bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct structural connections between auditory and visual motion selective regions in humans
Authors: Gurtubay-Antolin A. , Battal C. , Maffei C. , Rezk M. , Mattioni S , Jovicich J. , Collignon O. 
Published: June 2020

ABSTRACTIn humans, the occipital middle-temporal region (hMT+/V5) specializes in the processing of visual motion, while the Planum Temporale (hPT) specializes in auditory motion processing. It has been hypothesized that these regions might communicate directly to achieve fast and optimal exchange of multisensory motion information. In this study, we investigated for the first time in humans the existence of direct white matter connections between visual and auditory motion-selective regions using a combined functional- and diffusion-MRI approach. We found reliable evidence supporting the existence of direct white matter connections between individually and functionally defined hMT+/V5 and hPT. We show that projections between hMT+/V5 and hPT do not overlap with large white matter bundles such as the Inferior Longitudinal Fasciculus (ILF) nor the Inferior Frontal Occipital Fasciculus (IFOF). Moreover, we did not find evidence for the existence of reciprocal projections between the face fusiform area and hPT, supporting the functional specificity of hMT+/V5 – hPT connections. Finally, evidence supporting the existence of hMT+/V5 – hPT connections was corroborated in a large sample of participants (n=114) from the human connectome project. Altogether, this study provides first evidence supporting the existence of direct occipito-temporal projections between hMT+/V5 and hPT which may support the exchange of motion information between functionally specialized auditory and visual regions and that we propose to name the middle (or motion) occipito-temporal track (MOTT).
Dissecting the DNA binding landscape and gene regulatory network of p63 and p53
Authors: Riege Konstantin , Kretzmer Helene , Sahm Arne , McDade Simon S. , Hoffmann Steve , Fischer Martin 
Published: June 2020

AbstractThe transcription factor (TF) p53 is the best-known tumor suppressor, but its ancient sibling p63 (ΔNp63) is a master regulator of epidermis development and a key oncogenic driver in squamous cell carcinomas (SCC). Despite multiple gene expression studies becoming available in recent years, the limited overlap of reported p63-dependent genes has made it difficult to decipher the p63 gene regulatory network (GRN). In particular, analyses of p63 response elements differed substantially among the studies. To address this intricate data situation, we provide an integrated resource that enables assessing the p63-dependent regulation of any human gene of interest. Here, we use a novel iterative de novo motif search approach in conjunction with extensive publicly available ChIP-seq data to achieve a precise global distinction between p53 and p63 binding sites, recognition motifs, and potential co-factors. We integrate all these data with enhancer:gene associations to predict p63 target genes and identify those that are commonly de-regulated in SCC and, thus, may represent candidates for therapeutic interventions.
Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival
Authors: Gagliardi Paolo Armando , Dobrzyński Maciej , Jacques Marc-Antoine , Dessauges Coralie , Ender Pascal , Blum Yannick , Hughes Robert M , Cohen Andrew R. , Pertz Olivier 
Published: June 2020

AbstractCell death events continuously challenge epithelial barrier function, yet are crucial to eliminate old or critically damaged cells. How such apoptotic events are spatio-temporally organized to maintain epithelial homeostasis remains unclear. We observe waves of Extracellular Signal-Regulated Kinase (ERK) and AKT serine/threonine kinase (Akt) activity pulses that originate from apoptotic cells and propagate radially to healthy surrounding cells. This requires Epidermal Growth Factor Receptor (EGFR) and matrix metalloproteinase (MMP) signaling. At the single-cell level, ERK/Akt waves act as spatial survival signals that locally protect cells in the vicinity of the epithelial injury from apoptosis for a period of 3-4h. At the cell population level, ERK/Akt waves maintain epithelial homeostasis (EH) in response to mild or intense environmental insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to environmental insults.
The balancing act ofNipponites mirabilis(Nostoceratidae, Ammonoidea): managing hydrostatics during a complex ontogenetic trajectory
Authors: Peterman David J. , Mikami Tomoyuki , Inoue Shinya 
Published: June 2020

AbstractNipponitesis a heteromorph ammonoid with a complex and unique morphology that obscures its mode of life and ethology. The seemingly aberrant shell of this Late Cretaceous nostoceratid seems deleterious. However, hydrostatic simulations suggest that this morphology confers several advantages for exploiting a quasi-planktic mode of life. Virtual, 3D models ofNipponites mirabiliswere used to compute various hydrostatic properties through 14 ontogenetic stages. At each stage,Nipponiteshad the capacity for neutral buoyancy and was not restricted to the seafloor. Throughout ontogeny, horizontally facing to upwardly facing soft body orientations were preferred. These orientations were aided by the obliquity of the shell’s ribs, which were parallel to former positions of the aperture during life. Static orientations were somewhat fixed, inferred by stability values that are slightly higher than extantNautilus. The initial open-whorled, planispiral phase is well suited to horizontal backwards movement with little rocking.Nipponitesthen deviates from this coiling pattern with a series of alternating U-shaped bends in the shell. This modification allows for proficient rotation about the vertical axis, while possibly maintaining the option for horizontal backwards movement by redirecting its hyponome. These particular hydrostatic properties likely result in a tradeoff between hydrodynamic streamlining, suggesting thatNipponitesassumed a low energy lifestyle of slowly pirouetting in search for planktic prey. Each computed hydrostatic property influences the others in some way, suggesting thatNipponitesmaintained a delicate hydrostatic balancing act throughout its ontogeny in order to facilitate this mode of life.
ZBTB38 is dispensable for hematopoiesis and antibody responses
Authors: Wong Rachel , Bhattacharya Deepta 
Published: June 2020

AbstractMembers of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor. Germinal center B cells lacking ZBTB38 dysregulated very few genes relative to wild-type and heterozygous littermate controls. Accordingly, mice with hematopoietic-specific deletion ofZbtb38showed normal germinal center B cell numbers and antibody responses following immunization with hapten-protein conjugates. Memory B cells from these animals functioned normally in secondary recall responses. Despite expression of ZBTB38 in hematopoietic stem cells, progenitors and mature myeloid and lymphoid lineages were also present in normal numbers in mutant mice. These data demonstrate that ZBTB38 is dispensable for hematopoiesis and antibody responses. These conditional knockout mice may instead be useful in defining the functional importance of ZBTB38 in other cell types and contexts.
Catalytic domain plasticity of MKK7 reveals structural mechanisms of allosteric activation and new targeting opportunities
Authors: Schröder Martin , Tan Li , Wang Jinhua , Liang Yanke , Gray Nathanael S. , Knapp Stefan , Chaikuad Apirat 
Published: June 2020

AbstractMKK7 (MEK7) is a key regulator of the JNK stress signaling pathway and targeting MKK7 has been proposed as a chemotherapeutic strategy. Detailed understanding of the MKK7 structure and factors that impact its activity is therefore of critical importance. Here, we present a comprehensive set of MKK7 crystal structures revealing insights into catalytic domain plasticity and the role of the N-terminal regulatory helix, conserved in all MAP2Ks, mediating kinase activation. Crystal structures harboring this regulatory helix revealed typical structural features of active kinase, providing exclusively a first model of the MAP2K active state. A small molecule screening campaign yielded multiple scaffolds, including type-II irreversible inhibitors a binding mode that has not been reported previously. We also observed an unprecedented allosteric pocket located in the N-terminal lobe for the approved drug ibrutinib. Collectively, our structural and functional data expand and provide alternative targeting strategies for this important MAP2K kinase.
A natural variant of the essential host geneMMS21restricts the parasitic 2-micron plasmid inSaccharomyces cerevisiae
Authors: Hays Michelle , Young Janet M. , Levan Paula , Malik Harmit S. 
Published: June 2020

AbstractOngoing antagonistic coevolution with selfish genetic elements (SGEs) can drive the evolution of host genomes. Here, we investigated whether natural variation allows someSaccharomyces cerevisiaestrains to suppress 2-micron (2μ) plasmids, multicopy nuclear parasites that have co-evolved with budding yeasts. To quantitatively measure plasmid stability, we developed a new method, Single-Cell Assay for Measuring Plasmid Retention (SCAMPR) that measures copy number heterogeneity and 2μ plasmid loss in live cells. Next, in a survey of 52 naturalS. cerevisiaeisolates we identified three strains that lack endogenous 2μ plasmids and reproducibly inhibit mitotic plasmid stability. Thus, their lack of endogenous 2μ plasmids is genetically determined, rather than the result of stochastic loss. Focusing on one isolate (Y9 ragi strain), we determined that plasmid restriction is heritable and dominant. Using bulk segregant analysis, we identified a high-confidence Quantitative Trait Locus (QTL) for mitotic plasmid instability on Y9 chromosome V. We show that a single amino acid change inMMS21is associated with increased 2-micron instability.MMS21is an essential gene, encoding a SUMO E3 ligase and a member of the Smc5/6 complex, which is involved in sister chromatid cohesion, chromosome segregation, and DNA repair. Our analyses leverage natural variation to uncover a novel means by which budding yeasts can overcome a highly successful genetic parasite.
Biased agonists of the chemokine receptor CXCR3 differentially drive formation of Gαi:β-arrestin complexes
Authors: Zheng Kevin , Smith Jeffrey S. , Warman Anmol , Choi Issac , Gundry Jaimee N. , Pack Thomas F. , Inoue Asuka , Caron Marc G. , Rajagopal Sudarshan 
Published: June 2020

AbstractG-protein-coupled receptors (GPCRs), the largest family of cell surface receptors, signal through the proximal effectors G proteins and β-arrestins to influence nearly every biological process. Classically, the G protein and β-arrestin signaling pathways have largely been considered separable. Recently, direct interactions between Gαprotein and β-arrestin have been described and suggest a distinct GPCR signaling pathway. Within these newly described Gα:β-arrestin complexes, Gαi/o, but not other Gαprotein subtypes, have been appreciated to directly interact with β-arrestin, regardless of canonical GPCR Gαprotein subtype coupling. However it is unclear how biased agonists differentially regulate this newly described Gαi:β-arrestin interaction, if at all. Here we report that endogenous ligands (chemokines) of the GPCR CXCR3, CXCL9, CXCL10, and CXCL11, along with two small molecule biased CXCR3 agonists, differentially promote the formation of Gαi:β-arrestin complexes. The ability of CXCR3 agonists to form Gαi:β-arrestin complexes does not correlate well with either G protein signaling or β-arrestin recruitment. Conformational biosensors demonstrate that ligands that promoted Gαi:β-arrestin complex formation generated similar β-arrestin conformations. We find these Gαi:β-arrestin complexes can associate with CXCR3, but not with ERK. These findings further support that Gαi:β-arrestin complex formation is a distinct GPCR signaling pathway and enhance our understanding of biased agonism.
Chemoprophylaxis of COVID-19 with hydroxychloroquine - a study of health care workers attitude, adherence to regime and side effects
Authors: Bhattacharyya Debajyoti , Raizada Neeraj , Nagappa Bharathnag , Tomar Arvind , Maurya Prateek , Chaudhary Ashok , George Mini , Katiyal Deepty , Rajora Srishti , Singh Nikky 
Published: June 2020

AbstractBackgroundThere are apprehensions amongst healthcare worker (HCWs) about COVID-19. The HCWs have been given hydroxychloroquine (HCQ) chemoprophylaxis for seven weeks as per Government of India guidelines.ObjectivesTo assess the apprehensions amongst HCWs about COVID-19 and to document accessibility, adherence and side effects related to HCQ prophylaxis in HCWs.MethodsA longitudinal follow up study was conducted in a tertiary care hospital. HCQ was given in the dose of 400 mg twice on day one, and then 400 mg weekly for seven weeks. 391 HCWs were interviewed using semi structured questionnaire.Results62.2% HCWs expressed perceived danger posted by COVID-19 infection. Doctors (54%) showed least acceptance and paramedics (88%) showed highest acceptance to chemoprophylaxis. 17.5% participants developed at least one of the side effects to HCQ. Females and nursing profession were significantly associated with adverse effects. Common side effects were gastro-intestinal symptoms, headache and abnormal mood change. Most of these were mild, not requiring any intervention. Gender, professions and perceived threat of COVID-19 were significantly associated with acceptance and adherence to HCQ prophylaxis.ConclusionTwo third of HCWs had perceived danger due to COVID-19. Three fourth of the HCWs accepted chemoprophylaxis and four out of five who accepted had complete adherence to prophylaxis schedule. One out of five had developed at least one of side effects; however, most of these were mild not requiring any intervention.
Modelling the impact of reducing control measures on the COVID-19 pandemic in a low transmission setting
Authors: Scott Nick , Palmer Anna , Delport Dominic , Abeysuriya Romesh , Stuart Robyn , Kerr Cliff C. , Mistry Dina , Klein Daniel J. , Sacks-Davis Rachel , Heath Katie , Hainsworth Samuel , Pedrana Alisa , Stoove Mark , Wilson David P. , Hellard Margaret 
Published: June 2020

AbstractAimsWe assessed COVID-19 epidemic risks associated with relaxing a set of physical distancing restrictions in the state of Victoria, Australia – a setting with low community transmission – in line with a national framework that aims to balance sequential policy relaxations with longer-term public health and economic need.MethodsAn agent-based model, Covasim, was calibrated to the local COVID-19 epidemiological and policy environment. Contact networks were modelled to capture transmission risks in households, schools and workplaces, and a variety of community spaces (e.g. public transport, parks, bars, cafes/restaurants) and activities (e.g. community or professional sports, large events). Policy changes that could prevent or reduce transmission in specific locations (e.g. opening/closing businesses) were modelled in the context of interventions that included testing, contact tracing (including via a smartphone app), and quarantine.ResultsPolicy changes leading to the gathering of large, unstructured groups with unknown individuals (e.g. bars opening, increased public transport use) posed the greatest risk, while policy changes leading to smaller, structured gatherings with known individuals (e.g. small social gatherings) posed least risk. In the model, epidemic impact following some policy changes took more than two months to occur. Model outcomes support continuation of working from home policies to reduce public transport use, and risk mitigation strategies in the context of social venues opening, such as >30% population-uptake of a contact-tracing app, physical distancing policies within venues reducing transmissibility by >40%, or patron identification records being kept to enable >60% contact tracing.ConclusionsIn a low transmission setting, care should be taken to avoid lifting sequential COVID-19 policy restrictions within short time periods, as it could take more than two months to detect the consequences of any changes. These findings have implications for other settings with low community transmission where governments are beginning to lift restrictions.
Coronavirus Disease 2019 (COVID-19): Knowledge, attitudes, practices (KAP) and misconceptions in the general population of Katsina State, Nigeria
Authors: Isah Murtala Bindawa , Abdulsalam Mahmud , Bello Abubakar , Ibrahim Muawiyya Idris , Usman Aminu , Nasir Abdullahi , Abdulkadir Bashir , Usman Ahmed Rufai , Ibrahim Kabir Matazu , Sani Aminu , Aliu Ma’awuya , Kabir Shema’u Abba , Shuaibu Abdullahi , Nass Shafique Sani 
Published: June 2020

AbstractIntroductionOver six million cases of Coronavirus Disease 2019 (COVID-19) were reported globally by the second quarter of 2020. The various forms of interventions and measures adopted to control the disease affected people’s social and behavioural practices.AimThis study aims to investigate COVID-19 related knowledge, attitudes and practices (KAP) as well as misconceptions in Katsina state, one of the largest epicentres of the COVID-19 outbreak in Nigeria.MethodsThe study is a cross-sectional survey of 722 respondents using an electronic questionnaire through the WhatsApp media platform.ResultsOne thousand five hundred (1500) questionnaires were sent to the general public with a response rate of 48% (i.e. 722 questionnaires completed and returned). Among the respondents, 60% were men, 45% were 25-39 years of age, 56% held bachelor’s degree/equivalent and above and 54% were employed. The study respondents’ correct rate in the knowledge questionnaire was 80% suggesting high knowledge of the disease. A significant correlation (P < 0.05) exists between the average knowledge score of the respondents and their level of education (τb = 0.16). Overall, most of the respondents agreed that the COVID-19 will be successfully controlled (84%) and the Nigerian government would win the fight against the pandemic (71%). Men were more likely than female (P < 0.05) to have recently attended a crowded place. Being more educated (bachelor’s degree or equivalent and above vs diploma or equivalent and below) is associated with good COVID-19 related practices. Among the respondents, 83% held at least one misconception related to COVID-19, with the most frequent being that the virus was created in a laboratory (36%). Respondents with a lower level of education received and trust COVID-19 related information from local radio and television stations and respondents at all levels of education selected that they would trust health unit and health care workers for relevant COVID-19 information.ConclusionAlthough there is high COVID-19 related knowledge among the sample, misconceptions are widespread among the respondents. These misconceptions have consequences on the short- and long-term control efforts against the disease and hence should be incorporated in targeted campaigns. Health care related personnel should be at the forefront of the campaign.
Agreement between arterial and capillary pH, pCO2 and lactate in patients in the emergency department
Authors: Collot V. , Malinverni S. , Schweitzer E. , Haltout J. , Mols P. , Bartiaux M. 
Published: June 2020

AbstractStudy objectiveThe primary objective of the study was a quantitative analysis to assess the mean difference and 95% confidence interval of the difference between capillary and arterial blood gas analyses for pH, pCO2 and lactate. Secondary objective was to measure the sensitivity and specificity of capillary samples to detect altered pH, hypercarbia and lactic acidosis.MethodsAdults admitted to the ED for whom the treating physician deemed necessary an arterial blood gas analysis (BGA) were screened for inclusion. Simultaneous arterial and capillary samples were drawn for BGA. Agreement between the two methods for pH, pCO2 and lactate were studied with Bland-Altman bias plot analysis. Sensitivity, specificity, positive and negative predictive value as well as AUC were calculated for the ability of capillary samples to detect pH values outside normal ranges, hypercarbia and hyperlactatemia.Results197 paired analyses were included in the study. Mean difference for pH, between arterial and capillary BGA was 0.0095, 95% limits of agreement were -0.048 to 0.067. For pCO2, mean difference was -0.3 mmHg, 95% limits of agreement were -8.5 to 7.9 mmHg. Lactate mean difference was -0.93 mmol/L, 95% limits of agreement were -2.7 to 0.8 mmol/L. At a threshold of 7.34 for capillary pH had 98% sensitivity and 97% specificity to detect acidemia; at 45.9 mmHg capillary pCO2 had 89% sensitivity and 96% specificity to detect hypercarbia. Finally at a threshold of 3.5 mmol/L capillary lactate had 66% sensitivity to detect lactic acidosis.ConclusionCapillary measures of pH, pCO2 and lactate can’t replace arterial measurements although there is high concordance between the two methods for pH and pCO2 and moderate concordance for lactate. Capillary blood gas analysis had good accuracy when used as a screening tool to detect altered pH and hypercarbia but insufficient sensitivity and specificity when screening for lactic acidosis.
Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda
Authors: Nannyonga Betty K , Wanyenze Rhoda K , Kaleebu Pontiano , Ssenkusu John M , Lutalo Tom , Makumbi Fredrick Edward , Kwizera Arthur , Byakika Pauline , Kirungi Willford , Bosa Henry Kyobe , Ssembatya Vincent A , Mwebesa Henry , Atwine Diana , Aceng Jane Ruth , Woldermariam Yonas Tegegn ,   all members of the Uganda SARS-COV-2 Scientific Advisory Committee
Published: June 2020

AbstractEvidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of SARS-COV-2 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.