bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phagocytosis by Fibrocytes as a Mechanism to Decrease Bacterial Burden and Increase Survival in Sepsis
Authors: Collins Dalis , Fry Christopher , Moore Bethany B. , Nemzek Jean A. 
Published: April 2018

ABSTRACT
Fibrocytes are unique cells with innate and adaptive immune functions, but these mechanisms have not been fully explored. The aim of this study was to explain the mechanism by which adoptive transfer of exogenous fibrocytes improved bacterial clearance and increased sepsis survival. Initial flow cytometry-based, in vitro assays demonstrated phagocytosis by fibrocytes and intracellular bacterial killing was confirmed by direct plating of cell lysates after exposure to live bacteria. Intravenous adoptive transfer of fibrocytes at the time of cecal ligation and puncture (CLP) or 2 h after CLP in mice increased survivability. Decreased intraperitoneal bacterial burden was also observed. Quantification of peritoneal cell populations using flow cytometry demonstrated transferred and endogenous fibrocytes were significantly increased after CLP, while macrophage and neutrophil numbers were unchanged. To determine the impact in vivo, fluorescently labeled, killed bacteria were injected i.p. into mice 10 h after CLP or sham surgery ± adoptive transfer. Two hours later, flow cytometry of peritoneal cell populations after CLP alone revealed increased phagocytosis by macrophages, neutrophils, and endogenous fibrocytes. Transferred fibrocytes had significantly increased phagocytic activity in the septic peritoneum compared with sham and greater activity than any other cell type. Therefore, adoptive transfer may enhance bacterial clearance in early sepsis through the cumulative effects of endogenous and transferred fibrocytes rather than modulating the function of other endogenous phagocytes. Direct phagocytic activity coupled with previously described influences on T cell responses may explain the benefits of fibrocyte transfer in sepsis.
Chronic Alcohol Ingestion Worsens Survival and Alters Gut Epithelial Apoptosis and CD8+ T Cell Function After Pseudomonas Aeruginosa Pneumonia-Induced Sepsis
Authors: Klingensmith Nathan J. , Fay Katherine T. , Lyons John D. , Chen Ching-wen , Otani Shunsuke , Liang Zhe , Chihade Deena B. , Burd Eileen M. , Ford Mandy L. , Coopersmith Craig M. 
Published: April 2018

ABSTRACT
Mortality is higher in septic patients with a history of alcohol use disorder than in septic patients without a history of chronic alcohol usage. We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4+ T cells without alterations in CD8+ T cell function. The purpose of this study was to determine whether this represents a common host response to the combination of alcohol and sepsis by creating a new model in which mice with chronic alcohol ingestion were subjected to a different model of sepsis. C57Bl/6 mice were randomized to receive either alcohol or water for 12 weeks and then subjected to Pseudomonas aeruginosa pneumonia. Mice were sacrificed either 24 hours after the onset of sepsis or followed for survival. Alcohol-fed septic mice had significantly higher 7-day mortality than water-fed septic mice (96% vs 58%). This was associated with a 5-fold increase in intestinal apoptosis in alcohol-fed septic animals, accompanied by an increase in the pro-apoptotic protein Bax. Serum IL-6 levels were higher and IL-2 levels were lower in alcohol-fed septic mice. In contrast, CD8+ T cell frequency was lower in alcohol-fed mice than water-fed septic mice, associated with increased production of IFNγ and TNF in stimulated splenocytes. No significant differences were noted in CD4+ T cells, lung injury or bacteremia. Mice with chronic alcohol ingestion thus have increased mortality regardless of their septic insult, associated with changes in both the gut and the immune system.
The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock
Authors: Gröger Michael , Wepler Martin , Wachter Ulrich , Merz Tamara , McCook Oscar , Kress Sandra , Lukaschewski Britta , Hafner Sebastian , Huber-Lang Markus , Calzia Enrico , Georgieff Michael , Nagahara Noriyuki , Szabó Csaba , Radermacher Peter , Hartmann Clair 
Published: April 2018

ABSTRACT

Introduction:
Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock.

Methods:
Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption.

Results:
3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma.

Conclusions:
In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.
Effect of Prehospital Red Blood Cell Transfusion on Mortality and Time of Death in Civilian Trauma Patients
Authors: Rehn Marius , Weaver Anne , Brohi Karim , Eshelby Sarah , Green Laura , Røislien Jo , Lockey David J. 
Published: April 2018

ABSTRACT

Background:
Current management principles of hemorrhagic shock after trauma emphasize earlier transfusion therapy to prevent dilution of clotting factors and correct coagulopathy. London's Air Ambulance (LAA) was the first UK civilian prehospital service to routinely offer prehospital red blood cell (RBC) transfusion (phRTx). We investigated the effect of phRTx on mortality.

Methods:
Retrospective trauma database study comparing mortality before implementation with after implementation of phRTx in exsanguinating trauma patients. Univariate logistic regression was performed for the unadjusted association between phRTx and mortality was performed, and multiple logistic regression adjusting for potential confounders.

Results:
We identified 623 subjects with suspected major hemorrhage. We excluded 84 (13.5%) patients due to missing data on survival status. Overall 187 (62.3%) patients died in the before phRTx period and 143 (59.8%) died in the after phRTx group. There was no significant improvement in overall survival after the introduction of phRTx (P = 0.554). Examination of prehospital mortality demonstrated 126 deaths in the pre-phRTx group (42.2%) and 66 deaths in the RBC administered group (27.6%). There was a significant reduction in prehospital mortality in the group who received RBC (P < 0.001).

Conclusions:
phRTx was associated with increased survival to hospital, but not overall survival. The “delay death” effect of phRTx carries an impetus to further develop inhospital strategies to improve survival in severely bleeding patients.
Occupational exposure during emergency department thoracotomy: A prospective, multi-institution study
Authors: Nunn Andrew , Prakash Priya , Inaba Kenji , Escalante Alvarez , Maher Zoë , Yamaguchi Seiji , Kim Dennis Y. , Maciel James , Chiu William C. , Drumheller Byron , Hazelton Joshua P. , Mukherjee Kaushik , Luo-Owen Xian , Nygaard Rachel M. , Marek Ashley P. , Morse Bryan C. , Fitzgerald Caitlin A. , Bosarge Patrick L. , Jawa Randeep S. , Rowell Susan E. , Magnotti Louis J. , Ong Adrian W. , Brahmbhatt Tejal S. , Grossman Michael D. , Seamon Mark J. 
Published: April 2018

BACKGROUND
Occupational exposure is an important consideration during emergency department thoracotomy (EDT). While human immunodeficiency virus/hepatitis prevalence in trauma patients (0–16.8%) and occupational exposure rates during operative trauma procedures (1.9–18.0%) have been reported, exposure risk during EDT is unknown. We hypothesized that occupational exposure risk during EDT would be greater than other operative trauma procedures.

METHODS
A prospective, observational study at 16 US trauma centers was performed (2015–2016). All bedside EDT resuscitation providers were surveyed with a standardized data collection tool and risk factors analyzed with respect to the primary end point, EDT occupational exposure (percutaneous injury, mucous membrane, open wound, or eye splash). Provider and patient variables and outcomes were evaluated with single and multivariable logistic regression analyses.

RESULTS
One thousand three hundred sixty participants (23% attending, 59% trainee, 11% nurse, 7% other) were surveyed after 305 EDTs (gunshot wound, 68%; prehospital cardiopulmonary resuscitation, 57%; emergency department signs of life, 37%), of which 15 patients survived (13 neurologically intact) their hospitalization. Overall, 22 occupational exposures were documented, resulting in an exposure rate of 7.2% (95% confidence interval [CI], 4.7–10.5%) per EDT and 1.6% (95% CI, 1.0–2.4%) per participant. No differences in trauma center level, number of participants, or hours worked were identified. Providers with exposures were primarily trainees (68%) with percutaneous injuries (86%) during the thoracotomy (73%). Full precautions were utilized in only 46% of exposed providers, while multiple variable logistic regression determined that each personal protective equipment item utilized during EDT correlated with a 34% decreased risk of occupational exposure (odds ratio, 0.66; 95% CI, 0.48–0.91; p = 0.010).

CONCLUSIONS
Our results suggest that the risk of occupational exposure should not deter providers from performing EDT. Despite the small risk of viral transmission, our data revealed practices that may place health care providers at unnecessary risk of occupational exposure. Regardless of the lifesaving nature of the procedure, improved universal precaution compliance with personal protective equipment is paramount and would further minimize occupational exposure risks during EDT.

LEVEL OF EVIDENCE
Therapeutic/care management study, level III.
αB-crystallin inhibits amyloidogenesis by disassembling aggregation nuclei
Authors: Tkachenko Olga , Benesch Justin L.P. , Baldwin Andrew J. 
Published: April 2018

AbstractAmyloid formation is implicated in a range of neurodegenerative conditions including Alzheimer’s and Parkinson’s diseases. The small heat-shock protein αB-crystallin (αBC) is associated with both, and directly inhibits amyloid formation in vitro and its toxicity in cells. Studying the mechanism of aggregation inhibition is challenging owing to sample heterogeneity and the dynamic nature of the process. Here, by means of NMR spectroscopy and chemical kinetics, we establish the mechanism by which the protein α-lactalbumin aggregates and forms amyloid, and how this is inhibited by αBC. In particular, we characterise the lifetime of the unstable aggregation nucleus, and determine that this species is specifically destabilised by αBC. This mechanism allows the chaperone to delay the onset of aggregation, although it is overwhelmed on longer timescales. The methodology we present provides a mechanistic understanding of how αBC reduces the toxicity of amyloids, and is widely applicable to other complex mixtures.
A prior-based approach for hypothesis comparison and its utility to discern among temporal scenarios of divergence
Authors: Zarza Eugenia , O’Hara Robert B. , Klussmann-Kolb Annette , Pfenninger Markus 
Published: April 2018

AbstractOne of the major problems in evolutionary biology is to elucidate the relationships between historical events and the tempo and mode of lineage divergence. The development of relaxed molecular clock models and the increasing availability of DNA sequences resulted in more accurate estimations of taxa divergence times. However, finding the link between competing historical events and divergence is still challenging. Here we investigate assigning constrained-age priors to nodes of interest in a time-calibrated phylogeny as a means of hypothesis comparison. These priors are equivalent to historic scenarios for lineage origin. The hypothesis that best explains the data can be selected by comparing the likelihood values of the competing hypotheses, modelled with different priors. A simulation approach was taken to evaluate the performance of the prior-based method and to compare it with an unconstrained approach. We explored the effect of DNA sequence length and the temporal placement and span of competing hypotheses (i.e. historic scenarios) on selection of the correct hypothesis and the strength of the inference. Competing hypotheses were compared applying a posterior simulation analogue of the Akaike Information Criterion and Bayes factors (obtained after calculation of the marginal likelihood with three estimators: Harmonic Mean, Stepping Stone and Path Sampling). We illustrate the potential application of the prior-based method on an empirical data set to compare competing geological hypotheses explaining the biogeographic patterns inPleurodelesnewts. The correct hypothesis was selected on average 89% times. The best performance was observed with DNA sequence length of 3500-10000 bp. The prior-based method is most reliable when the hypotheses compared are not temporally too close. The strongest inferences were obtained when using the Stepping Stone and Path Sampling estimators. The prior-based approach proved effective in discriminating between competing hypotheses when used on empirical data. The unconstrained analyses performed well but it probably requires additional computational effort. Researchers applying this approach should rely only on inferences with moderate to strong support. The prior-based approach could be applied on biogeographical and phylogeographical studies where robust methods for historical inferences are still lacking.
Rules Governing Perception of Multiple Phosphenes by Human Observers
Authors: Bosking William , Foster Brett , Sun Ping , Beauchamp Mike , Yoshor Daniel 
Published: April 2018

AbstractStimulation of single sites in primary visual cortex results in the perception of a small flash of light known as a phosphene. Little is known about how phosphenes from multiple electrodes can be combined to form perception of coherent patterns. Here we examine the percepts reported by human observers as various spatial configurations of 2 to 5 electrodes in visual cortex were stimulated simultaneously. When two electrodes were stimulated simultaneously, subjects reliably perceived either one or two phosphenes depending on the physical distance separating the electrodes. In cases where two phosphenes were perceived, they were located in the same visual field location as when the two electrodes were stimulated separately. Adding a third electrode produced similar results. In several subjects, we obtained combination of 4 to 5 electrodes that generated individual phosphenes when stimulated concurrently. Subjects were able to reliably discriminate between different multiple electrode stimulation patterns that were presented in random order. These results demonstrate that simple pattern information can be conveyed to subjects with surface electrodes spaced at millimeters apart on the cortex.
HIR-1 Mediates Response to Hypoxia-Induced Extracellular Matrix Remodeling
Authors: Vozdek Roman , Long Yong , Ma Dengke K. 
Published: April 2018

ABSTRACTInadequate tissue oxygen, or hypoxia, is a central concept in pathophysiology of ischemic disorders and cancer. Hypoxia promotes extracellular matrix (ECM) remodeling, cellular metabolic adaptation and metastasis. To determine how cells respond to hypoxia-induced ECM remodeling, we performed a large-scale forward genetic screen inC.elegans. We identified a previously uncharacterized receptor tyrosine kinase (RTK) named HIR-1 as a key mediator in a pathway that orchestrates transcriptional responses to hypoxia-induced ECM remodeling. Impaired ECM integrity caused by hypoxia or deficiency of the oxygen-dependent procollagen hydroxylases, heme peroxidases or cuticular collagens activates gene expression through inhibition of HIR-1. Genetic suppressor screens identified NHR-49 and MDT-15 as transcriptional regulators downstream of HIR-1. Cellular responses through HIR-1 maintain ECM homeostasis and promote animal adaptation to severe hypoxia. We propose thatC.elegansHIR-1 defines an unprecedented type of RTK that mediates responses to hypoxia-induced ECM remodeling by mechanisms that are likely conserved in other organisms.ONE-SENTENCE SUMMARYA regulatory pathway for ECM homeostasis underlies adaptation to hypoxia and re-oxygenation
DraftAphaenogastergenomes expand our view of ant genome size variation across climate gradients
Authors: Lau Matthew K. , Ellison Aaron M. , Nguyen Andrew D. , Penick Clint , DeMarco Bernice , Gotelli Nicholas J. , Sanders Nathan J. , Dunn Robert R. , Cahan Sara Helms 
Published: April 2018

ABSTRACTGiven the abundance, broad distribution, and diversity of roles that ants play in many ecosystems, they are an ideal group to serve as ecosystem indicators of climatic change. At present, only a few whole-genome sequences of ants are available (19 of>16,000 species), mostly from tropical and sub-tropical species. To address this limited sampling, we sequenced genomes of temperate-latitude species from the genusAphaenogaster, a genus with important seed dispersers. In total, we sampled seven colonies of six species:A. ashmeadi,A. floridana,A. fulva,A. miamiana,A. picea, andA. rudis. The geographic ranges of these species collectively span eastern North America from southern Florida to southern Canada, which encompasses a latitudinal gradient in which many climatic variables are changing rapidly. For the six genomes, we assembled an average of 271,039 contigs into 47,337 scaffolds. The mean genome size was 370.5 Mb, ranging from 310.3 to 429.7, which is comparable to that of other sequenced ant genomes (212.8 to 396.0 Mb) and flow cytometry estimates (210.7 to 690.4 Mb). In an analysis of currently sequenced ant genomes and the newAphaenogastersequences, we found that after controlling for both spatial autocorrelation and phylogenetics ant genome size was marginally correlated with sample site climate similarity. Of all examined climate variables, minimum temperature showed the strongest correlation with genome size, with ants from locations with colder minimum temperatures having larger genomes. These results suggest that temperature extremes could be a selective force acting on ant genomes and point to the need for more extensive sequencing of ant genomes.
A new targeted capture method using bacterial artificial chromosome (BAC) libraries as baits for sequencing relatively large genes
Authors: Koganebuchi Kae , Gakuhari Takashi , Takeshima Hirohiko , Sato Kimitoshi , Fujii Kiyotaka , Kumabe Toshihiro , Kasagi Satoshi , Sato Takehiro , Tajima Atsushi , Shibata Hiroki , Ogawa Motoyuki , Oota Hiroki 
Published: April 2018

AbstractTo analyze a specific genome region using next-generation sequencing technologies, the enrichment of DNA libraries with targeted capture methods has been standardized. For enrichment of mitochondrial genome, a previous study developed an original targeted capture method that use baits constructed from long-range polymerase chain reaction (PCR) amplicons, common laboratory reagents, and equipment. In this study, a new targeted capture method is presented, that of bacterial artificial chromosome (BAC) double capture (BDC), modifying the previous method, but using BAC libraries as baits for sequencing a relatively large gene. We applied the BDC approach for the 214 kb autosomal region, ring finger protein 213, which is the susceptibility gene of moyamoya disease (MMD). To evaluate the reliability of BDC, cost and data quality were compared with those of a commercial kit. While the ratio of duplicate reads was higher, the cost was less than that of the commercial kit. The data quality was sufficiently the same as that of the kit. Thus, BDC can be an easy, low-cost, and useful method for analyzing individual genome region with substantial length.