New Ways to Tackle Malaria

Malaria is one of the oldest tropical diseases and still remains a focus of attention. Sub-Saharan African countries contribute 90% of the total malaria cases in the world. The World Health Organization (WHO) has advocated eliminating this disease by 2030 with the existing strategies and tools. Many initiatives are underway by several organizations, and 38 countries have achieved the elimination goal. The main backbone of the elimination process is smart surveillance followed by prompt public health responses. The control of the disease mainly relies on treatment of malaria positive cases with anti-malarials namely artemisinin-based combination therapy (ACT) for Plasmodium falciparum. In India, chloroquine is still effective against P. vivax. Use of 8-aminoquinolines primaquine and more recently tefenoquine warrants testing of G6PD deficiency status to avoid unnecessary hemolysis. Vector control operations mainly depend on the use of long-lasting insecticidal nets (LLINs) and indoor residual spray (IRS) with insecticides. The threat of resistance draws an open challenge in both treatment and vector management. New initiatives on surveillance, treatment, chemoprevention, and vector control using modern techniques of artificial intelligence, machine learning, genetic engineering, and digital approach of community engagement have great potential to accelerate the malaria elimination process

Innovations in Vector-Borne Disease Control in India

India is the second largest populous and democratic country in the world. Several geo-ecological settings are favorable for most of the vector borne diseases (VBDs) in the country. Malaria, Lymphatic Filariasis (LF), Japanese Encephalitis (JE), Dengue (DEN), Chikungunya (CHIK) and Kala-azar (KA) are major VBDs. Kyasanur Forest Disease (KFD), Plague and Chandipura virus (CHPV) infections have limited and localized foci, but needs attention. Crimean-Congo Hemorrhagic Fever (CCHF) and Zika are recent entries in India that also need to be handled on priority. National Vector Borne Disease Control Program (NVBDCP) is responsible for control and prevention of all these diseases. Malaria, LF, JE, DEN, CHIK and Zika are transmitted by different species of mosquitoes. KA and CHPV are transmitted by shadflies, while KFD, CCHF by ticks; plague by fleas. Scrub typhus (ST) responsible for acute encephalopathy syndrome (AES) is transmitted by Leptotrombidium mite species. It needs specific and strategic action plan in view of the diversified biodiversity. New innovations to strengthen the public health responses are the main intervention protocols. Already two diseases Guineaworm (Dracunculiasis) transmitted by different species of Cyclops, and polio have been successfully eradicated/eliminated from India. Such experience would be very helpful for the elimination of malaria, LF and KA, and all are on the elimination drive

New Challenges in Malaria Elimination

In recent years, efforts to eliminate malaria has gained a tremendous momentum, and many countries have achieved this goal — but it has faced many challenges. Recent COVID-19 pandemic has compounded the challenges due to cessation of many on-field operations. Accordingly, the World Health Organization (WHO) has advocated to all malaria-endemic countries to continue the malaria elimination operations following the renewed protocols. The recent reports of artemisinin resistance in Plasmodium falciparum followed by indication of chloroquine resistance in P. vivax, and reduced susceptibility of synthetic pyrethroids used in long lasting insecticide nets are some issues hindering the elimination efforts. Moreover, long distance night migration of vector mosquitoes in sub-Saharan Africa and invasion of Asian vector Anopheles stephensi in many countries including Africa and Southeast Asia have added to the problems. In addition, deletion of histidine rich protein 2 and 3 (Pfhrp2/3) genes in P. falciparum in many countries has opened new vistas to be addressed for point-of-care diagnosis of this parasite. It is needed to revisit the strategies adopted by those countries have made malaria elimination possible even in difficult situations. Strengthening surveillance and larval source management are the main strategies for successful elimination of malaria. New technologies like Aptamar, and artificial intelligence and machine learning would prove very useful in addressing many ongoing issues related to malaria elimination

Comparative transcriptomic profile analysis of fed-batch cultures expressing different recombinant proteins in Escherichia coli

There is a need to elucidate the product specific features of the metabolic stress response of the host cell to the induction of recombinant protein synthesis. For this, the method of choice is transcriptomic profiling which provides a better insight into the changes taking place in complex global metabolic networks. The transcriptomic profiles of three fed-batch cultures expressing different proteins viz. recombinant human interferon-beta (rhIFN-β), Xylanase and Green Fluorescence Protein (GFP) were compared post induction. We observed a depression in the nutrient uptake and utilization pathways, which was common for all the three expressed proteins. Thus glycerol transporters and genes involved in ATP synthesis as well as aerobic respiration were severely down-regulated. On the other hand the amino acid uptake and biosynthesis genes were significantly repressed only when soluble proteins were expressed under different promoters, but not when the product was expressed as an inclusion body (IB). High level expression under the T7 promoter (rhIFN-β and xylanase) triggered the cellular degradation machinery like the osmoprotectants, proteases and mRNA degradation genes which were highly up-regulated, while this trend was not true with GFP expression under the comparatively weaker ara promoter. The design of a better host platform for recombinant protein production thus needs to take into account the specific nature of the cellular response to protein expression

Developing Tailor-Made Microbial Consortium for Effluent Remediation

The work describes a biofilm-based soluble sulphate reduction system, which can treat up to 1600 ppm of soluble sulphate within 3.5 hours of incubation to discharge level under ambient condition using a well-characterized sulphate-reducing bacterial (SRB) consortium. This system ensures the treatment of 1509 litres of sulphate solution in 24 hours using a 220-litre bioreactor. Performance of the system during series operation was compromised, indicating the presence of inhibitor in solution at a toxic level. A single unit bioreactor would be the ideal configuration for this consortium. Modified designs of bioreactors were tested for optimization of the process using response surface methodology (RSM), where the system could function optimally at an initial sulphate concentration of 1250 ppm with a flow rate of 1.8 litre/hour. The time course of sulphate reduction yielded a parabolic profile (with coefficient of determination r 2 = 0.99 and p value < 0.05). The rate of sulphate reduction was found to be independent of seasonal variation as well as the specific design characteristic

A pro-convulsive carbamazepine metabolite: Quinolinic acid in drug resistant epileptic human brain

Drugs and their metabolites often produce undesirable effects. These may be due to a number of mechanisms, including biotransformation by P450 enzymes which are not exclusively expressed by hepatocytes but also by endothelial cells in brain from epileptics. The possibility thus exists that the potency of systemically administered central nervous system therapeutics can be modulated by a metabolic blood-brain barrier (BBB). Surgical brain specimens and blood samples (ex vivo) were obtained from drug-resistant epileptic subjects receiving the antiepileptic drug carbamazepine prior to temporal lobectomies. An in vitro blood-brain barrier model was then established using primary cell culture derived from the same brain specimens. The pattern of carbamazepine (CBZ) metabolism was evaluated in vitro and ex vivo using high performance liquid chromatography-mass spectroscopy. Accelerated mass spectroscopy was used to identify 14 C metabolites deriving from the parent 14 C-carbamazepine. Under our experimental conditions carbamazepine levels could not be detected in drug resistant epileptic brain ex situ; low levels of carbamazepine were detected in the brain side of the in vitro BBB established with endothelial cells derived from the same patients. Four carbamazepine-derived fractions were detected in brain samples in vitro and ex vivo. HPLC-accelerated mass spectroscopy confirmed that these signals derived from 14 C-carbamazepine administered as parental drug. Carbamazepine 10, 11 epoxide (CBZ-EPO) and 10, 11-dihydro-10, 11-dihydrooxy-carbamazepine (DiOH-CBZ) were also detected in the fractions analyzed. 14 C-enriched fractions were subsequently analyzed by mass spectrometry to reveal micromolar concentrations of quinolinic acid (QA). Remarkably, the disappearance of carbamazepine-epoxide (at a rate of 5% per hour) was comparable to the rate of quinolinic acid production (3% per hour). This suggested that quinolinic acid may be a result of carbamazepine metabolism. Quinolinic acid was not detected in the brain of patients who received antiepileptic drugs other than carbamazepine prior to surgery or in brain endothelial cultures obtained from a control patient. Our data suggest that a drug resistant BBB not only impedes drug access to the brain but may also allow the formation of neurotoxic metabolites

Whole-Genome Sequence of Drug-Resistant Mycobacterium tuberculosis Strain S7, Isolated from a Patient with Pulmonary Tuberculosis

Over the past decades, drug-resistant Mycobacterium tuberculosis strains have presented a significant challenge, with inadequate diagnosis of tuberculosis (TB) cases. Here, we report the draft whole-genome sequence of drug-resistant M. tuberculosis strain S7, which was isolated from a patient from Tripura, India, who was diagnosed with pulmonary TB

MicroRNA-mediated up-regulation of an alternatively polyadenylated variant of the mouse cytoplasmic β-actin gene

Actin is a major cytoskeletal protein in eukaryotes. Recent studies suggest more diverse functional roles for this protein. Actin mRNA is known to be localized to neuronal synapses and undergoes rapid deadenylation during early developmental stages. However, its 3′-untranslated region (UTR) is not characterized and there are no experimentally determined polyadenylation (polyA) sites in actin mRNA. We have found that the cytoplasmic β-actin (Actb) gene generates two alternative transcripts terminated at tandem polyA sites. We used 3′-RACE, EST end analysis and in situ hybridization to unambiguously establish the existence of two 3′-UTRs of varying length in Actb transcript in mouse neuronal cells. Further analyses showed that these two tandem polyA sites are used in a tissue-specific manner. Although the longer 3′-UTR was expressed at a relatively lower level, it conferred higher translational efficiency to the transcript. The longer transcript harbours a conserved mmu-miR-34a/34b-5p target site. Sequence-specific anti-miRNA molecule, mutations of the miRNA target region in the 3′-UTR resulted in reduced expression. The expression was restored by a mutant miRNA complementary to the mutated target region implying that miR-34 binding to Actb 3′-UTR up-regulates target gene expression. Heterogeneity of the Actb 3′-UTR could shed light on the mechanism of miRNA-mediated regulation of messages in neuronal cells

REVISION AND QUALITY ANALYSIS OF LIBRARY AND INFORMATION SCIENCE CONCEPTS IN WIKIPEDIA

Wikipedia is public encyclopedia contains articles on different subjects and different topics. The objective of the study is to evaluate the standard and status of revision of the library related articles. History page of Wikipedia article contains statistics of page from where the status and standard of the page has been derived. It has been concluded that Wikipedia covers 67 concepts of DDC 23rd edition arrived in 020 class (Library and Information Science Class). The content of Library and Information Science (LIS) related articles in Wikipedia was not enough informative as per Wikiproject. The concepts related to information science i.e. World Wide Web has been edited more times and it has been edited by more editors

Sterile Neuroinflammation and Strategies for Therapeutic Intervention

Sterile neuroinflammation is essential for the proper brain development and tissue repair. However, uncontrolled neuroinflammation plays a major role in the pathogenesis of various disease processes. The endogenous intracellular molecules so called damage-associated molecular patterns or alarmins or damage signals that are released by activated or necrotic cells are thought to play a crucial role in initiating an immune response. Sterile inflammatory response that occurs in Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, hemorrhage, epilepsy, or traumatic brain injury (TBI) creates a vicious cycle of unrestrained inflammation, driving progressive neurodegeneration. Neuroinflammation is a key mechanism in the progression (e.g., AD and PD) or secondary injury development (e.g., stroke, hemorrhage, stress, and TBI) of multiple brain conditions. Hence, it provides an opportunity for the therapeutic intervention to prevent progressive tissue damage and loss of function. The key for developing anti-neuroinflammatory treatment is to minimize the detrimental and neurotoxic effects of inflammation while promoting the beneficial and neurotropic effects, thereby creating ideal conditions for regeneration and repair. This review outlines how inflammation is involved in the pathogenesis of major nonpathogenic neuroinflammatory conditions and discusses the complex response of glial cells to damage signals. In addition, emerging experimental anti-neuroinflammatory drug treatment strategies are discussed