A critical review of anticancer properties of Withania somnifera (L.) Dunal with respect to the biochemical mechanisms of its phytochemical constituents

Cancer is a leading cause of mortality worldwide, the conventional chemotherapeutic drugs have been known for their toxicity and numerous side effects. A new approach to treat cancer involves phytochemical drugs. In the present review, anti-cancer activity of a class of steroidal lactones called withanolides obtained from Withania somnifera (L.) Dunal is discussed. The commonly studied bioactive compounds namely withaferin-A, withanoside IV, withanoside VI and withanolide-A among others obtained from methanolic and chloroform extract of the leaves and various alcoholic, aqueous and chloroform extract of roots have shown inhibition to various human cancer cell lines including skin, breast, colon, prostate, liver, ovary, cervical and lung. Prominent mechanisms of action include induction of apoptosis by NOS upregulation, ROS production and NBS2 or COX-2 inhibition; cytotoxicity by humoral and cell mediated immune response, activation of p53 and pRB and inhibition of various viral oncoproteins; cell cycle arrest by Cdc2 facilitated mitotic catastrophe, cyclin-D1 down-regulation and inhibition of transcription factors. Cancers are also controlled by inhibition of angiogenesis and metastasis of the tumor cells. In addition to anti-tumorogenic properties, W. somnifera also holds properties that make it a potential adjuvant in integrated cancer therapeutics and in enhancing the effectiveness of ongoing radiation therapy

Estimates of genetic parameters of fruit quality traits in teasle gourd (Momordica subangulata Blume. subsp. renigera)

The present investigation was carried out to assess genetic variability, heritability and genetic advance in five genotypes of teasle gourd. The experiment was laid out in a randomized block design with four replications. High phenotypic coefficients of variation were observed for all characters except ascorbic acid in excoarp, ascorbic acid in mesocarp, total soluble solids (TSS) in exocarp, b-carotene in exocarp, acidity in mesocarp, b-carotene in mesocarp, TSS in mesocarp, acidity in exocarp which showed high heritability coupled with high genetic advance indicating that these traits were gene control and simple phenotypic selection can be used for further improvement of these traits. Fruit weight, which showed the highest positive direct effect on fruit yield also showed positive correlation with β-carotene in exocarp. The most important fruit quality influencing traits from the study includes TSS content of exocarp and mesocarp since these traits character showed positive correlations with most important fruit quality characters.Keywords: Teasle gourd, clones, variability, heritability, genetic advance, correlation coefficientAfrican Journal of Biotechnology, Vol. 13(2), pp. 257-264, 8 January, 201

GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets.

G protein-coupled receptors (GPCRs) mediate the majority of platelet activation in response to agonists. However, questions remain regarding the mechanisms that provide negative feedback toward activated GPCRs to limit platelet activation and thrombus formation. Here we provide the first evidence that GPCR kinase 6 (GRK6) serves this role in platelets, using GRK6-/- mice generated by CRISPR-Cas9 genome editing to examine the consequences of GRK6 knockout on GPCR-dependent signaling. Hemostatic thrombi formed in GRK6-/- mice are larger than in wild-type (WT) controls during the early stages of thrombus formation, with a rapid increase in platelet accumulation at the site of injury. GRK6-/- platelets have increased platelet activation, but in an agonist-selective manner. Responses to PAR4 agonist or adenosine 5\u27-diphosphate stimulation in GRK6-/- platelets are increased compared with WT littermates, whereas the response to thromboxane A2 (TxA2) is normal. Underlying these changes in GRK6-/- platelets is an increase in Ca2+ mobilization, Akt activation, and granule secretion. Furthermore, deletion of GRK6 in human MEG-01 cells causes an increase in Ca2+ response and PAR1 surface expression in response to thrombin. Finally, we show that human platelet activation in response to thrombin causes an increase in binding of GRK6 to PAR1, as well as an increase in the phosphorylation of PAR1. Deletion of GRK6 in MEG-01 cells causes a decrease in PAR1 phosphorylation. Taken together, these data show that GRK6 regulates the hemostatic response to injury through PAR- and P2Y12-mediated effects, helping to limit the rate of platelet activation during thrombus growth and prevent inappropriate platelet activation

Observations on the biology of smooth dwarf monocle bream, Parascolopsis aspinosa (Rao & Rao, 1981) from Mangaluru, southwest coast of India

Some aspects of biological information is presented here for the little known smooth dwarf monocle bream, Parascolopsis aspinosa (Rao and Rao, 1981) (Perciformes: Nemipteridae) based on specimens collected from the bycatch of commercial shrimp trawlers operating in the Arabian Sea off the Karnataka coast. Eight-hundred forty seven specimens measuring 7.4 to 22.8 cm TL, and weighing between 15.0 -216 g total weight were analysed for the study. The lengthweight relationships were found to be significantly different between the sexes (P<0.001). The coefficients ‘a’, ‘b’ of the length-weight relationship were estimated as 0.0333, 2.7919 (r2 = 0.961) for females and 0.0194, 2.9791 (r2 = 0.962) for males and the species follows a negative allometric growth pattern (b<3). The fish attains maturity (TL50) at 12.5 cm TL for females and 11.5 cm TL for males. P. aspinosa was found to breed throughout the year with peak spawning during August-September and January. The overall sex ratio (M:F) favoured females at the rate of 1:1.15. A seven-stage maturity was found and a progressive increase in the size of the ova was traced to advanced stages of maturity. The total fecundity of P. aspinosa ranged from 45,823 (12.3 cm TL; 41g body weight) to 1,56,308 (22.8 cm TL; 216 g body weight) with an average fecundity of 84,367 eggs. Analysis of the stomach contents (%IRI) revealed that P. aspinosa mainly fed on Saurida tumbil (%IRI=18.2), followed by Penaeus indicus (%IRI=16.7), Loligo spp. (%IRI=15.2), Squilla (%IRI=6.4), and Acetes spp (%IRI=2.7). Other detailed biological observations such as the length composition, sex ratio, and length at maturity (TL50) of P. aspinosa are also provided in the study. Since the species has been poorly studied and assessed as Least Concern (LC) in the IUCN red list criterion, it is expected that the biological information from the present study will support the ongoing data generation and help in arriving at management decisions for the species in the future

Wearable Bluetooth Triage Healthcare Monitoring System.

Triage is the first interaction between a patient and a nurse/paramedic. This assessment, usually performed at Emergency departments, is a highly dynamic process and there are international grading systems that according to the patient condition initiate the patient journey. Triage requires an initial rapid assessment followed by routine checks of the patients' vitals, including respiratory rate, temperature, and pulse rate. Ideally, these checks should be performed continuously and remotely to reduce the workload on triage nurses; optimizing tools and monitoring systems can be introduced and include a wearable patient monitoring system that is not at the expense of the patient's comfort and can be remotely monitored through wireless connectivity. In this study, we assessed the suitability of a small ceramic piezoelectric disk submerged in a skin-safe silicone dome that enhances contact with skin, to detect wirelessly both respiration and cardiac events at several positions on the human body. For the purposes of this evaluation, we fitted the sensor with a respiratory belt as well as a single lead ECG, all acquired simultaneously. To complete Triage parameter collection, we also included a medical-grade contact thermometer. Performances of cardiac and respiratory events detection were assessed. The instantaneous heart and respiratory rates provided by the proposed sensor, the ECG and the respiratory belt were compared via statistical analyses. In all considered sensor positions, very high performances were achieved for the detection of both cardiac and respiratory events, except for the wrist, which provided lower performances for respiratory rates. These promising yet preliminary results suggest the proposed wireless sensor could be used as a wearable, hands-free monitoring device for triage assessment within emergency departments. Further tests are foreseen to assess sensor performances in real operating environments

Deciphering the regulatory landscapte of fetal and adult γδ T-cell development at single-cell resolution

γδ T cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases, and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of γδ T cells in the thymus is incompletely understood. Here, we establish a high‐resolution map of γδ T‐cell differentiation from the fetal and adult thymus using single‐cell RNA sequencing. We reveal novel sub‐types of immature and mature γδ T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult γδ T‐cell differentiation. By performing a combined single‐cell analysis of Sox13, Maf, and Rorc knockout mice, we demonstrate sequential activation of these factors during IL ‐17‐producing γδ T‐cell (γδT17) differentiation. These findings substantially expand our understanding of γδ T‐cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages

The 2010 nova outburst of the symbiotic Mira V407 Cyg

The nova outburst experienced in 2010 by the symbiotic binary Mira V407 Cyg has been extensively studied at optical and infrared wavelengths with both photometric and spectroscopic observations. This outburst, reminiscent of similar events displayed by RS Oph, can be described as a very fast He/N nova erupting while being deeply embedded in the dense wind of its cool giant companion. The hard radiation from the initial thermonuclear flash ionizes and excites the wind of the Mira over great distances (recombination is observed on a time scale of 4 days). The nova ejecta is found to progressively decelerate with time as it expands into the Mira wind. This is deduced from line widths which change from a FWHM of 2760 km/s on day +2.3 to 200 km/s on day +196. The wind of the Mira is massive and extended enough for an outer neutral and unperturbed region to survive at all outburst phases.Comment: MNRAS Letter, in pres

Emblica Officinalis: A Novel Therapy for Acute Pancreatitis — An Experimental Study

Acute necrotising pancreatitis is associated with an unacceptably high mortality for which no satisfactory remedy exists. Emblica officinalis (E.o.) is a plant prescribed in Ayurveda, the Indian traditional system of medicine, for pancreas-related disorders. This study was carried out to evaluate the protective effect of E.o. against acute necrotising pancreatitis in dogs. Pancreatitis was induced by injecting a mixture of trypsin, bile and blood into the duodenal opening of the pancreatic duct. Twenty eight dogs were divided into 4 groups (n = 6-8 each): GpI–control, GpII–acute pancreatitis, GpIII–sham-operated, GpIV–pretreatment with 28 mg E.o./kg/day for 15 days before inducing pancreatitis. Serum amylase increased from 541.99 ± 129.13 IU/ml to 1592.63 ± 327.83 IU (p<0.02) 2 hrs after the induction of pancreatitis in GpII. The rise in serum amylase in both GpIII and GpIV was not significant. On light microscopic examination, acinar cell damage was less and the total inflammatory score was significantly lower in the E.o. treated group as compared to GpII. Electron microscopy confirmed this and showed an increased amount of smooth, endoplasmic reticulum and small, condensed granules embedded in a vacuole. More studies are needed to explore the clinical potential of E.o. and its mechanism of action

Persistent activation of the ζ isoform of protein kinase C in the maintenance of long-term potentiation

Long-term potentiation in the CA1 region of the hippocampus, a model for memory formation in the brain, is divided into two phases. A transient process (induction) is initiated, which then generates a persistent mechanism (maintenance) for enhancing synaptic strength. Protein kinase C (PKC), a gene family of multiple isozymes, may play a role in both induction and maintenance. In region CA1 from rat hippocampal slices, most of the isozymes of PKC translocated to the particulate fraction 15 sec after a tetanus. The increase of PKC in the particulate fraction did not persist into the maintenance phase of long-term potentiation. In contrast, a constitutively active kinase, PKM, a form specific to a single isozyme (ζ), increased in the cytosol during the maintenance phase. The transition from translocation of PKC to formation of PKM may help to explain the molecular mechanisms of induction and maintenance of long-term potentiation

On a fin whale stranded at Someswara, South Kanara

A huge whale was observed floating near the shore at Ullal was dragged away from the shore into the sea for about 15-20 km and released by the trawler fishermen. But the whale was swept shoreward by strong waves and was stranded at Someswara beach which identified was Balaenoptera physalis. Morphometry were recorded and had Total length (tip of the lowerjaw to tipofthefluke) 1,402 cm Distance between flipper base to origin of fluke 1,037cm and Distance from origin of fluke to genito-anal slit 457cms. The whale was a female with prominent genital opening with maximum girth at the region of flippers