bluuebunny/crossref_metadata_2025_split huggingface dataset:
How antigen specificity directs regulatory T‐cell function: self, foreign and engineered specificity
Authors: Hoeppli R. E. , MacDonald K. G. , Levings M. K. , Cook L. 
Published: June 2016

AbstractRegulatory T cells (Tregs) are a suppressive subset of T cells that have important roles in maintaining self‐tolerance and preventing immunopathology. The T‐cell receptor (TCR) and its antigen specificity play a dominant role in the differentiation of cells to a Treg fate, either in the thymus or in the periphery. This review focuses on the effects of the TCR and its antigen specificity on Treg biology. The role of Tregs with specificity for self‐antigen has primarily been studied in the context of autoimmune disease, although recent studies have focused on their role in steady‐state conditions. The role of Tregs that are specific for pathogens, dietary antigens and allergens is much less studied, although recent data suggest a significant and previously underappreciated role for Tregs during memory responses to a wide range of foreign antigens. The development of TCR‐ or chimeric antigen receptor (CAR)‐transduced T cells means we are now able to engineer Tregs with disease‐relevant antigen specificities, paving the way for ensuring specificity with Treg‐based therapies. Understanding the role that antigens play in driving the generation and function of Tregs is critical for defining the pathophysiology of many immune‐mediated diseases, and developing new therapeutic interventions.
A reconsideration of the status of English in the Netherlands within the Kachruvian Three Circles model
Authors: GERRITSEN MARINEL , VAN MEURS FRANK , PLANKEN BRIGITTE , KORZILIUS HUBERT 
Published: June 2016

ABSTRACTThe English used in the Netherlands, a European Union country, is classified by many linguists as an ESL variety, or, within Kachru's (1985) Three Circles model, as an Outer Circle variety, or as being between an Outer and an Expanding Circle variety. This paper investigates the status of English in the Netherlands through a systematic application of the six criteria used by Kachru (1985) to classify the position of English in a country. The study is based on recent quantitative and qualitative data and shows that English in the Netherlands should be classified as an Expanding Circle variety.
Regeneration of hair and other skin appendages: A microenvironment‐centric view
Authors: Huang Chenyu , Du Yanan , Nabzdyk Christoph S. , Ogawa Rei , Koyama Taro , Orgill Dennis P. , Fu Xiaobing 
Published: June 2016

AbstractAdvances in skin regeneration have resulted in techniques and products that have allowed regeneration of both the dermis and epidermis. Yet complete skin regeneration requires the adnexal skin structures. Thus it is crucial to understand the regenerative potential of hair follicles where genetic, nutritional, and hormonal influences have important effects and are critical for skin regeneration. The follicular stem cell niche serves as an anatomical compartment, a structural unit, a functional integrator, and a dynamic regulator necessary to sustain internal homeostasis and respond to outside stimuli. In particular, mechanics such as pressure, compression, friction, traction, stretch, shear, and mechanical wounding can influence hair loss or growth. Relevant niche signaling pathways such as Wnt, bone morphogenetic protein, fibroblast growth factor, Shh, and Notch may yield potential targets for therapeutic interventions.
Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia
Authors: Bain Anthony R. , Ainslie Philip N. , Hoiland Ryan L. , Barak Otto F. , Cavar Marija , Drvis Ivan , Stembridge Mike , MacLeod Douglas M. , Bailey Damian M. , Dujic Zeljko , MacLeod David B. 
Published: June 2016

Key points
The present study describes the cerebral oxidative and non‐oxidative metabolism in man during a prolonged apnoea (ranging from 3 min 36 s to 7 min 26 s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide.
The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery‐jugular venous oxygen content difference, was reduced by ∼29% at the termination of apnoea, although there was no change in the non‐oxidative metabolism.
A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint.
A hypercapnia‐induced oxygen‐conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea.
AbstractProlonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea‐divers performed a maximal apnoea (range 3 min 36 s to 7 min 26 s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery‐internal jugular venous oxygen content difference. Non‐oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2 was reduced by ∼29% (P < 0.01, Cohen's d = 1.18) near the termination of apnoea compared to baseline, although non‐oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ∼38.4 mmHg), severe hypercapnia (arterial CO2 tension: ∼58.7 mmHg), but not mild‐hypercapnia (arterial CO2 tension: ∼46.3 mmHg), depressed the CMRO2 (∼17%, P = 0.04, Cohen's d = 0.87). Similarly to the apnoea, there was no change in the non‐oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic‐induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea.
A novel set‐up for the ex vivo analysis of mechanical properties of mouse aortic segments stretched at physiological pressure and frequency
Authors: Leloup Arthur J. A. , Van Hove Cor E. , Kurdi Ammar , De Moudt Sofie , Martinet Wim , De Meyer Guido R. Y. , Schrijvers Dorien M. , De Keulenaer Gilles W. , Fransen Paul 
Published: June 2016

Key points
Cyclic stretch is known to alter intracellular pathways involved in vessel tone regulation.
We developed a novel set‐up that allows straightforward characterization of the biomechanical properties of the mouse aorta while stretched at a physiological heart rate (600 beats min–1).
Active vessel tone was shown to have surprisingly large effects on isobaric stiffness.
The effect of structural vessel wall alterations was confirmed using a genetic mouse model.
This set‐up will contribute to a better understanding of how active vessel wall components and mechanical stimuli such as stretch frequency and amplitude regulate aortic mechanics.
AbstractCyclic stretch is a major contributor to vascular function. However, isolated mouse aortas are frequently studied at low stretch frequency or even in isometric conditions. Pacing experiments in rodents and humans show that arterial compliance is stretch frequency dependent. The Rodent Oscillatory Tension Set‐up to study Arterial Compliance is an in‐house developed organ bath set‐up that clamps aortic segments to imposed preloads at physiological rates up to 600 beats min–1. The technique enables us to derive pressure–diameter loops and assess biomechanical properties of the segment. To validate the applicability of this set‐up we aimed to confirm the effects of distension pressure and vascular smooth muscle tone on arterial stiffness. At physiological stretch frequency (10 Hz), the Peterson modulus (EP; 293 (10) mmHg) for wild‐type mouse aorta increased 22% upon a rise in pressure from 80–120 mmHg to 100–140 mmHg, while, at normal pressure, EP increased 80% upon maximal contraction of the vascular smooth muscle cells. We further validated the method using a mouse model with a mutation in the fibrillin‐1 gene and an endothelial nitric oxide synthase knock‐out model. Both models are known to have increased arterial stiffness, and this was confirmed using the set‐up. To our knowledge, this is the first set‐up that facilitates the study of biomechanical properties of mouse aortic segments at physiological stretch frequency and pressure. We believe that this set‐up can contribute to a better understanding of how cyclic stretch frequency, amplitude and active vessel wall components influence arterial stiffening.
A Modular, Tn
7
-Based System for Making Bioluminescent or Fluorescent Salmonella and Escherichia coli Strains
Authors: Shivak Dylan J. , MacKenzie Keith D. , Watson Nikole L. , Pasternak J. Alex , Jones Brian D. , Wang Yejun , DeVinney Rebekah , Wilson Heather L. , Surette Michael G. , White Aaron P. 
Published: June 2016

ABSTRACT

Our goal was to develop a robust tagging method that can be used to track bacterial strains
in vivo
. To address this challenge, we adapted two existing systems: a modular plasmid-based reporter system (pCS26) that has been used for high-throughput gene expression studies in
Salmonella
and
Escherichia coli
and Tn
7
transposition. We generated kanamycin- and chloramphenicol-resistant versions of pCS26 with bacterial luciferase, green fluorescent protein (GFP), and mCherry reporters under the control of σ
70
-dependent promoters to provide three different levels of constitutive expression. We improved upon the existing Tn
7
system by modifying the delivery vector to accept pCS26 constructs and moving the transposase genes from a nonreplicating helper plasmid into a temperature-sensitive plasmid that can be conditionally maintained. This resulted in a 10- to 30-fold boost in transposase gene expression and transposition efficiencies of 10
−8
to 10
−10
in
Salmonella enterica
serovar Typhimurium and
E. coli
APEC O1, whereas the existing Tn
7
system yielded no successful transposition events. The new reporter strains displayed reproducible signaling in microwell plate assays, confocal microscopy, and
in vivo
animal infections. We have combined two flexible and complementary tools that can be used for a multitude of molecular biology applications within the
Enterobacteriaceae
. This system can accommodate new promoter-reporter combinations as they become available and can help to bridge the gap between modern, high-throughput technologies and classical molecular genetics.

IMPORTANCE
This article describes a flexible and efficient system for tagging bacterial strains. Using our modular plasmid system, a researcher can easily change the reporter type or the promoter driving expression and test the parameters of these new constructs
in vitro
. Selected constructs can then be stably integrated into the chromosomes of desired strains in two simple steps. We demonstrate the use of this system in
Salmonella
and
E. coli
, and we predict that it will be widely applicable to other bacterial strains within the
Enterobacteriaceae
. This technology will allow for improved
in vivo
analysis of bacterial pathogens.
Complete and Closed Genome Sequences of 10 Salmonella enterica subsp.
enterica
Serovar Anatum Isolates from Human and Bovine Sources
Authors: Nguyen Scott V. , Harhay Dayna M. , Bono James L. , Smith Timothy P. L. , Fields Patricia I. , Dinsmore Blake A. , Santovenia Monica , Kelley Christy M. , Wang Rong , Bosilevac Joseph M. , Harhay Gregory P. 
Published: June 2016

ABSTRACT

Salmonella enterica
is an important pathogen transmitted by numerous vectors. Genomic comparisons of
Salmonella
strains from disparate hosts have the potential to further our understanding of mechanisms underlying host specificities and virulence. Here, we present the closed genome and plasmid sequences of 10
Salmonella enterica
subsp.
enterica
serovar Anatum isolates from bovine and human sources.
Complete Genome Sequences of the
Potyvirus Sweet potato virus 2
from East Timor and Australia
Authors: Maina Solomon , Edwards Owain R. , de Almeida Luis , Ximenes Abel , Jones Roger A. C. 
Published: June 2016

ABSTRACT

We present here the first complete genome sequences of
Sweet potato virus 2
(SPV2) from sweet potato in Australia and East Timor, and compare these with five complete SPV2 genome sequences from South Korea and one each from Spain and the United States. Both were closely related to SPV2 genomes from South Korea, Spain, and the United States.
Factors contributing to delayed diagnosis of cancer among Aboriginal people in Australia: a qualitative study
Authors: Shahid Shaouli , Teng Tiew-Hwa Katherine , Bessarab Dawn , Aoun Samar , Baxi Siddhartha , Thompson Sandra C 
Published: June 2016

Background/objectivesDelayed presentation of symptomatic cancer is associated with poorer survival. Aboriginal patients with cancer have higher rates of distant metastases at diagnosis compared with non-Aboriginal Australians. This paper examined factors contributing to delayed diagnosis of cancer among Aboriginal Australians from patient and service providers' perspectives.MethodsIn-depth, open-ended interviews were conducted in two stages (2006–2007 and 2011). Inductive thematic analysis was assisted by use of NVivo looking around delays in presentation, diagnosis and referral for cancer.ParticipantsAboriginal patients with cancer/family members (n=30) and health service providers (n=62) were recruited from metropolitan Perth and six rural/remote regions of Western Australia.ResultsThree broad themes of factors were identified: (1) Contextual factors such as intergenerational impact of colonisation and racism and socioeconomic deprivation have negatively impacted on Aboriginal Australians' trust of the healthcare professionals; (2) health service-related factors included low accessibility to health services, long waiting periods, inadequate numbers of Aboriginal professionals and high staff turnover; (3) patient appraisal of symptoms and decision-making, fear of cancer and denial of symptoms were key reasons patients procrastinated in seeking help. Elements of shame, embarrassment, shyness of seeing the doctor, psychological ‘fear of the whole health system’, attachment to the land and ‘fear of leaving home’ for cancer treatment in metropolitan cities were other deterrents for Aboriginal people. Manifestation of masculinity and the belief that ‘health is women's domain’ emerged as a reason why Aboriginal men were reluctant to receive health checks.ConclusionsSolutions to improved Aboriginal cancer outcomes include focusing on the primary care sector encouraging general practitioners to be proactive to suspicion of symptoms with appropriate investigations to facilitate earlier diagnosis and the need to improve Aboriginal health literacy regarding cancer. Access to health services remains a critical problem affecting timely diagnosis.
Risk factors for dermatitis in submariners during a submerged patrol: an observational cohort study
Authors: Flaxman Amy , Allen Elizabeth , Lindemann Claudia , Yamaguchi Yuko , O'Shea Matthew K , Fallowfield Joanne L , Lindsay Michael , Gunner Frances , Knox Kyle , Wyllie David H 
Published: June 2016

ObjectiveThe aim of this pilot study was to determine risk factors, includingStaphylococcus aureusnasal carriage, for dermatitis in submariners during a submarine patrol.Participants and methods36 submariners undertaking a submerged 6-week patrol participated in the study. Severity of dermatitis and its impact was assessed using visual analogue scales and questionnaires at baseline and weekly throughout the patrol.S. aureuscarriage levels in submariners were determined by nasal swabbing at baseline and shortly before disembarking the submarine. Occurrence of any skin or soft tissue infections (SSTI) were reported to the medical officer and swabs of the area were taken for subsequent analysis.ResultsS. aureuscarriers were significantly more likely than non-carriers to have previously received treatment for a cutaneous abscess (39% vs 5%, OR=13 (95% CI 1.3 to 130)) with a trend to being submariners longer (p=0.051). Skin scores at baseline and on patrol were not significantly associated with carriage status. Higher dermatitis scores were observed in those who had been submariners longer (p=0.045). Smoking and allergies were not found to be linked to carriage status or skin health score in this cohort.ConclusionsThis small pilot study investigatesS. aureuscarriage status and skin health in submariners. Length of submarine service but notS. aureuscarriage was identified as a risk factor for worsening skin health in this small cohort during a 6-week patrol. This does not supportS. aureusdecolonisation to improve skin health in this population. Further investigation into causes of dermatitis in submariners is required. This data supports a better understanding of the potential impact of exposure to environmental factors that could affect skin health in submariners.
How do women trade-off benefits and risks in chemotherapy treatment decisions based on gene expression profiling for early-stage breast cancer? A discrete choice experiment
Authors: Marshall Deborah A , Deal Ken , Bombard Yvonne , Leighl Natasha , MacDonald Karen V , Trudeau Maureen 
Published: June 2016

ObjectivesGene expression profiling (GEP) of tumours informs baseline risk prediction, potentially affecting adjuvant chemotherapy decisions for women with early-stage breast cancer. Since only 15% will experience a recurrence, concerns have been raised about potential harms from overtreatment and high GEP costs in publicly funded healthcare systems. We aimed to estimate preferences and personal utility of GEP testing information and benefit–risk trade-offs in chemotherapy treatment decisions.Design, setting and interventionBased on literature review and findings from our qualitative research (focus groups, interviews with patients with breast cancer and medical oncologists), we developed a discrete choice experiment (DCE) survey and administered it via an internet panel. The DCE included 12 choice tasks with 5 attributes and 3 alternatives considering orthogonality, D-efficiency and level balance.ParticipantsThe DCE survey was administered to 1004 Canadian women from the general population.Main outcome measuresPreferences were analysed using conditional logit and hierarchical Bayes and evaluated for goodness of fit. We conducted simulation analyses for alternative scenarios.ResultsGEP test score indicating likely benefit from chemotherapy was the most important attribute. Doctor's clinical estimate of the risk of cancer returning, trust in your cancer doctor and side effects of chemotherapy (temporary and permanent) were relatively less important but showed significant differences among levels. In the scenario analyses, 78% were likely to choose chemotherapy in a high-risk scenario, 55% in a moderate-risk scenario and 33% in a low-risk scenario, with the other attributes held constant. A high GEP score was more important in influencing the choice of chemotherapy for those at intermediate clinical risk.ConclusionsGEP testing information influences chemotherapy treatment decisions in early-stage breast cancer and varies depending on clinical risk. Clinicians should be aware of these differences and tailor the use of GEP testing accordingly.
DNA Methylation in Cancer and Aging
Authors: Klutstein Michael , Nejman Deborah , Greenfield Razi , Cedar Howard 
Published: June 2016

Abstract
DNA methylation is known to be abnormal in all forms of cancer, but it is not really understood how this occurs and what is its role in tumorigenesis. In this review, we take a wide view of this problem by analyzing the strategies involved in setting up normal DNA methylation patterns and understanding how this stable epigenetic mark works to prevent gene activation during development. Aberrant DNA methylation in cancer can be generated either prior to or following cell transformation through mutations. Increasing evidence suggests, however, that most methylation changes are generated in a programmed manner and occur in a subpopulation of tissue cells during normal aging, probably predisposing them for tumorigenesis. It is likely that this methylation contributes to the tumor state by inhibiting the plasticity of cell differentiation processes. Cancer Res; 76(12); 3446–50. ©2016 AACR.
Evaluating Ultra-long-Chain Fatty Acids as Biomarkers of Colorectal Cancer Risk
Authors: Perttula Kelsi , Edmands William M.B. , Grigoryan Hasmik , Cai Xiaoming , Iavarone Anthony T. , Gunter Marc J. , Naccarati Alessio , Polidoro Silvia , Hubbard Alan , Vineis Paolo , Rappaport Stephen M. 
Published: June 2016

Abstract
Background: Cross-sectional studies reported a novel set of hydroxylated ultra-long-chain fatty acids (ULCFA) that were present at significantly lower levels in colorectal cancer cases than controls. Follow-up studies suggested that these molecules were potential biomarkers of protective exposure for colorectal cancer. To test the hypothesis that ULCFAs reflect causal pathways, we measured their levels in prediagnostic serum from incident colorectal cancer cases and controls.
Methods: Serum from 95 colorectal cancer patients and 95 matched controls was obtained from the Italian arm of the European Prospective Investigation into Cancer and Nutrition cohort and analyzed by liquid chromatography–high-resolution mass spectrometry. Levels of 8 ULCFAs were compared between cases and controls with paired t tests and a linear model that used time to diagnosis (TTD) to determine whether case–control differences were influenced by disease progression.
Results: Although paired t tests detected significantly lower levels of four ULCFAs in colorectal cancer cases, confirming earlier reports, the case–control differences diminished significantly with increasing TTD (7 days–14 years).
Conclusion: Levels of several ULCFAs were lower in incident colorectal cancer cases than controls. However, because case–control differences decreased with increasing TTD, we conclude that these molecules were likely consumed by processes related to cancer progression rather than causal pathways.
Impact: ULCFA levels are unlikely to represent exposures that protect individuals from colorectal cancer. Future research should focus on the diagnostic potential and origins of these molecules. Our use of TTD as a covariate in a linear model provides an efficient method for distinguishing causal and reactive biomarkers in biospecimens from prospective cohorts. Cancer Epidemiol Biomarkers Prev; 25(8); 1216–23. ©2016 AACR.