bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia
Authors: Reynolds Conner D. , Nolan Suzanne O. , Smith Gregory D. , Jefferson Taylor S. , Hodges Samantha L. , Brewster Amy L. , Lugo Joaquin N. 
Published: August 2020

Objective
Focal cortical dysplasia (FCD) accounts for nearly half of all cases of medically refractory epilepsy in the pediatric and adult patient populations. This neurological disorder stems from localized malformations in cortical brain tissue due to impaired neuronal proliferation, differentiation, and migration patterns. Recent studies in animal models have highlighted the potential role of the Fragile X mental retardation protein (FMRP) levels in FCD. The purpose of this study was to investigate the status of FMRP activation in cortical brain tissues surgically resected from patients with FCD. In parallel, this study also investigated protein levels within the PI3K/AKT/mTOR and canonical Wnt signaling pathways.

Methods
Pathologic tissue from malformative lesions of FCD patients with medically refractory epilepsy was compared to relatively normal control non-epileptic tissue from patients with intracranial neoplasms. A series of western blotting assays were performed to assess key proteins in the PI3K/AKT/mTOR, canonical Wnt signaling pathways, and FMRP.

Results
There was suppression of S235/236-phosphorylated S6, GSK3α, and GSK3β protein levels in samples derived from FCD patients, compared to non-epileptic controls. FCD samples also had significantly greater levels of total and S499-phosphorylated FMRP.

Conclusion
These findings support our hypothesis that malformative lesions associated with FCD are characterized by high levels of FMRP activation along with dysregulation of both PI3K/AKT/mTOR and canonical Wnt signaling. These novel clinical findings extend previous work in animal models, further suggesting a potential unforeseen role of GSK3α and GSK3β in the pathophysiology of FCD and refractory epilepsy.
Microtubules enter centre stage for morphogenesis
Authors: Röper Katja 
Published: August 2020

Cell shape changes are key to observable changes at the tissue level during morphogenesis and organ formation. The major driver of cell shape changes in turn is the actin cytoskeleton, both in the form of protrusive linear or branched dynamic networks and in the form of contractile actomyosin. Over the last 20 years, actomyosin has emerged as the major cytoskeletal system that deforms cells in epithelial sheets during morphogenesis. By contrast, the second major cytoskeletal system, microtubules, have so far mostly been assumed to serve ‘house-keeping' functions, such as directed transport or cell division, during morphogenetic events. Here, I will reflect on a subset of studies over the last 10 years that have clearly shown a major direct role for the microtubule cytoskeleton in epithelial morphogenesis, suggesting that our focus will need to be widened to give more attention and credit to this cytoskeletal system in playing an active morphogenetic role.
This article is part of a discussion meeting issue ‘Contemporary morphogenesis'.
Epithelial–mesenchymal plasticity: emerging parallels between tissue morphogenesis and cancer metastasis
Authors: Plygawko Andrew T. , Kan Shohei , Campbell Kyra 
Published: August 2020

Many cells possess epithelial–mesenchymal plasticity (EMP), which allows them to shift reversibly between adherent, static and more detached, migratory states. These changes in cell behaviour are driven by the programmes of epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET), both of which play vital roles during normal development and tissue homeostasis. However, the aberrant activation of these processes can also drive distinct stages of cancer progression, including tumour invasiveness, cell dissemination and metastatic colonization and outgrowth. This review examines emerging common themes underlying EMP during tissue morphogenesis and malignant progression, such as the context dependence of EMT transcription factors, a central role for partial EMTs and the nonlinear relationship between EMT and MET.This article is part of a discussion meeting issue ‘Contemporary morphogenesis'.
Brassinosteroids Promote Parenchyma Cell and Secondary Xylem Development in Sugar Beet (Beta vulgaris L.) Root
Authors: Wang Wei , Sun Yaqing , Li Guolong , Zhang Shaoying 
Published: August 2020

AbstractIncreasing crop yield has always been an important goal in agriculture. Brassinosteroids (BRs) are growth-promoting steroid hormones with vital roles in many root developmental processes. Sugar beet (Beta vulgaris L.) is a root crop with a tertiary root structure. The differentiation of vascular bundles and division of cambial cells increases root diameter. However, little is known about how BRs regulate the transverse growth of beetroot. Therefore, sugar beet with eight leaves was grown in medium containing epibrassinolide or brassinazole, an inhibitor of brassinosteroid biosynthesis. BRs increased the spacing between the cambial rings by increasing the size of parenchyma cells between the rings and ultimately increasing root diameter. BRs also promoted secondary xylem differentiation. These findings indicate that brassinosteroids function in transverse development in beetroot.
Botanical Medicines with Activity against Stationary PhaseBartonella henselae
Authors: Ma Xiao , Leone Jacob , Schweig Sunjya , Zhang Ying 
Published: August 2020

ABSTRACTBartonella henselaeis a Gram-negative, facultative intracellular bacterium which is the causative agent of cat scratch disease. In humans, infections withB. henselaecan result in acute or chronic systemic infections with various clinical symptoms including local skin lesions, malaise, aches, chills, lymphadenopathy, endocarditis, or meningoencephalitis. The current treatment forBartonellainfections with antibiotics such as doxycycline and rifampin is not always effective presumably due to bacterial persistence. There have been various anecdotal reports of herbal extracts used for treating patients with persistentBartonellainfections but their activity onB. henselaeis unknown. To test the potential antimicrobial activity of botanical or herbal medicines and develop better therapies for persistentBartonellainfections, in this study, we screened an herbal product collection against stationary phaseB. henselae in vitrousing SYBR Green I/ propidium iodide (PI) viability assay. These herbal medicines were selected by the fact that they are commonly used to treat Lyme and co-infections by patients and herbalists, and as a follow-up to our recent study where these herbs were tested againstB. burgdorferi. We identified five herbal product extracts that had high activity against stationary phaseB. henselaeat 0.5% (v/v), includingCryptolepis sanguinolenta,Juglans nigra,Polygonum cuspidatum,Scutellaria baicalensis, andScutellaria barbata. Among them,Cryptolepis sanguinolenta,Juglans nigra, andPolygonum cuspidatumcould eradicate all stationary phaseB. henselaecells within 7 days at 0.25% (v/v) in drug exposure time-kill assay, whereasScutellaria baicalensisandScutellaria barbatashowed relatively poor activity. The minimum inhibitory concentration (MIC) determination of these top hits indicated they were not only active against stationary phase non-growingB. henselaebut also had good activity against log phase growingB. henselae. Our findings may help to develop more effective treatments for persistentBartonellainfections.
Genome assembly of a Mesoamerica-derivedPhaseolus lunatuscultivar enables the identification and comparative genomic analysis of a complex resistance locus
Authors: Wisser Randall J. , Oppenheim Sara J. , Ernest Emmalea G. , Mhora Terence T. , Scanlan Colin , Dumas Michael D. , Gregory Nancy F. , Evans Thomas A. , Donofrio Nicole M. 
Published: August 2020

ABSTRACTLima bean,Phaseolus lunatus, is closely related to common bean and is high in fiber and protein, with a low glycemic index. Lima bean is widely grown in the state of Delaware, where late summer and early fall weather are conducive to pod production. The same weather conditions also promote diseases such as pod rot and downy mildew, the latter of which has caused previous epidemics. A better understanding of the genes underlying resistance to this and other pathogens is needed to keep this industry thriving in the region. Our current study sought to sequence, assemble and annotate a commercially available cultivar called Bridgeton, which could then serve as a reference genome, a basis of comparison to otherPhaseolustaxa and a resource for identification of potential resistance genes. Combined efforts of sequencing, linkage and comparative mapping analysis resulted in a 625 Mb genome assembly, as well as a better understanding of a locus underlying resistance to the current downy mildew race in the field.
Characterizing the spatiotemporal variability of Alzheimer’s disease pathology
Authors: Vogel Jacob W. , Young Alexandra L. , Oxtoby Neil P. , Smith Ruben , Ossenkoppele Rik , Strandberg Olof T. , La Joie Renaud , Aksman Leon M. , J Grothe Michel , Iturria-Medina Yasser , Pontecorvo Michael J. , Devous Michael D. , Rabinovici Gil D. , Alexander Daniel C. , Hyoung Lyoo Chul , Evans Alan C. , Hansson Oskar ,   for the Alzheimer’s Disease Neuroimaging Initiative✶
Published: August 2020

AbstractAlzheimer’s disease (AD) is characterized by the progressive spread of tau pathology throughout the cerebral cortex. The pattern of spread is thought to be fairly consistent across individuals, though more recent work has demonstrated substantial variability in the AD population that is often associated with distinct clinical phenotypes. Still, a systematic, unbiased, wholebrain characterization of spatiotemporal variation in tau deposition in AD is lacking. We analyzed 1612 tau-PET scans and applied to this sample a disease progression modeling framework designed to identify spatiotemporal trajectories of pathological progression. We identified four distinct trajectories of tau progression, ranging in prevalence from 18–33%, with no one progession predominating. We replicated previously described limbic-predominant and medial temporal lobe-sparing variants, while also discovering posterior and lateral temporal subtypes resembling atypical clinical variants of AD. These “subtypes” were stable during longitudinal follow-up, and could be replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes, however, no “typical” variant predominated. Across all subtypes, younger age was related to worse cognition and more rapid tau accumulation. Additionally, network diffusion models implicated that pathology originates and spreads through distinct corticolimbic in the different subtypes. Together, our results suggest variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of “typical AD”, and a revisiting of tau pathological staging.
CG7379/ING1 suppress cancer cell invasion by maintaining cell-cell junction integrity
Authors: Rusu Alexandra D. , Cornhill Zoe E. , Coutino Brenda Canales , Uribe Marcos Castellanos , Lourdusamy Anbarasu , Markus Zsuzsa , May Sean T. , Rahman Ruman , Georgiou Marios 
Published: August 2020

AbstractApproximately 90% of cancer related deaths can be attributed to a tumour’s ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo inDrosophila, reduces the junctional localisation of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity.
Phosphate binding induced force-reversal occurs via slow backward cycling of cross-bridges
Authors: Stehle R 
Published: August 2020

ABSTRACTThe release of inorganic phosphate (Pi) from the cross-bridge is a pivotal step in the cross-bridge ATPase cycle leading to force generation. It is well known that Pirelease and the force-generating step are reversible, thus increase of [Pi] decreases isometric force by product inhibition and increases the rate constantkTRof mechanically-induced force redevelopment due to the reversible redistribution of cross-bridges among non-force-generating and force-generating states. The experiments on cardiac myofibrils from guinea pig presented here show that increasing [Pi] increaseskTRalmost reciprocally to force, i.e.,kTR≈ 1/force. To elucidate which cross-bridge models can explain the reciprocalkTR-force relation, simulations were performed for models varying in sequence and kinetics of 1) the Pirelease-rebinding equilibrium, 2) the force-generating step and its reversal, and 3) the transitions limiting forward and backward cycling of cross-bridges between non-force-generating and force-generating states. Models consisting of fast reversible force generation before/after rapid Pirelease-rebinding fail to describe thekTR–force relation observed in experiments. Models consistent with the experimentalkTR-force relation have in common that Pibinding and/or force-reversal are/is intrinsically slow, i.e., either Pibinding or force-reversal or both limit backward cycling of cross-bridges from force-generating to non-force-generating states.STATEMENT OF SIGNIFICANCEPrevious mechanical studies on muscle fibers, myofibrils and myosin interacting with actin revealed that force production associated to phosphate release from myosin’s active site presents a reversible process in the cross-bridge cycle. The correlation of this reversible process to the process(es) limiting kinetics of backward cycling from force-generating to non-force-generating states remained unclear.Experimental data of cardiac myofibrils and model simulations show that the combined effects of [Pi] on force and the rate constant of force redevelopment (kTR) are inconsistent with fast reversible force generation before/after rapid Pirelease-rebinding. The minimum requirement in sequential models for successfully describing the experimentally observed nearly reciprocal change of force andkTRis that either the Pibinding or the force-reversal step limit backward cycling.
Platelet-to-lymphocyte ratio (PLR), a novel biomarker to predict the severity of COVID-19 patients: a systematic review and meta-analysis
Authors: Simadibrata Daniel Martin , Pandhita Bashar Adi Wahyu , Ananta Muammar Emir , Tango Tamara 
Published: August 2020

AbstractBackgroundPlatelet-to-lymphocyte ratio (PLR), a novel inflammatory marker, has been suggested to be able to predict the severity of COVID-19 patients. This systematic review aims to evaluate the association between PLR levels on admission and the severity of COVID-19 patients.MethodsA systematic literature search was done on 23 July 2020 to identify peer-reviewed studies across four different databases (Ovid MEDLINE, EMBASE, SCOPUS, and the Cochrane Library), preprints from two databases (MedRxiv and SSRN), and grey literature from two databases (WHO COVID-19 Global Research Database and Center for Disease Control and Prevention COVID-19 Research Article). Research articles comparing the PLR value on admission in adult patients with COVID-19 with varying degrees of severity were included in the analysis. The following keywords were used for the search: “COVID-19”, “PLR”, “severity”, and “mortality”. The inverse variance method was used to calculate the pooled effect standardized mean difference (SMD) along with its 95% confidence interval (CI).ResultsA total of seven studies were included in the meta-analysis, six of which were conducted in China. From a total of 998 participants included, 316 (31.7%) had severe diseases; and those in the severe group were generally older and had underlying diseases compared to the non-severe group. In comparison to non-severe patients, the meta-analysis showed that severe COVID-19 patients had higher PLR levels on admission (SMD 0.68; 95%CI 0.43-0.93; I2 =58%).ConclusionHigh PLR levels on admission were associated with severe COVID-19 cases. Therefore, on-admission PLR level is a novel, cost-effective, and readily available biomarker with a promising prognostic role for determining the severity of COVID-19 patients.
Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility
Authors: van Blokland Irene V. , Lanting Pauline , Ori Anil P.S. , Vonk Judith M. , Warmerdam Robert C.A. , Herkert Johanna C. , Boulogne Floranne , Claringbould Annique , Lopera-Maya Esteban A. , Bartels Meike , Hottenga Jouke-Jan , Ganna Andrea , Karjalainen Juha ,   Lifelines COVID-19 cohort study,   The COVID-19 Host Genetics Initiative, Hayward Caroline , Fawns-Ritchie Chloe , Campbell Archie , Porteous David , Cirulli Elizabeth T. , Barrett Kelly M. Schiabor , Riffle Stephen , Bolze Alexandre , White Simon , Tanudjaja Francisco , Wang Xueqing , Ramirez Jimmy M. , Lim Yan Wei , Lu James T. , Washington Nicole L. , de Geus Eco J.C. , Deelen Patrick , Boezen H. Marike , Franke Lude H. 
Published: August 2020

AbstractEpidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict potential COVID-19 cases using cross-sectional self-reported disease-related symptoms. Using a previously reported COVID-19 prediction model, we show that it is possible to conduct a GWAS on predicted COVID-19, and this GWAS benefits from the larger sample size to provide new insights into the genetic susceptibility of the disease. Furthermore, we find suggestive evidence that genetic variants for other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. Our findings demonstrate the added value of using self-reported symptom assessments to quickly monitor novel endemic viral outbreaks in a scenario of limited testing. Should there be another outbreak of a novel infectious disease, we recommend repeatedly collecting data of disease-related symptoms.
Homologous and heterologous antibodies to coronavirus 229E, NL63, OC43, HKU1, SARS, MERS and SARS-CoV-2 antigens in an age stratified cross-sectional serosurvey in a large tertiary hospital in The Netherlands
Authors: Westerhuis Brenda M. , de Bruin Erwin , Chandler Felicity D. , Ramakers Chris R. B. , Okba Nisreen M.A. , Li Wentao , Goossens Herman , de Jong Menno D. , Bosch Berend Jan , Haagmans Bart L. , Fraaij Pieter L. A. , Sikkema Reina S. , Koopmans Marion P.G. 
Published: August 2020

AbstractUnderstanding the coronavirus (CoV) antibody landscape in relation to disease and susceptibility is critical for modelling of steps in the next phase during the current covid-19 pandemic. In March 2020, during the first month of the epidemic in The Netherlands, we performed cross sectional studies at two time points amongst patients of the Erasmus Medical Centre in Rotterdam, to assess the presence of antibodies against seasonal human coronaviruses (OC43, 229E, NL63, HKU1), emerging zoonotic coronaviruses (SARS, MERS) and SARS-CoV-2 in nine different age groups. We observed minimal SARS-CoV-2 reactivity early March (0.7% of sera), increasing to 3.0%, four weeks later, suggesting probably undetected cases during this early phase of the epidemic. Antibody responses were mostly coronavirus species specific at young age, but possible cross-reactivity between human seasonal CoVs was observed with increasing age.
Prevalence and outcome of Covid-19 infection in cancer patients: a national VA study
Authors: Fillmore Nathanael R. , La Jennifer , Szalat Raphael E. , Tuck David P. , Nguyen Vinh , Yildirim Cenk , Do Nhan V. , Brophy Mary T. , Munshi Nikhil C. 
Published: August 2020

AbstractBackgroundEmerging data suggest variability in susceptibility and outcome to Covid-19 infection. Identifying the risk-factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations.MethodsWe analyzed electronic health records of the US National Veterans Administration healthcare system and assessed the prevalence of Covid-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for Covid-19 and their confirmed positivity, with clinical characteristics, and outcome, and stratified by demographics, comorbidities, cancer treatment and cancer type.ResultsOf 22914 cancer patients tested for Covid-19, 1794 (7.8%) were positive. The prevalence of Covid-19 was similar across all ages. Higher prevalence was observed in African-American (AA) (15%) compared to white (5.5%; P<.001), in Hispanic vs non-Hispanic population and in patients with hematologic malignancy compared to those with solid tumors (10.9% vs 7.7%; P<.001). Conversely, prevalence was lower in current smoker patients, patients with other co-morbidities and having recently received cancer therapy (< 6 months). The Covid-19 attributable mortality was 10.9%. Highest mortality rates were observed in older patients, those with renal dysfunction, higher Charlson co-morbidity score and with certain cancer types. Recent (< 6 months) or past treatment did not influence mortality. Importantly, AA patients had 3.5-fold higher Covid-19 attributable hospitalization, however had similar mortality rate as white patients.ConclusionPre-existence of cancer affects both susceptibility to Covid-19 infection and eventual outcome. The overall Covid-19 attributable mortality in cancer patients is affected by age, co-morbidity and specific cancer types, however, race or recent treatment including immunotherapy does not impact outcome.FundingsVA Office of Research and Development and National Institutes of Health.