bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis
Authors: Solis Norma V. , Swidergall Marc , Bruno Vincent M. , Gaffen Sarah L. , Filler Scott G. 
Published: March 2017

ABSTRACT

Oropharyngeal candidiasis (OPC), caused predominantly by
Candida albicans
, is a prevalent infection in patients with advanced AIDS, defects in Th17 immunity, and head and neck cancer. A characteristic feature of OPC is fungal invasion of the oral epithelial cells. One mechanism by which
C. albicans
hyphae can invade oral epithelial cells is by expressing the Als3 and Ssa1 invasins that interact with the epidermal growth factor receptor (EGFR) on epithelial cells and stimulate endocytosis of the organism. However, the signaling pathways that function downstream of EGFR and mediate
C. albicans
endocytosis are poorly defined. Here, we report that
C. albicans
infection activates the aryl hydrocarbon receptor (AhR), leading to activation of Src family kinases (SFKs), which in turn phosphorylate EGFR and induce endocytosis of the fungus. Furthermore, treatment of oral epithelial cells with interferon gamma inhibits fungal endocytosis by inducing the synthesis of kynurenines, which cause prolonged activation of AhR and SFKs, thereby interfering with
C. albicans
-induced EGFR signaling. Treatment of both immunosuppressed and immunocompetent mice with an AhR inhibitor decreases phosphorylation of SFKs and EGFR in the oral mucosa, reduces fungal invasion, and lessens the severity of OPC. Thus, our data indicate that AhR plays a central role in governing the pathogenic interactions of
C. albicans
with oral epithelial cells during OPC and suggest that this receptor is a potential therapeutic target.

IMPORTANCE
OPC is caused predominantly by the fungus
C. albicans
, which can invade the oral epithelium by several mechanisms. One of these mechanisms is induced endocytosis, which is stimulated when fungal invasins bind to epithelial cell receptors such as EGFR. Receptor binding causes rearrangement of epithelial cell microfilaments, leading to the formation of pseudopods that engulf the fungus and pull it into the epithelial cell. We discovered AhR acts via SFKs to phosphorylate EGFR and induce the endocytosis of
C. albicans
. Our finding that a small molecule inhibitor of AhR ameliorates OPC in mice suggests that a strategy of targeting host cell signaling pathways that govern epithelial cell endocytosis of
C. albicans
holds promise as a new approach to preventing or treating OPC.
The Vitamin B
12
-Dependent Photoreceptor AerR Relieves Photosystem Gene Repression by Extending the Interaction of CrtJ with Photosystem Promoters
Authors: Fang Mingxu , Bauer Carl E. 
Published: March 2017

ABSTRACT

Purple nonsulfur bacteria adapt their physiology to a wide variety of environmental conditions often through the control of transcription. One of the main transcription factors involved in controlling expression of the
Rhodobacter capsulatus
photosystem is CrtJ, which functions as an aerobic repressor of photosystem genes. Recently, we reported that a vitamin B
12
binding antirepressor of CrtJ called AerR is required for anaerobic expression of the photosystem. However, the mechanism whereby AerR regulates CrtJ activity is unclear. In this study, we used a combination of next-generation sequencing and biochemical methods to globally identify genes under control of CrtJ and the role of AerR in controlling this regulation. Our results indicate that CrtJ has a much larger regulon than previously known, with a surprising regulatory function under both aerobic and anaerobic photosynthetic growth conditions. A combination of
in vivo
chromatin immunoprecipitation-DNA sequencing (ChIP-seq) and ChIP-seq and exonuclease digestion (ChIP-exo) studies and
in vitro
biochemical studies demonstrate that AerR forms a 1:2 complex with CrtJ (AerR-CrtJ
2
) and that this complex binds to many promoters under photosynthetic conditions. The results of
in vitro
and
in vivo
DNA binding studies indicate that AerR-CrtJ
2
anaerobically forms an extended interaction with the bacteriochlorophyll
bchC
promoter to relieve repression by CrtJ. This is contrasted by aerobic growth conditions where CrtJ alone functions as an aerobic repressor of
bchC
expression. These results indicate that the DNA binding activity of CrtJ is modified by interacting with AerR in a redox-regulated manner and that this interaction alters CrtJ’s function.

IMPORTANCE
Photoreceptors control a wide range of physiology often by regulating downstream gene expression in response to light absorption via a bound chromophore. Different photoreceptors are known to utilize a number of different compounds for light absorption, including the use of such compounds as flavins, linearized tetrapyrroles (bilins), and carotenoids. Recently, a novel class of photoreceptors that use vitamin B
12
(cobalamin) as a blue-light-absorbing chromophore have been described. In this study, we analyzed the mechanism by which the vitamin B
12
binding photoreceptor AerR controls the DNA binding activity of the photosystem regulator CrtJ. This study shows that a direct interaction between the vitamin B
12
binding photoreceptor AerR with CrtJ modulates CrtJ binding to DNA and importantly, the regulatory outcome of gene expression, as shown here with photosystem promoters.
Diabetes incidence and glucose intolerance prevalence increase with higher outdoor temperature
Authors: Blauw Lisanne L , Aziz N Ahmad , Tannemaat Martijn R , Blauw C Alexander , de Craen Anton J , Pijl Hanno , Rensen Patrick C N 
Published: March 2017

ObjectiveRising global temperatures might contribute to the current worldwide diabetes epidemic, as higher ambient temperature can negatively impact glucose metabolism via a reduction in brown adipose tissue activity. Therefore, we examined the association between outdoor temperature and diabetes incidence in the USA as well as the prevalence of glucose intolerance worldwide.Research design and methodsUsing meta-regression, we determined the association between mean annual temperature and diabetes incidence during 1996–2009 for each US state separately. Subsequently, results were pooled in a meta-analysis. On a global scale, we performed a meta-regression analysis to assess the association between mean annual temperature and the prevalence of glucose intolerance.ResultsWe demonstrated that, on average, per 1°C increase in temperature, age-adjusted diabetes incidence increased with 0.314 (95% CI 0.194 to 0.434) per 1000. Similarly, the worldwide prevalence of glucose intolerance increased by 0.170% (95% CI 0.107% to 0.234%) per 1°C rise in temperature. These associations persisted after adjustment for obesity.ConclusionsOur findings indicate that the diabetes incidence rate in the USA and prevalence of glucose intolerance worldwide increase with higher outdoor temperature.
Prevalence of undiagnosed asymptomatic bacteriuria and associated risk factors during pregnancy: a cross-sectional study at two tertiary centres in Cairo, Egypt
Authors: Abdel-Aziz Elzayat Mohamed , Barnett-Vanes Ashton , Dabour Mohamed Farag Elmorsy , Cheng Feng 
Published: March 2017

BackgroundThe prevalence of asymptomatic bacteriuria (ASB) during pregnancy is poorly understood in Egypt—a country with a high birth rate.ObjectivesTo determine the prevalence of ASB among pregnant women booking at El Hussein and Sayed Galal Hospitals in Al-Azhar University in Egypt; and to observe the relationship between ASB prevalence and risk factors such as socioeconomic level and personal hygiene.SettingObstetrics and gynaecology clinics of 2 university hospitals in the capital of Egypt. Both hospitals are teaching and referral hospitals receiving referrals from across over the country. They operate specialist antenatal clinics 6 days per week.ParticipantsA cross-sectional study combining the use of questionnaires and laboratory analysis was conducted in 171 pregnant women with no signs or symptoms of urinary tract infection (1 case was excluded). Samples of clean catch midstream urine were collected and cultured using quantitative urine culture and antibiotic sensitivity tests were performed.ResultsOf 171 pregnant women, 1 case was excluded; 17 cases (10%, 95% CI 5.93% to 15.53%) were positive for ASB. There was a statistically significant relation between the direction of washing genitals and sexual activity per week—and ASB.Escherichia coliwas the most commonly isolated bacteria followed byKlebsiella. Nitrofurantoin showed 100% sensitivity, while 88% of the isolates were resistant to cephalexin.ConclusionsThe prevalence of ASB seen in pregnant women in 2 tertiary hospitals in Egypt was 10%.E. coliandKlebsiellaare the common organisms isolated. The direction of washing genitals and sexual activity significantly influences the risk of ASB. Pregnant women should be screened early for ASB during pregnancy; appropriate treatment should be given for positive cases according to antibiotic sensitivity screening. Cephalexin is likely to be of limited use in this management.
Treatment trends for retinopathy of prematurity in the UK: active surveillance study of infants at risk
Authors: Adams Gillian G W , Bunce Catey , Xing Wen , Butler Lucilla , Long Vernon , Reddy Aravind , Dahlmann-Noor Annegret H 
Published: March 2017

ObjectivesTo estimate the incidence of severe retinopathy of prematurity (ROP) requiring treatment and describe current treatment patterns in the UK.DesignNationwide population-based case ascertainment study via the British Ophthalmic Surveillance Unit and a national collaborative ROP special interest group. Practitioners completed a standardised case report form (CRF).SettingAll paediatric ophthalmologists providing screening and/or treatment for retinopathy in the UK were invited to take part.ParticipantsAny baby with ROP treated or referred for treatment between 1 December 2013 and 30 November 2014, treated with laser, cryotherapy, vascular endothelial growth factor (VEGF) inhibitor or vitrectomy/scleral buckling, or a combination.Main outcome measureIncidence of ROP requiring treatment.ResultsWe received 370 CRFs; 327 were included. Denominator from epidemiological data: 8112 infants with birth weight of <1500 g. The incidence of ROP requiring treatment was 4% (327/8112, 95% CI 3.6% to 4.5%). Median gestational age was 25 weeks (IQR 24.3–26.1), and median birth weight 706 g (IQR 620–821). Median age at first treatment was 80 days (IQR 71–96). 204 right eyes (62.39%) had type 1 ROP, and 27 (8.26%) had aggressive posterior ROP. Infants were also treated for milder disease: 9 (2.75%) right eyes were treated for type 2 ROP, and 74 (22.63%) for disease milder than type 1 with plus or preplus, which we defined here as ‘type 2 plus’ disease. First-line treatment was diode laser photoablation of the avascular retina in 90.5% and injection of VEGF inhibitor in 8%.ConclusionsROP treatment incidence in the UK is 2.5 times higher than previously estimated. 8% of treated infants receive intravitreal VEGF inhibitor, currently unlicensed. Research is needed urgently to establish safety and efficacy of this approach. Earlier treatment and increasing numbers of surviving premature infants require an increase in appropriate eye care facilities and staff.Trial registration numberNCT02484989.
Incidence of bloodstream infections: a nationwide surveillance of acute care hospitals in Switzerland 2008–2014
Authors: Buetti Niccolò , Atkinson Andrew , Marschall Jonas , Kronenberg Andreas ,   the Swiss Centre for Antibiotic Resistance (ANRESIS)
Published: March 2017

BackgroundBloodstream infections are often associated with significant mortality and morbidity. We aimed to investigate changes in the epidemiology of bloodstream infections in Switzerland between 2008 and 2014.MethodsData on bloodstream infections were obtained from the Swiss antibiotic resistance surveillance system (ANRESIS).ResultsThe incidence of bloodstream infections increased throughout the study period, especially among elderly patients and those receiving care in emergency departments and university hospitals.Escherichia coliwas the predominant pathogen, withEnterococciexhibiting the most prominent increase over the study period.ConclusionsThe described trends may impact morbidity, mortality and healthcare costs associated with bloodstream infections.
Association of respiratory symptoms and asthma with occupational exposures: findings from a population-based cross-sectional survey in Telemark, Norway
Authors: Abrahamsen R , Fell A K M , Svendsen M V , Andersson E , Torén K , Henneberger P K , Kongerud J 
Published: March 2017

ObjectivesThe aim of this study was to estimate the prevalence of respiratory symptoms and physician-diagnosed asthma and assess the impact of current occupational exposure.DesignCross-sectional analyses of the prevalence of self-reported respiratory health and association with current occupational exposure in a random sample of the general population in Telemark County, Norway.SettingsIn 2013, a self-administered questionnaire was mailed to a random sample of the general population, aged 16–50, in Telemark, Norway. The overall response rate was 33%, comprising 16 099 responders.Outcome measuresThe prevalence for respiratory symptoms and asthma, and OR of respiratory symptoms and asthma for occupational groups and exposures were calculated. Occupational exposures were assessed using self-reported exposure and an asthma-specific job-exposure matrix (JEM).ResultsThe prevalence of physician-diagnosed asthma was 11.5%. For the occupational groups, the category with agriculture/fishery workers and craft/related trade workers was associated with wheezing and asthma attack in the past 12 months, showing OR 1.3 (1.1 to 1.6) and 1.9 (1.2 to 2.8), respectively. The group including technicians and associated professionals was also associated with wheezing OR 1.2 (1.0 to 1.3) and asthma attack OR 1.4 (1.1 to 1.9). The JEM data show that exposure to flour was associated with wheezing OR 3.2 (1.4 to 7.3) and woken with dyspnoea OR 3.5 (1.3 to 9.5), whereas exposures to diisocyanates, welding/soldering fumes and exposure to vehicle/motor exhaust were associated with dyspnoea OR 2.9 (1.5 to 5.7), 3.2 (1.6 to 6.4) and 1.4 (1.0 to 1.8), respectively.ConclusionsThe observed prevalence of physician-diagnosed asthma was 11.5%. The ‘manual’ occupations were associated with respiratory symptoms. Occupational exposure to flour, diisocyanates, welding/soldering fumes and vehicle/motor exhaust was associated with respiratory symptoms in the past 12 months and use of asthma medication. However, prospective data are needed to confirm the observed associations.
Presynaptic and extrasynaptic regulation of posterior nucleus of thalamus
Authors: Park Anthony , Li Ying , Masri Radi , Keller Asaf 
Published: March 2017

The posterior nucleus of thalamus (PO) is a higher-order nucleus involved in sensorimotor processing, including nociception. An important characteristic of PO is its wide range of activity profiles that vary across states of arousal, thought to underlie differences in somatosensory perception subject to attention and degree of consciousness. Furthermore, PO loses the ability to downregulate its activity level in some forms of chronic pain, suggesting that regulatory mechanisms underlying the normal modulation of PO activity may be pathologically altered. However, the mechanisms responsible for regulating such a wide dynamic range of activity are unknown. Here, we test a series of hypotheses regarding the function of several presynaptic receptors on both GABAergic and glutamatergic afferents targeting PO in mouse, using acute slice electrophysiology. We found that presynaptic GABAB receptors are present on both GABAergic and glutamatergic terminals in PO, but only those on GABAergic terminals are tonically active. We also found that release from GABAergic terminals, but not glutamatergic terminals, is suppressed by cholinergic activation and that a subpopulation of GABAergic terminals is regulated by cannabinoids. Finally, we discovered the presence of tonic currents mediated by extrasynaptic GABAA receptors in PO that are heterogeneously distributed across the nucleus. Thus we demonstrate that multiple regulatory mechanisms concurrently exist in PO, and we propose that regulation of inhibition, rather than excitation, is the more consequential mechanism by which PO activity can be regulated. NEW & NOTEWORTHY The posterior nucleus of thalamus (PO) is a key sensorimotor structure, whose activity is tightly regulated by inhibition from several nuclei. Maladaptive plasticity in this inhibition leads to severe pathologies, including chronic pain. We reveal here, for the first time in PO, multiple regulatory mechanisms that modulate synaptic transmission within PO. These findings may lead to targeted therapies for chronic pain and other disorders.
Molecular Pathways: Evaluating the Potential for B7-H4 as an Immunoregulatory Target
Authors: MacGregor Heather L. , Ohashi Pamela S. 
Published: March 2017

Abstract
With the clinical success of CTLA-4 and PD-1 blockade in treating malignancies, there is tremendous interest in finding new ways to augment antitumor responses by targeting other inhibitory molecules. In this review, we describe one such molecule. B7-H4, a member of the B7 family of immunoregulatory proteins, inhibits T cell proliferation and cytokine production through ligation of an unknown receptor expressed by activated T cells. Notably, B7-H4 protein expression is observed in a high proportion of patients' tumors across a wide variety of malignancies. This high expression by tumors in combination with its low or absent protein expression in normal tissues makes B7-H4 an attractive immunotherapeutic target. Preclinical investigation into B7-H4–specific chimeric antigen receptor (CAR) T cells, antibody-mediated blockade of B7-H4, and anti–B7-H4 drug conjugates has shown antitumor efficacy in mouse models. The first clinical trials have been completed to assess the safety and efficacy of a B7-H4 fusion protein in ameliorating rheumatoid arthritis. Clin Cancer Res; 23(12); 2934–41. ©2017 AACR.
Sessile Serrated Polyps and Colon Cancer Prevention
Authors: Rashtak Shahrooz , Rego Rafaela , Sweetser Seth R. , Sinicrope Frank A. 
Published: March 2017

Abstract
Evidence suggests that up to one fifth of colorectal carcinomas develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic colorectal carcinomas with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps. Dysplasia is detected in a subset of SSA/Ps with a high risk of progression to carcinoma. An uncommon serrated polyp is the traditional serrated adenoma that is typically found in the left colon, has a tubulovillous architecture, and frequently harbors mutant KRAS. To date, the epidemiology of these serrated lesions is poorly understood, and limited observational data suggest a potential chemopreventive benefit of nonsteroidal anti-inflammatory drugs. The current primary strategy to reduce the risk of colorectal carcinoma from serrated polyps is to enhance their detection at colonoscopy and to ensure their complete removal. This review provides insight into the epidemiologic, clinical, histopathologic, and molecular features of serrated polyps and includes data on their endoscopic detection and chemoprevention. Cancer Prev Res; 10(5); 270–8. ©2017 AACR.
DNA e volume nuclear em Enteropneusta, Tunicata cephalochordata e suas implicações filogenéticas
Authors: Schreiber Giorgio , Cavenaghi Thereza M. C. M. 
Published: March 2017

Foi estudado o teor em DNA per núcleo e o volume nuclear em espermatócitos de Salpa democratica, Balanoglossus gigas e Branchiostoma caribbaeum. Os valores de DNA encontrados expressos em picogramas colocam estas espécies al limite inferior da variação do DNA em vertebrados. Embora o Balanoglossus esteja em uma posição filogenética inferior à dos Tunicados, o teor de DNA desta espécie é maior do das salpas. O tamanho relevante desta espécie poderia fazer supor uma situação múltipla do genoma, faltando, porém, totalmente indicações citogenéticas. A variação do valor da relação entre DNA e volume nuclear entre as espécies estudadas sugere uma possível significação taxonômica deste caráter quantitativo.
Food and feeding behavior of Arcturella sawayae Moreira, 1973 (Crustacea, Isopoda, Valvifera)
Authors: Moreira Plínio Soares 
Published: March 2017

Jovens e fêmeas ovígeras de Arcturella sawayae Moreira, 1973, foram estudadas quanto ao hábito alimentar e comportamento relacionada à obtenção de alimento.
Sôbre Dipteropeltis hirundo Calman, crustáceo (Branchiura) parasito de peixes dágua doce
Authors: Carvalho João De Paiva 
Published: March 2017

O presente material que serve como base para a re-descrição de Dipteropeltis hirundo Calm. Consistem em quatro fêmeas nas quais foram encontrados Tretagonopterus aureus e T. rutilis em um pequeno rio do estado de S. Paulo, afluente do rio Paraná. O material original de Calman (1912) veio do Rio Paraguai (Corumbá) e espécimes de Moreira (1913; 1913a) foram coletados no mesmo rio. Dipteropeltis hirundo Calm. inclui, depois Moreira (1915), Talaus riberoi (mais tarde Moreiriella riberoi), mas este último trabalho tem sido negligenciado por Wilson (1932) que mencionem ambos os gêneros, Dipteropeltis Calm e Talaus Moreira como somente um válido. Como Dipteropeltis hirundo não parece ocorrer em tão grande número como as espécies de Argulus e Dolops, as vezes, o parasita não pode ser considerado muito nocivo aos peixes.
An Episode in Provincial Cosmopolitanism
Authors: Fernández Bravo Álvaro 
Published: March 2017

This article explores the relationship of the work of the Argentine poet Juan L. Ortiz with Chinese poetry, which he not only translated into Spanish, but also read and referred to in his own writing. In the first part of this paper, I read Ortiz’s oeuvre as building a position in the Argentine literary system from the margin, the “province” of Entre Ríos where the author lived and published his books. In the second part, I use the notion of provincial cosmopolitanism to perform a World Literature reading of two poems that may illuminate aspects of a literary formation that a national reading framework is not able to recover. Poetry can be provincial and cosmopolitan at the same time, as my approach to Ortiz’s poems—as a contribution to the erosion of national hegemony in the reading of literature—intends to demonstrate.
Masculinity and the Bible
Authors: Smit Peter-Ben 
Published: March 2017

Most characters in the Bible are men, yet they are hardly analysed as such.Masculinity and the Bibleprovides the first comprehensive survey of approaches that remedy this situation. These are studies that utilize insights from the field of masculinity studies to further biblical studies. The volume offers a representative overview of both fields and presents a new exegesis of a well-known biblical text (Mark 6) to show how this approach leads to new insights.By presenting the field of masculinity studies, the volume performs a service for those working in biblical studies and related disciplines, but do not have explored this approach yet. At the same time, the volume shows, by surveying the past two decades of publications in the field, what results have been achieved so far and where open questions remain. In the exegesis of Mark 6, it becomes clear that one of these challenges, the often very specific and intersectional character of masculinity, can be addressed successfully when consciously combining approaches such as narrative and ritual analyses.