Unveiling the Genetic Symphony: Harnessing CRISPR-Cas Genome Editing for Effective Insect Pest Management.

Phytophagous insects pose a significant threat to global crop yield and food security. The need for increased agricultural output while reducing dependence on harmful synthetic insecticides necessitates the implementation of innovative methods. The utilization of CRISPR-Cas (Clustered regularly interspaced short palindromic repeats) technology to develop insect pest-resistant plants is believed to be a highly effective approach in reducing production expenses and enhancing the profitability of farms. Insect genome research provides vital insights into gene functions, allowing for a better knowledge of insect biology, adaptability, and the development of targeted pest management and disease prevention measures. The CRISPR-Cas gene editing technique has the capability to modify the DNA of insects, either to trigger a gene drive or to overcome their resistance to specific insecticides. The advancements in CRISPR technology and its various applications have shown potential in developing insect-resistant varieties of plants and other strategies for effective pest management through a sustainable approach. This could have significant consequences for ensuring food security. This approach involves using genome editing to create modified insects or crop plants. The article critically analyzed and discussed the potential and challenges associated with exploring and utilizing CRISPR-Cas technology for reducing insect pest pressure in crop plants.

Insect-pathogen crosstalk and the cellular-molecular mechanisms of insect immunity: uncovering the underlying signaling pathways and immune regulatory function of non-coding RNAs.

Multicellular organisms are constantly subjected to pathogens that might be harmful. Although insects lack an adaptive immune system, they possess highly effective anti-infective mechanisms. Bacterial phagocytosis and parasite encapsulation are some forms of cellular responses. Insects often defend themselves against infections through a humoral response. This phenomenon includes the secretion of antimicrobial peptides into the hemolymph. Specific receptors for detecting infection are required for the recognition of foreign pathogens such as the proteins that recognize glucans and peptidoglycans, together referred to as PGRPs and ßGRPs. Activation of these receptors leads to the stimulation of signaling pathways which further activates the genes encoding for antimicrobial peptides. Some instances of such pathways are the JAK-STAT, Imd, and Toll. The host immune response that frequently accompanies infections has, however, been circumvented by diseases, which may have assisted insects evolve their own complicated immune systems. The role of ncRNAs in insect immunology has been discussed in several notable studies and reviews. This paper examines the most recent research on the immune regulatory function of ncRNAs during insect-pathogen crosstalk, including insect- and pathogen-encoded miRNAs and lncRNAs, and provides an overview of the important insect signaling pathways and effector mechanisms activated by diverse pathogen invaders.

Genetic and Epigenetic Basis of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Both biogenic and chemically synthesized metal sulfide nanoparticles induce oxidative stress and enhance lipid accumulation in Rhodococcus opacus.

Metallic nanoparticles (NPs) find applications in many different industrial sectors. However, the fate of these NPs in the environment and their potential impact on organisms living in different ecosystems are not fully known. In this work, the individual effect of biogenic and chemically synthesized lead sulfide nanoparticles (PbSNPs) and cadmium sulfide nanoparticles (CdSNPs) on the activity of the oleaginous bacterium Rhodococcus opacus PD630 which belongs to an ecologically important genus Rhodococcus was investigated. A dose-dependent increase in PbSNPs and CdSNPs uptake by the bacterium was observed upto a maximum of 16.4 and 15.6 mg/g cell, corresponding to 98% and 95% uptake. In the case of chemically synthesized NPs, the specific PbSNPs and CdSNPs uptake were slightly less [15.5 and 14.8 mg/g cell], corresponding to 93.2% and 88.4% uptake. Both biogenic and chemically synthesized PbSNPs and CdSNPs did not affect the bacterial growth. On the other hand, the triacylglycerol (biodiesel) content in the bacterium increased from 30% to a maximum of 75% and 73% CDW due to oxidative stress induced by biogenic PbSNPs and CdSNPs. The results of induced oxidative stress by biogenic metal nanoparticle were similar to that induced by the chemically synthesized NPs.

Spatio-temporal changes of winter and spring phytoplankton blooms in Arabian sea during the period 1997-2020.

Arabian Sea (AS) experiences Chlorophyll-a (Chl-a) blooms during winter and early spring (November-March) mainly due to the changes induced by seasonally reversing monsoon winds and associated processes. The seasonal blooms exhibit distinct regional patterns in their onset, duration, intensity and peak period. Recent changes in ocean dynamics and plankton composition have inflicted adverse effects in the distribution of Chl-a concentration in AS. Here, we analyse the long-term spatio-temporal changes in winter and early spring bloom events during the period 1997-2020, and evaluate the role of sea surface temperature (SST), mixed layer depth (MLD), sea surface salinity, winds, mesoscale eddies and surface currents on these bloom occurrences. We observe a significant reduction in these blooms, which started in the early 2000s and intensified in the last decade (2010-2020), with a notable drop in the adjacent gulfs (Gulf of Aden: 1.38 ± 0.7 × 10-5 mg m-3 yr-1, Gulf of Oman: 4.71 ± 1.35 × 10-6 mg m-3 yr-1) and West coast of India (-6.71 ± 2.85 × 10-6 mg m-3 yr-1). The MLD and ocean temperature are the major factors that govern bloom in Gulf of Oman and open waters. Conversely, the coastal upwelling and eddies drive blooms in Gulf of Aden. The winter cooling trigger the bloom in the northern Indian west coast, but the inter-basin exchange of surface waters through the West Indian Coastal Current inhibits its southward spread. This study, therefore, reveals unique processes that initiate and control the winter and early spring blooms in different regions of AS. The ongoing warming of AS could contribute to further decline in these seasonal blooms, which would be a great concern for regional marine productivity and associated regional food security.

Synthesis and Analysis of Impregnation on Activated Carbon in Multiwalled Carbon Nanotube for Cu Adsorption from Wastewater.

Industrial wastes contain more toxins that get dissolved in the rivers and lakes, which are means of freshwater reservoirs. The contamination of freshwater leads to various issues for microorganisms and humans. This paper proposes a novel method to remove excess copper from the water. The nanotubes are used as a powder in membrane form to remove the copper from the water. The multiwalled carbon nanotube is widely used as a membrane for filtration. It contains many graphene layers of nm size that easily adsorbs the copper when the water permeates through it. Activated carbon is the earliest and most economical method that also adsorbs copper to a certain extent. This paper proposes the methods of involving the activated carbon in the multiwalled carbon nanotube to improve the adsorption capability of the copper. Here, activated carbon is impregnated on the multiwalled carbon nanotube's defect and imperfect surface areas. It makes more adsorption sites on the surface, increasing the adsorption amount. The same method is applied to Hydroxyl functionalized multiwalled carbon nanotubes. Both the methods showed better results and increased the copper removal. The functionalized method removed 93.82% copper, whereas the nonfunctionalized method removed 80.62% copper from the water.

T helper cells in depression: central role of Th17 cells.

Depression is one of the most common neuropsychiatric disorders in the world. While conventional pharmaceutical therapy targets monoaminergic pathway dysfunction, it has not been totally successful in terms of positive outcomes, remission, and preventing relapses. There is an increasing amount of evidence that neuroinflammation may play a significant part in the pathophysiology of depression. Among the key components of the neuroinflammatory pathways already known to be active are the T helper (Th) cells, especially Th17 cells. While various preclinical and clinical studies have reported increased levels of Th17 cells in both serum and brain tissue of laboratory model animals, contradictory results have argued against a pertinent role of Th17 cells in depression. Recent studies have also revealed a role for more pathogenic and inflammatory subsets of Th17 in depression, as well as IL-17A and Th17 cells in non-responsiveness to conventional antidepressant therapy. Despite recent advances, there is still a significant knowledge gap concerning the exact mechanism by which Th17 cells influence neuroinflammation in depression. This review first provides a short introduction to the major findings that led to the discovery of the role of Th cells in depression. The major subsets of Th cells known to be involved in neuroimmunology of depression, such as Th1, Th17, and T regulatory cells, are subsequently described, with an in-depth discussion on current knowledge about Th17 cells in depression.

Frequency and amplitude modulation of a cw-dye laser for measuring hyperfine frequency separations in optogalvanic spectra of 139La I.

This paper describes frequency modulation of a cw-dye laser to generate a frequency-discriminant dispersive signal by phase-sensitive detection of the optogalvanic signal in a lanthanum hollow cathode lamp. The frequencies of the six major hyperfine components in 5d26s4F9/2 (4121.572cm-1)----→579.13nm⁡5d26p4F9/2(21384.0cm-1) transition in 139La I were measured with an accuracy of 50 MHz, using a calibrated wavemeter after locking the cw-dye laser frequency to the dispersive error signal of the constituent hyperfine component. The measured hyperfine separations are found to be consistent with separations measured using the standard amplitude modulation technique and also with earlier reported results. The relative ease of the optical setup for locking of the cw-dye laser to optogalvanic spectra can be adapted to atomic physics applications for stabilization of laser frequency in the visible region.

The application of human pluripotent stem cells to model the neuronal and glial components of neurodevelopmental disorders.

Cellular models of neurodevelopmental disorders provide a valuable experimental system to uncover disease mechanisms and novel therapeutic strategies. The ability of induced pluripotent stem cells (iPSCs) to generate diverse brain cell types offers great potential to model several neurodevelopmental disorders. Further patient-derived iPSCs have the unique genetic and molecular signature of the affected individuals, which allows researchers to address limitations of transgenic behavioural models, as well as generate hypothesis-driven models to study disorder-relevant phenotypes at a cellular level. In this article, we review the extant literature that has used iPSC-based modelling to understand the neuronal and glial contributions to neurodevelopmental disorders including autism spectrum disorder (ASD), Rett syndrome, bipolar disorder (BP), and schizophrenia. For instance, several molecular candidates have been shown to influence cellular phenotypes in three-dimensional iPSC-based models of ASD patients. Delays in differentiation of astrocytes and morphological changes of neurons are associated with Rett syndrome. In the case of bipolar disorders and schizophrenia, patient-derived models helped to identify cellular phenotypes associated with neuronal deficits (e.g., excitability) and mutation-specific abnormalities in oligodendrocytes (e.g., CSPG4). Further we provide a critical review of the current limitations of this field and provide methodological suggestions to enhance future modelling efforts of neurodevelopmental disorders. Future developments in experimental design and methodology of disease modelling represent an exciting new avenue relevant to neurodevelopmental disorders.

Inferring disease and pathway associations of long non-coding RNAs using heterogeneous information network model.

Recent findings from biological experiments demonstrate that long non-coding RNAs (lncRNAs) are actively involved in critical cellular processes and are associated with innumerable diseases. Computational prediction of lncRNA-disease association draws tremendous research attention nowadays. This paper proposes a machine learning model that predicts lncRNA-disease associations using Heterogeneous Information Network (HIN) of lncRNAs and diseases. A Support Vector Machine classifier is developed using the feature set extracted from a meta-path-based parameter, Association Index derived from the HIN. Performance of the model is validated using standard statistical metrics and it generated an AUC value of 0.87, which is better than the existing methods in the literature. Results are further validated using the recent literature and many of the predicted lncRNA-disease associations are identified as actually existing. This paper also proposes an HIN-based methodology to associate lncRNAs with pathways in which they may have biological influence. A case study on the pathway associations of four well-known lncRNAs (HOTAIR, TUG1, NEAT1, and MALAT1) has been conducted. It has been observed that many times the same lncRNA is associated with more than one biologically related pathways. Further exploration is needed to substantiate whether such lncRNAs have any role in determining the pathway interplay. The script and sample data for the model construction is freely available at http://bdbl.nitc.ac.in/LncDisPath/index.html.

A Stability-Indicating UPLC Method for the Determination of Potential Impurities and Its Mass by a New QDa Mass Detector in Daclatasvir Drug Used to Treat Hepatitis C Infection.

A stability-indicating ultraperformance liquid chromatographic method has been developed for the quantitative determination of degradation products and process-related impurities of daclatasvir in a pharmaceutical dosage form. Chromatographic separation was achieved on a polar Waters ACQUITY BEH phenyl 100 × 2.1 mm, 1.7-µm column using the gradient program consisting of mobile phase A: 0.03 M sodium perchlorate with 0.002 M of 1-octanesulfonic acid sodium salt (pH 2.5 buffer) and mobile phase B: 0.03 M sodium perchlorate with 0.02 M of 1-octanesulfonic acid sodium salt (pH 2.5 buffer) with acetonitrile in the ratio of 20:80% v/v. A flow rate of 0.4 mL/min is maintained under ultraviolet detection at 305 nm. The run time was 15 min, within which daclatasvir, its related impurities and unknown degradants were well resolved. The method was found to produce symmetric and sharp peaks with good separation between process-related impurities and degradation impurities. Samples were subjected to hydrolysis (acid and base), oxidative, photolytic and thermal stress conditions to prove the stability-indicating nature of the method. The unknown degradation products were identified by PDA/QDa mass detector. This mass spectrum reveals protonated molecular ion peaks [M + H]+ at m/z DP1-582.4 in acid and base hydrolyses and m/z DP2-778.5 in peroxide hydrolysis. The method was validated in terms of specificity, precision, linearity, accuracy, limit of detection, limit of quantification and robustness as per ICH guidelines.

A prospective, randomized, comparison study on effect of perioperative use of chloride liberal intravenous fluids versus chloride restricted intravenous fluids on postoperative acute kidney injury in patients undergoing off-pump coronary artery bypass grafting surgeries.

CONTEXT AND AIMS: Off-pump coronary artery bypass graft (OPCABG) is a form of CABG surgery. It is performed without the use of cardiopulmonary bypass machine as a surgical treatment for coronary heart disease. Acute kidney injury (AKI) is one of the common postoperative complications of OPCABG. Previous studies suggest important differences related to intravenous fluid (IVF) chloride content and renal function. We hypothesize that perioperative use of chloride restricted IVFs may decrease incidence and severity of postoperative AKI in patients undergoing OPCABG. METHODS: Six hundred patients were randomly divided into two groups of 300 each. In Group A (n = 300), chloride liberal IVFs, namely, hydroxyethyl starch (130/0.4) in 0.9% normal saline (Voluven), 0.9% normal saline, and Ringer's lactate were used for perioperative fluid management. In Group B (n = 300), chloride-restricted IVFs, namely, hydroxyethyl starch (130/0.4) in balanced colloid solution (Volulyte) and balanced salt crystalloid solution (PlasmaLyte A), were used for perioperative fluid management. Serum creatinine values were taken preoperatively, postoperatively at 24 h and at 48 h. Postoperative AKI was determined by AKI network (AKIN) criteria. RESULTS: In Group A, 9.2% patients and in Group B 4.6% patients developed Stage-I AKI determined by AKIN criteria which was statistically significant (P < 0.05). CONCLUSION: Perioperative use of chloride restricted IVF was found to decrease incidence of postoperative AKI. The use of chloride liberal IVF was associated with hyperchloremic metabolic acidosis.

An isothermal based recombinase polymerase amplification assay for rapid, sensitive and robust indexing of citrus yellow mosaic virus.

Management of viral diseases relies on definite and sensitive detection methods. Citrus yellow mosaic virus (CYMV), a double stranded DNA virus of the genus Badnavirus, causes yellow mosaic disease in citrus plants. CYMV is transmitted through budwood and requires a robust and simplified indexing protocol for budwood certification programme. The present study reports development and standardization of an isothermal based recombinase polymerase amplification (RPA) assay for a sensitive, rapid, easy, and cost-effective method for detection and diagnosis of CYMV. Two different oligonucleotide primer sets were designed from ORF III (coding for polyprotein) and ORF II (coding for virion associated protein) regions of CYMV to perform amplification assays. Comparative evaluation of RPA, PCR and immuno-capture recombinase polymerase amplification (IC-RPA) based assays were done using purified DNA and plant crude sap. CYMV infection was efficiently detected from the crude sap in RPA and IC-RPA assays. The primer set used in RPA was specific and did not show any cross-amplification with banana streak MY virus (BSMYV), another Badnavirus species. The results from the present study indicated that RPA assay can be used easily in routine indexing of citrus planting material. To the best of our knowledge, this is the first report on development of a rapid and simplified isothermal detection assay for CYMV and can be utilized as an effective technique in quarantine and budwood certification process.

Mesoscale process-induced variation of the West India Coastal Current during the winter monsoon.

This manuscript presents the analysis of current meter records at Kollam and Kannur along the 20-m isobaths during November-December 2005. Currents in the coastal waters are strongly influenced by winds (both local and remote forcing), tides, propagation of coastal Kelvin and Rossby waves, etc. We hypothesize that the mesoscale (spatial scales of 10-500 km and temporal scale of 10-100 days) features in ocean are also competent to alter the characteristics of coastal currents to a large extent. Analysis of sea level anomaly from the merged altimeter data reveals the existence of a large anticyclonic eddy in the southeastern Arabian Sea during the winter monsoon. The eddy moves westward with an average speed of ∼15 km day(-1) corresponding to an increase in sea level amplitude up to 28 cm. Off southwest India, the poleward flow is along the western flank of this anticyclonic eddy and the geostrophic current completes the circulation around the eddy. The eastward component of the geostrophic current at the northern edge of the eddy is bifurcated at ∼9° N: one flowing towards north and the other towards south. Current meter records at station Kollam revealed a dominant southward current due to the bifurcated southward component. The bifurcated northward component coalesced with the poleward flow along the western flank of the anticyclonic eddy. At Kannur, a poleward flow along the coast is responsible for a predominant northward trend in the observed current pattern during the initial phase of observation. A reversal in the current direction is caused by the southward-flowing geostrophic current along the eastern flank of the subsequent anticyclonic eddy centered at 73.5° E and 13° N. The stations were located at the eastern periphery of these anticyclonic eddies, where the mesoscale features overwhelm the seasonal characteristics of the West India Coastal Current (WICC).

Exploitation of microbes for enhancing bacoside content and reduction of Meloidogyne incognita infestation in Bacopa monnieri L.

Despite the vast exploration of rhizospheric microbial wealth for crop yield enhancement, knowledge about the efficacy of microbial agents as biocontrol weapons against root-knot disease is scarce, especially in medicinal plants, viz., Bacopa monnieri. In the present investigation, rhizospheric microbes, viz., Bacillus megaterium, Glomus intraradices, Trichoderma harzianum ThU, and their combinations were evaluated for the management of Meloidogyne incognita (Kofoid and White) Chitwood and bacoside content enhancement in B. monnieri var CIM-Jagriti. A novel validated method Fourier transform near infrared was used for rapid estimation of total bacoside content. A significant reduction (2.75-fold) in root-knot indices was observed in the combined treatment of B. megaterium and T. harzianum ThU in comparison to untreated control plants. The same treatment also showed significant enhancement (1.40-fold) in total bacoside contents (plant active molecule) content using Fourier transform near-infrared (FT-NIR) method that analyses samples rapidly in an hour without solvent usage and provides ample scope for natural product studies.

A study to demonstrate the use of FNA cytology rather than biopsy in the diagnosis of neonatal biliary atresia.

OBJECTIVE: To study the use of fine needle aspiration (FNA) cytology in neonatal biliary atresia (BA). METHODS: Twelve female and nine male patients (age range, 3-7 months; mean age, 4.5 months) with a pre-operative diagnosis of BA, who were scheduled for Kasia portoenterostomy and selected for intraoperative FNA, were studied. RESULTS: Cholestasis, bile deposits, bile infarcts, hepatitic rosettes enclosing bile plugs, feathery degeneration of hepatocytes and inflammatory cells were seen in the cytological slides. Bile infarcts, rosette formation and inflammatory cells were mainly noticed in type 3 BA. Bile infarcts and hepatitic rosettes are surrogate findings for the diagnosis of the obstructive type of cholestasis. CONCLUSION: With the help of imaging studies, FNA in a multidisciplinary setting can be diagnostic of neonatal BA when cytological features suggest the obstructive nature of cholestasis, but this procedure cannot replace completely liver biopsy for this diagnosis.

Bronchoscopic removal of aspergilloma from a cavitary lesion of the lung.

We report a 62-year-old diabetic male who had recurrent episodes of haemoptysis, diagnosed to have Aspergilloma in the right upper lobe cavitary lesion of the lung. Bronchoscopic biopsy revealed a fungal ball (Aspergillus niger) in the right upper lobe. Since the patient did not respond to medical treatment, unfit for any surgical interventions, mechanical removal of the fungal ball was done with both rigid and flexible bronchoscopes. Patient improved symptomatically after the removal of the fungal ball; haemoptysis subsided. The patient is still under follow up without any further episodes of hemoptysis. This case report highlights a new alternative treatment option in patients with open cavitary Aspergilloma.

Synthesis and structure-activity relationship study of 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one derivatives as anticancer agents.

The synthesis and structure-activity relationship (SAR) study of a series of 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) derivatives as anticancer agents are described. This series of thiazolopyrimidines were synthesized by the reaction of 7-(4-fluoro phenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a] pyrimidin-3(7H)-one (3) with appropriate substituted aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid. Their structures were confirmed by IR, (1)H-NMR, mass, and elemental analyses. These novel thiazolopyrimidine derivatives were screened for their anticancer activity on the U937 human histocytic lymphoma cell line by 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. The comparison of anticancer activity of thiazolopyrimidine was performed considering their structures. This study was done using 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) as a basic model, showing that i) presence of a hydrogen donor/acceptor domain [thiazolo[3,2-a]pyrimidin-3(7H)-one] on the thiazolopyrimidine ring; ii) presence of a hydrophobic [(4-fluorophenyl)] aryl ring system on the thiazolopyrimidine ring; iii) presence of an electron donor moiety [5-(furan-2-yl)] on the thiazolopyrimidine ring; iv) ortho and para substitution of the distal aryl ring [2-(substituted benzylidene)] function strongly influenced anticancer activity. Among these compounds (4a-4j) para substituted derivatives 4c, 4e, 4f, 4g, 4h, and 4j showed significant anticancer activity.

Submitral aneurysm of the left ventricle.

Submitral aneurysm is a rare cardiac pathology of uncertain origin with varied clinical manifestations. Recent studies have revealed a congenital basis of this pathology, although genetic link has been suspected because of the racial predilection. The other suggested aetiologies are infection and inflammation. The case reported here is that of a young female with a large submitral aneurysm presenting in a state of cardiogenic shock. In addition, the presence of raised inflammatory parameters indicates that the cause of origin of this aneurysm is related to inflammation.