Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcripts

In amphibian oocytes, most lateral loops of the lampbrush chromosomes correspond to active transcriptional sites for RNA polymerase II. We show that newly assembled small nuclear ribonucleoprotein (RNP [snRNP]) particles, which are formed upon cytoplasmic injection of fluorescently labeled spliceosomal small nuclear RNAs (snRNAs), target the nascent transcripts of the chromosomal loops. With this new targeting assay, we demonstrate that nonfunctional forms of U1 and U2 snRNAs still associate with the active transcriptional units. In particular, we find that their association with nascent RNP fibrils is independent of their base pairing with pre–messenger RNAs. Additionally, stem loop I of the U1 snRNA is identified as a discrete domain that is both necessary and sufficient for association with nascent transcripts. Finally, in oocytes deficient in splicing, the recruitment of U1, U4, and U5 snRNPs to transcriptional units is not affected. Collectively, these data indicate that the recruitment of snRNPs to nascent transcripts and the assembly of the spliceosome are uncoupled events

EVALUATION OF ANTIDEPRESSANT ACTIVITY OF HERBOMINERAL FORMULATION

Objective: In the search for new therapeutic products for the treatment of neurological disorders, medicinal plant research, worldwide, has constantly progressed, demonstrating the pharmacological effectiveness of different plant species in a variety of animal models. SOBEREX CAPSULE (SC) is a herbomineral formulation used by ayurvedic practitioners for treatment of depression. The present study was designed to generate scientific evidence for SC in animal models of depression in mice.Methods: The formulation was administered orally to the mice at a dose of 50 mg/kg for 14 d, and at the end of treatment animals were subjected to tail suspension test and the forced swimming test in mice.Results: The effect of SC at the dose of 50 mg/kg was comparable to that of reference antidepressant fluoxetine. The formulation and fluoxetine, at the doses tested, produced no significant effects on locomotor activity. These results demonstrated that SC had antidepressant effects without side effect.Conclusion: Thus, SC possesses antidepressant-like effects in mice, providing further support for the traditional use of the formulation against central nervous disorders.Keywords: Antidepressant, Herbomineral formulation, Forced swim test, Tail suspension tes

Evaluation of anti-inflammatory potential of ayurvedic formulation Rheumacure in animal model of rheumatoid arthritis

Background: Rheumacure (RC) is a herbomineral preparation recommended by Ayurvedic medical practitioners for treatment of rheumatoid arthritis. The present study was designed to evaluate the effect of oral treatment with the herbomineral formulation in animal model of Freund's adjuvant induced arthritis to develop scientific evidence to the efficacious claim of the use of ayurvedic proprietary medicine in the management of rheumatoid arthritis in folklore medicine.Methods: Arthritis was induced by sub plantar injection of 0.1ml of complete Freund’s adjuvant. Treatment with RC 100 mg/kg and dexamethasone 2 mg/kg was given to rats orally once a day from day 1 to day 21 and after which estimation of physical, biochemical, and haematological parameters were carried out.Results: Treatment of RC to arthritic animal showed statistically significant (p<0.05) improvement in physical parameters like arthritic index, paw edema, paw thickness, splenomegaly and thymus index of the animal. The treatment also showed significantly (p <0.05) reduction in inflammatory markers like C-reactive protein, serum rheumatoid factor, erythrocyte sedimentation rate and increase in % haemoglobin. The histopathological examination showed protective effect against hyperplasia of synovium, pannus formation and destruction of the joint space.Conclusions: The results obtained in experiments indicated significant anti-inflammatory effect comparable to dexamethasone and without significant side effect. Thus the RC may be a potential preventive or therapeutic candidate for the treatment of chronic inflammation and arthritis

Electrochemical decolorization of Reactive Black 5 in an undivided cell using Ti and graphite anodes: Effect of polypyrrole coating on anodes

Electrochemical decolorization of an azo dye Reactive Black 5 (RB5) was studied in an undivided cell using Ti and graphite, and polypyrrole (PPy) coated Ti (PPy-SLS-Ti) and graphite (PPy-SLS-G) anodes in the presence of sodium chloride as an electrolyte to investigate the effect of polypyrrol coating. The colour removal efficiencies were 52.6%, 96.3%, 51.6%, and 41.0% respectively, at the end of 90 minutes of electrolysis at current density of 5 mA/cm2. The presence of PPy coating resulted in lower decolorization than that in the absence of coating. No specific peak emerged in UV-Vis spectra obtained at various time points during electrolysis using uncoated Ti and Graphite anodes which indicated non-selective nature of oxidation process. In case of PPy-SLS/Ti and PPy-SLS/Graphite anodes, a peak at 254 nm emerged distinctly which was determined to be vinylsulfone (VS), an amine. Generation and accumulation of VS suggested that oxidation was suppressed and electrochemical reduction rather than oxidation, was a predominant mechanism responsible for RB5 decolourization in case of polypyrrole coated anodes. Normally, in an undivided cell, reactions on anode predominates (i.e. oxidation). The results obtained here may lead to development of anodes for undivided cells on which the extent of oxidation may be controlled by a suitable coating such as PPy

An analytical study of 50 women presenting with an adnexal mass

Background: The aim of this study was to detect and determine the origin of adnexal mass and to narrow down the diagnosis. Also, to determine the reliability of the bimanual pelvic examination in diagnosing adnexal mass and to determine clinical, radiological and histopathological co-relation of adnexal mass. Adnexal mass lesions are fairly common among women (with a prevalence of 0.17% to 5.9% in asymptomatic women and 7.1% to 12% in symptomatic women) of all age group but very common among reproductive age. Differential diagnosis of adnexal mass is difficult and complex. Recognition of the severity of the problem, appropriate and timely evaluation and treatment with good outcome is the goal.Methods: Prospective, observational study of 50 patients with suspected various adnexal masses were conducted for a period of 1.5yr i.e. from November 2014 to May 2016. All patients underwent pelvic and ultrasonography examination. All patients later underwent surgery. Results were correlated later.Results: The patient ages ranged from 19 to 58 with a mean age of 31.5. Most common site of origin of adnexal masses is the Ovary (Rt. 38% and Lt. 34%) Most common adnexal masses on histopathological diagnosis are mucinous cyst adenoma (20%), Benign and mature cystic teratoma (16% and 6%) and serous cyst adenoma (10%). About 92% patients with adnexal mass presents with abdominal pain as a chief complaint.Conclusions: Although bimanual palpation of the adnexal masses may not allow a very specific diagnosis, clinically useful information can usually be obtained and hence it is particularly useful as a first step in assessment of adnexal masses and as an adjunct to morphological assessment of ovarian lesions. Ultrasonography is an important noninvasive investigation and is helpful in diagnosing most of these cases, but the histopathological examination of specimen obtained from laparotomy of adnexal mass is the gold standard for confirming the diagnosis

IN SILICO MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF GALLIC ACID DERIVATIVES AS PPAR-γ AGONISTS

Objective: To perform molecular docking and pharmacokinetic prediction of gallic acid derivatives as Peroxisome proliferator-activated receptors-γ (PPAR-γ) agonist for the treatment of diabetes.Methods: Molecular docking study on gallic acid and different derivatives of gallic acid was performed using GOLD v5.2 software. In addition to this, all the derivatives were analysed for drug likeliness, Lipinski's rule and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties using online tools like admet SAR, Molinspiration and Medchem designer.Results: Molecular docking studies reveals that SSP-12, SSP-13 and SSP-40 demonstrated significant binding to the PPAR-γ receptor with good Gold score fitness (73.11, 69.86 and 75.51 respectively) and relative ligand energy (-8.26,-8.33 and-7.82, respectively) as compared to standard drugs i.e. rosiglitazone and pioglitazone, (64.10 and 66.72) and (-4.30 and-2.47) respectively.Conclusion: The final results of molecular docking along with information gathered from pharmacokinetic parameters of gallic acid derivatives may be utilised further for the development of newer PPAR-γ agonists having anti-diabetic potential with better pharmacokinetic and pharmacodynamic profile

Seeing Beyond Cancer: Multi-Institutional Validation of Object Localization and 3D Semantic Segmentation using Deep Learning for Breast MRI

The clinical management of breast cancer depends on an accurate understanding of the tumor and its anatomical context to adjacent tissues and landmark structures. This context may be provided by semantic segmentation methods; however, previous works have been largely limited to a singular focus on the tumor alone and rarely other tissue types. In contrast, we present a method that exploits tissue-tissue interactions to accurately segment every major tissue type in the breast including: chest wall, skin, adipose tissue, fibroglandular tissue, vasculature and tumor via standard-of-care Dynamic Contrast Enhanced MRI. Comparing our method to prior state-of-the-art, we achieved a superior Dice score on tumor segmentation while maintaining competitive performance on other studied tissues across multiple institutions. Briefly, our method proceeds by localizing the tumor using 2D object detectors, then segmenting the tumor and surrounding tissues independently using two 3D U-nets, and finally integrating these results while mitigating false positives by checking for anatomically plausible tissue-tissue contacts. The object detection models were pre-trained on ImageNet and COCO, and operated on MIP (maximum intensity projection) images in the axial and sagittal planes, establishing a 3D tumor bounding box. By integrating multiple relevant peri-tumoral tissues, our work enables clinical applications in breast cancer staging, prognosis and surgical planning.Comment: 9 pages, 2 figures, to appear in SPIE: Medical Imaging 202

Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

BACKGROUND: We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants ‘progenitors’ termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively spliced receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in literature of which FSH-R1 and FSH-R3 have biological activity. Present study was undertaken to identify FSHR isoforms mediating FSH action on ovarian stem cells, using sheep OSE cells culture as the study model. METHODS: Cultures of sheep OSE cells (a mix of epithelial cells, VSELs, OGSCs and few contaminating red blood cells) were established with and without FSH 5IU/ml treatment. Effect of FSH treatment on self-renewal of VSELs and their differentiation into OGSCs was studied after 15 hrs by qRT-PCR using markers specific for VSELs (Oct-4A, Sox-2) and OGSCs (Oct-4). FSH receptors and its specific transcripts (R1 and R3) were studied after 3 and 15 hrs of FSH treatment by immunolocalization, in situ hybridization and qRT-PCR. FSHR and OCT-4 were also immuno-localized on sheep ovarian sections, in vitro matured follicles and early embryos. RESULTS: FSH treatment resulted in increased stem cells self-renewal and clonal expansion evident by the appearance of stem cell clusters. FSH receptors were expressed on ovarian stem cells whereas the epithelial cells were distinctly negative. An increase in R3 mRNA transcripts was noted after 3 hrs of FSH treatment and was reduced to basal levels by 15 hrs, whereas R1 transcript expression remained unaffected. Both FSHR and OCT-4 were immuno-localized in nuclei of stem cells, showed nuclear or ooplasmic localization in oocytes of primordial follicles and in cytoplasm of granulosa cells in growing follicles. CONCLUSIONS: FSH modulates ovarian stem cells via FSH-R3 to undergo potential self-renewal, clonal expansion as ‘cysts’ and differentiation into oocytes. OCT-4 and FSHR proteins (required initially to maintain pluripotent state of VSELs and for FSH action respectively) gradually shift from nuclei to cytoplasm of developing oocytes and are later possibly removed by surrounding granulosa cells as the oocyte prepares itself for fertilization

Particle Size Dependent Gas Sensing Performance of Zno Nanorods based Thick Film Resistors

Pure bulk ZnO was observed to be less sensitive to hazardous, toxic and inflammable gases. As the particle size of the materials get reduced from bulk to nanoscale, the gas sensing performance of pure ZnO was observed to increase crucially. It was also observed that, further decrease in the particle size would leads to decrease in the gas response. The optimized average diameter of ZnO Nanorod / particle size is 12 nm, which exhibits crucial gas response. The disc type ultrasonicated microwave assisted centrifuge technique was used for the synthesis of materials. The dry powders of synthesized materials were transformed into thick films by screen printing technique. Various characterizations techniques were employed to study the surface topography, crystal structure, phase, particle size, etc. effect of the surface nanostructure, different gases, gas concentrations, particle size, long duration for ageing, etc. on the gas response of the samples were studied and discussed. DOI: 10.17762/ijritcc2321-8169.15080

Transfusion effect of random donor platelet and single donor platelet in thrombocytopenic patients at tertiary care hospital of South Gujarat

Background: Platelet transfusion plays a key role in therapy for the patients with thrombocytopenia. Superiority of Single donor platelet (SDP) over Random donor platelet (RDP) transfusions is largely assumed, but unproven. Platelet Rich Plasma-Platelet concentrate (PRP-PC) and Apheresis-PC were prepared and their therapeutic efficacy were assessed in thrombocytopenic patients.Methods: This study included 60 transfusion episodes consisting of 30 SDP and 30 RDP (147units of RDP). The post transfusion efficacy of transfused platelets was assessed at 1 hour and 24 hours by corrected count increment (CCI) and percentage recovery (PR). Paired ‘t’-test was used for statistical analysis and a probability of p<0.05 was used to reject null hypothesis.Results: The mean platelet dose of SDP (n=30) and RDP (n=30) was 2.86±1.05 x 1011 and 2.36±0.54 x 1011 respectively. The mean platelet increments of SDP at 1 hour and 24 hours were 38±18.1 x 103/μl and 37.3±20.7x 103/μl. The mean platelet increments of RDP at 1 hour and 24 hours were 28.5±11.4 x 103/μl and 26 ±11.6 x 103/μl. The mean CCI of SDP at 1hour and 24 hours were 21.4 ±7.3 x 103/μl and 20.8±7.4 x 103/μl respectively. The mean CCI of RDP at 1hour and 24 hours were 18.5±6.3x 103/μl and 17.4±7.6 x 103/μl respectively.Conclusions: Post-transfusion increments were significantly higher in patients who received SDP as compared to RDP, but the CCI and PR were comparable in both groups of patients