关键词： Apoptosis   Tumour biomarkers  

摘要： Long noncoding RNAs (lncRNAs) emerge as essential roles in the regulation of alternative splicing (AS) in various malignancies. Serine- and arginine-rich splicing factor 1 (SRSF1)-mediated AS events are the most important molecular hallmarks in cancer. Nevertheless, the biological mechanism underlying tumorigenesis of lncRNAs correlated with SRSF1 in esophageal squamous cell carcinoma (ESCC) remains elusive. In this study, we found that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) was upregulated in ESCC clinical samples, which associated with poor prognosis. Through RNA interference and overexpression approaches, we confirmed that DGCR5 contributed to promote ESCC cell proliferation, migration, and invasion while inhibited apoptosis in vitro. Mechanistically, DGCR5 could directly bind with SRSF1 to increase its stability and thus stimulate alternative splicing events. Furthermore, we clarified that SRSF1 regulated the aberrant splicing of myeloid cell leukemia-1 (Mcl-1) and initiated a significant Mcl-1L (antiapoptotic) isoform switch, which contributed to the expression of the full length of Mcl-1. Moreover, the cell-derived xenograft (CDX) model was validated that DGCR5 could facilitate the tumorigenesis of ESCC in vivo. Collectively, our findings identified that the key biological role of lncRNA DGCR5 in alternative splicing regulation and emphasized DGCR5 as a potential biomarker and therapeutic target for ESCC.

关键词： family physician   primary health care   refugee   reproductive health family planning   Syrian migration   women health  

摘要： Purpose: Reproductive health includes the capability to reproduce and the freedom to decide. In this context, both women and men have rights. In this study, it is aimed to reveal the obstacles in using these rights and to describe perceptions on marriage and family planning (FP) of Syrian women and men and to increase awareness for developing new policies on the Primary Health Care. Methods: The study was conducted using qualitative method, consisting of in-depth interviews with 54 participants;43 women and 11 men who had to emigrate from varied regions of Syria at different times since 2011. Syrian women living in Hatay, in the south of Turkey were identified from Primary Health Care Center. Most of the Syrian women had given birth to the first two children before the age of 20 years. The interviewees were selected by purposive and snowball sampling. Results: The result was examined under seven headings: knowledge about FP and contraceptive methods, hesitation about contraceptive methods, emotional pressure of family and fear of maintaining marriage, embarrassing of talking about sexuality and contraception, the effects of belief and culture on contraception, psychological reflections of war, and changes in the perception of health during the process of immigration. The most significant factors affecting the approaches to FP and contraceptive methods of the women in this study were determined to be education, traditions, economic status, and religious beliefs. The most important factors affecting participants' FP and contraceptive method approaches are education, cultural beliefs, economic status, and religious beliefs. Conclusions: The primary healthcare centers are at a very strategical point for offering FP services to help address patients' unmet contraceptive needs and improve pregnancy outcomes. More attention should be paid to social determinants that influence the access to reproductive health. Moreover, efforts can be done to address gender inequality that

关键词： Toluene   Activated charcoal patch   Organic vapor monitor   Gloves   Personal protective equipment (PPE)   Permeation  

摘要： Previously, we have demonstrated the capability of activated charcoal cloth (ACC) to assess dermal exposure to VOCs. Here we investigated whether ACC patches can be used as an under-glove indicator to evaluate the ingress of toluene through disposable gloves in a controlled environment, and compared these results to the amount of toluene ingress determined from the standardized test methods for determining chemical permeation through PPE. In a test chamber, with plugs for air sampling, five to six ACC patches were placed on a mannequin hand underneath disposable gloves (latex, nitrile, neoprene, polymer laminate). Three work-exposure scenarios were simulated to assess toluene ingress through the different gloves: vapor exposure;spray exposure, and immersion. The standard permeation test, using a diffusion cell, was carried with glove material of the palm, with continuous contact conditions. In all of ACC test, the order of toluene ingress was latex > neoprene > nitrile > Barrier, but for the standardized testing, the order of the neoprene and nitrile was reversed, and nitrile had higher levels of toluene ingress. These results show the need to think beyond standard testing techniques for occupational exposure to hazardous substances, and the added value of ?application style? testing.

关键词： Non-coding RNA   E   coli   3MODIFIER LETTER PRIMEutr   RNA-RNA interactions   stress response   next-generation sequencing  

摘要： Previous high-throughput studies in Gram-negative bacteria identified a large number of 3MODIFIER LETTER PRIMEUTR fragments that potentially function as sRNAs. Here we extensively characterize the MalH sRNA. We show that MalH is a stable degradation intermediate derived from the 3MODIFIER LETTER PRIME end ofmalG, which is part of the maltose uptake operon transcriptmalEFG. Unlike the majority of bacterial sRNAs, MalH is transiently expressed during the transition from the exponential to the stationary growth phase, suggesting that it contributes to adaptation to changes in nutrient availability. Over-expression of MalH reduces expression of general outer membrane porins and MicA, a repressor of the high-affinity maltose/maltodextrin transporter LamB. Disrupting MalH production and function significantly reduceslamBaccumulation when maltose is the only available carbon source, presumably due to the accumulation of the MicA repressor. We propose that MalH is part of a regulatory network that, during the transition phase, directly or indirectly promotes accumulation of high-affinity maltose transporters in the outer membrane by dampening competing pathways.

关键词： Beef cattle   alternative splicing events   gene co-expression   four tissue transcriptomics   fatty acid composition  

摘要： Increasing the healthy/unhealthy fatty acid (FA) ratio in meat is one of the urgent tasks required to address consumer concerns. However, the regulatory mechanisms ultimately resulting in FA profiles vary among animals and remain largely unknown. In this study, using similar to 1.2 Tb high-quality RNA-Seq-based transcriptomic data of 188 samples from four key metabolic tissues (rumen, liver, muscle, and backfat) together with the contents of 49 FAs in backfat, the molecular regulatory mechanisms of these tissues contributing to FA formation in cattle were explored. Using this large dataset, the alternative splicing (AS) events, one of the transcriptional regulatory mechanisms in four tissues were identified. The highly conserved and absent AS events were detected in rumen tissue, which may contribute to its functional differences compared with the other three tissues. In addition, the healthy/unhealthy FA ratio related AS events, differential expressed (DE) genes, co-expressed genes, and their functions in four tissues were analysed. Eight key genes were identified from the integrated analysis of DE, co-expressed, and AS genes between animals with high and low healthy/unhealthy FA ratios. This study provides an applicable pipeline for AS events based on comprehensive RNA-Seq analysis and improves our understanding of the regulatory mechanism of FAs in beef cattle.

关键词： hTERT   telomerase   telomeres   alternative splicing   SON   pluripotent cells  

摘要： Telomere length control is critical for cellular lifespan and tumor suppression. Telomerase is transiently activated in the inner cell mass of the developing blastocyst to reset telomere reserves. Its silencing upon differentiation leads to gradual telomere shortening in somatic cells. Here, we report that transcriptional regulation through cis-regulatory elements only partially accounts for telomerase activation in pluripotent cells. Instead, developmental control of telomerase is primarily driven by an alternative splicing event, centered around hTERT exon 2. Skipping of exon 2 triggers hTERT mRNA decay in differentiated cells, and conversely, its retention promotes telomerase accumulation in pluripotent cells. We identify SON as a regulator of exon 2 alternative splicing and report a patient carrying a SON mutation and suffering from insufficient telomerase and short telomeres. In summary, our study highlights a critical role for hTERT alternative splicing in the developmental regulation of telomerase and implicates defective splicing in telomere biology disorders.

关键词： African meningitis belt   booster   catch-up campaigns   dosing schedule   impact   pneumococcal conjugate vaccines pneumococcal disease  

摘要： Introduction: Besides meningococcal disease, the African meningitis belt (AMB) region is also affected by pneumococcal disease. Most AMB countries have introduced pneumococcal conjugate vaccines (PCV) following a schedule of three primary doses without a booster or a catch-up campaign. PCV is expected to help control pneumococcal disease through both direct and indirect effects. Whether and how fast this will be achieved greatly depends on implementation strategies. Pre-PCV data from the AMB indicate high carriage rates of the pneumococcus, not only in infants but also in older children, and a risk of disease and death that spans lifetime. Post-PCV data highlight the protection of vaccinated children, but pneumococcal transmission remains important, resulting in a lack of indirect protection for unvaccinated persons. Areas covered: A non-systematic literature review focused on AMB countries. Relevant search terms were used in PubMed, and selected studies before and after PCV introduction were summarized narratively to appraise the suitability of current PCV programmatic strategies. Expert opinion: The current implementation strategy of PCV in the AMB appears suboptimal regarding the generation of indirect protection. We propose and discuss alternative programmatic strategies, including the implementation of broader age group mass campaigns, to accelerate disease control in this high transmission setting.

关键词： decision-making   strategy selection   exploration   learning   anterior cingulate cortex   rat   intra-telencephalic tract   pyramidal tract  

摘要： The ability to adjust one's behavioral strategy in complex environments is at the core of cognition. Doing so efficiently requires monitoring the reliability of the ongoing strategy and, when appropriate, switching away from it to evaluate alternatives. Studies in humans and non-human primates have uncovered signals in the anterior cingulate cortex (ACC) that reflect the pressure to switch away from the ongoing strategy, whereas other ACC signals relate to the pursuit of alternatives. However, whether these signals underlie computations that actually underpin strategy switching or merely reflect tracking of related variables remains unclear. Here we provide causal evidence that the rodent ACC actively arbitrates between persisting with the ongoing behavioral strategy and temporarily switching away to re-evaluate alternatives. Furthermore, by individually perturbing distinct output pathways, we establish that the two associated computations-determining whether to switch strategy and committing to the pursuit of a specific alternative-are segregated in the ACC microcircuitry.

关键词： 汪曾祺   《受戒》   沈从文   玩笑话   短篇小说  

摘要： 汪曾祺短篇小说《受戒》里,写到一个叫仁渡的和尚比较风流。他平常可是很规矩,看到姑娘媳妇总是老老实实的,连一句玩笑话都不说,一句山歌小调都不唱。但有一回在打谷场乘凉的时侯,一伙人把他围起来,非叫他唱两个不可。"他却情不过,说:‘好,唱一个。不唱家乡的。家乡的你们都熟。唱个安徽的。’"实际唱了两首,先一首以"姐和小郎打大麦"起头,四句,比较素,算是引子。"唱完了,大家还嫌不够,他就又唱了一个",如下:姐儿生得漂漂的,两个奶子翘翘的。

关键词： 茶叶   玫瑰   加工研究   香气  

摘要： 为了丰富茶的种类,增加茶香品质,将玫瑰花与茶叶一起进行发酵加工,融合白茶和红茶部分制备工艺技术特点,用同一种原料制备的一种玫瑰香茶与其他茶类加工进行对比分析。结果表明,玫瑰香茶在感官品质方面表现较佳,旨在为新款花香茶研究提供参考。