Biodiversity of few Indian charophyte taxa based on molecular characterization and construction of phylogenetic tree

The world charophyte flora suffered reshuffling in the taxonomic status of many taxa on the basis of certain morphological characters. Large numbers of species were reduced to the status of subspecies, variety or forma while some distant species were merged together. In this study, molecular characteristics such as band frequency, RAPD polymorphism, genetic identity index or similarity index, band sharing frequency and genetic distance within and in between Chara and Nitella were evaluated. With the help of scorable bands, range of molecular sizes was recorded in amplified products of 12charophyte taxa by using five random primers. This investigation requires further elaboration to reach a definite conclusio

Effect of insecticides on foraging behaviour and pollination role of Apis mellifera L. (Hymenoptera: Apidae) on toria (Brassica campestris var. toria) crop

The effects of insecticide application on foraging and pollination by honeybees in toria (Brassica campestris var. toria) cultivar RSPT-1 were studied at Jammu (India).Under field conditions the application of betacylfluthrin, betacyfluthrin + imidacloprid and carbaryl resulted in 100% bee mortality within one hour of spraying. After 48 hours, 100% mortality was recorded in all the treatments except malathion (94%). The post-spraying effects of the insecticides were much higher during the first hour after treatment, but after 48 hr there was 100% mortality in all treatments except imidacloprid (43%). Residual effects after spraying were high for flowers sprayed with imidacloprid (76% mortality), demeton-o-methyl, carbaryl, and ethiprole, moderate for betacyfluthrin (49%), betacyfluthrin + imidacloprid, and profenophos, and low for malathion (12%). The residual effect decreases with time and after 96 hours of spraying, the residual effect was reduced in almost all the insecticides. The number of foraging bees were greatly reduced in all treatments 24 hr after spraying, compared to levels before spraying, recovering considerably after 3 days, and normal after 7 days. Open pollination resulted in 1.80 times more yield compared to caged condition and crop pollinated by bees alone. This study suggests that both protective application of insecticides and use of honeybees for pollination are essential for maximum crop yields

Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions with proteins of the Bcl-2 family

Rottlerin is a polyphenolic compound derived from Mallotus philipinensis. In the present study, we show that rottlerin decreased tumor size and stimulated apoptosis in an orthotopic model of pancreatic cancer with no effect on normal tissues in vivo. Rottlerin also induced apoptosis in pancreatic cancer (PaCa) cell lines by interacting with mitochondria and stimulating cytochrome c release. Immunoprecipitation results indicated that rottlerin disrupts complexes of prosurvival Bcl-xL with Bim and Puma. Furthermore, siRNA knockdown showed that Bim and Puma are necessary for rottlerin to stimulate apoptosis. We also showed that rottlerin and Bcl-2 and Bcl-xL inhibitor BH3I-2' stimulate apoptosis through a common mechanism. They both directly interact with mitochondria, causing increased cytochrome c release and mitochondrial depolarization, and both decrease sequestration of BH3-only proteins by Bcl-xL. However, the effects of rottlerin and BH3I-2' on the complex formation between Bcl-xL and BH3-only proteins are different. BH3I-2' disrupts complexes of Bcl-xL with Bad but not with Bim or Puma, whereas rottlerin had no effect on the Bcl-xL interaction with Bad. Also BH3I-2', but not rottlerin, required Bad to stimulate apoptosis. In conclusion, our results demonstrate that rottlerin has a potent proapoptotic and antitumor activity in pancreatic cancer, which is mediated by disrupting the interaction between prosurvival Bcl-2 proteins and proapoptotic BH3-only proteins. Thus rottlerin represents a promising novel agent for pancreatic cancer treatment

Acute mental health presentations before and during the COVID-19 pandemic

Background: A number of community based surveys have identified an increase in psychological symptoms and distress but there has been no examination of symptoms at the more severe end of the mental health spectrum. // Aims: We aimed to analyse numbers and types of psychiatric presentations to inform planning for future demand on mental health services in light of the COVID-19 pandemic. // Method: We analysed electronic data between January and April 2020 for 2534 patients referred to acute psychiatric services, and tested for differences in patient demographics, symptom severity and use of the Mental Health Act 1983 (MHA), before and after lockdown. We used interrupted time-series analyses to compare trends in emergency department and psychiatric presentations until December 2020. // Results: There were 22% fewer psychiatric presentations the first week and 48% fewer emergency department presentations in the first month after lockdown initiated. A higher proportion of patients were detained under the MHA (22.2 v. 16.1%) and Mental Capacity Act 2005 (2.2 v. 1.1%) (χ2(2) = 16.3, P < 0.0001), and they experienced a longer duration of symptoms before seeking help from mental health services (χ2(3) = 18.6, P < 0.0001). A higher proportion of patients presented with psychotic symptoms (23.3 v. 17.0%) or delirium (7.0 v. 3.6%), and fewer had self-harm behaviour (43.8 v. 52.0%, χ2(7) = 28.7, P < 0.0001). A higher proportion were admitted to psychiatric in-patient units (22.2 v. 18.3%) (χ2(6) = 42.8, P < 0.0001) after lockdown. // Conclusions: UK lockdown resulted in fewer psychiatric presentations, but those who presented were more likely to have severe symptoms, be detained under the MHA and be admitted to hospital. Psychiatric services should ensure provision of care for these patients as well as planning for those affected by future COVID-19 waves

Resistance to receptor-blocking therapies primes tumors as targets for HER3-homing nanobiologics

Resistance to anti-tumor therapeutics is an important clinical problem. Tumor-targeted therapies currently used in the clinic are derived from antibodies or small molecules that mitigate growth factor activity. These have improved therapeutic efficacy and safety compared to traditional treatment modalities but resistance arises in the majority of clinical cases. Targeting such resistance could improve tumor abatement and patient survival. A growing number of such tumors are characterized by prominent expression of the human epidermal growth factor receptor 3 (HER3) on the cell surface. This study presents a “Trojan-Horse” approach to combating these tumors by using a receptor-targeted biocarrier that exploits the HER3 cell surface protein as a portal to sneak therapeutics into tumor cells by mimicking an essential ligand. The biocarrier used here combines several functions within a single fusion protein for mediating targeted cell penetration and non-covalent self-assembly with therapeutic cargo, forming HER3-homing nanobiologics. Importantly, we demonstrate here that these nanobiologics are therapeutically effective in several scenarios of resistance to clinically approved targeted inhibitors of the human EGF receptor family. We also show that such inhibitors heighten efficacy of our nanobiologics on naïve tumors by augmenting HER3 expression. This approach takes advantage of a current clinical problem (i.e. resistance to growth factor inhibition) and uses it to make tumors more susceptible to HER3 nanobiologic treatment. Moreover, we demonstrate a novel approach in addressing drug resistance by taking inhibitors against which resistance arises and re-introducing these as adjuvants, sensitizing tumors to the HER3 nanobiologics described here

Evidence-based national vaccine policy

India has over a century old tradition of development and production of vaccines. The Government rightly adopted self-sufficiency in vaccine production and self-reliance in vaccine technology as its policy objectives in 1986. However, in the absence of a full-fledged vaccine policy, there have been concerns related to demand and supply, manufacture vs. import, role of public and private sectors, choice of vaccines, new and combination vaccines, universal vs. selective vaccination, routine immunization vs. special drives, cost-benefit aspects, regulatory issues, logistics etc. The need for a comprehensive and evidence based vaccine policy that enables informed decisions on all these aspects from the public health point of view brought together doctors, scientists, policy analysts, lawyers and civil society representatives to formulate this policy paper for the consideration of the Government. This paper evolved out of the first ever ICMR-NISTADS national brainstorming workshop on vaccine policy held during 4-5 June, 2009 in New Delhi, and subsequent discussions over email for several weeks, before being adopted unanimously in the present form

Temporary techno-social gatherings? A (hacked) discussion about open practices

This paper is rooted in an experimental inquiry of issue-oriented temporary techno-social gatherings or TTGs, which are typically referred to as hackathons, workshops or pop-ups and employ rapid design and development practices to tackle technical challenges while engaging with social issues. Based on a collaboration between three digital practitioners (a producer, a researcher and a designer), qualitative and creative data was gathered across five different kinds of TTG events in London and in Tartu which were held in partnership with large institutions, including Art:Work at Tate Exchange within Tate Modern, the Mozilla Festival at Ravensbourne College and the 2017 Association of Internet Researchers conference hosted in Tartu. By analysing data using an open and discursive approach manifested in both text and visual formats, we reflect on the dynamic and generative characteristics of TTG gatherings while also arriving at our own conclusions as situated researchers and practitioners who are ourselves engaged in increasingly messy webs where new worlds of theory and practice are built

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

G protein-coupled receptors (GPCRs) play crucial roles in cell physiology and pathophysiology. There is increasing interest in using structural information for virtual screening (VS) of libraries and for structure-based drug design to identify novel agonist or antagonist leads. However, the sparse availability of experimentally determined GPCR/ligand complex structures with diverse ligands impedes the application of structure-based drug design (SBDD) programs directed to identifying new molecules with a select pharmacology. In this study, we apply ligand-directed modeling (LDM) to available GPCR X-ray structures to improve VS performance and selectivity towards molecules of specific pharmacological profile. The described method refines a GPCR binding pocket conformation using a single known ligand for that GPCR. The LDM method is a computationally efficient, iterative workflow consisting of protein sampling and ligand docking. We developed an extensive benchmark comparing LDM-refined binding pockets to GPCR X-ray crystal structures across seven different GPCRs bound to a range of ligands of different chemotypes and pharmacological profiles. LDM-refined models showed improvement in VS performance over origin X-ray crystal structures in 21 out of 24 cases. In all cases, the LDM-refined models had superior performance in enriching for the chemotype of the refinement ligand. This likely contributes to the LDM success in all cases of inhibitor-bound to agonist-bound binding pocket refinement, a key task for GPCR SBDD programs. Indeed, agonist ligands are required for a plethora of GPCRs for therapeutic intervention, however GPCR X-ray structures are mostly restricted to their inactive inhibitor-bound state