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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Functional characterization of protein kinase NLK (nemo-like kinase)

145 p.Nemo-like kinase (NLK) is a species conserved serine/threonine kinase that belongs to the mitogen activated protein kinases (MAPKs) and cyclin-dependent kinases (CDKs) families. TAK.1 (Transforming Growth Factor-beta activated protein kinase) acts as the upstream kinase of NLK and regulates the function of NLK in multiple signaling pathways such as Wnt-1, IL6 and TGF0. The preliminary findings of my research work highlight the versatile function of NLK because of its substrates that range from adaptor proteins like TAB2/3 (TAK1 binding protein 2/3) to transcriptional factors like c-jun (Activator protein 1 or AP-1) in the same signaling pathway to regulate TAK1 mediated signaling.DOCTOR OF PHILOSOPHY (SBS

Study on the Extraction and Utilization of Natural Dye from Tamarind Seed Testa

The present research work is emphasized on the preparation of natural dye (concentrated solution) from tamarind seed testa. Tamarind seed contains nearly 30 percent of testa and 70 percent of kernel. The testa was removed from the seeds by roasting and subsequent pounding. The testa contains a dyestuff which was used for dyeing of cotton fabrics. The physico-chemical properties such as pH, acidity, moisture content, ash content and total solids content of tamarind seed testa were determined by Association of Official Analytical Chemists (AOAC) method. The chemical compounds present in tamarind seed testa were investigated by phytochemical tests. An attempt was made on the dyeing of cotton fabrics using of natural dye (concentrated solution) from tamarind seed testa with different mordants such as zinc sulphate, potassium dichromate, ferrous sulphate and three different dyeing methods such as pre-mordanting, post-mordanting and simultaneous mordanting and dyeing method. Moreover, fastness for rubbing and washing of dyed cotton fabrics was determined. Staining and colour change of dyed cotton fabrics were assessed by using standard Grey scale. The dye extraction was carried out at testa to water ratio of 1:40 and the resulting natural dye (concentrated solution) was employed for dyeing of cotton fabrics. Dyeing at 90ºC for 45 min followed by postmordanting with potassium dichromate enhanced the highest amount of dye adsorbed on cotton fabrics and good fastness properties

Multidimensional Analysis for Census Data by Applying Star Schema Model

In recent years, the high value of multidimensional data has been recognized in both the academic and business communities. Star schemas are the primary storage mechanism for multidimensional data that is to be queried efficiently. It supports relationships between fact and dimension tables and creating combination dimensions with a key, resulted to improve query performance for large quantities of data. This paper is presented for multidimensional data model, that is called star schema to store large amount of census data. This star schema can be used for business related queries on Census data for visualization report. This paper aims to enhance the interactive visualization process with more relevant operations for manipulation of various attributes by using the Pentaho Business Analytics (BA) Suite

Attrition among HIV positive children enrolled under integrated HIV care programme in Myanmar: 12 years cohort analysis

Background: In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program for HIV treatment and care since 2005. Objectives: To assess the: (a) attrition (death or loss-to-follow-up) rates among children (aged ≥ 18 months to < 15 years) enrolled into the programme before and after initiation of anti-retroviral therapy (ART) (pre-ART and ART periods); (b) demographic and clinical factors associated with attrition during these two periods. Methods: Children enrolled in IHC Programme and their status (death, lost to follow-up, regular follow-up or transferred out) was assessed as on 30 June 2017. Attrition rates (per 100 person-years) at pre – ART and ART periods were calculated and the association between demographic and clinical characteristics with attrition was assessed using Cox proportional hazards model. Results: Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100 person-years of follow-up (95% CI: 17–21) and ART attrition rate was 4 per 100 person-years of follow-up (95% CI: 3–4) with higher levels during the initial few months of enrolment. The 36-month retention rates during pre-ART period was 75% (95% CI: 72–78) and during ART period was 87% (95% CI: 86–88). The children ‘at enrolment’ with relatively lower levels of haemoglobin, immune deficiency, underweight for age, higher WHO clinical stages, presence of hepatitis B infection had higher hazards of attrition in both periods. Conclusion: The attrition rates are high particularly among children with relatively poorer clinical, nutritional profiles at enrolment. The study suggests the urgent need for improving adherence counselling especially during the initial few months of enrolment and early ART initiation

TAK1, more than just innate immunity

Transforming growth factor β-activated kinase 1 (TAK1) is a key regulator of the innate immunity and the proinflammatory signaling pathway. In response to interleukin-1, tumor necrosis factor-α, and toll-like receptor agonists, it mediates the activation of the nuclear factor κB (NF-κB), c-Jun N-terminal kinase (JNK), and p38 pathways. In addition, TAK1 plays a central role in adaptive immunity, in which it mediates signaling from T- and B-cell receptors. This review will focus on recent developments and also examine the regulation of TAK1 in response to a diverse range of other stimuli including DNA damage, transforming growth factor-β, Wnt, osmotic stress, and hypoxia

Single-Cell Identity Generated by Combinatorial Homophilic Interactions between α, β, and γ Protocadherins

Individual mammalian neurons express distinct repertoires of protocadherin (Pcdh) -α, -β and -γ proteins that function in neural circuit assembly. Here we show that all three types of Pcdhs can engage in specific homophilic interactions, that cell surface delivery of alternate Pcdhα isoforms requires cis interactions with other Pcdh isoforms, and that the extracellular cadherin domain EC6 plays a critical role in this process. Analysis of specific combinations of up to five Pcdh isoforms showed that Pcdh homophilic recognition specificities strictly depend on the identity of all of the expressed isoforms, such that mismatched isoforms interfere with cell-cell interactions. We present a theoretical analysis showing that the assembly of Pcdh-α, −β and −γ isoforms into multimeric recognition units, and the observed tolerance for mismatched isoforms can generate the cell surface diversity necessary for single-cell identity. However, competing demands of non-self discrimination and self-recognition place limitations on the mechanisms by which recognition units can function

The context of REDD+ in Myanmar: Drivers, agents and institutions [Burmese]

The Republic of the Union of Myanmar is a forest resource-rich country, but is also facing serious deforestation and forest degradation problems. Currently, Myanmar's forest still covers more than 40% of the country's land area (Aung (2001) but 70% of its population live in rural areas, and the agricultural sector is the main contributor to the country's gross domestic product (GDP) (30%) (World Bank 2014). The country faces the all-too-common dilemma of how to develop its economy while at the same time curbing environmental degradation and contributing to carbon emissions reduction. In 2013, Myanmar adopted a REDD+ program and started its preparatory phase. Myanmar established and developed its National Forest Monitoring System (NFMS) and Reference Emission Levels (RELs) for REDD+ following the guidance and modalities set out by the United Nations Framework Convention on Climate Change (UNFCCC). Implementing REDD+ requires political commitment to address direct and indirect drivers of deforestation, an adequate funding mechanism that is based on a thorough analysis of all costs and benefits, a transparent and equitable benefit-sharing mechanism, and a participatory decision-making approach in which all stakeholders can take part in REDD+. The Global Comparative Study on REDD+, together with its country partners, is compiling profiles of 14 countries to better understand the socioeconomic contexts in which REDD+ policies and processes emerge