COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management

Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3–7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients.     

Chemical speciation of arsenic in urine of patients with blackfoot disease

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Although extensive epidemiological study has implicated high arsenic content in artesian well water of the endemic area bears some important connection with the disease, the etiology of the disease is still not clarified. In this study, attention is paid to chemical speciation of arsenic in order to find out whether the concentrations of arsenic species in urine of Blackfoot disease patients are different from those of controls. Experimental results indicate that the total arsenic, inorganic arsenic, monomethylarsonic acid, and other forms of arsenic in the urine of patients are significantly higher than those of the contols. The possible connection of those arsenic species with the etiology of the disease is discussed.     

Selective dimerization of cysteines in glycopeptides and phosphopeptides

Summary To study the influence of phosphorylation and oxidation on the repeat domains of human Tau protein, we faced the challenge to selectively dimerize two cysteine-containing peptides in the presence of a nearby phosphate group. To this end, we were able to demonstrate the utility of a selective dimerization approach by forming disulfide bonds in unprotected phosphopeptides and extended the methodology to unprotected glycopeptides. Activation of one cysteine of a peptide chain with 2,2-dithiodipyridine and coupling this thiopyridyl-peptide to another peptide chain, containing an unprotected cysteine residue, yielded the mixed dimers in high purities and reasonable yields. Phosphate or sugar side chains on either peptide component remained unaffected during the activation and dimerization processes. While for mixed dimers the activated peptides were isolated by chromatography, homodimers were obtained by a simple one-pot reaction after 1 h. We demonstrate that cysteines can be dimerized in unprotected phosphopeptides and glycopeptides, without any side reactions affecting these posttranslational modifications.Abbreviations DCM dichloromethane - DMF N,N-dimethylformamide - DTP 2,2-dithiodipyridine - Fmoc 9-fluorenylmethyloxycarbonyl - HPLC high-performance liquid chromatography - MALDI matrix-assisted laser desorption/ionization - MS mass spectrometry - NFT neurofibrillary tangles - PHF paired helical filaments - PKC protein kinase C - RP reversed phase - human Tau protein - TFA trifluoroacetic acid Parts of this paper were presented at the 24th European Peptide Symposium in Edinburgh, Scotland, U.K., September 8–13, 1996.     

The dental awareness and needs of a Parkinson's disease population

The dental awareness and needs of a population with Parkinson's disease were assessed by means of postal questionnaires sent to members of Parkinson's disease societies of Belfast and London. A total of 228 valid replies were received representing a response rate of 31%. Results showed that dental problems were reported often, xerostomia and burning sensation being at least twice that of the general population. Satisfaction with dental care was high although it was significantly reduced in those with loose dentures and burning sensation. The results of this study support a greater participation by dentists in the planning and provision of healthcare for sufferer of Parkinson's disease.     

Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates

Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex.     

Renal function during vasoactive intestinal peptide (VIP) infusions in normal man and patients with liver disease

VIP containing nerves are present in the kidney and plasma VIP levels are elevated in cardiac failure and severe liver disease. We studied the effects of intravenous VIP; 6 pmol kg-1 min-1 on 6 normal subjects and 3 patients with liver disease. In normal subjects VIP produced flushing and significant rises in heart rate and pulse pressure but the clearance rates of paraaminohippurate and creatinine did not change significantly. Urine flow fell to about 1/3 and the rate of excretion of electrolytes (except phosphate) fell to about a half of control values. Plasma renin activity rose about 3-fold and there were significant rises in haematocrit and the plasma concentrations of solids, calcium and phosphate. The patients with liver disease responded similarly. Elevated plasma VIP could contribute to salt and water retention in disease states.     

Periodontal disease in the prehistoric Ipiutak and Tigara skeletal remains from Point Hope,Alaska

Two large groups of prehistoric Eskimo skeletons from Point Hope, Alaska, were evaluated for dental wear and several measures of periodontal disease. Occlusal attrition was found to increase steadily with increasing age. Crown height decreased proportionately. Assessing periodontal disease by inspecting apparent alveolar recession was judged ineffective due to possible supereruption. Infrabony pockets, the result of severe localized periodontal disease indicated that in Ipiutak people between the ages of 25 and 30, and Tigara people between 35 and 40, more dental sites were affected by periodontal disease than were not. This suggests a cultural, genetic, or dietary difference between the two groups. Male/female differences were slight in all parameters studied.