146 research outputs found

    Mutation of daf‐2 extends lifespan via tissue‐specific effectors that suppress distinct life‐limiting pathologies

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    In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF-1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf-2 insulin/IGF-1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf-2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS-regulated DAF-16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF-16 also promotes p Age in class 2 daf-2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf-2 interactions with the daf-12 steroid receptor implies that previously described opposing effects of daf-12 on daf-2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF-1 and steroid signaling. These findings support the view that wild-type IIS acts through multiple distinct mechanisms which promote different life-limiting pathologies, each of which contribute to late-life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan

    The stromal vascular fraction from fat tissue in the treatment of osteochondral knee defect: Case report

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    © 2018 Salikhov, Masgutov, Chekunov, Tazetdinova, Masgutova, Teplov, Galimov, Plakseichuk, Yagudin, Pankov and Rizvanov. In this study we applied autologous fat tissue stromal vascular fraction (SVF) cells in combination with microfracturing technique in a 36-year-old man with an osteochondral lesion of the medial femoral condyle 8 months after the injury. Cell material was generated by fat tissue liposuction from the anterior abdominal wall with subsequent extraction of the SVF and injected through a mini-arthrotomy portal with subsequent fibrin sealant fixation. The follow-up period was 2 years. Clinical score improved from 23 to 96 according to IKDC and from 10 to 90 according to EQ-VAS at 24 months follow-up. Magnetic resonance imaging (MRI) before the surgery revealed an osteochondral lesion with development of significant trabecular edema that remained unchanged for 6 months despite conservative treatment. MRI 1 and 2 years after the surgery showed the recovery of the damaged cartilage thickness with somewhat uneven structure and a decrease in the trabecular edema of the femoral condyle. The use of SVF cells with fibrin sealant fixation might be a promising approach in the treatment of osteochondral joint lesions. Further studies are required

    Production of YP170 vitellogenins promotes intestinal senescence in C. elegans

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    During aging, etiologies of senescence cause multiple pathologies, leading to morbidity and death. To understand aging requires identification of these etiologies. For example, C. elegans hermaphrodites consume their own intestinal biomass to support yolk production, which in later life drives intestinal atrophy and ectopic yolk deposition. Yolk proteins (vitellogenins) exist as 3 abundant species: YP170, derived from vit-1 - vit-5, and YP115 and YP88, derived from vit-6. Here we show that inhibiting YP170 synthesis leads to a reciprocal increase in YP115/YP88 levels and vice versa, an effect involving post-transcriptional mechanisms. Inhibiting YP170 production alone, despite increasing YP115/YP88 synthesis, reduces intestinal atrophy as much as inhibition of all YP synthesis, which increases lifespan. By contrast, inhibiting YP115/YP88 production alone accelerates intestinal atrophy and reduces lifespan, an effect that is dependent upon increased YP170 production. Thus, despite copious abundance of both YP170 and YP115/YP88, only YP170 production is coupled to intestinal atrophy and shortened lifespan. In addition, increasing levels of YP115/YP88 but not of YP170 increases resistance to oxidative stress; thus, longevity resulting from reduced vitellogenin synthesis is not attributable to oxidative stress resistance

    Use of Gene-Activated Demineralized Bone Allograft in the Therapy of Ulnar Pseudarthrosis. Case Report

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    © 2016, Springer Science+Business Media New York.This paper presents a clinical case of successful ulnar pseudarthrosis treatment using a gene-activated bone allograft containing VEGF (vascular endothelial growth factor) and BMP2 (bone morphogenetic protein 2) in the form of a multicystron plasmid. Demineralized bone matrix with applied recombinant plasmid DNA was grafted into the bone defect using the classical open surgical approach. Two months after the surgery, the patient noticed the disappearance of pain including pain during activity. On X-rays of ulna, signs of union in the form of callus formation were found

    Results of implementation of viral hepatitis B elimination program in the North-West Russia

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    Introduction. Vaccination contributed to reduce the incidence of acute hepatitis B in the territories of the North-West Russia. The urgency of this problem remains due to the high incidence of chronic hepatitis B. This accounted for the need to develop a hepatitis B elimination program in the district discussed that was approved in 2013 by the head of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing. Objective is to characterize the results of the program for the elimination of acute hepatitis B virus implemented in the North-Western Federal District. Materials and methods. The 2010–2020 incidence rate of acute and chronic hepatitis B virus (HBV) infection in the regions of the North-West Russia was carried out. To determine HBV genotypes and subgenotypes, 160 blood plasma samples from patients with acute hepatitis B were studied using molecular genetic methods (PCR, sequencing). The prevalence of latent hepatitis B in various population groups was assessed. The 2016–2020 hepatitis B vaccination coverage and relevant serological monitoring in adults was carried out. Results. While implementing the program, it was found that the incidence rate of acute hepatitis B in the district decreased by 4.5-fold, revealing in 2020 no cases of the disease in 5 regions, with incidence rate in the 6 subfederal units being lower than 1.0 per 100,000 population. Moreover, the incidence rate for chronic hepatitis B decreased by 2.6 times. The 2020 vaccination coverage of children under 17 and adults in all territories comprised more than 95% and 90%, respectively. In addition, it was shown the circulation of genotypes D and A of hepatitis B virus is dominated by genotype D (91.8%), subgenotype D2 (47.8%). The prevalence of latent hepatitis B among migrants was 6.5%, pregnant women — 4.9%, hemodialysis patients — 1.7%. Conclusion. Implementation of the program on elimination of acute viral hepatitis B in the territory of the North-West Russia contributed to raise in the vaccination coverage in adult population and lowered incidence rate of acute and chronic HBV infection

    The Eurasian Modern Pollen Database (EMPD), version 2

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    The Eurasian (née European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60 % from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019)Swiss National Science Foundation | Ref. 200021_16959

    Triple F - a comet nucleus sample return mission

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    The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-and-go sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS. © The Author(s) 2008

    The Eurasian Modern Pollen Database (EMPD), version 2

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    The Eurasian (nee European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60% from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019).Peer reviewe

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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