bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of AMP-Activated Protein Kinase by A769662 Ameliorates Sepsis-Induced Acute Lung Injury in Adult Mice
Authors: Kitzmiller Laura , Ledford John R. , Hake Paul W. , O’Connor Michael , Piraino Giovanna , Zingarelli Basilia 
Published: December 2018

ABSTRACT
A serious consequence of sepsis is acute lung injury, whose severity is particularly impacted by the age of the patient. AMP-activated protein kinase (AMPK) is a crucial regulator of cellular metabolism, which controls mitochondrial biogenesis and autophagy. Here, we investigated the effect of pharmacological activation of AMPK with A769662 on lung injury by using a model that would preferably mimic the clinical condition of adult patients. Male C57BL/6 retired breeder mice (7–9 months old) were subjected to sepsis by cecal ligation and puncture (CLP). Mice received vehicle or A769662 (10 mg/kg) intraperitoneally at 1 h after CLP. At 6 h after CLP, vehicle-treated mice exhibited severe lung injury and elevation of plasma pro-inflammatory cytokines when compared with control mice. At molecular analysis, lung injury was associated with downregulation of AMPKα1/α2 catalytic subunits and reduced phosphorylation of AMPKβ1 regulatory subunit. Treatment with A769662 ameliorated lung architecture, reduced bacterial load in lung and blood, and attenuated plasma levels of interleukin-6. This protective effect was associated with nuclear phosphorylation of AMPKα1/α2 and AMPKβ1, increased nuclear expression of peroxisome proliferator-activated receptor γ co-activator-α and increased autophagy, as evaluated by the light-chain (LC)3B-I and LC3B-II content, without changes in sirtuin-1 cellular dynamics. Treatment with A769662 alone or in combination with the antimicrobial agent imipenem (25 mg/kg) increased survival rate (29% and 51%, respectively) when compared with vehicle treatment (10%) at 7 days after CLP. These data suggest that pharmacological activation of AMPK might be a beneficial approach for the treatment of sepsis in adult population.
Redefining postinjury fibrinolysis phenotypes using two viscoelastic assays
Authors: Stettler Gregory R. , Moore Ernest E. , Moore Hunter B. , Nunns Geoffrey R. , Silliman Christopher C. , Banerjee Anirban , Sauaia Angela 
Published: December 2018

INTRODUCTION
Fibrinolysis was initially defined using rapid thrombelastography (rTEG). The cutoffs for the pathologic extremes of the fibrinolytic system, hyperfibrinolysis and shutdown, were both defined based on association with mortality. We propose to redefine these phenotypes for both TEG and for rotational thrombelastometry, the other commonly used viscoelastic assay.

METHODS
Rotational thrombelastometry, rTEG, and clinical data were prospectively collected on trauma patients admitted to an urban Level I trauma center from 2010 to 2016. Hyperfibrinolysis was defined as the Youden index from EXTEM-clot lysis index 60 minutes after clotting time (CLI60) and rTEG-fibrinolysis 30 minutes after achieving MA (LY30) for predicting massive transfusion (>10 red blood cell units, or death per 6 hours after injury) as a surrogate for severe bleeding. Patients identified as having hyperfibrinolysis were then removed from the data set, and the cutoff for fibrinolysis shutdown was derived as the optimal cutoff for predicting mortality in the remaining patients.

RESULTS
Overall, 216 patients (median age, 36 years (interquartile range, 27–49 years), 82% men, 58% blunt injury) were included. Of these, 16% required massive transfusion, and 12.5% died. Rapid thrombelastography phenotypes were redefined as hyperfibrinolysis: rTEG-LY30 greater than7.7%, physiologic rTEG-LY30 0.6% to7.6%, and shutdown rTEG-LY30 less than 0.6%. EXTEM-CLI60 fibrinolysis phenotypes were hyperfibrinolysis CLI60 less than 82%, physiologic (CLI60, 82–97.9%), and shutdown (CLI60 > 98%). Weighted kappa statistics revealed moderate agreement between rotational thrombelastometry– and rTEG-defined fibrinolysis (k = 0.51; 95% confidence interval, 0.39–0.63), with disagreement mostly in the shutdown and physiologic categories.

CONCLUSION
We confirmed the U-shaped distribution of death related to fibrinolysis system abnormalities. Both rTEG LY30 and EXTEM CLI60 can identify the spectrum of fibrinolytic phenotypes, have moderate agreement, and can be used to guide hemostatic resuscitation.

LEVEL OF EVIDENCE
Diagnostic study, level III.
Outcomes after single-look trauma laparotomy: A large population-based study
Authors: Bowie Jason M. , Badiee Jayraan , Calvo Richard Y. , Sise Michael J. , Wessels Lyndsey E. , Butler William J. , Dunne Casey E. , Sise C. Beth , Bansal Vishal 
Published: December 2018

BACKGROUND
Outcomes following damage control laparotomy for trauma have been studied in detail. However, outcomes following a single operation, or “single-look trauma laparotomy” (SLTL), have not. We evaluated the association between SLTL and both short-term and long-term outcomes in a large population-based data set.

METHODS
The California Office of Statewide Health Planning and Development patient discharge database was evaluated for calendar years 2007 through 2014. Injured patients with SLTL during their index admission were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. Diagnosis and procedure codes were used to identify specific abdominal organ injuries, surgical interventions, and perioperative complications. Subsequent acute care admissions were examined for postoperative complications and related surgical interventions. Clinical characteristics, injuries, surgical interventions, and outcomes were analyzed by mechanism of injury.

RESULTS
There were 2113 patients with SLTL during their index admission; 712 (33.7%) had at least one readmission to an acute care facility. Median time to first readmission was 110 days. Penetrating mechanism was more common than blunt (60.6% vs. 39.4%). Compared to patients with penetrating injury, blunt-injured patients had a significantly higher median Injury Severity Score (9 vs. 18, p < 0.0001) and a significantly higher mortality rate during the index admission (4.1% vs. 27.0%, p < 0.0001). More than 30% of SLTL patients requiring readmission had a surgery-related complication. The most common primary reasons for readmission were bowel obstruction (17.7%), incisional hernia (11.8%), and infection (9.1%). There was no significant association between mechanism of injury and development of surgery-related complications requiring readmission.

CONCLUSIONS
Patients with SLTL had postinjury morbidity and mortality, and more than 30% required readmission. Complication rates for SLTL were comparable to those reported for emergency general surgery procedures. Patients should be educated on signs and symptoms of the most common complications before discharge following SLTL. Further investigation should focus on the factors associated with the development of these complications.

LEVEL OF EVIDENCE
Prognostic and epidemiologic study, level III.
Highly reproducible 16S sequencing facilitates measurement of host genetic influences on the stickleback gut microbiome
Authors: Small Clayton M. , Currey Mark , Beck Emily A. , Bassham Susan , Cresko William A. 
Published: December 2018

AbstractMulticellular organisms interact with resident microbes in important ways, and a better understanding of host-microbe interactions is aided by tools such as high-throughput 16S sequencing. However, rigorous evaluation of the veracity of these tools in a different context from which they were developed has often lagged behind. Our goal was to perform one such critical test by examining how variation in tissue preparation and DNA isolation could affect inferences about gut microbiome variation between two genetically divergent lines of threespine stickleback fish maintained in the same lab environment. Using careful experimental design and intensive sampling of individuals, we addressed technical and biological sources of variation in 16S-based estimates of microbial diversity. After employing a two-tiered bead beating approach consisting of tissue homogenization followed by microbial lysis in subsamples, we found an extremely minor effect of DNA isolation protocol relative to among-host microbial diversity differences. Individual abundance estimates for rare OTUs, however, showed much lower reproducibility. We found that the stickleback gut microbiome was highly variable, even among siblings housed together, but that an effect of host genotype (stickleback lineage) was detectable for some microbial taxa. Our findings demonstrate the importance of appropriately quantifying biological and technical variance components when attempting to understand major influences on high-throughput microbiome data.
Biased visibility in HiC datasets marks dynamically regulated condensed and decondensed chromatin states genome-wide
Authors: Chandradoss Keerthivasan Raanin , Guthikonda Prashanth Kumar , Kethavath Srinivas , Dass Monika , Singh Harpreet , Nayak Rakhee , Kurukuti Sreenivasulu , Sandhu Kuljeet Singh 
Published: December 2018

AbstractProximity ligation based techniques, like HiC, involve restriction digestion followed by ligation of formaldehyde cross-linked chromatin. We showed that the HiC datasets have significant bias due to differential accessibility of chromatin domains to restriction endonucleases. Through analysis of lamina-associated domains (LADs), inactive X-chromosome in mammals and polytene bands in fly, we established that the DNA in condensed chromatin had lesser accessibility to nucleases used in HiC as compared to that in decondensed chromatin. The observed bias was independent of known systematic biases attributed to length and GC content of the restriction fragments and was not appropriately corrected by computational methods. We identified novel condensed domains outside LADs, which were bordered by insulators and were dynamically associated with the developmentally regulated epigenetic and transcriptional states. Our observations suggested that the corrected read counts of existing HiC datasets can be reliably repurposed to study the dynamics of chromatin condensation and decondensation and that the existing HiC datasets should be interpreted with cautions.
Analysis of the structural variability of topologically associated domains as revealed by Hi-C
Authors: Sauerwald Natalie , Singhal Akshat , Kingsford Carl 
Published: December 2018

AbstractThree-dimensional chromosome structure plays an integral role in gene expression and regulation, replication timing, and other cellular processes. Topologically associating domains (TADs), one of the building blocks of chromosome structure, are genomic regions with higher contact frequencies within the region than outside the region. A central question is the degree to which TADs are conserved or vary between conditions. We analyze a set of 137 Hi-C samples from 9 different studies under 3 measures in order to quantify the effects of various sources of biological and experimental variation. We observe significant variation in TAD sets between both non-replicate and replicate samples, and show that this variability does not seem to come from genetic sequence differences. The effects of experimental protocol differences are also measured, demonstrating that samples can have protocol-specific structural changes, but that TADs are generally robust to lab-specific differences. This study represents a systematic quantification of the key factors influencing comparisons of chromosome structure.
Terminal Reproductive Investment, Physiological Trade-offs and Pleiotropic Effects: Their effects produce complex immune/reproductive interactions in the cricket Gryllus texensis
Authors: Miyashita Atsushi , Lee Ting Yat Marco , McMillan Laura E , Easy Russell , Adamo Shelley A 
Published: December 2018

1.	Should females increase or decrease reproduction when attacked by pathogens? Two hypotheses provide opposite predictions. Terminal reproductive investment theory predicts an increase in reproduction, but hypothesized physiological trade-offs between reproduction and immune function might be expected to produce a decrease. There is evidence for both hypotheses. What determines the choice between the two responses remains unclear. We examine the effect of age on the reproductive response to immune challenge in long-wing females of the Texas field cricket, Gryllus texensis, when fed an ecologically valid (limited) diet.
2.	The limited diet reduced reproductive output. However, immune challenge had no effect on their reproductive output either in young or middle-aged crickets, which is contrary to either prediction.
3.	Flight muscle maintenance correlated negatively with reproductive output, suggesting a physiological trade-off between flight muscle maintenance and reproduction. Within the long-wing variant there was considerable variability in flight muscle maintenance. This variability may mask physiological trade-offs between immunity and reproduction.
4.	Middle-aged crickets had higher total phenoloxidase (PO) activity in their hemolymph, compared to young females, which is contrary to the terminal investment theory. Given that PO is involved in both immunity and reproduction, the increased PO may reflect simultaneous investment in both functions.
5.	We identified four proPO transcripts in a published RNA-seq dataset (transcriptome). Three of the proPO genes were expressed either in the fat body or the ovaries (supporting the hypothesis that PO is bifunctional); however, the two organs expressed different subsets. The possible bifunctionality of PO suggests that it may not be an appropriate immune measure for immune/reproductive trade-offs in some species.
6.	Increasing age may not cue terminal reproductive investment prior to senescence.
TDP-43 oligomers detected as initial intermediate species during aggregate formation
Authors: French Rachel L. , Reeb Ashley N. , Aligireddy Himani , Kedia Niraja , Dhavale Dhruva D. , Grese Zachary R. , Kotzbauer Paul T. , Bieschke Jan , Ayala Yuna M. 
Published: December 2018

ABSTRACTAggregates of the RNA binding protein TDP-43 are a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which are neurodegenerative disorders with overlapping clinical, genetic and pathological features. Mutations in the TDP-43 gene are causative of ALS, supporting its central role in pathogenesis. The process of TDP-43 aggregation remains poorly understood and whether this includes formation of intermediate complexes is unknown. We characterized aggregates derived from purified TDP-43 as a function of time and analyzed them under semi-denaturing conditions. Our assays identified oligomeric complexes at the initial time points prior to the formation of large aggregates, suggesting that ordered oligomerization is an intermediate step of TDP-43 aggregation. In addition, we analyzed liquid-liquid phase separation of TDP-43 and detected similar oligomeric assembly upon the maturation of liquid droplets into solid-like fibrils. These results strongly suggest that the oligomers form during the early steps of TDP-43 misfolding. Importantly, ALS-linked mutations A315T and M337V significantly accelerate aggregation, rapidly decreasing the monomeric population and shortening the oligomeric phase. We also show that the aggregates generated from purified protein seed intracellular aggregation, which is detected by established markers of TDP-43 pathology. Remarkably, cytoplasmic aggregate propagation is detected earlier with A315T and M337V and is 50% more widespread than with wild-type aggregates. Our findings provide evidence for a controlled process of TDP-43 self-assembly into intermediate structures that provide a scaffold for aggregation. This process is altered by ALS-linked mutations, underscoring the role of perturbations in TDP-43 homeostasis in protein aggregation and ALS-FTD pathogenesis.
SGK regulates pH increase and cyclin B-Cdk1 activation to resume meiosis in starfish ovarian oocytes
Authors: Hosoda Enako , Hiraoka Daisaku , Hirohashi Noritaka , Omi Saki , Kishimoto Takeo , Chiba Kazuyoshi 
Published: December 2018

AbstractTight regulation of intracellular pH (pHi) is essential for biological processes. Fully-grown oocytes, having a large nucleus called the germinal vesicle, arrest at meiotic prophase-I. Upon hormonal stimulus, oocytes resume meiosis to acquire fertilizability. At this time, pHi increases through Na+/H+ exchanger activity. However, regulation and function of this change remains obscure. Here we show that in starfish oocytes, serum- and glucocorticoid-regulated kinase (SGK) is activated by the PI3K/TORC2/PDK1 signaling after hormonal stimulus, and is required for the pHi increase and cyclin B–Cdk1 activation. Furthermore, when we clamped pHi at 6.7, corresponding to the pHi of unstimulated ovarian oocytes, hormonal stimulus normally induced cyclin B–Cdk1 activation; thereafter, oocytes initiated germinal vesicle breakdown (GVBD), but failed to complete it. Thus, SGK-dependent pHi increase is likely prerequisite for completion of GVBD in ovarian oocytes. We propose a model that SGK drives meiotic resumption through concomitant regulation of pHi and the cell-cycle machinery.
Differential cell fates of muscle stem cells are accompanied by symmetric segregation of canonical H3 histones in vivo
Authors: Evano Brendan , Carrou Gilles Le , Almouzni Geneviève , Tajbakhsh Shahragim 
Published: December 2018

AbstractStem cells are maintained through symmetric or asymmetric cell divisions. While various mechanisms initiate asymmetric cell fates during mitosis, possible epigenetic control of this process has emerged recently. The asymmetrical distribution of a canonical histone H3 variant during mitosis in fly germline has suggested a role for partitioning old and new nucleosomes in asymmetric cell fates. Here, we provide resources for single cell assays and show the asymmetric segregation of transcription factors along with old and new DNA in mouse muscle stem cells ex vivo and in vivo. However, these differential fate outcomes contrast with a symmetric distribution of the canonical H3.1 vertebrate variant. These findings point to different evolutionary mechanisms operating in fly germline stem cells and vertebrate somatic stem cells to mitigate epigenetic regulation of asymmetric cell fates.
Interstellar medium magnetic field in bow shock modelling
Authors: Kotlarz Jan , Ratkiewicz Romana , Konior Wojciech 
Published: December 2018

Purpose
This paper aims to demonstrate the impact of interstellar (IS) magnetic field on stellar shocks existence, shape and size in the stellar wind (SW) vs interstellar medium (ISM) numerical models.

Design/methodology/approach
Comparison of hydrodynamics (HD) and magnetohydrodynamic (MHD) models results with or without ISM magnetic field, its intensity and ISM parameters.

Findings
ISM magnetic field facilitates formation and stabilises bow shocks around all astrophysical objects. ISM magnetic field may also be one of the reasons for a bow shock existence around the Sun.

Practical implications
ISM magnetic field should be implemented in MHD and future kinetic numerical models of the SW interaction with ISM plasma.

Originality/value
This paper presents the results of HD and MHD models of bow shocks and the importance of ISM magnetic field implementation, according to astronomical bow shock observations. The study also presents a review of the most important papers showing the numerical results of bow shock formation.
Innovative time-based separation procedures for civil RPAS integration
Authors: Fusaro Roberta , Viola Nicole , Cresto Aleina Sara , Di Meo Giovanni Antonio 
Published: December 2018

Purpose
This paper aims to suggest feasible solutions to overcome the problem of unmanned aerial vehicles integration within the existing airspace.

Design/methodology/approach
It envisages innovative time-based separation procedures that will enhance the integration in the future air traffic management (ATM) system of next generation of large remotely piloted aircraft system (RPAS). 4D navigation and dynamic mobile area concepts, both proposed in the framework of Single European Sky ATM Research program, are brought together to hypothesize innovative time-based separation procedures aiming at promoting integration of RPAS in the future ATM system.

Findings
Benefits of proposed procedures, mainly evaluated in terms of volume reduction of segregated airspace, are quantitatively analyzed on the basis of realistic operational scenarios focusing on monitoring activities in both nominal and emergency conditions. Eventually, the major limits of time-based separation for RPAS are investigated.

Practical implications
The implementation of the envisaged procedures will be a key enabler in RPAS integration in future ATM integration.

Originality/value
In the current ATM scenario, separation of RPAS from air traffic is ensured by segregating a large amount of airspace areas with fixed dimensions, dramatically limiting the activities of these vehicles.
Evaluating impact of entrepreneurship education programs
Authors: Daneshjoovash Seyedeh Khatereh , Hosseini Mirza Hassan 
Published: December 2018

Purpose
The purpose of this paper is to evaluate the impact of Entrepreneurship Education Programs (EEPs) from students’ and educators’ viewpoint to improve the quality of EEPs.

Design/methodology/approach
This research applies a qualitative-quantitative methodology. Its sample is included 291 students were selected randomly and 35 educators were chosen by convenience technique from universities of Applied Science and Technology of Iran.

Findings
The results revealed that essence of EEPs had a positive direct effect on objectives and content of EEPs; objectives and content of EEPs had a positive direct effect on methods of EEPs; essence of EEPs had a positive direct effect on impact of EEPs; and essence of EEPs had a positive indirect effect on methods through objectives and content based on students’ and educators’ perspective. Moreover, as opposed to educators’, students believed that methods of EEPs have not a positive direct effect on impact, while educators were opponent to students approach about the positive direct effect of essence of EEPs on methods.

Research limitations/implications
The study was limited to Applied Science and Technology universities were selected by convenience sampling method. Similar studies in other universities are needed to be conducted by simple random sampling to evaluate EEPs.

Practical implications
The study recommends policy-makers to be aware of students’ needs of EEPs’ methods, as well inform educators about effective and initiative methods.

Originality/value
Evaluating impact of EEPs based on demand and supply-side viewpoint is the first study conducted in Applied Science and Technology universities of Iran.