Autophosphorylation of the Smk1 MAPK is spatially and temporally regulated by Ssp2 during meiotic development in yeast.

Smk1 is a meiosis-specific MAPK that controls spore wall morphogenesis in Saccharomyces cerevisiae. Although Smk1 is activated by phosphorylation of the threonine (T) and tyrosine (Y) in its activation loop, it is not phosphorylated by a dual-specificity MAPK kinase. Instead, the T is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase, Cak1. The Y is autophosphorylated in an intramolecular reaction that requires a meiosis-specific protein named Ssp2. The meiosis-specific CDK-like kinase, Ime2, was previously shown to positively regulate Smk1. Here we show that Ime2 activity is required to induce the translation of SSP2 mRNA at anaphase II. Ssp2 protein is then localized to the prospore membrane, the structure where spore wall assembly takes place. Next the carboxy-terminal portion of Ssp2 forms a complex with Smk1 and stimulates the autophosphorylation of its activation-loop Y residue. These findings link Ime2 to Smk1 activation through Ssp2 and define a developmentally regulated mechanism for activating MAPK at specific locations in the cell

Multisite Phosphorylation of the Sum1 Transcriptional Repressor by S-Phase Kinases Controls Exit from Meiotic Prophase in Yeast.

Activation of the meiotic transcription factor Ndt80 is a key regulatory transition in the life cycle of Saccharomyces cerevisiae because it triggers exit from pachytene and entry into meiosis. The NDT80 promoter is held inactive by a complex containing the DNA-binding protein Sum1 and the histone deacetylase Hst1. Meiosis-specific phosphorylation of Sum1 by the protein kinases Cdk1, Ime2, and Cdc7 is required for NDT80 expression. Here, we show that the S-phase-promoting cyclin Clb5 activates Cdk1 to phosphorylate most, and perhaps all, of the 11 minimal cyclin-dependent kinase (CDK) phospho-consensus sites (S/T-P) in Sum1. Nine of these sites can individually promote modest levels of meiosis, yet these sites function in a quasiadditive manner to promote substantial levels of meiosis. Two Cdk1 sites and an Ime2 site individually promote high levels of meiosis, likely by preparing Sum1 for phosphorylation by Cdc7. Chromatin immunoprecipitation reveals that the phosphorylation sites are required for removal of Sum1 from the NDT80 promoter. We also find that Sum1, but not its partner protein Hst1, is required to repress NDT80 transcription. Thus, while the phosphorylation of Sum1 may lead to dissociation from DNA by influencing Hst1, it is the presence of Sum1 on DNA that determines whether NDT80 will be expressed

Cutaneous nerves of the trunk of the domestic pig with special reference to the spinal nerves.

http://www.worldcat.org/oclc/1101328

Vascular Calcification in Chronic Kidney Disease

Cardiovascular disease (CVD) is the major cause of death in chronic kidney disease (CKD). Of the various risk factors, vascular calcification has only recently come into prominence. CKD is associated with an increased risk of vascular calcification. In routine practice, clinicians usually overlook this finding. Screening for vascular calcification is often missed during first contact with nephrologists. With this article, we would like to reiterate the importance of preventing vascular calcification in early stages of CKD and once it starts appearing, its progression needs to be halted early with individualized treatment. The prevalence, sites of involvement, detection, quantification, pathogenesis, risk factors, clinical manifestations and management options have been discussed

Feto-maternal outcome of pregnancies diagnosed as hypothyroidism after 28 weeks of gestation, at a tertiary hospital

Background: The most frequent thyroid alteration observed in pregnancy is hypothyroidism with subclinical hypothyroidism being more common than overt hypothyroidism. Women with thyroid dysfunction both overt and subclinical are at increased risk of pregnancy-related complications. In present study we assessed feto-maternal outcome of pregnancies in whom hypothyroidism was diagnosed after 28 weeks of gestation.Methods: This study was conducted in the department of obstetrics and gynaecology, Adesh institute of medical sciences and research Medical College, Bathinda. The present study was of prospective, observational design, conducted in pregnant women with more than 28 weeks pregnancy, first time diagnosed as hypothyroid (TSH>3.0 mIU/l).Results: In present study total 37 patients completed study protocol, 6 patients were delivered at other hospital. Most patients were less than 20 years (32%), nulliparous (68%). 19% patients delivered preterm either due to spontaneous labour or labour induction for obstetric reason. 62% patients delivered vaginally, 35% underwent LSCS. In present study maternal complications such as preterm labour (24%), hypertensive disorders of pregnancy (22%), oligohydramnios (16%), overt/gestational diabetes mellitus (8%) and post-partum haemorrhage (5%) were noted. 2.5-3.4 kg birth weight was most common group (65%). Total 16 % babies required neonatal resuscitation. Babies requiring neonatal resuscitation were admitted in NICU for observation and for any further management. Neonatal jaundice was noted in 30% babies. Total 22% babies needed NICU admission. We noted early neonatal death in one baby. No maternal mortality was noted.Conclusions: Treatment of maternal hypothyroidism is essential, because adverse outcomes for both mother and baby are greatly reduced, if not eliminated, when patients are treated

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study

Background: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. Methods: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. Results: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. Conclusions: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health

Epidemiology and risk factors of chronic kidney disease in India – results from the SEEK (Screening and Early Evaluation of Kidney Disease) study

Background: There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually. Methods: We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected. Results: The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18–98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively. Conclusion: The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies. It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India

Errors in diabetic insulin therapy and the vitality of proper precautions in Bangladesh: Real-life insights from the developing world

Copyright: © 2024 Journal of Family Medicine and Primary CareBackground: Insulin therapy errors can have life-threatening consequences in patients with diabetes. Given the increasing prevalence of diabetes and insulin therapy in Bangladesh, it is crucial to identify and prevent these errors. This study uses case-based clinical experiences to thematically analyze insulin therapy errors and propose preventive measures. The study aims to provide valuable insights into the challenges faced in managing insulin therapy in a developing country setting and the importance of involving various stakeholders. Materials and Methods: This is a qualitative research that used a case study approach to identify and analyze errors in insulin therapy in diabetic patients who had experienced adverse clinical consequences. The cases were thematically analyzed to generate insights into current global health problems resulting from erroneous insulin therapy. Results: The two case studies highlight potential risks of errors in insulin therapy, including poor glycemic control, complications, and death. The analysis also highlights the importance of careful monitoring, checks, and communication among health-care providers, patients, and pharmacists to prevent such errors. In addition, it emphasizes the need for education and awareness among patients and health-care providers to ensure safe and effective insulin therapy. Conclusion: Accurate insulin therapy is crucial for diabetes management and preventing adverse outcomes. Identified themes emphasize improved communication, education, and monitoring to minimize therapy errors. Insights from this study can inform policies and practices for better patient outcomes. Further research can identify the root causes and develop interventions to prevent errors, leading to improved quality of life for diabetics.VoR added to CR 19/02/202