Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Chlorotoxin-Fc Fusion Inhibits Release of MMP-2 from Pancreatic Cancer Cells

Chlorotoxin (CTX) is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which inhibits low-conductance chloride channels in colonic epithelial cells. It has been reported that CTX also binds to matrix metalloproteinase-2 (MMP-2), membrane type-1 MMP, and tissue inhibitor of metalloproteinase-2, as well as CLC-3 chloride ion channels and other proteins. Pancreatic cancer cells require the activation of MMP-2 during invasion and migration. In this study, the fusion protein was generated by joining the CTX peptide to the amino terminus of the human IgG-Fc domain without a hinge domain, the monomeric form of chlorotoxin (M-CTX-Fc). The resulting fusion protein was then used to target pancreatic cancer cells (PANC-1) in vitro. M-CTX-Fc decreased MMP-2 release into the media of PANC-1 cells in a dose-dependent manner. M-CTX-Fc internalization into PANC-1 cells was observed. When the cells were treated with chlorpromazine (CPZ), the internalization of the fusion protein was reduced, implicating a clathrin-dependent internalization mechanism of M-CTX-Fc in PANC-1 cells. Furthermore, M-CTX-Fc clearly exhibited the inhibition of the migration depending on the concentration, but human IgG, as negative control of Fc, was not affected. The M-CTX-Fc may be an effective instrument for targeting pancreatic cancer

Studies on the Flower Pigments in Snapdragon, Antirrhinum majus L. : Effects of Light Control with the Various Covering Materials on the Anthocyanin Accumulation

In order to clarify the effect of restriction of solar rays on the anthocyanin accumulation in flower petals of snapdragon, whole or a part of plants was covered with various covering materials. Removal of ultraviolet light by covering the whole plant with some kind of UV-cut plastic film or FIRON did not affect on the anthocyanin content in flower petals. In covering the whole plant with various colored plastic films, the anthocyanin content was lowest under the green film and relatively high under the blue and the purple films. By covering either the flower spike or the leaves and stem except spike with cheesecloth the anthocyanin accumulation in petals was reduced, and the reduction effect was higher in covering the flower spike. The anthocyanin content in flower petals declined with the rise in the rate of shade of flower spikes, and the rate of decrease in the anthocyanin content depended on the cultivars.1.キンギョソウの植物体全体または一部を各種資材により被覆して太陽光を制限し,花弁のアン卜シアニン蓄積におよぼす影響をみた.2.紫外線カットオフフィルムおよびファイロンによる植物体全体の被覆では,花弁のアン卜シアニン蓄積量および新鮮重に対して,明らかな影響はみられなかった.3.着色フィルムによる植物体全体の被覆では,花弁の新鮮重の増大に対して,緑色および紫色フィルムの抑制効果は大であり,赤色,青色およびラジアントフィルムでは小であった.またアン卜シアニン蓄積量に対する抑制効果は,緑色フィルムが最も大きく,青色および紫色フィルムでは比較的小であった.4.花穂および花穂以外の茎葉をそれぞれ寒冷紗によって被覆したところ,花弁の新鮮重は花穂以外の茎葉の被覆によってより強く抑制された.しかし,花穂のみの被覆による抑制も明白であった.アン卜シアニン蓄積量は,花穂および花穂以外の被覆ともに抑制されたが,その効果は花穂のみの被覆の方がより強かった.5.数品種(系統を含む)のキンギョソウの花穂のみを寒冷紗(クレモナ#600)1枚,2枚,3枚およびアルミはくで被覆した実験では,花弁の新鮮重およびアン卜シアニン蓄積量ともに,遮光率を高めるに従って減少した.ただし,光度の減少に伴うアントシアニンの減少率は品種によって大きく異なった

Sex Difference in the Safety and Efficacy of Bariatric Procedures: a Systematic Review and Meta-analysis

with the prevalence of obesity alarmingly increasing, it is of primary interest to identify those factors predicting the success of anti-obesity therapeutic strategies currently adopted in clinical practice, and in particular, those of bariatric procedures showing the greatest success in terms of weight loss and maintenance in both the short and long term. Given sex-related differences in psychosocial status, hormonal homeostasis, and body fat distribution, it is likely that the response to different weight management strategies differs by sex. The objective was to elucidate the effect of sex on different bariatric procedures’ efficacy and safety outcomes. Searches of PubMed, Cochrane, and Embase databases were performed, followed by hand-searching of reference lists from all relevant articles. We included all the studies evaluating the effect of bariatric procedures on body mass index loss (BMIL), and/or percentage excess weight loss (%EWL), and/or percentage excess body mass index loss, and/or percentage of responders, and/or short-/long-term complications and co-morbidity resolution, broken down by sex. Twenty-seven studies with a total of 114,919 patients were included. Men were more likely to achieve greater BMIL, consistent with higher male baseline BMI, and women were 2.87 times more likely to be classified as weight responders (95% confidence interval [CI]: 1.90–4.34), as well as to perform better in terms of %EWL (95% CI: .13–.54). Upon subgroup analysis based on bariatric procedure, women were more likely to be successful in terms of %EWL upon bioenteric intragastric balloon (BIB) placement (.72, 95% CI: .42–1.02). There was no sex difference regarding investigated co-morbidity resolution (hypertension, diabetes, and obstructive sleep apnea syndrome) or occurrence of short-term complications, whereas women were more likely to develop long-term complications, with an odds ratio of 1.97 (95% CI: 1.57–2.49). Sex does not have a clear effect on efficacy outcomes of bariatric procedures. Differentiating by procedure, BIB may be more effective in women, although results are discordant based on the weight loss outcome considered. If the short-term postoperative complication rate is similar across both sexes, long-term complications occur more frequently in women. To clarify the real effect of sex on bariatric procedure–derived health benefits, it is crucial to report sex-stratified results in future studies, as well as evaluate body composition changes that go beyond simple body weight reduction

The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes

Abstract Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation

Correction: Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-Determination: the Italian Road to Bariatric Surgery

Purpose Bariatric surgery (BS) is considered the most efcient treatment for severe obesity. International guidelines recommend multidisciplinary approach to BS (general practitioners, endocrinologists, surgeons, psychologists, or psychiatrists), and access to BS should be the fnal part of a protocol of treatment of obesity. However, there are indications that general practitioners (GPs) are not fully aware of the possible benefts of BS, that specialty physicians are reluctant to refer their patients to surgeons, and that patients with obesity choose self-management of their own obesity, including internet-based choices. There are no data on the pathways chosen by physicians and patients to undergo BS in the real world in Italy. Methods An exploratory exam was performed for 6 months in three pilot regions (Lombardy, Lazio, Campania) in twentythree tertiary centers for the treatment of morbid obesity, to describe the real pathways to BS in Italy. Results Charts of 2686 patients (788 men and 1895 women, 75.5% in the age range 30–59 years) were evaluated by physicians and surgeons of the participating centers. A chronic condition of obesity was evident for the majority of patients, as indicated by duration of obesity, by presence of several associated medical problems, and by frequency of previous dietary attempts to weight loss. The vast majority (75.8%) patients were self-presenting or referred by bariatric surgeons, 24.2% patients referred by GPs and other specialists. Self-presenting patients were younger, more educated, more professional, and more mobile than patients referred by other physicians. Patients above the age of 40 years or with a duration of obesity greater than 10 years had a higher prevalence of all associated medical problems. Conclusions The majority of patients referred to a tertiary center for the treatment of morbid obesity have a valid indication for BS. Most patients self-refer to the centers, with a minority referred by a GP or by specialists. Self-presenting patient