bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptor 2 and 9 expression on circulating neutrophils is associated with increased mortality in critically ill patients
Authors: Lenz Max , Draxler Dominik F. , Zhang Chao , Kassem Mona , Kastl Stefan P. , Niessner Alexander , Huber Kurt , Wojta Johann , Heinz Gottfried , Speidl Walter S. , Krychtiuk Konstantin A. 
Published: November 2019

ABSTRACT

Background:
Toll-like receptors (TLRs) play an important role in inflammatory processes in critically ill patients by binding to pathogen-associated molecular patterns and danger-associated molecular patterns (DAMPs). Whether neutrophil or monocyte TLR expression patterns are associated with outcome in critical illness is unknown.

Objectives:
To answer this question, we conducted a prospective, observational study including 215 consecutive patients admitted to a medical ICU at a tertiary care center.

Methods:
Blood was drawn at admission and expression of TLR-2, TLR-4, and TLR-9 on neutrophils and monocytes were analyzed by flow cytometry.

Results:
Median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 19, and 30-day mortality was 26%. TLR-2 expression on neutrophils was associated with APACHE II, Simplified Acute Physiology Score II, and Sepsis-related Organ Failure Assessment score. TLR-2 (P < 0.001) and TLR-9 (P < 0.05) expression on neutrophils was significantly higher in nonsurvivors. In contrast, neutrophil TLR-4 expression and monocyte TLR expression were not associated with survival. Neutrophil TLR-2 (odds ratio 3.8; 95% confidence interval 1.4–10.2; P < 0.05) and TLR-9 (odds ratio 4.0; 95% confidence interval 2.0–8.1; P < 0.001) expression in the third tertile predicted mortality independent from APACHE II, serum lactate, serum creatinine, and procalcitonin, respectively.

Conclusion:
We provide evidence for prognostic properties of neutrophil TLR-2 and TLR-9 expression regarding 30-day mortality in unselected critically ill patients, independent from baseline clinical characteristics, and laboratory values. These findings suggest that specific TLR-dependent activation of the innate immune system via neutrophils possibly caused by cell damage and release of otherwise intracellular components may play a significant role in the pathophysiology of critical illness.
Stochastic simulation platform for visualization and estimation of transcriptional kinetics
Authors: Gorin Gennady , Wang Mengyu , Golding Ido , Xu Heng 
Published: November 2019

AbstractWe present an implementation of the Gillespie algorithm that simulates the stochastic kinetics of nascent and mature RNA. Our model includes two-state gene regulation, RNA synthesis initiation and stepwise elongation, release to the cytoplasm, and stepwise degradation, a granular description currently tractable only by simulation. To facilitate comparison with experimental data, the algorithm predicts fluorescent probe signals measurable by single-cell RNA imaging. We approach the inverse problem of estimating underlying parameters in a five-dimensional parameter space and suggest optimization heuristics that successfully recover known reaction rates from simulated gene expression turn-on data. The simulation framework includes a graphical user interface, available as a MATLAB app at https://data.caltech.edu/records/1287.
Immunoglobulin gene conversion identification and analysis
Authors: Bonissone Stefano R. 
Published: November 2019

ABSTRACTImmunoglobulins are highly diverse, diverging from their originating germline genes driven primarily by somatic recombination and hypermutation. However, somatic gene conversion is a strong driver of immunoglobulin diversity in some species, including rabbits and chickens. It is considerably harder to detect by sequence analysis than point mutations, and currently no dedicated tools exist for identifying these events. We presentGECCO, the first dedicated gene conversion identification tool for immunoglobulins based on modified, simultaneous, pairwise alignments to host and donor references. We benchmark our approach on simulated repertoires and findGECCOhas high recall, low false positive rate, and is insensitive to somatic mutations. We apply this new approach to characterize gene conversion events at the repertoire level in hyper-immunized rabbits, to show patterns of donor V gene preferences and donor tract length distributions. The dedicated gene conversion identification method we present allows for the characterization of a new feature of antibody repertoires that has not been possible thus far.GECCOwill benefit future studies to explore the prevalence of immunoglobulin gene conversion in additional species.
Identifying Refugia and Barriers to the Spread of A. graminifolia and D. crumenatum in Puerto Rico
Authors: Foster Evan , Ackerman James D. , Falcón L. Wilfredo 
Published: November 2019

SummaryEstablishment of new populations is contingent on overcoming abiotic and biotic barriers. While this applies to all species, these hurdles are at the forefront of invasion biology where prediction, prevention, eradication, and control strategies depend on an understanding and exploitation of barriers to establishment and spread. Arundina graminifolia and Dendrobium crumenatum are two invasive orchids spreading throughout Puerto Rico. Current records on their distributions across the island are sparse, and their interactions with the surrounding ecosystem are unknown. Through a direct population survey of all known localities, we identified a new, acquired enemy of both orchids: the orchid-specialist weevil, Stethobaris polita. In this study, we used niche modelling to identify suitable habitats for each orchid on the island and map their current distributions and interactions with S. polita, along with their distributions in the most extreme climate scenario in 2050, in order to contextualize projected patterns of establishment on the island. Our findings show that D. crumenatum flourishes in urban environments which also provide refugia from S. polita. In contrast, there is currently no refugia for A. graminifolia from S. polita attack, as it is more sensitive to the same climatic variables as S. polita. Furthermore, projections into the most extreme climate scenario suggests Puerto Rico will be unsuitable for A. graminifolia and S. polita’s survival, and become less suitable for D. crumenatum, by 2050.
TRIM14 is a key regulator of the type I interferon response during Mycobacterium tuberculosis infection
Authors: Hoffpauir Caitlyn T. , Bell Samantha L. , West Kelsi O. , Jing Tao , Torres-Odio Sylvia , Cox Jeffery S. , West A. Phillip , Li Pingwei , Patrick Kristin L. , Watson Robert O. 
Published: November 2019

ABSTRACTTripartite motif-containing proteins (TRIMs) play a variety of recently described roles in innate immunity. While many TRIMs regulate type I interferon (IFN) expression following cytosolic nucleic acid sensing of viruses, their contribution to innate immune signaling and gene expression during bacterial infection remains largely unknown. Because Mycobacterium tuberculosis is a potent activator of cGAS-dependent cytosolic DNA sensing, we set out to investigate a role for TRIM proteins in regulating macrophage responses to M. tuberculosis. Here we demonstrate that TRIM14, a non-canonical TRIM that lacks an E3 ligase RING domain, is a critical negative regulator of the type I IFN response in macrophages. We show that TRIM14 physically interacts with both cGAS and TBK1 and that macrophages lacking TRIM14 dramatically hyperinduce interferon stimulated gene (ISG) expression following cytosolic nucleic acid transfection, IFN-β treatment, and M. tuberculosis infection. Consistent with a defect in resolution of the type I IFN response, Trim14 knockout (KO) macrophages have more phospho-Ser754 STAT3 relative to phospho-727 and fail to upregulate the STAT3 target Socs3 (Suppressor of Cytokine Signaling 3), which is required to turn off IFNAR signaling. These data support a model whereby TRIM14 acts as a scaffold between TBK1 and STAT3 to promote phosphorylation of STAT3 at Ser727 and enhance negative regulation of ISG expression. Remarkably, Trim14 KO macrophages hyperinduce antimicrobials like Inos2 and are significantly better than control cells at limiting M. tuberculosis replication. Collectively, these data reveal a previously unappreciated role for TRIM14 in resolving type I IFN responses and controlling M. tuberculosis infection.
Ebselen attenuates mycobacterial virulence through inhibition of ESX-1 secretion
Authors: Osman Morwan M. , Pinckert Malte L. , Peak-Chew Sew , Troll Mark A. , Conrad William H. , Ramakrishnan Lalita 
Published: November 2019

ABSTRACTThe type VII secretion system ESX-1 mediates virulence in Mycobacterium tuberculosis and Mycobacterium marinum. We find that in M. marinum, the synthetic organoselenium compound ebselen inhibits secretion of ESAT-6, a major ESX-1 substrate. We find that ebselen inhibits the in vitro activity of the ESX-1 AAA+ ATPase EccA1, which potentiates ESX-1 substrate secretion and function. Ebselen modifies a cysteine in its N-terminal tetratricopeptide repeat domain that is required for EccA1’s in vitro ATPase activity. Surprisingly, mutational analyses show this this cysteine is not required for ESX-1 secretion or ebselen’s activity, showing that ebselen inhibits ESX-1 secretion independently of inhibiting EccA1 activity in vitro. While the mechanism by which ebselen inhibits ESX-1 secretion remains elusive, we show that it attenuates ESX-1-mediated damage of M. marinum-containing macrophage phagosomes and inhibits intramacrophage growth. Extending our studies to M. tuberculosis, we find that ebselen inhibits ESX-1 secretion and phagosomal membrane damage in this organism. This work provides insight into EccA1 biology. Ebselen is an orally active drug in clinical trials for other conditions and this work suggests its potential in tuberculosis therapy.
Low-disturbance Farming Regenerates Healthy Deep Soil towards Sustainable Agriculture
Authors: Deng Fangbo , Wang Hongjun , Xie Hongtu , Bao Xuelian , He Hongbo , Zhang Xudong , Liang Chao 
Published: November 2019

AbstractIntensive conventional farming has degraded farmland topsoil and seriously threaten food and environment security globally. Although low-disturbance practices have been widely adapted to restore soil health, whether this measure in a long run can potentially recover the critical deep soil to meet sustainable intensification of crop production are still unclear. Here we compared soil microbiome, physicochemical parameters along 3-m deep soil profiles, and crop yield in Northeast China subjected to ten years of farming practices at 3 levels of disturbance, including conventional tillage (CT), no-tillage without stover mulching (NTNS), and no-tillage with stover mulching (NTSM). We found that low-disturbance practices (NTNS and NTSM) promoted the ability of the deep soil to retain water, nitrogen and salt-extractable organic, regenerated whole-soil microbial diversity and metabolic function, improved topsoil organic carbon stock and corn yield in the drought year, showed the potential to reduce energy consumption and greenhouse gas emissions, thus regenerating highly efficient, sustainable agriculture.
Motivated for near impossibility: How task type and reward modulate task enjoyment and the striatal activation for extremely difficult task
Authors: Sakaki Michiko , Meliss Stef , Murayama Kou , Yomogida Yukihito , Matsumori Kaosu , Sugiura Ayaka , Matsumoto Madoka , Matsumoto Kenji 
Published: November 2019

AbstractEconomic and decision-making theories suppose that people would disengage from a task with near zero success probability, because this implicates little normative utility values. However, humans are often motivated for an extremely challenging task, even without any extrinsic incentives. The current study aimed to address the nature of this challenge-based motivation and its neural correlates. We found that, when participants played a skill-based task without extrinsic incentives, their task enjoyment increased as the chance of success decreased, even if the task was almost impossible to achieve. However, such challenge-based motivation was not observed when participants were rewarded for the task or the reward was determined in a probabilistic manner. The activation in the ventral striatum/pallidum tracked the pattern of task enjoyment. These results suggest that people are intrinsically motivated to challenge a nearly impossible task, but only when the task requires certain skills and extrinsic rewards are unavailable.
Population structure of chum salmon and selection on the markers collected for stock identification
Authors: Kitada Shuichi , Kishino Hirohisa 
Published: November 2019

AbstractGenetic stock identification (GSI) is a major management tool of Pacific salmon (Oncorhynchus Spp.) that has provided rich genetic baseline data of allozymes, microsatellites, and single nucleotide polymorphisms (SNPs) across the Pacific Rim. Here, we analyzed published data sets for adult chum salmon (Oncorhynchus keta), namely 10 microsatellites, 53 SNPs, and a mitochondrial DNA locus (mtDNA3, control region and NADH-3 combined) from 495 locations in the same distribution range (n = 61,813). TreeMix analysis of the microsatellite loci identified the highest level of genetic drift towards Japanese/Korean populations and suggested two admixture events from Japan/Korea to Russia and the Alaskan Peninsula. The SNPs had been purposively collected from rapidly evolving genes to increase the power of GSI. The highest expected heterozygosity was observed in Japanese/Korean populations for microsatellites, whereas it was highest in Western Alaskan populations for SNPs, reflecting the SNP discovery process. By regressing the SNP population structures on those of the microsatellites, we estimated the selection on the SNP loci according to deviations from the predicted structures. Specifically, we matched the sampling locations of the SNPs with those of the microsatellites according to geographical information and performed regression analyses of SNP allele frequencies on the two coordinates of multi-dimensional scaling (MDS) of matched locations obtained from microsatellite pairwise FST values. The MDS first axis indicated a latitudinal cline in American and Russian populations, whereas the second axis found a differentiation of Japanese/Korean populations. The top five outlier SNPs were mtDNA3 (combined locus of the control region and NADH-3), U502241 (unknown), GnRH373, ras1362, and TCP178, which were consistently identified by principal component analysis. We summarized the functions of the 53 nuclear SNPs and mtDNA3 locus by referring to a gene database system and discussed the functions of the outlier SNPs and fitness of chum salmon.
Lessons from Japan marine stock enhancement and sea ranching programmes over 100 years
Authors: Kitada Shuichi 
Published: November 2019

AbstractMore than 26 billion juveniles of 180 marine species are released annually into the wild in over 20 countries, but the usefulness of this strategy remains unclear. Here, I analyse the effects of stocking by Japanese marine and salmon stock-enhancement programmes and evaluate their efficacy through a Bayesian meta-analysis of new and previously considered cases. The posterior mean recapture rate (± SD) was 8.3 ± 4.7%. Without considering personnel costs and negative impacts on wild populations, the mean economic efficiency was 2.8 ± 6.1, with many cases having values of 1 to 2. On the macro-scale, the proportion of released seeds to total catch was 76 ± 20% for Japanese scallop, 28 ± 10% for abalone, 20 ± 5% for swimming crab, 13 ± 5% for kuruma prawn, 11 ± 4% for Japanese flounder, and 7 ± 2% for red sea bream; according to these percentages, stocking effects were generally small, and population dynamics were unaffected by releases but dependent on the carrying capacity of the nursery habitat. All cases of Japanese releases, except for Japanese scallop, were probably economically unprofitable. Captive breeding reduces the fitness of hatchery fish in the wild. In addition, long-term releases replace wild genes and may cause fitness decline in the recipient population when the proportion of hatchery fish is very high. Short-term hatchery stocking can be useful, particularly for conservation purposes, but large-scale programmes may harm the sustainability of populations. Nursery habitat recovery and fishing pressure reduction often outperform hatcheries in the long run.
Offset-related brain activity in the ventrolateral prefrontal cortex promotes long-term memory formation of verbal events
Authors: Medvedeva Angela , Saw Rebecca , Sirota Miroslav , Fuggetta Giorgio , Galli Giulia 
Published: November 2019

ABSTRACTRecent evidence suggests that brain activity following the offset of a stimulus during encoding contributes to long-term memory formation, however the exact mechanisms underlying offset-related encoding are still unclear. Here we used repetitive transcranial magnetic stimulation (rTMS) to investigate offset-related activity in the left ventrolateral prefrontal cortex (VLPFC). rTMS was administered at different points in time around stimulus offset while male and female participants encoded visually-presented words (first rTMS experiment) or pairs of words (second rTMS experiment) and the analyses focused on the effects of the stimulation on subsequent memory performance. The results show that rTMS administered at the offset of the stimuli, but not during online encoding, disrupted subsequent memory performance. In the first experiment we show that rTMS specifically disrupted encoding mechanisms initiated by the offset of the stimuli rather than general, post-stimulus processes. In the second experiment, we show a robust decline in associative memory performance when rTMS was delivered at the offset of the word pairs, suggesting that offset-related encoding may contribute to the binding of information into an episodic memory trace. A meta-analysis conducted on the two studies and on a previously published dataset confirmed that the involvement of the left VLPFC in memory formation is initiated by the offset of the stimulus. The offset of the stimulus may represent an event boundary that promotes the reinstatement of the previously experienced event and episodic binding.SIGNIFICANCE STATEMENTHow well an event is encoded predicts how well it is remembered, and verbal encoding is an important part of everyday memory that, if disrupted, can lead to difficulties and disorders. The timing of encoding processes relative to the presentation of an event is important for successful retrieval, and little is known about the interval immediately after an event’s presentation (post-stimulus offset) which is thought to involve critical encoding processes in the VLPFC and hippocampus. The current studies demonstrate that indeed, verbal encoding processes in the VLPFC that are necessary for memory formation are triggered by the offset of the word, and these processes may involve VLPFC-hippocampal interactions that promote binding of event features into a single, coherent memory trace.
Motor imagery practice during arm-immobilization benefits sensorimotor cortical functions and plasticity-related sleep features
Authors: Debarnot Ursula , Perrault Aurore. A. , Sterpenich Virginie , Legendre Guillaume , Huber Chieko , Guillot Aymeric , Schwartz Sophie 
Published: November 2019

ABSTRACTMotor imagery (MI) is known to engage motor networks and could compensate for the maladaptive neuroplasticity elicited by immobilization. This hypothesis and associated underlying neural mechanisms remain underexplored. Here, we investigated how MI practice during 11 h of arm-immobilization influences sensorimotor and cortical representations of the hands, as well as sleep. Fourteen participants were first tested after a normal day, followed by two 11-h periods of immobilization, either with concomitant MI treatment or control tasks. Data revealed that MI prevented the consequences of immobilization: (i) alteration of the sensorimotor representation of hands, (ii) decrease of cortical excitability over the primary motor cortex (M1) contralateral to arm-immobilization, and (iii) reduction of sleep spindles over both M1s. Furthermore, (iv) the time spent in REM sleep was significantly longer after MI. These results support that implementing MI during immobilization can limit the deleterious effects of limb disuse, at several levels of sensorimotor functioning.
Dietary fat promotes antibiotic-induced Clostridioides difficile mortality in mice
Authors: Hazleton Keith Z. , Martin Casey G. , Orlicky David J , Arnolds Kathleen L. , Nusbacher Nichole M. , Moreno-Huizar Nancy , Armstrong Michael , Reisdorph Nichole , Lozupone Catherine A. 
Published: November 2019

AbstractClostridioides difficile infection (CDI), is the leading cause of hospital-acquired diarrhea and emerging evidence has linked dietary components with CDI pathogenesis, suggesting that dietary modulation may be an effective strategy for prevention. Here, we show that mice fed a high-fat/low-fiber “Western type” diet (WD) had dramatically increased mortality in a murine model of antibiotic-induced CDI compared to a low-fat/low-fiber (LF/LF) diet and standard mouse chow controls. We found that the WD had a pro- C. difficile bile acid composition that was driven in part by higher levels of primary bile acids that are produced to digest fat, and a lower level of secondary bile acids that are produced by the gut microbiome. This lack of secondary bile acids was associated with a greater disturbance to the gut microbiome with antibiotics in both the WD and LF/LF diet compared to mouse chow. Mice fed the WD also had the highest level of toxin TcdA just prior to the onset of mortality, but not of TcdB or increased inflammation. These findings indicate that dietary intervention to decrease fat may complement previously proposed dietary intervention strategies to prevent CDI in high-risk individuals.One Sentence SummaryA high-fat/low-fiber Western type diet promoted mortality in a mouse model of antibiotic-induced C. difficile infection compared to a low-fat/low-fiber diet and chow diet, suggesting that lower dietary fat may be an effective strategy for preventing C. difficile pathology.