The methuselah family of g protein coupled receptors

G protein-coupled receptors (GPCRs) are one of the largest class of transmembrane signaling proteins that regulate essential developmental and physiological processes in a cell. GPCR success is illustrated by their abundance across both invertebrate and vertebrate genomes. Phylogenetic analyses show that GPCR families have undergone a lot of gene gain and loss during insect evolution. In Drosophila melanogaster, the fifteen Methuselah/Methuselah-like (Mth/Mthl) genes are in fact an insect specific family of GPCRs. In our study, we conducted a phylogenetic analysis using receptor sequences from five Drosophila species and two related insects, including Tribolium and Anopheles to examine the evolution of this gene family. Clearly Mthl1, 5, and 14 form their own separate clades. The remaining Drosophila genes along with a single gene in Tribolium form a fourth clade defined by the presence of the Mth ectodomain. Expression patterns of the Tribolium gene and all Drosophila paralogs were determined by in situ hybridization. The Tribolium Mthl gene is expressed in the hindgut and mesodermal crystal cells of the embryo which is divided between Drosophila Mthl9 and Mthl10. Mthl10 also evolves other more specific expression patterns in both the embryo third instar larvae which is divided between the other Mthl genes. In summary, six genes (Mthl 1, 5, 9, 11, 13 and 14) are expressed in the embryo, four (Mthl3, 4, 6 and 8) in the larval CNS and imaginal discs and two (Mthl10 and Mth) in both embryos and larvae. We further show Mthl5 expression in the cardiac mesoderm of stage 11 embryos and later restricted to cardioblast cells of the aorta. Loss of mthl5 decreases pericardial-cardial cell association necessary to maintain cardiac intergrity. We show that mthl5 genetically interacts with Goa to increase the loss of cell-cell adhesion in the Drosophila aorta. Together these data clearly show the expansion of the Mth/Mthl family in insects and the evolution of novel gene functions required for organ morphogenesis

PRELIMINARY PHYTOCHEMICAL ANALYSIS OF LEAVES OF GUCHAKARANJA (QUASSIA INDICA GAERTN)

The drug Guchakaranja is mentioned as one of Karanja variety by Raj Nighantu and Nighantu Ratnakara. The references of the drug are not seen in other classical textbooks of Ayurveda and the only references seen in these two Nighantus. The drug had been correlated to Karinjotta, a locally available plant in Kerala. The drug Guchakaranja is botanically correlated as Quassia indica Gaertn (Samadera indica Gaertn) belonging to the family Simaroubaceae commonly known as Niepa bark tree. The drug had been extensively used in folklore practices and usage of the plant in main stream clinical practices is less. So giving a standardization and to justify its traditional usages preliminary phyochemical analysis had been done. The preliminary phytochemical analysis aims at analyzing the physico chemical property of drugs, their qualitative analysis, ash values, extractive values, moisture and volatile contents, estimation of Tannins and Phenols and HPTLC. Previous studies are available regarding the Qualitative Analysis of phytochemicals, tannin and total phenolic estimation. References regarding ash values, quantitative estimation of fiber, reducing sugar and total sugar, pH, cold and hot alcohol and water soluble extractives, moisture content were not available from previous research works On analyzing the phytochemical constituents present in the crude drug, the drug revealed the presence of alkaloids, flavonoids, saponins, carbohydrates, proteins, phenols, steroids, and tannins. This phytoconstituents present in the drug may be responsible for specific action of the drug. This preliminary phytochemical evaluation may be helpful to identify the potential of Guchakaranja and should be helpful in developing new formulations with additional therapeutic effect

Is low amniotic fluid index an indicator of fetal distress and hence delivery?

Background: Amniotic fluid Index (AFI) is an indicator of fetal well-being. Low AFI is considered to be one of the indications for delivery as it may be associated with fetal distress and birth asphyxia. We sought to determine whether low AFI is an indicator of fetal compromise and an indication to deliver.Methods: This prospective, observational study was conducted at Department of Obstetrics & Gynecology, KMC, Manipal University, India, between August 2013 and Aug 2014. A total of 150 subjects that had induced labor or direct caesarean section for various indications and also having low-normal (5-8) / low (<5) AFI, were recruited. Subjects with fetal anomalies were excluded. Outcome variables studied were, fetal distress in labor, thick meconium stained amniotic fluid, mode of delivery in induced labor, perinatal asphyxia, and respiratory distress syndrome.Results: Out of 150 subjects, 68 (45.4%) had low and 82 (54.6%) had low-normal AFI. Both the groups were matched for demographic characteristics and confounding factors for neonatal outcome. In low AFI group the incidence of Low APGAR (11.7%), perinatal asphyxia (11.7%) and RDS (16.1%) were significantly higher compared to those in low-normal group (3.6%, 1.2% and 2.4% respectively) p = 0.057, 0.006 and 0.002. There was no significant difference between the groups with respect to mode of delivery when labor was induced.Conclusions: Low AFI, especially when it is <5, is an indicator of fetal compromise and one may anticipate perinatal asphyxia and RDS. Hence it is prudent to contemplate delivery when the AFI is between 5 and 8

Implementation of Decoy Deception based Detection System for Ransomware Attack

Ransomware poses a dangerous threat to&nbsp; cybersecurity. Data as well as rights owned by the user are&nbsp; adversely impacted. The situation has become considerably&nbsp; more critical as a result of the emergence of new ransomware&nbsp; varieties and Ransomware-as-a-Service. In this paper, we&nbsp; presented a novel deception-based and behaviour-based&nbsp; method for real-time ransomware detection. In order to avoid&nbsp; any loss before ransomware is discovered, we build pretend&nbsp; files and directories for nefarious behaviours. We conducted a&nbsp; pilot study using Locky, and the results demonstrate the&nbsp; effectiveness of our strategy with little system resource usage&nbsp; and geographical cost.&nbsp

Measurement of 92Mo(n,α)89Zr and 97Mo(n,p)97Nb reactions at the neutron energy 13.52 MeV with covariance analysis

218-222The cross sections have been estimated for the Nuclear reactions 92Mo(n,α)89Zr and 97Mo(n,p)97Nb produced in Purnima neutron generator at neutron energy of 13.52±0.0045 MeV using activation analysis and off-line γ -ray spectrometric techniques. 27Al(n,α)24Na has been used as a monitor reaction. The covariance analysis for these cross sections has been carried out by taking into consideration of partial uncertainties of different attributes and correlations between the attributes. The cross section values of the present study have been compared with EXFOR, ENDF data of various libraries and theoretical data of TALYS-1.8 code

Concomitant mandibular hypo-hyperdontia: Report of two rarest cases with the literature review

Concomitant occurrence of both hypodontia (congenital tooth agenesis) and hyperdontia (supernumerary tooth) in the same dental arch is an extremely rare dental anomaly. Literature search shows very few cases of this anomalous condition with all cases depicting the unilateral presence of supernumerary tooth. Therefore, the intention of the current article is to report two cases of concomitant occurrence of mandibular both hypo-hyperdontia. In that one case exhibited bilateral occurrence of mesiodens teeth in the midline of mandible with associated agenesis of permanent both central incisors and taurodontism in permanent molars, which is not published so far. The article also provides comprehensive literature review on this rarest clinical entity

New steps on an old path: Novel estrogen receptor inhibitors in breast cancer

: Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in hormone receptor positive (HR+) breast cancer (BC). Thus, endocrine therapy (ET) alone or in combination with targeted agents constitutes the mainstay of the treatment for this BC subtype. Despite its efficacy, intrinsic or acquired resistance to ET occurs in a large proportion of cases, mainly due to aberrant activation of ER signaling (i.e. through ligand-independent ER activation, in the presence of estrogen receptor 1 (ESR1) gene aberration or ER protein phosphorylation) and/or the upregulation of escape pathways, such as the PI3K/AKT/mTOR pathway. Therefore, the development of new ER pathway targeting agents remains essential to delay and overcome ET resistance, enhance treatment efficacy and tolerability, and ultimately prolong patient survival and improve their quality of life. Several novel ER targeting agents are currently under investigation. Among these, the oral selective ER degraders (SERDs) represent the pharmacological class at the most advanced stage of development and promise to enrich the therapeutic armamentarium of HR+&nbsp;BC in the next few years, as they showed promising results in several clinical trials, either as single ET agents or in combination with targeted therapies. In this manuscript, we aim to provide a comprehensive overview on the clinical development of novel ER targeting agents, reporting the most up-to-date evidence on oral SERDs and other compounds, including new selective ER modulators (SERMs), ER proteolysis targeting chimera (PROTACs), selective ER covalent antagonists (SERCAs), complete ER antagonists (CERANs), selective human ER partial agonists (ShERPAs). Furthermore, we discuss the potential implications of introducing these novel treatment strategies in the evolving and complex therapeutic scenario of HR+&nbsp;BC

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Measurement of 92Mo(n,α)89Zr and 97Mo(n,p)97Nb reactions at the neutron energy 13.52 MeV with covariance analysis

The cross sections have been estimated for the Nuclear reactions 92Mo(n,α)89Zr and 97Mo(n,p)97Nb produced in Purnima neutron generator at neutron energy of 13.52±0.0045 MeV using activation analysis and off-line γ -ray spectrometric techniques. 27Al(n,α)24Na has been used as a monitor reaction. The covariance analysis for these cross sections has been carried out by taking into consideration of partial uncertainties of different attributes and correlations between the attributes. The cross section values of the present study have been compared with EXFOR, ENDF data of various libraries and theoretical data of TALYS-1.8 code

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine