β-Elimination of phosphate and subsequent addition of pyridoxamine as a method for identifying and sequencing peptides containing phosphoseryl residues

AbstractPeptides containing phosphoseryl residues can be modified by removal of the phosphate groups via β-elimination followed by addition of pyridoxamine to the resulting dehydroalanyl residue. Peptides containing the modified residues can be detected at nanomole levels by monitoring absorbance at 328 nm or at picomole levels by monitoring fluorescence. Photolysis of the modified peptide converts the pyridoxamino adduct to a form which can be readily identified after Edman degradation

Purification and Characterization of a cAMP- and Ca2+-Calmodulin-Independent Glycogen Synthase Kinase from Porcine Renal Cortex

We recently reported the partial purification of a cAMP-independent and Ca2+-calmodulin-independent glycogen synthase kinase from porcine renal cortex (Schlender, K. K., Beebe, S. J., and Reimann, E. M. (1981) Cold Spring Harbor Conf. Cell Proliferation, 389-400). Subsequent purification indicated that the enzyme preparation consisted of at least three forms of glycogen synthase kinase which could be resolved by ATP gradient elution from aminoethylphosphate-agarose (AEP-agarose). The predominant form of glycogen synthase kinase, which eluted from AEP-agarose between 2 and 6 mM ATP, was purified approximately 800-fold and is designated GSK-A1. It had a molecular weight of 45,000-50,000 as determined by gel filtration and sucrose density gradient centrifugation. It catalyzed the transfer of 1 mol of 32P/mol of synthase subunit into a low molecular weight (10,000) CNBr peptide which was tentatively identified as Ser-7 (site 2) by high performance liquid chromatography. This phosphorylation decreased the activity ratio (activity in the absence of glucose-6-P divided by activity in the presence of 7.2 mM glucose-6-P) from 0.95 to about 0.55. GSK-A1 appeared to be specific for and had low s0.5 values for both substrates, ATP (13 µM) and glycogen synthase (0.3-0.4 µM). The enzyme could not use GTP as the phosphate donor. GSK-A1 was not affected by the protein kinase inhibitor, cAMP, cGMP, Ca2+-calmodulin, EGTA, or trifluoperazine and had a broad pH optimum (pH 7.0-8.5). A second form, GSK-A2, was eluted from AEP-agarose between 7 and 9 mM ATP. GSK-A2 could transfer a 2nd mol of 32P/mol of synthase subunit and decreased the activity ratio to 0.30. The interrelation among these multiple forms is not clear, but the data suggest that multiple kinases are required to form the highly inactivated glycogen synthase in renal tissues

Prevalence and significance of sexually transmitted diseases among Ethiopian women attending antenatal clinics in Addis Ababa

Abstract: To determine the prevalence of sexually transmitted diseases (STDs) and the risk for (i) the mother regarding pregnancy wastage and puerperal sepsis and (ii) the child with regard to congenital and neonatal infection, 342 routine antenatal clinic (ANC) at tenders were investigated. The prevalence of antibodies showing exposure to specific STD pathogens in pregnant women attending ANC was: syphilis (TPHA) 27%, (VDR:) 28%, gonorrhoea 43%, genital chlamydiae 54%, HBV 37%, HSV-2 35 %, H ducreyi 10%. High titre seropositivity suggestive of active infection was: gonorrhoea 10%, genital chlamydiae 31 %, HSV2 19%; with HBV SAg 5% -all of which are likely to be transmitted to the foetus in utero or during delivery. Only 10% of ANC at tenders had no serological evidence of any STD: 72% had serological evidence for two or more STDs. Among conditions requiring treatment vaginitis was the most important, 20% having a severe trichomonal infection. Despite the frequency of this condition it was noted that few women (4%) complained of vaginal discharge. Thus women attending the ANC revealed a high prevalence of STD. Consequently the foetus and neonate are put at risk because of intrauterine or intrapartum transmission of infection. The high prevalence among ANC at tenders also reflects the relative prevalence of STDs in the community. Measures such as screening at ANC and information and education regarding prevention are required to reduce STDs in pregnant women and their sexual partners. Prophylaxis for the neonate can be considered until this goal is achieved. [Ethiop. J. Health Dev. 1995;9(1):31-40

A sociological and serological study of at tenders of family planning clinics in Addis Ababa

Abstract: A study of 542 women attending family planning clinics (FPC) and 1568 women attending obstetric and gynaecologic clinics in Addis Ababa showed utilisation of FPC was highest in those with a family income of 100-500 EB per month (36%), in women who were: Tigrawi (33%) or Amara (31 %), aged 20-34 years (30%), age 16 or older at first marriage/coitus (28%), parity of 2... 2 children (35%), > 5 lifetime husbands/sexual partners (39%), or were bargirls (73%) or prostitutes (43%). FPC attendance was lowest among the nulliparous (2.3%), women from rural areas (10%), the Guragie (10%) and Oromo women (19%), Moslem women 14(%), those of subsistence income ( < 10EB per month) (14%). The seroprevalence rates indicative of exposure to STD pathogens were high as was the prevalence of essentially asymptomatic pelvic inflammatory disease (PID). Only 4% of FPC at tenders had no serological evidence of STD: 64% had 3 or more different STD. Specific present or active STD infection prevalence for syphilis (VDRL) 28%, Neisseria gonorrhoea 31 %, genital chlamydia 46% and HSV-2 21% was higher in FPC at tenders than among women attending other clinics. Clinical evidence of PID was also more common in the FPC at tenders (54%), 37% having evidence of salpingitis. Thus FPCs provide a useful setting for screening women particularly at risk. Because of lack of symptoms, these women are unlikely to attend either an STDs clinic or a hospital for routine check up, and as such are not treated and represent a population from which STDs can spread into the population. Measures to screen, treat and educate FPC at tenders, their partners and their clients, are recommended in an attempt to Control STDs and ultimately HIV in the community. [Ethiop. J. Hea/th Dev. 1995;9(1):19-30

Perspectives for systems biology in the management of tuberculosis

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.Publisher PDFPeer reviewe

Semiconductor Spintronics

Spintronics refers commonly to phenomena in which the spin of electrons in a solid state environment plays the determining role. In a more narrow sense spintronics is an emerging research field of electronics: spintronics devices are based on a spin control of electronics, or on an electrical and optical control of spin or magnetism. This review presents selected themes of semiconductor spintronics, introducing important concepts in spin transport, spin injection, Silsbee-Johnson spin-charge coupling, and spindependent tunneling, as well as spin relaxation and spin dynamics. The most fundamental spin-dependent nteraction in nonmagnetic semiconductors is spin-orbit coupling. Depending on the crystal symmetries of the material, as well as on the structural properties of semiconductor based heterostructures, the spin-orbit coupling takes on different functional forms, giving a nice playground of effective spin-orbit Hamiltonians. The effective Hamiltonians for the most relevant classes of materials and heterostructures are derived here from realistic electronic band structure descriptions. Most semiconductor device systems are still theoretical concepts, waiting for experimental demonstrations. A review of selected proposed, and a few demonstrated devices is presented, with detailed description of two important classes: magnetic resonant tunnel structures and bipolar magnetic diodes and transistors. In most cases the presentation is of tutorial style, introducing the essential theoretical formalism at an accessible level, with case-study-like illustrations of actual experimental results, as well as with brief reviews of relevant recent achievements in the field.Comment: tutorial review; 342 pages, 132 figure

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

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