Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization

The origin recognition complex (ORC) is a DNA replication initiator protein also known to be involved in diverse cellular functions including gene silencing, sister chromatid cohesion, telomere biology, heterochromatin localization, centromere and centrosome activity, and cytokinesis. We show that, in human cells, multiple ORC subunits associate with hetereochromatin protein 1 (HP1) alpha- and HP1beta-containing heterochromatic foci. Fluorescent bleaching studies indicate that multiple subcomplexes of ORC exist at heterochromatin, with Orc1 stably associating with heterochromatin in G1 phase, whereas other ORC subunits have transient interactions throughout the cell-division cycle. Both Orc1 and Orc3 directly bind to HP1alpha, and two domains of Orc3, a coiled-coil domain and a mod-interacting region domain, can independently bind to HP1alpha; however, both are essential for in vivo localization of Orc3 to heterochromatic foci. Direct binding of both Orc1 and Orc3 to HP1 suggests that, after the degradation of Orc1 at the G1/S boundary, Orc3 facilitates assembly of ORC/HP1 proteins to chromatin. Although depletion of Orc2 and Orc3 subunits by siRNA caused loss of HP1alpha association to heterochromatin, loss of Orc1 and Orc5 caused aberrant HP1alpha distribution only to pericentric heterochromatin-surrounding nucleoli. Depletion of HP1alpha from human cells also shows loss of Orc2 binding to heterochromatin, suggesting that ORC and HP1 proteins are mutually required for each other to bind to heterochromatin. Similar to HP1alpha-depleted cells, Orc2 and Orc3 siRNA-treated cells also show loss of compaction at satellite repeats, suggesting that ORC together with HP1 proteins may be involved in organizing higher-order chromatin structure and centromere function

Tissue- and development-specific induction and turnover of hsp70 transcripts from loci 87A and 87C after heat shock and during recovery in Drosophila melanogaster

The haploid genome of Drosophila melanogaster normally carries at least five nearly identical copies of heat-shock-inducible hsp70 genes, two copies at the 87A7 and three copies at the 87C1 chromosome sites. We used in situ hybridization of the cDNA, which hybridizes with transcripts of all five hsp70 genes, and of two 3' untranslated region (3'UTR; specific for the 87A7- and 87C1-type hsp70 transcripts) riboprobes to cellular RNA to examine whether all these copies were similarly induced by heat shock in different cell types of D. melanogaster. Our results revealed remarkable differences not only in the heat-shock-inducibility of the hsp70 genes at the 87A7 and 87C1 loci, but also in their post-transcriptional metabolism, such as the stability of the transcripts and of their 3'UTRs in different cell types in developing embryos and in larval and adult tissues. Our results also revealed the constitutive presence of the heat-shock-inducible form of Hsp70 in a subset of late spermatogonial cells from the second-instar larval stage onwards. We suggest that the multiple copies of the stress-inducible hsp70 genes do not exist in the genome of D. melanogaster only to produce large amounts of the Hsp70 rapidly and at short notice, but that they are specifically regulated in a developmental-stage-specific manner. It is likely that the cost/benefit ratio of not producing or of producing a defined amount of Hsp70 under stress conditions varies for different cell types and under different physiological conditions and, accordingly, specific regulatory mechanisms operating at the transcriptional and post-transcriptional levels have evolved

Role of clinical pharmacist in drug utilization evaluation, medication adherence and pharmacovigilance

A series of systematic, criterion-based drug evaluation known as Drug utilization review are conducted on a regular basis to ensure that medication is utilized appropriately. It’s a mean of learning more about the issues brought on by drug usage, if done properly, may help to solve the issues. Medication adherence generally refers to a patient’s ability to take prescription drugs as directed and their continued use of those drugs. The increasing body of research linking medication non adherence to unfavorable outcomes and increased healthcare cost has raised concerns among clinicians, healthcare institutions, and other stakeholders. Pharmacovigilance, in which the procedures keeping an eye on the assessing adverse medication reactions, is essential to clinical practice, public health and efficient drug regulating system.  Aim of the study was wo study about the role of pharmacist in drug utilization review, medication adherence and pharmacovigilance

Pharmacognostical and preliminary phytochemical studies of Urena lobata linn

In the present study was to determine the pharmacognostical and preliminary phytochemical analysis of Urena lobata Linn. In pharmacognostoical studies powder characteristics of leaf and stem, leaf constant and analytical parameters like ash values extractive value analysis of major elements and in preliminary phytochemical studies were carried out .All these characters were determined will help the researches in their phytochemical as well as pharmacognostical analysis of this species.Keywords: Urena lobata Linn, Malvaceae, pharmacognostic, phytochemical analysi

The many ways of returning to the refrain in Telugu song

A refrain (abbreviated R) is a line in a song repeated after each verse, and often used as the\ua0song’s name. Returns to R are usually high points both melodically and lyrically. E.g., a verse\ua0ending "I feel upon my lips again" makes a smooth lead-in (abbreviated L) to the refrain R =\ua0"A taste of honey" (Scott/Marlow, 1962). We notate this "(I feel upon my lips again) A taste of\ua0honey", and call such patterns (lead-in)refrains or (L)R’s. The song goes R … LR … LR, where\ua0L could change verse to verse. In our examples, R and (L)R are often both full sentences. More\ua0interesting L’s are often phrases, clauses or rather than interjections. A word-prefix L can\ua0transform R.Our main contribution is to point out that (L)R patterns are a striking feature of Telugu (TEL)\ua0song, remarkably various and profuse in both old and new songs, yet little remarked in the\ua0literature as far as we are aware. We give examples from the 15th c. to the 21st. In transcription, a\ua0colon marks long vowels, and M, nasalized ones. Retroflexion is shown by capitalization, and\ua0aspiration by h, also a consonant by itself. Glosses are given, some also /morpheme-wise/.Kannada (KAN) and Tamil (TAM) share features with TEL that help make L(R)’s: fairly free word\ua0order, agglutinative particles, and adjectives and relative clauses preceding the noun. We give\ua0only lone KAN and TAM examples, but expect to find more when we search. Hindi (HIN) shares\ua0fewer features with TEL; perhaps therefore, we have so far looked but found few (L)R s in HIN

A review on novel COVID-19: background, etiology, pathogenesis, transmission, prevention and management

Mankind's history is watching a bizarre time battling an imperceptible adversary, the novel COVID-19 Coronavirus. At first seen in the Wuhan province of China, presently limitlessly spreading all over world. How the COVID 19 has been made on the globe become Pandemic needs no depiction. The virus has been accounted for affecting the lungs and related respiratory tracts promoting harm of the alveoli. It has been accounted that the respiratory sickness is the prevailing Clinical symptom of COVID-19. This review article discusses an easily understanding of the causes, different type of Human viruses regarded of Coronavirus, clinical diagnosis of RT-PCR, FET, Primary prevention and control of the virus. Therefore, this review article main theme is to provide more reliable and valid information to control and manage public emergency in both acute and chronic conditions of coronaviru

Study of magnitude of anaemic problem in rural tertiary care centre in outpatient department

Background: Prevalence of anaemia is very high in rural tertiary care hospital O.P.D patients. Anemia is the most common morbidity among micronutrients and affects health, education, economy, and productivity of the entire nation. Anemia, like fever, is a manifestation and not a disease per se. The most common group among the causes for anemia is malnutrition and among that group, iron deficiency makes up the bulk of it. Girls are more likely to be a victim due to various reasons. In a family with limited resources, the female child is more likely to be neglected. She is deprived of good food and education and is utilized as an extra working hand to carry out the household chores. The added burden of menstrual blood loss, normal or abnormal, precipitates the crises too often. Anemia can usually be prevented at a low cost, and the benefit/cost ratio of implementing preventive programs is recognized as one of the highest in the realm of public health. This information has equipped everyone in public health to take action against this long-standing problem and to do whatever is needed to be done.Methods: In our study 200 people attending medical outpatient department at a tertiary care centre were enrolled. Assessment of the anaemic problem is worked out.Results: Out of 200 patients, 107 were females and 93 were males. 49 females out of 107 had haemoglobin less than 10 and 9 males out of 93 are having haemoglobin less than 10. Among people with hemoglobin less than 10, 84.5% are females. Significant p value was observed in females (<0.0001).Conclusions:Anemia continues to be a major health problem in developing countries like India, particularly rural India. Despite different strategies and programs have been taken by government of India the growing menace of anaemia is not solved. So newer strategies must be taken.Background: Prevalence of anaemia is very high in rural tertiary care hospital O.P.D patients. Anemia is the most common morbidity among micronutrients and affects health, education, economy, and productivity of the entire nation. Anemia, like fever, is a manifestation and not a disease per se. The most common group among the causes for anemia is malnutrition and among that group, iron deficiency makes up the bulk of it. Girls are more likely to be a victim due to various reasons. In a family with limited resources, the female child is more likely to be neglected. She is deprived of good food and education and is utilized as an extra working hand to carry out the household chores. The added burden of menstrual blood loss, normal or abnormal, precipitates the crises too often. Anemia can usually be prevented at a low cost, and the benefit/cost ratio of implementing preventive programs is recognized as one of the highest in the realm of public health. This information has equipped everyone in public health to take action against this long-standing problem and to do whatever is needed to be done.Methods: In our study 200 people attending medical outpatient department at a tertiary care centre were enrolled. Assessment of the anaemic problem is worked out.Results: Out of 200 patients, 107 were females and 93 were males. 49 females out of 107 had haemoglobin less than 10 and 9 males out of 93 are having haemoglobin less than 10. Among people with hemoglobin less than 10, 84.5% are females. Significant p value was observed in females (<0.0001).Conclusions: Anemia continues to be a major health problem in developing countries like India, particularly rural India. Despite different strategies and programs have been taken by government of India the growing menace of anaemia is not solved. So newer strategies must be taken

Non linear buckling analysis of laminated composite twisted plates

The twisted plate has various applications in turbine blades, compressor blades, fan blades and particularly in gas turbines. Many of these plates are subjected to in-plane load due to fluid or aerodynamic pressures. Buckling of such plates is of special importance especially if the plates are thin. Hence it is necessary to study their behaviour under different types of loads. Laminated composite materials are increasingly used as load bearing structural components in aerospace and naval structures, automobiles, pressure vessels, turbine blades and many other engineering applications because of their high specific strength and stiffness. For a complete buckling study, a geometrically nonlinear analysis should be carried out. In a geometrically nonlinear analysis, the stiffness matrix of the structure is updated between loading increments to take into account deformations which affect the structural behaviour unlike a linear buckling analysis where the stiffness matrix is constant through the analysis. The analysis is carried out using ANSYS software. In ANSYS, the shell 281 element with six degrees of freedom per node is used. A twelve by twelve mesh is found to give good accuracy.The buckling of twisted plates was investigated by a nonlinear analysis. The effect of number of layers, changing angle of twist, width to thickness ratio, aspect ratio, etc is also studied. It was observed in all cases that the buckling load by nonlinear analysis is lesser than that predicted by a linear analysis which proves the importance of the present study

Developmental regulation and complex organization of the promoter of the non-coding hsrω gene of Drosophila melanogaster

The nucleus-limited large non-coding hsr&#969;-n RNA product of the93D or the hsr&#969; gene of Drosophila melanogaster binds to a variety of RNA-binding proteins involved in nuclear RNA processing. We examined the developmental and heat shock induced expression of this gene by in situ hybridization of nonradioactively labelled riboprobe to cellular transcripts in intact embryos, larval and adult somatic tissues of wild type and an enhancer-trap line carrying the hsr&#969;05241 allele due to insertion of aP-LacZ-rosy + transposon at - 130 bp position of the hsr&#969; promoter. We also examined LacZ expression in the enhancer-trap line and in two transgenic lines carrying different lengths of the hsr&#969; promoter upstream of the LacZ reporter. The hsr&#937; gene is expressed widely at all developmental stages; in later embryonic stages, its expression in the developing central nervous system was prominent. In spite of insertion of a big transposon in the promoter, expression of the hsr&#969;05241 allele in the enhancer-trap line, as revealed byin situ hybridization to hsr&#969; transcripts in cells, was similar to that of the wild type allele in all the embryonic, larval and adult somatic tissues examined. Expression of the LacZ gene in this enhancer-trap line was similar to that of the hsr&#969; RNA in all diploid cell types in embryos and larvae but in the polytene cells, the LacZ gene did not express at all, neither during normal development nor after heat shock. Comparison of the expression patterns of hsr&#969; gene and those of the LacZ reporter gene under its various promoter regions in the enhancer-trap and transgenic lines revealed a complex pattern of regulation, which seems to be essential for its dynamically varying expression in diverse cell types

Male sterility associated with overexpression of the noncoding hsr&#969; gene in cyst cells of testis of Drosophila melanogaster

Of the several noncoding transcripts produced by the hsr&#937; gene of Drosophila melanogaster, the nucleus-limited &gt; 10-kb hsr&#937;-n transcript colocalizes with heterogeneous nuclear RNA binding proteins (hnRNPs) to form fine nucleoplasmic omega speckles. Our earlier studies suggested that the noncoding hsr&#937;-n transcripts dynamically regulate the distribution of hnRNPs in active (chromatin bound) and inactive (in omega speckles) compartments. Here we show that a P transposon insertion in this gene's promoter (at -130 bp) in the hsr&#937;05241 enhancer-trap line had no effect on viability or phenotype of males or females, but the insertion-homozygous males were sterile. Testes of hsr&#937;05241 homozygous flies contained nonmotile sperms while their seminal vesicles were empty. RNA:RNA in situ hybridization showed that the somatic cyst cells in testes of the mutant male flies contained significantly higher amounts of hsr&#937;-n transcripts, and unlike the characteristic fine omega speckles in other cell types they displayed large clusters of omega speckles as typically seen after heat shock. Two of the hnRNPs, viz. HRB87F and Hrp57A, which are expressed in cyst cells, also formed large clusters in these cells in parallel with the hsr&#937;-n transcripts. A complete excision of the P transposon insertion restored male fertility as well as the fine-speckled pattern of omega speckles in the cyst cells. The in situ distribution patterns of these two hnRNPs and several other RNA-binding proteins (Hrp40, Hrb57A, S5, Sxl, SRp55 and Rb97D) were not affected by hsr&#937; mutation in any of the meiotic stages in adult testes. The present studies, however, revealed an unexpected presence (in wild-type as well as mutant) of the functional form of Sxl in primary spermatocytes and an unusual distribution of HRB87F along the retracting spindle during anaphasetelophase of the first meiotic division. It appears that the P transposon insertion in the promoter region causes a misregulated overexpression of hsr&#937; in cyst cells, which in turn results in excessive sequestration of hnRNPs and formation of large clusters of omega speckles in these cell nuclei. The consequent limiting availability of hnRNPs is likely totrans-dominantly affect processing of other pre-mRNAs in cyst cells. We suggest that a compromise in the activity of cyst cells due to the aberrant hnRNP distribution is responsible for the failure of individualization of sperms in hsr&#937;05241 mutant testes. These results further support a significant role of the noncoding hsr&#937;-n transcripts in basic cellular activities, namely regulation of the availability of hnRNPs in active (chromatin bound) and inactive (in omega speckles) compartments