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Abstract: Operculina turpethum (Linn.) Silva Manso belongs to the family convolvulaceae. It is an important plant in the Indian conventional system of medicine, which is extensively employed by different tribes in many countries to cure edema and painful conditions like arthritis, back pain, hyperlipidemia, diabetes mellitus, liver disorders, skin disorders, and regulation of bowel functions. The roots of O. turpethum (Linn.) were subjected to physicochemical and phytochemical standardization and chromatographic separation, which was accomplished by column chromatography, TLC, and HPTLC. Further, the acute toxicity, cytotoxic and anti-inflammatory activities of Operculina turpethum roots were estimated by in vivo and in vitro models. This study includes percentage yield of extraction and organoleptic evaluation, along with the analysis of its physicochemical investigations and preliminary phytochemical estimation. The isolation of active phytoconstituents was done by column chromatography, and the isolated compound was then exposed to TLC and HPTLC analysis. Cytotoxic activity was tested by WST-1 based cell viability assay on HepG2 cells. The anti-inflammatory activity of methanol extract (ME) was evaluated against inflammation occur by both in vitro and in vivo methods. The methanolic extract exhibited the presence of most of the phytoconstituents out of all the extracts. The phytoconstituent phytosterol, i.e., β-sitosterol, was isolated by column chromatography, identified, and quantified by TLC and HPTLC, which was liable for anti-inflammatory activity. The amount of β- sitosterol was estimated to be 14.09 μg in a 10.00 mg fraction of MEOT. MEOT was devoid of toxicity up to 2000 mg/kg in Wistar albino rats. It was analysed that in vitro anti-inflammatory activity of MEOT by egg albumin denaturation method exhibited an incredible decrement in turbidity and increased the percentage inhibition of albumin denaturation (60.52%) in MEOT treated group as compared with the control group. In egg albumin-induced edema in rats, MEOT at the dose of 400 mg/kg reduced the edema formation (3.03 ± 0.02) induced by egg albumin at 4th h. In cotton pellet-induced granuloma in rats, MEOT at the dose of 400 mg/kg displayed maximum granuloma inhibition (51.06%), which was similar to that of indomethacin. From the obtained findings, it is confirmed that O. turpethum contains β-sitosterol, which is responsible for potent anti-inflammatory activity without causing cytotoxicity to the plant. The results suggested that ME of O. turpethum roots had a high potential for application as an anti-inflammatory agent. The recognization and confirmation of the plant can be obtained from the study and will present data that is aidful in determining the quality and purity of a crude drug which further helps in preventing its adulteration.

Introduction Information processing in cortical cell microcircuits involves regulation of excitatory pyramidal (PYR) cells by inhibitory Somatostatin- (SST), Parvalbumin- (PV), and Vasoactive intestinal peptide- (VIP) expressing interneurons. Human post-mortem and rodent studies show impaired PYR-cell dendritic morphology and decreased SST-cell markers in MDD or after chronic stress. However, knowledge of coordinated changes across microcircuit cell-types is virtually absent. Methods We investigated the transcriptomic effects of unpredictable chronic mild stress (UCMS) on distinct microcircuit cell-types in the medial prefrontal cortex (Cingulate regions 24a/b and 32) in mice. C57Bl/6 mice, exposed to UCMS or control housing for five weeks, were assessed for anxiety- and depressive-like behaviors. Microcircuit cell-types were laser-microdissected and processed for RNA-sequencing. Results UCMS induced predicted elevations in behavioral emotionality in mice. DESeq2 analysis revealed unique differentially-expressed genes in each cell-type after UCMS. Pre-synaptic functions, oxidative stress response, metabolism, and translational regulation were differentially dysregulated across cell-types, whereas nearly all cell-types showed downregulated post-synaptic gene signatures. Across the cortical microcircuit, we observed a shift from a distributed transcriptomic coordination across cell-types in controls towards UCMS-induced increased coordination between PYR-, SST- and PV-cells, and hub-like role for PYR-cells. Lastly, we identified a microcircuit-wide coexpression network enriched in synaptic, bioenergetic, and oxidative stress response genes that correlated with UCMS-induced behaviors. Conclusions These findings suggest cell-specific deficits, microcircuit-wide synaptic reorganization, and a shift in cells regulating the cortical excitation-inhibition balance, suggesting increased coordinated regulation of PYR-cells by SST- and PV-cells.

Plant branch and root growth relies on metabolism of the strigolactone (SL) hormone. The interaction between the SL molecule, Oryza sativa DWARF14 (D14) SL receptor, and D3 F-box protein has been shown to play a critical role in SL perception. Previously, it was believed that D3 only interacts with the closed form of D14 to induce downstream signaling, but recent experiments indicate that D3, as well as its C-terminal helix (CTH), can interact with the open form as well to inhibit strigolactone signaling. Two hypotheses for the CTH induced inhibition are that either the CTH affects the conformational ensemble of D14 by stabilizing catalytically inactive states, or the CTH interacts with SLs in a way that prevents them from entering the binding pocket. In this study, we have performed molecular dynamics (MD) simulations to assess the validity of these hypotheses. We used an apo system with only D14 and the CTH to test the active site conformational stability and a holo system with D14, the CTH, and an SL molecule to test the interaction between the SL and CTH. Our simulations show that the CTH affects both active site conformation and the ability of SLs to move into the binding pocket. In the apo system, the CTH allosterically stabilized catalytic residues into their inactive conformation. In the holo system, significant interactions between SLs and the CTH hindered the ability of SLs to enter the D14 binding pocket. These two mechanisms account for the observed decrease in SL binding to D14 and subsequent ligand hydrolysis in the presence of the CTH.

Introduction: Serological surveys estimating the cumulative incidence of the disease are powerful and effective tools for monitoring the epidemic and in determining the immunity status. Objectives: To compare the percentage sero-positivity for IgG antibodies against SARS-CoV2 at two different time period in the same population to understand the pandemic and predict about the immunity status of the population. Methods: As a part of Covid19 pandemic management, two separate population based sero-survey within a gap of 1½ months were carried in Ahmedabad city to scientifically document the progress of the Covid19 pandemic. Various demographic factors and other parameters from both the survey were compared with seropositivity for valid and precise estimation of disease situation as well as immunity status of the population. Results: The study documents an increase in seropositivity by 5.32% (from 17.92% to 23.24%). The seropositivity shows increasing trend with increase in the age group and the seropositivity is significantly higher among females. Overall higher seropositivity against the reported cases in the first sero-survey and the narrow increase in the seropositivity during the subsequent sero-survey inspite of high number of cases may indicate temporary status of the antibodies. This may also be due to the difference in the level of stigma, health care service delivery, service utilization and related field level situation affecting the asymptomatic/unreported case positivity. Conclusion: The result of seropositivity comparison indicates the scopes for further research to confirm and generate greater evidences regarding the factors affecting seropositivity.

The serotonin transporter, SERT, initiates the reuptake of extracellular serotonin in the synapse to terminate neurotransmission. Recently, the cryo-EM structures of SERT bound to ibogaine resolved in different states provided the first glimpse of functional conformations at atomistic resolution. However, the conformational dynamics and structural transitions to various intermediate states are not fully understood. Furthermore, while experimental SERT structures were complexed with drug molecules and inhibitors, the molecular basis of how the physiological substrate, serotonin, is recognized, bound, and transported remains unclear. In this study, we performed microsecond long simulations of the human SERT to investigate the structural dynamics to various intermediate states and elucidated the complete substrate import pathway. Using Markov state models, we characterized a sequential order of conformational driven ion-coupled substrate binding and transport events and calculated the free energy barriers of conformation transitions associated with the import mechanism. We identified a set of crucial residues that recognize the substrate at the extracellular surface of SERT and our biochemical screening results show that mutations causes dramatic reduction in transport function. Our simulations also revealed a third sodium ion binding site coordinated by Glu136 and Glu508 in a buried cavity which helps maintain the conserved fold adjacent to the orthosteric site for transport function. The mutation of these residues results in a complete loss of transport activity. Our study provides novel insights on the molecular basis of dynamics driven ion-substrate recognition and transport of SERT that can serve as a model for other closely related neurotransmitter transporters.

Background: The current study was conducted to prepare an efficient super-paramagnetic iron oxide nanoparticle (SPIONs) to remove Aeromonas hydrophila from water. Methods: The nanoparticles were synthesized by the co-precipitation method and characterized by DLS, UV-Vis spectrophotometer, FT-IR, XRD, FEG-TEM, and VSM analysis. Results and Discussion: The results showed that the synthesized SPIONs were having a size range of 8-12nm with magnetic property. Bacteria removal efficiency and antibacterial activity of SPIONs were assessed in sterile distilled water by adding different concentrations of SPIONs viz. 0, 6.25, 12.5, 25, 50, 100, 200, 500, and 1000μM with different initial bacterial loads viz. 1×103, 1×104, 1×105, 1×106, and 1×107 CFU mL−1 at different time intervals 15, 30, 45, and 60 min. At low bacterial load (1×103 to 1×105 CFU mL−1), 95 to 99.99% of bacteria were removed by low SPIONs concentration (6.25-100μM) by 15min which was increased up to 100% by 30min. However, at high bacterial load (1×106 to 1×107 CFU mL−1), more than 87 to 95% of bacteria were removed by the highest SPIONs concentration (1000μM) by 15min, which was increased above 93 to 99.99% by increasing the exposure time to 60min. At low bacterial load (1×103 to1×105 CFU mL−1), the effective concentration was 3.21 to 6.42μM at 15-60 min intervals. Meanwhile, the effective concentration at high bacterial load was 267.81 μM at 15min, which was decreased to 104.09 μM with increasing exposure time to 60min. Conclusion: Based on the results, it is concluded that the antibacterial effect against A. hydrophila depends on the concentration as well as the exposure time of SPIONs. A low concentration of SPIONs is sufficient to remove 100% of bacterial load in lower exposure time and increasing concentration of SPIONs increases the antibacterial effect. However, further research requires to find the safe concentration of SPIONs for using it as a novel antibacterial agent for the treatment of aeromonads disease in aquaculture.

Abstract: Recent advancements in medicinal research have identified several antiviral and anticancer terpenoids that are usually deployed as a source of flavor, fragrances and pharmaceuticals. Under the current COVID-19 pandemic conditions, natural therapeutics with the least side effects are the need of the hour to save the patients, especially, which are pre-affected with other medical complications. Although plants are the major sources of terpenoids; however, for the environmental concerns, the global interest has shifted to the biocatalytic production of molecules from microbial sources. The gram-positive bacterium Bacillus subtilis is a suitable host in this regard due to its GRAS (generally regarded as safe) status, ease in genetic manipulations and wide industrial acceptability. The B. subtilis synthesizes its terpenoid molecules from 1-deoxy-d-xylulose-5-phosphate (DXP) pathway, a common route in almost all microbial strains. Here, we summarize the computational and synthetic biology approaches to improve the production of terpenoid-based therapeutics from B. subtilis by utilizing DXP pathway. We focus on the in-silico approaches for screening the functionally improved enzyme-variants of the two crucial enzymes namely, the DXP synthase (DXS) and Farnesyl Pyrophosphate Synthase (FPPS). The approaches for engineering the active sites are subsequently explained. It will be helpful to construct the functionally improved enzymes for the high-yield production of terpenoid-based anticancer and antiviral metabolites, which would help to reduce the cost and improve the availability of such therapeutics for the humankind.

Ehretia acuminata R. Br. is a plant with alternative medicinal properties, commonly found in Asian, African and North American countries. The present study was undertaken to prepare crude extracts of E. acuminata leaves with different polarity solvents (petroleum ether (PE), chloroform (CH), ethyl acetate (EA), ethanol (EOL) and aqua (AQ)) by using successive Soxhelet extraction method and assessing antidiabetic, antiinflammatory and antihemolytic activities by the spectrophotometric method and antimicrobial activity by the zone inhibition method. The highest antidiabetic activity was found in the chloroform extract (IC50 260-265 µg/mL) and the lowest was in the aqueous extract (IC50 1560-1550 µg/mL). In anti-inflammatory assay, highest potential was shown by ethyl acetate (IC50 290 µg/mL) extract and lowest in petroleum ether (IC50 750µg/mL) extract. The zone of inhibition is highest in ethanol extract (12-18mm) by different food poisoning microbes, similarly, ethyl acetate extract showed the highest potential in antihemolytic activity with IC50 90 µg/mL. Many extracts of E. acuminata leaves showed a high biological potential that could be attributed to the high amount of phytoconstituents and thus could be utilized as value added functional food.

Column chromatography of purified ethyl acetate extract of bark part of Boehmeria rugulosa afforded triterpenoids (3-oxo-20-demethylisoaleuritolic-28,29-dioic acid and 3-oxo-20-demethylisoaleuritolic-28,30-dioic acid.). Structure of these compounds was elucidated using spectroscopic techniques. This is the first report of isolation of this compound from bark of B. rugulosa.

Wood joinery is an essential part of woodworking for product manufacture. Wood sections are mostly joined together with adhesives. Wood welding brings a new dimension to joinery by using mechanical friction to induce a flow of wood components ensuring adhesion. In this study, a customized spin wood-welding machine was used to join wood sections of Dalbergia sissoo. Butt and tongue-and-groove joints were prepared and welded using the machine. The tensile strength of the joints was tested. The impact on joint strength of increasing the friction area by introducing tongue-and-groove joints was tested and analyzed. The tensile strength for butt joints at 1,200 rpm welding was estimated at 5.3 MPa. Joint strength was found to increase substantially (by 66%) with a tongue-and-groove welding section. Weld line temperatures at different spin times were also investigated. The aim of this study is to apply welding technology to Dalbergia sissoo to achieve greater joint strength.

Long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs and potent regulatory elements in the living cells. High throughput RNA sequencing analyses have generated a tremendous amount of transcript sequence data. A large proportion of these transcript sequences does not code for proteins and are known as non-coding RNAs. Among them, lncRNAs are a unique class of transcripts longer than 200 nucleotides with diverse biological functions and regulatory mechanisms. Recent emerging studies and next-generation sequencing technologies show a substantial amount of lncRNAs within the plant genome, which are yet to be identified. The computational identification of lncRNAs from these transcripts is a challenging task due to the involvement of a series of filtering steps. We have developed lncRNADetector, a bioinformatics pipeline for the identification of novel lncRNAs, especially from medicinal and aromatic plant (MAP) species. The lncRNADetector has been utilized to analyse and identify more than 88,459 lncRNAs from 21 species of MAPs. To provide a knowledge resource for the plant research community towards elucidating the diversity of biological roles of lncRNAs, the information generated about MAP lncRNAs (post-filtering steps) through lncRNADetector has been stored and organized in MAPslnc database (MAPslnc, https://lncrnapipe.cimap.res.in). The lncRNADetector web server and MAPslnc database have been developed in order to facilitate researchers for accurate identification of lncRNAs from the next-generation sequencing data of different organisms for downstream studies. To the best of our knowledge no such MAPslnc database is available till date.

Background: Malnutrition is a common universal health problem, but it is more chronic for developing countries. Due to increasing nursing home recognition, it has become a major research priority internationally. Lower immunity due to malnutrition has a high prevalence and other clinical consequences. Disease-related malnutrition is potentially severe for patients and has a high economic impact on the healthcare system. Objectives: The aim of this review is to describe various experimental models employed for the evaluation of malnutrition and immunomodulatory activities. Methods: This review is intended for both clinicians and researchers to describe several screening methods that better suit the type of lead compounds and are suitable for screening molecules for better treatment outcomes. Results: This review focuses on the various screening methods for the evaluation of malnutrition and suggests their implications in the research and practice. Conclusion: The malnutrition-induced diseases cause a rise in health care costs that can be minimized with an introduction of drugs and nutritional supplements by selecting proper screening models and performing exhaustive research.

Objective: To estimate Covid19 seropositivity among contacts of cases and to compare the seropositivity among different types of contact for assessing the differential risk & transmission dynamics.Material and Methods: A large-scale population-based serosurvey was carried out among the general population of Ahmedabad during the second half of October 2020. The contacts of cases were selected based on the population proportion and enrolled as an additional category. The seropositivity among the contacts was estimated using the enzyme-linked immunosorbent assay and compared with different types of contact and available demographic factors.Results: As of October 2020, the seropositivity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) among contacts of cases in Ahmedabad was 26.0% [95% confidence interval 24.2–28.0]. The seropositivity among family contacts was significantly higher (28.8%) compared to other contacts (24.4%) (Z=2.19, p-value=0.028). This trend was seen across all age groups and both sexes. The seropositivity was higher among females (27.7%) compared to males (24.5%) but the difference was statistically not significant (Z=1.64, p-value=0.101). In terms of age groups, the positivity had an increasing trend up to 60 years but declined after that.Conclusion: A seropositivity of 26.0% among contacts indicates that a large proportion of contacts demonstrated Immunoglobulin-G antibodies. This highlights asymptomatic transmission and/or low sensitivity of the diagnostic tests. The current strategy for contact tracing and testing among contacts is justified based on the significantly higher seropositivity among family contacts.

Nanotechnology is a new area of research with new possibilities in various fields. Nanotechnology is a having the potential to take forward the agriculture with new tools which promises to increase food production and also protect the agriculture crops from pests, diseases etc. The present study focuses on the green synthesis of silver nanoparticles using plant extracts of Cassytha filiformis. Aqueous silver ions when exposed to plant leaf extract were reduced and resulted in a color change to dark brown indicating the formation of silver nanoparticles by using UV–Vis Spectroscopy which showed peak at in range from 400 nm to 480 nm which are characteristic peaks of silver nanoparticles. Synthesized silver nanoparticles were also characterized by other techniques such as Field Emission Scanning Electron Microscopy (FESEM) showed even shaped spherical nanoparticles with particle size of 42 nm. Energy Dispersive X-Ray (EDX) showed absorption peak approximately at 3 keV. Fourier Transform Infra Red (FTIR) showed chemical interactions of silver nanoparticles and Atomic force microscope (AFM) depicted the three dimensional structure of silver nanoparticle.

The present investigation was carried out to evaluate the efficacy of mycogenic zinc oxide nanoparticles (ZNONPs) as antifungal agents against Alternaria solani (early blight of potato). The nanoparticles were synthesized biologically by using Aspergillus niger biomass and characterization was done by UV–Vis Spectroscopy, Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X-Ray (EDX), Dynamic Light Scattering (DLS), Fourier Transform Infra Red (FTIR), Atomic Force Microscopy (AFM) and inductively coupled plasma mass spectrometry (ICPMS). The UV–Vis spectroscopy showed peaks between the range 250 nm to 340 nm, corresponding to ZNONPs. The FESEM results also confirmed the synthesis of fine sized and spherical ZNONPs. EDX analysis result showed the optical absorption peak corresponding to ZNONPs. The DLS result confirmed the synthesis of ZNONPs with average size of 96.43 nm. FTIR analysis depicted information about all the chemical interactions of ZNONPs. AFM image depicted the three dimensional conformations of ZNONPs. The ZNONPs were tested against A. solani in vitro and minimum inhibitory concentration (MIC) was calculated. Field experiment was conducted for comparison of the efficacy of nanoparticles and chemical fungicide at the parameters of disease severity, tuber number and tuber weight. The data were analyzed by SPSS for analysis of variance (ANOVA) with least significance difference (LSD) and results were found to be significant for different parameters at 0.05 significance levels. It may be concluded by the experiment that ZNONPs may be proved to be potential fungicides in near future and it is an excellent alternative to chemical fungicides.

In the present study, mycogenic silver nanoparticles (AgNPs) were synthesized by using Fusarium pallidoroseum biomass and its efficacy was tested against third instar white grubs (Holotrichia sp), a potent pest of sugarcane in western Uttar Pradesh (India). The AgNPs were characterized by UV (ultra voilet) – Visible Spectroscopy, Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X-Ray (EDX), Dynamic Light Scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), Atomic Force Microscopy (AFM) and Inductively coupled plasma mass spectroscopy (ICPMS). The UV-Vis spectroscopy showed peak at 430 nm, corresponding to AgNPs. The FESEM results also confirmed the synthesis of nano sized particles. EDX analysis result showed the optical absorption peak at 3 keV which is specific to AgNPs. The DLS result confirmed the synthesis of AgNPs with average size of 93.48 nm. FTIR analysis depicted information about all the chemical interactions of AgNPs. AFM image depicted the three dimensional conformations of AgNPs. The AgNPs were applied against third instar white grub larvae in vitro and lethal dosage (LD50) was formulated by Probit analysis, which was further validated and found to be significant at 0.05 levels by chi-square test.

Pancreatic ductal adenocarcinoma (PDAC) represents 3% of all cancer cases and 7% of all cancer deaths in the United States. Late diagnosis and inadequate response to standard chemotherapies contribute to an unfavorable prognosis and an overall 5-year survival rate of less than 10% in PDAC. Despite recent advances in tumor immunology, tumor-induced immunosuppression attenuates the immunotherapy response in PDAC. To date, studies have focused on IgG-based therapeutic strategies in PDAC. With the recent interest in IgE-based therapies in multiple solid tumors, we explored the MUC1-targeted IgE potential against pancreatic cancer. Our study demonstrates the notable expression of FceRI (receptor for IgE antibody) in tumors from PDAC patients. Our study showed that administration of MUC1 targeted-IgE (mouse/human chimeric anti-MUC1.IgE) antibody at intermittent levels in combination with checkpoint inhibitor (anti-PD-L1) and TLR3 agonist (PolyICLC) induces a robust antitumor response that is dependent on NK and CD8 T cells in pancreatic tumor-bearing mice. Subsequently, our study showed that the antigen specificity of the IgE antibody plays a vital role in executing the antitumor response as nonspecific IgE, induced by ovalbumin (OVA), failed to restrict tumor growth in pancreatic tumor-bearing mice. Utilizing the OVA-induced allergic asthma-PDAC model, we demonstrate that allergic phenotype induced by OVA cannot restrain pancreatic tumor growth in orthotopic tumor-bearing mice. Together, our data demonstrate the novel tumor protective benefits of tumor antigen-specific IgE-based therapeutics in a preclinical model of pancreatic cancer, which can open new avenues for future clinical interventions.

BACKGROUND: Leukocyte infiltration plays an critical role in outcome of various diseases including Lung adenocarcinoma (LUAD). OBJECTIVES: To understand the genetic and epigenetic factors affecting leukocyte infiltration and identification and validation of immune based biomarkers. METHOD: Correlation analysis was done to get the associations of the factors. CIBERSORT analysis was done for immune cell infiltration. Genetic and epigenetic analysis were performed. Cox regression was carried out for survival. RESULTS: We categorized the TCGA-LUAD patients based on Leukocyte fraction (LF) and performed extensive immunogenomic analysis. Interestingly, we showed that LF has a negative correlation with copy number variation (CNV) but not with mutational load. However, several individual genetic mutations, including KRAS and KEAP1, were significantly linked with LF. Also, as expected, patients with high LF showed significantly increased expression of genes involved in leukocyte migration and activation. DNA methylation changes also showed a strong association with LF and regulated a significant proportion of genes associated with LF. We also developed and validated an independent prognostic immune signature using the top six prognostic genes associated with LF. CONCLUSION: Together, we have identified clinical, genetic, and epigenetic variations associated with LUAD LF and developed an immune gene-based signature for disease prognostication.

An assemblage of microfossils of moderate diversity, with the remarkable occurrence of ECAP acritarchs, is reported from the Ediacaran Krol ‘A’ (= the Mahi Formation) succession of Lesser Himalaya, India. Microfossils occur in the chert nodules exposed in Solan district, Himachal Pradesh. Two microfossils, Barogophycus symmetricus n. gen. n. sp. and Botominella lineata are new to the well-established Krol assemblage. The paper concentrates predominantly on fossil eukaryotic filamentous and coccoidal micro-organism of simple morphology. The assemblage is dominated by remains of prokaryotic cyanobacteria and demonstrates the diversity achieved by microorganisms at the beginning of the Ediacaran Period in the aftermath of the Marinoan glaciation. Filamentous and coccoidal microorganisms differ in taxonomic composition from the Mesoproterozoic microbiotas. The Krol microfossils assemblage has biostratigraphic potential and usefulness in broadly demarcating the different levels of the Ediacaran strata. Because of the presence of ECAP acritarchs, along with the appearance of other eukaryotic microorganisms of filamentous and coccoidal morphology, the general level of the Krol ‘A’ assemblage is considered as Ediacaran.

This study reports the oldest fossil record of the genus Adina, A. vastanenesis n. sp., from the early Eocene of Vastan lignite mine (Cambay Shale Formation), Surat district, Gujarat. This fossil wood is characterized by diffuse porous wood, predominantly solitary tylosed vessels, simple perforations, scanty paratracheal to diffuse to sometimes diffuse in aggregate axial parenchyma, predominantly uniseriate to occasionally biseriate rays, and non septate fibres with bordered pits and shows its best resemblance with the modern species, Adina multifolia Haviland, belonging to the tribe Naucleeae (subfamily Cinchonoideae) of the family Rubiaceae. The present discovery becomes the first fossil record of the wood of Adina, which provides an insight about the Gondwanan origin either for the genus Adina or the tribe Naucleeae and its further dispersal to Southeast Asia.

Zika virus (ZIKV) is a positive-single strand RNA virus that belongs to the Flaviviridae family. ZIKV infection causes congenital ZIKV syndrome (CZS) in children and Guillain Barre Syndrome (GBS) in adults. ZIKV infected cells secrete non-structural protein 1 (sNS1), which plays an important role in viral replication and immune evasion. The microglial cells are the brain resident macrophages that mediate the immune responses in CNS. The miRNAs are small non-coding RNAs that regulate the expression of their target genes by binding to the 3'UTR region. The present study highlights the bystander effect of ZIKV-NS1 via miR-146a. The Real-Time PCR, Immunoblotting, overexpression, knockdown studies, and reactive oxygen species measurement have been done to study the immunomodulatory effects of ZIKV-NS1 in human microglial cells. ZIKV-NS1 induced the expression of miR-146a and suppressed the ROS activity in human microglial cells. The up-regulated miR-146a led to the decreased expression of TRAF6 and STAT-1. The reduced expression of TRAF6 in turn led to the suppression of pNF-κBp65 and TNF-α downstream. The miR-146a suppressed the pro-inflammatory and cellular antiviral responses in microglial cells. Our findings demonstrate the bystander role of ZIKV-NS1 in suppressing the pro-inflammatory and cellular antiviral responses through miR-146a in human microglial cells.

In many cases over the years the diversity of Isoetes in India has been defined by inconsistent morphological analyses and questionable data. This has resulted in substantial confusion, dramaticall...

The Cladocerans, commonly known as “Water fleas” form a primitive freshwater group of micro crustacean zooplankton of the freshwater ecosystem. They play an important role in the aquatic food chain and also contribute significantly to zooplankton dynamics and secondary productivity in freshwater ecosystems. The animals used in the present study were identified as Simocephalus vetulus with the help of identification keys described by various authors in the previous studies from other parts of India. In the present study, the occurrence of “freshwater tailless flea”, S. vetulus (Crustacea- cladocera) is reported for the first time from freshwater bodies in Haridwar, located in foothills of Shivalik Himalayan region in Uttarakhand. The presence of S. vetulus “tailless water flea” will be helpful as a lab model for the health status of aquatic bodies as well as environmental monitoring.

Modern globalisation has escalated anthropocentric sources for heavy metal contamination in diverse natural habitats. Pernicious nature of heavy metals poses a major threat to all life forms in the environment. Heavy metals are not degradable like the organic pollutants but could be transformed to be persistent in a less toxic form. Microbes are the cheap tool as they evolve rapidly to combat heavy metal stress by developing various survival strategies, for instance sequestration or active transportation of metal. Their short generation time, large surface area and ease of genetic manipulation makes them ideal candidates to use for the bioremediation process. Many heavy metal resistant microbes such as species of Bacillus, Pseudomonas, Acidothiobacillus, Saccharomyces, Geobacter and Rhizophus have been used for remediation of heavy metal contaminated sites. The effectiveness of bioremediation technique depends upon various factors, including biotic as well as abiotic, which mainly determine bio-availability of metal for remediation. The different metal microbe interactions such as sorption, accumulation, mineralization, transformation and solubilization are responsible for tapering heavy metal concentration at various loci or sites. The review emphasizes on the different interactions of the microbes with heavy metals, their survival strategies and the applications of the resistant strains in remediation.

Fascioliasis, a neglected foodborne disease caused by liver flukes (genus Fasciola), affects more than 200 million people worldwide. Despite technological advances, little is known about the molecu...

Inefficient physiological transitions are known to cause metabolic disorders. Therefore, investigating mechanisms that constitute molecular switches in a central metabolic organ like the liver becomes crucial. Specifically, upstream mechanisms that control temporal engagement of transcription factors, which are essential to mediate physiological fed–fast–refed transitions are less understood. SIRT1, a NAD(+)-dependent deacetylase, is pivotal in regulating hepatic gene expression and has emerged as a key therapeutic target. Despite this, if/how nutrient inputs regulate SIRT1 interactions, stability, and therefore downstream functions are still unknown. Here, we establish nutrient-dependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a crucial determinant of hepatic functions. Our findings demonstrate that during a fasted-to-refed transition, glycosylation of SIRT1 modulates its interactions with various transcription factors and a nodal cytosolic kinase involved in insulin signaling. Moreover, sustained glycosylation in the fed state causes nuclear exclusion and cytosolic ubiquitin-mediated degradation of SIRT1. This mechanism exerts spatiotemporal control over SIRT1 functions by constituting a previously unknown molecular relay. Of note, loss of SIRT1 glycosylation discomposed these interactions resulting in aberrant gene expression, mitochondrial dysfunctions, and enhanced hepatic gluconeogenesis. Expression of nonglycosylatable SIRT1 in the liver abrogated metabolic flexibility, resulting in systemic insulin resistance, hyperglycemia, and hepatic inflammation, highlighting the physiological costs associated with its overactivation. Conversely, our study also reveals that hyperglycosylation of SIRT1 is associated with aging and high-fat–induced obesity. Thus, we establish that nutrient-dependent glycosylation of SIRT1 is essential to gate its functions and maintain physiological fitness.

Osimertinib (OB) is a third-generation irreversible tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), overexpressed in non-small cell lung cancer. Systemic administration of drug often results in poor drug levels at the primary tumor in the lungs and is associated with systemic side effects. In this study, we developed inhalable OB liposomes that can locally accumulate at the tumor site thereby limiting systemic toxicity. OB was loaded into liposomes via active and passive loading methods. The OB active liposomes achieved a higher encapsulation (78%) compared to passive liposomes (25%). The liposomes (passive and active) exhibited excellent aerosolization performance with an aerodynamic diameter of 4 µm and fine particle fraction of 82%. In H1975 cells, OB active and passive liposomes reduced IC50 by 2.2 and 1.2-fold, respectively, compared to free drug. As the OB active liposomes demonstrated higher cytotoxicity compared to OB passive liposomes, they were further investigated for in vitro anti-cancer activity. The OB active liposomes inhibited tumor cell migration and colonization as determined by the scratch assay and clonogenic assay, respectively. Furthermore, the 3D spheroid studies showed that the liposomes were successful in inhibiting tumor growth. These results highlight the potential of OB liposomes to suppress lung cancer. Owing to these attributes, the inhalable OB liposomes can potentially promote better therapeutic outcomes with limited systemic toxicity.

Klaibya is defined in Ayurveda as the inability to achieve and maintain sufficient rigidity in the penis, which is essential for his sexual urges or the needs of his female partner during sexual activity. Chakrapani limits the concept of Klaibya to merely erectile dysfunction. Dhwajbhang, according to Acharya Sushruta, is a form of Klaibya caused by excessive coitus. The standard initial evaluation of a man experiencing ED is conducted in person and involves sexual, medical, and psychosocial histories, as well as laboratory tests comprehensive enough to identify comorbid diseases that may predispose the patient to ED and may contraindicate particular treatments. Properties of Ayurvedic drug; Kuchla (Strychnos nux-vomica) in classical text Rasatarangani as therapeutic of Klaibya (ED) and Brahmi (Bacopa monnieri) is well known Medhya drug that works on neuro- psychological disorders. The current study evaluated the effects of Kuchla and Brahmi on 36 erectile dysfunction patients, having 30 of them completing the trial. The patients were categorized into two parts: Group A administered an ED 250 capsule (Hypothetical) once a day (250mg) with milk, and Group B received a placebo once a day with milk HS for 30 days, followed by another 30 days.

A PCR-based detection method was developed for Ceratocystis fimbriata detection, the main causal agent of mango wilt in India. Two primer pairs (one forward and two reverse primers) targeting the ITS region of the fungal ribosomal DNA were developed which proved to be highly specific and sensitive to C. fimbriata. The primer pairs produced the amplification product of 473 bp and ~ 350 bp, respectively while no amplification was observed in the case of C. paradoxa, Berkeleyomyces basicola (member of Ceratocystidaceae family), and other common soil-inhabiting fungi viz., Fusarium oxysporum and Trichoderma harzianum as well as other mango pathogens viz., Colletotrichum gloeosporioides, Diaporthe phyllanthicola, and Botryosphaeria dothidea. The primers were able to detect the pathogen at DNA concentration of 0.1 pg/25 μl both directly from pure fungal culture as well as rhizospheric soil. The protocol developed was further validated in the field by detecting C. fimbriata from the rhizospheric soil of partially and completely wilted mango trees. The absence of amplification in the rhizospheric soil samples of healthy mango trees, as well as other horticultural and vegetable crops, ruled out the possibility of false positives. Though, we failed to detect the pathogen from trunk wood samples of wilted mango trees despite the isolation of decent quality as well as quantity of DNA possibly due to the presence of many PCR inhibitors in wood samples. The method developed in the present study can be applied in the field to detect the pathogen from the soil which is a major infection pathway and thus can aid in the better management of this disease.

Pseudoachondroplasia (PSACH) is an autosomal dominant disorder characterized by rhizomelic short-limbed skeletal dysplasia. The primary clinical and radiographic features include disproportionate dwarfism, joint laxity and hyperextensibility, exaggerated lumbar lordosis, and late ossification of the epiphyses. Identification of disease-causing variants in heterozygous state in COMP establishes the molecular diagnosis of PSACH. We examined 11 families with clinical features suggestive of PSACH. In nine families, we used Sanger sequencing of exons 8-19 of COMP (NM_000095.2) and in two families exome sequencing was used for confirming the diagnosis. We identified 10 de novo variants, including five known variants (c.925G>A, c.976G>A, c.1201G>T, c.1417_1419del, and c.1511G>A) and five variants (c.874T>C, c.1201G>C, c.1309G>A, c.1416_1421delCGACAA, and c.1445A>T) which are not reported outside Indian ethnicity. We hereby report the largest series of individuals with molecular diagnosis of PSACH from India and reiterate the well-known genotype-phenotype corelation in PSACH.

BACKGROUND & AIMS: SIRT5 plays pleiotropic roles via post-translational modifications, serving as a tumor suppressor, or an oncogene, in different tumors. However, the role SIRT5 plays in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Published datasets and tissue arrays with SIRT5 staining were used to investigate the clinical relevance of SIRT5 in PDAC. Furthermore, to define the role of SIRT5 in the carcinogenesis of PDAC, we generated autochthonous mouse models with conditional Sirt5 knockout. Moreover, to examine the mechanistic role of SIRT5 in PDAC carcinogenesis, SIRT5 was knocked down in PDAC cell lines and organoids, followed by metabolomics and proteomics studies. A novel SIRT5 activator was utilized for therapeutic studies in organoids and patient-derived xenografts. RESULTS: SIRT5 expression negatively regulated tumor cell proliferation and correlated with a favorable prognosis in PDAC patients. Genetic ablation of Sirt5 in PDAC mouse models promoted acinar-to-ductal metaplasia, precursor lesions, and pancreatic tumorigenesis, resulting in poor survival. Mechanistically, SIRT5 loss enhanced glutamine and glutathione metabolism via acetylation-mediated activation of GOT1. A selective SIRT5 activator, MC3138, phenocopied the effects of SIRT5 overexpression and exhibited anti-tumor effects on human PDAC cells. MC3138 also diminished nucleotide pools, sensitizing human PDAC cell lines, organoids, and patient-derived xenografts to gemcitabine. CONCLUSIONS: Collectively, we identify SIRT5 as a key tumor suppressor in PDAC, whose loss promotes tumorigenesis through increased non-canonical utilization of glutamine via GOT1, and that SIRT5 activation is a novel therapeutic strategy to target PDAC.

Freshwater prawn are promising candidates for aquaculture and knowledge of food and feeding habit is must for successful culture. Present study investigates the feeding mechanism and role of appendages in feeding behaviour of freshwater prawn, Macrobrachium lamarrei. Mostly preferred food was dried prawn powder and least preferred was groundnut cake. Prawns showed cannibalistic behaviour frequently in lab. Antenna and antennules were the main sensory appendages which help in locating and orientation while I & II chelate legs were used for detection, catching and transferring of food up to the mouth. Maxillipedes, maxilla and maxillula played the supportive role. Mechanism of feeding and functional role of different appendages in feeding behaviour have been discussed.

PURPOSE The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) can be abnormally activated in neuroblastoma, and somatic ALK mutations occur in 6%-10% of patients. The differential clinical impact of these mutations has not been clearly elucidated. METHODS Data on patients with neuroblastoma harboring ALK mutations were retrospectively analyzed. ALK sequencing was performed by whole-genome sequencing, hybrid-based capture of targeted exomes, or hotspot ALK mutation profiling. The differential impact of ALK mutation site on clinical characteristics, response to treatment, and survival was analyzed. In a subgroup of patients with locoregional neuroblastoma diagnosed after 2014, the impact of all ALK mutations was compared with wild-type ALK. RESULTS Of 641 patients with neuroblastoma with ALK status analyzed on at least one tumor sample, 103 (16%) had tumors harboring ALK mutations. Mutations existed across all ages (birth to 67.8 years), stages (30% locoregional and 70% metastatic), and risk groups (20%, 11%, and 69% with low-, intermediate-, and high-risk disease, respectively). Mutation sites included F1174 (51%), R1275 (29%), R1245 (10%), and others (10%). Mutation site was not prognostic for progression-free survival or overall survival in the entire cohort, high-risk subgroup, or locoregional subgroup. Locoregional tumors with any ALK mutation were generally invasive: L2 by International Neuroblastoma Research Group staging in 30/31 patients with a 2-year progression-free survival (59%, 95% CI, 37.4 to 80.5) that was inferior to historical controls. This observation was corroborated in the post-2014 subgroup in which gross total resection was less likely for ALK-mutated tumors. CONCLUSION Somatic ALK mutations are present across all stages and risk groups of neuroblastoma. No specific mutation carries differential prognostic significance. Locoregional neuroblastoma has an invasive phenotype when harboring somatic ALK mutations in this population.

The genes for grain softness and rust resistance were transferred from a soft grained Australian wheat variety (Barham) to a hard grained Indian wheat variety (DBW14) through marker assisted back cross breeding. Backcrosses were made with recurrent parent in the BC1F1 plants that were found positive for markers of Pina-D1a, Pina-D1b and Lr37b genes. The BC2F1 plants were further screened and those that possessed the PinaD1a and Lr37b alleles were advanced up to BC2F4 with continued marker assisted selection and field screening. 48 SSR markers that were heterozygous in the BC1F1 plants were used for background selection in three BC2F1 plants derived from three respective BC1F1s. Further generations were screened for morphological traits in the field and 16 BC2F4 lines were finally selected through combined field and marker screening. These 16 near isogenic lines (NILs) had lower grain hardness index (13.86–47.13) than the recurrent parent DBW 14 (81.76) and displayed more than 95% of the recurrent parent genome. 12 of the NILs had significantly higher grain yield than DBW 14. Combined foreground and background selection strategy coupled with field screening, was thus, found to be an effective strategy for transferring grain softness in wheat.

Considering the public health demands for stronger and effective personal protective clothing, herein, antimicrobial fabrics using a known bacteriostatic and fungistatic drug zinc pyrithione (ZPT) have been reported. ZPT was synthesized in situ on cellulosic fabric, viscose (VC), using a zinc metal precursor and 2-mercaptopyridine-N-oxide as a ligand (VC-ZPT). For comparison, viscose was also phosphorylated (VP) before in situ functionalization with ZPT (VP-ZPT). Both approaches provided adequate protection from microbes; however, functionalization of cellulose with phosphate (VP) resulted in the formation of a linking group between cellulose and ZPT, which exhibited better uniformity of ZPT over the fabric surface and higher durability to washing. The functionalization was confirmed by inductively coupled plasma mass spectroscopy (ICP-MS), scanning electron microscopy (SEM), and Raman spectroscopy. Further, the bonding of phosphate with ZPT was confirmed by 31P solid-state NMR. The physical properties, such as appearance, bending length, and mechanical strength, of the treated fabrics remained unchanged. The antimicrobial activities of VP-ZPT with VC-ZPT were studied against Escherichia coli, Staphylococcus aureus, and Candida albicans, which were found to be effective until 20 laundry cycles in VP-ZPT. Additionally, VP-ZPT samples exhibited poor adherence of bacteria on the fabric surface. The functionalized fabrics may find applications for topical skin diseases in reducing the necessity of repeated use of antibiotic ointments.

A greenhouse experiment was conducted to study the effect of effect of varying levels of boron and sulphur on yield and nutrient uptake of linseed (Linum usitatissimum L.) grown in a Mollisol. The experiment was conducted under factorial completely randomized design with three replications and consisted of six levels of each of boron (0, 0.5, 1.0, 1.5, 2.0 mg kg−1soil and two foliar sprays of 0.2% boron) and sulphur (0, 10, 20, 30, 40 and 60 mg kg−1soil). The different doses of sulphur and boron and their interaction had significant effect on seed and stover yields, B and S concentrations and uptake by linseed crop indicating a differential requirement of boron and sulphur by the crop. The highest seed yield was recorded under the combined application of 2 mg B kg−1 soil and 60 mg S kg−1 soil.

SARS-CoV-2 harbors many known unknown regions in the form of hypothetical open reading frames (ORFs). Although the mechanisms underlying the disease pathogenesis are not clearly understood, molecules such as long noncoding RNAs (lncRNAs) play a key regulatory role in the viral pathogenesis from endocytosis. We asked whether or not the lncRNAs in the host are associated with the viral proteins and argue that lncRNA-mRNAs molecules related to viral infection may regulate SARS-CoV-2 pathogenesis. Toward the end of the perspective, we provide challenges and insights into investigating these transgression pathways.

Neurodegenerative disorders affecting a large populace involve neuronal loss in central nervous system (CNS) system. Recently, viral vector having particle size

Purpose: In this study, a novel D-α-tocopheryl polyethylene glycol succinate (TPGS) modified bovine serum albumin (BSA) nanoparticles (NPs) were developed for delivery of Anastrozole (ANZ) which is optimized by Box-Behnken design (BBD). Fabricated TPGS-ANZ-BSA NPs were evaluated for their physicochemical and drug release characteristics. Methods: TPGS-ANZ-BSA NPs were prepared by desolvation thermal gelation method and the effects of critical process parameter (CPP) which are BSA amount, TPGS concentration and stirring speed on the critical quality attributes (CQA) such as % drug loading (%DL) and particle size were studied using BBD. TPGS-ANZ-BSA NPs were characterized using different spectroscopic techniques including UV-Visible and FTIR is used to confirm the entrapment of ANZ in BSA. DSC and PXRD revealed the amorphization of ANZ in the TPGS-ANZ-BSA NPs after freeze drying. Scanning electron microscopy (SEM) analysis was performed for the surface morphology analyses NPs. In vitro release studies were performed at pH 5.5 and pH 7.4 for 48h to mimic tumour microenvironment. Results: The BBD optimized TPGS-ANZ-BSA NPs showed 107 nm particle size with %DL 8.5± 0.5%. The spectroscopic and thermal characterizations revealed the successful encapsulation of ANZ inside the NPs. The TPGS-ANZ-BSA NPs were found to exhibit burst release at pH 5.5 and sustained release at pH 7.4. The short-term stability displayed no significant changes in physical properties TPGS-ANZ-BSA NPs at room temperature for a period one month. Conclusion: The BBD optimized TPGS-ANZ-BSA nanoparticles showed enhanced physiochemical properties for ANZ and potential candidates for anticancer agent drugs delivery.

In this study, we have unveiled the novel potential of xylanase production by Bacillus velezensis, previously known only for its PGPR traits. According to our investigations, Bacillus velezensis AG20 produced extracellular xylanase with a fold purification of 5.3 and a yield of 21 %. The purified xylanase (45 kDa) aptly cleaved linear β-(1→4)-xylan with a maximum velocity of 21.0 ± 3.0 U/mL, a turnover of 1.75/s, and a catalytic cycle of 0.571 at optimum pH 7. The temperature of 50 °C was found optimum for enzyme activity. Purified endoxylanase was thermostable and retained its significant residual activities at 50 °C and 60 °C. Metal cations such as Ca2+ and Mg2+ enhanced the substrate catalysis up to 1.5 fold. The purified endoxylanase also demonstrated multi-substrate hydrolyzing properties. However, the enzymatic hydrolysis of sugarcane bagasse produced xylooligosaccharides (XOS), including xylobiose, xylotriose, and xylotetrose. The mixture of released XOS has profound stability in gastric juice, intestinal fluid, and α-amylase and facilitates probiotic bacteria Bifidobacterium. The mixed XOS (300 μg/mL) significantly inhibited the HT-29 and Caco-2 cell proliferation by 90 % and 75 %, respectively, at 48 h. The possible mechanism of XOS uptake through the BIAXP receptor of Bifidobacterium has been contemplated and established using the caver analysis, Molecular Dynamics (MD) simulation, and Density Functional Theory (DFT) studies. Thus, here we reveal the utility of this novel bacterial strain in industries as high-temperature catalysts.