Fungicidal Control of Downy Mildew of Pearl Millet

Among the three fungicides tested in vitro against Sclerospora graminicola, metalaxyl and oxadixyl were effective in completely inhibiting sporangial production and germination at 250 ppm concentration. With mancozeb, complete inhibition of sporangial production was observed only at 1000 ppm concentration while there was no complete inhibition of sporangial germination even at 1000 ppm. In a field trial conducted during the kharif season of 1985, metalaxyl 25 WP seed treatment protected the pearl millet crop from downy mildew upto 30 days. Seed treatment followed by one foliar spray with metalaxyl or mancozeb was more effective than seed treatment alone. Seed treatment with metalaxyl followed by a single combined foliar spray of metalaxyl + mancozeb was superior to seed treatment with metalaxyl followed by a single foliar spray of either of these fungicides

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact

Study of relationship between CRP, bilirubin and selected anthropometric parameters with hypertension

Background: There are many recent studies showing that hypertension, and cardio-vascular disease is linked to inflammation. The higher CRP levels are significantly correlated with hypertension. CRP estimation is used as a surrogate marker in evaluation and predicting the prognosis of all hypertensive patients. Many of the epidemiologic studies had shown the association of CRP levels with future cardiovascular events and hypertension. Bilirubin has been shown to be an effective antioxidant both in vitro and in vivo. The excess body fat and distribution is an important contributor to the association between obesity and high BP. Aims and objectives: The objective was to study the relationship between CRP, Bilirubin and selected anthropometric parameters among both hypertensive and non hypertensive subjects. Methods: We have conducted a hospital based descriptive observational study using purposive non random sampling method on 150 subjects; 87 hypertensive and 77 were non hypertensive. Age, systolic BP, diastolic BP, weight, height, waist circumference, hip circumference, SAD, total Bilirubin, T cholesterol, HDL-C, Triglycerides, LDL-C were primary continuous variables. BMI, WHR, WHtR were taken as secondary variables. Results: CRP, Waist circumference, WHtR and SAD have a positive correlation with both systolic and diastolic BP. Odds ratio was 12.18 for CRP. Total Bilirubin levels have a negative correlation with systolic and diastolic BP. Odds ratio was 7.81. Diastolic BP had positive correlation with Weight, Hip circumference and BMI. Conclusion: We had demonstrated elevated CRP, low Bilirubin levels, abnormal SAD and Waist circumference were associated with blood pressure levels. These parameters are useful and cost-effective tool for predicting and evaluating Hypertension

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

BACKGROUND Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT). OBJECTIVES This study sought to characterize HCT outcomes in APDS. METHODS Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT. RESULTS Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure-free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT. CONCLUSIONS Graft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

BackgroundActivated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).ObjectivesThis study sought to characterize HCT outcomes in APDS.MethodsRetrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.ResultsPre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure-free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT.ConclusionsGraft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time