The transcription factor encyclopedia

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field.

The apoptotic and proliferation rate of tumour budding cells in colorectal cancer outlines a heterogeneous population of cells with various impacts on clinical outcome

AIMS In colorectal cancer (CRC), tumour buds represent an aggressive cell type at the invasive front with apparently low proliferation. The aim of this study was to determine proliferation and apoptotic rates of buds in comparison to tumour centre, front and mucosa. METHODS AND RESULTS Whole tissue sections from 188 CRC patients underwent immunohistochemistry for Ki67. Ten high-power fields (HPFs) were evaluated in mucosa, tumour centre, tumour front and tumour buds (total = 40 HPFs/case). Caspase-3 and M30 immunohistochemistry were performed on a multipunch tissue microarray from the same cohort. Ki67, caspase-3 and M30 immunoreactivity were correlated with outcome. The average percentage of cells showing Ki67 positivity was 5.2% in mucosa, and was not significantly different between the centre and front of the tumour (38.2% and 34.9%; P < 0.0001); 0.3% of buds showed Ki67 positivity (P < 0.0001). Caspase-3 expression was similar in mucosa, tumour centre and tumour front, but lower in tumour buds (<0.1%; P < 0.0001). M30 staining in buds was decreased (0.01%; P < 0.0001) in comparison to other areas. Ki67 positivity in buds was detrimental to survival in univariate (P = 0.0352) and multivariate (P = 0.0355) analysis. Caspase-3-positive tumours showed better outcome than negative tumours (P = 0.0262); but tumours with caspase-3-positive buds showed a worse outcome than those with caspase-3-negative buds (P = 0.0235). CONCLUSIONS Ki67, caspase-3 and M30 staining is absent in most tumour buds, suggesting decreased proliferation and apoptosis. However, the fact that Ki67 and caspase-3 immunoreactivity was associated with unfavourable prognosis points to a heterogeneous population of tumour buds.

Possible role of Cdx2 in the serrated pathway of colorectal cancer characterized by BRAF mutation, high-level CpG Island methylator phenotype and mismatch repair-deficiency

Colorectal cancer is a heterogeneous disease at the histomorphological, clinical and molecular level. Approximately 20% of cases may progress through the "serrated" pathway characterized by BRAF mutation and high-level CpG Island Methylator Phenotype (CIMP). A large subgroup are additionally microsatellite instable (MSI) and demonstrate significant loss of tumor suppressor Cdx2. The aim of this study is to determine the specificity of Cdx2 protein expression and CpG promoter hypermethylation for BRAF(V600E) and high-level CIMP in colorectal cancer. Cdx2, Mlh1, Msh2, Msh6, and Pms2 were analyzed by immunohistochemistry using a multi-punch tissue microarray (TMA; n = 220 patients). KRAS and BRAF(V600E) mutation analysis, CDX2 methylation and CIMP were investigated. Loss of Cdx2 was correlated with larger tumor size (P = 0.0154), right-sided location (P = 0.0014), higher tumor grade (P < 0.0001), more advanced pT (P = 0.0234) and lymphatic invasion (P = 0.0351). Specificity was 100% for mismatch repair (MMR)-deficiency (P < 0.0001), 92.2% (P < 0.0001) for BRAF(V600E) and 91.8% for CIMP-high. Combined analysis of BRAF(V600E) /CIMP identified Cdx2 loss as sensitive (80%) and specific (91.5%) for mutation/high status. These results were validated on eight well-established colorectal cancer cell lines. CDX2 methylation correlated with BRAF(V600E) (P = 0.0184) and with Cdx2 protein loss (P = 0.0028). These results seem to indicate that Cdx2 may play a role in the serrated pathway to colorectal cancer as underlined by strong relationships with BRAF(V600E) , CIMP-high and MMR-deficiency. Whether this protein can only be used as a "surrogate" marker, or is functionally involved in the progression of these tumors remains to be elucidated.

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries

OBJECTIVE To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. RESULTS In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/μL (76% increase), 88 to 135 cells/μL (53%), and 209 to 274 cells/μL (31%). In 2009, compared with LIC, median counts were 13 cells/μL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/μL (-62 to +18) lower in UMIC, and 112 cells/μL (+75 to +149) higher in HIC. They were 23 cells/μL (95% CI: +18 to +28 cells/μL) higher in women than men. Median counts were 88 cells/μL (95% CI: +35 to +141 cells/μL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. CONCLUSIONS Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/μL in LIC and MIC and below 300 cells/μL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Humane Orientation as a New Cultural Dimension of the GLOBE Project: A Validation Study of the GLOBE Scale and Out-Group Humane Orientation in 25 Countries

We validate, extend, and empirically and theoretically criticize the cultural dimension of humane orientation of the project GLOBE (Global Leadership and Organizational Behavior Effectiveness Research Program). Theoretically, humane orientation is not just a one-dimensionally positive concept about being caring, altruistic, and kind to others as discussed by Kabasakal and Bodur (2004), but there is also a certain ambivalence to this concept. We suggest differentiating humane orientation toward in-group members from humane orientation toward out-group members. A multicountry construct validation study used student samples from 25 countries that were either high or low in humane orientation (N = 876) and studied their relation to the traditional GLOBE scale and other cultural-level measures (agreeableness, religiosity, authoritarianism, and welfare state score). Findings revealed a strong correlation between humane orientation and agreeableness, welfare state score, and religiosity. Out-group humane orientation proved to be the more relevant subfacet of the original humane orientation construct, suggesting that future research on humane orientation should make use of this measure instead of the vague original scale. The ambivalent character of out-group humane orientation is displayed in its positive correlation to high authoritarianism. Patriotism was used as a control variable for noncritical acceptance of one���s society but did not change the correlations. Our findings are discussed as an example of how rigid expectations and a lack of tolerance for diversity may help explain the ambivalent nature of humane orientation

The relationship between calcium and fluoride intake, pregnancy and lactation and the risk of height loss in white women

This study was designed to investigate the effect of calcium and fluoride intake, and parity and lactation on the risk of spinal osteoporosis. Height loss was used as a surrogate measure for spinal fractures by taking advantage of documented changes in height found during the 25-year follow-up of the Charleston Heart Study cohort. Women who had lost 2-4" in height or who had no change in height during the follow-up period were defined as case and comparison subjects respectively. Calcium intake when the subjects were "about 25" and in the recent past, average intake of fluoride over 25 years, and parity and history of breastfeeding were ascertained by questionnaire from 54 case and 77 comparison subjects. Low calcium intake in the past decreased the risk of height loss (age-adjusted OR = 0.3, 95%CI: 0.1-0.96) although several potentially important confounding variables could not be adjusted for. There was no association between risk of height loss and present calcium intake (OR = 0.8, 95%CI: 0.3-2.6 for low versus high intake) after adjustment for past calcium intake. High fluoride intake decreased the risk of height loss (adjusted OR = 0.4, 95%CI: 0.1-1.2). The effect of fluoride or calcium intake in the present was modified by the level of the other nutrient. Compared to a low intake of both calcium and fluoride, a high intake of one increased the risk of height loss (crude OR = 3.3 for high fluoride/low calcium, crude OR = 6.0 for high calcium/low fluoride) although a high intake of both was slightly protective (crude OR = 0.7). It is estimated that a "high" nutrient intake in this population was greater than 850mg/day for calcium and 2mg/day for fluoride. After adjustment for age, increasing parity decreased the risk of height loss in women who had never breastfed (OR = 0.2, 95%CI: 0.01-1.7 for 4 or more children). Women who had breastfed were also at lower risk of height loss than nulliparous women (OR = 0.3, 95%CI: 0.1-1.2 for 4 or more children) although at any level of parity, breastfeeding women had a greater risk of height loss than did non-breastfeeding women. ^

The impact of social support networks on compliance with hypertensive therapeutic regimens among noninstitutionalized black adults

A conceptual framework based on the Health Belief Model was proposed which identified those factors most significant in the prediction of compliance behavior. The hypothesized model was applied to analyze the effects of sociodemographic characteristics, self-assessed health status, and social support networks on compliance with antihypertensive regimens, focusing on black adults.^ The study population was selected from the National Health and Examination Survey II (NHANES II) which produced a sample of 3,957 eligible persons 35-74 years of age.^ The study addressed the following research questions: (a) what is the relationship between demographic variables and self-assessed health status, (b) what is the relationship between social support network and self-assessed health status, (c) what is the compliance, (d) what factors, e.g., demographic characteristics, social support network, self-assessed health status, are most related to compliance, and (e) does the effect of these factors on compliance differ between black and white adults?^ The results of the study found that blacks: (a) had poorer health than whites, and education and income were significantly related to self-assessed health status, (b) the stronger social support networks of blacks, the better their health status, and (c) older blacks and those in poorer health were more likely to comply with recommended treatment. The hypothesized conceptual model for the prediction of compliance behavior was partially substantiated for both blacks and whites.^ Implications for the application of the conceptual model are also discussed. ^

Potential roles for bcl-2 in the pathogenesis, progression, and treatment of prostate cancer

The most common molecular alterations observed in prostate cancer are increased bcl-2 protein expression and mutations in p53. Understanding the molecular alterations associated with prostate cancer are critical for successful treatment and designing new therapeutic interventions. Hormone-ablation therapy remains the most effective nonsurgical treatment; however, most patients will relapse with hormone-independent, refractory disease. This study addresses how hormone-ablation therapy may increase bcl-2, develops a transgenic model to elucidate the role of bcl-2 multistep prostate carcinogenesis, and assesses how bcl-2 may confer resistance to cell death induction using adenoviral wild-type p53 gene therapy. ^ Two potential androgen response elements were identified in the bcl-2 promoter. Bcl-2 promoter luciferase constructs were transfected into the hormone- sensitive LNCaP prostate cell line. In the presence of dihydrotestosterone, the activity of one bcl-2 promoter luciferase construct was repressed 40% compared to control cells grown in charcoal-stripped serum. Additionally, it was demonstrated that both bcl-2 mRNA and protein were downregulated in the LNCaP cells grown in the presence DHT. This suggests that DHT represses bcl-2 expression through possible direct and indirect mechanisms and that hormone-ablation therapy may actually increases bcl-2 protein. ^ To determine the role of bcl-2 in prostate cancer progression in vivo, probasin-bcl-2 mice were generated where human bcl-2 was targeted to the prostate. Increased bcl-2 expression rendered the ventral prostate more resistant to apoptosis induction following castration. When the probasin-bcl-2 mice were crossed with TRAMP mice, the latency to tumor formation was decreased. The expression of bcl-2 in the double transgenic mice did not affect the incidence of metastases. The double transgenic model will facilitate the study of in vivo effects of specific genetic lesions during the pathogenesis of prostate cancer. ^ The effects of increased bcl-2 protein on wild-type adenoviral p53-mediated cell death were determined in prostatic cell lines. Increased bcl-2 protected PC3 and DU145 cell lines, which possess mutant p53, from p53-mediated cell death and reductions in cell viability. Bcl-2 did not provide the same protective effect in LNCaP cell line, which expresses wild-type p53. This suggests that the ability of bcl-2 to protect against p53-mediated cell death is dependent upon the endogenous status of p53. ^

AS MARCAS E O CONSUMIDOR: Um estudo dos discursos da publicidade na perspectiva da modificação dos estere��tipos na representação da família.The

Os papeis de homens e mulheres na sociedade contemporânea têm sido reestruturados, assim como a própria noção das estruturas familiares se renova. Algumas marcas estão atentas a essas mudanças e, no contexto mercadológico, fica evidente que os consumidores são diversos, com novas demandas e expectativas pelo reconhecimento dessa diversidade. Esta dissertação discute a mudança de abordagem na representação da família, demonstrando suas mutações de papeis na publicidade, esta vista como um produto sociocultural. Para tanto foi desenvolvida uma pesquisa qualitativa subsidiada pela análise de discurso de linha francesa. Primeiramente, o estudo qualitativo se desenvolve a partir de uma abordagem bibliográfica e documental e uma parte empírica de análise de discurso de campanhas publicitárias dos últimos anos, selecionadas a partir de seu foco nas representações familiares contemporâneas, de marcas que as tratem com naturalidade e demonstrem aceitar essas transições, buscando-as através da análise de casos múltiplos de amostras intencionais os avanços quando se trata dos modelos familiares, elementos que se desviam de representação conservadora da família. Demonstrou-se que há uma tendência de algumas marcas reforçarem qual é o público que desejam atingir através de suas construções discursivas que apontam para o reconhecimento das famílias reconstituídas, para a adoção e para a homo e monoparentalidade, ou seja, para a confirmação da existência dos variados tipos de família.

MÍDIAS SOCIAIS DIGITAIS: ESPAÇO DE RELACIONAMENTO E COMUNICAÇÃO ESTRATÉGICA

O trabalho tem como proposta avaliar a postura das organizações nas mídias sociais digitais, considerando o fato de que esses novos ambientes virtuais têm modificado drasticamente a maneira pela qual elas promovem o relacionamento com seus públicos estratégicos. O objetivo principal da pesquisa é identificar e compreender como as organizações se posicionam diante de comentários desfavoráveis nas mídias sociais digitais que possam impactar sua imagem e reputação, bem como mostrar a importância de monitorar constantemente o consumidor e dialogar com ele nos canais digitais para evitar riscos à marca. A metodologia aplicada denomina-se Estudo de Casos Múltiplos, por meio da qual analisaram-se os comentários desfavoráveis às marcas: Vivo, Tim e Oi, na página do Facebook, durante o mês de setembro de 2015. Construiu-se um protocolo de pesquisa, e realizou-se o acompanhamento dessas marcas analisando-lhes os posts e os comentários desfavoráveis coletados no período. Constatou-se, após tais procedimentos que as operadoras apresentam frequentemente dificuldades para se relacionar com os públicos nas mídias sociais digitais, o que as coloca em risco quanto à sua imagem e reputação.

A Prospective Surveillance Study of Candidaemia : Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients

Funding This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. GR was also supported by a research fellowship grant from Gilead Sciences. The collection of the isolates was funded by a Gilead Fellowship to GR.

Midwife's testimony, Bristol Co. Massachusetts, 1727

Manuscript testimony, dated April 11, 1727, regarding the declaration of the paternity of a child out of wedlock born to Charity Caswell, probably in January of 1727. Signed by midwife Mary Crossman; also by Sarah Dean and Elizabeth Caswell.