bluuebunny/crossref_metadata_2025_split huggingface dataset:
GamR, the LysR-Type Galactose Metabolism Regulator, Regulates
hrp
Gene Expression via Transcriptional Activation of Two Key
hrp
Regulators, HrpG and HrpX, in Xanthomonas oryzae pv. oryzae
Authors: Rashid M. Mamunur , Ikawa Yumi , Tsuge Seiji 
Published: April 2016

ABSTRACT

Xanthomonas oryzae
pv. oryzae is the causal agent of bacterial leaf blight of rice. For the virulence of the bacterium, the
hrp
genes, encoding components of the type III secretion system, are indispensable. The expression of
hrp
genes is regulated by two key
hrp
regulators, HrpG and HrpX: HrpG regulates
hrpX
, and HrpX regulates other
hrp
genes. Several other regulators have been shown to be involved in the regulation of
hrp
genes. Here, we found that a LysR-type transcriptional regulator that we named GamR, encoded by
XOO_2767
of
X. oryzae
pv. oryzae strain MAFF311018, positively regulated the transcription of both
hrpG
and
hrpX
, which are adjacent to each other but have opposite orientations, with an intergenic upstream region in common. In a gel electrophoresis mobility shift assay, GamR bound directly to the middle of the upstream region common to
hrpG
and
hrpX
. The loss of either GamR or its binding sites decreased
hrpG
and
hrpX
expression. Also, GamR bound to the upstream region of either a galactose metabolism-related gene (
XOO_2768
) or a galactose metabolism-related operon (
XOO_2768
to
XOO_2771
) located next to
gamR
itself and positively regulated the genes. The deletion of the regulator gene resulted in less bacterial growth in a synthetic medium with galactose as a sole sugar source. Interestingly, induction of the galactose metabolism-related gene was dependent on galactose, while that of the
hrp
regulator genes was galactose independent. Our results indicate that the LysR-type transcriptional regulator that regulates the galactose metabolism-related gene(s) also acts in positive regulation of two key
hrp
regulators and the following
hrp
genes in
X. oryzae
pv. oryzae.

IMPORTANCE
The expression of
hrp
genes encoding components of the type III secretion system is essential for the virulence of many plant-pathogenic bacteria, including
Xanthomonas oryzae
pv. oryzae. It is specifically induced during infection. Research has revealed that in this bacterium,
hrp
gene expression is controlled by two key
hrp
regulators, HrpG and HrpX, along with several other regulators in the complex regulatory network, but the details remain unclear. Here, we found that a novel LysR-type transcriptional activator, named GamR, functions as an
hrp
regulator by directly activating the transcription of both
hrpG
and
hrpX
. Interestingly, GamR also regulates a galactose metabolism-related gene (or operon) in a galactose-dependent manner, while the regulation of
hrpG
and
hrpX
is independent of the sugar. Our finding of a novel
hrp
regulator that directly and simultaneously regulates two key
hrp
regulators provides new insights into an important and complex regulation system of
X. oryzae
pv. oryzae
hrp
genes.
Contribution of Vegetation to the Microbial Composition of Nearby Outdoor Air
Authors: Lymperopoulou Despoina S. , Adams Rachel I. , Lindow Steven E. 
Published: April 2016

ABSTRACT
Given that epiphytic microbes are often found in large population sizes on plants, we tested the hypothesis that plants are quantitatively important local sources of airborne microorganisms. The abundance of microbial communities, determined by quantifying bacterial 16S RNA genes and the fungal internal transcribed spacer (ITS) region, in air collected directly above vegetation was 2- to 10-fold higher than that in air collected simultaneously in an adjacent nonvegetated area 50 m upwind. Nonmetric multidimensional scaling revealed that the composition of airborne bacteria in upwind air samples grouped separately from that of downwind air samples, while communities on plants and downwind air could not be distinguished. In contrast, fungal taxa in air samples were more similar to each other than to the fungal epiphytes. A source-tracking algorithm revealed that up to 50% of airborne bacteria in downwind air samples were presumably of local plant origin. The difference in the proportional abundances of a given operational taxonomic unit (OTU) between downwind and upwind air when regressed against the proportional representation of this OTU on the plant yielded a positive slope for both bacteria and fungi, indicating that those taxa that were most abundant on plants proportionally contributed more to downwind air. Epiphytic fungi were less of a determinant of the microbiological distinctiveness of downwind air and upwind air than epiphytic bacteria. Emigration of epiphytic bacteria and, to a lesser extent, fungi, from plants can thus influence the microbial composition of nearby air, a finding that has important implications for surrounding ecosystems, including the built environment into which outdoor air can penetrate.

IMPORTANCE
This paper addresses the poorly understood role of bacterial and fungal epiphytes, the inhabitants of the aboveground plant parts, in the composition of airborne microbes in outdoor air. It is widely held that epiphytes contribute to atmospheric microbial assemblages, but much of what we know is limited to qualitative assessments. Elucidating the sources of microbes in outdoor air can inform basic biological processes seen in airborne communities (e.g., dispersal and biogeographical patterns). Furthermore, given the considerable contribution of outdoor air to microbial communities found within indoor environments, the understanding of plants as sources of airborne microbes in outdoor air might contribute to our understanding of indoor air quality. With an experimental design developed to minimize the likelihood of other-than-local plant sources contributing to the composition of airborne microbes, we provide direct evidence that plants are quantitatively important local sources of airborne microorganisms, with implications for the surrounding ecosystems.
Microbiota of an Italian Grana-Like Cheese during Manufacture and Ripening, Unraveled by 16S rRNA-Based Approaches
Authors: Alessandria Valentina , Ferrocino Ilario , De Filippis Francesca , Fontana Mauro , Rantsiou Kalliopi , Ercolini Danilo , Cocolin Luca 
Published: April 2016

ABSTRACT

The microbial ecology of cheese involves a rich and complex interaction between starter lactic acid bacteria and nonstarter lactic acid bacteria (NSLAB), mainly originating from raw milk and/or from the environment, that can contribute to the final characteristics of cheese. The aim of the present research was the exploration of the active microbiota by RNA-based approaches during the manufacturing and ripening of a Grana-like cheese. Reverse transcriptase PCR (RT-PCR)-denaturing gradient gel electrophoresis (DGGE) and RNA-based high-throughput sequencing were applied to profile microbial populations, while the enumeration of active bacteria was carried out by using quantitative PCR (qPCR). Three different cheese productions (named D, E, and F) collected in the same month from the same dairy plant were analyzed. The application of the qPCR protocol revealed the presence of 7 log CFU/ml of bacterial load in raw milk, while, during ripening, active bacterial populations ranged from <4 to 8 log CFU/ml. The natural whey starters used in the three productions showed the same microbiota composition, characterized by the presence of
Lactobacillus helveticus
and
Lactobacillus delbrueckii
. Nevertheless, beta-diversity analysis of the 16S rRNA sequencing data and RT-PCR-DGGE showed a clear clustering of the samples according to the three productions, probably driven by the different milks used. Milk samples were found to be characterized by the presence of several contaminants, such as
Propionibacterium acnes
,
Acidovorax
,
Acinetobacter
,
Pseudomonas
, and NSLAB. The core genera of the starter tended to limit the development of the spoilage bacteria only in two of the three batches. This study underlines the influence of different factors that can affect the final microbiota composition of the artisanal cheese.

IMPORTANCE
This study highlights the importance of the quality of the raw milk in the production of a hard cheese. Independent from the use of a starter culture, raw milk with low microbiological quality can negatively affect the populations of lactic acid bacteria and, as a consequence, impact the quality of the final product due to metabolic processes associated with spoilage bacteria.
Prevalence of metabolic syndrome and diabetes mellitus in Sami and Norwegian populations. The SAMINOR—a cross-sectional study
Authors: Broderstad Ann Ragnhild , Melhus Marita 
Published: April 2016

ObjectivesMetabolic syndrome (MetS) is recognised as a reliable long-term predictor of adverse health outcomes. Elevated prevalence rates of MetS and chronic lifestyle diseases have been documented in different indigenous groups. We aimed to evaluate the prevalence of MetS and diabetes mellitus in relation to ethnicity in Northern Norway. In addition, we discussed different cut-off values for waist circumference (WC) and what impact this has on the prevalence of MetS.Materials and methodsSAMINOR is a population-based study of health and living conditions in areas home to Sami and non-Sami populations. The survey was carried out in 2003–2004. All eligible residents in specific age groups were invited. In total, 16 538 males and females aged 36–79 years participated and gave informed consent for medical research.ResultsThis study involved a total of 7822 female and 7290 male participants. Sami affiliation was reported by 5141 participants (34%). The prevalence of MetS was high in both ethnic groups independent of which WC cut-off value was used. No ethnic differences in prevalence of diabetes mellitus were demonstrated. However, ethnicity appeared to affect diabetes treatment, which was more prevalent among Sami than non-Sami women.ConclusionsIn this study, there was no ethnic difference in diabetes prevalence, but ethnicity appeared to affect diabetes treatment. Tablet treatment was more commonly in use among Sami women than among non-Sami women. We demonstrated a high share of negative metabolic components. These metabolic components have important health implications. Therefore, determining preventive initiatives is important in the primary and specialist healthcare system. These initiatives must be made culture and linguistic specific, in order to reduce differences and improve health status in the whole population.
Feasibility study to examine discrepancy rates in prespecified and reported outcomes in articles submitted toThe BMJ
Authors: Weston Jennifer , Dwan Kerry , Altman Douglas , Clarke Mike , Gamble Carrol , Schroter Sara , Williamson Paula , Kirkham Jamie 
Published: April 2016

ObjectivesAdding, omitting or changing prespecified outcomes can result in bias because it increases the potential for unacknowledged or post hoc revisions of the planned analyses. Journals have adopted initiatives such as requiring the prospective registration of trials and the submission of study protocols to promote the transparency of reporting in clinical trials. The main objective of this feasibility study was to document the frequency and types of outcome discrepancy between prespecified outcomes in the protocol and reported outcomes in trials submitted toThe BMJ.MethodsA review of all 3156 articles submitted toThe BMJbetween 1 September 2013 and 30 June 2014. Trial registry entries, protocols and trial reports of randomised controlled trials published byThe BMJand a random sample of those rejected were reviewed. Editorial, peer reviewer comments and author responses were also examined to ascertain any reasons for discrepancies.ResultsIn the study period,The BMJreceived 311 trial manuscripts, 21 of which were subsequently published by the journal. In trials published byThe BMJ, 27% (89/333) of the prespecified outcomes in the protocol were not reported in the submitted paper and 11% (31/275) of reported outcomes were not prespecified. In the sample of 21 trials rejected byThe BMJ, 19% (63/335) of prespecified outcomes went unreported and 14% (45/317) of reported outcomes were not prespecified. None of the reasons provided by published authors were suggestive of outcome reporting bias as the reasons were unrelated to the results.ConclusionsMandating the prospective registration of a trial and requesting that a protocol be uploaded when submitting a trial article to a journal has the potential to promote transparency and safeguard the evidence base against outcome reporting biases as a result of outcome discrepancies. Further guidance is needed with regard to documenting reasons for outcome discrepancies.
Protocol for studying cough frequency in people with pulmonary tuberculosis
Authors: Proaño Alvaro , Bravard Marjory A , Tracey Brian H , López José W , Comina German , Zimic Mirko , Coronel Jorge , O'Neill Lee Gwenyth , Caviedes Luz , Luis Cabrera Jose , Salas Antonio , Ticona Eduardo , Kirwan Daniela E , Friedland Jon S , Evans Carlton A , Moore David A , Gilman Robert H ,   Tuberculosis Working Group in Peru
Published: April 2016

IntroductionCough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution.MethodsThis study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders.Ethics and disseminationEthical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed.
The Moment Study: protocol for a mixed method observational cohort study of the Alternative Nicotine Delivery Systems (ANDS) initiation process among adult cigarette smokers
Authors: Pearson Jennifer L , Smiley Sabrina L , Rubin Leslie F , Anesetti-Rothermel Andrew , Elmasry Hoda , Davis Megan , DeAtley Teresa , Harvey Emily , Kirchner Thomas , Abrams David B 
Published: April 2016

IntroductionAlternative Nicotine Delivery Systems (ANDS) such as e-cigarettes are battery-powered devices that aerosolize nicotine and other substances to simulate smoking without using tobacco. Little is known about the ANDS initiation process among adult smokers. The aims of this research are threefold to: (1) examine how ANDS use affects cigarette use; (2) examine how the immediate environmental and psychosocial contexts of cigarette and ANDS use vary within—and between—participants in general and by menthol preference and race; and, (3) examine participants' ‘lived experience’ of the subjective perceptions, meaning, influences and utility of cigarette and ANDS use.Methods and analysesThis study's mixed method, 6-week longitudinal design will produce a detailed description of the ANDS initiation process among adult smokers (N=100). Qualitative and quantitative data collection will include 3 weeks of: (1) ecological momentary assessment of patterns of cigarette/ANDS use, satisfaction, mood and craving; (2) geospatial assessment of participants' environment, including indoor and outdoor cigarette/ANDS norms and rules; (3) in-depth interviews about the meaning and utility of cigarette smoking and ANDS use; and, (4) saliva cotinine and exhaled carbon monoxide (CO) biomarkers. A diverse sample will be recruited with an equal number of menthol and non-menthol cigarette smokers. As the primary independent variable, we will investigate how ANDS use affects cigarette consumption. We will also examine how smoking-related and ANDS-related rules and norms surrounding product use influence cigarette and ANDS product use, and how the subjective effects of ANDS use affect ANDS perceptions, beliefs and use.Ethics and disseminationThis study was funded by the National Institute on Drug Abuse of the US National Institutes of Health (1R21DA036472), registered at ClinicalTrials.gov (NCT02261363), and approved by the Chesapeake IRB (Pro00008526). Findings will be disseminated to the scientific and lay community through presentations, reports and scientific publications.Trial registration numberNCT02261363; Pre-results.
Serine protease inhibitor Kazal type 1 (SPINK1) as a prognostic marker in stage IV colon cancer patients receiving cetuximab based targeted therapy
Authors: Chen Yi-Ting , Tsao Shu-Chuan , Tsai Hung-Pei , Wang Jaw-Yuan , Chai Chee-Yin 
Published: April 2016

BackgroundSerine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, has well established associations with inflammation, cancer cell proliferation and carcinogenesis. However, the role of SPINK1 has not been investigated in stage IV colorectal cancer (CRC) patients receiving cetuximab based targeted therapy. The aim of this study was to evaluate the use of SPINK1 as a biomarker for predicting how patients with end stage CRC respond to anti-epidermal growth factor receptor (EGFR) therapies.MethodsImmunohistochemical staining was used for semiquantitative analysis of SPINK1 protein expression in 51 CRC cases. Expression of SPINK1 protein was then analysed to identify correlations with clinicopathological variables.ResultsHigh SPINK1 expression was significantly associated with males (p=0.018). Kaplan–Meier analyses also showed that patients with high SPINK1 expression had significantly longer overall survival compared with controls (p=0.004). Multivariable analyses showed that SPINK1 expression and tumour size were significantly associated with prognosis (HR 0.416 and 0.437; 95% CI 0.217 to 0.797 and 0.236 to 0.810; p=0.008 and p=0.009, respectively) in these stage IV CRC cases.ConclusionsHigh SPINK1 expression is associated with a good prognosis in stage IV CRC cases receiving cetuximab based targeted therapy. As SPINK1 expression is also an independent prognostic marker in these patients, it has potential use as a biomarker for clinical decision making and for designing personalised targeted therapies.
Src as a Therapeutic Target in Biliary Tract Cancer
Authors: Nam Ah-Rong , Kim Ji-Won , Park Ji Eun , Bang Ju-Hee , Jin Mei Hua , Lee Kyung-Hun , Kim Tae-Yong , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Oh Do-Youn , Bang Yung-Jue 
Published: April 2016

Abstract
Src, a nonreceptor tyrosine kinase, is involved in a number of cancer-related signaling pathways and aberrantly activated in biliary tract cancer (BTC). This study aimed to elucidate the potential role of Src as a therapeutic target in BTC. We tested bosutinib, an orally active c-Src/Abl kinase inhibitor, alone or in combination with cytotoxic agents using 9 human BTC cell lines: SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079, SNU-1196, HuCCT1, TFK-1, and EGI-1. Of these, SNU-308 and SNU-478 were relatively sensitive to bosutinib. Bosutinib abrogated phosphorylation of Src and its downstream molecules, and significantly increased G1 cell-cycle arrest and apoptosis. Bosutinib significantly inhibited cell migration and invasion and decreased epithelial–mesenchymal transition markers. Bosutinib combined with gemcitabine or cisplatin showed synergistic antiproliferative and antimigratory effects. In addition, this combination further inhibited phosphorylation of Src and its downstream molecules and decreased epithelial–mesenchymal transition marker expression compared with bosutinib alone. We established a SNU-478 xenograft model for in vivo experiments, because SNU-478 was more tumorigenic than SNU-308. Bosutinib combined with gemcitabine or cisplatin showed significantly more potent antitumor effects than bosutinib alone. Bosutinib combined with gemcitabine further decreased Ki-67 expression and Src phosphorylation, and further increased TUNEL expression. Our data suggest that Src might be a potential therapeutic target in BTC. Bosutinib demonstrated promising antitumor activity alone or in combination with gemcitabine or cisplatin in BTC cells, which supports further clinical development in patients with advanced BTC. Mol Cancer Ther; 15(7); 1515–24. ©2016 AACR.
Oxidative Stress–Induced Protein Damage Inhibits DNA Repair and Determines Mutation Risk and Therapeutic Efficacy
Authors: McAdam Elizabeth , Brem Reto , Karran Peter 
Published: April 2016

Abstract
The relationship between sun exposure and nonmelanoma skin cancer risk is well established. Solar UV (wavelength 280–400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280–320 nm). How the 20-fold more abundant UVA (320–400 nm) component of solar UV radiation increases skin cancer risk is not understood. Here it is demonstrated that the contribution of UVA to the effect of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the susceptibility of the cells to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin.
Implications: As NER is both a defense against cancer and a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative stress has implications for both cancer risk and for the effectiveness of anticancer therapy. Mol Cancer Res; 14(7); 612–22. ©2016 AACR.