bluuebunny/crossref_metadata_2025 huggingface dataset:
Rumen Bacteria and Serum Metabolites Predictive of Feed Efficiency Phenotypes in Beef Cattle
Authors: Clemmons Brooke A , Martino Cameron , Powers Joshua B , Campagna Shawn R , Voy Brynn H , Donohoe Dallas R. , Gaffney James , Embree Mallory M , Myer Phillip R
Published: July 2019

The rumen microbiome is critical in ruminant nutrition and contributes to nutrient utilization and feed efficiency in cattle. Therefore, the objective of this study was to interrogate microbial and biochemical factors affecting divergences in feed efficiency in Angus steers using 16S amplicon sequencing and untargeted metabolomics. Average residual feed intake (RFI) was calculated, and steers were divided into low- and high-RFI groups. Features were ranked in relation to RFI through supervised machine learning on microbial and metabolite compositions. Residual feed intake was associated with several attributes of the rumen bacterial community. Low-RFI steers were associated with decreased bacterial α- (P=0.03) and β-diversity (P<0.001). Several serum metabolites were associated with RFI. Based on fold change (high/low RFI), low-RFI steers had greater abundances of pantothenate (P=0.02). Machine learning on RFI was predictive of both serum metabolomic signature and rumen bacterial composition (AUC ≥0.7). Log-ratio proportions of the bacterial classes Flavobacteriia over Fusobacteriia were enriched in low-RFI steers (F=6.8, P=.01). Greater proportions of pantothenate-producing bacteria, such as Flavobacteriia, and/or reductions in Fusobacteriia may result in improved nutrient utilization in low-RFI steers. Pantothenate and Flavobacteriia may serve as potentially novel biomarkers to assess or predict feed efficiency in Angus steers.
Estradiol-inducible AvrRps4 expression reveals distinct properties of TIR-NLR-mediated effector-triggered immunity
Authors: Ngou Bruno Pok Man , Ahn Hee-Kyung , Ding Pingtao , Redkar Amey , Brown Hannah , Ma Yan , Youles Mark , Tomlinson Laurence , Jones Jonathan DG
Published: July 2019

Plant nucleotide-binding domain, leucine-rich repeat receptor (NLR) proteins play important roles in recognition of pathogen-derived effectors. However, the mechanism by which plant NLRs activate immunity is still largely unknown. The paired Arabidopsis NLRs RRS1-R and RPS4, that confer recognition of bacterial effectors AvrRps4 and PopP2, are well studied, but how the RRS1/RPS4 complex activates early immediate downstream responses upon effector detection is still poorly understood. To study RRS1/RPS4 responses without the influence of cell-surface receptor immune pathways, we generated an Arabidopsis line with inducible expression of effector AvrRps4. Induction does not lead to hypersensitive cell death response (HR) but can induce electrolyte leakage, which often correlates with plant cell death. Activation of RRS1 and RPS4 without pathogens cannot activate mitogen-associated protein kinase cascades, but still activates upregulation of defense genes, and therefore resistance against bacteria.

Highlight

Inducible expression of AvrRps4 activates RRS1/RPS4-mediated effector-triggered immunity without the presence of pathogens, allowing us to characterise downstream immune responses triggered by TIR-NLRs without cell-surface receptor-mediated immunity.
A Statistical Pipeline for Identifying Physical Features that Differentiate Classes of 3D Shapes
Authors: Wang Bruce , Sudijono Timothy , Kirveslahti Henry , Gao Tingran , Boyer Douglas M. , Mukherjee Sayan , Crawford Lorin
Published: July 2019

The recent curation of large-scale databases with 3D surface scans of shapes has motivated the development of tools that better detect global patterns in morphological variation. Studies which focus on identifying differences between shapes have been limited to simple pairwise comparisons and rely on pre-specified landmarks (that are often known). We present SINATRA: the first statistical pipeline for analyzing collections of shapes without requiring any correspondences. Our novel algorithm takes in two classes of shapes and highlights the physical features that best describe the variation between them. We use a rigorous simulation framework to assess our approach. Lastly, as a case study, we use SINATRA to analyze mandibular molars from four different suborders of primates and demonstrate its ability recover known morphometric variation across phylogenies.
Oxygen supply capacity in animals evolves to meet maximum demand at the current oxygen partial pressure regardless of size or temperature
Authors: Seibel Brad A. , Deutsch Curtis
Published: July 2019

Physiological oxygen supply capacity is associated with athletic performance and cardiovascular health and is thought to cause hypometabolic scaling in diverse species. Environmental oxygen is widely believed to be limiting of metabolic rate and aerobic scope, setting thermal tolerance and body size limits with implications for species diversity and biogeography. Here we derive a quantifiable linkage between maximum and basal metabolic rate and their temperature, size and oxygen dependencies. We show that, regardless of size or temperature, the capacity for oxygen supply precisely matches the maximum evolved demand at the highest persistently available oxygen pressure which, for most species assessed, is the current atmospheric pressure. Any reduction in oxygen partial pressure from current values will result in a decrement in maximum metabolic performance. However, oxygen supply capacity does not constrain thermal tolerance and does not cause hypometabolic scaling. The critical oxygen pressure, typically viewed as an indicator of hypoxia tolerance, instead reflects adaptations for aerobic scope. This simple new relationship redefines many important physiological concepts and alters their ecological interpretation.

One sentence summary: Metabolism is not oxygen limited
Uncovering Photolyase/Cryptochrome Genes Diversity in Aquatic Microbiomes Exposed to Diverse UV-B Regimes
Authors: Alonso-Reyes Daniel G. , Farias Maria Eugenia , Albarracín Virginia Helena
Published: July 2019

During evolution, microorganisms exposed to high UV-B doses developed a fine-tuned photo-enzymes called “photolyases” to cope with DNA damage by UV-B. These photoreceptors belonging to the Cryptochrome/Photolyase Family (CPF) were well characterized at the genomic and proteomic level in bacteria isolated from a wide range of environments. In this work, we go further towards studying the abundance of CPF on aquatic microbial communities from different geographic regions across the globe. Metagenomics data combined with geo-referenced solar irradiation measurements indicated that the higher the UV-B dose suffered by the microbiome’s environment, the higher the abundance of CPF genes and lower the microbial diversity. A connection between CPF abundance and radiation intensity/photoperiod was reported. Likewise, cryptochrome-like genes were found abundant in most exposed microbiomes, indicating a complementary role to standard photolyases. Also, we observed that CPFs are more likely present in dominant taxa of the highly irradiated microbiomes, suggesting an evolutionary force for survival and dominance under extreme solar exposure. Finally, this work reported three novel CPF clades not identified so far, proving the potential of global metagenomic analyses in detecting novel proteins.
A reference library for the identification of Canadian invertebrates: 1.5 million DNA barcodes, voucher specimens, and genomic samples
Authors: deWaard Jeremy R. , Ratnasingham Sujeevan , Zakharov Evgeny V. , Borisenko Alex V. , Steinke Dirk , Telfer Angela C. , Perez Kate H.J. , Sones Jayme E. , Young Monica R. , Levesque-Beaudin Valerie , Sobel Crystal N. , Abrahamyan Arusyak , Bessonov Kyrylo , Blagoev Gergin , deWaard Stephanie L. , Ho Chris , Ivanova Natalia V. , Layton Kara K. S. , Lu Liuqiong , Manjunath Ramya , McKeown Jaclyn T.A. , Milton Megan A. , Miskie Renee , Monkhouse Norm , Naik Suresh , Nikolova Nadya , Pentinsaari Mikko , Prosser Sean W.J. , Radulovici Adriana E. , Steinke Claudia , Warne Connor P. , Hebert Paul D.N.
Published: July 2019

The reliable taxonomic identification of organisms through DNA sequence data requires a well parameterized library of curated reference sequences. However, it is estimated that just 15% of described animal species are represented in public sequence repositories. To begin to address this deficiency, we provide DNA barcodes for 1,500,003 animal specimens collected from 23 terrestrial and aquatic ecozones at sites across Canada, a nation that comprises 7% of the planet’s land surface. In total, 14 phyla, 43 classes, 163 orders, 1123 families, 6186 genera, and 64,264 Barcode Index Numbers (BINs; a proxy for species) are represented. Species-level taxonomy was available for 38% of the specimens, but higher proportions were assigned to a genus (69.5%) and a family (99.9%). Voucher specimens and DNA extracts are archived at the Centre for Biodiversity Genomics where they are available for further research. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, and the Global Genome Biodiversity Network Data Portal.
Microarray Gene Expression Dataset Re-Analysis Reveals Variability in Influenza Infection and Vaccination
Authors: Rogers Lavida R. K. , de los Campos Gustavo , Mias George I.
Published: July 2019

Influenza, a communicable disease, affects thousands of people worldwide. Young children, elderly, immunocompromised individuals and pregnant women are at higher risk for being infected by the influenza virus. Our study aims to highlight differentially expressed genes in influenza disease compared to influenza vaccination. We also investigate genetic variation due to the age and sex of samples. To accomplish our goals, we conducted a meta-analysis using publicly available microarray expression data. Our inclusion criteria included subjects with influenza, subjects who received the influenza vaccine and healthy controls. We curated 18 microarray datasets for a total of 3,481 samples (1,277 controls, 297 influenza infection, 1,907 influenza vaccination). We pre-processed the raw microarray expression data in R using packages available to pre-process Affymetrix and Illumina microarray platforms. We used a Box-Cox power transformation of the data prior to our down-stream analysis to identify differentially expressed genes. Statistical analyses were based on linear mixed effects model with all study factors and successive likelihood ratio tests (LRT) to identify differentially-expressed genes. We filtered LRT results by disease (Bonferroni adjusted p-value<0.05) and used a two-tailed 10% quantile cutoff to identify biologically significant genes. Furthermore, we assessed age and sex effects on the disease genes by filtering for genes with a statistically significant (Bonferroni adjusted p-value<0.05) interaction between disease and age, and disease and sex. We identified 4,889 statistically significant genes when we filtered the LRT results by disease factor, and gene enrichment analysis (gene ontology and pathways) included innate immune response, viral process, defense response to virus, Hematopoietic cell lineage and NF-kappa B signaling pathway. Our quantile filtered gene lists comprised of 978 genes each associated with influenza infection and vaccination. We also identified 907 and 48 genes with statistically significant (Bonferroni adjusted p-value<0.05) disease-age and disease-sex interactions respectively. Our meta-analysis approach highlights key gene signatures and their associated pathways for both influenza infection and vaccination. We also were able to identify genes with an age and sex effect. This gives potential for improving current vaccines and exploring genes that are expressed equally across ages when considering universal vaccinations for influenza.
Comparative analysis of intracellular and extracellular antibiotic resistance gene abundance in anaerobic membrane bioreactor effluent
Authors: Wang Phillip , Harb Moustapha , Zarei-Baygi Ali , Stadler Lauren B. , Smith Adam L.
Published: July 2019

The growing practice of wastewater reuse poses a significant risk to further dissemination of antibiotic resistance due to the abundance of antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) in wastewater effluents. Anaerobic membrane bioreactors (AnMBRs) are an emerging wastewater treatment technology capable of reducing the total ARGs and ARB load discharged to receiving environments compared to conventional aerobic treatment processes. While size exclusion is effective at retaining ARB and its associated intracellular ARGs, the abundance and fate of extracellular ARGs in an AnMBR effluent have not been examined. This study elucidates the effect of combined antibiotics loading (ampicillin, erythromycin, and sulfamethoxazole) on the abundance of intracellular and extracellular ARGs in an AnMBR effluent over a period of five weeks. Quantification of targeted genes revealed an overall enrichment of intracellular ARGs (iARGs) and depletion of extracellular (exARGs) in response to antibiotics addition, which suggests exARG uptake as a significant mode of horizontal gene transfer in AnMBR effluents. Comparison of the iARG and exARG abundance profiles showed a potential bias for exARG uptake located on small plasmids compared to large plasmids.

Importance

Antibiotic resistance dissemination is facilitated through horizontal gene transfer (HGT) of ARGs. Currently, conjugation is considered to be the dominant mechanism during wastewater treatment. However, recent studies have detected high abundances of exARGs, implying that transformation may play a greater role in dissemination. While previous studies quantified iARGs and exARGs in wastewater treatment facilities, they did not evaluate temporal changes between the two forms. Further, almost no research has differentiated between iARGs and exARGs in anaerobic processes, which are being considered to replace aerobic activated sludge processes. This study specifically investigates the abundance of targeted iARGs and exARGs in AnMBRs in response to antibiotic pressure to quantify potential exchange of ARGs between intracellular and extracellular compartments. Our findings suggest that exARGs located on small plasmids are preferentially taken up by cells under antibiotic pressure compared to large plasmids, which implies heterogenous HGT mechanisms among the plasmid community.
Brain network dynamics correlate with personality traits
Authors: Kabbara Aya , Paban Veronique , Weill Arnaud , Modolo Julien , Hassan Mahmoud
Published: July 2019

Introduction

Identifying the neural substrates underlying the personality traits is a topic of great interest. On the other hand, it is now established that the brain is a dynamic networked system which can be studied using functional connectivity techniques. However, much of the current understanding of personality-related differences in functional connectivity has been obtained through the stationary analysis, which does not capture the complex dynamical properties of brain networks.

Objective

In this study, we aimed to evaluate the feasibility of using dynamic network measures to predict personality traits.

Method

Using the EEG/MEG source connectivity method combined with a sliding window approach, dynamic functional brain networks were reconstructed from two datasets: 1) Resting state EEG data acquired from 56 subjects. 2) Resting state MEG data provided from the Human Connectome Project. Then, several dynamic functional connectivity metrics were evaluated.

Results

Similar observations were obtained by the two modalities (EEG and MEG) according to the neuroticism, which showed a negative correlation with the dynamic variability of resting state brain networks. In particular, a significant relationship between this personality trait and the dynamic variability of the temporal lobe regions was observed. Results also revealed that extraversion and openness are positively correlated with the dynamics of the brain networks.

Conclusion

These findings highlight the importance of tracking the dynamics of functional brain networks to improve our understanding about the neural substrates of personality.
Adult crowding induces sexual dimorphism in chronic stress-response inDrosophila melanogaster
Authors: Lall Shraddha , Mudunuri Akhila , Santhosh S. , Malwade Akshay , Thadi Aarcha , Kondakath Gayathri , Dey Sutirth
Published: July 2019

Stress-induced mood disorders such as depression and anxiety are sexually dimorphic in human beings. Studying behavioural stress-responses in non-human animal models can help better understand the behavioural manifestations of these disorders and the dimorphism in their prevalence. Here we explore how sexes show differential behavioural responses to different chronic stressors, both abiotic and biotic, by using outbred populations ofDrosophila melanogaster. The behaviours studied – namely, anhedonia, motivation to explore a novel habitat, locomotor activity and sleep levels – have been well-investigated in human and rodent-based models of stress disorders. These behaviours were studied in the context of two different stressors – mechanical perturbation and adult crowding. Responses to stress were found to be sexually dimorphic, and stressed females showed more behavioural changes, such as a reduced motivation to explore a novel habitat. Furthermore, adult crowding caused a greater number of sexually dimorphic behavioural changes than mechanical perturbation. For instance, while mechanical perturbation caused anhedonia across sexes, only females were anhedonic after crowding. We thus make a case forDrosophila melanogasteras a model system for studying sexual dimorphism in stress-induced mood disorders in humans.

SUMMARY STATEMENT

Female fruit flies, like their human counterparts, are more prone to chronic stress-induced mood disorders like anhedonia or reduced activity. This sexual dimorphism was more evident in a biotic stress.
Increased temperatures reduce the vectorial capacity ofAedesmosquitoes for Zika virus
Authors: Gorreti Onyango Maria , Sean Bialosuknia , Ann Payne , Nicholas Mathias , Lilli Kuo , Aurelien Vigneron , Matthew DeGennaro , Alexander T Ciota , Laura D Kramer
Published: July 2019

Rapid and significant range expansion of both ZIKV and itsAedeshost species has resulted in ZIKV being declared a global health threat. Mean temperatures are projected to increase globally, likely resulting in alterations of the transmission potential of mosquito-borne pathogens. The relationship between temperature and ZIKV transmission has not been well characterised forAedes aegyptiandAedes albopictus.

To understand the effect of diurnal temperature range on the vectorial capacity ofAedes aegyptiandAedes albopictusfor ZIKV, factors contributing to transmission potential were measured at different temperature regimens. Their longevity and blood feeding rates were assessed, and vector competence was determined following feeding on blood meals with 8.3 log10PFU/ml ZIKV.

Higher temperature resulted in decreased longevity ofAe. aegypti[Log-rank (Mantel-Cox) Test, Chi-square, df 35.66, 5 P (<0.0001)] and a significant decrease in blood feeding rates across groups [Z score (−5.8478) P (0.0444)]. Temperature had a population and species-specific impact on ZIKV infection rates. Overall,Ae. albopictusreared at the lowest temperature regimen demonstrated the highest vectorial capacity (1.63) and the highest transmission efficiency (57%). Temperature increases decreased vectorial capacity across groups, yet the largest decreases were measured forAe. aegypti.

The results of this study suggest that future climate change could significantly impact vector competence, blood feeding behavior and longevity, and therefore decrease the overall vectorial capacity ofAedesmosquitoes. It is also clear that this impact is likely to be both species and population-specific.
RNAPosers: Machine Learning Classifiers For RNA-Ligand Poses
Authors: Chhabra Sahil , Xie Jingru , Frank Aaron T.
Published: July 2019

Determining the 3-dimensional (3D) structures of ribonucleic acid (RNA)-small molecule complexes is critical to understanding molecular recognition in RNA. Computer docking can, in principle, be used to predict the 3D structure of RNA-small molecule complexes. Unfortunately, retrospective analysis has shown that the scoring functions that are typically used to rank poses tend to misclassify non-native poses as native, andvice versa. This misclassification of non-native poses severely limits the utility of computer docking in the context pose prediction, as well as in virtual screening. Here, we use machine learning to train a set of pose classifiers that estimate the relative “nativeness” of a set of RNA-ligand poses. At the heart of our approach is the use of a pose “fingerprint” that is a composite of a set of atomic fingerprints, which individually encode the local “RNA environment” around ligand atoms. We found that by ranking poses based on the classification scores from our machine learning classifiers, we were able to recover native-like poses better than when we ranked poses based on their docking scores. With a leave-one-out training and testing approach, we found that one of our classifiers could recover poses that were within 2.5 Å of the native poses in ∼80% of the 88 cases we examined, and similarly, on a separate validation set, we could recover such poses in ∼70% of the cases. Our set of classifiers, which we refer to as RNAPosers, should find utility as a tool to aid in RNA-ligand pose prediction and so we make RNAPosers open to the academic community viahttps://github.com/atfrank/RNAPosers.
Predicting the risk of sarcopenia in elderly patients with patellar fracture: Development and assessment of a new predictive nomogram
Authors: Yisheng Chen , Jie Tao
Published: July 2019

Purpose

This study was aimed at developing a risk prediction model for postoperative dysplasia in elderly patients with patellar fractures in China.

Patients and methods

We conducted a community survey of patients aged ≥55 years who underwent surgery for patellar fractures between January 2013 and October 2018, through telephone interviews, community visits, and outpatient follow-up. We established a predictive model for assessing the risk of sarcopenia after patellar fractures. We developed the prediction model by combining multivariate logistic regression analysis with the least absolute shrinkage model and selection operator regression (Lasso analysis). The predictive quality and clinical utility of the predictive model were determined using C-index, calibration plots, and decision curve analysis. We conducted internal sampling methods for qualitative assessment.

Result

We recruited 61 participants (males: 20, mean age: 68.1 years). Various risk factors were assessed, and low body mass index and diabetes mellitus were identified as the most important risk factors (P<0.05). The model showed a good prediction rate (C-index: 0.909; 95% confidence interval: 0.81–1.00) and good correction effect. The C-index remained high (0.828) even after internal sample verification. Decision curve analysis showed that the risk of sarcopenia was 8.3–80.0%, suggesting good clinical practicability.

Conclusion

Our prediction model shows promise as a cost-effective tool for predicting the risk of postoperative sarcopenia in elderly patients based on the following: advanced age, low body mass index, diabetes, longer postoperative hospital stay, no higher education, no postoperative rehabilitation, removal of internal fixation, and less outdoor exercise.
Resolution and co-occurrence patterns ofGardnerella leopoldii,Gardnerella swidsinskii,Gardnerella piotiiandGardnerella vaginaliswithin the vaginal microbiome
Authors: Hill Janet E. , Albert Arianne Y.K. ,   the VOGUE Research Group
Published: July 2019

Background

Gardnerella vaginalisis a hallmark of vaginal dysbiosis, but is found in the microbiomes of women with and without vaginal symptoms.G. vaginalisencompasses diverse taxa differing in attributes that are potentially important for virulence, and there is evidence that ‘clades’ or ‘subgroups’ within the species are differentially associated with clinical outcomes. TheG. vaginalisspecies description was recently emended, and three new species within the genus were defined (leopoldii,swidsinskii,piotii). 16S rRNA sequences for the fourGardnerellaspecies are all >98.5% identical and no signature sequences differentiate them.

Results

We demonstrated thatGardnerellaspecies can be resolved using partial chaperonin-60 (cpn60) sequences, with pairwise percent identities of 87.1-97.8% among the type strains. Pairwise co-occurrence patterns ofGardnerellaspp. in the vaginal microbiomes of 413 reproductive aged Canadian women were investigated, and several significant co-occurrences of species were identified. Abundance ofG. vaginalis, andswidsinskiiwas associated with vaginal symptoms of abnormal odour and discharge.

Conclusions

cpn60 barcode sequencing can provide a rapid assessment of the relative abundance ofGardnerellaspp. in microbiome samples, providing a powerful method of elucidating associations between these diverse organisms and clinical outcomes. Researchers should consider using cpn60 in place of 16S RNA for better resolution of these important organisms.
Egocentric boundary vector tuning of the retrosplenial cortex
Authors: Alexander Andrew S. , Carstensen Lucas C. , Hinman James R. , Raudies Florian , Chapman G. William , Hasselmo Michael E.
Published: July 2019

The retrosplenial cortex is reciprocally connected with a majority of structures implicated in spatial cognition and damage to the region itself produces numerous spatial impairments. However, in many ways the retrosplenial cortex remains understudied. Here, we sought to characterize spatial correlates of neurons within the region during free exploration in two-dimensional environments. We report that a large percentage of retrosplenial cortex neurons have spatial receptive fields that are active when environmental boundaries are positioned at a specific orientation and distance relative to the animal itself. We demonstrate that this vector-based location signal is encoded in egocentric coordinates, localized to the dysgranular retrosplenial sub-region, independent of self-motion, and context invariant. Further, we identify a sub-population of neurons with this response property that are synchronized with the hippocampal theta oscillation. Accordingly, the current work identifies a robust egocentric spatial code in retrosplenial cortex that can facilitate spatial coordinate system transformations and support the anchoring, generation, and utilization of allocentric representations.
Rotavirus re-programs multiple IFN receptors and restricts their intestinal antiviral and inflammatory functions
Authors: Sen Adrish , Namsa Nima D. , Feng Ningguo , Greenberg Harry B.
Published: July 2019

Rotaviruses (RV) cause acute severe diarrhea in the absence of substantial intestinal inflammation. They are also highly infectious in their homologous host species. The efficient replication capacity of RV in the small bowel is substantially linked to its ability to inhibit different types of interferons (IFNs). Here, we find that during RV infectionin vitro, both virus-infected and uninfected bystander cells resist STAT1 phosphorylation and IRF7 induction in response to exogenous IFN. Functionally, cellular transcription in response to exogenous stimulation with IFN, but not intracellular dsRNA, was inhibited by RV. Further, IFNAR1 stimulation during RV infection significantly repressed a set of virus-induced transcripts. Regulation of IFN signalingin vivowas studied in suckling mice using the highly infectious homologous murine EW RV strain. Kinetic studies indicated that whereas sustained EW RV replication and IFN induction occurred in the small intestine, IFN-stimulated transcripts significantly decreased over time. In addition, LPS-mediated intestinal damage, driven by STAT1-induced inflammation, was prevented in EW RV-infected mice. Remarkably, ectopic stimulation of either IFNAR1 or IFNGR1 in murine RV-infected mice eliminated several intestinal antiviral and inflammatory transcriptional responses to RV. In contrast to homologous murine RV, infection with a STAT1-sensitive heterologous simian RV strain induced multiple IFN-stimulated transcripts, inflammatory cytokines, and intestinal expression of STAT1-pY701. Finally, RV strain-specific STAT1 regulation in the gut plays a prominent role in the activation of multiple intestinal caspases. On the other hand, the simian RRV strain, but not murine EW RV, uniquely triggers the cleavage of both extrinsic and intrinsic caspases (−8, −9, and −3) in a STAT1-mediated manner. Collectively, these findings reveal efficient re-programing of multiple IFN receptors in the gut towards a negative feedback mode of signaling, accompanied by suppression of IFN-mediated antiviral, apoptotic, and inflammatory functions, during natural RV intestinal infection.
Posterior hippocampal spindle-ripples co-occur with neocortical theta-bursts and down-upstates, and phase-lock with parietal spindles during NREM sleep in humans
Authors: Jiang Xi , Gonzalez-Martinez Jorge , Halgren Eric
Published: July 2019

Human anterior and posterior hippocampus (aHC, pHC) differ in connectivity and behavioral correlates. Here we report physiological differences. During NREM sleep, the human hippocampus generates sharpwave-ripples (SWR) similar to those which in rodents mark memory replay. We show that while pHC generates SWR, it also generates about as many spindle-ripples (SSR: ripples phase-locked to local spindles). In contrast, SSR are rare in aHC. Like SWR, SSR often co-occur with neocortical theta bursts (TB), downstates (DS), spindles (SS) and upstates (US), which coordinate cortico-hippocampal interactions and facilitate consolidation in rodents. SWR co-occur with these waves in widespread cortical areas, especially fronto-central. These waves typically occur in the sequence TB-DS-SS-US, with SWR usually occurring prior to SS-US. In contrast, SSR occur ∼350 ms later, with a strong preference for co-occurrence with posterior-parietal SS. pHC-SS were strongly phase-locked with parietal-SS, and pHC-SSR were phase-coupled with pHC-SS and parietal-SS. Human SWR (and associated replay events, if any) are separated by ∼5 s on average, whereas ripples on successive SSR peaks are separated by only ∼80 ms. These distinctive physiological properties of pHC-SSR enable an alternative mechanism for hippocampal engagement with neocortex.

Significance Statement

Rodent hippocampal neurons replay waking events during sharpwave-ripples in NREM sleep, facilitating memory transfer to a permanent cortical store. We show that human anterior hippocampus also produces sharpwave-ripples, but spindle-ripples predominate in posterior. Whereas sharpwave-ripples typically occur as cortex emerges from inactivity, spindle-ripples typically occur at peak cortical activity. Furthermore, posterior hippocampal spindle-ripples are tightly coupled to posterior parietal locations activated by conscious recollection. Finally, multiple spindle-ripples can recur within a second, whereas sharpwave-ripples are separated by about 5s. The human posterior hippocampus is considered homologous to rodent dorsal hippocampus, which is thought to be specialized for consolidation of specific memory details. We speculate that these distinct physiological characteristics of posterior hippocampal spindle-ripples may support a related function in humans.
Identification of essential oils with strong activity against stationary phase uropathogenic Escherichia coli
Authors: Xiao Shuzhen , Cui Peng , Shi Wanliang , Zhang Ying
Published: July 2019

Escherichia coli is the most dominant pathogen causing urinary tract infections (UTIs), but the current most frequently prescribed antibiotics do not always effectively cure the infection due to quiescent persister bacteria. While it has been reported that some essential oils have antimicrobial activity against growing E. coli, the activity of essential oils against the non-growing stationary phase E. coli which is enriched in persisters has not been investigated. We evaluated the activity of 140 essential oils against stationary phase uropathogenic E. coli UTI89 and identified 39, 8 and 3 essential oils at 0.5%, 0.25% and 0.125% concentrations to have high activity against stationary phase E. coli. Among the top eight essential oils, Oregano showed higher activity than the known persister drug tosufloxacin. The other top seven hits included Allspice, Bandit "Thieves", Cinnamon bark, Syzygium aromaticum, Health shield, Cinnamon leaf and Clove bud. In Oregano essential oil drug combination studies with common UTI antibiotics, Oregano plus quinolone drugs (tosufloxacin, levofloxacin, ciprofloxacin) completely eradicated all stationary phase E. coli cells, partially enhanced the activity of nitrofurantoin, but had no apparent enhancement for fosfomycin, meropenem and cefdinir. Our findings may facilitate development of more effective treatments for persistent UTIs.
Intraperitoneal injection of sodium pentobarbital is associated with pain in rats
Authors: Reimer JN , Schuster C , Knight CG , Pang DSJ , Leung VSY
Published: July 2019

An effective and pain-free killing method is required to achieve the goal of euthanasia, a “good death”. Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control.

Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 112) were block randomised by sex and strain to receive one of four treatments: 1) 800 mg/kg PB (pH 11); 2) 800 mg/kg PB with 4 mg/kg lidocaine (PB+lido); 3) saline or 4) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale [RGS], writhing, back arching) was evaluated at baseline, before loss of righting reflex (PB and PB+lido groups), 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups).

In the vehicle control groups, the RGS scores were increased at 151s PI (SD: p = 0.0008, 95%CI −0.731 to −0.202) from baseline, as was relative frequency of writhing (SD: p < 0.00001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0070, 95%CI −0.768 to −0.118; Wistar: p = 0.0236, 95%CI −0.907 to −0.0742) but the relative frequency of writhing did not (p > 0.05). The RGS scores and the relative frequency of writhing remained low in the PB, PB+lido and saline groups (p > 0.05). Back arching increased from baseline in the PB+lido group before loss of righting reflex and in the vehicle control group (SD rats) at 151s PI (p < 0.05).

These results show that IP PB results in signs associated with pain. The sedative effects of PB limit behavioral assessment.
Dimensional Reduction of Emergent Spatiotemporal Cortical Dynamics via a Maximum Entropy Moment Closure
Authors: Shao Yuxiu , Zhang Jiwei , Tao Louis
Published: July 2019

Modern electrophysiological recordings and optical imaging techniques have revealed a diverse spectrum of spatiotemporal neural activities underlying fundamental cognitive processing. Oscillations, traveling waves and other complex population dynamical patterns are often concomitant with sensory processing, information transfer, decision making and memory consolidation. While neural population models such as neural mass, population density and kinetic theoretical models have been used to capture a wide range of the experimentally observed dynamics, a full account of how the multi-scale dynamics emerges from the detailed biophysical properties of individual neurons and the network architecture remains elusive. Here we apply a recently developed coarse-graining framework for reduced-dimensional descriptions of neuronal networks to model visual cortical dynamics. We show that, without introducing any new parameters, how a sequence of models culminating in an augmented system of spatially-coupled ODEs can effectively model a wide range of the observed cortical dynamics, ranging from visual stimulus orientation dynamics to traveling waves induced by visual illusory stimuli. In addition to an efficient simulation method, this framework also offers an analytic approach to studying large-scale network dynamics. As such, the dimensional reduction naturally leads to mesoscopic variables that capture the interplay between neuronal population stochasticity and network architecture that we believe to underlie many emergent cortical phenomena.
Long term outcomes of Everolimus therapy in de novo liver transplantation: a systematic review and meta-analysis of randomized controlled trials
Authors: Khalid Bzeizi , Richard Smith , Ali Benmousa , M.V.SC Dama Madhukar , Faisal Aba-Alkhail , Rajiv Jalan , Dieter Broering
Published: July 2019

Background

Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of Everolimus (EVR) in minimizing this risk when combined with a reduced CnIs dose.

Objective

To systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post liver transplantation.

Methods

We searched MEDLINE, Scopus and the Cochrane Library for randomized controlled trials (RCTs) comparing EVR and CnI based regimens post liver transplanation. Assessment of studies and data extraction was undertaken independently.

Results

Eight studies were selected describing 769 patients. Cockcroft-Gault GFR (CG-GFR) was significantly higher at one (p=0.05), 3 & 5 years (p=0.030) in patients receiving EVR as compared to those receiving CnI therapy. The composite end point of efficacy failure was similar between the two arms after 1, 3 & 5 years of study. Higher number of patients discontinued EVR due to adverse effects in one year, however no difference was noted after 3 & 5 years. A higher rates of proteinuria, peripheral edema and incisional hernia were noted in patients on EVR.

Conclusion

The analysis confirms non-inferiority of EVR and reduced CnI combination. Patients on the combination regimen had better renal function compared to standard CnI therapy.
Similarity of species composition of sand flies (Diptera: Psychodidae) in caves of Quadrilátero Ferrífero, state Minas Gerais, Brasil
Authors: Campos Aldenise Martins , dos Anjos Maia Rodrigo , Capucci Débora , Paglia Adriano Pereira , Andrade Filho José Dilermando
Published: July 2019

Caves, though seemingly inhospitable due to the lack of light in areas furthest from the cave entrance and the low availability and variety of resources, can harbor many species of vertebrates and invertebrates, including phlebotomine sand flies, the vectors of species of parasites of the genus Leishmania that cause leishmaniasis. This study aimed to evaluate the species composition of sand flies in located caves at Moeda Sul (MS) and Parque Estadual Serra do Rola Moça (PESRM), in southeastern Brazil at region of the Quadrilátero Ferrífero, state of Minas Gerais. The collections of sand flies were performed with automatic light traps. Were used the Non-Metric Multidimensional Scaling based on dissimilarity matrix calculated with the Jaccard índex and Multivariate Analysis of Permutation to evaluate similarity of the species composition of sand flies among entrance, interior, and surroundings environments of each sampled cave at MS and PESRM, and thus to infer biological mechanisms from the patterns of distribution of sand flies among these different cave environments. A total of 375 phlebotomine sand flies were collected from six genera and 14 species. The most abundant species were Evandromyia tupynambai (54.7%), Brumptomyia troglodytes (25.6%), Evandromyia edwardsi, (6.1%) Psathyromyia brasiliensis (4.8%) and Lutzomyia longipalpis (4.3%). In place MS, 30 individuals were collected, 16 inside the MS cave and 14 its surroundings. In place PESRM, five individuals were collected in surroundings of RM38 cave; a total of 190 individuals at RM39 cave (48 in the cave and 142 its surroundings) and 150 individuals at RM40 cave, 42 in the cave and 108 its surroundings. Our results showed rich fauna of sand flies with a species composition of sand flies similar among the entrance, interior, and surroundings environments of each sampled cave, suggesting that both caves and their surroundings are important for the maintenance of sand fly communities.
Drug related and psychopathological symptoms in HIV-positive men who have sex with men who inject drugs during sex (Slamsex): Data from the U-SEX GESIDA 9416 Study
Authors: Dolengevich-Segal Helen , Gonzalez-Baeza Alicia , Valencia Jorge , Valencia-Ortega Eulalia , Cabello Alfonso , Tellez Molina Maria Jesus , Perez Elias Maria Jesus , Serrano Regino , Perez Latorre Leire , Martín-Carbonero Luz , Arponen Sari , Sanz Moreno Jose , De La Fuente Sara , Bisbal Otilia , Santos Ignacio , Casado Jose Luis , Troya Jesus , Cervero Jimenez Miguel , Nistal Sara , Cuevas Guillermo , Correas Lauffer Javier , Torrens Marta , Ryan Pablo ,   on Behalf of the U-SEX GESIDA 9416 Study
Published: July 2019

Objectives

Intravenous sexualized drug use also known as slamsex seems to be increasing among HIV-positive men who have sex with men (MSM). This practice may entail severe consequences for physical and mental health in this population. Research on the subject is scarce. The aim of our study was to describe the psychopathological background of a sample of HIV positive MSM who practiced slamsex during the previous year and compare the physical and psychological symptoms between these participants and those who practiced sexualized drug use (SDU) or chemsex without slamsex.

Design and Methods

Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional survey on sexual behaviour and recreational drug use. The present analysis is based on HIV-positive MSM who had practiced SDU.

Results

The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) practiced chemsex, and of these, 34 (15.7%) had practiced slamsex. Participants who practiced slamsex were more likely to have current psychopathology (depression, anxiety and drug related disorders) than chemsex users. In addition, participants who practiced slamsex had more high-risk sexual behaviours, polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with patients who did not inject drugs, patients who engaged in slamsex showed more severe drug related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms related to SDU, such as paranoid thoughts and suicidal behaviour.

Conclusion

Slamsex (intravenous SDU) is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.
Cloning human dental pulp cells and studying inter-clone diversity
Authors: Guo Linna , Zou Ziang , Yan Ming , Freytag Marcus , Friedrich Reinhard E , Kluwe Lan
Published: July 2019

Heterogeneity within a putative stem cell population presents a challenge for studies and applications of such cells. Cloning may provide a strategy for reducing heterogeneity. However, previous studies have the weakness in reliability of single-cell-origin of the colonies. The present study aims to apply an alternative method to obtain clonal dental pulp cells with increased reliability of single cell origin. Dental pulp cells were cultured from 13 human wisdom teeth. Primary cultures of 3 human benign tumors were included as comparison. Cells were seeded into wells of a 96-plate at a mean density of 1 cell/well. On the next day, wells were inspected one by one to identify wells with single cells which were followed for 3 weeks. Survived clones were expanded and further characterized. Single cells were observed in all cases, the number of single-cell-wells varied from 16 to 33. Three weeks later, survived and grown clonal cells were observed in 10 to 29 wells, giving surviving rates of 33-91%. By contrast, though single tumor cells were also observed, none of them survived. Expanded clones exhibited diversity in viability and osteogenic differentiation which also differed from their parental cells. Seeding cells at clonal density into physically separated compartments like wells in a 96 plate and comprehensive observation provides a practical strategy for increasing reliability of single-cell origin of clonal cells. Cellular heterogeneity seems to be an intrinsic feature of dental pulp cells.
Occasion setters attain incentive motivational value: implications for contextual influences on reward-seeking
Authors: Fraser Kurt M. , Janak Patricia H.
Published: July 2019

The context in which reward-paired cues are encountered can resolve ambiguity and set the occasion for appropriate reward-seeking. The psychological processes by which contexts regulate reward-seeking remain unclear as contexts are diffuse and difficult to isolate from other stimuli. To overcome this, we modeled a context as a phasic and discrete event—an occasion setter (OS)—which allowed for control over its presentation and influence on cue-driven reward-seeking. This allowed us to directly assess how OSs regulate the predictive and motivational significance of Pavlovian cues. Male rats (n = 50) were trained in a Pavlovian procedure where the presentation of an ambiguous conditioned stimulus (CS) was reinforced only if preceded by an occasion setting cue. We assessed the motivational value of the OS and CS alone or in combination using tests of conditioned reinforcement. Rats enhanced conditioned approach to the reward port during the CS when it was preceded by the OS. When allowed the opportunity, rats responded more to obtain presentations of the CS in combination with the OS than the CS alone. Critically, rats also worked to obtain presentations of the OS alone more than the CS alone, and this was resistant to manipulations of the value of the OS. We conclude that occasion setting can act via incentive motivational mechanisms and that, apart from resolving predictive information about ambiguous reward-paired cues, OSs themselves generate states of appetitive motivation that can facilitate reward-seeking.