whole-genome sequencing to detect copy number alterations (CNA) from the circulating tumor DNA (ctDNA) of cancer patients. Here, we show that cell-type and cancer-specific methylation changes can also be detected, as well as cancer-associated fragmentation signatures. This feasibility study suggests that ONT shallow WGS could be a powerful tool for liquid biopsy, especially real-time medical applications.
Widespread Utilization of Diverse Organophosphate Pollutants by Marine Bacteria
Authors: Despotović Dragana , Aharon Einav , Trofimyuk Olena , Dubovetskyi Artem , Cherukuri Kesava Phaneendra , Ashani Yacov , Leader Haim , Castelli Andrea , Fumagalli Laura , Savidor Alon , Levin Yishai , Longo Liam M. , Segev Einat , Tawfik Dan S. 
Published: October 2021

AbstractAnthropogenic organophosphates (AOPs), such as phosphotriesters, are used extensively as plasticizers, flame retardants, nerve agents and pesticides. Soil bacteria bearing a phosphotriesterase (PTE) can degrade AOPs, but whether bacteria are capable of utilizing AOPs as a phosphorus source, and how widespread PTEs are in nature, remains unclear. Here, we report the utilization of diverse AOPs by four model marine bacteria and seventeen bacterial isolates from seawater samples. To unravel the details of AOP utilization, two novel PTEs from marine bacteria were isolated and characterized. When expressed in E. coli, these PTEs enabled growth on a pesticide analog as the sole phosphorus source. Utilization of AOPs provides bacteria with a source of phosphorus in depleted environments and offers a new prospect for the bioremediation of a pervasive class of anthropogenic pollutants.One sentence summaryWidespread utilization of diverse organophosphate pollutants by over 20 marine bacterial strains represents a new hope for ocean bioremediation.
ARGONAUTE proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells
Authors: Müller Madlen , Schaefer Moritz , Fäh Tara , Spies Daniel , Peña-Hernández Rodrigo , Santoro Raffaella , Ciaudo Constance 
Published: October 2021

ABSTRACTThe Argonaute proteins (AGO) are well-known for their essential role in post-transcriptional gene silencing in the microRNA (miRNA) biogenesis pathway. Only two AGOs (AGO1 and AGO2) are expressed in mouse embryonic stem cells (mESCs). The transcriptome ofAgomutant mESCs revealed a large and specific set of misregulated genes, compared to other miRNA biogenesis factor mutant cells, suggesting additional functions for the AGOs in stem cells. In this study, we endeavored to understand miRNA-independent roles of the AGOs in gene expression regulation through the integration of multiple datasets. Correlation ofAgomutant differential gene expression with ENCODE histone modification data of WT mESCs revealed that affected genes were regulated by the repressive histone modification H3K27me3. We validated this observation by performing chromatin immunoprecipitation followed by sequencing and observed a global loss of H3K27me3 inAgomutant cells. Nevertheless, this reduction explains only a small part of the specific differential gene expression observed inAgomutant mESCs. By integrating chromatin accessibility data in conjunction with prediction of transcription factor binding sites, we identified differential binding for five transcription factors, including KLF4 as a key modulator of more than half of the specific misregulation of gene expression in the absence of AGO proteins. Our findings illustrate that in addition to chromatin state, information about transcription factor binding is more revelatory in understanding the multi-layered mechanism adopted by cells to regulate gene expression. These data also highlight the importance of an integrative approach to unravel the variety of noncanonical functions of AGOs in mESCs.
Concentration fluctuations due to size-dependent gene expression and cell-size control mechanisms
Authors: Jia Chen , Singh Abhyudai , Grima Ramon 
Published: October 2021

AbstractIntracellular reaction rates depend on concentrations and hence their levels are often regulated. However classical models of stochastic gene expression lack a cell size description and cannot be used to predict noise in concentrations. Here, we construct a model of gene product dynamics that includes a description of cell growth, cell division, size-dependent gene expression, gene dosage compensation, and size control mechanisms that can vary with the cell cycle phase. We obtain expressions for the approximate distributions and power spectra of concentration fluctuations which lead to insight into the emergence of concentration homeostasis. Furthermore, we find that (i) the conditions necessary to suppress cell division-induced concentration oscillations are difficult to achieve; (ii) mRNA concentration and number distributions can have different number of modes; (iii) certain size control strategies are ideal because they maintain constant mean concentrations whilst minimising concentration noise. Predictions are confirmed using lineage data for E. coli, fission yeast and budding yeast.
Remembering the pattern: A longitudinal case study on statistical learning in spatial navigation and memory consolidation
Authors: Graves Kathryn N. , Sherman Brynn E. , Huberdeau David , Damisah Eyiyemisi , Quraishi Imran H. , Turk-Browne Nicholas B. 
Published: October 2021

AbstractDistinct brain systems are thought to support statistical learning over different timescales. Regularities encountered during online perceptual experience can be acquired rapidly by the hippocampus. Further processing during offline consolidation can establish these regularities gradually in cortical regions, including the medial prefrontal cortex (mPFC). These mechanisms of statistical learning may be critical during spatial navigation, for which knowledge of the structure of an environment can facilitate future behavior. Rapid acquisition and prolonged retention of regularities have been investigated in isolation, but how they interact in the context of spatial navigation is unknown. We had the rare opportunity to study the brain systems underlying both rapid and gradual timescales of statistical learning using intracranial electroencephalography (iEEG) longitudinally in the same patient over a period of three weeks. As hypothesized, spatial patterns were represented in the hippocampus but not mPFC for up to one week after statistical learning and then represented in the mPFC but not hippocampus two and three weeks after statistical learning. Taken together, these findings clarify that the hippocampus may do the initial work of extracting regularities and transfer these integrated memories to cortex, rather than only storing individual experiences and leaving it up to cortex to extract regularities.HighlightsCase study of an epilepsy patient tested longitudinally over three weeks.We tracked time-dependent changes in neural representations of spatial patterns.Representations reconstructed from hippocampal activity reflected patterns learned within a week.Representations reconstructed from activity in the mPFC reflected patterns learned 2–3 weeks ago.
Release of the ribosome biogenesis factor Bud23 from small subunit precursors in yeast
Authors: Black Joshua J. , Johnson Arlen W. 
Published: October 2021

AbstractRibosomes are the universally conserved ribonucleoprotein complexes that synthesize proteins. The two subunits of the eukaryotic ribosome are produced through a quasi-independent assembly-line-like pathway involving the hierarchical actions of numerous trans-acting biogenesis factors and the incorporation of ribosomal proteins. The factors work together to shape the nascent subunits through a series of intermediate states into their functional architectures. The earliest intermediate of the small subunit (SSU or 40S) is the SSU Processome which is subsequently transformed into the pre-40S intermediate. This transformation is, in part, facilitated by the binding of the methyltransferase Bud23. How Bud23 is released from the resultant pre-40S is not known. The ribosomal proteins Rps0, Rps2, and Rps21, termed the Rps0-cluster proteins, and several biogenesis factors are known to bind the pre-40S around the time that Bud23 is released, suggesting that one or more of these factors induce Bud23 release. Here, we systematically examined the requirement of these factors for the release of Bud23 from pre-40S particles. We found that the Rps0-cluster proteins are needed but not sufficient for Bud23 release. The atypical kinase/ATPase Rio2 shares a binding site with Bud23 and is thought to be recruited to pre-40S after the Rps0-cluster proteins. Depletion of Rio2 prevented the release of Bud23 from the pre-40S. More importantly, the addition of recombinant Rio2 to pre-40S particles affinity-purified from Rio2-depleted cells was sufficient for Bud23 release in vitro. The ability of Rio2 to displace Bud23 was independent of nucleotide hydrolysis. We propose a novel role for Rio2 in which its binding to the pre-40S actively displaces Bud23 from the pre-40S, and we suggest a model in which the binding of the Rps0-cluster proteins and Rio2 promote the release of Bud23.
Two distinct classes of co-chaperones compete for the EEVD motif in heat shock protein 70 (Hsp70) to tune its activity
Authors: Johnson Oleta T. , Nadel Cory M. , Carroll Emma C. , Arhar Taylor , Gestwicki Jason E. 
Published: October 2021

AbstractChaperones of the heat shock protein 70 (Hsp70) family engage in protein-protein interactions (PPIs) with many co-chaperones. One hotspot for co-chaperone binding is the EEVD motif that is found at the extreme C-terminus of cytoplasmic Hsp70s. This motif is known to bind tetratricopeptide repeat (TPR) domain co-chaperones, such as the E3 ubiquitin ligase CHIP, and Class B J-domain proteins (JDPs), such as DnaJB4. Although complexes between Hsp70-CHIP and Hsp70-DnaJB4 are both important for chaperone functions, the molecular determinants that dictate the competition between these co-chaperones are not clear. Using a collection of EEVD-derived peptides, we find that DnaJB4 binds to the IEEVD motif of Hsp70s, but not the related MEEVD motif of cytoplasmic Hsp90s. Then, we explored which residues are critical for binding to CHIP and DnaJB4, revealing that they rely on some shared features of the IEEVD motif, such as the C-terminal carboxylate. However, they also had unique preferences, especially at the isoleucine position. Finally, we observed a functionally important role for competition between CHIP and DnaJB4 in vitro, as DnaJB4 can limit the ubiquitination activity of the Hsp70-CHIP complex, while CHIP suppresses the chaperone activities of Hsp70-DnaJB4. Together, these results suggest that the EEVD motif has evolved to support diverse PPIs, such that competition between co-chaperones could help guide whether Hsp70-bound proteins are folded or degraded.
Cryo-ET distinguishes platelets during pre-acute myeloid leukemia from steady state hematopoiesis
Authors: Wang Yuewei , Huo Tong , Tseng Yu-Jung , Dang Lan , Yu Zhili , Yu Wenjuan , Foulks Zachary , Ludtke Steven J. , Nakada Daisuke , Wang Zhao 
Published: October 2021

AbstractEarly diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement. A large proportion of platelets exhibited changes in the overall shape and depletion of organelles in AML. Notably, 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae, accompanied by a significant drop in ATP levels and altered expression of metabolism-related gene signatures. Our study demonstrates that detectable structural changes in pre-leukemic platelets may serve as a biomarker for the early diagnosis of AML.
p38α-MAPK-deficient myeloid cells ameliorate symptoms and pathology of APP-transgenic AD mice
Authors: Luo Qinghua , Schnöder Laura , Hao Wenlin , Litzenburger Kathrin , Decker Yann , Tomic Inge , Menger Michael D. , Fassbender Klaus , Liu Yang 
Published: October 2021

AbstractMicroglial activation is a hall marker of Alzheimer’s disease (AD); its pathogenic role and regulating mechanisms are unclear. p38α-MAPK, a stress-responding kinase, is activated in AD brain in early disease stages. In APP-transgenic mice, we deleted p38α-MAPK in whole myeloid cells from birth or specifically in microglia from 9 months, and analysed AD pathology at the age of 4, 9 and 12 months. In both experimental settings, p38α-MAPK deficiency decreased cerebral Aβ and improved cognitive function of AD mice; however, p38α-MAPK-deficient myeloid cells were more effective than p38α-MAPK-deficient microglia in preventing AD pathogenesis. Deficiency of p38α-MAPK in myeloid cells inhibited the inflammatory activation of individual microglia by 4 months, but enhanced it by 9 months. Inflammatory activation was essential for p38α-MAPK deficiency to promote microglial internalization of Aβ. Interestingly, p38α-MAPK deficiency in peripheral myeloid cells reducedil-17atranscription in CD4-positive spleen cells. By cross-breeding APP-transgenic mice and IL-17a knockout mice, we further observed that IL-17a deficiency activated microglia and decreased Aβ deposits in AD mouse brain. Thus, p38α-MAPK deficiency in myeloid cells prevents AD pathogenesis, perhaps through reducing IL-17a-expressing T lymphocytes, and promoting Aβ clearance in the brain. Our study supports p38α-MAPK as a novel target for AD therapy.
EZTraits: a Programmable Tool to Evaluate Multi-site Deterministic Traits
Authors: Carland Matt , Bose Madhuchanda , Novković Biljana , Pedersen Haley , Manson Charles , Lahan Shany , Pavlenko Alex , Yazdi Puya G. , Grabherr Manfred G. 
Published: October 2021

ABSTRACTThe vast majority of human traits, including many disease phenotypes, are affected by alleles at numerous genomic loci. With a continually increasing set of variants with published clinical disease or biomarker associations, an easy-to-use tool for non-programmers to rapidly screen VCF files for risk alleles is needed. We have developed EZTraits as a tool to quickly evaluate genotype data (e.g., from microarrays) against a set of rules defined by the user. These rules can be defined directly in the scripting language Lua, for genotype calls using variant ID (RS number) or chromosomal position. Alternatively, EZTraits can parse simple and intuitive text including concepts like ‘any’ or ‘all’. Thus, EZTraits is designed to support rapid genetic analysis and hypothesis-testing by researchers, regardless of programming experience or technical background. The software is implemented in C++ and compiles and runs on Linux and MacOS. The source code is available under the MIT license from https://github.com/selfdecode/rd-eztraitsContact: manfred@selfdecode.com
Getting our voice heard: empowering people with a learning disability to influence adult safeguarding policy
Authors: Montgomery Lorna , Davidson Gavin , Kelly Berni , McKendry Linda , Newton Leslie-Anne , Webb Paul , Wood Lisamarie 
Published: October 2021

Purpose
The purpose of this paper is to present an examination of the development of adult safeguarding policy from the perspectives of both policymakers and those who have sought to influence policy, to empower individuals with a learning disability to have a say in how policies, that influence their life and impact their right to independence, are developed.

Design/methodology/approach
This paper is based on a project which was led by a UK-wide interdisciplinary and multi-agency team, which included the central involvement of peer researchers who had lived experience of learning disability. It was based on a participatory disability research design.

Findings
Factors which enabled or restrained individuals with a learning disability, and their supporting organisations, from getting their voice heard in policy development, are identified.

Originality/value
This paper builds on policy theory and research, making recommendations for policy makers, disabled people and their supporting organisations as to how adult safeguarding policy, could be more effectively informed and influenced.
Application of tools to support Linked Open Data
Authors: Saha Sujan , Mandal Sukumar 
Published: October 2021

Purpose
These projects aim to improve library services for users in the future by combining Link Open Data (LOD) technology with data visualization. It displays and analyses search results in an intuitive manner. These services are enhanced by integrating various LOD technologies into the authority control system.

Design/methodology/approach
The technology known as LOD is used to access, recycle, share, exchange and disseminate information, among other things. The applicability of Linked Data technologies for the development of library information services is evaluated in this study.

Findings
Apache Hadoop is used for rapidly storing and processing massive Linked Data data sets. Apache Spark is a free and open-source data processing tool. Hive is a SQL-based data warehouse that enables data scientists to write, read and manage petabytes of data.

Originality/value
The distributed large data storage system Apache HBase does not use SQL. This study’s goal is to search the geographic, authority and bibliographic databases for relevant links found on various websites. When data items are linked together, all of the data bits are linked together as well. The study observed and evaluated the tools and processes and recorded each data item’s URL. As a result, data can be combined across silos, enhanced by third-party data sources and contextualized.