bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compensatory hippocampal neurogenesis in the absence of cognitive impairment following experimental hippocampectomy in adult rats
Authors: Cardoso Giuliana T. M. , Gomes-Leal Walace , Franco Edna C. S. , Gama Jessica S. , Gomes Francinaldo L. , Brino Ana Leda F. , Pereira Antonio , Lima. Silene M. A. 
Published: June 2020

AbstractTemporal lobe epilepsy (TLE) is the commonest type of focal epilepsy in adult humans. In refractory TLE, patients are indicated for unilateral resection of the affected hippocampus (hippocampectomy), which generally does not cause any cognitive impairment. Once adult hippocampus is a region of endogenous neurogenesis, we have hypothesized that a compensatory increase in hippocampal neurogenesis might occur in the remaining hippocampus after unilateral hippocampectomy. To test this hypothesis, we performed unilateral hippocampectomy in adult Wistar rats (n=12). Sham animals were not hippocampectomized (n=6). Animals were deeply anesthetized and adjacent cortex and hippocampus of the left hemisphere were completely removed. They were perfused at 15 (G15, n=6) or 30 (G30, n=6) days post-surgery. Behavioral tests were performed to address possible cognitive impairments. We did not find any cognitive impairment in the hippocampectomized animals. Histopathology was performed using thionine staining and mature neurons and migratory neuroblasts were immunolabeled using anti-NeuN and anti-doublecortin (DCX) antibodies, respectively. The remaining hippocampus presented higher numbers of DCX positive cells compared to control (p<0.001) at both G15 and G30. The results suggest increased compensatory adult neurogenesis following experimental unilateral hippocampectomy in adult rats, which may contribute to absence of cognitive impairments.
Post-weaning social isolation increases ΔFosB/FosB protein expression in the prefrontal cortex and hippocampus in mice
Authors: Noback Michael , Zhang Gongliang , White Noelle , Barrow James C. , Carr Gregory V. 
Published: June 2020

AbstractSocial isolation is a growing public health concern across the lifespan. Specifically, isolation early in life, during critical periods of brain development, increases the risk of psychiatric disorders later in life. Previous studies of isolation models in mice have shown distinct neurological abnormalities in various regions of the brain, but the mechanism linking the experience of isolation to these phenotypes is unclear. In this study, we show that ΔFosB, a long-lived transcription factor associated with chronic stress responses and drug-induced neuroplasticity, is upregulated in the medial prefrontal cortex and hippocampus of adult C57BL/6J mice isolated for two weeks post-weaning. Additionally, a related transcription factor, FosB, is also increased in the medial prefrontal cortex in socially isolated females. These results show that short-term isolation during the critical post-weaning period has long-lasting and sex-dependent effects on gene expression in brain.
Comparative study of four SARS-CoV-2 Nucleic Acid Amplification Test (NAAT) platforms demonstrates that ID NOW performance is impaired substantially by patient and specimen type
Authors: Lephart Paul R. , Bachman Michael , LeBar William , McClellan Scott , Barron Karen , Schroeder Lee , Newton Duane W. 
Published: June 2020

AbstractThe advent of the COVID-19 pandemic in the United States created a unique situation where multiple molecular diagnostic assays with various indications for use in the detection of SARS-CoV-2 rapidly received Emergency Use Authorization by the FDA, were validated by laboratories and utilized clinically, all within a period of a few weeks. We compared the performance of four of these assays that were being evaluated for use at our institution: Abbott RealTime m2000 SARS-CoV-2 Assay, DiaSorin Simplexa COVID-19 Direct, Cepheid Xpert Xpress SARS-CoV-2 and Abbott ID NOW COVID-19. Nasopharyngeal and nasal specimens were collected from 88 ED and hospital-admitted patients and tested by the four methods in parallel to compare performance. ID NOW performance stood out as significantly worse than the other three assays despite demonstrating comparable analytic sensitivity. Further study determined that the use of a foam nasal swab compared to a nylon flocked nasopharyngeal swab, as well as use in a population chronically vs. acutely positive for SARS-CoV-2, were significant factors in the poor comparable performance.
Effect of gamma sterilization on filtering efficiency of various respiratory facemasks
Authors: Kumar Amit , Sangeetha D.N. , Yuvaraj Ramani , Menaka M. , Subramanian V. , Venkatraman B. 
Published: June 2020

AbstractThree types of respiratory masks viz N95, nonwoven fabric and double layer cotton cloth are being used as an essential inhalation protective measure against COVID-19 by suppressing the entry of respiratory droplets. The filtering efficiency of these masks were tested before and after sterilisation using gamma radiation for the two flow rate conditions corresponding normal breath rate (20lpm) and during sneezing/coughing (90lpm).Sterilisation is carried out using a gamma irradiator containing Co-60 source for the two dose exposures viz. 15kGy and 25kGy.The filtering efficiency for surgical (nonwoven fabric) and double layer cotton cloth mask is found to vary from 18% to 22% for the cumulative particle of size ≥ 0.3µm in both un-irradiated and irradiated condition. The filtration efficiency of N95 mask is found to be reduced to 70% for the most penetrating particle size (0.3 µm) with the flow rate of 20lpm and further reduced for particles in the range of 0.1 and 0.2µm with flow rate of 90 lpm. The reduction in efficiency after gamma sterilization is associated with reduction of electrostatic interaction of filter medium with particles laden in the air stream. Even with reduced filtering efficiency due to gamma sterilisation, the N95 masks are much superior than the surgical and cloth masks. Instead of disposing N95 mask after single use, they can be reused a few times as N70 mask during this pandemic crisis after sterilisation using gamma radiation.
Anemia and iron metabolism in COVID-19: A systematic review and meta-analysis
Authors: Taneri Petek Eylul , Alejandro Gómez-Ochoa Sergio , Llanaj Erand , Francis Raguindin Peter , Rojas Lyda Z. , Wyssmann Beatrice Minder , Kopp-Heim Doris , Hautz Wolf E. , Eisenga Michele F. , Franco Oscar H. , Glisic Marija , Muka Taulant 
Published: June 2020

ABSTRACTIron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). If confirmed, this has important implications for the more than 1.62 billion people estimated to have anemia globally. We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and prevalence of anemia) in patients diagnosed with COVID-19, and explore their prognostic value. Six bibliographic databases were searched up to May 5th2020. We included 56 unique studies, with data from 14,044 COVID-19 patients (59 years median age). Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 130.41 g/L (95% Confidence Interval (CI), 128.42; 132.39) and 673.91 ng/mL (95% CI, 420.98; 926.84), respectively. Hemoglobin levels decreased with advancing age and increasing percentage of comorbid and critically ill patients, while levels of ferritin increased with increasing male proportion and mean hemoglobin levels. Compared to moderate cases, severe cases had lower pooled mean hemoglobin [weighted mean difference (WMD), –4.21 (95% CI –6.63; –1.78)] and higher ferritin [WMD, –730.55 ng/mL (95% CI 413.24; 1047.85)]. A significant difference in mean ferritin level of 1027.23 ng/mL (95% CI 819.53; 1234.94) was found between survivors and non-survivors, but not in hemoglobin levels. No studies provided information on anemia or other biomarkers of interest. Future studies should explore the impact of iron metabolism and anemia and in the pathophysiology, prognosis, and treatment of COVID-19.
Are antibodies tests accurate? Understanding predictive values and uncertainty of serology tests for the novel coronavirus
Authors: Brownstein Naomi C , Chen Yian Ann 
Published: June 2020

ABSTRACTAntibodies testing in the coronavirus era is frequently promoted, but the underlying statistics behind their validation has come under more scrutiny in recent weeks. We provide calculations, interpretations, and plots of positive and negative predictive values under a variety of scenarios. Prevalence, sensitivity, and specificity are estimated within ranges of values from researchers and antibodies manufacturers. Illustrative examples are highlighted, and interactive plots are provided in the Supplementary Material. Implications are discussed for society overall and across diverse locations with different levels of disease burden. Specifically, the proportion of positive serology tests that are false can differ drastically from up to 3% to 88% for people from different places with different proportions of infected people in the populations while the false negative rate is typically under 10%.
Applying a Prospective Space-Time Scan Statistic to Examine the Evolution of COVID-19 Clusters in the State of São Paulo, Brazil
Authors: Ferreira R.V. , Martines M.R. , Toppa R.H. , Assunção L.M. , Desjardins M.R. , Delmelle E.M. 
Published: June 2020

AbstractWe present the first geographic study that uses space-time statistics to monitor COVID-19 in Brazil. The first cases of COVID-19 were confirmed in December 2019 in Wuhan, China, caused by the contamination of the SARS-CoV-2 virus, and quickly turned into a pandemic. In Brazil, the first case occurred on January 23rd, 2020 but was officially reported by the Brazilian Ministry of Health on February 25th. Since then, the number of deaths and people infected by COVID-19 in Brazil have been steadily increasing. Despite the underreporting of coronavirus cases by government agencies across the country, the State of São Paulo has the highest rate among all Brazilian States. Thus, it is essential to detect which areas contain the highest concentration of COVID-19 to implement public policies, to mitigate the spread of the epidemic. To identify these critical areas, we utilized daily confirmed case data from the Brasil.IO website between February 25th, 2020 to May 5th, 2020; which were aggregated to the municipality level. A prospective space-time scan statistic was applied to evaluate possible active clusters in three different time periods. The results visualize the space-time evolution and dynamics of COVID-19 clusters in the State of São Paulo. Since the first study period, the results highlight approximately 4.6 times the number of municipalities belonging to a significant cluster with a RR>1 on May 5th. These results can inform health authorities and public management to take the necessary measures to minimize the transmission of COVID-19 and track the evolution of significant space-time clusters.HIGHLIGHTSProspective space-time statistics can improve COVID-19 surveillance in BrazilAll statistically significant clusters are located near São Paulo MunicipalityThere are municipalities with relative risk highest than one in the countryside4.6 times the number of municipalities belong to a significant cluster on May 5th
YAP and β-catenin co-operate to drive oncogenesis in basal breast cancer
Authors: Quinn Hazel , Koren Elle , Vogel Regina , Popp Oliver , Mertins Philipp , Messerschmidt Clemens , Marangoni Elisabetta , Fuchs Yaron , Birchmeier Walter 
Published: June 2020

AbstractTargeting cancer stem cells (CSCs) can serve as an effective approach toward limiting resistance to therapies and the development of metastases in many forms of cancer. While basal breast cancers encompass cells with CSC features, rational therapies remain poorly established. Here, we show that receptor tyrosine kinase Met signalling promotes the activity of the Hippo component YAP in basal breast cancer. Further analysis revealed enhanced YAP activity within the CSC population. Using both genetic and pharmaceutical approaches, we show that interfering with YAP activity delays basal cancer formation, prevents luminal to basal trans-differentiation and reduces CSC survival. Gene expression analysis of YAP knock-out mammary glands revealed a strong decrease in β-catenin target genes in basal breast cancer, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, we find that nuclear YAP interacts and overlaps with β-catenin and TEAD4 at common gene regulatory elements. Analysis of proteomic data from primary breast cancer patients identified a significant upregulation of the YAP activity signature in basal compared to other breast cancers, suggesting that YAP activity is limited to basal types. Our findings demonstrate that in basal breast cancers, β-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal (triple-negative) breast cancers.
Transcontrol of cardiac mRNA translation in a protein length-dependent fashion
Authors: Witte Franziska , Ruiz-Orera Jorge , Ciolli Mattioli Camilla , Blachut Susanne , Adami Eleonora , Schulz Jana Felicitas , Schneider-Lunitz Valentin , Hummel Oliver , Patone Giannino , Mücke Michael Benedikt , Šilhavý Jan , Heinig Matthias , Bottolo Leonardo , Sanchis Daniel , Vingron Martin , Chekulaeva Marina , Pravenec Michal , Hubner Norbert , van Heesch Sebastiaan 
Published: June 2020

ABSTRACTLittle is known about the impact of naturally occurring genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate how genetic influences on mRNA translational efficiency are associated with complex disease phenotypes using a panel of rat recombinant inbred lines. We identify a locus for cardiac hypertrophy that is associated with a translatome-wide and protein length-dependent shift in translational efficiency. This master regulator primarily affects the translation of very short and very long protein-coding sequences, altering the physiological stoichiometric translation rates of sarcomere proteins. Mechanistic dissection of this locus points to altered ribosome assembly, characterized by accumulation of polysome half-mers, changed ribosomal configurations and misregulation of the small nucleolar RNASNORA48. We postulate that this locus enhances a pre-existing negative correlation between protein length and translation initiation in diseased hearts. Our work shows that a single genomic locus can trigger a complex, translation-driven molecular mechanism that contributes to phenotypic variability between individuals.Graphical AbstractHighlightsGenetic variability impacts protein synthesis rates in a rat model for cardiac hypertrophyAtranslocus affects stoichiometric translation rates of cardiac sarcomeric proteinsThis master regulator locus induces a global, protein length-dependent shift in translationDysregulated ribosome assembly induces half-mer formation and affects translation initiation rate
Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box
Authors: Reader Janette , van der Watt Mariёtte E. , Taylor Dale , Le Manach Claire , Mittal Nimisha , Ottilie Sabine , Theron Anjo , Moyo Phanankosi , Erlank Erica , Nardini Luisa , Venter Nelius , Lauterbach Sonja , Bezuidenhout Belinda , Horatscheck Andre , van Heerden Ashleigh , Boyle Grant A. , Calvo David , Mancama Dalu , Coetzer Theresa L. , Winzeler Elizabeth A. , Duffy James , Koekemoer Lizette L. , Basarab Gregory , Chibale Kelly , Birkholtz Lyn-Marié 
Published: June 2020

AbstractNew chemical matter is needed to target the divergent biology associated with the different life cycle stages ofPlasmodium. Here, we report the parallel screening of the Medicines for Malaria Venture Pandemic Response Box to identify multistage-active and stage-specific compounds against various life cycle stages ofPlasmodiumparasites (asexual parasites, stage IV/V gametocytes, gametes, oocysts and liver stages) and for endectocidal activity. Hits displayed unique chemotypes and included two multistage-active compounds, 16 asexual-targeted, six with prophylactic potential and ten gametocyte-targeted compounds. Notably, four structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity were identified: the JmjC inhibitor ML324, two azole antifungals including eberconazole, and the antitubercular clinical candidate SQ109. Besides ML324, none of these have previously attributed antiplasmodial activity, emphasizing the success ofde novoparallel screening against differentPlasmodiumstages to deliver leads with novel modes-of-action. Importantly, the discovery of such transmission-blocking targeted compounds covers a previously unexplored base for delivery of compounds required for malaria elimination strategies.
Robust T-cell signaling triggered on soft polydimethylsiloxane-supported lipid-bilayers
Authors: Lippert Anna H. , Dimov Ivan B. , Winkel Alexander , McColl James , Humphrey Jane , Chen Kevin Y. , Santos Ana Mafalda , Jenkins Edward , Franze Kristian , Davis Simon J. , Klenerman David 
Published: June 2020

AbstractThe T-cell receptor (TCR) is thought to be triggered either by mechano-transduction or local tyrosine phosphatase exclusion at cell-cell contacts. However, the effects of the mechanical properties of activating surfaces have only been tested for late-stage T-cell activation, and phosphatase segregation has mostly been studied on glass-supported lipid bilayers that favor imaging but are orders-of-magnitude stiffer than typical cells. We developed a method for attaching lipid bilayers to polydimethylsiloxane polymer supports, producing ‘soft bilayers’ with physiological levels of mechanical resistance (Young’s modulus of 4 kPa). Comparisons of T-cell behavior on soft and glass-supported bilayers revealed that early calcium signaling is unaffected by substrate rigidity, implying that early steps in TCR triggering are not mechanosensitive. Robust phosphatase exclusion was observed on the soft bilayers, however, suggesting it likely occurs at cell-cell contacts. This work sets the stage for an imaging-based exploration of receptor signaling under conditions closely mimicking physiological cell-cell contact.
Lipid membranes from naked mole-rat brain lipids are cholesterol-rich, highly phase-separated, and sensitive to amyloid-induced damage
Authors: Frankel Daniel , Davies Matthew , Bhushan Bharat , Kulaberoglu Yavuz , Urriola-Munoz Paulina , Bertrand-Michel Justine , Pergande Melissa R. , Smith Andrew A. , Preet Swapan , Park Thomas J. , Vendruscolo Michele , Rankin Kenneth , Cologna Stephanie M. , Kumita Janet R. , Cenac Nicolas , John Smith Ewan St 
Published: June 2020

AbstractNaked mole-rats are extraordinarily long-lived rodents that do not develop age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta peptide, even from a young age Therefore, these animals offer an opportunity to investigate mechanisms of resistance against the neurotoxicity of amyloid beta aggregation. Working in this direction, here we examine the composition, phase behaviour, and amyloid beta interactions of naked mole-rat brain lipids. Relative to mouse, naked mole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorter chain lengths. Proteins associated with metabolism of ceramides, sphingomyelin and ceramide receptor activity were also found to be decreased in naked mole-rat brain lysates. Correspondingly, we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, with the liquid ordered phase occupying up to 80% of the supported lipid bilayer. These observations are consistent with the ‘membrane pacemaker’ hypothesis of ageing, according to which long-living species have lipid membranes particularly resistant to oxidative damage. However, we found that exposure to amyloid beta disrupts the naked mole-rat brain lipid membranes while those formed from mouse brain lipids exhibit small, well-defined footprints, whereby the amyloid beta penetrates deeply into the lipid membranes. These results suggest that in naked mole-rats the lipid composition of cell membranes may offer neuroprotection through resistance to oxidative processes rather than through mechanical effects.
Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia
Authors: Morales-Nebreda Luisa , Helmin Kathryn A. , Markov Nikolay S. , Piseaux Raul , Acosta Manuel A. Torres , Abdala-Valencia Hiam , Politanska Yuliya , Singer Benjamin D. 
Published: June 2020

AbstractRegulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury following viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell pro-repair function following lung injury remains unknown. Here, we show that aging results in a cell-autonomous impairment of reparative Treg cell function following experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provide insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Novel strategies that restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia.
The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure
Authors: Sun Yunpeng , Zhao Kun , Xia Wencheng , Gu Jinge , Ma Yeyang , Gui Xinrui , Zhang Xia , Fang Yanshan , Sun Bo , Liu Cong , Li Dan 
Published: June 2020

AbstractHuman heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminate structural understandings on the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.