bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerant crops increase growers’ yields but promote selfishness: how the epidemiology of disease resistant and tolerant varieties affect grower behaviour
Authors: Murray-Watson Rachel E. , Cunniffe Nik J. 
Published: June 2022

1SummaryDisease management often involves genetically improved crops. Resistant varieties are less susceptible, and so less likely to act as reservoirs of inoculum. Tolerant varieties can be highly susceptible, but limit yield loss for those who grow them. Population-scale effects of deploying resistant or tolerant varieties have received little consideration from epidemiologists.We examined how tolerant and resistant crop have opposing consequences upon the uptake of control using a behavioural model based on strategic-adaptive expectations. Growers compared last season’s profit with an estimate of what could be expected from the alternative crop type, thereby assessing whether to alter their strategy for the next season.Tolerant crop only benefited growers using it, decreasing yields for others. This incentivises widespread use via a negative feedback loop. Resistant crop was more widely beneficial, with reduced population-scale disease pressure leading to increased yields for all. However, this positive externality allows growers who do not deploy resistant crop to “free-ride” upon the management of others.This work highlights how a community of growers responds to the contrasting incentives caused by tolerant and resistant crop varieties, and how this leads to very distinct effects on yields and population-scale deployment.
Exploration of DPP-IV inhibitory peptide design rules assisted by deep learning pipeline that identifies restriction enzyme cutting site
Authors: Guan Changge , Luo Jiawei , Li Shucheng , Tan Zheng Lin , Wang Yi , Chen Haihong , Yamamoto Naoyuki , Zhang Chong , Lu Yuan , Chen Junjie , Xing Xin-Hui 
Published: June 2022

AbstractMining of anti-diabetic dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (DPP-IV-IPs) is currently a costly and laborious process. Due to the absence of rational peptide design rules, it relies on cumbersome screening of unknown enzyme hydrolysates. Here, we present an enhanced deep learning (DL) model called BERT-DPPIV, specifically designed to classify DPP-IV-IPs and exploring their design rules to discover potent candidates. The end-to-end model utilizes a fine-tuned bidirectional encoder representations (BERT) architecture to extract structural/functional information from input peptides and accurately identify DPP-IV-Ips from input peptides. Experimental results in benchmark dataset showed BERT-DPPIV yielded state-of-the-art accuracy of 0.894, surpassing the 0.797 obtained by sequence-feature model. Furthermore, we leverage the attention mechanism to uncover that our model could recognize restriction enzyme cutting site and specific residues that contribute to the inhibition of DPP-IV. Moreover, guided by BERT-DPPIV, proposed design rules of DPP-IV inhibitory tripeptides and pentapeptides were validated and they can be used to screen potent DPP-IV-IPs.
The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis
Authors: Pleuger Christiane , Ai Dingding , Hoppe Minea , Winter Laura , Bohnert Daniel , Karl Dominik , Guenther Stefan , Epelman Slava , Kantores Crystal , Fijak Monika , Ravens Sarina , Middendorff Ralf , Mayer Johannes U. , Loveland Kate L. , Hedger Mark P. , Bhushan Sudhanshu , Meinhardt Andreas 
Published: June 2022

Summary/ AbstractThe epididymis constitutes an important transition zone for post-testicular sperm maturation and storage. As the organ consists of a single convoluted duct, inflammation-associated tissue damage has a severe impact on fertility. In order to clarify the reasons for region-specific differences in the intensity of immune responses observed in a mouse model of acute bacterial epididymitis, we investigated the heterogeneity of resident immune cell populations within the epididymis under physiological conditions by scRNASeq analysis of extravascular CD45+ cells. 12 distinct immune cell subsets were identified, displaying substantial differences in distribution along the epididymis. Several distinct subsets of macrophages constituted the majority of these cells. Crucially, the proximal and distal regions showed striking differences in their immunological landscapes. These findings indicate that resident immune cells are strategically positioned along the epididymal duct, potentially providing different immunological environments required for sperm maturations and elimination of pathogens ascending the urogenital tract.
Inhibition of the TPL2-MKK1/2-ERK1/2 pathway has cytostatic effect on B-Cell Lymphoma
Authors: Asslan Mariana , Martel Guy , Rousseau Simon 
Published: June 2022

1)AbstractDiffuse Large B-Cell Lymphoma (DLBCL) are the most common form of non-Hodgkin lymphoma. Their molecular origin is heterogeneous and therefore treatments aimed at DLBCL must be adapted in function of the underlying molecular mechanisms driving cellular transformation. Constitutive activation of the protein kinases ERK1/2 is a hallmark of many B-cell malignancies. ERK1/2 activation which can occur downstream of the classical MAPK cascade via RAF or, in response to TLR stimulation, via the Tumor Promoting Locus 2 (TPL2) protein kinase. This pathway also relays signals from the MYD88 oncogenic mutant L265P, frequently found in hematologic malignancies. We report here that TPL2 participate to ERK1/2 activation downstream of BCR in a DLBCL cell line (OCI-Ly2). Moreover, we showed that a ERK2[Y316F] mutant increased c-Myc-luciferase reporter expression. We then investigated the impact of ERK1/2 inhibition on the proliferation of OCI-Ly2 cells. We found that blocking ERK1/2 MAPK signaling cascade using either MKK1/2 inhibitors (PD184352 and MEK162) or TPL2 inhibitor (Compound 1) was mainly cytostatic. Finally, we showed that while TPL2-MKK1/2 inhibition leads to cytostatic effect, Compound 1 has cytocidal effect at high concentrations, that is mediated via additional targets. Taken together, this study demonstrates the involvement of TPL2 in oncogenic signaling of DLBCL and supports the idea that combination therapy targeting multiple molecular pathways linked to cellular transformation is a superior avenue for future therapies.
Trem2 deficiency does not worsen metabolic function in diet-induced obese mice
Authors: Winn Nathan C. , Wolf Elysa M. , Garcia Jamie N. , Hasty Alyssa H. 
Published: June 2022

ABSTRACTTriggering receptor expressed on myeloid cells 2 (Trem2) is highly expressed on myeloid cells and is involved in cellular lipid homeostasis and inflammatory processes. Trem2 deletion in mice (Trem2-/-) has been implicated in evoking adipose tissue dysfunction, but its role in worsening obesity-induced metabolic dysfunction is not resolved. Here we aimed to determine the causal role of Trem2 in regulating glucose homeostasis and insulin sensitivity in mice. Nine-week-old male and female littermate WT and Trem2-/- mice were fed low fat or high fat diet for 18 weeks and phenotyped for metabolic function. Diet-induced weight gain was similar between genotypes, irrespective of sex. Consistent with prior reports, we find that loss of Trem2 causes massive adipocyte hypertrophy and an attenuation in the lipid associated macrophage transcriptional response to obesity. In contrast to published data, we find that loss of Trem2 does not worsen metabolic function in obese mice. No differences in intraperitoneal glucose tolerance (ipGTT), oral GTT, or mixed meal substrate control, including postprandial glucose, non-esterified fatty acids, insulin, or triglycerides were found between WT and Trem2-/- animals. Similarly, no phenotypic differences existed when animals were challenged with stressors on metabolic demand (i.e., acute exercise or environmental temperature modulation) or when animals were challenged with a non-lethal dose of endotoxin. Collectively, we report a disassociation between adipose tissue remodeling caused by loss of Trem2 and whole-body metabolic homeostasis in obese mice. The complementary nature of experiments conducted gives credence to the conclusion that loss of Trem2 is unlikely to worsen glucose homeostasis in mice.
SERCA2 regulates proinsulin processing and processing enzyme maturation in the pancreatic β cell
Authors: Iida Hitoshi , Kono Tatsuyoshi , Lee Chih-Chun , Krishnan Preethi , Arvin Matthew C. , Weaver Staci A. , Jarvela Timothy S. , Bone Robert N. , Tong Xin , Arvan Peter , Lindberg Iris , Evans-Molina Carmella 
Published: June 2022

AbstractIncreased circulating levels of incompletely processed insulin (i.e. proinsulin) are observed clinically in both type 1 and type 2 diabetes; however, the mechanisms underlying impaired proinsulin processing remain incompletely understood. Here, we identify the sarcoendoplasmic reticulum Ca2+ ATPase-2 (SERCA2) pump and β cell ER Ca2+ as key regulators of systemic glucose tolerance and proinsulin processing. We generated mice with a β cell-specific SERCA2 deletion (βS2KO) and SERCA2 deficient INS-1 cells to show that SERCA2 loss increases systemic and pancreatic levels of proinsulin protein and leads to aberrant localization of proinsulin within the proximal β cell secretory pathway. These defects in proinsulin processing were linked to reduced maturation of the proinsulin processing enzymes PC1/3 and PC2, suggesting a model whereby chronic ER Ca2+ depletion in the β cell, which is observed in many pathological conditions, impairs the spatial regulation of prohormone trafficking, processing, and maturation within the β cell secretory pathway.
DriverSEAT: A spatially-explicit stochastic modelling framework for the evaluation of gene drives in novel target species
Authors: Legros Mathieu , Barrett Luke G. 
Published: June 2022

AbstractGene drives represent a potentially ground breaking technology for the control of undesirable species or the introduction of desirable traits in wild population, and there is strong interest in applying these technologies to a wide range of species across many domains including agriculture, health, conservation and biosecurity. There remains however considerable uncertainty regarding the feasibility and efficacy of gene drives in various species, based in particular on biological and ecological specificities of each target. In this paper we introduce DriverSEAT, a new spatial, modular modelling framework designed to assess the outcome of gene drives in a range of target species based on their specific ecological dynamics and genetics. In addition to the main structure and characteristics of the model, we present an example of its application on scenarios of genetic control of weeds, a potential candidate for gene drive control that presents significant challenges associated with plant population dynamics. We illustrate here how the results from DriverSEAT can inform on the potential value of gene drives in this specific context, and generally provide ecologically informed guidance for the development and feasibility of gene drives as a control method in new target species.
Simple Human Response Times are Governed by Dual Anticipatory Processes with Distinct and Distributed Neural Signatures
Authors: Ramayya Ashwin G. , Buch Vivek , Richardson Andrew , Lucas Timothy , Gold Joshua I. 
Published: June 2022

AbstractHuman behavior can be highly sensitive to anticipation, but the mechanisms underlying this sensitivity are poorly understood. We obtained intracranial electrocephalography (iEEG) measurements in neurosurgical patients as they performed a simple sensory-motor task with variable (short or long) foreperiod delays that affected anticipation of the cue to respond. Participants showed two forms of anticipatory response biases, distinguished by more premature false alarms (FAs) or faster response times (RTs) on long-delay trials. These biases had distinct neural signatures in prestimulus neural activity modulations that were distributed and intermixed across the brain: the FA bias was most evident in preparatory motor activity immediately prior to response-cue presentation, whereas the RT bias was most evident in visuospatial activity at the beginning of the foreperiod. These results suggest that human anticipatory behavior emerges from a combination of motor-preparatory and attention-like modulations of neural activity, implemented by anatomically widespread and intermixed, but functionally identifiable, brain networks.Graphical Abstract
Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study
Authors:   The OpenSAFELY Collaborative, Parker Edward PK , Tazare John , Hulme William J , Bates Christopher , Beale Rupert , Carr Edward J , Cockburn Jonathan , Curtis Helen J , Fisher Louis , Green Amelia CA , Harper Sam , Hester Frank , Horne Elsie MF , Loud Fiona , Lyon Susan , Mahalingasivam Viyaasan , Mehrkar Amir , Nab Linda , Parry John , Santhakumaran Shalini , Steenkamp Retha , Sterne Jonathan AC , Walker Alex J , Williamson Elizabeth J , Willicombe Michelle , Zheng Bang , Goldacre Ben , Nitsch Dorothea , Tomlinson Laurie A 
Published: June 2022

AbstractBackgroundKidney disease is a significant risk factor for COVID-19-related mortality. Achieving high COVID-19 vaccine coverage among people with kidney disease is therefore a public health priority.MethodsWith the approval of NHS England, we performed a retrospective cohort study using the OpenSAFELY-TPP platform. Individual-level routine clinical data from 24 million people in England were included. A cohort of individuals with stage 3–5 chronic kidney disease (CKD) or receiving renal replacement therapy (RRT) at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate or inclusion in the UK Renal Registry. Individual-level factors associated with vaccine uptake were explored via Cox proportional hazards models.Results948,845 people with stage 3–5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 11th May 2022 was 97.5%, 97.0%, and 93.5% for doses 1, 2, and 3, respectively, and 61.1% among individuals with one or more indications for receipt of a fourth dose. Delayed 3-dose vaccine uptake was associated with non-White ethnicity, social deprivation, and severe mental illness – associations that were consistent across CKD stages and in RRT recipients. Similar associations were observed for 4-dose uptake, which was also delayed among care home residents.ConclusionAlthough high primary and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across demographic groups. Identifying how to address these disparities remains a priority to reduce the risk of severe disease in this vulnerable patient group.
Association of lithocholic acid with skeletal muscle hypertrophy through TGR5-IGF-1 and skeletal muscle mass in chronic liver disease rats and humans
Authors: Tamai Yasuyuki , Eguchi Akiko , Shigefuku Ryuta , Kitamura Hiroshi , Tempaku Mina , Sugimoto Ryosuke , Kobayashi Yoshinao , Iwasa Motoh , Takei Yoshiyuki , Nakagawa Hayato 
Published: June 2022

Abstract[Background & aims] Hepatic sarcopenia is one of many complications associated with chronic liver disease (CLD) and has a high mortality rate, however, the liver-muscle axis is not fully understood. Therefore, few effective treatments exist for hepatic sarcopenia, the best of which being branched-amino acid (BCAA) supplementation to help increase muscle mass. Our aim was to investigate the molecular mechanism(s) of hepatic sarcopenia focused on bile acid (BA) composition. [Methods] Gastrocnemius muscle phenotype and serum BA levels were assessed in CLD rats treated with BCAA. Mouse skeletal muscle cells (C2C12) were incubated with lithocholic acid (LCA), G-protein-coupled receptor 5 (TGR5) agonist or TGR5 antagonist to assess skeletal muscle hypertrophy. The correlation between serum BA levels and psoas muscle area index (PMI) was examined in 73 CLD patients. [Results] Gastrocnemius muscle weight significantly increased in CLD rats treated with BCAA via suppression of protein degradation pathways, coupled with a significant increase in serum LCA levels. LCA treated C2C12 hypertrophy occurred in a concentration-dependent manner linked with TGR5-Akt pathways based upon inhibition results via a TGR5 antagonist. In human CLD, serum LCA levels were the sole factor positively correlated with PMI and were significantly decreased in both the low muscle mass group and the deceased group. Serum LCA levels were also shown to predict patient survival. [Conclusion] Our results indicate LCA-mediated skeletal muscle hypertrophy via activation of TGR5-IGF1-Akt signaling pathways. In addition, serum LCA levels were associated with skeletal muscle mass in cirrhotic rats, as well as CLD patients, and predicted overall patient survival. [Funding] This research was supported by JSPS KAKENHI Grant Number 22K08011 and 21H02892, and AMED under Grant Number JP21fk0210090 and JP22fk0210115.
Changes in basal insulin secretion capacity after pancreatectomy: a retrospective study
Authors: Kihara Yasuhiro , Murotani Kenta , Yokomizo Hiroshi 
Published: June 2022

AbstractThis study evaluated the changes in basal insulin secretion capacity (BISC) after pancreatectomy across two surgical procedures. We also investigated the association between decreased BISC and the introduction of postoperative insulin therapy. The data on 110 patients who underwent pancreatectomy during October 2018–February 2022 at our hospital were analyzed retrospectively. We focused on the C-peptide index (CPI) as an index for BISC. A decreased postoperative BISC was defined as a postoperative CPI (post-CPI) <1.0, which was in turn defined as the event occurrence in our study. The receiver operating characteristic curve for the event occurrence was plotted for factors related to preoperative glucose tolerance. Of the preoperative non-diabetic 73 patients, 44 and 29 who underwent pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), respectively, were examined. A post-CPI of <1.0 was observed in 29 patients (39%). Although the proportion of remnant pancreatic volume was significantly smaller in patients with PD than in patients with DP (38% vs. 68%, p <0.0001), no significant difference was observed in the event rates (39% vs. 41%). In patients with PD, preoperative CPI (area under the curve: 0.75) was used for predicting post-CPI <1.0. Multivariate analysis revealed that preoperative CPI <1.65 (odds ratio: 7.69, 95% confidence interval: 1.87–31.5) was an independent predictor of decreased postoperative BISC. However, in patients with DP, no significant predictors were identified. Induction of insulin therapy was significantly lower in preoperative non-diabetic patients (n=73) after undergoing a pancreatectomy (1.4% vs. 37.5%, p<0.0001) than in preoperative medically treated patients (n=16); there was no significant difference in event (post-CPI <1.0) rates (39.7% vs. 56.2%, p=0.23). Although pancreatectomy reduces BISC after surgery, the coexistence of insulin resistance, which is a pathophysiology of type 2 diabetes mellitus, may play a role in whether postoperative glucose tolerance is reduced to the point where insulin therapy is necessary.
The relationship between response dynamics and the formation of confidence varies across the lifespan
Authors: Overhoff Helen , Ko Yiu Hong , Fink Gereon R. , Stahl Jutta , Weiss Peter H. , Bode Stefan , Niessen Eva 
Published: June 2022

AbstractAccurate metacognitive judgements, such as forming a confidence judgement, are crucial for goaldirected behaviour but decline with older age. Besides changes in the sensory processing of stimulus features, there might also be changes in the motoric aspects of giving responses that account for age-related changes in confidence. In order to assess the association between confidence and response parameters across the adult lifespan, we measured response times and peak forces in a four-choice flanker task with subsequent confidence judgements. In 65 healthy adults from 20 to 76 years of age, we showed divergent associations of each measure with confidence, depending on decision accuracy. Participants indicated higher confidence after faster responses in correct but not incorrect trials. They also indicated higher confidence after less forceful responses in errors but not in correct trials. Notably, these associations were age-dependent as the relationship between confidence and response time was more pronounced in older participants, while the relationship between confidence and response force decayed with age. Our results add to the notion that confidence is related to response parameters and demonstrate noteworthy changes in the observed associations across the adult lifespan. These changes potentially constitute an expression of general age-related deficits in performance monitoring or, alternatively, index a failing mechanism in the computation of confidence in older adults.
CellScape: Protein structure visualization with vector graphics cartoons
Authors: Silvestre-Ryan Jordi , Fletcher Daniel A. , Holmes Ian 
Published: June 2022

AbstractMotivationIllustrative renderings of proteins are useful aids for scientific communication and education. Nevertheless, few software packages exist to automate the generation of these visualizations.ResultsWe introduce CellScape, a tool designed to generate 2D molecular cartoons from atomic coordinates and combine them into larger cellular scenes. These illustrations can outline protein regions in different levels of detail. Unlike most molecular visualization tools which use raster image formats, these illustrations are represented as vector graphics, making them easily editable and composable with other graphics.Availability and ImplementationCellScape is implemented in Python 3 and freely available at https://github.com/jordisr/cellscape. It can be run as a command-line tool or interactively in a Jupyter notebook.Contactjordisr@berkeley.edu