bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of multidrug and extensive-drug resistant Gam-negative bacteria in skin and soft tissue infections
Authors: Brink Adrian J. , Richards Guy A.
Published: January 2020

Purpose of review

Whereas Staphylococcus aureus remains the leading cause of skin and soft tissue infections (SSTI), Gram-negative bacilli (GNB) are increasingly reported as a cause of monomicrobial or polymicrobial infections. This review examines the expanding role of GNB in SSTI and discusses the risks for and the frequency of multidrug-resistance (MDR) and extensive drug-resistance (XDR) and the implications with regard to outcome and therapy.

Recent findings

Although the global epidemiology and role of GNB in SSTIs have not been studied systematically, complicated SSTIs caused by resistant GNB are increasing particularly in vulnerable patients with long-standing infections, those in long-term care facilities, and those with a history of recent hospitalization or prior antibiotic therapy. Mixed infections also occur in up to 25% of SSTIs, and inappropriate therapy occurs in 40% of cases. Prompt identification of the causative pathogen requires that patients with SSTI be risk stratified according to the likelihood of resistance to enable early recognition and swift initiation of appropriate therapy.

For individual treatment decisions in SSTIs, institutional diagnostic and treatment algorithms based on local epidemiology and risk factors are pivotal to reducing the incidence of treatment failure and improving outcomes associated with resistant GNB.
A Single-Center Retrospective Chart Review to Determine Whether the Presence of Comorbidities Affects Colon Cancer Screenings in African Americans
Authors: Hodges Stacey S.
Published: January 2020

Colon cancer is the third leading cause of cancer-related death in African Americans. Although the rates of colon screenings have risen, African Americans remain to be underscreened, and are more likely to present with advanced lesions. This population has a higher prevalence of inflammatory comorbidities, and their effects on screenings have not been fully explored. Along with higher rates of comorbidities, the Southeastern United States is one region for the highest rates of colorectal cancer. The purpose of this study was to determine whether people with comorbidities were more likely to have a screening colonoscopy. Convenience sampling was used to procure 408 patients. The median age was 55 years, and the majority were females (52.2%), who were obese (29.2%), and nonsmokers (52.2%). The most common comorbidity was hypertension (70.3%), followed by osteoarthritis (39%), and diabetes (25.5%). There is a well-documented trend between certain inflammatory comorbidities and higher death rates in patients with colorectal cancer. Clarifying the relationship between comorbidities and cancer starts with screening as many patients as possible. Therefore, interventions that support increasing the number of colorectal cancer screenings are imperative in order to improve morbidity and mortality in this despaired population.
Complications After Reperitonealization of Mesh at Time of Sacrocolpopexy: A Retrospective Cohort Study
Authors: Glass Clark Stephanie M. , Shannon Megan B. , Gill Edward , Clark Michael D. , Lamb Elizabeth , Carroll Ashley
Published: January 2020

Objectives

To determine if there is a difference in rates of surgical complications among patients who have reperitonealization of mesh versus no reperitonealization at time of sacrocolpopexy.

Methods

This was a retrospective cohort study of all patients who underwent sacrocolpopexy at an academic medical center between 2008 and 2017. The medical record was reviewed for the operative method of sacrocolpopexy, concomitant surgeries, intraoperative or postoperative complications, and readmissions. Groups were compared on whether mesh was reperitonealized under pelvic peritoneum or not.

Results

A total of 209 patients underwent sacrocolpopexy, with mesh reperitonealization performed in 115 (55%). Demographics were similar in both groups, except race/ethnicity and stage of prolapse. The majority (190 [91%]) of surgeries included concomitant procedures. A total of 18 intraoperative or postoperative complications (8.6%) were recorded. Relative risk of complication with mesh reperitonealization is 0.81 (95% confidence interval, 0.1–1.70). Complications for subjects without mesh reperitonealization included 4 cystostomies, 1 urethrotomy, 3 postoperative ileuses, and 1 small bowel obstruction. Among subjects with mesh reperitonealization, complications included 5 cystotomies, 2 proctotomies, 1 ureteral obstruction, and 1 small bowel obstruction. Rates of hospital readmission among both groups were not significantly different, with 3.2% of subjects without mesh reperitonealization versus 3.5% of mesh reperitonealization patients (P = 0.91) (relative risk, 1.09; 95% confidence interval, 0.38–2.56).

Conclusions

There is no significant difference in rates of complications or readmissions among patients with and without mesh reperitonealization at time of sacrocolpopexy. The only intraoperative complication solely attributed to mesh closure was a case with ureteral obstruction at time of reperitonealization.
Racial and Ethnic Differences in Urodynamic Parameters in Women With Overactive Bladder Symptoms
Authors: Zuo Stephanie W. , English Keara , Agalliu Ilir , Leegant Ava , Abraham Nitya
Published: January 2020

Objectives

This study aimed to identify differences in severity of overactive bladder (OAB) symptoms in women of different races and ethnicities using urodynamic study (UDS) parameters.

Methods

We performed a 5-year retrospective chart review from January 2014 to January 2019 of women 18 years and older who endorsed OAB symptoms and underwent UDS at a racially and ethnically diverse academic urban medical center. Logistic and linear regressions were used to examine the associations of various UDS parameters between racial/ethnic groups, after adjusting for age, diabetes, and parity.

Results

A total of 161 women with an average age of 59 years were included in the study. The racial/ethnic composition of the group was Hispanic (62%), black (24%), and white (11%). Symptoms on presentation included urgency and/or frequency (11.8%), urge incontinence (23.0%), or mixed urinary symptoms (65.2%). Black and Hispanic women presented with differing symptoms (urgency/frequency vs mixed urinary symptoms). Half of the patients (n = 82) had detrusor overactivity. Compared with whites, blacks were 3.4-fold more likely to have detrusor overactivity (95% confidence interval, 0.99–11.40) and had lower volumes at time of “strong desire” (−102.6 mL, P = 0.003). Hispanics had on average 75.88 mL less volume at sensation of “strong desire” (P = 0.016) than did whites.

Conclusions

Our study suggests that minority race and ethnicity may be associated with worse performance on certain UDS parameters. Future studies should aim to understand if these differences are due to genetic, disease-related, behavioral, and/or socioeconomic factors and whether these differences are associated with worse subjective OAB.
Caffeine stabilises fission yeast Wee1 in a Rad24-dependent manner but attenuates its expression in response to DNA damage identifying a putative role for TORC1 in mediating its effects on cell cycle progression
Authors: Alao John P. , Johansson-Sjölander Johanna , Rallis Charalampos , Sunnerhagen Per
Published: January 2020

The widely consumed neuroactive compound caffeine has generated much interest due to its ability to override the DNA damage and replication checkpoints. Previously Rad3 and its homologues was thought to be the target of caffeine’s inhibitory activity. Later findings indicate that the Target of Rapamycin Complex 1 (TORC1) is the preferred target of caffeine. Effective Cdc2 inhibition requires both the activation of the Wee1 kinase and inhibition of the Cdc25 phosphatase. The TORC1, DNA damage, and environmental stress response pathways all converge on Cdc25 and Wee1. We previously demonstrated that caffeine overrides DNA damage checkpoints by modulating Cdc25 stability. The effect of caffeine on cell cycle progression resembles that of TORC1 inhibition. Furthermore, caffeine activates the Sty1 regulated environmental stress response. Caffeine may thus modulate multiple signalling pathways that regulate Cdc25 and Wee1 levels, localisation and activity. Here we show that the activity of caffeine stabilises both Cdc25 and Wee1. The stabilising effect of caffeine and genotoxic agents on Wee1 was dependent on the Rad24 chaperone. Interestingly, caffeine inhibited the accumulation of Wee1 in response to DNA damage. Caffeine therefore modulates cell cycle progression contextually through increased Cdc25 activity and Wee1 repression following DNA damage via TORC1 inhibition.
Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: a cross-sectional study
Authors: Christensen Jacob J. , Ulven Stine M. , Thoresen Magne , Westerman Kenneth , Holven Kirsten B. , Andersen Lene F.
Published: January 2020

Background

Diet may alter gene expression in immune cells involved in cardio-metabolic disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans.

Objective

Our objective was to examine the associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults.

Methods

We used factor analysis to definea posterioriDPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. All analyses were gender-stratified (n = 130 women and 105 men).

Results

We detected three DPs that broadly reflectedWestern, Vegetarian, andLow carbohydratediets. CIBERSORT-predicted percentage of monocytes associated strongly and negatively with theVegetarianDP in both women and men. For women, theVegetarianDP associated most strongly with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription. For men, theWesternDP inversely associated most strongly with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. In subsequent protein-protein interaction network analysis, the most importantdriver geneswithin these WGCNA gene clusters seemed to physically interact in biological networks.

Conclusions

DPs may affect percentage monocytes and regulation of key biological processes within the PBMC pool. Although the present findings are exploratory, our analysis pipeline serves a useful framework for studying the association between diet and gene expression.
Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation
Authors: Zuo Kun , Li Jing , Zhang Jing , Wang Pan , Jiao Jie , Liu Zheng , Yin Xiandong , Liu Xiaoqing , Li Kuibao , Yang Xinchun
Published: January 2020

Specific alterations of gut microbiota (GM) in atrial fibrillation (AF) patients, including elevated microbial diversity, particularly perturbed composition, imbalanced microbial function, and associated metabolic pattern modifications have been described in our previous report. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation, and to construct a GM-based predictive model for RAF. Gut microbial composition and metabolic profiles were assessed based on metagenomic sequencing and metabolomic analyses. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and the non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the familiesNitrosomonadaceaeandLentisphaeraceae, the generaMarinitogaandRufibacter, and the speciesFaecalibacteriumsp. CAG:82,Bacillus gobiensis, andDesulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. An elevated area under curve (0.954) and positive net reclassification index (1.5601) for predicting RAF compared with traditional clinical scoring (AUC=0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance. These data provide novel evidence that supports incorporating the GM factor into future recurrent risk stratification.
The incubation period of 2019-nCoV infections among travellers from Wuhan, China
Authors: Backer Jantien A. , Klinkenberg Don , Wallinga Jacco
Published: January 2020

Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 – 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.
ctDNAtools: An R package to work with sequencing data of circulating tumor DNA
Authors: Alkodsi Amjad , Meriranta Leo , Pasanen Annika , Leppä Sirpa
Published: January 2020

Sequencing of cell-free DNA (cfDNA) including circulating tumor DNA (ctDNA) in minimally-invasive liquid biopsies is rapidly maturing towards clinical utility for cancer diagnostics. However, the publicly available bioinformatics tools for the specialized analysis of ctDNA sequencing data are still scarce. Here, we present the ctDNAtools R package, which provides functionalities for testing minimal residual disease (MRD) and analyzing cfDNA fragmentation. MRD detection in ctDNAtools utilizes a Monte Carlo sampling approach to test ctDNA positivity through tracking a set of pre-detected reporter mutations in follow-up samples. Additionally, ctDNAtools includes various functionalities to study cfDNA fragment size histograms, profiles and fragment ends patterns.

Availability

The ctDNAtools package is freely available under MIT license athttps://github.com/alkodsi/ctDNAtools.
An analysis of Species Conservation Action Plans in Guinea
Authors: Couch Charlotte , Molmou Denise , Magassouba Sékou , Doumbouya Saïdou , Diawara Mamadou , Yaya Diallo Muhammad , Keita Sékou Moussa , Koné Falaye , Diallo Mahamadou Cellou , Kourouma Sékou , Diallo Mamadou Bella , Keita Mamady Sayba , Oulare Aboubacar , Darbyshire Iain , Nic Lughadha Eimear , Van Der Burgt Xander , Larridon Isabel , Cheek Martin
Published: January 2020

To achieve conservation success, we need to support the recovery of threatened species. Yet, <5% of plant species listed as threatened on the IUCN Red List have Species Conservation Action Plans (CAPs). If we are to move from a Red List to a Green List for threatened plant species, CAPs need to be devised and implemented. Guinea is one of the most botanically diverse countries in West Africa. Recent research found that nearly 4000 vascular plants occur in Guinea, a 30% increase from previous estimates. 273 of these plant species are now assessed as threatened with global extinction. There is increasing pressure on the environment from the extractive industry and a growing population. In parallel with implementation of an Important Plant Area programme in Guinea, CAPs were developed for 20 threatened plant species. These plans elaborate conservation efforts needed first to safeguard threatened species bothin situandex situand then to support their recovery. We document the approach used to assemble the Species Conservation Action Plans, and we discuss the importance of having up to date field information, IUCN Red List assessments, and use of a collaborative approach. The need for these plans is increasingly important with recent calculations suggesting a third of African plants are threatened with extinction. This paper outlines initial detailed plant conservation planning in Guinea and offers a template for conservation practitioners in other tropical African countries to follow.
The Role of Spatial Separation on Selective and Distributed Attention to Speech
Authors: Pinto Danna , Agmon Galit , Zion Golumbic Elana
Published: January 2020

Abstract

Processing speech in multi-speaker environments poses substantial challenges to the human perceptual and attention system. Moreover, different contexts may require employing different listening strategies. For instance, in some cases individuals pay attentionSelectivelyto one speaker and attempt to ignore all other task-irrelevant sounds, whereas other contexts may require listeners toDistributetheir attention among several speakers. Spatial and spectral acoustic cues both play an important role in assisting listeners to segregate concurrent speakers. However, how these cues interact with varying demands for allocating top-down attention is less clear. In the current study, we test and compare how spatial cues are utilized to benefit performance on these different types of attentional tasks. To this end, participants listened to a concoction of two or four speakers, presented either as emanating from different locations in space or with no spatial separation. In separate trials, participants were required to employ different listening strategies, and detect a target-word spoken either by one pre-defined speaker (Selective Attention) or spoken by any of the speakers (Distributed Attention). Results indicate that the presence of spatial cues improved performance, particularly in the two-speaker condition, which is in line with the important role of spatial cues in stream segregation. However, spatial cues provided similar benefits to performance under Selective and Distributed attention. This pattern suggests that despite the advantage of spatial cues for stream segregation, they were nonetheless insufficient for directing a more focused ‘attentional spotlight’ towards the location of a designated speaker in the Selective attention condition.
Canine cognitive dysfunction (CCD) patients have reduced total hippocampal volume compared with aging control dogs: a comparative MRI study
Authors: Dewey Curtis Wells , Rishniw Mark , Platt Simon , Robinson Kelsey , Sackman Joseph , O’Donnell Marissa
Published: January 2020

Hippocampal atrophy is a key pathologic and MRI feature of human Alzheimer’s disease (AD). Hippocampal atrophy has not been documented via MRI in canine cognitive dysfunction (CCD), which is considered the dog model of human AD. The purpose of this retrospective comparative volumetric MRI study was to compare total hippocampal volumes between successfully aging (control) dogs and dogs diagnosed with CCD. Mimics®software was used to derive total hippocampal volumes and total brain volumes from the MRI studies of 42 aging dogs (≥ 9 years): 16 dogs diagnosed with CCD and 26 successfully aging controls. Total hippocampal volume normalized to total brain volume was significantly less for CCD patients compared with control dogs (p=0.04). The results of this study suggest that-similar to human AD-hippocampal atrophy is a pathological feature of CCD. This finding has potential importance for both investigating disease mechanisms related to dementia as well as future hippocampal-targeted therapies.
Genetic diversity, structure, and kinship analysis ofTrachemys venusta venustain Wildlife Management Units and wild populations in south Mexico. Implications for conservation and management
Authors: Recino-Reyes Elsi B. , Lesher-Gordillo Julia M. , Machkour-M’Rabet Salima , Gallardo-Alvárez Manuel I. , Zenteno-Ruiz Claudia E. , Olivera-Gómez León D. , Valdés-Marín Alejandra , Gómez-Carrasco Guadalupe , Ríos-Rodas Liliana , Barragán-Vázquez María del Rosario , Martínez Raymundo Hernández
Published: January 2020

The Meso-American slider turtle (Trachemys venusta) is a freshwater turtle endemic to Mexico and Central America. Due to the overexploitation of its natural populations, it is in the at risk category formulated by the Official Mexican Standard NOM-059-ECOL-2010. In the state of Tabasco, Management Units for the Conservation of Wildlife (UMA) were created to reduce the impact of overexploitation of freshwater turtles. However, no genetic management plan was considered. This study presents the level of genetic diversity of the founder individuals in order to develop a management plan which will optimize reproduction in the UMA. Genetic diversity was compared between captive (n = 45) and wild (n = 86) individuals using 14 microsatellite molecular markers. Level of genetic diversity could be considered as low (He< 0.6) for a species of turtle and suggests that a higher level of protection is required for this particular species. Furthermore, values were slightly higher for the captive group reflecting the mix of genetic sources (founding individuals from different localities) and demonstrating that the captive population is genetically representative of natural populations. The genetic structure analysis revealed a relationship between captive and wild populations, indicating the influence of the two principal river basins in this region on the population of freshwater turtles. Finally, according to the results obtained from the analysis conducted using Stormand ML-Relateprograms, we recommend the use of 19 females and 13 males, generating a potential of 247 dyads with no relationship. These first results of genetic management in a Mexican UMA, demonstrate the importance of molecular approaches at the time of managing and conserving species in captivity.
Culex erythrothorax: Insecticide Susceptibility and Mosquito Control
Authors: Esterly AT , Alemayehu D , Rusmisel B , Busam J , Shelton TL , Sebay T , Zahiri N , Huston JW , Clausnitzer RJ , Haas-Stapleton EJ
Published: January 2020

Culex erythrothoraxDyar is a West Nile virus (WNV) vector that breeds in wetland habitats with emergent vegetation. Urbanization and recreational activities near wetlands place humans and birds in close proximity toCx. erythrothorax, increasing the risk of WNV transmission. High adultCx. erythrothoraxabundance peaked in a marsh bordering the San Francisco Bay of California (USA) during the first 3 hours after sunset (5527 ± 4070 mosquitoes / trap night) during which adult mosquito control efforts are likely most effective. These adult mosquitoes were highly sensitive to permethrin, resmethrin, naled, and etofenprox insecticides when tested in a bottle bioassay (LC50 = 0.35, 0.68, 0.71, and 4.1 µg/bottle, respectively). The synergist piperonyl butoxide increased the sensitivity of the mosquitoes to a low concentration of permethrin (0.5 µg/bottle) while also reducing knock down time, but did not have similar effects with a higher permethrin concentration (2.0 µg/bottle). Biochemical enzyme assays measuring bulk mixed-function oxidase, alpha-esterase, or beta-esterase activities in mosquito homogenates were significantly higher inCx. erythrothoraxrelative to a strain ofCulex pipiensthat is sensitive to permethrin. Larvicide that was applied to the site had limited impact on reducing the abundance of adultCx. erythrothorax. Subsequent removal of emergent vegetation in concert with reduced daily temperature in the environment substantially reducedCx. erythrothoraxabundance. Land managers who have a need to controlCx. erythrothoraxin wetlands should consider vegetation removal over applying larvicide, while vector control agencies are likely to successfully control viremicCx. erythrothoraxthat enter nearby neighborhoods by applying insecticides that target the adult stage of the mosquito within 3 h of sunset.
Brain size predicts learning abilities in bees
Authors: Collado Miguel Á. , Montaner Cristina M. , Molina Francisco P. , Sol Daniel , Bartomeus Ignasi
Published: January 2020

A large brain is widely considered a distinctive feature of intelligence, a notion that mostly derives from studies in mammals. However, studies in insects demonstrates that cognitively sophisticated processes, such as social learning and tool use, are still possible with very small brains. Even after accounting for the allometric effect of body size, substantial variation in brain size still remains unexplained. A plausible advantage of a disproportionately larger brain might be an enhanced ability to learn new behaviors to cope with novel or complex challenges. While this hypothesis has received ample support from studies in birds and mammals, similar evidence is not available for small-brained animals like insects. Our objective is to compare the learning abilities of different bee species with their brain size investment. We conducted an experiment in which field-collected individuals had to associate an unconditioned stimulus (sucrose), with a conditioned stimulus (colored strip). We show that the probability of learning the reward-colour association was related to both absolute and relative brain size. This study shows that other bee species aside from the long studied honeybees and bumblebees, can be used in cognitive experiments and opens the door to explore the importance of relative brain sizes in cognitive tasks for insects and its consequences for species survival in a changing world.
Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition
Authors: Xu Wanfeng , Che Yuan , Zhang Quan , Huang Hai , Ding Chujie , Wang Yun , Wang Guangji , Cao Lijuan , Hao Haiping
Published: January 2020

Caspase-4 directly senses and is activated by cytosolic LPS in conditions of pathogen infection. It is unclear whether and how caspase-4 detects host derived factors for triggering pyroptosis. Here we show that mitochondrial permeability transition (MPT) promotes the assembly of a protein complex comprised of Apaf-1 and caspase-4 (caspase-11 in mice), defined herein as pyroptosome, for the execution of facilitated pyroptosis. MPT induced by bile acids and calcium overload, and specifically by an adenine nucleotide translocator 1 (ANT1) activator, triggered pyroptosome assembly. Different from the direct cleavage of GSDMD by LPS-activated caspase-4, caspase-4 activated in the Apaf-1 pyroptosome proceeds to cleave caspase-3 and thereby gasdermin E (GSDME) to induce pyroptosis. Caspase-11 initiated and GSDME executed pyroptosis underlies cholesteric liver failure. These findings identify Apaf-1 pyroptosome as a pivotal machinery for cells sensing MPT signals and may shed lights on understanding how cells execute pyroptosis under sterile conditions.

Highlights

Bile acids trigger caspase-4/11 and GSDME dependent pyroptosis

Caspase-4/11 is a general sensor of mitochondrial permeability transition (MPT)

MPT drives Apaf-1/capase-4 pryoptosome assembly

Caspase-11 and GSDME mediated pyroptosis underlies cholesteric liver damage

eTOC Blurb

Persistent mitochondrial permeability transition elicited by bile acids, calcium overload and specifically ANT1 activators drives assembly of Apaf-1-capase-4/11 pyroptosome triggering GSDME dependent pryroptosis.
ASC oligomer favor caspase-1CARDdomain recruitment after intracellular potassium efflux
Authors: Martín-Sánchez Fátima , Compan Vincent , Tapia-Abellán Ana , Gómez-Sánchez Ana I. , Baños María C. , Schmidt Florian I. , Pelegrín Pablo
Published: January 2020

Signaling through the inflammasome is important for the inflammatory response. Low concentrations of intracellular K+are associated with the specific oligomerization and activation of the NLRP3 inflammasome, a type of inflammasome involved in sterile inflammation. Subsequent to NLRP3 oligomerization, ASC protein binds and form oligomeric filaments culminating in large protein complexes named ASC specks. ASC specks are also initiated from different inflammasome scaffolds, as AIM2, NLRC4 or Pyrin. ASC oligomers induce the recruitment of caspase-1 through interactions between their respective caspase activation and recruitment domains (CARD), and favoring its activation. So far ASC oligomerization and caspase-1 activation are considered as a K+-independent process. Here we found that ASC oligomers change their structure upon low intracellular K+independently of NLRP3 and allow the ASCCARDdomain to be more accessible for the recruitment of pro-caspase-1CARDdomain. Therefore, conditions that decrease intracellular K+not only drive NLRP3 responses, but also enhance the recruitment of pro-caspase-1 by ASC specks formed by different inflammasomes, indicating that intracellular K+homeostasis is a key regulatory step for inflammasome regulation.
A unified computational model for cortical post-synaptic plasticity
Authors: Mäki-Marttunen Tuomo , Iannella Nicolangelo , Edwards Andrew G. , Einevoll Gaute T. , Blackwell Kim T.
Published: January 2020

Cortical synapses possess a machinery of signalling pathways that leads to various modes of post-synaptic plasticity. Such pathways have been examined to a great detail separately in many types of experimental studies. However, a unified picture on how multiple biochemical pathways collectively shape the observed synaptic plasticity in the neocortex is missing. Here, we built a biochemically detailed model of post-synaptic plasticity that includes the major signalling cascades, namely, CaMKII, PKA, and PKC pathways which, upon activation by Ca2+, lead to synaptic potentiation or depression. We adjusted model components from existing models of intracellular signalling into a single-compartment simulation framework. Furthermore, we propose a statistical model for the prevalence of different types of membrane-bound AMPA-receptor tetramers consisting of GluR1 and GluR2 subunits in proportions suggested by the biochemical signalling model, which permits the estimation of the AMPA-receptor-mediated maximal synaptic conductance. We show that our model can reproduce neuromodulator-gated spike-timing-dependent plasticity as observed in the visual cortex. Moreover, we demonstrate that our model can be fit to data from many cortical areas and that the resulting model parameters reflect the involvement of the pathways pinpointed by the underlying experimental studies. Our model explains the dependence of different forms of plasticity on the availability of different proteins and can be used for the study of mental disorder-associated impairments of cortical plasticity.

Significance statement

Neocortical synaptic plasticity has been studied experimentally in a number of cortical areas, showing how interactions between neuromodulators and post-synaptic proteins shape the outcome of the plasticity. On the other hand, non-detailed computational models of long-term plasticity, such as Hebbian rules of synaptic potentiation and depression, have been widely used in modelling of neocortical circuits. In this work, we bridge the gap between these two branches of neuroscience by building a detailed model of post-synaptic plasticity that can reproduce observations on cortical plasticity and provide biochemical meaning to the simple rules of plasticity. Our model can be used for predicting the effects of chemical or genetic manipulations of various intracellular signalling proteins on induction of plasticity in health and disease.
Prior selection prevents the loss of an ecosystem cycle during acidification
Authors: van Moorsel Sofia J. , Marleau Justin N. , Negrín Dastis Jorge O. , Bazerghi Charles , Fugère Vincent , Petchey Owen L. , Gonzalez Andrew
Published: January 2020

Ecosystem processes vary temporally due to variation in environmental variables, such as when diurnal variation in sunlight causes diurnal cycles in net primary production. This variability can be characterized by its frequency and amplitude, used to define “normal” functioning of an ecosystem. Relatively little research has addressed how normal modes of variability, such as diurnal cycles, are lost or recovered, following anthropogenic stress. We conducted an aquatic mesocosm experiment to test whether prior application of environmental stress, in the form of moderate acidification, affected the diurnal cycle of dissolved oxygen when exposed to severe acidification. High-frequency data from sensor loggers deployed in 12 mesocosms showed that severe acidification caused a temporary loss of diurnal variation in dissolved oxygen concentration. However, pre-exposure to an acidic environment resulted in the persistence of the diurnal cycle. We hypothesize that pre-exposure shifted the community to acid tolerant genotypes and/or species of algae and other photosynthetic organisms. Our findings suggest that the stability of ecosystem cycles is intrinsically liked to the stress tolerance of the species assemblage.
Curcumin Analogues as the Inhibitors of TLR4 Pathway in Inflammation and Their Drug Like Potentialities: A Computer-based Study
Authors: Ullah Md. Asad , Johora Fatema Tuz , Sarkar Bishajit , Araf Yusha , Rahman MD. Hasanur
Published: January 2020

In this study Curcumin and their different analogues have been analyzed as the inhibitors of signaling proteins i.e., Cycloxygenase-2 (COX-2), Inhibitor of Kappaβ Kinase (IKK) and TANK binding kinase-1 (TBK-1) of Toll Like Receptor 4 (TLR4) pathway involved in inflammation using computational tools. Multiple analogues showed better binding affinity than the approved drugs for the respective targets. Upon continuous computational exploration 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK and TBK-1 respectively. Then their drug like potentialities were analyzed in different experiments where they also performed sound and similar. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.
Protective Population Behavior Change in Outbreaks of Emerging Infectious Disease
Authors: Lodge Evans K. , Schatz Annakate M. , Drake John M.
Published: January 2020

During outbreaks of emerging infections, the lack of effective drugs and vaccines increases reliance on non-pharmacologic public health interventions and behavior change to limit human-to-human transmission. Interventions that increase the speed with which infected individuals remove themselves from the susceptible population are paramount, particularly isolation and hospitalization. Ebola virus disease (EVD), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) are zoonotic viruses that have caused significant recent outbreaks with sustained human-to-human transmission. This investigation quantified changing mean removal rates (MRR) and days from symptom onset to hospitalization (DSOH) of infected individuals from the population in seven different outbreaks of EVD, SARS, and MERS, to test for statistically significant differences in these metrics between outbreaks. We found that epidemic week and viral serial interval were correlated with the speed with which populations developed and maintained health behaviors in each outbreak.
Thermodynamics of Homopeptide Aggregation
Authors: Phan Tam T. M. , Schmit Jeremy D.
Published: January 2020

Amyloid aggregates are found in many neurodegenerative diseases including Huntington’s, Alzheimer’s, and prion diseases. The precise role of the aggregates in disease progression has been difficult to elucidate due to the diversity of aggregated states they can adopt. Here we study the formation of fibrils and oligomers by exon 1 of huntingtin protein. We show that the oligomer states are consistent with polymer micelles that are limited in size by the stretching entropy of the polyglutamine region. The model shows how the sequences flanking the amyloid core modulate aggregation behavior. The N17 region promotes aggregation through weakly attractive interactions, while the C38 tail opposes aggregation via steric repulsion. We also show that the energetics of cross-βstacking by polyglutamine would produce fibrils with many alignment defects, but minor perturbations from the flanking sequences are sufficient to reduce the defects to the level observed in experiment. We conclude with a discussion of the implications of this model for other amyloid forming molecules.
Warming-enhanced priority effects at population and community levels in aquatic bacteria
Authors: Vass Máté , Székely Anna J. , Lindström Eva S. , Osman Omneya A. , Langenheder Silke
Published: January 2020

The immigration history of communities can profoundly affect community composition. For instance, early-arriving species can have a lasting effect on community structure by reducing the immigration success of late-arriving ones through priority effects. Warming could possibly enhance priority effects by increasing growth rates of early-arriving bacteria. Here we implemented a full-factorial experiment with aquatic bacteria where both temperature and dispersal rate of a better-adapted community were manipulated to test their effects on the importance of priority effects, both on a community and a population level. Our results suggest that priority effects in aquatic bacteria might be primarily driven by niche preemption and strengthened by increasing temperature as warming increased the resistance of recipient communities against dispersal, and decreased the relative abundance of successfully established late-arriving bacteria. However, warming-enhanced priority effects were not always found and their strengths differed between recipient communities and dispersal rates. Nevertheless, our findings highlight the importance of context dependence of priority effects and the potential role of warming in mitigating the effects of invasion.
Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice
Authors: Binning William , Hogan-Cann Aja E. , Sakae Diana Yae , Maksoud Matthew , Ostapchenko Valeriy , Al-Onaizi Mohammed , Matovic Sara , Lu Wei-Yang , Prado Marco A. M. , Inoue Wataru , Prado Vania F.
Published: January 2020

Microglia express muscarinic G protein-coupled receptors (GPCRs) that sense cholinergic activity and are activated by acetylcholine to potentially regulate microglial functions. Knowledge about how distinct types of muscarinic GPCR signaling regulate microglia functionin vitroandin vivois still poor, partly due to the fact that some of these receptors are also present in astrocytes and neurons. We generated mice expressing the hM3Dq Designer Receptor Exclusively Activated by Designer Drugs (DREADD) selectively in microglia to investigate the role of muscarinic M3Gq-linked signaling. We show that activation of hM3Dq using clozapine N-oxide (CNO) elevated intracellular calcium levels and increased phagocytosis of FluoSpheresin vitro. Acute treatment with CNOin vivodid not affect male mouse behavior, however chronic CNO treatment decreased sickness behavior triggered by lipopolysaccharide (LPS) treatment. Interestingly, whereas acute treatment with CNO increased synthesis of cytokine mRNA, chronic treatment attenuated LPS-induced cytokine mRNA changes in the brain, likely explaining the improvement in sickness behavior by chronic hM3Dq activation. No effect of CNO was observed in DREADD-negative mice. These results suggest that chronic activation of M3 muscarinic receptors (the hM3Dq progenitor) in microglia, and potentially other Gq-coupled GPCRs, preconditions microglia to decrease their response to further immunological challenges. Our results indicate that hM3Dq can be a useful tool to modulate neuroinflammation and study microglial immunological memoryin vivo, which may be applicable for manipulations of neuroinflammation in neurodegenerative and psychiatric diseases.

Highlights

Microglial function was manipulated by specific activation of hM3Dq signaling.

Chronic hM3Dq activation prevented LPS-induced sickness behavior in mice.

Microglial hM3Dq signaling modulated expression of pro-inflammatory cytokines.
A variant inSMOC2,inhibiting BMP signaling by competitively binding to BMPR1B, causes multiple epiphyseal dysplasia
Authors: Long Feng , Li Lin , Shi Hongbiao , Li Pengyu , Guo Shaoqiang , Ma Yuer , Li Yan , Wei Shijun , Gao Fei , Gao Shang , Wang Meitian , Duan Ruonan , Wang Xiaojing , Yang Kun , Liu Ai , Wang Anran , Chen Xiao , Sun Wenjie , Li Xi , Li Jiangxia , Liu Qiji
Published: January 2020

Previously study showed that SMOC, a matricellular protein, inhibits BMP signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In our study, exome sequencing revealed a missense mutation (c.1076T>G, p.Leu359Arg) in EC domain of SMOC2 in a Chinese family with multiple epiphyseal disease (MED). The pathogenicity of this SMOC2 variant was verified bySmoc2L359R/L359Rknock-in mice. Of note, decreasing phosphorylation of SMAD1/5/9 was detected in growth plates and primary chondrocytes fromSmoc2L359R/L359Rmice. Furthermore, binding affinity of mutant SMOC2 with collagen IX and HSPG in the extracellular matrix of cartilage were reduced while binding affinity with BMPRIB was intact. In addition, in contrast to previously results, that SMOC2 cannot antagonize BMP activity in the presence of a constitutively activated BMP receptor. These results support thatSMOC2with p.Leu359Arg variant act as an antagonist of canonical BMP pathway by competitively binding with BMP receptors.
DeepTE: a computational method for de novo classification of transposons with convolutional neural network
Authors: Yan Haidong , Bombarely Aureliano , Li Song
Published: January 2020

Motivation

Transposable elements (TEs) classification is an essential step to decode their roles in genome evolution. With a large number of genomes from non-model species becoming available, accurate and efficient TE classification has emerged as a new challenge in genomic sequence analysis.

Results

We developed a novel tool, DeepTE, which classifies unknown TEs using convolutional neural networks. DeepTE transferred sequences into input vectors based on k-mer counts. A tree structured classification process was used where eight models were trained to classify TEs into super families and orders. DeepTE also detected domains inside TEs to correct false classification. An additional model was trained to distinguish between non-TEs and TEs in plants. Given unclassified TEs of different species, DeepTE can classify TEs into seven orders, which include 15, 24, and 16 super families in plants, metazoans, and fungi, respectively. In several benchmarking tests, DeepTE outperformed other existing tools for TE classification. In conclusion, DeepTE successfully leverages convolutional neural network for TE classification, and can be used to precisely identify and annotate TEs in newly sequenced eukaryotic genomes.

Availability

DeepTE is accessible athttps://github.com/LiLabAtVT/DeepTE

Contact

songli@vt.edu
Implantation technique, safety and complications of robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy
Authors: Chaitanya Ganne , Romeo Andrew K. , Ilyas Adeel , Irannejad Auriana , Toth Emilia , Elsayed Galal , Bentley J. Nicole , Riley Kristen O. , Pati Sandipan
Published: January 2020

Introduction

Despite numerous imaging studies highlighting the importance of thalamus in surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei in patients with suspected temporal lobe epilepsy (TLE).

Methods

After obtaining informed consent, 24 adults with drug-resistant suspected TLE undergoing Stereo-EEG evaluation were enrolled in this prospective study. The trajectory of one electrode planned for clinical sampling the operculo-insular cortex was modified to extend to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior thalamus (ANT) (N=13) and the medial group of thalamic nuclei (MED) (N=11), including mediodorsal (MD) and centromedian (CeM) were targeted. The post-implantation CT was co-registered to the pre-operative MRI, and Morel’s thalamic atlas was used to confirm the accuracy of implantation.

Results

Ten out of 13 (77%) in the ANT group and 10 out of 11 patients (90%) in the medial group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical level entry site were noted in 20.8% of patients and they did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from the medial group at the entry point i.e., precentral gyrus in the former and postcentral gyrus in the latter.

Conclusions

Using judiciously planned robot-assisted SEEG, we demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes, or comprising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.
Investigation into the development and historical roots of collection development by referenced publication year spectroscopy
Authors: Malik Basharat Ahmad , Ahmadi Ashiya
Published: January 2020

Purpose

The purpose of this study is the application of a recently developed quantitative method named Referenced Publication Year Spectroscopy (RPYS) in the spectrum of Collection Development. RPYS portrays peak years to be recognized in citations in a research field that guarantees to assist in the identification of significant contributions and groundbreaking revelations in a research field.

Design/methodology/approach

Preliminary data of the study has been extracted from Web of Science (WoS) by using two phrases “collection development” and “collection building” to search in terms of the topic (comprising four parts: title, abstract, author keywords and KeyWords Plus). The search was restricted to the time period 1974-2017, which formulated a data set of 1,682 documents covering 29,017 cited references. The program CRExplorer (www.crexplorer.net) was used for the extraction of cited references from the data sets downloaded from WoS. Further analysis was performed manually using MS-Excel 2016.

Findings

The present study identified seminal works, which contributed to a high extent to the evolution and development of collection development. The analysis of all cited references using the RPYS method showed nine peaks, which present historical roots of collection development and revealed that the basic idea of this very subfield of library science dates centuries back. Moreover, the results of the investigation on most effective documents (in the form of peaks) revealed that the field of collection development significantly influenced by the works of authors such as Gabriel Naudé, Gabriel Peignot, Giulio Petzholdt, P L Gross, E M Gross, Richard Trueswell, Allen Kent, Ross Atkinson, etc.

Practical implications

The analysis of works cited in publications helps to ascertain important intellectual contributions related to a particular domain of knowledge. It not only helps in extracting the most important works but also it helps to reconstruct the history of a specific research field by examining the specific role of the cited references. Therefore, the results of the study could be useful for researchers, practitioners, scholars and more specifically bibliophiles, bibliographers and librarians to gain a better understanding of seminal works in the spectrum of collection development.

Originality/value

To the best of authors’ knowledge, the present research work is unique and novel in the spectrum of collection development, which explored and examined the pivotal works in the field by using the RPYS method.