bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior
Authors: Kutlu Munir Gunes , Tat Jennifer , Zachry Jennifer E. , Calipari Erin S. 
Published: April 2022

AbstractBackgroundThe inability to predict when aversive stimuli will and will not occur in is a hallmark of anxiety and stress disorders. Dopamine release in the nucleus accumbens (NAc) is sufficient and necessary for aversive learning and has been linked to both anxiety and stress disorder symptomatology. Thus, understanding how dopamine controls associative learning in response to aversive stimuli is critical to understanding the role of dopamine in behavior in health and disease.MethodsUsing an optical dopamine sensor combined with in-vivo fiber photometry in the NAc core of male and female C57BL/6J mice (N=38), we recorded dopamine responses to expected and omitted aversive outcomes during learning. We derived predictions from a theory-driven model of associative learning (Kutlu-Calipari-Schmajuk, KCS model) and tested the causality of these predictions using optogenetics.ResultsDopamine release was evoked by the predicted omission of aversive stimuli in a fashion that cannot be explained by dopamine as a reward-based prediction signal. The magnitude of the dopamine response during omissions scaled with predictions about the probability of their occurrence; however, dopamine did not track the associative value of predictive cues. Finally, we showed that the observed effects are causal to learned behavior and can only be explained by dopamine signaling the perceived saliency of predicted aversive events.ConclusionsWe elucidate the role of NAc core dopamine signaling in aversive learning in a theory-based and stimulus-specific fashion and offer potential avenues for understanding the neural mechanisms involved in anxiety and stress disorders.
Growing up unloved: the enduring consequence of childhood emotional neglect on the qualia of memory and imagination
Authors: Mullally Sinéad L. , Grafton-Clarke Désirée , Mawson Eleanor R , Unwin Matthew , Stapleton Molly , Webber Kat , Dodd Alyson L , Pepper Gillian V , Cokal Derya , Robinson Lucy J , Gallagher Peter , Watson Stuart 
Published: April 2022

ABSTRACTChildhood Adversity (CA) is one of the strongest factors associated with the onset of Major Depressive Disorder (MDD), and both CA and MDD have been linked to altered hippocampal structure/function. The current study aimed to explore the relationships between retrospectively reported childhood emotional neglect (CEN), current wellbeing and depressive symptoms, and a range of hippocampal-dependent cognitive functions i.e., anterograde learning and memory, episodic memory recollection, and imagination (episodic future thinking and scene construction). In two-wave recruitment periods at undergraduate intake 2014-15 (Cohort 1) and 2016-17 (Cohort 2), a combined cohort of n=1485 university students completed online surveys, with n=64 further participating in experimental testing session. As anticipated, higher CEN ratings consistently correlated with poorer current wellbeing and higher depressive symptoms. However, whilst the anticipated relationships between CEN, current wellbeing, and subjectively reported estimates of hippocampal-dependent cognitions were observed in the data reported in the online survey, an unexpectedly circumscribed pattern was observed on formal in-person examination of these cognitive functions. More specifically, higher CEN related to less vivid and less detailed imagined future/scene constructions and with an attenuated sense of presence and emotional valence during these simulations. A similar pattern was not evidence when participants simulated experienced past events (i.e. episodic memories). Current depression scores did not consistently correlate with vividness, detail, or emotional valence. In addition, and contrary to expectation, no relationship between CEN, depressive symptoms, and the spatial coherence of imagined or recollected events was seen. Moreover, neither CEN nor depressive symptoms correlated with many key measures of anterograde memory. Hence, we observed a highly specific constellation of impairment related to CEN when explored on a simulation per simulation basis, that was not obviously linked to altered hippocampal function, indicating that the relationship between CEN, hippocampal function, and subsequent psychopathology may not readily explained by either spatial or mnemonic hippocampal- related deficits. We consider whether the observed experiential differences in the qualia of imagined simulations may represent an important therapeutic target to decrease a CEN-driven latent vulnerability to MDD.
The impact of HIV on women living with HIV and their families in low- and middle-income countries: A systematic review
Authors: Fauk Nelsensius Klau , Mwanri Lillian , Hawke Karen , Mohammadi Leila , Ward Paul Russell 
Published: April 2022

AbstractHIV infection adds a significant burden to women in low- and middle-income countries (LMICs), often leading to severe detrimental impact, not only on themselves, but also on their families and communities. Given that more than half of all people living with HIV globally are females (53%), this review seeks to understand the impact of HIV infection on women living with HIV (WLHIV) and their families in LMICs, and the interrelationships between one impact and another. A systematic review was conducted to find literature using the following databases: Medline, PsycINFO, CINAL, Emcare, Scopus and ProQuest. Research articles were included if they met the following inclusion criteria: conducted in LMICs, published in English language between January 1st 1990 and October 31st 2021, had full text available, involved WLHIV (married and unmarried), and focused on the impact of HIV on these women and their families. Critical appraisal tools developed by Joanna Briggs Institute (JBI) were used to assess the methodological quality of the studies and thematic narrative synthesis was used to analyse the findings. A total of 22 articles met the inclusion criteria. The review showed that HIV has a range of negative consequences on WLHIV and their families including: (i) psychological impact, (ii) poor physical health and intimate partner violence, (iii) social impact, and (iv) economic impact. The findings indicate the need for targeted interventions, specific to WLHIV, that address the inequity and discrimination they face. These interventions should also incorporate education and sustainable support structures for WLHIV and their families.
A Kinetic Map of the Influence of Biomimetic Lipid Membrane Models on Aβ42Aggregation
Authors: Baumann Kevin N. , Sanguanini Michele , Rimon Oded , Šneiderienė Greta , Greer Heather , Thacker Dev , Schneider Matthias , Linse Sara , Knowles Tuomas P. J. , Vendruscolo Michele 
Published: April 2022

ABSTRACTThe aggregation of the amyloid β peptide (Aβ) is one of the major molecular hallmarks of Alzheimer’s disease. Although Aβ deposits have been mostly observed extracellularly, various studies have reported the presence of also intracellular Aβ assemblies. Because these intracellular Aβ aggregates might play a role in the onset and progression of Alzheimer’s disease, it is important to investigate their possible origins at different locations of the cell along the secretory pathway of the amyloid precursor protein (APP), from which Aβ is derived by proteolytic cleavage. Since lipid bilayers have been shown to promote the aggregation of Aβ, in this study we measure the effects of the lipid membrane composition on the in vitro aggregation kinetics of the 42-residue form of Aβ (Aβ42). By using small unilamellar vesicles modelling cellular membranes at different locations, including the inner and outer leaflets of the plasma membrane, late endosomes, the endoplasmic reticulum (ER), and the Golgi apparatus, we show that Aβ42aggregation is inhibited by the ER and Golgi membranes. These results provide a preliminary map of the possible effects of the membrane composition in different cellular locations on Aβ aggregation, and suggest the presence of an evolutionary optimization of lipid composition to prevent the intracellular aggregation of Aβ.
SATINN: An automated neural network-based classification of testicular sections allows for high-throughput histopathology of mouse mutants
Authors: Yang Ran , Stendahl Alexandra , Vigh-Conrad Katinka A. , Held Madison , Lima Ana C. , Conrad Donald F. 
Published: April 2022

AbstractMotivationThe mammalian testis is a complex organ with a hierarchical organization that changes smoothly and stereotypically over time in normal adults. While testis histology is already an invaluable tool for identifying and describing developmental differences in evolution and disease, methods for standardized, digital image analysis of testis are needed to expand the utility of this approach.ResultsWe developed SATINN (Software for Analysis of Testis Images with Neural Networks), a multi-level framework for automated analysis of multiplexed immunofluorescence images from mouse testis. This approach uses a convolutional neural network (CNN) to classify nuclei from seminiferous tubules into 7 distinct cell types with an accuracy of 94.2%. These cell classifications are then used in a second-level tubule CNN, which places seminiferous tubules into one of 7 distinct tubule stages with 90.4% accuracy. We further describe numerous cell- and tubule-level statistics that can be derived from wildtype testis. Finally, we demonstrate how the classifiers and derived statistics can be used to rapidly and precisely describe pathology by applying our methods to image data from two mutant mouse lines. Our results demonstrate the feasibility and potential of using computer-assisted analysis for testis histology, an area poised to evolve rapidly on the back of emerging, spatially-resolved genomic and proteomic technologies.Availability and implementationScripts to apply the methods described here are available from http://github.com/conradlab/SATINN.
Acute kidney injury in patients with non-valvular atrial fibrillation treated with rivaroxaban or warfarin: a population-based study from the United Kingdom
Authors: González-Pérez Antonio , Balabanova Yanina , Sáez María E , Brobert Gunnar , Garcia Rodriguez Luis A 
Published: April 2022

AbstractAcute kidney injury (AKI) has been associated with use of oral anticoagulants (OACs) in patients with non-valvular atrial fibrillation (NVAF). We aimed to compare AKI risk among users of rivaroxaban vs. warfarin. We identified two cohorts of NVAF patients who initiated rivaroxaban (15/20 mg/day, N=6436) or warfarin (N=7129) excluding those without estimated glomerular filtration rate values recorded in the year before OAC initiation and those with a history of end-stage renal disease or AKI. We used two methods to define AKI during follow-up (mean 2.5 years): coded entries (method A), and the Aberdeen AKI phenotyping algorithm (method B), using recorded renal function laboratory values during the study period to identify a sudden renal deterioration event. Cox regression was used to calculate hazard ratios (HRs) for AKI with rivaroxaban vs. warfarin use, adjusted for confounders. The number of identified incident AKI cases was 249 (method) A and 723 (method B). Of the latter, 104 (14.4%) were also identified by method A. After adjusting for age, sex, baseline renal function and comorbidity, HRs (95% CIs) for AKI were 1.20 (0.93–1.55; p=0.16) using method A, and 0.80 (0.68–0.93; p<0.01) using method B. Estimates stratified by baseline level of chronic kidney disease were largely consistent with the main estimates. In conclusion, our results support a beneficial effect of rivaroxaban over warfarin in terms of AKI occurrence in patients with NVAF. More research into how best to define AKI using primary care records would be valuable for future studies.
Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis
Authors: Ouidja Mohand Ouidir , Biard Denis S.F. , Chantepie Sandrine , Laffray Xavier , Douaron Gael Le , Huynh Minh-Bao , Rebergue Nicolas , Maïza Auriane , Rubio Karla , González-Velasco Oscar , Barreto Guillermo , De Las Rivas Javier , Papy-Garcia Dulce 
Published: April 2022

AbstractProteoglycans are complex macromolecules formed of glycosaminoglycan chains covalently linked to core proteins through a linker tetrasaccharide common to heparan sulfate proteoglycans (HSPG) and chondroitin sulfate proteoglycans (CSPG). Biosynthesis of a single proteoglycan requires the expression of dozens of genes, which together create the large structural and functional diversity reflected by the numerous diseases or syndromes associated to their genetic variability. Among proteoglycans, HSPG are the most structurally and functionally complex. To decrease this complexity, we retrieved and linked information on pathogenic variants, polymorphism, expression, and literature databases for 50 genes involved in the biosynthesis of HSPG core proteins, heparan sulfate (HS) chains, and their linker tetrasaccharide. This resulted in a new gene organization and biosynthetic pathway representation in which the phenotypic continuum of disorders as linkeropathies and other pathologies could be predictable. Moreover, ubiquitous NDST1, GLCE, HS2ST1, and HS6ST1 appeared to generate ubiquitous heparan sulfate (HS) sequences essential for normal development and homeostasis, whereas the tissue restricted NDST2-4, HS6ST2-3, and HS3ST1-6 appeared to generate specialized HS sequences mainly involved in responsiveness to stimuli. Supported by data on genetic polymorphism and clinical variants, we afford a new vision of HSPG involvement in homeostasis, disease, vulnerability to disease, and behavioral disorders.
Prognostic Significance of WT1 Expression Level Thershold in Acute Myeloid Leukemia Patients Receiving Hematopoietic Stem Cell Transplantation: Meta-Analysis
Authors: Wang Dandan , Qin Ling , Li Boya , Li Tong 
Published: April 2022

AbstractObjectiveThe WT1 gene is considered as a poor prognostic factor for acute myeloid leukemia (AML) after Allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, the effect of the expression threshold of WT1 on the prognosisis controversial, which is evaluated in this meta-analysis.MethodsRelevant studies about the expression threshold of WT1 on the prognosis of AML after Allo-HSCT were searched in online databases. Data were extracted from them and analyzed by Stata16.0 software.ResultsFive studies involving 739 patients were screened out, including 433 cases experimental group and 306 cases control group. The experimental group and control group were compared for 1-year disease-free survival rate (DFS) [RR=1.19, 95%CI (1.03, 1.38), P =0.02] and 4-year DFS [RR= 1.18, 95%CI (0.98, 1.42), P =0.09]. The experimental group was lower than the control group in 1-year DFS, and there was no statistical significance in 4-year DFS. 1-year overall survival rate (OS) [RR=1.06, 95%CI (0.92, 1.23), P =0.40] and 4-year OS [RR= 1.16, 95%CI (1.03, 1.32), P =0.02], suggesting that the experimental group had a lower 4-year OS than the control group, and 1-year OS had no statistical significance.ConclusionsHigh WT1 expression is unfavorable to the prognosis of AML patients undergoing Allo-HSCT. A threshold of 250 copies/104ABL of WT1 may be the best value for predicting the poor prognosis in these patients.
Extracellular matrix assembly stress drives Drosophila central nervous system morphogenesis
Authors: Serna-Morales Eduardo , Sánchez-Sánchez Besaiz J. , Marcotti Stefania , Bhargava Anushka , Dragu Anca , Hirvonen Liisa M. , Díaz-de-la-Loza María-del-Carmen , Mink Matyas , Cox Susan , Rayfield Emily , Stramer Brian M. 
Published: April 2022

SummaryThe forces controlling tissue morphogenesis are attributed to cellular-driven activities and any role for extracellular matrix (ECM) is assumed to be passive. However, all polymer networks, including ECM, can theoretically develop autonomous stresses during their assembly. Here we examine the morphogenetic function of an ECM prior to reaching homeostatic equilibrium by analyzing de novo ECM assembly during Drosophila ventral nerve cord (VNC) condensation. Asymmetric VNC shortening and a rapid decrease in surface area correlate with exponential assembly of Collagen-IV (Col4) surrounding the tissue. Concomitantly, a transient developmentally-induced Col4 gradient leads to coherent long-range flow of ECM, which equilibrates the Col4 network. Finite element analysis and perturbation of Col4 network formation through the generation of dominant Col4-truncations that affect assembly, reveals that VNC morphodynamics is driven by a sudden increase in ECM-driven surface tension. These data highlight that ECM assembly stress and associated network instabilities can actively participate in tissue morphogenesis.
Benchmarking the accuracy of structure-based binding affinity predictors on Spike-ACE2 Deep Mutational Interaction Set
Authors: Ozden Burcu , Şamiloğlu Eda , Özsan Atakan , Erguven Mehmet , Koşaca Mehdi , Oktayoğlu Melis , Yükrük Can , Arslan Nazmiye , Karakülah Gökhan , Barlas Ayşe Berçin , Savaş Büşra , Karaca Ezgi 
Published: April 2022

ABSTRACTSince the start of COVID-19 pandemic, a huge effort has been devoted to understanding the Spike (SARS-CoV-2)-ACE2 recognition mechanism. To this end, two deep mutational scanning studies traced the impact of all possible mutations across Receptor Binding Domain (RBD) of Spike and catalytic domain of human ACE2. By concentrating on the interface mutations of these experimental data, we benchmarked six commonly used structure-based binding affinity predictors (FoldX, EvoEF1, MutaBind2, SSIPe, HADDOCK, and UEP). These predictors were selected based on their user-friendliness, accessibility, and speed. As a result of our benchmarking efforts, we observed that none of the methods could generate a meaningful correlation with the experimental binding data. The best correlation is achieved by FoldX (R = -0.51). Also, when we simplified the prediction problem to a binary classification, i.e., whether a mutation is enriching or depleting the binding, we showed that the highest accuracy is achieved by FoldX with 64% success rate. Surprisingly, on this set, simple energetic scoring functions performed significantly better than the ones using extra evolutionary-based terms, as in Mutabind and SSIPe. Furthermore, we also demonstrated that recent AI approaches, mmCSM-PPI and TopNetTree, yielded comparable performances to the force field-based techniques. These observations suggest plenty of room to improve the binding affinity predictors in guessing the variant-induced binding profile changes of a host-pathogen system, such as Spike-ACE2. To aid such improvements we provide our benchmarking data athttps://github.com/CSB-KaracaLab/RBD-ACE2-MutBenchwith the option to visualize our mutant models athttps://rbd-ace2-mutbench.github.io/
Restoration and resilience to sea level rise of a salt marsh affected by dieback events in Charleston, SC
Authors: Rolando JL , Hodges M , Garcia KD , Krueger G , Williams N , Carr J , Robinson J , George A , Morris J , Kostka JE 
Published: April 2022

AbstractThe frequency of salt marsh dieback events has increased over the last 25 years with unknown consequences to the resilience of the ecosystem to accelerated sea level rise (SLR). Salt marsh ecosystems impacted by sudden vegetation dieback events were previously thought to recover naturally within a few months to years. In this study, we provide evidence that approximately 14% of total marsh area has not revegetated 10-years after a dieback event in Charleston, SC. Dieback onset coincided with a severe drought in 2012, and a second dieback event occurred in 2016 after a historic flood influenced by Hurricane Joaquin in October of 2015, with unvegetated zones reaching nearly 30% of total marsh area in 2017. Most affected areas were associated with lower elevation zones in the interior of the marsh (midmarsh). During the 2013 dieback event, we estimate that unvegetated midmarsh area expanded by 300%. Grass planting was shown to be an effective restoration practice, with restored plants having greater aboveground biomass than relict sites after two years of transplanting. A positive restoration outcome indicated that the stressors that caused the initial dieback are no longer present. Despite that, many dieback areas have not recovered naturally even as they are located within the typical elevation range of a healthy vegetated marsh. A mechanistic modelling approach was used to assess the effects of vegetation dieback on salt marsh resilience to SLR. Predictions indicate that a highly productive restored marsh (2000 g m-2y-1) would persist at a moderate SLR rate of 60 cm 100 y-1, whereas a non- restored mudflat would lose all of its elevation capital after 100 years. Thus, rapid restoration of marsh dieback is critical to avoid further degradation. Also, failure to incorporate the increasing frequency and intensity of extreme climatic events which trigger irreversible marsh diebacks underestimates salt marsh vulnerability to climate change. At an elevated SLR rate of 122 cm 100 y-1, most likely an extreme climate change scenario, even highly productive ecosystems augmented by sediment placement would not keep pace with SLR. Thus, climate change mitigation actions are also urgently needed to preserve present-day marsh ecosystems.
Transcriptome-guided annotation and functional classification of long non-coding RNAs in Arabidopsis thaliana
Authors: Corona-Gomez Jose Antonio , Coss-Navarrete Evelia Lorena , Garcia-Lopez Irving Jair , Pérez-Patiño Jaime Alejandro , Fernandez-Valverde Selene L. 
Published: April 2022

AbstractLong non-coding RNAs (lncRNAs) are a prominent class of eukaryotic regulatory genes. Despite the numerous available transcriptomic datasets, the annotation of plant lncRNAs remains based on dated annotations that have been historically carried over. We present a substantially improved annotation of Arabidopsis thaliana lncRNAs, generated by integrating 224 transcriptomes in multiple tissues, conditions, and developmental stages. We annotate 6764 lncRNA genes, including 3772 that are novel. We characterize their tissue expression patterns and find 1425 lncRNAs are co-expressed with coding genes, with enriched functional categories such as chloroplast organization, photosynthesis, RNA regulation, transcription, and root development. This improved transcription-guided annotation constitutes a valuable resource for studying lncRNAs and the biological processes they may regulate.
NuRD independent Mi-2 activity represses ectopic gene expression during neuronal maturation
Authors: Aughey Gabriel N , Forsberg Elhana , Grimes Krista , Zhang Shen , Southall Tony D 
Published: April 2022

AbstractDuring neuronal development, extensive changes to chromatin states occur to regulate lineage-specific gene expression. The molecular factors underlying the repression of non-neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues the precise nature of the gene expression programmes that it coordinates are ill-defined. Furthermore, evidence from several species suggests that Mi-2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. We show that Mi-2 activity is required for suppressing ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of NuRD, including Mi-2, regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi-2 binding in the genome is dynamic during neuronal maturation and Mi-2 mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi-2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation.