bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two softwood GUX clades are responsible for distinct glucuronic acid patterns on xylan
Authors: Lyczakowski Jan J , Yu Li , Terrett Oliver M , Fleischmann Christina , Temple Henry , Thorlby Glenn , Sorieul Mathias , Dupree Paul 
Published: January 2021

AbstractWood of coniferous (softwood) trees, is a globally significant carbon sink and an important source of biomass for industrial applications. Despite its importance, very little is known about the genetic basis of softwood biosynthesis. Glucomannan and xylan are the main hemicelluloses in softwood secondary cell walls. Xylan interacts with the cellulose fibrils in a two-fold screw configuration. Moreover, we have shown that xylan GUX (GlucUronic acid substitution of Xylan)-dependent branching with glucuronic acid is critical for biomass recalcitrance. Here, we investigated the decoration patterns of xylan by softwood GUX enzymes. Usingin vitroandin plantaassays we demonstrate that two distinct clades of conifer GUX enzymes are active glucuronyltransferases. Interestingly, these enzymes have different specific activities, with one adding evenly spaced GlcA branches and the other one being also capable of glucuronidating two consecutive xyloses. Since xylan patterning might modulate xylan-cellulose and xylan-lignin interactions, our result further the understanding of softwood biosynthesis and can contribute to strategies aimed at modifying softwood cell wall properties.
Fluoxetine acts concomitantly on dorsal and ventral hippocampus to Trk-dependently modulate the extinction of fear memory
Authors: Diniz Cassiano Ricardo Alves Faria , da Silva Leandro Antero , Domingos Luana Barreto , Sonego Andreza Buzolin , Moraes Leonardo Resstel Barbosa , Joca Sâmia 
Published: January 2021

ABSTRACTBackgroundHippocampus can be divided along its longitudinal axis into dorsal and ventral parts. Both are usually committed to modulate different aspects of behavior and stress response. However, it is not clear whether the hippocampal subregions could differently modulate the effect of antidepressant drugs. Since fluoxetine (FLX) effect on extinction of aversive memory is well known to depend on hippocampal BDNF levels, we hypothesized that the hippocampal subregions might play different roles in fluoxetine efficacy in decreasing fear response.MethodWistar rats were fear-cued conditioned and treated chronically with fluoxetine to enhance their subsequent extinction memory. First, FLX effect on BDNF levels was assessed considering the dorsal (dHC) and ventral (vHC) hippocampus apart. Then, K252a (a functional Trk blocker) was infused either into the dHC or vHC to assay its interaction with FLX treatment over the fear response. Next, BDNF was directly infused into either the dHC or vHC to compare its behavioral effects with FLX. Finally, FLX effect on c-Fos expression was evaluated also considering the dHC and vHC apart, along with subareas of amygdala and medial prefrontal cortex.ResultsChronic FLX treatment increased BDNF in the dHC, whereas BDNF was increased in the vHC after acute treatment only. K252a infused after the extinction protocol into either dHC or vHC was able to prevent FLX effect on fear response. BDNF directly infused into the dHC increased fear response, however its administration into the vHC induced an opposite effect. Besides, a negative correlation between the fear response and c-Fos expression was observed after chronic FLX treatment specifically in the dHC CA3/CA1 and vHC CA1/DG.ConclusionBoth dHC and vHC are important for the Trk-dependent FLX effect on extinction memory, although a discrepancy on the fear response was observed with the direct infusion of BDNF into the dHC or vHC.
Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamineN-oxide
Authors: Hoyles Lesley , Pontifex Matthew G. , Rodriguez-Ramiro Ildefonso , Anis-Alavi M. Areeb , Jelane Khadija S. , Snelling Tom , Solito Egle , Fonseca Sonia , Carvalho Ana L. , Carding Simon R. , Müller Michael , Glen Robert C. , Vauzour David , McArthur Simon 
Published: January 2021

ABSTRACTBackgroundCommunication between the gut microbiota and the brain is primarily mediatedviasoluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied.ResultsHere we use an integratedin vitro/in vivoapproach to show that physiologically relevant concentrations of the dietary methylamine trimethylamineN-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner.ConclusionOur findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function.
Female immunity protects from cutaneous squamous cell carcinoma
Authors: Budden Timothy , Gaudy-Marqueste Caroline , Craig Sarah , Hu Yuan , Earnshaw Charles , Gurung Shilpa , Ra Amelle , Akhras Victoria , Shenjere Patrick , Green Ruth , Jamieson Lynne , Lear John , Motta Luisa , Caulín Carlos , Oudit Deemesh , Furney Simon J , Virós Amaya 
Published: January 2021

AbstractPurposeCancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women are more protected from aggressive cutaneous squamous cell carcinoma (cSCC) due to strong immune activation.MethodsWe explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients (N= 738, N=160) with carcinoma cSCC, in FVB/N mice exposed to equal doses of DMBA, and in human keratinocytes by whole exome sequencing, bulk and single cell RNA sequencing.ResultsWe show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test if sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T cell infiltration independently of mutations. In contrast, males increase the rate of mitoses and proliferation in response to carcinogen. Human female skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at ultraviolet radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women.ConclusionsThis work shows the immune response is sex biased in cSCC, and highlights female immunity offers greater protection than male immunity.
Impaired refinement of kinematic variability in Huntington disease mice on an automated home-cage forelimb motor task
Authors: Woodard Cameron L. , Sepers Marja D. , Raymond Lynn A. 
Published: January 2021

AbstractThe effective development of novel therapies in mouse models of neurological disorders relies on behavioural assessments that provide accurate read-outs of neuronal dysfunction and/or degeneration. We designed an automated behavioural testing system (‘PiPaw’) which integrates an operant lever-pulling task directly into the mouse home-cage. This task is accessible to group-housed mice 24-hours per day, enabling high-throughput longitudinal analysis of forelimb motor learning. Moreover, this design eliminates the need for exposure to novel environments and minimizes experimenter interaction, significantly reducing two of the largest stressors associated with animal behaviour. Mice improved their performance of this task over one week of testing by reducing inter-trial variability of reward-related kinematic parameters (pull amplitude or peak velocity). In addition, mice displayed short-term improvements in reward rate, and a concomitant decrease in movement variability, over the course of brief (<10 minutes) bouts of task engagement. We used this system to assess motor learning in mouse models of the inherited neurodegenerative disorder, Huntington disease (HD). Despite having no baseline differences in task performance, Q175-FDN HD mice were unable to modulate the variability of their movements in order to increase reward on either short or long timescales. Task training was associated with a decrease in the amplitude of spontaneous excitatory activity recorded from striatal medium spiny neurons in the hemisphere contralateral to the trained forelimb in wildtype mice; however, no such changes were observed in Q175-FDN mice. This behavioural screening platform should prove useful for preclinical drug trials towards improved treatments in HD and other neurological disorders.Significance StatementIn order to develop effective therapies for neurological disorders such as Huntington disease (HD), it’s important to be able to accurately and reliably assess the behaviour of mouse models of these conditions. Moreover, these behavioural assessments should provide an accurate readout of underlying neuronal dysfunction and/or degeneration. In this paper, we employed an automated behavioural testing system to assess motor learning in mice within their home-cage. Using this system, we were able to study motor abnormalities in HD mice with an unprecedented level of detail, and identified a specific behavioural deficit associated with an underlying impairment in striatal neuronal plasticity. These results validate the usefulness of this system for assessing behaviour in mouse models of HD and other neurological disorders.
Glucose inhibits haemostasis and accelerates diet-induced hyperlipidaemia in zebrafish larvae
Authors: Morris Simone , Cholan Pradeep Manuneedhi , Britton Warwick J , Oehlers Stefan H 
Published: January 2021

ABSTRACTHyperglycaemia damages the microvasculature in part through the reduced recruitment of immune cells and interference with platelet signalling, leading to poor wound healing and accelerated lipid deposition in mammals. We investigated the utility of zebrafish larvae to model the effect of glucose on neutrophil and macrophage recruitment to a tail wound, wound-induced haemostasis, and chicken egg yolk feed challenge-induced hyperlipidaemia by supplementing larvae with exogenous glucose by immersion or injection. Neither method of glucose supplementation affected the recruitment of neutrophils and macrophages following tail transection. Glucose injection reduced thrombocyte retention and fibrin plug formation while only thrombocyte retention was reduced by glucose immersion following tail transection. We observed accelerated lipid accumulation in glucose-injected larvae challenged with high fat chicken egg yolk feeding. Our study identifies conserved and divergent effects of high glucose on inflammation, haemostasis, and hyperlipidaemia in zebrafish larvae compared to mammals.
Validation of the Munich Actimetry Sleep Detection Algorithm for estimating sleep-wake patterns from activity recordings
Authors: Loock Ann-Sophie , Sullivan Ameena Khan , Reis Catia , Paiva Teresa , Ghotbi Neda , Pilz Luisa K. , Biller Anna M. , Molenda Carmen , Vuori-Brodowski Maria , Roenneberg Till , Winnebeck Eva C. 
Published: January 2021

SummaryPeriods of sleep and wakefulness can be estimated from wrist-locomotor activity recordings via algorithms that identify periods of relative activity and inactivity. Here, we evaluated the performance of our Munich Actimetry Sleep Detection Algorithm (MASDA). MASDA uses a moving 24-hour-threshold and correlation procedure estimating relatively consolidated periods of sleep and wake.MASDA was validated against sleep logs and polysomnography. Sleep-log validation was performed on 2 field samples collected over 54 and 34 days (median) in 34 adolescents and 28 young adults. Polysomnographic validation was performed on a clinical sample of 23 individuals undergoing 1 night of polysomnography. Epoch-by-epoch analyses were conducted and comparisons of sleep measures via Bland-Altman plots and correlations.Compared with sleep logs, MASDA classified sleep with a median sensitivity of 80% (IQR = 75-86%) and specificity of 91% (87-92%). Mean onset and offset times were highly correlated (r = 0.86-0.91). Compared with polysomnography, MASDA reached a median sensitivity of 92% (85-100%), but low specificity of 33% (10-98%), owing to the low frequency of wake episodes in the nighttime polysomnographic recordings. MASDA overestimated sleep onset (~21 min) and underestimated wake after sleep onset (~26 min), while not performing systematically different from polysomnography in other sleep parameters.These results demonstrate the validity of MASDA to faithfully estimate sleep-wake patterns in field studies. With its good performance across day- and nighttime, it enables analyses of sleep-wake patterns in long recordings performed to assess circadian and sleep regularity and is therefore an excellent objective alternative to sleep logs in field settings.
Biomembranes undergo complex, non-axisymmetric deformations governed by Kirchhoff-Love kinematics and revealed by a three dimensional computational framework
Authors: Auddya Debabrata , Zhang Xiaoxuan , Gulati Rahul , Vasan Ritvik , Garikipati Krishna , Rangamani Padmini , Rudraraju Shiva 
Published: January 2021

AbstractBiomembranes play a central role in various phenomena like locomotion of cells, cell-cell interactions, packaging and transport of nutrients, transmission of nerve impulses, and in maintaining organelle morphology and functionality. During these processes, the membranes undergo significant morphological changes through deformation, scission, and fusion. Modeling the underlying mechanics of such morphological changes has traditionally relied on reduced order axisymmetric representations of membrane geometry and deformation. Axisymmetric representations, while robust and extensively deployed, suffer from their inability to model symmetry breaking deformations and structural bifurcations. To address this limitation, a three-dimensional computational mechanics framework for high fidelity modeling of biomembrane deformation is presented. The proposed framework brings together Kirchhoff-Love thin-shell kinematics, Helfrich-energy based mechanics, and state-of-the-art numerical techniques for modeling deformation of surface geometries. Lipid bilayers are represented as spline-based surface discretizations immersed in a three-dimensional space; this enables modeling of a wide spectrum of membrane geometries, boundary conditions, and deformations that are physically admissible in a 3D space. The mathematical basis of the framework and its numerical machinery are presented, and their utility is demonstrated by modeling three classical, yet non-trivial, membrane deformation problems: formation of tubular shapes and their lateral constriction, Piezo1-induced membrane footprint generation and gating response, and the budding of membranes by protein coats during endocytosis. For each problem, the full three dimensional membrane deformation is captured, potential symmetry-breaking deformation paths identified, and various case studies of boundary and load conditions are presented. Using the endocytic vesicle budding as a case study, we also present a “phase diagram” for its symmetric and broken-symmetry states.
AP2 regulates Thickveins trafficking through Rab11 to attenuate NMJ growth signaling inDrosophila
Authors: Dwivedi Manish Kumar , Choudhury Saumitra Dey , Patnaik Abhinandan , Mishra Shirish , Padinjat Raghu , Kumar Vimlesh 
Published: January 2021

ABSTRACTCompromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remains poorly understood. Here we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with BMP type I receptor, Thickveins (Tkv), and Daughter against decapentaplegic (Dad), two of the components of BMP signaling. We found that mutations in σ2-adaptin lead to an accumulation of Tkv receptors at the NMJ and results in a significant reduction in Tkv-positive early endosomes in the presynaptic terminals. Interestingly, the level of small GTPase Rab11 was significantly reduced in the σ2-adaptin mutant synapses. Consistent with the role of σ2-adaptin and Rab11 in the regulation of the same signaling pathway, a mutation in Rab11 or overexpression of a GDP-locked form of Rab11 (Rab11S25N) phenocopies the morphological and signaling defects of the σ2-adaptin mutants. Finally, we demonstrate thatσ2-adaptinmutants show an accumulation of large vesicles and massive membranous structures, akin to endosomes at the synapse. Thus, we propose a model in which AP2 regulates Tkv internalization and recycling through a process that requires Rab11 activity to control the synaptic growth.
A comparative baseline of coral disease across the central Red Sea
Authors: Aeby Greta Smith , Shore Amanda , Jensen Thor , Ziegler Maren , Work Thierry , Voolstra Christian R. 
Published: January 2021

AbstractThe Red Sea is a unique environment for corals with a strong environmental gradient characterized by temperature extremes and high salinities, but minimal terrestrial runoff or riverine input and their associated pollution. Disease surveys were conducted along 22 reefs in the central Red Sea along the Saudi Arabian coast in October 2015, which coincided with a bleaching event. Our objectives were to 1) document types, prevalence, and distribution of coral diseases in a region with minimal terrestrial input, 2) compare regional differences in diseases and bleaching along a latitudinal gradient of environmental conditions, and 3) use histopathology to characterize disease lesions at the cellular level. Coral reefs of the central Red Sea had a widespread but a surprisingly low prevalence of disease (<0.5%), based on the examination of >75,750 colonies. Twenty diseases were recorded affecting 16 coral taxa and included black band disease, white syndromes, endolithic hypermycosis, skeletal eroding band, growth anomalies and focal bleached patches. The three most common diseases wereAcroporawhite syndrome (59.1% of the survey sites),Poritesgrowth anomalies (40.9%), andPoriteswhite syndrome (31.8%). Over half of the coral genera within transects had lesions and corals from the generaAcropora, MilleporaandLobophylliawere the most commonly affected. Cell-associated microbial aggregates were found in four coral genera resembling patterns found in the Indo-Pacific. Differences in disease prevalence, coral cover, amount of heat stress as measured by degree heating weeks (DHW) and extent of bleaching was evident among sites. Disease prevalence was not explained by coral cover or DHW, and a negative relationship between coral bleaching and disease prevalence was found. The northern-most sites off the coast of Yanbu had the highest average DHW values but absence of bleaching and the highest average disease prevalence was recorded. Our study provides a foundation and baseline data for coral disease prevalence in the Red Sea, which is projected to increase as a consequence of increased frequency and severity of ocean warming.
Collective Regulation of Metabolism, Development and Longevity Through a
Socially Exchanged Fluid
Authors: Hakala SM , Meurville M-P , Stumpe M , LeBoeuf AC 
Published: January 2021

Abstract
Socially exchanged fluids, like seminal fluid and milk, allow individuals to
molecularly influence conspecifics. Many social insects have a social
circulatory system, where food and endogenously produced molecules are
transferred mouth-to-mouth (stomodeal trophallaxis), connecting all the
individuals in the society. To understand how these endogenous molecules relate
to colony life, we used quantitative proteomics to investigate the trophallactic
fluid within colonies of the carpenter ant Camponotus
floridanus. We show that different stages of the colony life
cycle circulate different types of proteins: young colonies prioritize direct
carbohydrate processing; mature colonies prioritize accumulation and
transmission of stored resources. Further, colonies circulate proteins
implicated in oxidative stress, ageing, and social insect caste determination,
potentially acting as superorganismal hormones. Brood-caring individuals that
are also closer to the queen in the social network (nurses) showed higher
abundance of oxidative stress-related proteins. Thus, trophallaxis behavior
provides a mechanism for distributed metabolism in social insect
societies.
Reaching to inhibit a prepotent response: a wearable 3-axis accelerometer kinematic analysis
Authors: Angeli Alessia , Valori Irene , Farroni Teresa , Marfia Gustavo 
Published: January 2021

AbstractThe present work explores the distinctive contribution of motor planning and control to human reaching movements. In particular, the movements were triggered by the selection of a prepotent response (Dominant) or, instead, by the inhibition of the prepotent response, that required the selection of an alternative one (Non-dominant). To this aim, we adapted aGo/No-Gotask to investigate both the dominant and non-dominant movements of a cohort of 19 adults, utilizing kinematic measures to discriminate between the planning and control components of the two actions. To sample such measures, a low-cost, easy to use, 3-axis wrist worn accelerometer was put to good use to obtain raw acceleration data and to compute and break down its velocity components. The values obtained with such task indicate that with the inhibition of a prepotent response, the selection and execution of the alternative one yields both a longer reaction time and movement duration. Moreover, the peak velocity occurred later in time with respect to the dominant response, revealing that participants tended to indulge more in motor planning rather than in adjusting their movement along the way. Finally, comparing such results to the findings obtained by other means in literature, we discuss the feasibility of an accelerometer-based analysis to disentangle distinctive cognitive mechanisms of human movements.
Fish primary embryonic stem cells self-assemble into retinal tissue mirroringin vivoearly eye development
Authors: Zilova Lucie , Weinhardt Venera , Tavhelidse Tinatini , Thumberger Thomas , Wittbrodt Joachim 
Published: January 2021

AbstractOrganoids derived from pluripotent stem cells promise the solution to current challenges in basic and biomedical research. Further progress and widespread applications are however limited by long developmental time, variable success, and lack of direct comparison to anin vivoreference. To overcome those limitations, we derived organoids from rapidly developing teleosts. We demonstrate how primary embryonic stem cells from zebrafish and medaka efficiently self-organize into anterior neural structures, particularly retina. Within four days, blastula-stage cell aggregates reproducibly execute key steps of eye development: retinal specification, morphogenesis and differentiation. The number of aggregated cells as well as genetic factors crucially impacted upon the concomitant morphological changes that were intriguingly reflecting thein vivosituation. High reproducibility and rapid development of fish-derived organoids in combination with advanced genome editing techniques immediately allow addressing aspects of development and disease, and systematically probing the impact of the physical environment on morphogenesis and differentiation.