A de novo germline mutation of APC for inheritable colon cancer in a Chinese family using multigene next generation sequencing

Inheritable colorectal cancers (CRC) accounted for about 20% of the CRC cases, such as hereditary nonpolyposis colorectal cancer (HNPCC), Gardner syndrome and familial adenomatous polyposis (FAP). A four-generation Han Chinese family was found affected with polyposis in colons. Inferred from the pedigree structure, the disease in this family showed an autosomal dominant inheritance model. To locate the causal mutations in this family, genomic DNAs were extracted and the next generation sequencing for 5 genes relating to colon cancer performed by Ion Torrent Personal Genome Machine with a 314 chip. The reads were aligned with human reference genome hg19 to call variants in the 5 genes. After analysis, 14 variants were detected in the sequenced sample and 13 been collected in dbSNP database and assigned with a rs identification number. In these variants, 9 were synonymous, 4 missense and 1 non-sense. In them, 2 rare variants (c.694C>T in APC and c.1690A>G in MSH2) might be the putative causal mutations for familial adenomatous polyposis (FAP) since the rarity of the mutated allele in normal controls. c.694C>T was detected in only affected members and generated a premature stop codon in APC. It should be a de novo germline mutation making APC containing this stop codon as targets for nonsense-mediated mRNA decay (NMD). c.1690A>G in MSH2 was not only detected in affected members, but also in normal ones in the family. Functional prediction revealed that the amino acid affected by this variant had no effect on the function of MSH2. Here, we report a de novo germline mutation of APC as the causal variant in a Chinese family with inheritable colon cancer by the next generation sequencing.     

Changes in Elephant Abundance Affect Forest Composition or Regeneration?

While overall numbers of African elephant have declined dramatically in recent times, some populations are now confined to protected areas and are locally overabundant—an undesirable situation for both biodiversity conservation and elephants. In forested protected areas, options to manage elephants are limited because it is difficult to safely approach animals, yet it is vital that these populations are managed because browsing by elephants can dramatically alter forest ecosystems. Using data collected over 50 yr in Kibale National Park, Uganda, we examine the prediction that increasing elephant numbers and associated changes in their foraging behavior have caused a shift in tree community composition. Although the relative abundance of elephants increased significantly between 1996 and 2010, the population structure of their preferred tree food species did not change, nor did tree community composition change in favor of species able to re‐sprout after elephant damage. Furthermore, over the last 50 yr Kibale elephants have not become more selective foragers, as would be expected if more nutritious tree species were declining. However, elephants are more abundant in disturbed areas dominated by shrubs and grasses and appear to have arrested forest succession in these areas. At their current abundance, elephants have not selectively altered the composition of intact old growth forest, but they do inhibit the regeneration of disturbed areas.     

Resultados preliminares de un programa comunitario de prevención de caídas: estudio Precari (prevención de caídas en La Ribera)

Objective

To evaluate the results of a fall prevention programme designed to be applied to the elderly living in the community.

Material and methods

The sample consisted of 249 participants ≥70 years of age, who were randomly assigned to one of three groups. The monthly intervention group (GIM): instructions on fall prevention and healthy exercises to improve physical function and balance at beginning of the study, and a monthly theoretical and practical refresher session. The quarterly intervention group (GIT), with the same beginning intervention and a refresher session every three months. The control group (GC), the same beginning intervention but no refresher sessions.

Results

The mean age of the sample was 74.47 years (SD 5.33), with 64% women. The incidence of falls was reduced from 0.64 per patient year in the previous year to 0.39 in the post-intervention year in GIM, from 0.49 to 0.47 in GIT, and in the GC it remained at 0.47 before and twelve months after, but with no significant differences in the reduction between groups (P=.062). At the end of the study there was a decrease in Rizzo scale of 0.72 points (95% CI: 0.57-0.88, P<.001).

Conclusion

An interdisciplinary community intervention programme can contribute to reducing the incidence of falls. Further studies are required to continue research into the incidence of falls in the elderly living in the community.     

La calidad de vida en ancianos polimedicados con multimorbilidad

Objectives

To estimate the values of the quality of life dimensions using the SF-12 questionnaire in the elderly on polymedication and with multiple morbidities, and identify the variables associated with it.

Material and methods

A cross-sectional study on a sample of 393 patients selected from the elderly population over 67 years and who took more than 5 drugs. The SF-12 was complemented by a personal interview in the clinic or in the home of the patient. Central tendency, dispersion, and the percentiles of the 8 dimensions were calculated, as well as the SF-36 physical and mental component summary measures (PCS and MCS). All patients below the 25th percentile of the PCS and MCS were classified as patients with a deterioration. Logistic regression was used to determine the variables that were associated with the deterioration in the quality of life.

Results

It is a population with high morbidity. The subjects showed very low scores on the general health scales −mean (SD): 25.7 (17.4)−; physical function −32.6 (32.1)−; and PCS: [(37.8 (25.1)]. Women had a worse quality of life than men in all the scales. Female sex, being over 80 years, frequent falls, chronic pain, cancerous disease, and depression, are variables that determine the health-related quality of life (HR-QoL).

Conclusion

This population has a poor HR-QoL, particularly in the physical dimensions. Chronic pain and depression, together with age and being female are variables that determine the deterioration in the HR-QoL.     

谷氧还蛋白2与人类健康

谷氧还蛋白2(Glutaredoxin 2,GLRX2)是一种相对分子质量较小的氧化还原酶,属于硫氧还蛋白家族成员,以谷胱甘肽为辅基调节细胞的氧化还原内环境。在非应激条件下,GLRX2结合铁硫簇,以二聚体形式存在,可能参与铁硫簇的转运或运输;当氧化压力增加时,铁硫簇解聚,GLRX2二聚体转化为GLRX2单体,利用单巯基或双巯基机制,发挥抗氧化应激和抗细胞凋亡的功能。GLRX2与人类健康和疾病,如心血管疾病、神经退行性疾病、白内障、肿瘤细胞生长与分化和精子成熟等密切相关。因此,对GLRX2的深入研究将有助于设计针对氧化应激的药物,为治疗和预防由此产生的疾病或健康问题带来新的希望。     

Hommes et environnements au Paléolithique supérieur en Ukraine continentale et en Crimée : introduction

Research, conducted under the ANR project “Mammouths”, on “the end of the mammoth steppe: Man/Environment relationship during late Pleniglacial in Eastern Europe”, is the subject of several contributions, a part of them is published in this volume, under the heading “Humans and environments during Upper Paleolithic in mainland Ukraine and Crimea”, in the French journal L’anthropologie.     

Brief Report: Autophagy during beef aging

The conversion of muscle into meat is a complex process of major concern for meat scientists due to its influence on the final meat quality. The aim of this study was to investigate the occurrence of autophagic processes in the conversion of muscle into meat. Our findings demonstrated, for the first time, the occurrence of autophagic processes in the muscle tissue at early postmortem period (2 h to 24 h) in both beef breeds studied (Asturiana de los Valles and Asturiana de la Montaña) showing significant time-scale differences between breeds, which could indicate a role of this process in meat maturation. These breeds have different physiological features: while Asturiana de los Valles is a meat-specialized breed showing high growth rate, an elevated proportion of white fibers in the muscle and low intramuscular fat level, Asturiana de la Montaña is a small- to medium-sized rustic breed adapted to less-favored areas, showing more red fibers in the muscle and a high intramuscular fat content.     

Non-referenced genome assembly from epigenomic short-read data

Current computational methods used to analyze changes in DNA methylation and chromatin modification rely on sequenced genomes. Here we describe a pipeline for the detection of these changes from short-read sequence data that does not require a reference genome. Open source software packages were used for sequence assembly, alignment, and measurement of differential enrichment. The method was evaluated by comparing results with reference-based results showing a strong correlation between chromatin modification and gene expression. We then used our de novo sequence assembly to build the DNA methylation profile for the non-referenced Psammomys obesus genome. The pipeline described uses open source software for fast annotation and visualization of unreferenced genomic regions from short-read data.