bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel immune cell subtypes linked to survival among African American women with triple-negative breast cancer
Authors: Purrington Kristen S. , Holowatyj Andreana N. , Cote Michele L. , Schwartz Ann G. , Chaudhry Rahman , Ali-Fehmi Rouba , Dyson Gregory , Colacino Justin , Boerner Julie , Bandyopadhyay Sudeshna 
Published: May 2018

ABSTRACTTriple negative breast cancer (TNBC) is an aggressive disease that is twice as likely to be diagnosed in African American (AA) women compared to white women, with poor clinical outcomes. Tumor infiltrating lymphocytes (TILs) are associated with improved survival for TNBC, but the relevance of TILs and immune cell subtypes to survival in AA women with TNBC is unknown. We evaluated histopathologic TIL counts and molecular characteristics among 60 AA women diagnosed with TNBC with linkage to clinical outcomes using data from the Metropolitan Detroit Cancer Surveillance System. We utilized whole genome expression profiling of TN tumors and cell type deconvolution analysis to evaluate the underlying mechanisms and immune cell subtypes associated with survival patterns in the context of TILs. TILs were significantly associated with improved survival [1-10% Hazard Ratio (HR)=0.32, 95% Confidence Interval (CI) 0.12-0.90, p=0.031; >10% HR=0.18, 95% CI 0.05-0.67, 9.9×10−3]. 524 transcripts (326 coding, 198 non-coding) were associated with TIL levels, 34 of which were associated with both TILs and survival (p<0.05). While only naïve B cells were associated with survival when considering individual cell types [Median HR=2.43, 95% CI 1.07-5.55, p=0.035], increased naïve B cells, plasma cells, and activated NK cells, and decreased resting mast cells, M1 macrophages, and monocytes were associated with transcripts that predicted worse survival. These data provide evidence for novel roles for these immune cells types in TNBC, and further studies are needed to validate these findings and identify determinants of patterns of immune response in TNBC relevant to the AA population.SummaryWe found that increased naïve B cells, plasma cells, and activated natural killer cells, and decreased resting mast cells, M1 macrophages, and monocytes were associated with expression biomarkers of worse survival among African American women with triple negative breast cancer.
Wild Steps in a Semi-wild Setting? Habitat Selection and Behavior of European Bison reintroduced to an Anthropogenic Landscape
Authors: Pedersen Pil Birkefeldt Møller , Olsen Joanna B. , Sandel Brody , Svenning Jens-Christian 
Published: May 2018

AbstractRecently, several wild or semi-wild herds of European bison have been reintroduced across Europe. It is essential for future successful bison reintroductions to know how the European bison use different habitats, which environmental parameters drive their habitat selection, and whether their habitat use and behavioural patterns in new reintroduction sites differ from habitats where European bison have been roaming freely for a long time.Here, we address these questions for a 40-ha enclosed site that has been inhabited by semi-free ranging European bison since 2012. The site, Vorup Meadows, is adjacent to the Gudenå river in Denmark and consists of human-modified riparian meadows. During 2013 we monitored the behavioural pattern and spatial use of the 11 bison present and in parallel carried out floristic analyses to assess habitat structure and food quality in the enclosure. We tested habitat use and selection against environmental parameters such as habitat characteristics, plant community traits, topography, and management area (release area vs. meadow area) using linear regression and spatial models.The bison herd had comparable diurnal activity patterns as observed in previous studies on free-roaming bison herds. Topography emerged as the main predictor of the frequency of occurrence in our spatial models, with high-lying drier areas being used more. Bison did not prefer open areas over areas with tree cover when accounting for habitat availability. However, they spent significantly more time in the release area, a former agricultural field with supplementary fodder, than expected from availability compared to the rest of the enclosure, a meadow with tree patches. We wish to increase awareness of possible long-term ethological effects of the release site and the management protocols accomplished here that might reduce the ecological impact by the bison in the target habitat, and thereby compromise or even oppose the conservation goals of the conservation efforts.
Genome-wide discovery of epistatic loci affecting antibiotic resistance using evolutionary couplings
Authors: Schubert Benjamin , Maddamsetti Rohan , Nyman Jackson , Farhat Maha R. , Marks Debora S. 
Published: May 2018

ABSTRACTThe analysis of whole genome sequencing data should, in theory, allow the discovery of interdependent loci that cause antibiotic resistance. In practice, however, identifying this epistasis remains a challenge as the vast number of possible interactions erodes statistical power. To solve this problem, we extend a method that has been successfully used to identify epistatic residues in proteins to infer genomic loci that are strongly coupled and associated with antibiotic resistance. Our method reduces the number of tests required for an epistatic genome-wide association study and increases the likelihood of identifying causal epistasis. We discovered 38 loci and 250 epistatic pairs that influence the dose needed to inhibit growth for five different antibiotics in 1,102 isolates ofNeisseria gonorrhoeaethat were confirmed in an independent dataset of 495 isolates. Many known resistance-affecting loci were recovered; however, the majority of loci occurred in unreported genes, includingmurEwhich was associated with cefixime. About half of the novel epistasis we report involved at least one locus previously associated with antibiotic resistance, including interactions betweengyrAandparCassociated with ciprofloxacin. Still, many combinations involved unreported loci and genes. Our work provides a systematic identification of epistasis pairs affecting antibiotic resistance inN. gonorrhoeaeand a generalizable method for epistatic genome-wide association studies.
Evolutionary Highways to Persistent Bacterial Infection
Authors: Bartell Jennifer A , Sommer Lea M , Haagensen Janus A J , Loch Anne , Espinosa Rocio , Molin Søren , Johansen Helle Krogh 
Published: May 2018

ABSTRACTPersistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host. This optimization involves coordinated adaptation of multiple traits, obscuring evolutionary trends and complicating infection management. Accordingly, we screen 8 infection-relevant phenotypes of 443 longitudinalPseudomonas aeruginosaisolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: 1) a 2-3 year timeline of rapid adaptation after colonization, 2) variant “naïve” and “adapted” states reflecting discordance between phenotypic and genetic adaptation, 3) adaptive trajectories leading to persistent infection via 3 distinct evolutionary modes, and 4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.
Horizontal transfer and finalization of a reliable detection method for the olive fruit fly endosymbiont,CandidatusErwinia dacicolax
Authors: Bigiotti Gaia , Pastorelli Roberta , Guidi Roberto , Belcari Antonio , Sacchetti Patrizia 
Published: May 2018

AbstractBackgroundThe olive fly,Bactrocera oleae, is the most important insect pest in olive production, causing economic damage to olive crops worldwide. In addition to extensive research onB. oleaecontrol methods, scientists have devoted much effort in the last century to understanding olive fly endosymbiosis with a bacterium eventually identified asCandidatusErwinia dacicola. This bacterium plays a relevant role in olive fly fitness. It is vertically transmitted, and it benefits both larvae and adults in wild populations; however, the endosymbiont is not present in lab colonies, probably due to the antibiotics and preservatives required for the preparation of artificial diets. Endosymbiont transfer from wildB. oleaepopulations to laboratory-reared ones allows olive fly mass-rearing, thus producing more competitive flies for future Sterile Insect Technique (SIT) applications.ResultsWe tested the hypothesis thatCa.E. dacicola might be transmitted from wild, naturally symbiotic adults to laboratory-reared flies. Several trials have been performed with different contamination sources ofCa.E. dacicola, such as ripe olives and gelled water contaminated by wild flies, wax domes containing eggs laid by wild females, cages dirtied by faeces dropped by wild flies and matings between lab and wild adults. PCR-DGGE, performed with the primer set 63F-GC/518R, demonstrated that the transfer of the endosymbiont from wild flies to lab-reared ones occurred only in the case of cohabitation.ConclusionsCohabitation of symbiotic wild flies and non-symbiotic lab flies allows the transfer ofCa.E. dacicola through adults. Moreover, PCR-DGGE performed with the primer set 63F-GC/518R was shown to be a consistent method for screeningCa.E. dacicola, also showing the potential to distinguish between the two haplotypes (htA and htB). This study represents the first successful attempt at horizontal transfer ofCa.E. dacicola and the first step in acquiring a better understanding of the endosymbiont physiology and its relationship with the olive fly. Our research also represents a starting point for the development of a laboratory symbiotic olive fly colony, improving perspectives for future applications of the Sterile Insect Technique.
Ecology Shapes Microbial Immune Strategy: Temperature and Oxygen as Determinants of the Incidence of CRISPR Adaptive Immunity
Authors: Weissman Jake L. , Laljani Rohan M. R. , Fagan William F. , Johnson Philip L. F. 
Published: May 2018

AbstractBacteria and archaea are locked in a near-constant battle with their viral pathogens. Despite previous mechanistic characterization of numerous prokaryotic defense strategies, the underlying ecological drivers of different strategies remain largely unknown and predicting which species will take which strategies remains a challenge. Here, we focus on the CRISPR immune strategy and develop a phylogenetically-corrected machine learning approach to build a predictive model of CRISPR incidence using data on over 100 traits across over 2600 species. We discover a strong but hitherto-unknown negative interaction between CRISPR and aerobicity, which we hypothesize may result from interference between CRISPR associated proteins and non-homologous end-joining DNA repair due to oxidative stress. Our predictive model also quantitatively confirms previous observations of an association between CRISPR and temperature. Finally, we contrast the environmental associations of different CRISPR system types (I, II, III) and restriction modification systems, all of which act as intracellular immune systems.
Leadership styles and their relationship with TQM focus for Indian firms
Authors: Kumar Vimal , Sharma R.R.K. 
Published: May 2018

Purpose
The purpose of this paper is to examine leadership styles and their impact on TQM focus within Indian firms.

Design/methodology/approach
The empirical data for this study were drawn from a survey of 111 firms in India to examine the validity and reliability of the independent constructs (leadership styles: transformational, servant, adaptive, rational and kinesthetic); and two dependent constructs (TQM focus: continuous improvement and innovation). The data were analyzed employing correlation and multiple regression analysis to identify the influence of leadership styles on TQM focus.

Findings
The results of the study revealed that six of the nine hypotheses have a significant and positive relationship with TQM focus; one hypothesis is partial while rest two hypotheses are not associated with TQM focus. It is also found that leadership styles are more inclined to continuous improvement and perceived as dominant TQM practices than innovation.

Research limitations/implications
This study used only two major variables, continuous improvement and innovation, as the outcome of TQM focus, but the outcomes are not limited. TQM focus is also related to other variables such as customer focus, product quality, employee involvement, benchmarking, etc. Future research should be extended by using other variables as the outcome of TQM focus.

Originality/value
The results can be beneficial for the current organization’s leaders to achieve appropriate leadership styles for effective and TQM focus. Moreover, this paper also attempts to inspire researchers to include the TQM focus in studying the effect of the leaders on TQM focus while implementing it effectively in the organizations.
Production of ‐aminobutyric acid (GABA) by Lactobacillus otakiensis and other Lactobacillus sp. isolated from traditional Pico cheese
Authors: Ribeiro Susana C , Domingos‐Lopes Marina F P , Stanton Catherine , Ross R Paul , Silva Célia CG 
Published: May 2018

Gamma‐aminobutyric acid (GABA) is a major inhibitory neurotransmitter with several physiological functions. Fifty‐seven strains isolated from an Azorean cheese were tested for their capacity to convert monosodium glutamate to GABA. Lactobacillus otakiensis, strain L3C1R1, along with three Lactobacillus paracasei and three Lactobacillus plantarum strains exhibited the highest GABA‐producing capacity (>300 mg/L). None of the strains from the genera Lactococcus, Leuconostoc and Enterococcus were GABA producers. Lactobacillus plantarum (strain L2A21R1) produced the highest amount of GABA (936.8 mg/L). Technological properties were also assessed, confirming the potential of the GABA‐producing strains as adjunct cultures for the development of fermented foods with health‐promoting properties.
Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers
Authors: Chun Sung Kook , Lee Sooyeon , Flores‐Toro Joseph , U Rebecca Y. , Yang Ming‐Jim , Go Kristina L. , Biel Thomas G. , Miney Catherine E. , Pierre Louis Schiley , Law Brian K. , Law Mary E. , Thomas Elizabeth M. , Behrns Kevin E. , Leeuwenburgh Christiaan , Kim Jae‐Sung 
Published: May 2018

SummaryIschemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age‐mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23–26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo. Primary hepatocytes isolated from each age group were also exposed to simulated in vitro I/R. Biochemical, genetic, and imaging analyses were performed to assess cell death, autophagy flux, mitophagy, and mitochondrial function. Compared to young mice, old livers showed accelerated liver injury following mild I/R. Reperfusion of old hepatocytes also showed necrosis, accompanied with defective autophagy, onset of the mitochondrial permeability transition, and mitochondrial dysfunction. Biochemical analysis indicated a near‐complete loss of both SIRT1 and MFN2 after I/R in old hepatocytes, which did not occur in young cells. Overexpression of either SIRT1 or MFN2 alone in old hepatocytes failed to mitigate I/R injury, while co‐overexpression of both proteins promoted autophagy and prevented mitochondrial dysfunction and cell death after reperfusion. Genetic approaches with deletion and point mutants revealed that SIRT1 deacetylated K655 and K662 residues in the C‐terminus of MFN2, leading to autophagy activation. The SIRT1‐MFN2 axis is pivotal during I/R recovery and may be a novel therapeutic target to reduce I/R injury in aged livers.
Genome‐wide association analysis reveals novel loci for hypoxia adaptability in Tibetan chicken
Authors: Jiang S. Y. , Xu H. Y. , Shen Z. N. , Zhao C. J. , Wu C. 
Published: May 2018

SummaryThe Tibetan chicken (TBC), an indigenous chicken breed of the Tibetan Plateau, has adapted to its hypoxic, high‐altitude environment over hundreds of years. The objective of this study was to identify the polymorphisms and genes associated with adaptation to hypoxia in this chicken breed. In the present study, samples were collected during days 18–21 of the incubation period from both surviving chicks and dead embryos, all of which were hatched under hypoxic conditions. A genome‐wide association study was conducted using the Illumina iSelect 60K SNP array with a case–control design, in which the case group consisted of the dead chicken embryos (n = 54) and controls were the surviving chicks (n = 82). Four significant SNPs were detected at the genome‐wide level (P < 0.05), and the results indicated that fork head box G1 (FOXG1) was the main candidate gene. The lead SNP NC_006092.4:g.33368893T>C was confirmed with a polymerase chain reaction‐restriction fragment length polymorphism analysis of 122 cases and 212 controls. A chi‐square test showed a significant association between NC_006092.4:g.33368893T>C and hatchability under hypoxic conditions (P < 0.01). Our results revealed novel polymorphisms and a candidate gene associated with hypoxic adaptation, facilitating further study in this field.
Morphology and quantification of sheep pineal glands at pre‐pubertal, pubertal and post‐pubertal periods
Authors: Bolat Durmuş , Kürüm Aytül , Canpolat Sıla 
Published: May 2018

SummaryThe pineal gland is a neuroendocrine organ associated with photoperiodic regulation in mammals. The aim of this study was to evaluate the pineal gland at the pre‐pubertal, pubertal and post‐pubertal periods by means of morphology and stereology. The study examined at total of 24 ovine pineal glands collected from healthy female Akkaraman breed. Thick sections (40 μm) were cut and treated with synaptophysin. Following each thick section, six consecutive sections at a thickness of 5 μm were cut. Each thin section was stained with one of the following dyes: Crossman’s modified triple dye, glial fibrillary acidic protein (GFAP), melatonin marker, periodic acid–Schiff, Von Kossa and AgNOR. The pineal gland volume was measured using Cavalieri’s method. The optical fractionator was used to estimate the total number of pinealocytes. The percentage of parenchyma and connective tissue and degree of vascularization were estimated by the area fraction fractionator method. The pineal gland volumes in the pre‐pubertal, pubertal and post‐pubertal groups were 7.53 ± 1.715 mm3, 11.20 ± 1.336 mm3 and 17.75 ± 1.188 mm3, respectively (p < .5). The number of pinealocytes in the pre‐pubertal, pubertal and post‐pubertal groups was 3,244,000 ± 228,076, 4,438,000 ± 243,610, 7,381,766 ± 406,223, respectively (p < .05). The glands of the post‐pubertal group contained the highest amount of connective tissue (11.49 ± 2.103%; p < .5) and the largest GFAP staining area (p < .05). The melatonin staining density was the highest in the pubertal group. The density of lipofuscin staining was higher in the pubertal and post‐pubertal groups.
Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA
Authors: Hsueh Wen‐Chi , Bennett Peter H , Esparza‐Romero Julian , Urquidez‐Romero Rene , Valencia Mauro E , Ravussin Eric , Williams Robert C , Knowler William C , Baier Leslie J , Schulz Leslie O , Hanson Robert L 
Published: May 2018

AbstractPrevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence in US Pima Indians is high. Although lifestyle likely accounts for much of the difference, the role of genetic factors is not well explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome‐wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. A multimarker risk score of obesity variants was associated with body mass index (BMI; β = 0.81 kg/m2 per SD, P = 0.0066). The mean value of the score was lower in Mexican Pimas than in US Pimas (P = 4.3 × 10−11), and differences in allele frequencies at established loci could account for approximately 7% of the population difference in BMI; however, the difference in risk scores was consistent with evolutionary neutrality given genetic distance. To identify loci potentially under recent natural selection, allele frequencies at 283 variants were compared between US and Mexican Pimas, accounting for genetic distance. The largest differences were seen at HLA markers (e.g., rs9271720, difference = 0.75, P = 8.7 × 10–9); genetic distances at HLA were greater than at random markers (P = 1.6 × 10–46). Analyses of GWAS data in 937 US Pimas also showed sharing of alleles identical by descent at HLA that exceeds its genomic expectation (P = 7.0 × 10–10). These results suggest that, in addition to the widely recognized balancing selection at HLA, recent directional selection may also occur, resulting in marked allelic differentiation between closely related populations.
Clinical and molecular characterization of Indian patients with fructose‐1, 6‐bisphosphatase deficiency: Identification of a frequent variant (E281K)
Authors: Bhai Pratibha , Bijarnia‐Mahay Sunita , Puri Ratna D. , Saxena Renu , Gupta Deepti , Kotecha Udhaya , Sachdev Anil , Gupta Dhiren , Vyas Vyomesh , Agarwal Divya , Jain Vivek , Bansal Rajeev K. , Kumar Tapisha G. , Verma Ishwar Chander 
Published: May 2018

AbstractFructose‐1, 6‐bisphosphatase deficiency is an autosomal recessive disorder of gluconeogenesis caused by genetic defect in the FBP1 gene. It is characterized by episodic, often life‐threatening metabolic acidosis, liver dysfunction, and hyperlactatemia. Without a high index of suspicion, it may remain undiagnosed with devastating consequences. Accurate diagnosis can be achieved either by enzyme assay or gene studies. Enzyme assay requires a liver biopsy and is tedious, invasive, expensive, and not easily available. Therefore, genetic testing is the most appropriate method to confirm the diagnosis. Molecular studies were performed on 18 suspected cases presenting with episodic symptoms. Seven different pathogenic variants were identified. Two common variants were noted in two subpopulations from the Indian subcontinent; p.Glu281Lys (E281K) occurred most frequently (in 10 patients) followed by p.Arg158Trp (R158W, in 4 patients). Molecular analysis confirmed the diagnosis and helped in managing these patients by providing appropriate genetic counseling. In conclusion, genetic studies identified two common variants in the Indian subcontinent, thus simplifying the diagnostic algorithm in this treatable disorder.