2,005 research outputs found

    Homoeologous gene silencing in tissue cultured wheat callus

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    Abstract Background In contrast to diploids, most polyploid plant species, which include the hexaploid bread wheat, possess an additional layer of epigenetic complexity. Several studies have demonstrated that polyploids are affected by homoeologous gene silencing, a process in which sub-genomic genomic copies are selectively transcriptionally inactivated. This form of silencing can be tissue specific and may be linked to developmental or stress responses. Results Evidence was sought as to whether the frequency of homoeologous silencing in in vitro cultured wheat callus differ from that in differentiated organs, given that disorganized cells are associated with a globally lower level of DNA methylation. Using a reverse transcription PCR (RT-PCR) single strand conformation polymorphism (SSCP) platform to detect the pattern of expression of 20 homoeologous sets of single-copy genes known to be affected by this form of silencing in the root and/or leaf, we observed no silencing in any of the wheat callus tissue tested. Conclusion Our results suggest that much of the homoeologous silencing observed in differentiated tissues is probably under epigenetic control, rather than being linked to genomic instability arising from allopolyploidization. This study reinforces the notion of plasticity in the wheat epi-genome.</p

    Brand equity and willingness to pay for condoms in zimbabwe

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    <p>Abstract</p> <p>Background</p> <p>Zimbabwe suffers from one of the greatest burdens of HIV/AIDS in the world that has been compounded by social and economic instability in the past decade. However, from 2001 to 2009 HIV prevalence among 15-49 year olds declined from 26% to approximately 14%. Behavior change and condom use may in part explain this decline.</p> <p>PSI-Zimbabwe socially markets the Protector Plus (P+) branded line of condoms. When Zimbabwe converted to a dollar-based economy in 2009, the price of condoms was greatly increased and new marketing efforts were undertaken. This paper evaluates the role of condom marketing, a multi-dimensional scale of brand peceptions (brand equity), and price in condom use behavior.</p> <p>Methods</p> <p>We randomly sampled sexually active men age 15-49 from 3 groups - current P+ users, former users, and free condom users. We compared their brand equity and willingness to pay based on survey results. We estimated multivariable logistic regression models to compare the 3 groups.</p> <p>Results</p> <p>We found that the brand equity scale was positive correlated with willingness to pay and with condom use. Former users also indicated a high willingness to pay for condoms. We found differences in brand equity between the 3 groups, with current P+ users having the highest P+ brand equity. As observed in previous studies, higher brand equity was associated with more of the targeted health behavior, in this case and more consistent condom use.</p> <p>Conclusions</p> <p>Zimbabwe men have highly positive brand perceptions of P+. There is an opportunity to grow the total condom market in Zimbabwe by increasing brand equity across user groups. Some former users may resume using condoms through more effective marketing. Some free users may be willing to pay for condoms. Achieving these objectives will expand the total condom market and reduce HIV risk behaviors.</p

    The Non-Canonical CTD of RNAP-II Is Essential for Productive RNA Synthesis in Trypanosoma brucei

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    The carboxy-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II (RNAP-II) is essential for gene expression in metazoa and yeast. The canonical CTD is characterized by heptapeptide repeats. Differential phosphorylation of canonical CTD orchestrates transcriptional and co-transcriptional maturation of mRNA and snRNA. Many organisms, including trypanosomes, lack a canonical CTD. In these organisms, the CTD is called a non-canonical CTD or pseudo-CTD (ΨCTD. In the African trypanosome, Trypanosoma brucei, the ΨCTD is ∼285 amino acids long, rich in serines and prolines, and phosphorylated. We report that T. brucei RNAP-II lacking the entire ΨCTD or containing only a 95-amino-acid-long ΨCTD failed to support cell viability. In contrast, RNAP-II with a 186-amino-acid-long ΨCTD maintained cellular growth. RNAP-II with ΨCTD truncations resulted in abortive initiation of transcription. These data establish that non-canonical CTDs play an important role in gene expression

    53BP1 can limit sister-chromatid rupture and rearrangements driven by a distinct ultrafine DNA bridging-breakage process

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    Chromosome missegregation acts as one of the driving forces for chromosome instability and cancer development. Here, we find that in human cancer cells, HeLa and U2OS, depletion of 53BP1 (p53-binding protein 1) exacerbates chromosome non-disjunction resulting from a new type of sister-chromatid intertwinement, which is distinct from FANCD2-associated ultrafine DNA bridges (UFBs) induced by replication stress. Importantly, the sister DNA intertwinements trigger gross chromosomal rearrangements through a distinct process, named sister-chromatid rupture and bridging. In contrast to conventional anaphase bridge-breakage models, we demonstrate that chromatid axes of the intertwined sister-chromatids rupture prior to the breakage of the DNA bridges. Consequently, the ruptured sister arms remain tethered and cause signature chromosome rearrangements, including whole-arm (Robertsonian-like) translocation/deletion and isochromosome formation. Therefore, our study reveals a hitherto unreported chromatid damage phenomenon mediated by sister DNA intertwinements that may help to explain the development of complex karyotypes in tumour cells

    The estrogen-injected female mouse: new insight into the etiology of PCOS

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    <p>Abstract</p> <p>Background</p> <p>Female mice and rats injected with estrogen perinatally become anovulatory and develop follicular cysts. The current consensus is that this adverse response to estrogen involves the hypothalamus and occurs because of an estrogen-induced alteration in the GnRH delivery system. Whether or not this is true has yet to be firmly established. The present study examined an alternate possibility in which anovulation and cyst development occurs through an estrogen-induced disruption in the immune system, achieved through the intermediation of the thymus gland.</p> <p>Methods, Results and Conclusion</p> <p>A putative role for the thymus in estrogen-induced anovulation and follicular cyst formation (a model of PCOS) was examined in female mice by removing the gland prior to estrogen injection. Whereas all intact, female mice injected with 20 ug estrogen at 5–7 days of age had ovaries with follicular cysts, no cysts were observed in animals in which thymectomy at 3 days of age preceded estrogen injection. In fact, after restoring immune function by thymocyte replacement, the majority of thymectomized, estrogen-injected mice had ovaries with corpora lutea. Thus, when estrogen is unable to act on the thymus, ovulation occurs and follicular cysts do not develop. This implicates the thymus in the cysts' genesis and discounts the role of the hypothalamus. Subsequent research established that the disease is transferable by lymphocyte infusion. Transfer took place between 100-day-old estrogen-injected and 15-day-old naïve mice only when recipients were thymectomized at 3 days of age. Thus, a prerequisite for cyst formation is the absence of regulatory T cells. Their absence in donor mice was judged to be the result of an estrogen-induced increase in the thymus' vascular permeability, causing de facto circumvention of the final stages of regulatory T cell development. The human thymus has a similar vulnerability to steroid action during the fetal stage. We propose that in utero exposure to excessive levels of steroids such as estrogen has a long-term effect on the ability of the thymus to produce regulatory T cells. In female offspring this can lead to PCOS.</p

    Racial Similarities in Response to Standardized Offer of Influenza Vaccination

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    Despite known benefits of influenza vaccination and coverage by Medicare Part B, elderly minority patients are less likely to receive influenza vaccination than whites. OBJECTIVES : To test whether a nonphysician-initiated standardized offer of influenza vaccination to all elderly primary care patients would result in similar proportions of African-American and white patients accepting vaccine. DESIGN : In 7 metropolitan Detroit primary care practices during the 2003 influenza vaccination season, medical assistants assessed influenza immunization status of all patients 65 years and older and collected limited demographic data. Eligible patients were offered vaccination. MEASUREMENTS : Proportion of patients accepting influenza vaccination by race and predictors of vaccine acceptance. RESULTS : Four hundred and fifty-four eligible patients with complete racial information were enrolled: 40% African American, 52% white, 8% other race/ethnicity. Similar proportions of African Americans and whites had already received the 2003 vaccine (11.6% and 11.0%, respectively) or stated vaccination as the reason for visit (23.8% and 30.5%, respectively). Among the remainder, there also were similar proportions who accepted vaccination: 68.9% white and 62.1% African-American patients. History of previous vaccination was the only statistically significant predictor of vaccine acceptance (odds ratio [OR] 8.64, 95% confidence interval [CI] 4.17, 17.91, P <.001). After adjusting for history of previous vaccination, age, gender, and education, the odds of vaccine acceptance were no different for whites and African Americans (OR 1.20, 95% CI 0.63, 2.29, P =.57). CONCLUSIONS : Vaccination acceptance differed little between African-American and white elderly patients. Using nonphysician personnel to identify and offer influenza vaccine to eligible patients is easily accomplished in primary care offices and has the potential to eliminate racial disparities in influenza vaccination.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74908/1/j.1525-1497.2006.00401.x.pd

    Options for early breast cancer follow-up in primary and secondary care : a systematic review

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    Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed
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