Alteration of renal respiratory Complex-III during experimental type-1 diabetes

<p>Abstract</p> <p>Background</p> <p>Diabetes has become the single most common cause for end-stage renal disease in the United States. It has been established that mitochondrial damage occurs during diabetes; however, little is known about what initiates mitochondrial injury and oxidant production during the early stages of diabetes. Inactivation of mitochondrial respiratory complexes or alteration of their critical subunits can lead to generation of mitochondrial oxidants, mitochondrial damage, and organ injury. Thus, one goal of this study was to determine the status of mitochondrial respiratory complexes in the rat kidney during the early stages of diabetes (5-weeks post streptozotocin injection).</p> <p>Methods</p> <p>Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE), Complex III immunoprecipitation, and an ATP assay were performed to examine the effects of diabetes on the status of respiratory complexes and energy levels in renal mitochondria. Creatinine clearance and urine albumin excretion were measured to assess the status of renal function in our model.</p> <p>Results</p> <p>Interestingly, of all four respiratory complexes only cytochrome c reductase (Complex-III) activity was significantly decreased, whereas two Complex III subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic renal mitochondria. The BN-PAGE data suggested that Complex III failed to assemble correctly, which could also explain the compensatory upregulation of specific Complex III subunits. In addition, the renal F₀F₁-ATPase activity and ATP levels were increased during diabetes.</p> <p>Conclusion</p> <p>In summary, these findings show for the first time that early (and selective) inactivation of Complex-III may contribute to the mitochondrial oxidant production which occurs in the early stages of diabetes.</p

What do we (not) know about research software engineering?

As recognition of the vital importance of software for contemporary research is increasing, Research Software Engineering (RSE) is emerging as a discipline in its own right. We present an inventory of relevant research questions about RSE as a basis for future research and initiatives to advance the field, highlighting selected literature and initiatives. This work is the outcome of a RSE community workshop held as part of the 2020 International Series of Online Research Software Events (SORSE) which identified and prioritized key questions across three overlapping themes: people, policy and infrastructure. Almost half of the questions focus on the people theme, which addresses issues related to career paths, recognition and motivation; recruitment and retention; skills; and diversity, equity and inclusion. However, the people and policy themes have the same number of prioritized questions. We recommend that different types of stakeholders, such as RSE employers and policy makers, take responsibility for supporting or encouraging answering of these questions by organizations that have an interest. Initiatives such as the International Council of RSE Associations should also be engaged in this work

What Do We (Not) Know About Research Software Engineering?

As recognition of the vital importance of software for contemporary research is increasing, Research Software Engineering (RSE) is emerging as a discipline in its own right. We present an inventory of relevant research questions about RSE as a basis for future research and initiatives to advance the field, highlighting selected literature and initiatives. This work is the outcome of a RSE community workshop held as part of the 2020 International Series of Online Research Software Events (SORSE) which identified and prioritized key questions across three overlapping themes: people, policy and infrastructure. Almost half of the questions focus on the people theme, which addresses issues related to career paths, recognition and motivation; recruitment and retention; skills; and diversity, equity and inclusion. However, the people and policy themes have the same number of prioritized questions. We recommend that different types of stakeholders, such as RSE employers and policy makers, take responsibility for supporting or encouraging answering of these questions by organizations that have an interest. Initiatives such as the International Council of RSE Associations should also be engaged in this work

DNA Methyltransferase Controls Stem Cell Aging by Regulating BMI1 and EZH2 through MicroRNAs

Epigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16INK4A and p21CIP1/WAF1 expression. DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16INK4A and p21CIP1/WAF1 promoter regions. Enrichment of EZH2, the key factor that methylates histone H3 lysine 9 and 27 residues, was decreased on the p16INK4A and p21CIP1/WAF1 promoter regions. We found that DNMT inhibition decreased expression levels of Polycomb-group (PcG) proteins and increased expression of microRNAs (miRNAs), which target PcG proteins. Decreased CpG island methylation and increased levels of active histone marks at genomic regions encoding miRNAs were observed after 5-AzaC treatment. Taken together, DNMTs have a critical role in regulating the cellular senescence of hUCB-MSCs through controlling not only the DNA methylation status but also active/inactive histone marks at genomic regions of PcG-targeting miRNAs and p16INK4A and p21CIP1/WAF1 promoter regions

Designed Metal-ATCUN Derivatives: Redox- and Non-redox-Based Applications Relevant for Chemistry, Biology, and Medicine

UID/QUI/50006/2019The designed "ATCUN'' motif (amino-terminal copper and nickel binding site) is a replica of naturally occurring ATCUN site found in many proteins/peptides, and an attractive platform for multiple applications, which include nucleases, proteases, spectroscopic probes, imaging, and small molecule activation. ATCUN motifs are engineered at periphery by conjugation to recombinant proteins, peptides, fluorophores, or recognition domains through chemically or genetically, fulfilling the needs of various biological relevance and a wide range of practical usages. This chemistry has witnessed significant growth over the last few decades and several interesting ATCUN derivatives have been described. The redox role of the ATCUN moieties is also an important aspect to be considered. The redox potential of designed M-ATCUN derivatives is modulated by judicious choice of amino acid (including stereochemistry, charge, and position) that ultimately leads to the catalytic efficiency. In this context, a wide range of M-ATCUN derivatives have been designed purposefully for various redox- and non-redox-based applications, including spectroscopic probes, target-based catalytic metallodrugs, inhibition of amyloid-beta toxicity, and telomere shortening, enzyme inactivation, biomolecules stitching or modification, next-generation antibiotic, and small molecule activation.publishersversionpublishe

Measurement of the W-Pair Production Cross Section and W-Decay Branching Fractions in e+e−e^{+}e^{-} Interactions at s\sqrt{s}= 189 GeV

The data collected by the L3 experiment at LEP at a centre-of-mass energy of $188.6~\rm{Ge\kern -0.1em V}$ are used to measure the W-pair production cross section and the W-boson decay branching fractions. These data correspond to an integrated luminosity of 176.8~pb$^{-1}$. The total cross section for W-pair production, combining all final states, is measured to be $\sigma_{\rm{WW}}= 16.24 \pm 0.37~(stat.) \pm 0.22~(syst.)$~pb. Including our data collected at lower centre-of-mass energies, the hadronic branching fraction of the W-boson is determined to be $B(\rm{W} \rightarrow \rm{qq})= \left[ 68.20 \pm 0.68~(stat.) \pm 0.33~(syst.)\right]~\%$. The results agree with the Standard Model predictions.The data collected by the L3 experiment at LEP at a centre-of-mass energy of 188.6 GeV are used to measure the W-pair production cross section and the W-boson decay branching fractions. These data correspond to an integrated luminosity of 176.8pb^-1. The total cross section for W-pair production, combining all final states, is measured to be sigma_WW = 16.24 +/- 0.37(stat.) +/- 0.22(syst.) pb. Including our data collected at lower centre-of-mass energies, the hadronic branching fraction of the W-boson is determined to be B(W ->qq) = [68.20 +/- 0.68 (stat.) +/- 0.33 (syst.) ] %. The results agree with the Standard Model predictions.The data collected by the L3 experiment at LEP at a centre-of-mass energy of 188.6 GeV are used to measure the W-pair production cross section and the W-boson decay branching fractions. These data correspond to an integrated luminosity of 176.8 pb −1 . The total cross section for W-pair production, combining all final states, is measured to be σ WW =16.24±0.37 (stat.)±0.22 (syst.) pb. Including our data collected at lower centre-of-mass energies, the hadronic branching fraction of the W-boson is determined to be B (W→qq)=[68.20±0.68 (stat.)±0.33 (syst.)]%. The results agree with the Standard Model predictions

Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216