Fe65 Is Phosphorylated on Ser289 after UV-Induced DNA Damage

Fe65 undergoes a phosphatase-sensitive gel mobility shift after DNA damage, consistent with protein phosphorylation. A recent study identified Ser228 as a specific site of phosphorylation, targeted by the ATM and ATR protein kinases, with phosphorylation inhibiting the Fe65-dependent transcriptional activity of the amyloid precursor protein (APP). The direct binding of Fe65 to APP not only regulates target gene expression, but also contributes to secretase-mediated processing of APP, producing cytoactive proteolytic fragments including the APP intracellular domain (AICD) and cytotoxic amyloid β (Aβ) peptides. Given that the accumulation of Aβ peptides in neural plaques is a pathological feature of Alzheimer’s disease (AD), it is essential to understand the mechanisms controlling Aβ production. This will aid in the development of potential therapeutic agents that act to limit the deleterious production of Aβ peptides. The Fe65-APP complex has transcriptional activity and the complex is regulated by multiple post-translational modifications and other protein binding partners. In the present study, we have identified Ser289 as a novel site of UV-induced phosphorylation. Interestingly, this phosphorylation was mediated by ATM, rather than ATR, and occurred independently of APP. Neither phosphorylation nor mutation of Ser289 affected the Fe65-APP interaction, though this was markedly decreased after UV treatment, with a concomitant decrease in the protein levels of APP in cells. Using mutagenesis, we demonstrated that Fe65 Ser289 phosphorylation did not affect the transcriptional activity of the Fe65-APP complex, in contrast to the previously described Ser228 site

Modelling Accessibility based on Urbanization using Artificial Neural Networks (ANN)

The present study involves modelling the accessibility index with respect to the traffic volume, Right of Way width and Population density. It also involves the collection of number of different types of opportunities like schools, hospitals, ATMs, bus-stops and parks to determine the accessibility index. Two different methods are used in the study such as Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) to develop models in order to predict the accessibility index. Based on the R2 value obtained in the models, it is observed that ANN has better prediction capability than MLR model. The study acts as a guide to the urban transportation planners to understand the change in accessibility index when there is a change in urbanization variables

HEPATOPROTECTIVE ACTIVITY OF ALSTONIA SCHOLARIS FRUITS AGAINST CARBON TETRACHLORIDE-INDUCED HEPATOTOXICITY IN RATS

The hepatoprotective activity of ethanolic extract of fruits of Alstonia scholaris was evaluated by carbon tetrachloride (CCL4)-induced hepatotoxicity in rats. The toxicant CCL4 was used to induce hepatotoxicity at a dose of 2 ml/kg as 1:1 mixture with olive oil. The ethanolic extract of fruits of Alstonia scholaris was administered in the dose of 150 and 300 mg/kg/day orally for 5 days. Silymarin (50 mg/kg) was used as standard drug. The hepatoprotective effect of the ethanolic extract was evaluated by the assessment of biochemical parameters such as SGOT, SGPT, SALKP, total bilirubin and histopathological studies of the liver. Treatment of animals with the ethanolic extract significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver as indicated by lower levels of serum bilirubin as compared with the normal and silymarin treated groups

DEVELOPMENT AND VALIDATION OF STABILITY INDICATING REVERSED PHASE HIGHPRESSURE LIQUID CHROMATOGRAPHY METHOD FOR SIMULTANEOUS ESTIMATION OF METFORMIN AND EMPAGLIFLOZIN IN BULK AND TABLET DOSAGE FORM

ABSTRACT Objective: To develop accurate, fast, simple, and precise reversed-phase high-pressure liquid chromatography method for simultaneous determination of the binary mixture of metformin (MET) and empagliflozin (EMPA) in dosage forms. Methods: The method uses a mobile phase consisting of phosphate buffer, acetonitrile, methanol (15:80:5 v/v/v), an octadecyl silica C-18 column (4.6 mm × 250 mm, 5 μ particle size) in isocratic mode, detection wavelength of 227 nm, and a flow rate of 1 mL/minutes. Results:  The  measured  retention  times  for  MET  and  EMPA  and  were  2.528  and  4.140 minutes,  respectively.  The  percentage  recoveries  of  MET  and  EMPA  were 101.12% and 100.55%, respectively. The relative standard deviation for assay of tablets was found to beÂ

Evaluating the efficacy and safety of simple combination of analgesics with and without low dose opioid for perioperative analgesia, hemodynamic and recovery profile in various surgeries posted under general anaesthesia: a prospective randomised controlled study

Background: Multimodal analgesia is an emerging technique.It has been consistently demonstrated to minimise opioid consumption, related side effects and vital component of enhanced recovery after surgery pathways. The current study presents use of combination of readily available medication as a part of multimodal analgesia. Balanced anaesthesia with multimodal analgesia is harmonious use of combination of agents to produce desired effects with minimal side effects of individual agents. Methods: This study was done in a tertiary health care centre, Government General Hospital, Kakinada over a duration of two months from August 2022 to September 2022. 60 adult patients of either sex of physical status ASA grade 1and 2 undergoing elective surgery under general anaesthesia were randomly allocated into Group A and Group B of 30 patients. Group 1: received Inj. Lignocaine+Inj. Paracetamol+Inj. Magnesium sulphate+Inj. Fentanyl. Group 2:received Inj. Lignocaine+Inj. Paracetamol+Inj. Magnesium sulphate+Normal saline (control group) as premedication for perioperative analgesia. Results: All patients were hemodynamically stable for first 30 minutes period of observation in Group A compared to Group B. There is clinically and statistically significant difference in the duration of analgesia in Group A compared to Group B. There is no statistically significant difference in the Numerical Rating Scale (NRS) for pain in both the groups. Conclusions: This study concluded that simple analgesia combination of multimodal analgesia regimen comprising of Inj. Lignocaine, Inj. Paracetamol and Inj. Magnesium sulphate produces safe and effective analgesia with good recovery profiles and no adverse opioid related side effects for ASA 1 and 2 patients posted under general anaesthesia

Validation of Molecular Markers Genetically Linked to S-Cytoplasm and Restoration-of-fertility (Rf) Loci in Hot Pepper (Capsicum annuum L.)

Existence of CGMS system in hot pepper is due to the rearrangements in the mitochondrial genome and is largely used in economized and pure F 1 hybrid seed production around the world. The orf456, a new ORF present at flanking region of the coxII gene at the 3’ end, was distinguished male sterile cytoplasm in hot peppers along with atp6-2gene. In the current study, eighteen pepper genotypes (nine each of A and corresponding B lines) of varied origin were used to validate with two male sterile cytoplasm (S-cytoplasm) specific sequence characterised amplified region (SCAR) markers viz., atp6-2 (875 bp) and orf456 (456 bp) and one restoration-of-fertility (Rf) locus specific marker, CRF (550 bp). The results clearly showed that the presence of CMS-S-cytoplasm and absence of restoration-of-fertility (Rf) gene in the pepper genotypes studied and is comparable with the phenotypic data. In view of the outcomes it has been reasoned that the accessible S and Rf markers available in the public domain are reproducible and can be promptly utilized for marker assisted selection (MAS) in hot pepper crop improvement program

PRELIMINARY PHYTOCHEMICAL, PHARMACOGNOSTIC AND PHYSICOCHEMICAL EVALUATION OF ERANTHEMUM NIGRUM LEAF

Objective: To analyze the pharmacognostic characteristics and physiochemical parameters of the leaves of Eranthemum nigrum (E. nigrum). Methods: Microscopic characters and powder analysis had been carried out with the help of a microscope. The physiochemical properties such as loss on drying, total ash value, acid insoluble ash value, water soluble ash value, extractive values and fluorescence of E. nigrum had been performed. Results: Macroscopically, the leaves are simple, elliptical in shape, dull with smooth margins and acute apex. Microscopically, the leaf showed the presence of epidermal cells with uniseriate multicellular covering trichomes and diacytic stomata, followed by 4-6 layered collenchymatous cells and 10-14 numbered conjoint, collateral closed vascular bundles are some of the diagnostic characteristics observed from an anatomical study. Powder microscopy of leaf revealed the presence of uniseriate multicellular covering trichomes, lignified xylem vessels, epidermis with diacytic stomata and parenchyma cells. The investigations also included leaf surface data i.e., quantitative leaf microscopy and fluorescence analysis. Physiochemical parameters such as loss on drying, extractive values and ash values were also determined. Preliminary phytochemical screening showed the presence of steroids, alkaloids, tannins, saponins, carbohydrates, glycosides, amino acids and proteins. Conclusion: The morphological, microscopical and physicochemical parameter results provided in this paper may be utilized as a basis for the preparation of a monograph on E. nigrum leaves

Characterization and evaluation of morphological and yield traits of tamarind genotypes

The evaluation of morphological and yield traits of tamarind genotypes was carried out during 2017-18 at Forest Research Station, Govinkovi, Honnali taluk, Davangere district. The experiment was laid out in randomized complete block design with 16 genotypes and three replications. Trees were 14-years-old and of grafted origin. All the morphological and yield traits showed significant difference among the selected genotypes indicating the presence of adequate variations. The genotypes recorded morphological variation in terms of tree shape (semi-circle to irregular shape), foliage arrangement (dense to sparse), flowering time (early, mid and late), stem colour (dark brown, brown and light brown), bud colour (greenish white, pink, dark pink), petal colour (yellow and pale yellow), pod colour (greyish brown, brown, light brown and dark brown), pulp colour (light brown, brown and reddish brown), pod shape (straight, slightly curved, curved and deeply curved) and pod size (very big, big, medium and small). The analysis of variance revealed significant difference with respect to tree height, stem girth, pod traits, pod yield per tree (K-9 : 12.80 kg), number of pods per tree (NTI-52 : 989.07) and pulp per cent (K-9 : 48.87). Among the 16 genotypes, the genotype K-9 was found superior with respect to pod size, pod weight, pulp weight and pod yield per tree. Genotype K-9 was found promising and due to perennial in nature further evaluation is required for stability