Candida albicans responds to glycostructure damage by Ace2-mediated feedback regulation of Cek1 signaling.

Candida albicans uses the Cek1 MAPK pathway to restore cells from damage of its cell wall glycostructures. Defective protein N- or O-glycosylation activates Cek1 and the transcription factor Ace2 as its downstream target, to upregulate genes encoding protein O-mannosyltransferases (Pmt proteins). In unstressed cells, Cek1-Ace2 activity blocks expression of PMT1, which is de-repressed by tunicamycin.

Diversity Exiting the Academy: Influential Factors for the Career Choice of Well-Represented and Underrepresented Minority Scientists.

A national sample of PhD-trained scientists completed training, accepted subsequent employment in academic and nonacademic positions, and were queried about their previous graduate training and current employment. Respondents indicated factors contributing to their employment decision (e.g.

Western boundary currents regulated by interaction between ocean eddies and the atmosphere.

Current climate models systematically underestimate the strength of oceanic fronts associated with strong western boundary currents, such as the Kuroshio and Gulf Stream Extensions, and have difficulty simulating their positions at the mid-latitude ocean's western boundaries. Even with an enhanced grid resolution to resolve ocean mesoscale eddies-energetic circulations with horizontal scales of about a hundred kilometres that strongly interact with the fronts and currents-the bias problem can still persist; to improve climate models we need a better understanding of the dynamics governing these oceanic frontal regimes. Yet prevailing theories about the western boundary fronts are based on ocean internal dynamics without taking into consideration the intense air-sea feedbacks in these oceanic frontal regions.

International pooled study on diet and bladder cancer: the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics.

Background: In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7(th) most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage.

Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.

Background: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.

Methods: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression.

Alcohol and Dietary Folate Intake and Promoter CpG Island Methylation in Clear-Cell Renal Cell Cancer.

We investigated whether alcohol and dietary folate intakes were associated with promoter methylation in clear-cell renal cell carcinoma (ccRCC). The Netherlands Cohort Study with a case-cohort design included 120,852 subjects aged 55-69 yr in 1986. Diet was measured with a food-frequency questionnaire.

Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).

Patients And Methods: Among 1.

Discovery of pyrazinone based compounds that potently inhibit the drug-resistant enzyme variant R155K of the hepatitis C virus NS3 protease.

Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors with variations in the C-terminus. Biochemical evaluation was performed using genotype 1a, both the wild-type and the drug resistant enzyme variant, R155K. Surprisingly, compounds without an acidic sulfonamide retained good inhibition, challenging our previous molecular docking model.

A prospective cohort study on dietary acrylamide intake and the risk for cutaneous malignant melanoma.

Epidemiological studies have shown inconsistent associations between dietary acrylamide exposure and the risk for various malignancies. This is the first epidemiological study on the association between acrylamide intake and the risk for cutaneous malignant melanoma (CMM). A case-cohort analysis was carried out within the prospective Netherlands Cohort Study on diet and cancer.

Unexpected Metabolic Versatility in a Combined Fungal Fomannoxin/Vibralactone Biosynthesis.

The secondary metabolome of an undescribed stereaceous basidiomycete (BY1) was investigated for bioactive compounds. Along with a known fomannoxin derivative and two known vibralactones, we here describe three new compounds of these natural product families, whose structures were elucidated using 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. The new compound vibralactone S (4) shows a 3,6-substituted oxepin-2(7H)-one ring system, which is unprecedented for the vibralactone/fomannoxin class of compounds.

Diabetes mellitus type 2 and subsite-specific colorectal cancer risk in men and women: results from the Netherlands Cohort Study on diet and cancer.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC); however, studies differentiating between subsites of CRC are limited. We investigated how diabetes mellitus (DM) was associated with subsite-specific CRC risk in men and women.

Methods: The Netherlands Cohort Study on diet and cancer is a prospective study among 120 852 men and women aged 55-69 years old at baseline in 1986.

Toenail selenium status and risk of subtypes of head-neck cancer: The Netherlands Cohort Study.

Background: There is limited prospective data on the relationship between selenium status and the risk of head-neck cancer (HNC) and HNC subtypes (i.e., oral cavity cancer [OCC], oro-/hypopharyngeal cancer [OHPC] and laryngeal cancer [LC]).

Vegetarianism, low meat consumption and the risk of lung, postmenopausal breast and prostate cancer in a population-based cohort study.

Background/objectives: The few prospective studies that examined lung, female breast and prostate cancer risk in vegetarians have yielded mixed results, whereas none have studied the effects of low meat diets. Moreover, little is known about the explanatory role of (non-) dietary factors associated with these diets.

Subjects/methods: The Netherlands Cohort Study-Meat Investigation Cohort (NLCS-MIC)- is an analytical cohort of 11 082 individuals including 1133 self-reported vegetarians (aged 55-69 years at baseline).

Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors.

Purpose: Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2-10 years post-diagnosis.

Methods: A cross-sectional study was conducted in stage I-III CRC survivors (n = 145) diagnosed at Maastricht University Medical Center+, the Netherlands (2002-2010).

[The assessment of spirituality and religiousness in patients with psychosis].

Objectives: There is evidence that psychiatrists are rarely aware of how religion may intervene in their patient's life. That is particularly obvious concerning patients with psychosis. Yet, even for patients featuring delusions with religious content, religious activities and spiritual coping may have a favourable influence.

Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies.

Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality.

Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models.

Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors.

Background: About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We therefore investigated epigenome-wide DNA methylation profiles of PCa stratified by T2E status.

Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies.

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men.

Body mass index and risk of subtypes of head-neck cancer: the Netherlands Cohort Study.

Low body mass index (BMI) has been associated with risk of head-neck cancer (HNC), but prospective data are scarce. We investigated the association between BMI, BMI at age 20 years and change in BMI during adulthood with risk of HNC and HNC subtypes. 120,852 participants completed a questionnaire on diet and other cancer risk factors, including anthropometric measurements, at baseline in 1986.

Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.

Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.

Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases).

Mitochondrial DNA copy number in colorectal cancer: between tissue comparisons, clinicopathological characteristics and survival.

Low mitochondrial DNA (mtDNA) copy number in tumors has been associated with worse prognosis in colorectal cancer (CRC). This study further deciphers the role of mtDNA copy number in CRC by comparing mtDNA copy number between healthy, adenoma and carcinoma tissue, by investigating its association according to several clinicopathological characteristics in CRC, and by relating it to CRC-specific survival in CRC patients. A hospital-based series of samples including cancer, adenoma and adjacent histologically normal tissue from primary CRC patients (n = 56) and recurrent CRC (n = 16) was studied as well as colon mucosa samples from healthy subjects (n = 76).

Attachment and coping in psychosis in relation to spiritual figures.

Background: Studies have found higher levels of insecure attachment in individuals with schizophrenia. Attachment theory provides a framework necessary for conceptualizing the development of interpersonal functioning. Some aspects of the attachment of the believer to his/her spiritual figure are similar to those between the child and his/her parents.

Messing Up Texas?: A Re-Analysis of the Effects of Executions on Homicides.

Executions in Texas from 1994-2005 do not deter homicides, contrary to the results of Land et al. (2009). We find that using different models--based on pre-tests for unit roots that correct for earlier model misspecifications--one cannot reject the null hypothesis that executions do not lead to a change in homicides in Texas over this period.

Genetic Variants in the Insulin-like Growth Factor Pathway and Colorectal Cancer Risk in the Netherlands Cohort Study.

Interrelationships between insulin-like growth factors (IGFs), hyperinsulinaemia, diabetes, and colorectal cancer (CRC) indicate involvement of IGFs in colorectal tumorigenesis. We investigated the CRC risk associated with 24 single nucleotide polymorphisms (SNPs) in 9 genes related to the IGF pathway and an IGF1 19-CA repeat polymorphism. Variants were selected from literature and genotyped in toenail DNA from 3,768 subcohort members and 2,580 CRC cases from the Netherlands Cohort Study, which has a case-cohort design (n = 120,852).

Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies.

Background: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts.

Methods: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified.