bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock
Authors: Clavier Thomas , Besnier Emmanuel , Maucotel Julie , Arabo Arnaud , Desrues Laurence , El Amki Mohamad , Perzo Nicolas , Richard Vincent , Tamion Fabienne , Gandolfo Pierrick , Dubois Martine , Castel Hélène , Compère Vincent 
Published: October 2019

ABSTRACT

Introduction:
Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock.

Methods:
C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.9% 3, 6, and 9 h (H3, H6, H9) after LPS. The effect of urantide on the survival rate, the levels of cytokines in plasma at H6, H9, H12, the expression level of nuclear factor-kappa B (NF-κB-p65) in liver and kidney (at H12), and the cardiac function by trans-thoracic echocardiography from H0 to H9 was evaluated.

Results:
Urantide treatment improved survival (88.9% vs. 30% on day 6, P < 0.05). This was associated with changes in cytokine expression: a decrease in IL-6 (2,485 [2,280–2,751] pg/mL vs. 3,330 [3,119–3,680] pg/mL, P < 0.01) at H6, in IL-3 (1.0 [0.40–2.0] pg/mL vs. 5.8 [3.0–7.7] pg/mL, P < 0.01), and IL-1β (651 [491–1,135] pg/mL vs. 1,601 [906–3,010] pg/mL, P < 0.05) at H12 after LPS administration. Urantide decreased the proportion of cytosolic NF-κB-p65 in liver (1.3 [0.9–1.9] vs. 3.2 [2.3–4], P < 0.01) and kidney (0.3 [0.3–0.4] vs. 0.6 [0.5–1.1], P < 0.01). Urantide improved cardiac function (left ventricular fractional shortening: 24.8 [21.5–38.9] vs. 12.0 [8.7–17.6] %, P < 0.01 and cardiac output: 30.3 [25.9–39.8] vs. 15.1 [13.0–16.9] mL/min, P < 0.0001).

Conclusion:
These results show a beneficial curative role of UT antagonism on cytokine response (especially IL-3), cardiac dysfunction, and survival during endotoxic shock in mice, highlighting a potential new therapeutic target for septic patients.
Living Donor Kidney Transplantation Should Be Promoted Among “Elderly” Patients
Authors: Laging Mirjam , Kal-van Gestel Judith A. , Weimar Willem , Roodnat Joke I. 
Published: October 2019

Background.
Age criteria for kidney transplantation have been liberalized over the years resulting in more waitlisted elderly patients. What are the prospects of elderly patients on the waiting list?

Methods.
Between 2000 and 2013, 2622 patients had been waitlisted. Waiting time was defined as the period between dialysis onset and being delisted. Patients were categorized according to age upon listing: <25; 25–44; 45–54; 55–64; and >64 years. Furthermore, the influence of ABO blood type and panel reactive antibodies on outflow patterns was studied.

Results.
At the end of observation (November 2017), 1957 (75%) patients had been transplanted, 333 (13%) had been delisted without a transplantation, 271 (10%) had died, and 61 (2%) were still waiting. When comparing the age categories, outflow patterns were completely different. The percentage of patients transplanted decreased with increasing age, while the percentage of patients that had been delisted or had died increased with increasing age, especially in the population without living donor. Within 6 years, 93% of the population <25 years had received a (primarily living) donor kidney. In the populations >55 years, 39% received a living donor kidney, while >50% of patients without a living donor had been delisted/died. Multivariable analysis showed that the influence of age, ABO blood type, and panel reactive antibodies on outflow patterns was significant, but the magnitude of the influence of the latter 2 was only modest compared with that of age.

Conclusions.
“Elderly” (not only >64 y but even 55–64 y) received a living donor kidney transplantation less often. Moreover, they cannot bear the waiting time for a deceased donor kidney, resulting in delisting without a transplant in more than half the population of patients without a living donor. Promoting living donor kidney transplantation is the only modification that improves transplantation and decreases delisting/death on the waiting list in this population.
Intergenerational transmission of longevity is not affected by other familial factors: Evidence from 16,905 Dutch families from Zeeland, 1812-1962
Authors: Mourits R.J. , van den Berg N.M.A. , Rodríguez-Girondo M. , Mandemakers K. , Slagboom P.E. , Beekman M. , Janssens A.A.P.O. 
Published: October 2019

AbstractStudies have shown that long-lived individuals seem to pass their survival advantage on to their offspring. Offspring of long-lived parents had a lifelong survival advantage over individuals without long-lived parents, making them more likely to become long-lived themselves. We test whether the survival advantage enjoyed by offspring of long-lived individuals is explained by environmental factors. 101,577 individuals from 16,905 families in the 1812-1886 Zeeland cohort were followed over time. To prevent that certain families were overrepresented in our data, disjoint family trees were selected. Offspring was included if the age at death of both parents was known. Our analyses show that multiple familial resources are associated with survival within the first 5 years of life, with stronger maternal than paternal effects. However, between ages 5 and 100 both parents contribute equally to offspring’s survival chances. After age 5, offspring of long-lived fathers and long-lived mothers had a 16-19% lower chance of dying at any given point in time than individuals without long-lived parents. This survival advantage is most likely genetic in nature, as it could not be explained by other, tested familial resources and is transmitted equally by fathers and mothers.
Gap junction coding innexin inLymnaea stagnalis: sequence analysis and characterization in tissues and the central nervous system
Authors: Mersman Brittany A. , Jolly Sonia N. , Lin Zhenguo , Xu Fenglian 
Published: October 2019

AbstractConnections between neurons called synapses are the key components underlying all nervous system functions of animals and humans. However, important genetic information on the formation and plasticity of one type, the electrical (gap junction-mediated) synapse, is severely understudied, especially in invertebrates. In the present study, we set forth to identify and characterize the gap junction-encoding gene innexin in the central nervous system (CNS) of the mollusc pond snailLymnaea stagnalis(L. stagnalis). With PCR, 3’ and 5’ RACE, and BLAST searches, we identified eight innexin genes in theL. stagnalisnervous system namedLst Inx1-8. Phylogenetic analysis revealed that theL. stagnalisinnexin genes originated from a single copy in the common ancestor of molluscan species by multiple gene duplication events and have been maintained inL. stagnalissince they were generated. The paralogous innexin genes demonstrate distinct expression patterns among tissues. In addition, one paralog,Lst Inx1, exhibits heterogeneity in cells and ganglia, suggesting the occurrence of functional diversification after gene duplication. These results introduce possibilities to study an intriguing potential relationship between innexin paralog expression and cell-specific functional outputs such as heterogenic ability to form channels and exhibit synapse plasticity. TheL. stagnalisCNS contains large neurons and a functionally defined network for behaviors; with the introduction ofL. stagnalisin the gap junction field, we are providing novel opportunities to combine genetic research with direct investigation of functional outcomes at the cellular, synaptic, and behavioral levels.Summary StatementBy characterizing the gap junction gene innexin inLymnaea stagnalis, we open opportunities for novel studies on the regulation, plasticity, and evolutionary function of electrical synapses throughout the animal kingdom.
Selecting the most important self-assessed features for predicting conversion to Mild Cognitive Impairment with Random Forest and Permutation-based methods
Authors: Gómez-Ramírez Jaime , Ávila-Villanueva Marina , Fernández-Blázquez Miguel Ángel 
Published: October 2019

ABSTRACTAlzheimer’s Disease (AD) is a complex, multifactorial and comorbid condition. The asymptomatic behavior in the early stages makes the identification of the disease onset particularly challenging. Mild cognitive impairment (MCI) is an intermediary stage between the expected decline of normal aging and the pathological decline associated with dementia. The identification of risk factors for MCI is thus sorely needed. Self-reported personal information such as age, education, income level, sleep, diet, physical exercise, etc. are called to play a key role not only in the early identification of MCI but also in the design of personalized interventions and the promotion of patients empowerment. In this study we leverage onThe Vallecas Project, a large longitudinal study on healthy aging in Spain, to identify the most important self-reported features for future conversion to MCI. Using machine learning (random forest) and permutation-based methods we select the set of most important self-reported variables for MCI conversion which includes among others, subjective cognitive decline, educational level, working experience, social life, and diet. Subjective cognitive decline stands as the most important feature for future conversion to MCI across different feature selection techniques.
Including measures of high gamma power can improve the decoding of natural speech from EEG
Authors: Synigal Shyanthony R. , Teoh Emily S. , Lalor Edmund C. 
Published: October 2019

ABSTRACTThe human auditory system is adept at extracting information from speech in both single-speaker and multi-speaker situations. This involves neural processing at the rapid temporal scales seen in natural speech. Non-invasive brain imaging (electro-/magnetoencephalography [EEG/MEG]) signatures of such processing have shown that the phase of neural activity below 16 Hz tracks the dynamics of speech, whereas invasive brain imaging (electrocorticography [ECoG]) has shown that such rapid processing is even more strongly reflected in the power of neural activity at high frequencies (around 70-150 Hz; known as high gamma). The aim of this study was to determine if high gamma power in scalp recorded EEG carries useful stimulus-related information, despite its reputation for having a poor signal to noise ratio. Furthermore, we aimed to assess whether any such information might be complementary to that reflected in well-established low frequency EEG indices of speech processing. We used linear regression to investigate speech envelope and attention decoding in EEG at low frequencies, in high gamma power, and in both signals combined. While low frequency speech tracking was evident for almost all subjects as expected, high gamma power also showed robust speech tracking in a minority of subjects. This same pattern was true for attention decoding using a separate group of subjects who undertook a cocktail party attention experiment. For the subjects who showed speech tracking in high gamma power, the spatiotemporal characteristics of that high gamma tracking differed from that of low-frequency EEG. Furthermore, combining the two neural measures led to improved measures of speech tracking for several subjects. Overall, this indicates that high gamma power EEG can carry useful information regarding speech processing and attentional selection in some subjects and combining it with low frequency EEG can improve the mapping between natural speech and the resulting neural responses.
Model-based assessments of differential introgression and linked natural selection during divergence and speciation
Authors: Sethuraman Arun , Sousa Vitor , Hey Jody 
Published: October 2019

AbstractDemographic changes such as fluctuating population size and differential introgression can mask the effects of natural selection, and affect rates of genome evolution, local adaptation, reproductive isolation, and eventual speciation. Besides identifying differentially introgressing genes (and genomic regions) that are “labeled” to be retroactively causal to adaptive evolution and speciation, there is significant impetus to understand, and perhaps estimate the underlying demography that affects current genomic diversity. Using model-based likelihood methods to directly estimate, and decouple the effects of differential intogression and demography across genomic loci offers an ideal solution to detect differential introgression, and population demography and build hypotheses around its underlying evolutionary processes. We describe a computationally efficient parallelized implementation of mixture-model based isolation with migration (IM) analyses to assign loci to classes based on their shared coalescent histories (population sizes, or migration rates). We apply this method to several genomic data sets (great apes - chimpanzees and bonobos, Anopheles mosquitoes, threespine sticklebacks, Mullerian mimics of Heliconius butterflies, mice, European rabbits, and fruitflies), that have been previously characterized (perhaps erroneously) using genome-wide scans of differentiation. We show that we cannot reject a model of differential introgression, or linked selection across a majority of species analyzed, with two species showing the combined effects of differential introgression and linked natural selection across multiple, non-independent genomic loci.
Prey partitioning between sympatric canid species revealed by DNA metabarcoding
Authors: Shi Yue , Hoareau Yves , Reese Ellie , Wasser Samuel K. 
Published: October 2019

AbstractThe recovery of apex predators relies on restoring the full suite of trophic interactions within the ecosystem. Diet analysis with DNA metabarcoding technology can help deliver insights into these trophic interactions with fine-grained resolution. The recovery of wolves in Washington state offers an excellent case to study the trophic cascade impacts of the apex predators on the ecosystem and explore prey partitioning between sympatric canid species. We used DNA metabarcoding technology on scats to characterize the diet composition and its spatiotemporal variations of wolves and coyotes and quantified the diet niche overlap between these two canid species in northeastern Washington. In total, 19 different prey taxa were detected. Frequency of occurrence data showed that wolves primarily preyed upon deer (Odocoileus sp.) (47.47%) and moose (Alces alces) (42.42%). Coyotes also consumed moose (30.10%) and deer (21.36%), but snowshoe hares (Lepus americanus) were the most common prey (61.17%) in their diet. There were significant spatial variations in the wolf diet composition (p = 0.001) with wolves in the Dirty Shirt pack range consuming more moose (71.43%). Coyotes showed significant spatial and temporal dietary variations (season: p = 0.037; pack: p = 0.003; pack:season p = 0.043). Our data suggested that coyotes use ungulate carrion subsidies from wolves as food resources. DNA metabarcoding with fecal DNA provides an excellent noninvasive tool to characterize diet profile at the fine-grained level and can be applied to other carnivore species to help understand the impacts of recovery of apex predators on the local ecosystems.
Mutual information reveals a homonucleotide bias at 6 bp distance in promoters
Authors: Dannemiller James L. 
Published: October 2019

MotivationStatistical dependencies between nucleotides at different positions within a DNA sequence have been used for several purposes including distinguishing coding from noncoding regions of a genome. Coding sequences show correlations within and between codon positions. This study asked whether such correlations between positions separated by short distances might also exist in noncoding DNA. To this end, positional nucleotide dependencies were examined in the promoter regions of four eukaryotic species:Homo sapiens(Hs),Mus musculus(Mm),Drosophila melanogaster(Dm), andSaccharomyces cerevisiae(Sc). The degree of dependency between pairwise positions across a set of aligned sequences was quantified by Mutual Information (MI) and visualized using a novel heatmap method.ResultsMI in promoter sequences aligned at their putative Transcription Start Site (TSS) generally decreased with increasing distance between two positions, but also showed a prominent increase at a distance of 6 base pairs (bp) (i.e., between nucleotides atxandx+ 6 in a sequence) in the three multicellular species, but much less so inSc. This dependency at a distance of 6 bp appears to reflect anN1…N7homonucleotide bias in promoters.AvailabilityR code and data files available at github/dannemil/promoters.Contactdannemil@rice.eduSupplementary informationDannemiller-supplementary-documents.zip
Benchmarking metagenomic marine microbial growth prediction from codon usage bias and peak-to-trough ratios
Authors: Long Andrew M. , Hou Shengwei , Ignacio-Espinoza J. Cesar , Fuhrman Jed A. 
Published: October 2019

AbstractGrowth rates are fundamental to all organisms and essential for characterizing microbial ecologies. Despite this, we do not know the instantaneous nor maximum growth rates of most naturally-occurring microorganisms. Recent reports indicate DNA replication rates can be estimated from metagenomic coverage, and maximum growth rates can be estimated from genomic characteristics. We tested these approaches with native marine bacteria (<0.6 um size fraction) as 10% inoculum grown in unamended virus-free seawater from the San Pedro Channel, California. This allowed microbial growth without grazing and with greatly reduced viral infection. At multiple time points up to 48 h, we sampled for cell abundances and metagenomic analyses. We generated 101 unique Metagenome-assembled genomes (MAGs) including α, β, and γ Proteobacteria, Flavobacteria, Actinobacteria, Verrucomicrobia, Marine Group A/SAR406, MGII archaea, and others. We tracked the growth of each as the fraction of total metagenomic reads mapped to each MAG normalized with length, completeness, and total cell counts. Some MAGs did not grow appreciably, but those we could estimate had growth rates ranging from 0.08 to 5.99 d−1; these are the first reported growth rates for several of the groups. These metagenome-determined growth rates, which often changed within experiments, were compared to (a) DNA replication estimates from the ‘peak-to-trough’ ratio (PTR) as determined by three different approaches, and (b) maximum growth rates predicted from codon usage bias (CUB). For the large majority of taxa, observed growth rates were not correlated to PTR indices (r ~ −0.26 - 0.08), with exceptions being rapidly growingOceanospirillalesandSaccharospirillaceae(r ~ 0.63 - 0.92). However, CUB was moderately well correlated to observed maximum growth rates (r = 0.57). This suggests that maximum growth rates can be reasonably well-estimated from genomic information alone, but current PTR approaches poorly predict actual growth of most marine planktonic bacteria in unamended seawater.
Computational redesign of a PETase for plastic biodegradation by the GRAPE strategy
Authors: Cui Yinglu , Chen Yanchun , Liu Xinyue , Dong Saijun , Tian Yu’e , Qiao Yuxin , Mitra Ruchira , Han Jing , Li Chunli , Han Xu , Liu Weidong , Chen Quan , Du Wenbin , Tang Shuangyan , Xiang Hua , Liu Haiyan , Wu Bian 
Published: October 2019

AbstractThe excessive use of plastics has been accompanied by severe ecologically damaging effects. The recent discovery of a PETase from Ideonella sakaiensis that decomposes poly(ethylene terephthalate) (PET) under mild conditions provides an attractive avenue for the biodegradation of plastics. However, the inherent instability of the enzyme limits its practical utilization. Here, we devised a novel computational strategy (greedy accumulated strategy for protein engineering, GRAPE). A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the design of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 °C and strikingly enhanced degradation performance toward semicrystalline PET films (23%) at mild temperatures (over two orders of magnitude improvement). The mechanism underlying the robust promotion of enzyme performance has been demonstrated via a crystal structure and molecular dynamics simulations. This work shows the capabilities of computational enzyme design to circumvent antagonistic epistatic effects and provides a valuable tool for further understanding and advancing polyester hydrolysis in the natural environment.
CD146+CD107a+ Mesenchymal Stem/Stromal Cells with Signature Attributes Correlate to Therapeutic Potency as “First Responders” to Injury and Inflammation
Authors: Bowles Annie C. , Kouroupis Dimitrios , Willman Melissa A. , Orfei Carlotta Perucca , Agarwal Ashutosh , Correa Diego 
Published: October 2019

ABSTRACTCD146+ bone marrow–derived Mesenchymal Stem/Stromal Cells (BM-MSC) play key roles in the perivascular niche, skeletogenesis and hematopoietic support, however elucidation of therapeutic potency has yet to be determined. Here, inflammatory challenge to crude BM-MSC captured a baseline of signatures including enriched expression of CD146+ with CD107a+, CXCR4+, and LepR+, transcriptional profile, enhanced secretory capacity, robust secretome and immunomodulatory function with stimulated target immune cells. These responses were significantly more pronounced in CD146+ (POS)-selected subpopulation than in the CD146- (NEG). Mechanistically, POS uniquely mediated robust immunosuppression while inducing significant frequencies of Naïve and Regulatory T cells in vitro. Moreover, POS promoted a pivotal M1-to-M2 macrophage shift in vivo, ameliorating inflammation/fibrosis of joint synovium and fat pad of the knee, failed by NEG. This study provides high-content evidence of CD146+CD107a+ BM-MSC, herein deemed ‘first responders’ to inflammation, as the underrepresented subpopulation within crude BM-MSC with innately higher secretory capacity and therapeutic potency.HIGHLIGHTSSignature phenotypic, transcriptional, and secretome profiles were identified and enriched in human CD146+ (POS)-selected subpopulation in response to inflammationInflammatory challenge consistently altered stemness (LIF) and differentiation master regulators (SOX9, RUNX2, PPARγ) in crude, POS, and NEG BM-MSC, and deduced unique expressions in POS compared to NEGPOS BM-MSC mediated the strongest immunomodulation, e.g. target immune cell suppression, Treg induction, diminished T cell differentiationPOS BM-MSC promoted the largest M1-to-M2 shift in vivo alleviating induced synovitis and infrapatellar fat pad fibrosis of the knee