bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes and predictors of harmful relapse following liver transplantation for alcoholic liver disease in an Australian population
Authors: Wigg Alan J. , Mangira Dileep , Chen John W. , Woodman Richard W. 
Published: March 2017

BackgroundLimited studies of patient survival and alcoholic relapse following transplantation for alcoholic liver disease have been described in Australian populations.AimTo describe these outcomes in an Australian population, to determine the association between harmful alcoholic relapse and patient survival, and to examine pre‐transplant variables associated with harmful relapse.MethodsSingle centre, retrospective review of consecutive patients transplanted at the South Australian Liver Transplant Unit. Relapse was identified by an independent investigator using case note review and confidential patient questionnaire.ResultsA total of 87 patients (median age 52 years, 84% male, median Model for End‐Stage Liver Disease (MELD) score 18) was included in the study with a median follow‐up time of 50 months. The 1‐, 3‐ and 5‐year survival of patients was 93.1, 87.4 and 82.0% respectively. Two deaths were directly attributable to graft failure due to alcohol. Fourteen (16%) patients fulfilled criteria for harmful relapse and 18 (21%) patients experienced any form of relapse to alcohol. Harmful relapse was associated with increased mortality (hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.1–9.7, P = 0.041). Only two factors were independently associated with harmful relapse on multivariate analysis; prior alcohol rehabilitation (HR 8.4, 95% CI 2.5–28.4, P = 0.001) and single versus married status (HR 0.09, 95% CI 0.02–1.2, P = 0.019).ConclusionGood patient survival outcomes were seen for this South Australian population. Harmful alcohol relapse occurs in a minority of patients and rarely results in direct graft loss. Modifiable pre‐transplant factors that predict harmful relapse were not identified.
Tadpole begging reveals high quality
Authors: Dugas M. B. , Strickler S. A. , Stynoski J. L. 
Published: March 2017

AbstractParents can benefit from allocating limited resources nonrandomly among offspring, and offspring solicitation (i.e. begging) is often hypothesized to evolve because it contains information valuable to choosy parents. We tested the predictions of three ‘honest begging’ hypotheses – Signal of Need, Signal of Quality and Signal of Hunger – in the tadpoles of a terrestrial frog (Oophaga pumilio). In this frog, mothers provision tadpoles with trophic eggs, and when mothers visit, tadpoles perform a putative begging signal by stiffening their bodies and vibrating rapidly. We assessed the information content of intense tadpole begging with an experimental manipulation of tadpole condition (need/quality) and food deprivation (hunger). This experiment revealed patterns consistent with the Signal of Quality hypothesis and directly counter to predictions of Signal of Need and Signal of Hunger. Begging effort and performance were higher in more developed and higher condition tadpoles and declined with food deprivation. Free‐living mothers were unlikely to feed tadpoles of a nonbegging species experimentally cross‐fostered with their own, and allocated larger meals to more developed tadpoles and those that vibrated at higher speed. Mother O. pumilio favour their high‐quality young, and because their concurrent offspring are reared in separate nurseries, must do so by making active allocation decisions. Our results suggest that these maternal choices are based at least in part on offspring signals, indicating that offspring solicitation can evolve to signal high quality.
A Cautionary Tale About Control Variables in IV Estimation
Authors: Deuchert Eva , Huber Martin 
Published: March 2017

AbstractMany instrumental variable (IV) regressions include control variables to justify (conditional) independence of the instrument and the potential outcomes. The plausibility of conditional IV independence crucially depends on the timing when the control variables are determined. This paper works through different IV models and discusses the (conditions for the) satisfaction of conditional IV independence depending on whether the control variables are measured prior to or after instrument assignment. To illustrate the identification issues, we consider the Vietnam War draft risk as instrument either for veteran status or education to evaluate the effects of these variables on labour market and health outcomes. Our empirical analysis based on the ‘Young Men in High School and Beyond’ survey suggests that commonly used conditional IV strategies to estimate the impact of draft induced military service or education may be severely biased due to the use of improper controls.
Effects of 6‐month aerobic interval training on skeletal muscle metabolism in middle‐aged metabolic syndrome patients
Authors: Guadalupe‐Grau A. , Fernández‐Elías V. E. , Ortega J. F. , Dela F. , Helge J. W. , Mora‐Rodriguez R. 
Published: March 2017

Aerobic interval training (AIT) improves the health of metabolic syndrome patients (MetS) more than moderate intensity continuous training. However, AIT has not been shown to reverse all metabolic syndrome risk factors, possibly due to the limited duration of the training programs. Thus, we assessed the effects of 6 months of AIT on cardio‐metabolic health and muscle metabolism in middle‐aged MetS. Eleven MetS (54.5±0.7 years old) underwent 6 months of 3 days a week supervised AIT program on a cycle ergometer. Cardio‐metabolic health was assessed, and muscle biopsies were collected from the vastus lateralis prior and at the end of the program. Body fat mass (−3.8%), waist circumference (−1.8%), systolic (−10.1%), and diastolic (−9.3%) blood pressure were reduced, whereas maximal fat oxidation rate and VO2peak were significantly increased (38.9% and 8.0%, respectively; all P<.05). The remaining components of cardio‐metabolic health measured (body weight, blood cholesterol, triglycerides, and glucose) were not changed after the intervention, and likewise, insulin sensitivity (CSi) remained unchanged. Total AMPK (23.4%), GLUT4 (20.5%), endothelial lipase (33.3%) protein expression, and citrate synthase activity (26.0%) increased with training (P<.05). Six months of AIT in MetS raises capacity for fat oxidation during exercise and increases VO2peak in combination with skeletal muscle improvements in mitochondrial enzyme activity. Muscle proteins involved in glucose, fat metabolism, and energy cell balance improved, although this was not reflected by parallel improvements in insulin sensitivity or blood lipid profile.
Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants
Authors: Kieffer Nicolas , Nordmann Patrice , Poirel Laurent 
Published: March 2017

ABSTRACT

Plasmid-mediated resistance to polymyxins mediated by the MCR-1/2 determinants has been reported in
Enterobacteriaceae
worldwide. Using PCR-based and cloning strategies, a series of
Moraxella
spp. were screened for
mcr
-like genes.
Moraxella
spp. that are mainly animal pathogens but may also be human pathogens were identified as potential reservoirs of
mcr
-like genes.
Primary Clofazimine and Bedaquiline Resistance among Isolates from Patients with Multidrug-Resistant Tuberculosis
Authors: Xu Jian , Wang Bin , Hu Minghao , Huo Fengmin , Guo Shaochen , Jing Wei , Nuermberger Eric , Lu Yu 
Published: March 2017

ABSTRACT

Clofazimine has been repurposed for the treatment of tuberculosis, especially for multidrug-resistant tuberculosis (MDR-TB). To test the susceptibility to clofazimine of
Mycobacterium tuberculosis
clinical isolates, MICs of clofazimine were determined using the microplate alamarBlue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. For five clofazimine-resistant strains isolated from previously treated pre-extensively drug-resistant TB (pre-XDR-TB) and XDR-TB patients without prior exposure to clofazimine or bedaquiline, clofazimine MICs were ≥1.2 μg/ml. Four isolates with cross-resistance to bedaquiline had
Rv0678
mutations. The other isolate with no resistance to bedaquiline had an
Rv1979c
mutation. This study adds to a recent study showing that 6.3% of MDR-TB patients without prior clofazimine or bedaquiline exposure harbored isolates with
Rv0678
mutations, which raises concern that preexisting resistance to these drugs may be associated with prior TB treatment. Furthermore, we propose a tentative breakpoint of 1.2 μg/ml for clofazimine resistance using the MABA method. More-widespread surveillance and individualized testing for clofazimine and bedaquiline resistance, together with assessment of their clinical usage, especially among previously treated and MDR-TB patients, are warranted.
Bacteria, Rev Your Engines: Stator Dynamics Regulate Flagellar Motility
Authors: Baker Amy E. , O'Toole George A. 
Published: March 2017

ABSTRACT
Many bacteria move through liquids and across surfaces by using flagella—filaments propelled by a membrane-embedded rotary motor. Much is known about the flagellum: its basic structure, the function of its individual motor components, and the regulation of its synthesis. However, we are only beginning to identify the dynamics of flagellar proteins and to understand how the motor structurally adapts to environmental stimuli. In this review, we discuss the external and cellular factors that influence the dynamics of stator complexes (the ion-conducting channels of the flagellar motor). We focus on recent discoveries suggesting that stator dynamics are a means for controlling flagellar function in response to different environments.
Robust Microbiota-Based Diagnostics for Inflammatory Bowel Disease
Authors: Eck A. , de Groot E. F. J. , de Meij T. G. J. , Welling M. , Savelkoul P. H. M. , Budding A. E. 
Published: March 2017

ABSTRACT
Strong evidence suggests that the gut microbiota is altered in inflammatory bowel disease (IBD), indicating its potential role in noninvasive diagnostics. However, no clinical applications are currently used for routine patient care. The main obstacle to implementing a gut microbiota test for IBD is the lack of standardization, which leads to high interlaboratory variation. We studied the between-hospital and between-platform batch effects and their effects on predictive accuracy for IBD. Fecal samples from 91 pediatric IBD patients and 58 healthy children were collected. IS-pro, a standardized technique designed for routine microbiota profiling in clinical settings, was used for microbiota composition characterization. Additionally, a large synthetic data set was used to simulate various perturbations and study their effects on the accuracy of different classifiers. Perturbations were validated in two replicate data sets, one processed in another laboratory and the other with a different analysis platform. The type of perturbation determined its effect on predictive accuracy. Real-life perturbations induced by between-platform variation were significantly greater than those caused by between-laboratory variation. Random forest was found to be robust to both simulated and observed perturbations, even when these perturbations had a dramatic effect on other classifiers. It achieved high accuracy both when cross-validated within the same data set and when using data sets analyzed in different laboratories. Robust clinical predictions based on the gut microbiota can be performed even when samples are processed in different hospitals. This study contributes to the effort to develop a universal IBD test that would enable simple diagnostics and disease activity monitoring.
Maintenance of the HIV Reservoir Is Antagonized by Selective BCL2 Inhibition
Authors: Cummins Nathan W. , Sainski-Nguyen Amy M. , Natesampillai Sekar , Aboulnasr Fatma , Kaufmann Scott , Badley Andrew D. 
Published: March 2017

ABSTRACTDecay of the HIV reservoir is slowed over time in part by expansion of the pool of HIV-infected cells. This expansion reflects homeostatic proliferation of infected cells by interleukin-7 (IL-7) or antigenic stimulation, as well as new rounds of infection of susceptible target cells. As novel therapies are being developed to accelerate the decay of the latent HIV reservoir, it will be important to identify interventions that prevent expansion and/or repopulation of the latent HIV reservoir. Our previous studies showed that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and activate Bak to induce apoptosis of infected cells. In circumstances where expression of the anti-apoptotic protein BCL2 is high, Casp8p41 instead binds BCL2, and cell death does not occur. This effect can be overcome by treating cells with the clinically approved BCL2 antagonist venetoclax, which prevents Casp8p41 from binding BCL2, thereby allowing Casp8p41 to bind Bak and kill the infected cell. Here we assess whether the events that maintain the HIV reservoir are also antagonized by venetoclax. Using the J-Lat 10.6 model of persistent infection, we demonstrate that proliferation and HIV expression are countered by the use of venetoclax, which causes preferential killing of the HIV-expressing cells. Similarly, during new rounds of infection of primary CD4 T cells, venetoclax causes selective killing of HIV-infected cells, resulting in decreased numbers of HIV DNA-containing cells.IMPORTANCECure of HIV infection requires an intervention that reduces the HIV reservoir size. A variety of approaches are being tested for their ability to impact HIV reservoir size. Even if successful, however, these approaches will need to be combined with additional complementary approaches that prevent replenishment or repopulation of the HIV reservoir. Our previous studies have shown that the FDA-approved BCL2 antagonist venetoclax has a beneficial effect on the HIV reservoir size following HIV reactivation. Here we demonstrate that venetoclax also has a beneficial effect on HIV reservoir size in a model of homeostatic proliferation of HIV as well as in acute spreading infection of HIV in primary CD4 T cells. These results suggest that venetoclax, either alone or in combination with other approaches to reducing HIV reservoir size, is a compound worthy of further study for its effects on HIV reservoir size.
Herpes Simplex Virus gE/gI and US9 Promote both Envelopment and Sorting of Virus Particles in the Cytoplasm of Neurons, Two Processes That Precede Anterograde Transport in Axons
Authors: DuRaine Grayson , Wisner Todd W. , Howard Paul , Williams Melissa , Johnson David C. 
Published: March 2017

ABSTRACT

Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently infected ganglia to epithelial tissues, where viral progeny are produced in numbers allowing spread to other hosts. The HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport, ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. We previously described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons. Here we show that gE
−
US9
−
double mutants accumulate large quantities of unenveloped and partially enveloped capsids in neuronal cytoplasm. These defects in envelopment can explain the defects in axonal transport of enveloped virions. In addition, the unenveloped capsids that accumulated were frequently bound to cytoplasmic membranes, apparently immobilized in intermediate stages of envelopment. A gE-null mutant produced enveloped virions, but these accumulated in large numbers in the neuronal cytoplasm rather than reaching cell surfaces as wild-type HSV virions do. Thus, in addition to the defects in envelopment, there was missorting of capsids and enveloped particles in the neuronal cytoplasm, which can explain the reduced anterograde transport of unenveloped capsids and enveloped virions. These mechanisms differ substantially from existing models suggesting that gE/gI and US9 function by tethering HSV particles to kinesin microtubule motors. The defects in assembly of gE
−
US9
−
mutant virus particles were novel because they were neuron specific, in keeping with observations that US9 is neuron specific.

IMPORTANCE
Herpes simplex virus (HSV) and other alphaherpesviruses, such as varicella-zoster virus, depend upon the capacity to navigate in neuronal axons. To do this, virus particles tether themselves to dyneins and kinesins that motor along microtubules from axon tips to neuronal cell bodies (retrograde transport) or from cell bodies to axon tips (anterograde transport). This transit in axons is essential for alphaherpesviruses to establish latency in ganglia and then to reactivate and move back to peripheral tissues for spread to other hosts. Anterograde transport of HSV requires two membrane proteins: gE/gI and US9. Our studies reveal new mechanisms for how gE/gI and US9 initiate anterograde axonal transport. HSV mutants lacking both gE and US9 fail to properly assemble enveloped virus particles in the cytoplasm, which blocks anterograde transport of enveloped particles. In addition, there are defects in the sorting of virus particles such that particles, when formed, do not enter proximal axons.
Hili Inhibits HIV Replication in Activated T Cells
Authors: Peterlin B. Matija , Liu Pingyang , Wang Xiaoyun , Cary Daniele , Shao Wei , Leoz Marie , Hong Tian , Pan Tao , Fujinaga Koh 
Published: March 2017

ABSTRACT

P-element-induced wimpy-like (Piwil) proteins restrict the replication of mobile genetic elements in the germ line. They are also expressed in many transformed cell lines. In this study, we discovered that the human Piwil 2 (Hili) protein can also inhibit HIV replication, especially in activated CD4
+
T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express Hili, its expression was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of Hili increased levels of viral proteins and new viral particles. Further studies revealed that Hili binds to tRNA. Some of the tRNAs represent rare tRNA species, whose codons are overrepresented in the viral genome. Targeting tRNA
Arg
(UCU) with an antisense oligonucleotide replicated effects of Hili and also inhibited HIV replication. Finally, Hili also inhibited the retrotransposition of the endogenous intracysternal A particle (IAP) by a similar mechanism. Thus, Hili joins a list of host proteins that inhibit the replication of HIV and other mobile genetic elements.

IMPORTANCE
Piwil proteins inhibit the movement of mobile genetic elements in the germ line. In their absence, sperm does not form and male mice are sterile. This inhibition is thought to occur via small Piwi-interacting RNAs (piRNAs). However, in some species and in human somatic cells, Piwil proteins bind primarily to tRNA. In this report, we demonstrate that human Piwil proteins, especially Hili, not only bind to select tRNA species, including rare tRNAs, but also inhibit HIV replication. Importantly, T cell activation induces the expression of Hili in CD4
+
T cells. Since Hili also inhibited the movement of an endogenous retrovirus (IAP), our finding shed new light on this intracellular resistance to exogenous and endogenous retroviruses as well as other mobile genetic elements.
Divergent Requirement of Fc-Fcγ Receptor Interactions for
In Vivo
Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies
Authors: Wang Shuangshuang , Ren Huanhuan , Jiang Wenbo , Chen Honglin , Hu Hongxing , Chen Zhiwei , Zhou Paul 
Published: March 2017

ABSTRACT

Recent studies have shown that Fc-Fcγ receptor (FcγR) interactions are required for
in vivo
protection against influenza viruses by broadly reactive anti-hemagglutinin (HA) stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single-challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for
in vivo
protection by Abs recognizing epitopes outside the RBS and whether the requirement is virus strain specific or epitope specific. In the present study, we therefore investigated the requirements for
in vivo
protection using two pan-H5 Abs, 65C6 and 100F4. We generated chimeric Abs, 65C6/IgG2a and 100F4/IgG2a, which preferentially engage activating FcγRs, and isogenic forms, 65C6/D265A and 100F4/D265A, which do not bind FcγR. Virus neutralizing activity, binding, antibody-dependent cellular cytotoxicity (ADCC), and
in vivo
protection of these Abs were compared using three H5 strains, A/Shenzhen/406H/2006 (SZ06), A/chicken/Shanxi/2/2006 (SX06), and A/chicken/Netherlands/14015526/2014 (NE14). We found that all four chimeric Abs bound and neutralized the SZ06 and NE14 strains but poorly inhibited the SX06 strain. 65C6/IgG2a and 100F4/IgG2a, but not 65C6/D265A and 100F4/D265A, mediated ADCC against target cells expressing HA derived from all three virus strains. Interestingly, both 65C6/IgG2a and 65C6/D265A demonstrated comparable protection against all three virus strains
in vivo
; however, 100F4/IgG2a, but not 100F4/D265A, showed
in vivo
protection. Thus, we conclude that Fc-FcγR interactions are required for
in vivo
protection by 100F4, but not by 65C6, and therefore, protection is not virus strain specific but epitope specific.

IMPORTANCE
Abs play an important role in immune protection against influenza virus infection. Fc-FcγR interactions are required for
in vivo
protection by broadly neutralizing antistem, but not by virus strain-specific, anti-receptor binding site (RBS), Abs. Whether such interactions are necessary for protection by Abs that recognize epitopes outside RBS is not fully understood. In the present study, we investigated
in vivo
protection mechanisms against three H5 strains by two pan-H5 Abs, 65C6 and 100F4. We show that although these two Abs have similar neutralizing, binding, and ADCC activities against all three H5 strains
in vitro
, they have divergent requirements for Fc-FcγR interactions to protect against the three H5 strains
in vivo
. The Fc-FcγR interactions are required for
in vivo
protection by 100F4, but not by 65C6. Thus, we conclude that Fc-FcγR interactions for
in vivo
protection by pan-H5 Abs is not strain specific, but epitope specific.