bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silicoprediction of host–pathogen protein interactions in melioidosis pathogenBurkholderia pseudomalleiand human reveals novel virulence factors and their targets
Authors: Loaiza Cristian D , Duhan Naveen , Lister Matthew , Kaundal Rakesh 
Published: November 2019

AbstractThe aerobic, Gram-negative motile bacillus, Burkholderia pseudomallei is a facultative intracellular bacterium causing melioidosis, a critical disease of public health importance, which is widely endemic in the tropics and subtropical regions of the world. Melioidosis is associated with high case fatality rates in animals and humans; even with treatment, its mortality is 20–50%. It also infects plants and is designated as a biothreat agent. B. pseudomallei is pathogenic due to its ability to invade, resist factors in serum and survive intracellularly. Despite its importance, to date only a few effector proteins have been functionally characterized, and there is not much information regarding the host–pathogen protein–protein interactions (PPI) of this system, which are important to studying infection mechanisms and thereby develop prevention measures. We explored two computational approaches, the homology-based interolog and the domain-based method, to predict genome-scale host–pathogen interactions (HPIs) between two different strains of B. pseudomallei (prototypical, and highly virulent) and human. In total, 76 335 common HPIs (between the two strains) were predicted involving 8264 human and 1753 B. pseudomallei proteins. Among the unique PPIs, 14 131 non-redundant HPIs were found to be unique between the prototypical strain and human, compared to 3043 non-redundant HPIs between the highly virulent strain and human. The protein hubs analysis showed that most B. pseudomallei proteins formed a hub with human dnaK complex proteins associated with tuberculosis, a disease similar in symptoms to melioidosis. In addition, drug-binding and carbohydrate-binding mechanisms were found overrepresented within the host–pathogen network, and metabolic pathways were frequently activated according to the pathway enrichment. Subcellular localization analysis showed that most of the pathogen proteins are targeting human proteins inside cytoplasm and nucleus. We also discovered the host targets of the drug-related pathogen proteins and proteins that form T3SS and T6SS in B. pseudomallei. Additionally, a comparison between the unique PPI patterns present in the prototypical and highly virulent strains was performed. The current study is the first report on developing a genome-scale host–pathogen protein interaction networks between the human and B. pseudomallei, a critical biothreat agent. We have identified novel virulence factors and their interacting partners in the human proteome. These PPIs can be further validated by high-throughput experiments and may give new insights on how B. pseudomallei interacts with its host, which will help medical researchers in developing better prevention measures.
Simulated maternal stress reduces offspring aerobic swimming performance in Pacific salmon
Authors: Banet Amanda I , Healy Stephen J , Eliason Erika J , Roualdes Edward A , Patterson David A , Hinch Scott G 
Published: November 2019

AbstractPacific salmon routinely encounter stressors during their upriver spawning migration, which have the potential to influence offspring through hormonally-mediated maternal effects. To disentangle genetic vs. hormonal effects on offspring swimming performance, we collected gametes from three species of Pacific salmon (Chinook, pink and sockeye) at the end of migration and exposed a subset of eggs from each female to cortisol baths to simulate high levels of maternal stress. Fertilised eggs were reared to fry and put through a series of aerobic swim trials. Results show that exposure to cortisol early in development reduces maximum oxygen consumption while swimming, and decreases aerobic scope in all three species. Resting oxygen consumption did not differ between cortisol and control treatment groups. We also examined several metrics that could influence aerobic performance, and found no differences between treatment groups in haematocrit%, haemoglobin concentration, heart mass, citrate synthase activity or lactate dehydrogenase activity. Though it was not the focus of this study, an interesting discovery was that pink salmon had a higher MO2max and aerobic scope relative to the other species, which was supported by a greater haematocrit, haemoglobin, a larger heart and higher CS activity. Some management and conservation practices for Pacific salmon focus efforts primarily on facilitating adult spawning. However, if deleterious effects of maternal stress acquired prior to spawning persist into the next generation, consideration will need to be given to sub-lethal effects that could be imparted onto offspring from maternal stress.
Variation in Wing Load of Female Spruce Budworms (Lepidoptera: Tortricidae) During the Course of an Outbreak: Evidence for Phenotypic Response to Habitat Deterioration in Collapsing Populations
Authors: Rhainds Marc 
Published: November 2019

AbstractReproduction in female spruce budworms, Choristoneura fumiferana, entails sedentary oviposition early in life (gravid females with their heavy abdomen full of eggs are unable to sustain flight), followed by short- and long-range dispersal by females that have laid a portion of their eggs. Body size measurements (wing surface area and dry weight) of gravid females, spent females at death (after all eggs are laid), and inflight females captured at light traps were collected at one location (forest stands near Fredericton in New Brunswick) over multiple years, from the outbreak stage (1976–1979: peak budworm abundance) to late declining phase with collapsing populations (1988–1989, following near two-fold magnitude of decline in adult density after 1987). For both demographic phases, females rarely flew until having laid at least 40% of their eggs, in contradiction to the hypothesis that females in defoliated forest stands can fly upon emergence due to their light-weight abdomen. As expected, the weight and fecundity of females in 1988–1989 was significantly lower than early on; in terms of body size (wing surface area), however, females were larger in late outbreak phase. These trends suggest that females have evolved morphological adaptation to further dispersal from deteriorated habitats.
Impact of Combined Lifestyle Factors on All-Cause and Cause-Specific Mortality and Life Expectancy in Chinese: The Singapore Chinese Health Study
Authors: Pan Xiong-Fei , Li Yanping , Franco Oscar H , Yuan Jian-Min , Pan An , Koh Woon-Puay 
Published: November 2019

Abstract

Background
To examine the impact of combined lifestyle factors on premature mortality and life expectancy in Chinese adults.

Methods
A total of 44,052 Chinese adults aged 45–74 years free of cardiovascular disease (CVD), cancer, and diabetes were followed from recruitment (1993–1998) to the end of 2016 in the Singapore Chinese Health Study. A composite score (0–5 scale) was calculated based on five baseline healthy lifestyle factors including healthy diet, nonsmoking status, light to moderate alcohol drinking, being physically active and optimal body mass index. Mortality cases were identified through linkage with the nationwide death registry.

Results
Adopting five healthy versus none was associated with a lower risk of all-cause and cause-specific mortality, and the hazard ratio (95% confidence interval [CI]) was 0.38 (0.29, 0.51) for all-cause mortality, 0.26 (0.13, 0.52) for CVD mortality, and 0.59 (0.37, 0.92) for cancer mortality. Nonadherence to 4–5 healthy lifestyle factors accounted for 34.9% (95% CI = 29.2, 40.2) in population attributable fraction for all-cause mortality, 35.1% (23.7, 44.9) for CVD mortality, and 18.0% (6.5, 28.0) for cancer mortality. Conversely, adherence to 4–5 healthy lifestyle factors versus none could achieve a gain of 8.1 years in women and 6.6 years in men for the life expectancy at 50 years.

Conclusions
A healthier lifestyle is associated with a substantially reduced risk of mortality and a longer life expectancy in the Chinese population. Our findings highlight the necessity of coordinated actions targeting combined lifestyle factors in reducing the overall burden of diseases and premature deaths.
Transpersonal Genetic Effects Among Older U.S. Couples: A Longitudinal Study
Authors: Das Aniruddha 
Published: November 2019

AbstractBackgroundEmerging social genetics research suggests one’s genes may influence not just one’s own outcomes but also those of close social alters. Health implications, particularly in late life, remain underexplored. Using combined genetic and survey data, this study examined such transpersonal genetic associations among older U.S. couples.MethodData were from married or cohabiting couples in the 2006–2016 waves of the Health and Retirement Study, nationally representative of U.S. adults over 50. Measures included a polygenic score for educational attainment, and self-rated health. Analysis was through parallel process latent growth models.ResultsWomen’s and men’s genetic scores for education had transpersonal linkages with their partner’s health. Such associations were solely with life-course variations and not late-life change in outcomes. Moreover, they were indirect, mediated by educational attainment itself. Evidence also emerged for individual-level genetic effects mediated by the partner’s education.DiscussionIn addition to the subject-specific linkages emphasized in extant genetics literature, relational contexts involve multiple transpersonal genetic associations. These appear to have consequences for a partner’s and one’s own health. Life-course theory indicates that a person is never not embedded in such contexts, suggesting that these patterns may be widespread. Research is needed on their implications for the life-course and gene–environment correlation literature.
Imaging 3-D faults using diffractions with modified dip-angle gathers
Authors: Li Zhengwei , Zhang Jianfeng 
Published: November 2019

SUMMARY
Accurate identification of the locations and orientations of small-scale faults plays an important role in seismic interpretation. We have developed a 3-D migration scheme that can image small-scale faults using diffractions in time. This provides a resolution beyond the classical Rayleigh limit of half a wavelength in detecting faults. The scheme images weak diffractions by building a modified dip-angle gather, which is obtained by replacing the two dip angles dimensions of the conventional 2-D dip-angle gather with tangents of the dip angles. We build the modified 2-D dip-angle gathers by calculating the tangents of dip angles following 3-D prestack time migration (PSTM). In the resulting modified 2-D dip-angle gathers, the Fresnel zone related to the specular reflection exhibits an ellipse. Comparing with the conventional 2-D dip-angle gather, diffraction event related a fault exhibits a straight cylinder shape with phase-reversal across a line related the orientation of the fault. As a result, we can not only mute the Fresnel zones related to reflections, correct phase for edge diffractions and obtain the image of faults, but also detect the orientations of 3-D faults using the modified dip-angle gathers. Like the conventional dip-angle gathers, the modified dip-angle gathers can also be used to image diffractions resulting from other sources. 3-D Field data tests demonstrate the validity of the proposed diffraction imaging scheme.
Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients
Authors: Basson Abigail R , Gomez-Nguyen Adrian , Menghini Paola , Buttó Ludovica F , Di Martino Luca , Aladyshkina Natalia , Osme Abdullah , Lasalla Alexandria , Fischer Derek , Ezeji Jessica C , Erkkila Hailey L , Brennan Connery J , Lam Minh , Rodriguez-Palacios Alexander , Cominelli Fabio 
Published: November 2019

AbstractBackgroundInflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD.MethodsWe conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn’s disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice).ResultsEngraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% ± 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn’s or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD.ConclusionThe gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients’ best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups.
The JAK-Inhibitor Tofacitinib Rescues Human Intestinal Epithelial Cells and Colonoids from Cytokine-Induced Barrier Dysfunction
Authors: Sayoc-Becerra Anica , Krishnan Moorthy , Fan Shujun , Jimenez Jossue , Hernandez Rebecca , Gibson Kyle , Preciado Reyna , Butt Grant , McCole Declan F 
Published: November 2019

AbstractBackgroundAlterations to epithelial tight junctions can compromise the ability of the epithelium to act as a barrier between luminal contents and the underlying tissues, thereby increasing intestinal permeability, an early critical event in inflammatory bowel disease (IBD). Tofacitinib (Xeljanz), an orally administered pan-Janus kinase (JAK) inhibitor, was recently approved for the treatment of moderate to severe ulcerative colitis. Nevertheless, the effects of tofacitinib on intestinal epithelial cell functions are largely unknown. The aim of this study was to determine if JAK inhibition by tofacitinib can rescue cytokine-induced barrier dysfunction in intestinal epithelial cells (IECs).MethodsT84 IECs were used to evaluate the effects of tofacitinib on JAK-signal transducer and activator of transcription (STAT) activation, barrier permeability, and expression and localization of tight junction proteins. The impact of tofacitinib on claudin-2 promoter activity was assessed in HT-29 IECs. Tofacitinib rescue of barrier function was also tested in human colonic stem cell-derived organoids.ResultsPretreatment with tofacitinib prevented IFN-γ-induced decreases in transepithelial electrical resistance (TER) and increases in 4 kDa FITC-dextran permeability (FD4), partly due to claudin-2 transcriptional regulation and restriction of ZO-1 rearrangement at tight junctions. Although tofacitinib administered after IFN-γ challenge only partially normalized TER and claudin-2 levels, FD4 permeability and ZO-1 localization were fully recovered. The IFN-γ-induced FD4 permeability in primary human colonoids was fully rescued by tofacitinib.ConclusionsThese data suggest differential therapeutic efficacy of tofacitinib in the rescue of pore vs leak-tight junction barrier defects and indicate a potential contribution of improved epithelial barrier function to the beneficial effects of tofacitinib in IBD patients.
A Specific Mutation in Muc2 Determines Early Dysbiosis in Colitis-Prone Winnie Mice
Authors: Liso Marina , De Santis Stefania , Verna Giulio , Dicarlo Manuela , Calasso Maria , Santino Angelo , Gigante Isabella , Eri Rajaraman , Raveenthiraraj Sathuwarman , Sobolewski Anastasia , Palmitessa Valeria , Lippolis Antonio , Mastronardi Mauro , Armentano Raffaele , Serino Grazia , De Angelis Maria , Chieppa Marcello 
Published: November 2019

Abstract

Background
Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. Dysbiosis, a condition defined by dysregulation of the gut microbiome, has been reported in patients with IBD and in experimental models of colitis. Although several factors have been implicated in directly affecting gut microbial composition, the genetic determinants impacting intestinal dysbiosis in IBD remain relatively unknown.

Methods
We compared the microbiome of normal, uninflamed wild-type (WT) mice with that of a murine model of UC (ie, Winnie strain). Winnie mice possess a missense mutation in Muc2 that manifests in altered mucus production as early as 4 weeks of age, with ensuing colonic inflammation. To better address the potential role of mutant Muc2 in promoting dysbiosis in Winnie mice, we evaluated homozygous mutant mice (Winnie-/-) with their WT littermates that, after weaning from common mothers, were caged separately according to genotype. Histologic and inflammatory status were assessed over time, along with changes in their respective microbiome compositions.

Results
Dysbiosis in Winnie mice was already established at 4 weeks of age, before histologic evidence of gut inflammatory changes, in which microbial communities diverged from that derived from their mothers. Furthermore, dysbiosis persisted until 12 weeks of age, with peak differences in microbiome composition observed between Winnie and WT mice at 8 weeks of age. The relative abundance of Bacteroidetes was greater in Winnie compared with WT mice. Verrucomicrobia was detected at the highest relative levels in 4-week-old Winnie mice; in particular, Akkermansia muciniphila was among the most abundant species found at 4 weeks of age.

Conclusions
Our results demonstrate that mutant genetic determinants involved in the complex regulation of intestinal homeostasis, such as that observed in Winnie mice, are able to promote early gut dysbiosis that is independent from maternal microbial transfer, including breastfeeding. Our data provide evidence for intestinal dysbiosis attributed to a Muc2-driven mucus defect that leads to colonic inflammation and may represent an important target for the design of future interventional studies.
Great cormorant (Phalacrocorax carbo sinensis) predation on juvenile down-migrating trout (Salmo trutta) in a lowland stream
Authors: Källo Kristi , Baktoft Henrik , Jepsen Niels , Aarestrup Kim 
Published: November 2019

Abstract
Since in 1980s, the number of great cormorants (Phalacrocorax carbo sinensis) has increased all over its European distribution area. This has led to conflicts between bird conservation and fisheries. Mariager fjord in Denmark is an important feeding and transition area for a large population of migrating seatrout (Salmo trutta), but it also provides resting and breeding places for cormorants. Thus, juvenile anadromous salmonids migrating from the river to the sea may be exposed to high predation risk during a critical and vulnerable time in their development. A total of 31 123 down-migrating wild seatrout were tagged with Passive Integrated Transponder (PIT) tags in 2008, 2009, 2015, and 2016 in river Villestrup, the main tributary flowing into Mariager fjord. Tagged fish were measured and grouped by their developmental stage as parr, pre-smolt, or smolt. To quantify cormorant predation, nearby cormorant colonies and roosting sites were repeatedly scanned for PIT tags with a manual antenna to record tags from predated fish. Minimum predation rate was 27% but varied among years. Body length of the fish and predation risk were negatively correlated and the latter was dependent on the group of the fish. This study demonstrates a potential negative effect of predation by great cormorants on an important population of wild trout.
Topological structure of solution sets for control problems governed by semilinear fractional impulsive evolution equations with nonlocal conditions
Authors: Jiang Yi-rong , Zhang Qiong-fen , Song Qi-qing 
Published: November 2019

Abstract
This article investigates the topological structural of the mild solution set for a control problem monitored by semilinear fractional impulsive evolution equations with nonlocal conditions. The $R_{\delta }$-property of the mild solution set is obtained by applying the measure of noncompactness and a fixed point theorem of condensing maps and a fixed point theorem of nonconvex valued maps. Then this result is applied to prove that the presented control problem has a reachable invariant set under nonlinear perturbations. The obtained results are also applied to characterize the approximate controllability of the presented control problem.
Total and Unbound Bictegravir Concentrations and Viral Suppression in Cerebrospinal Fluid of Human Immunodeficiency Virus-Infected Patients (Spanish HIV/AIDS Research Network, PreEC/RIS 56)
Authors: Tiraboschi Juan , Imaz Arkaitz , Khoo Saye , Niubo Jordi , Prieto Paula , Saumoy Maria , Penchala Sujan Dilly , Garcia Benito , Padilla Cristina , Videla Sebastian , Podzamczer Daniel 
Published: November 2019

AbstractWe determined total and unbound concentrations of bictegravir (BIC) in cerebrospinal fluid (CSF) in 15 asymptomatic, virologically suppressed patients. The median plasma and CSF total BIC concentrations were 1837.1 ng/mL (interquartile range [IQR], 1237.2–2586.7) and 6.9 (IQR, 4.8–10.9), respectively. Median unbound BIC concentration was 2.48 ng/mL (IQR, 1.6–3.7). Total and unbound BIC CSF concentrations were above the half-maximal effective concentration value in all patients, and all subjects had human immunodeficiency virus viral suppression in plasma and CSF. Bictegravir may contribute to inhibit viral replication in this compartment.
Conflict-induced Food Insecurity and the War Crime of Starvation of Civilians as a Method of Warfare
Authors: Akande Dapo , Gillard Emanuela-Chiara 
Published: November 2019

Abstract
This article examines the rules of international humanitarian law (IHL) relevant to avoiding or minimizing conflict-induced food insecurity. It is important to consider these rules in order to appreciate the range of protections to which civilians are entitled. Understanding these rules is also essential for interpreting the relevant provisions of international criminal law, including, most notably, the war crime of starvation of the civilian population. After providing a brief outline of the general rules of IHL respect of which can reduce the risk of food insecurity, the article focuses on two sets of rules of direct relevance to food insecurity: the prohibition of starvation of civilians as a method of warfare and the rules regulating humanitarian relief operation. With regard to the former, the article considers whether, under IHL, the prohibition requires that the party that has engaged in the conduct must act with the purpose of causing starvation. It is argued that while the general prohibition of starvation in IHL requires such purpose, there are other, more specific, rules of IHL directed at reducing food insecurity which do not require such purpose. Consideration is also given to the application of the principle of proportionality to measures which have the effect of causing starvation. While most of this article focuses on IHL, it also provides some reflections on the interplay between the rules of IHL relating to humanitarian relief operations and the war crime of starvation in the International Criminal Court’s Statute. Moving briefly away from IHL, the article also highlights a normative tension that can impede humanitarian action and therefore exacerbate food insecurity.