bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking
Authors: Bieri Jan , Leisi Remo , Bircher Cornelia , Ros Carlos 
Published: March 2021

AbstractThe glycosphingolipid (GSL) globoside (Gb4) is essential for parvovirus B19 (B19V) infection. Historically considered the cellular receptor of B19V, the role of Gb4 and its interaction with B19V are controversial. In this study, we applied artificial viral particles, genetically modified cells, and specific competitors to address the interplay between the virus and the GSL. Our findings demonstrate that Gb4 is not involved in the binding or internalization process of the virus into permissive erythroid cells, a function that corresponds to the VP1u cognate receptor. However, Gb4 is essential at a post-internalization step before the delivery of the single-stranded viral DNA into the nucleus. In susceptible erythroid Gb4 knockout cells, incoming viruses were arrested in the endosomal compartment, showing no cytoplasmic spreading of capsids as observed in Gb4-expressing cells. Hemagglutination and binding assays revealed that pH acts as a switch to modulate the affinity between the virus and the GSL. Capsids interact with Gb4 exclusively under acidic conditions and dissociate at neutral pH. Inducing a specific Gb4-mediated attachment to permissive erythroid cells by acidification of the extracellular environment led to a non-infectious uptake of the virus, indicating that low pH-mediated binding to the GSL initiates active membrane processes resulting in vesicle formation. In summary, this study provides mechanistic insight into the interaction of B19V with Gb4. The strict pH-dependent binding to the ubiquitously expressed GSL prevents the redirection of the virus to nonpermissive tissues while promoting the interaction in acidic intracellular compartments as an essential step in infectious endocytic trafficking.Author summaryThe neutral glycosphingolipid globoside (Gb4) has been historically considered the cellular receptor of B19V, however, its wide expression profile does not correlate well with the restricted tropism of the virus. Here, we show that Gb4 is essential for the infection at a step following virus uptake and before the delivery of the viral ssDNA into the nucleus. B19V interacts with Gb4 exclusively under acidic conditions, prohibiting the interaction on the plasma membrane and promoting it inside the acidic endosomal compartments, which are engaged by the virus and the GSL after internalization. In the absence of Gb4, incoming viruses are retained in the endocytic compartment and the infection is aborted. This study reveals the mechanism of the interaction between the virus and the glycosphingolipid and redefines the role of Gb4 as an essential intracellular partner required for infectious entry.
Microglia show differential transcriptomic response to Aβ peptide aggregatesex vivoandin vivo
Authors: McFarland Karen N. , Ceballos Carolina , Rosario Awilda , Ladd Thomas , Moore Brenda , Golde Griffin , Wang Xue , Allen Mariet , Ertekin-Taner Nilüfer , Funk Cory C , Robinson Max , Baloni Priyanka , Rappaport Noa , Chakrabarty Paramita , Golde Todd E. 
Published: March 2021

AbstractAggregation and accumulation of amyloid-β (Aβ) is a defining feature of Alzheimer’s disease (AD) pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, to primary mouse microglial cultures and evaluated system level transcriptional changes and then compared these to transcriptomic changes in the brains of CRND8 APP mice. We find that primary microglial cultures have rapid and massive transcriptional change to in response to Aβ. Transcriptomic responses to oligomeric or fibrillar Aβ in primary microglia, though partially overlapping, are distinct and are not recapitulatedin vivowhere Aβ progressively accumulates. Furthermore, though classic immune mediators show massive transcriptional changes in the primary microglial cultures, these changes are not observed in the mouse model. Together, these data extend previous studies which demonstrate that microglia responsesex vivoare poor proxies forin vivoresponses. Finally, these data demonstrate the potential utility of using microglia as biosensors of different aggregate conformation, as the transcriptional responses to oligomeric and fibrillar Aβ can be distinguished.
Distinct forms of synaptic plasticity during ascending vs. descending control of medial olivocochlear efferent neurons
Authors: Romero Gabriel E. , Trussell Laurence O. 
Published: March 2021

AbstractActivity in each brain region is shaped by the convergence of ascending and descending axonal pathways, and the balance and characteristics of these determine neural output. The medial olivocochlear (MOC) efferent system is part of a reflex arc that critically controls auditory sensitivity. Multiple central pathways contact MOC neurons, raising the question of how a reflex arc could be engaged by diverse inputs. We examined functional properties of synapses onto brainstem MOC neurons from ascending (ventral cochlear nucleus, VCN), and descending (inferior colliculus, IC) sources in mice using an optogenetic approach. We found that these pathways exhibited opposing forms of short-term plasticity, with VCN input showing depression and IC input showing marked facilitation. By using a conductance clamp approach, we found that combinations of facilitating and depressing inputs enabled firing of MOC neurons over a surprisingly wide dynamic range, suggesting an essential role for descending signaling to a brainstem nucleus.
Daily changes in neuronal activities of the dorsal motor nucleus of the vagus under standard and short-term high fat diet – implications for circadian modulation of parasympathetic outflow
Authors: Chrobok Lukasz , Klich Jasmin D , Jeczmien-Lazur Jagoda S , Pradel Kamil , Palus-Chramiec Katarzyna , Sanetra Anna M , Piggins Hugh D , Lewandowski Marian H 
Published: March 2021

ABSTRACTThe suprachiasmatic nuclei (SCN) of the hypothalamus functions as the brain’s primary circadian clock, but circadian clock genes are also rhythmically expressed in several extra-SCN brain sites where they can exert local temporal control over physiology and behaviour. Recently, we found that the hindbrain dorsal vagal complex possesses strong daily timekeeping capabilities, with the area postrema and nucleus of the solitary tract exhibiting the most robust clock properties. The possibility that the executory part of this complex – the dorsal motor nucleus of the vagus (DMV), also exhibits daily changes has not been extensively studied. The DMV is the source of vagal efferent motoneurons largely responsible for the regulation of gastric motility and emptying and consequently influence meal size and energy homeostasis. We used a combination of multi-channel electrophysiology and patch clamp recordings to gain insight into possible daily variation in these DMV cells and how this is influenced by diet. We found that DMV neurons increase their spontaneous activity, excitability and responsiveness to metabolic neuromodulators at late day which was paralleled with an enhanced synaptic input to these neurons. A high-fat diet typically damps circadian rhythms, but we found that short-term exposure to a high-fat diet paradoxically amplified daily variation of DMV neuronal activity, while blunting their responsiveness to metabolic neuromodulators. In summary, we show for the first time that neural activity at a source of vagal efferents varies with time of day and that this temporal variation is modulated by diet. These findings have clear implications for our understanding of the daily control of parasympathetic outflow.
Variation in bacterial composition, diversity, and activity across different subglacial basal ice types
Authors: Doyle Shawn M. , Christner Brent C. 
Published: March 2021

ABSTRACTGlaciers and ice sheets possess layers of basal ice characterized by high amounts of entrained debris that can serve as sources of nutrients and organic matter, providing habitat for microorganisms adapted to the frozen conditions. Basal ice forms through various mechanisms and is classified based on its ice and debris content; however, little is known about variation in microbial composition, diversity, and activity across different basal ice types. We investigated these parameters in four different types of basal ice from a cold-based and temperate glacier and used a meta-analysis to compare our findings with microbiome studies from other frozen environments. We found basal ice environments harbor a diverse range of microbiomes whose composition and activity can vary significantly between basal ice types, even within adjacent facies from the same glacier. In some debris-rich basal ices, elevated ATP concentrations, isotopic gas signatures, and high ratios of amplified sequences for 16S rRNA relative to that for 16S rRNA genes implicated certain bacterial taxa (e.g.,Paenisporosarcina,Desulfocapsa,Syntrophus, Desulfosporosinus) as being potentially active, with ice temperature appearing to be an important predictor for the diversity of taxa inferred to be active. Compared to those of other sympagic environments, these microbiomes often resembled those found in permafrost or perennial cave ice rather than other glacial ice environments. In contrast, debris-poor basal ices harbored microbiomes more like those found in oligotrophic englacial ice. Collectively, these results suggest that different basal ice types contain distinct microbiomes that are actively structured by the diagenesis of their habitat.IMPORTANCEThe discharge of material from the basal ice zones of glaciers and ice sheets is an important source of dissolved organic matter, nutrients, and trace metals to downstream environments. Microorganisms with the ability to remain metabolically active while frozen have the potential to alter these substrates before they are released and may thus be a vital biogeochemical component of proglacial environments. However, basal ice environments are among the least explored areas of the cryosphere and information on their microbiology is limited. Here, we examine several basal ice types that were collected from different glaciers to investigate how their microbiomes varied. Our results indicate that sediment-rich basal ice from cold-based and temperate glaciers harbor microbiomes that conduct biogeochemical transformations at subzero temperatures and raises the intriguing possibility that subsurface regions of the cryosphere may be more biogeochemically active than previously thought.
No balance between glutamate+glutamine and GABA+ in visual and motor cortices of the human brain
Authors: Rideaux Reuben 
Published: March 2021

ABSTRACTTheoretical work, supported by electrophysiological evidence, asserts that a balance between excitation and inhibition (E/I) is critical for healthy brain function. In magnetic resonance spectroscopy (MRS) studies, the ratio of excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters is often used as a proxy for this E/I balance. Recent MRS work found a positive correlation between GABA+ and Glx (glutamate+glutamine) in medial parietal cortex, providing validation for this proxy and supporting the link between the E/I balance observed in electrophysiology and that detected with MRS. Here we assess the same relationship, between GABA+ and Glx, in primary visual and motor cortices of resting male and female human participants. We find moderate to strong evidence that there is no positive correlation between these neurotransmitters in either location. We show this holds true when controlling for a range of other factors (i.e., demographics, signal quality, tissue composition, other neurochemicals) and regardless of the state of neural activity (i.e., resting/active). These results show that there is no brain-wide balance between excitatory and inhibitory neurotransmitters and indicates a dissociation between the E/I balance observed in electrophysiological work and the ratio of MRS-detected neurotransmitters.
Opposing motors provide mechanical and functional robustness in the human spindle
Authors: Neahring Lila , Cho Nathan H. , Dumont Sophie 
Published: March 2021

SummaryAt each cell division, the spindle self-organizes from microtubules and motors. How the spindle’s diverse motors, often acting redundantly or in opposition, collectively give rise to its emergent architecture, mechanics, and function is unknown. In human spindles, the motors dynein and Eg5 generate contractile and extensile stress, respectively. Inhibiting dynein or its targeting factor NuMA leads to unfocused, turbulent spindles and inhibiting Eg5 leads to monopoles, yet bipolar spindles form when both are inhibited together. What, then, are the roles of these opposing motors? Here we generate NuMA/dynein- and Eg5-doubly inhibited spindles that not only attain a typical metaphase shape and size, but also undergo anaphase. However, these spindles have reduced microtubule dynamics and are mechanically fragile, fracturing under force. Further, they exhibit lagging chromosomes and dramatic left-handed twist at anaphase. Thus, while these opposing motor activities are not required for the spindle’s shape, they are essential to its mechanical and functional robustness. Together, this work suggests a design principle whereby opposing active stresses provide robustness to force-generating cellular structures.
PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta
Authors: Shiura Hirosuke , Ono Ryuichi , Tachibana Saori , Kohda Takashi , Kaneko-Ishino Tomoko , Ishino Fumitoshi 
Published: March 2021

AbstractThe therian-specific gene paternally expressed 10 (Peg10) plays an essential role in placenta formation:Peg10knockout (KO) mice exhibit early embryonic lethality due to severe placental defects. The PEG10 protein exhibits homology to long terminal repeat (LTR) retrotransposon GAG and POL proteins, therefore mice harboring a mutation in its highly conserved viral aspartic protease motif in the POL-like region were generated because it is essential for LTR retrotransposons/retroviruses. Intriguingly, frequent perinatal lethality, not early embryonic lethality, was observed with fetal and placental growth retardation starting mid-gestation. In the mutant placentas, severe defects were observed in the fetal vasculature, where PEG10 is expressed in the three trophoblast cell layers that surround fetal capillary endothelial cells. Thus,Peg10has essential roles not only in early placenta formation, but also in placental vasculature maintenance from mid- to late-gestation. This implies that along the feto-maternal placenta interface an interaction occurs between two retrovirus-derived genes,Peg10and retrotransposon Gag like 1 (Rtl1,also calledPeg11), that is essential for the maintenance of fetal capillary endothelial cells.Summary statementDisruption of the highly conserved viral aspartic protease domain in PEG10 causes placental abnormality leading to perinatal lethality in mice.
Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair
Authors: Furman Christopher M. , Wang Ting-Yi , Zhao Qiuye , Yugandhar Kumar , Yu Haiyuan , Alani Eric 
Published: March 2021

AbstractThe DNA mismatch repair (MMR) factor Mlh1-Pms1 contains long intrinsically disordered regions (IDRs). While essential for MMR, their exact functions remain elusive. We performed cross-linking mass spectrometry to identify the major interactions within the Mlh1-Pms1 heterodimer and used this information to insert FRB and FKBP dimerization domains into the IDRs of Mlh1 and Pms1. Yeast bearing these constructs were grown with rapamycin to induce dimerization. Strains containing FRB and FKBP domains in the Mlh1 IDR displayed complete MMR defects when grown with rapamycin, but removing rapamycin restored MMR functions. Furthermore, linking the Mlh1 and Pms1 IDRs through FRB-FKBP dimerization disrupted Mlh1-Pms1 binding to DNA, inappropriately activated Mlh1-Pms1, and caused MMR defectsin vivo. We conclude that dynamic and coordinated rearrangements of the MLH IDRs regulate how the complex clamps DNA to catalyze MMR. The application of the FRB-FKBP dimerization system to interrogatein vivofunctions of a critical repair complex will be useful for probing IDRs in diverse enzymes and to probe transient loss of MMR on demand.
Impact of COVID-19 pandemic on Black, Asian and Minority Ethnic (BAME)
communities: a qualitative study on the perspectives of BAME community
leaders
Authors: Mahmood Fesani , Acharya Dev , Kumar Kanta , Paudyal Vibhu 
Published: March 2021

ABSTRACT

Objectives
The aim of this study was to explore the perspectives of BAME community
leaders in relation to - the impact of the COVID-19 pandemic on their
communities; and BAME community’s perception, understanding and adherence to
Government guidelines on COVID-19 public health measures.

Design
A phenomenological approach was adopted using qualitative
semi-structured interviews.

Settings
Community organisations and places of worships in the West Midlands
region of England.

Participants
Community leaders were recruited through organisations representing BAME
communities and religious places of worship.

Results
A total of 19 participants took part. Participants alluded to historical
and structural differences for the observed disparities in COVID-19
morbidity and mortality. Many struggled with lockdown measures which impeded
cultural and religious gatherings that were deemed to be integral to the
community. Cultural and social practices led to many suffering on their own
as discussion of mental health was still deemed a taboo within many
communities. Many expressed their community’s reluctance to report symptoms
for the fear of financial and physical health implications. They reported
increase in hate crime which was deemed to be exacerbated due to perceived
insensitive messaging from authority officials and historical structural
biases. Access and adherence to government guidelines was an issue for many
due to language and digital barriers. Reinforcement from trusted community
and religious leaders encouraged adherence. Points of support such as food
banks were vital in ensuring essential supplies during the pandemic. Many
could not afford masks and sanitisers.

Conclusion
The study highlights the perceived impact of COVID-19 pandemic on BAME
communities. Government agencies and public health agencies need to
integrate with the community, and community leaders to penetrate the key
messages and deliver targeted yet sensitive public health advice which
incorporates cultural and religious practices. Addressing route cause of
disparities is imperative to mitigate current and future pandemics.

Strengths and limitations of this study

To our knowledge, this is the first study in England to
investigate the understanding of risk and impact of COVID-19 using
the perspectives of BAME community leaders.

Participants represented diverse BAME community organisations
and places of worship.

Participant recruitment was limited to one of the seven regions
within England with the highest proportion of BAME
populations.

Results may not be generalizable to any BAME communities not
represented in the data.
Low-dose lung radiotherapy for COVID-19 lung disease: a preclinical efficacy study in a bleomycin model of pneumonitis
Authors: Jackson Mark R , Stevenson Katrina , Chahal Sandeep K , Curley Emer , Finney George E , Gutierrez-Quintana Rodrigo , Onwubiko Evarest , Rupp Angelika F , Strathdee Karen , MacLeod Megan KL , McSharry Charles , Chalmers Anthony J 
Published: March 2021

AbstractPurposeLow-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.Materials and methodsFemale C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).ResultsBleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall,bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) prevented further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not modulate bodyweight or flow cytometric readouts of bleomycin-induced pneumonitis.ConclusionsOur data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide preliminary evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.
Knowledge discovery in research on domestic violence: an overview of the last fifty years
Authors: Basilio Marcio Pereira , Pereira Valdecy , de Oliveira Max William Coelho Moreira , da Costa Neto Antonio Fernandes , Moraes Orlinda Claudia Rosa de , Siqueira Samya Cotta Brandão 
Published: March 2021

PurposeThe database of the Web of Science (WoS) was searched for publications from January 1945–May 7, 2020 on the topic of domestic violence in titles, abstracts and keywords. The references were analyzed using the R bibliometrix package, and abstracts were analyzed using latent Dirichlet allocation (LDA) with collapsed Gibbs sampling to obtain topics related to domestic violence.Design/methodology/approachThe aim of the study is to explore and provide an overview of research carried out on domestic violence, in its various aspects, over the past fifty years.FindingsAs a result of the research, the authors can assert that in the last fifty years, 32,298 authors have produced 19,495 documents on the theme of policing strategy and related subjects in 111 countries. Scientific production in this area grows at a rate of 12.81 per year. The United States of America is the leading country in publications with 48.14%, followed by the United Kingdom with 7.57% and Australia with 6.05%. Regarding universities, the highlight is the University of California with 664 publications, followed by the University of London with 515 and the University of North Carolina with 484. As for journals, the highlight is the Journal of Interpersonal Violence, Journal of Family Violence and Violence Against Women, which account for more than 14.32% of all indexed literature. Regarding the authors, the highlight is Campbell J.C and Feder G. Probabilistic topic modeling revealed that 18% of the topics concentrate 90% of all tokens. Topic 1 accounts for 27.9% of the sample and conducts research related to intimate partner violence.Practical implicationsAs a practical implication of using the LDA in the bibliographic review, we infer that its capacity to explore large masses of data allows the researcher to explore an infinitely greater amount than the traditional methods of systematic literature review.Originality/valueThe value of these studies is summarized in the presentation of an overview on the theme in the last fifty years, offering the opportunity for other researchers to use this research as a starting point for other analyses.