Extra-Transcriptional Effects of Chromatin Bound RNA Polymerase III Transcription Complexes

Transcription by RNA polymerase III (Pol III) requires sequential assembly of Pol III-specific transcription factors. At the tRNA gene, the TFIIIC complex recognizes and specifically binds at intragenic promoter elements A-box and B-box and aids the assembly of TFIIIB to upstream of the transcriptional start site. Upon binding, Pol III is recruited near start sites and transcription of tRNA genes is initiated. Apart from transcription of a gene, these bound Pol III complexes influence transcription, chromatin state and genome organization of neighboring RNA polymerase II (Pol II)-transcribed genes. Such effects are known as extra-transcriptional effects of Pol III complex. Our study provides evidence of a unique “extra-transcriptional” activity of assembled Pol III transcription complexes at the tRNA gene that blocks progression of intergenic RNA polymerase II transcription. We demonstrated that the Pol III transcription complex bound to the tRNA gene upstream of the Saccharomyces cerevisiae ATG31 gene protects the ATG31 promoter against readthrough transcriptional interference from the upstream non-coding intergenic SUT467. The protection is predominately mediated by binding of the TFIIIB complex. Failure to block this readthrough resulted in compromised ATG31 translation. Given the recent discovery of widespread pervasive transcription in yeast, protection of neighboring genes from intergenic transcriptional interference may be a key extra-transcriptional function of assembled RNA polymerase III complexes. Our data from RNA-seq analysis demonstrated genome-wide effects of DNA bound Pol III complexes on neighboring chromosomal loci, by comparing expression profiles from tfc6 under-expressing mutants and wild-type S. cerevisiae strains. Reduced TFIIIC occupancy in mutant strains altered Pol II derived transcripts and displayed 5’ or 3’ extension of protein-coding genes, readthrough from non-coding transcripts and increase in the transcription of genes near the potential TFIIIC binding sites, including tRNA genes and putative ETC sites. Interestingly, not all genes in the vicinity of TFIIIC binding sites were transcriptionally mis-regulated, suggesting variable strength of influence on Pol II transcripts by TFIIIC bound sites. Finally, as observed in SUT467-ATG31 readthrough, we anticipated translation defects in 5’ or 3’ extended transcripts in mutants. Overall these genome-wide results suggest much complex regulatory role of Pol III transcription factors bound sites than previously anticipated

Optimal damping profiles for a heaving buoy wave-energy converter

This paper explores optimal damping profiles for a heaving buoy wave energy converter (WEC). The approach is mathematical and the model of Eidsmoen (1995) is used as a basis. In order to permit analytical development, the model is initially simplified and an optimal damping profile is determined using numerical optimization. Having found the optimal damping profile, a semi-analytical solution methodology is developed to determine the optimal damping parameters. Finally, the procedure is validated on the original model and some aspects related to the control problem are addressed

Pregnancy in a rare case of Takayasu’s arteritis: a case report

In Takayasu’s arteritis is a rare, chronic idiopathic vasculitis affecting aorta and its major branches, commonly seen in young women of Asian origin. Incidence is 2.6 cases/million/year. Female of reproductive age group are commonly affected. A 32-year female G3A2 with known case of Takayasu arteritis wanted to continue this pregnancy under tremandous social pressure and came for antenatal care at tertiary care hospital. As the pregnancy advanced, she developed uncontrolled hypertension and severe IUGR. At 30 weeks of gestation, elective LSCS had to be done in view of reduced fetal blood flow and severe growth restriction. She delivered male baby of 1 kg which was shifted to NICU. Patient required cardiac intensive care unit for first 48 hrs and later shifted to ward. Postoperative period was uneventful, and patient could be discharged on 8th day. Baby received intensive NICU care and discharged after 1 month with 2 kg weight. Pregnancy with takayasu arteritis requires a multipronged management from gynaecologist, cardiologist, cardiac anaesthetist and neonatologist for favourable maternal and fetal outcome

A KAP study of pharmacovigilance among junior residents and interns of a tertiary care hospital

Background: Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems. An “adverse drug reaction” is any noxious, unintended and undesired effect of a drug, which occurs at a dose used in humans for prophylaxis, diagnosis, therapy or modification of physiological functions. Reporting of adverse events and adverse drug reactions is the commonest method utilized for generating safety data. Lack of awareness about Pharmacovigilance is one of the most important causes of such under-reporting. Spontaneous reporting system is considered the main mechanism of pharmacovigilance study for gathering information about ADRs. Hence this study was undertaken to assess the knowledge, attitude and practice regarding Pharmacovigilance among junior residents and interns in a tertiary care hospital.Methods: A cross-sectional study was carried out in 134 doctors using pre-validated 20 item questionnaire with details of participant’s information followed by questions regarding knowledge, attitude and prescribing practice of pharmacovigilance was used as a tool, administrated to all the resident doctors and the collected data was analysed.Results: Our study revealed that knowledge about pharmacovigilance was not adequate to JRs and INTs. Survey results revealed that the knowledge of pharmacovigilance among doctors 63 (88.73%) JR and 49 (77.78%) INTs had a knowledge score of less than 50%. This shows that only few doctors are aware about the pharmacovigilance programme. The assessment of questionnaire based on attitude regarding pharmacovigilance shows that 21 (29.58%) JR and 17 (26.98%) of INTs had attitude score of 70% and above. The attitude score was less compared to the knowledge score of JRs and INTs. 52 JR and 58 INTs stated that they have not been trained on how to report ADRs and basic orientation about pharmacovigilance which hinders the process of practicing pharmacovigilance. Conclusions: For the success of Pharmacovigilance programmes only knowledge and attitude regarding Pharmacovigilance is not enough as is evident from our study. Success of Pharmacovigilance programmes depend also upon the effective practice of Pharmacovigilance by healthcare professionals

Antimicrobial utilization pattern in indoor patients of obstetrics and gynecology ward of a tertiary care hospital

Background: Rational prescribing of antimicrobials is fundamentally necessary to reduce incidence of antimicrobial resistance. To evaluate the rationality of antimicrobial prescribing practices in patients admitted to obstetrics and gynecology ward of a tertiary care hospital using ICMR guidelines and to check how many drugs were prescribed from NLEMI.          Methods: It was a prospective observational study. Study included newly admitted patients in obstetrics and gynecology ward receiving antimicrobial therapy. Drugs prescribed to the patients during their hospital stay were noted from case sheets in case record form. WHO core and economic indicators were used to analyze prescribing patterns. Medguideindia.com was referred for prices of drugs. Results: Average number of drugs prescribed for a patient admitted in the obstetrics and gynecology ward were 3.22 and 4.31 respectively. Percentage of drugs prescribed by their generic name were 37.11% and 39.42% in obstetrics and gynecology ward respectively. 26.85% and 34.14% of patients received drugs through parenteral route in obstetrics and gynecology wards respectively. All antimicrobials were prescribed from NLEMI. Conclusions: WHO recommends prescribing all drugs by their generic names. Average duration of antimicrobial treatment was higher than recommended average duration suggested by ICMR. ICMR recommends use of 2nd generation cephalosporins but in the present study 3rd generation cephalosporins were used. For rational use of antimicrobials and to reduce their cost it is recommended to prescribe antimicrobials by their generic names and reduce treatment duration by referring to ICMR Guidelines and NLEMI

Comparison of Effectiveness of Supervised Exercise Program and Cyriax Physiotherapy in Patients with Tennis Elbow (Lateral Epicondylitis): A Randomized Clinical Trial

Objective. To compare the effectiveness of supervised exercise program and Cyriax physiotherapy in the treatment of tennis elbow (lateral epicondylitis). Design. Randomized clinical trial. Setting. Physiotherapy and rehabilitation centre. Subjects. This study was carried out with 20 patients, who had tennis elbow (lateral epicondylitis). Intervention. Group A (n = 10) had received supervised exercise program. Group B (n = 10) was treated with Cyriax physiotherapy. All patients received three treatment sessions per week for four weeks (12 treatment sessions). Outcome measures. Pain was evaluated using a visual analogue scale (VAS), and functional status was evaluated by completion of the Tennis Elbow Function Scale (TEFS) which were recorded at base line and at the end of fourth week. Results. Both the supervised exercise program and Cyriax physiotherapy were found to be significantly effective in reduction of pain and in the improvement of functional status. The supervised exercise programme resulted in greater improvement in comparison to those who received Cyriax physiotherapy. Conclusion. The results of this clinical trial demonstrate that the supervised exercise program may be the first treatment choice for therapist in managing tennis elbow

Intergenic transcriptional interference is blocked by RNA polymerase III transcription factor TFIIIB in Saccharomyces cerevisiae

The major function of eukaryotic RNA polymerase III is to transcribe transfer RNA, 5S ribosomal RNA, and other small non-protein-coding RNA molecules. Assembly of the RNA polymerase III complex on chromosomal DNA requires the sequential binding of transcription factor complexes TFIIIC and TFIIIB. Recent evidence has suggested that in addition to producing RNA transcripts, chromatin-assembled RNA polymerase III complexes may mediate additional nuclear functions that include chromatin boundary, nucleosome phasing, and general genome organization activities. This study provides evidence of another such extratranscriptional activity of assembled RNA polymerase III complexes, which is the ability to block progression of intergenic RNA polymerase II transcription. We demonstrate that the RNA polymerase III complex bound to the tRNA gene upstream of the Saccharomyces cerevisiae ATG31 gene protects the ATG31 promoter against readthrough transcriptional interference from the upstream noncoding intergenic SUT467 transcription unit. This protection is predominately mediated by binding of the TFIIIB complex. When TFIIIB binding to this tRNA gene is weakened, an extended SUT467-ATG31 readthrough transcript is produced, resulting in compromised ATG31 translation. Since the ATG31 gene product is required for autophagy, strains expressing the readthrough transcript exhibit defective autophagy induction and reduced fitness under autophagy-inducing nitrogen starvation conditions. Given the recent discovery of widespread pervasive transcription in all forms of life, protection of neighboring genes from intergenic transcriptional interference may be a key extratranscriptional function of assembled RNA polymerase III complexes and possibly other DNA binding proteins. © 2014 by the Genetics Society of America

Retrospective study of clinico-pathological features of ovarian tumors

Background: Ovarian masses are a frequent clinical diagnosis in general Gynecology. The aim of the present study was to assess risk factors, clinical features, CA 125 levels, histopathological diagnosis of the patients of all ovarian tumors that underwent surgical management between August 2013 to August 2017.Methods: This was the retrospective study conducted in the department of Obstetrics and Gynecology in MIMER Medical College. We studied 50 patients those who underwent surgical management. Most of the patients 56% were in the reproductive age group, 28% patients were in the perimenopausal age group, 14% were in the postmenopausal age group. 82% patients were parous.Results: Pain abdomen was most common symptom in 50% patients. Bilaterality of the tumor was common in malignant tumors. CA 125 was found to be increased more in malignant tumors. Most common co morbid condition was hypertension found in 12% patients. Most common ovarian tumor found was serous cystadenoma 34% and most common malignant tumors were serous cystadenoma carcinoma 16%.Conclusions: Out of all operated patients 11 (22%) were malignant, 37 (74%) were benign and 2 (%) were borderline tumors. Out of all malignant tumors 8 (72%) were serous cysadenocarcinoma. It is difficult to always differentiate between malignant and benign tumors clinically. Analysis of risk factors and protective factors, thorough abdomino-pelvicbimanual examination, certain features on radiological imaging, presence of ascites and bilaterality, CA125 levels, helps increasing the accuracy of the diagnosis

On the tuning of a wave-energy driven oscillating-water-column seawater pump to polychromatic waves

Performance of wave-energy devices of the oscillating water column (OWC) type is greatly enhanced when a resonant condition with the forcing waves is maintained. The natural frequency of such systems can in general be tuned to resonate with a given wave forcing frequency. In this paper we address the tuning of an OWC sea-water pump to polychromatic waves. We report results of wave tank experiments, which were conducted with a scale model of the pump. Also, a numerical solution for the pump equations, which were proven in previous work to successfully describe its behavior when driven by monochromatic waves, is tested with various polychromatic wave spectra. Results of the numerical model forced by the wave trains measured in the wave tank experiments are used to develop a tuning criterion for the sea-water pump.Comment: 21 pages, 14 figure