bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hinge Influences in Murine IgG Binding toCryptococcus neoformansCapsule
Authors: de Oliveira Diane Sthefany Lima , Paredes Verenice , Caixeta Adrielle Veloso , Henriques Nicole Moreira , Wear Maggie P. , Albuquerque Patrícia , Felipe Maria Sueli Soares , Casadevall Arturo , Nicola André Moraes 
Published: January 2021

AbstractDecades of studies on antibody structure led to the tenet that the V region binds antigens while the C region interacts with immune effectors. In some antibodies, however, the C region affects affinity and/or specificity for the antigen. One such case is that of the 3E5 antibodies, a family of monoclonal murine IgGs in which the mIgG3 isotype has different fine specificity to theCryptococcus neoformanscapsule polysaccharide than the other mIgG isotypes. Our group serendipitously found another pair of mIgG1/mIgG3 antibodies based on the 2H1 hybridoma to theC. neoformanscapsule that recapitulated the differences observed with 3E5. In this work, we report the molecular basis of the constant domain effects on antigen binding using recombinant antibodies. As with 3E5, immunofluorescence experiments show a punctate pattern for 2H1-mIgG3 and an annular pattern for 2H1-mIgG1. Also as observed with 3E5, 2H1-mIgG3 bound on ELISA to both acetylated and non-acetylated capsular polysaccharide, whereas 2H1-mIgG1 only bound well to the acetylated form, consistent with differences in fine specificity. In engineering hybrid mIgG1/mIgG3 antibodies, we found that switching the 2H1-mIgG3 hinge for its mIgG1 counterpart changed the immunofluorescence pattern to annular, but a 2H1-mIgG1 antibody with a mIgG3 hinge still had an annular pattern. The hinge is thus necessary but not sufficient for these changes in binding to the antigen. This important role for the constant region in binding of antibodies to the antigen could affect the design of therapeutic antibodies and our understanding of their function in immunity.Key pointsKey point 1- 2H1 antibodies recapitulate differences between mIgG isotypes observed with 3E5.Key point 2 – The hinge region is necessary but not sufficient for these differences.Key point 3 - The antibody constant region can also play a role in mIgG binding to antigen.
The long non-coding RNASAMMSONis essential for uveal melanoma cell survival
Authors: Dewaele Shanna , Delhaye Louis , De Paepe Boel , De Bony Eric , De Wilde Jilke , Vanderheyden Katrien , Anckaert Jasper , Yigit Nurten , Eynde Eveline Vanden , Nemati Fariba , Decaudin Didier , Jochemsen Aart , Leucci Eleonora , Vandesompele Jo , Dorpe Jo Van , Marine Chris , Van Coster Rudy , Eyckerman Sven , Mestdagh Pieter 
Published: January 2021

AbstractPurposeLong non-coding RNAs (lncRNAs) can exhibit cell-type and cancer-type specific expression profiles, making them highly attractive as therapeutic targets. Pan-cancer RNA sequencing data revealed broad expression of theSAMMSONlncRNA in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Currently, there are no effective treatments for UM patients with metastatic disease, resulting in a median survival time of 6-12 months. We aimed to investigate the therapeutic potential ofSAMMSONinhibition in UM.Experimental DesignThe impact of antisense oligonucleotide (ASO)-mediatedSAMMSONinhibition was evaluated in a panel of UM cell lines and patient derived xenograft (PDX) models. Cell proliferation and apoptosis were quantifiedin vitroandin vivoand complemented with molecular profiles established through RNA-sequencing.SAMMSONinteraction partners were identified using ChIRP-MS.ResultsSAMMSONinhibition impaired the growth and viability of a genetically diverse panel of uveal melanoma cell lines. These effects were accompanied by an induction of apoptosis and were recapitulated in two uveal melanoma PDX models through subcutaneous ASO delivery.SAMMSONpulldown revealed several candidate interaction partners, including various proteins involved in mitochondrial translation. Consequently, inhibition ofSAMMSONimpaired global protein translation levels and mitochondrial function in uveal melanoma cells.ConclusionSAMMSONexpression is essential for uveal melanoma cell survival. ASO-mediated silencing ofSAMMSONmay provide an effective treatment strategy to treat primary and metastatic uveal melanoma patients.
Microscope-Cockpit: Python-based bespoke microscopy for bio-medical science
Authors: Phillips Mick A , Pinto David Miguel Susano , Hall Nicholas , Mateos-Langerak Julio , Parton Richard M , Titlow Josh , Stoychev Danail V , Parks Thomas , Pinto Tiago Susano , Sedat John W , Booth Martin J , Davis Ilan , Dobbie Ian M 
Published: January 2021

AbstractWe have developed “Microscope-Cockpit” (Cockpit), a highly adaptable open source user-friendly Python-based GUI environment for precision control of both simple and elaborate bespoke microscope systems. The user environment allows next-generation near-instantaneous navigation of the entire slide landscape for efficient selection of specimens of interest and automated acquisition without the use of eyepieces. Cockpit uses “Python-Microscope” (Microscope) for high-performance coordinated control of a wide range of hardware devices using open source software. Microscope also controls complex hardware devices such as deformable mirrors for aberration correction and spatial light modulators for structured illumination via abstracted device models. We demonstrate the advantages of the Cockpit platform using several bespoke microscopes, including a simple widefield system and a complex system with adaptive optics and structured illumination. A key strength of Cockpit is its use of Python, which means that any microscope built with Cockpit is ready for future customisation by simply adding new libraries, for example machine learning algorithms to enable automated microscopy decision making while imaging.HighlightsUser-friendly setup and use for simple to complex bespoke microscopes.Facilitates collaborations between biomedical scientists and microscope technologists.Touchscreen for near-instantaneous navigation of specimen landscape.Uses Python-Microscope, for abstracted open source hardware device control.Well-suited for user training of AI-algorithms for automated microscopy.
Long-term changes in the breeding biology of a New Zealand bellbird population suggest plasticity in life-history responses to ecological restoration
Authors: Roper Michelle M. , Aaron M.T. Harmer , Brunton Dianne H 
Published: January 2021

AbstractEcological restoration projects provide excellent opportunities to study how animals adapt their life-history strategies in response to changeable environments. A fundamental way animals can optimise reproductive success in changing conditions is trading-off aspects of their breeding system. The New Zealand bellbird (Anthornis melanura) has had a long-term presence on the small restoration island, Tiritiri Matangi Island (Tiri), spanning the island’s degraded agricultural past to its current extensively restored state. We studied the breeding biology of this bellbird population to assess how their reproductive life-history strategies have responded over time to the restoration on Tiri. We compared the current breeding data (2012–2016) of the bellbirds with data from between 2001–2010 (including Baillie, 2011, Cope, 2007), and from 1977–1978 (Anderson and Craig, 2003), prior to the island’s restoration. We also explored associations between abiotic/biotic factors and bellbird reproductive success for the most recent period (2012–2016). Our main finding was that clutch size significantly declined over time from a mean of 3.6 to 2.4 eggs per nest and this decline correlated with increasing population density. This is consistent with a density dependent effect, although further data are required to empirically test this conclusion. Overall, the earliest spring laying dates were in late August and the latest extended to January, with all chicks fledged by the end of February. Nest success was 47% (range 40 – 54%) across 2012–2016, falling within a similar range as previous studies. We found little effect of year, weather, parental age or morphometrics on reproductive success. We observed directional change in patterns of parental investment between 1977–1978 and 2012–2016; in 2012–2016, parents persisted with raising single broods rather than abandoning and re-nesting to raise larger broods. These results suggest that the bellbirds’ life-history traits are plastic in response to local conditions which provides an advantage when repopulating a regenerating or changing habitat.
Modelling the COVID-19 Fatality Rate in England and its Regions
Authors: Saunders Nigel 
Published: January 2021

AbstractA model to account for the fatality rate in England and its regions is proposed. It follows the clear observation that, rather than two connected waves, there have been many waves of infections and fatalities in the regions of England of various magnitudes, usually overlapping. The waves are self-limiting, in that clear peaks are seen, particularly in reported positive test rates. The present model considers fatalities as the data reported are more reliable than positive test rates, particularly so during the first wave when so little testing was done.The model considers the observed waves are essentially similar in form and can be modelled using a single wave form, whose final state is only dependent on its peak height and start date. The basic wave form was modelled using the observed fatality rates for London, which unlike the other regions, exhibited almost completely as a single wave in the “first wave”. Its form matches rather well with the “Do Nothing” model reported by Imperial College on 16th March 2020, but reduced substantially from its expected peak.There are, essentially, only two adjustable parameters used in the model, the start date of the relevant wave and its height. The modelled fatalities for each wave are summated per day and a cumulative curve is matched to that reported. The minimal number of adjustable parameters, alongside the fact that the waves invariably overlap, provides highly stringent conditions on the fitting process.Results are presented for each region for both the “first” and “second’ waves. High levels of accuracy are obtained with R2 values approaching 100% against the ideal fit for both waves. It can also be seen that there are fundamental differences between the underlying behaviour of the “first” and “second” waves and reasons as to why those differences have arisen is briefly discussed.
The COVID-19 Infodemic: The complex task of elevating signal and eliminating noise
Authors: Desai Tejas , Conjeevaram Arvind 
Published: January 2021

AbstractIn Situation Report #3 and 39 days before declaring COVID-19 a pandemic, the WHO declared a -19 infodemic. The volume of coronavirus tweets was far too great for one to find accurate or reliable information. Healthcare workers were flooded with which drowned the of valuable COVID-19 information. To combat the infodemic, physicians created healthcare-specific micro-communities to share scientific information with other providers. We analyzed the content of eight physician-created communities and categorized each message in one of five domains. We coded 1) an application programming interface to download tweets and their metadata in JavaScript Object Notation and 2) a reading algorithm using visual basic application in Excel to categorize the content. We superimposed the publication date of each tweet into a timeline of key pandemic events. Finally, we created NephTwitterArchive.com to help healthcare workers find COVID-19-related signal tweets when treating patients. We collected 21071 tweets from the eight hashtags studied. Only 9051 tweets were considered signal: tweets categorized into both a domain and subdomain. There was a trend towards fewer signal tweets as the pandemic progressed, with a daily median of 22% (IQR 0-42%. The most popular subdomain in Prevention was PPE (2448 signal tweets). In Therapeutics, Hydroxychloroquine/chloroquine wwo Azithromycin and Mechanical Ventilation were the most popular subdomains. During the active Infodemic phase (Days 0 to 49), a total of 2021 searches were completed in NephTwitterArchive.com, which was a 26% increase from the same time period before the pandemic was declared (Days −50 to −1). The COVID-19 Infodemic indicates that future endeavors must be undertaken to eliminate noise and elevate signal in all aspects of scientific discourse on Twitter. In the absence of any algorithm-based strategy, healthcare providers will be left with the nearly impossible task of manually finding high-quality tweets from amongst a tidal wave of noise.
Incidence and Relative Risk of infection with SARS-CoV-2 virus in European Soccer Players
Authors: Andersen Thomas B. , Dahl Andreas B. , Carstensen Jeppe B. 
Published: January 2021

AbstractThe purpose of the present study was to investigate the incidence and relative risk of infection Covid-virus in soccer players. Data from five leagues was used and compared to data from the normal population in each country. Our results revealed that the relative risk was higher in soccer players in three countries when correcting for the estimated true number of infected people in the populations. We discuss that the reason for the higher incidence in soccer players is caused by the virus entering a group of players that work closely together.
Wild-captive contrasts in non-vocal communicative repertoires and functional specificity in orang-utans
Authors: Fröhlich Marlen , Bartolotta Natasha , Fryns Caroline , Wagner Colin , Momon Laurene , Jaffrezic Marvin , Setia Tatang Mitra , Schuppli Caroline , van Noordwijk Maria , van Schaik Carel P. 
Published: January 2021

AbstractThe creation of novel communicative acts is an essential element of human language. Although some research suggests the presence of this ability in great apes, this claim remains controversial. Here, we use orang-utans (Pongospp.) to systematically assess the effect of the wild-captive contrast on the repertoire size of communicative acts. We find that individual communicative repertoires are significantly larger in captive compared to wild settings, irrespective of species, age-sex class or sampling effort. Twenty percent of the orang-utan repertoire in captivity were not observed in the wild. In Sumatran orang-utans, the more sociable species, functional specificity was also higher in captive versus wild settings. We thus conclude that orang-utans, when exposed to a more sociable and terrestrial lifestyle, have the behavioural plasticity to invent new communicative behaviours that are highly functionally specific. This productive capacity by great apes is a major prerequisite for the evolution of language and seems to be ancestral in the hominid lineage.
Control over patch encounters changes foraging behaviour
Authors: Hall-McMaster Sam , Dayan Peter , Schuck Nicolas W. 
Published: January 2021

SummaryForaging is a common decision problem in natural environments. When new exploitable sites are always available, a simple optimal strategy is to leave a current site when its return falls below a single average reward rate. Here, we examined foraging in a more structured environment, with a limited number of sites that replenished at different rates and had to be revisited. When participants could choose sites, they visited fast-replenishing sites more often, left sites at higher levels of reward, and achieved a higher net reward rate. Decisions to exploit-or-leave a site were best explained with a computational model that included both the average reward rate for the environment and reward information about the unattended sites. This suggests that unattended sites influence leave decisions, in foraging environments where sites can be revisited.HighlightsBeing able to select sites during foraging increased visits to high value sitesThis visitation pattern was efficient, producing higher average reward ratesDecisions to leave a site were influenced by information about alternative sitesGraphical Abstract
PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape
Authors: Sánchez-Álvarez Miguel , Lolo Fidel , Sailem Heba , Pascual-Vargas Patricia , Fulgoni Giulio , Arias-García Mar , del Pozo Miguel Ángel , Bakal Chris 
Published: January 2021

ABSTRACTThe architecture of the endoplasmic reticulum (ER) is tightly controlled as a key determinant of its function. Its dynamics are linked to those of the cytoskeleton, but our understanding of how this coordination occurs and what its functional relevance is, is limited. We found the Unfolded Protein Response (UPR) transducer EIF2AK3/PERK is essential for acute stress-induced peripheral redistribution and remodeling of the ER, through eIF2a phosphorylation and translation initiation shutdown. PERK-mediated eIF2a phosphorylation can be bypassed by blocking ribosome activity; by depleting microtubule-anchoring ER proteins such as REEP4, p180/RRBP1 and Climp63/CKAP4; or by disrupting the microtubule cytoskeleton. Notably, specific disruption of non-centrosomal microtubules, but not centrosome depletion, relieved blockade of ER redistribution in PERK-deficient cells. Conversely, PERK deficiency stabilized non-centrosomal microtubules, promoting polarized protrusiveness in epithelial cells and neuroblasts. We propose that PERK coordinates ER architecture and homeostasis with cell morphogenesis by coupling ER remodeling and non-centrosomal MT dynamics.
The impact of antigenic escape on the evolution of virulence
Authors: Sasaki Akira , Lion Sébastien , Boots Mike 
Published: January 2021

AbstractUnderstanding the evolutionary drivers determining the transmission rate and virulence of pathogens remains an important challenge for evolutionary theory with clear implications to the control of human, agricultural and wildlife infectious disease. Although disease is often very dynamic, classical theory examines the long-term outcome of evolution at equilibrium and, in simple models, typically predicts that R0is maximized. For example, immune escape may lead to complex disease dynamics including repeated epidemics, fluctuating selection and diversification. Here we model the impact of antigenic drift and escape on the evolution of virulence and show analytically that these non-equilibrium dynamics select for more acute pathogens with higher virulence. Specifically, under antigenic drift and when partial cross immunity leads to antigenic escape, our analysis predicts the long-term maximization of the intrinsic growth rate of the parasite resulting in more acute and virulent pathogens than those predicted by classic R0maximization. Furthermore, it follows that these pathogens will have a lower R0leading to implications for epidemic, endemic behavior and control. Our analysis predicts both the timings and outcomes of antigenic shifts leading to repeated epidemics and predicts the increase in variation in both antigenicity and virulence before antigenic escape. There is considerable variation in the degree of antigenic escape that occurs across pathogens and our results may help to explain the difference in virulence between related pathogens most clearly seen in the human A, B and C influenzas. More generally our results show the importance of examining the evolutionary consequences of non-equilibrium dynamics.
Silencing of lncRNA NEAT1 inhibits esophageal squamous cell carcinoma proliferation, migration, and invasion via regulation of the miR-1299/MMP2 axis
Authors: Yang Zhanfeng , Zhu Meilin , Zhang Jingjing , Zhang Guangchong , Hu Jun , He Qunli 
Published: January 2021

AbstractEsophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer worldwide. Considerable evidence has verified that abnormal expression of lncRNAs can effectively influence the progression of various malignant tumors. However, the regulatory mechanisms of lncRNAs underlying ESCC development and progression remain poorly defined. Here, we investigated the role of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in ESCC via regulating microRNA 1299 (miR-1299) and matrix metalloproteinase 2 (MMP2). A total of 32 ESCC tissue samples were obtained from the First Affiliated Hospital of Zhengzhou University. The mRNA levels of lncRNA NEAT1, miR-1299, and MMP2 mRNA were measured via quantitative real-time PCR. Interactions among miR-1299, lncRNA NEAT1, and MMP2 mRNA in EC9706 cells were confirmed by dual-luciferase reporter assays and RNA immunoprecipitation (RIP) assays. The proliferation and migration/invasion of ESCC cells were verified by CCK-8 and transwell assays, respectively. lncRNA NEAT1 was up-regulated in ESCC tissues and cells. lncRNA NEAT1 silencing inhibited migration, invasion, and proliferation of ESCC cells. Furthermore, lncRNA NEAT1 sponged and negatively regulated miR-1299, thus giving rise to increased expression of MMP2. Moreover, miR-1299 inhibitors and MMP2 rescued the invasion of ESCC cells following silencing of lncRNA NEAT1. lncRNA NEAT1 was overexpressed in ESCC tissues and cells. Silencing of lncRNA NEAT1 inhibited ESCC proliferation, migration, and invasion via reducing competitive binding of lncRNA NEAT1 with miR-1299 and enhancing miR-1299-targeted suppression of MMP2. Taken together, our findings suggest that lncRNA NEAT1 is a potential target for ESCC therapy and rehabilitation.
VEGF-A/VEGFR-1: a painful astrocyte-mediated signaling blocked by the anti-VEGFR-1 mAb D16F7
Authors: Micheli Laura , Parisio Carmen , Lucarini Elena , Vona Alessia , Toti Alessandra , Pacini Alessandra , Mello Tommaso , Boccella Serena , Ricciardi Flavia , Maione Sabatino , Graziani Grazia , Lacal Pedro Miguel , Failli Paola , Ghelardini Carla , Mannelli Lorenzo Di Cesare 
Published: January 2021

AbstractChemotherapy-induced neuropathic pain is a clinically relevant adverse effect of several anticancer drugs leading to dose reduction or therapy discontinuation. The lack of knowledge about the mechanisms of neuropathy development and pain chronicization makes chemotherapy-induced neuropathic pain treatment an unmet medical need. In this context, the vascular endothelial growth factor A (VEGF-A) has emerged as a neurotoxicity biomarker in a model of chemotherapy-induced neuropathy, and its decrease has been related to pain relief. Aim of this study was to clarify the VEGF-A-dependent pain signaling in the CNS for individuating new targeted therapeutic approaches. In mice, the intrathecal infusion of VEGF-A induced a dose-dependent noxious hypersensitivity mediated by the VEGF receptor 1 (VEGFR-1) as demonstrated by pharmacological and genetic tools. In electrophysiological study, VEGF-A stimulated the spinal nociceptive neurons activity through VEGFR-1. In the dorsal horn of the spinal cord, VEGF-A increased in astrocytes of animals affected by neuropathy suggesting this cell population as a source of the potent pain mediator. Accordingly, the selective knockdown of astrocytic VEGF-A, by shRNAmir, blocked the development of oxaliplatin-induced neuropathic pain. Besides, the anti-VEGFR-1 mAb D16F7 (previously described as anticancer) effectively relieved neuropathic pain induced by chemotherapeutic agents. In conclusion, astrocyte-released VEGF-A is a new player in the complex neuron-glia network that oversees physiological and pathological pain and D16F7 mAb rises as a potent pain killer strategy.