Among-population variation in drought responses is consistent across life stages but not between native and non-native ranges.

Understanding how widespread species adapt to variation in abiotic conditions across their ranges is fundamental to ecology. Insight may come from studying how among-population variation (APV) in the common garden corresponds with the environmental conditions of source populations. However, there are no such studies comparing native vs non-native populations across multiple life stages. We examined APV in the performance and functional traits of 59 Conyza canadensis populations, in response to drought, across large aridity gradients in the native (North America) and non-native (Eurasia) ranges in three experiments. Our treatment (dry vs wet) was applied at the recruitment, juvenile, and adult life stages. We found contrasting patterns of APV in drought responses between the two ranges. In the native range, plant performance was less reduced by drought in populations from xeric than mesic habitats, but such relationship was not apparent for non-native populations. These range-specific patterns were consistent across the life stages. The weak adaptive responses of non-native populations indicate that they can become highly abundant even without complete local adaptation to abiotic environments and suggest that long-established invaders may still be evolving to the abiotic environment. These findings may explain lag times in invasions and raise concern about future expansions.

Spatial variability in herbaceous plant phenology is mostly explained by variability in temperature but also by photoperiod and functional traits.

Whereas temporal variability of plant phenology in response to climate change has already been well studied, the spatial variability of phenology is not well understood. Given that phenological shifts may affect biotic interactions, there is a need to investigate how the variability in environmental factors relates to the spatial variability in herbaceous species' phenology by at the same time considering their functional traits to predict their general and species-specific responses to future climate change. In this project, we analysed phenology records of 148 herbaceous species, which were observed for a single year by the PhenObs network in 15 botanical gardens. For each species, we characterised the spatial variability in six different phenological stages across gardens. We used boosted regression trees to link these variabilities in phenology to the variability in environmental parameters (temperature, latitude and local habitat conditions) as well as species traits (seed mass, vegetative height, specific leaf area and temporal niche) hypothesised to be related to phenology variability. We found that spatial variability in the phenology of herbaceous species was mainly driven by the variability in temperature but also photoperiod was an important driving factor for some phenological stages. In addition, we found that early-flowering and less competitive species characterised by small specific leaf area and vegetative height were more variable in their phenology. Our findings contribute to the field of phenology by showing that besides temperature, photoperiod and functional traits are important to be included when spatial variability of herbaceous species is investigated.

Chemokines in triple-negative breast cancer heterogeneity: New challenges for clinical implications.

Tumor heterogeneity is a hallmark of cancer and one of the primary causes of resistance to therapies. Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers and is the most aggressive subtype, is very diverse, connected to metastatic potential and response to therapy. It is a very diverse disease at the molecular, pathologic, and clinical levels. TNBC is substantially more likely to recur and has a worse overall survival rate following diagnosis than other breast cancer subtypes. Chemokines, low molecular weight proteins that stimulate chemotaxis, have been shown to control the cues responsible for TNBC heterogeneity. In this review, we have focused on tumor heterogeneity and the role of chemokines in modulating tumor heterogeneity, since this is the most critical issue in treating TNBC. Additionally, we examined numerous cues mediated by chemokine networks that contribute to the heterogeneity of TNBC. Recent developments in our knowledge of the chemokine networks that regulate TNBC heterogeneity may pave the way for developing effective therapeutic modalities for effective treatment of TNBC.

Microglial mTOR Activation Upregulates Trem2 and Enhances ß-Amyloid Plaque Clearance in the 5XFAD Alzheimer's Disease Model.

The mechanistic target of rapamycin (mTOR) signaling pathway plays a major role in key cellular processes including metabolism and differentiation; however, the role of mTOR in microglia and its importance in Alzheimer's disease (AD) have remained largely uncharacterized. We report that selective loss of Tsc1, a negative regulator of mTOR, in microglia in mice of both sexes, caused mTOR activation and upregulation of Trem2 with enhanced ß-Amyloid (Aß) clearance, reduced spine loss, and improved cognitive function in the 5XFAD AD mouse model. Combined loss of Tsc1 and Trem2 in microglia led to reduced Aß clearance and increased Aß plaque burden revealing that Trem2 functions downstream of mTOR. Tsc1 mutant microglia showed increased phagocytosis with upregulation of CD68 and Lamp1 lysosomal proteins. In vitro studies using Tsc1-deficient microglia revealed enhanced endocytosis of the lysosomal tracker indicator Green DND-26 suggesting increased lysosomal activity. Incubation of Tsc1-deficient microglia with fluorescent-labeled Aß revealed enhanced Aß uptake and clearance, which was blunted by rapamycin, an mTOR inhibitor. In vivo treatment of mice of relevant genotypes in the 5XFAD background with rapamycin, affected microglial activity, decreased Trem2 expression and reduced Aß clearance causing an increase in Aß plaque burden. Prolonged treatment with rapamycin caused even further reduction of mTOR activity, reduction in Trem2 expression, and increase in Aß levels. Together, our findings reveal that mTOR signaling in microglia is critically linked to Trem2 regulation and lysosomal biogenesis, and that the upregulation of Trem2 in microglia through mTOR activation could be exploited toward better therapeutic avenues to Aß-related AD pathologies.SIGNIFICANCE STATEMENT Mechanistic target of rapamycin (mTOR) signaling pathway is a key regulator for major cellular metabolic processes. However, the link between mTOR signaling and Alzheimer's disease (AD) is not well understood. In this study, we provide compelling in vivo evidence that mTOR activation in microglia would benefit ß-Amyloid (Aß)-related AD pathologies, as it upregulates Trem2, a key receptor for Aß plaque uptake. Inhibition of mTOR pathway with rapamycin, a well-established immunosuppressant, downregulated Trem2 in microglia and reduced Aß plaque clearance indicating that mTOR inactivation may be detrimental in Aß-associated AD patients. This finding will have a significant public health impact and benefit, regarding the usage of rapamycin in AD patients, which we believe will aggravate the Aß-related AD pathologies.

Drosophila Homolog of the Human Carpenter Syndrome Linked Gene, MEGF8, Is Required for Synapse Development and Function.

Drosophila multiple epidermal growth factor-like domains 8 (dMegf8) is a homolog of human MEGF8 MEGF8 encodes a multidomain transmembrane protein which is highly conserved across species. In humans, MEGF8 mutations cause a rare genetic disorder called Carpenter syndrome, which is frequently associated with abnormal left-right patterning, cardiac defects, and learning disabilities. MEGF8 is also associated with psychiatric disorders. Despite its clinical relevance, MEGF8 remains poorly characterized; and although it is highly conserved, studies on animal models of Megf8 are also very limited. The presence of intellectual disabilities in Carpenter syndrome patients and association of MEGF8 with psychiatric disorders indicate that mutations in MEGF8 cause underlying defects in synaptic structure and functions. In this study, we investigated the role of Drosophila dMegf8 in glutamatergic synapses of the larval neuromuscular junctions (NMJ) in both males and females. We show that dMegf8 localizes to NMJ synapses and is required for proper synaptic growth. dMegf8 mutant larvae and adults show severe motor coordination deficits. At the NMJ, dMegf8 mutants show altered localization of presynaptic and postsynaptic proteins, defects in synaptic ultrastructure, and neurotransmission. Interestingly, dMegf8 mutants have reduced levels of the Type II BMP receptor Wishful thinking (Wit). dMegf8 displays genetic interactions with neurexin-1 (dnrx) and wit, and in association with Dnrx and Wit plays an essential role in synapse organization. Our studies provide insights into human MEGF8 functions and potentially into mechanisms that may underlie intellectual disabilities observed in Carpenter syndrome as well as MEGF8-related synaptic structural and/or functional deficits in psychiatric disorders.SIGNIFICANCE STATEMENT Carpenter syndrome, known for over a century now, is a genetic disorder linked to mutations in Multiple Epidermal Growth Factor-like Domains 8 (MEGF8) gene and associated with intellectual disabilities among other symptoms. MEGF8 is also associated with psychiatric disorders. Despite the high genetic conservation and clinical relevance, the functions of MEGF8 remain largely uncharacterized. Patients with intellectual disabilities and psychiatric diseases often have an underlying defect in synaptic structure and function. This work defines the role of the fly homolog of human MEGF8, dMegf8, in glutamatergic synapse growth, organization, and function and provide insights into potential functions of MEGF8 in human central synapses and synaptic mechanisms that may underlie psychiatric disorders and intellectual disabilities seen in Carpenter syndrome.

Calcium Oxalate Crystals, the Plant 'Gemstones': Insights into Their Synthesis and Physiological Implications in Plants.

From simple algal forms to the most advanced angiosperms, calcium oxalate (CaOx) crystals (CRs) occur in the majority of taxonomic groups of photosynthetic organisms. Various studies have demonstrated that this biomineralization is not a simple or random event but a genetically regulated coordination between calcium uptake, oxalate (OX) synthesis and, sometimes, environmental stresses. Certainly, the occurrence of CaOx CRs is old; however, questions related to their genesis, biosynthesis, significance and genetics exhibit robust evolution. Moreover, their speculated roles in bulk calcium regulation, heavy metal/OX detoxification, light reflectance and photosynthesis, and protection against grazing and herbivory, besides other characteristics, are gaining much interest. Thus, it is imperative to understand their synthesis and regulation in relation to the ascribed key functions to reconstruct future perspectives in harnessing their potential to achieve nutritious and pest-resistant crops amid anticipated global climatic perturbations. This review critically addresses the basic and evolving concepts of the origin (and recycling), synthesis, significance, regulation and fate vis-à-vis various functional aspects of CaOx CRs in plants (and soil). Overall, insights and conceptual future directions present them as potential biominerals to address future climate-driven issues.

Antibacterial potential of Thymus linearis essential oil collected from Wasturwan mountain: A combination of experimental and theoretical studies involving in silico molecular docking simulation of the major compounds against Novobiocin-resistant mutant of DNA Gyrase-B.

Antibiotic resistant bacteria are immune to most antibiotics and are therefore very difficult to treat and in most cases lead to death. As such there is a pressing need for alternative and more efficient antibacterial drugs which can target these drug-resistant strains as well. The objective of this research work was to investigate the antibacterial properties of Thymus linearis essential oil (EO) against multiple disease-causing bacterial pathogens. Additionally, the study aimed to examine the molecular docking and molecular dynamic (MD) simulations of the primary components of the EO with the essential bacterial proteins and enzymes. Gas chromatography-mass spectrometry was employed to analyse the chemical composition of Thymus linearis EO. The initial screening for antibacterial properties involved the use of disc diffusion and microdilution techniques. Molecular docking studies were conducted utilising Autodock Vina. The outcomes were subsequently visualised through BIOVIA Discovery Studio. MD simulations were conducted using iMODS, an internet-based platform designed for MD simulations. The essential oil (EO) was found to contain 26 components, with thymol, carvacrol, p-cymene, and γ-terpinene being the primary constituents. The study findings revealed that Thymus linearis EO demonstrated antibacterial effects that were dependent on both the dose and time. The results of molecular docking studies revealed that the primary constituents of the EO, namely thymol, carvacrol, and p-cymene, exhibited robust interactions with the active site of the bacterial DNA gyrase enzyme. This finding provides an explanation for the antibacterial mechanism of the EO. The results indicate that Thymus linearis EO possesses potent antibacterial properties against the MDR microorganisms. Molecular docking analyses revealed that the essential oil's primary components interact with the amino acid residues of the DNA-Gyrase B enzyme, resulting in a favourable docking score.

Tbx1, a gene encoded in 22q11.2 copy number variant, is a link between alterations in fimbria myelination and cognitive speed in mice.

Copy number variants (CNVs) have provided a reliable entry point to identify the structural correlates of atypical cognitive development. Hemizygous deletion of human chromosome 22q11.2 is associated with impaired cognitive function; however, the mechanisms by which the CNVs contribute to cognitive deficits via diverse structural alterations in the brain remain unclear. This study aimed to determine the cellular basis of the link between alterations in brain structure and cognitive functions in mice with a heterozygous deletion of Tbx1, one of the 22q11.2-encoded genes. Ex vivo whole-brain diffusion-tensor imaging (DTI)-magnetic resonance imaging (MRI) in Tbx1 heterozygous mice indicated that the fimbria was the only region with significant myelin alteration. Electron microscopic and histological analyses showed that Tbx1 heterozygous mice exhibited an apparent absence of large myelinated axons and thicker myelin in medium axons in the fimbria, resulting in an overall decrease in myelin. The fimbria of Tbx1 heterozygous mice showed reduced mRNA levels of Ng2, a gene required to produce oligodendrocyte precursor cells. Moreover, postnatal progenitor cells derived from the subventricular zone, a source of oligodendrocytes in the fimbria, produced fewer oligodendrocytes in vitro. Behavioral analyses of these mice showed selectively slower acquisition of spatial memory and cognitive flexibility with no effects on their accuracy or sensory or motor capacities. Our findings provide a genetic and cellular basis for the compromised cognitive speed in patients with 22q11.2 hemizygous deletion.

Species composition of root-associated mycobiome of ruderal invasive Anthemis cotula L. varies with elevation in Kashmir Himalaya.

Investigating the microbial communities associated with invasive plant species can provide insights into how these species establish and thrive in new environments. Here, we explored the fungal species associated with the roots of the invasive species Anthemis cotula L. at 12 sites with varying elevations in the Kashmir Himalaya. Illumina MiSeq platform was used to identify the species composition, diversity, and guild structure of these root-associated fungi. The study found a total of 706 fungal operational taxonomic units (OTUs) belonging to 8 phyla, 20 classes, 53 orders, 109 families, and 160 genera associated with roots of A. cotula, with the most common genus being Funneliformis. Arbuscular mycorrhizal fungi (AMF) constituted the largest guild at higher elevations. The study also revealed that out of the 12 OTUs comprising the core mycobiome, 4 OTUs constituted the stable component while the remaining 8 OTUs comprised the dynamic component. While α-diversity did not vary across sites, significant variation was noted in ß-diversity. The study confirmed the facilitative role of the microbiome through a greenhouse trial in which a significant effect of soil microbiome on height, shoot biomass, root biomass, number of flower heads, and internal CO2 concentration of the host plant was observed. The study indicates that diverse fungal mutualists get associated with this invasive alien species even in nutrient-rich ruderal habitats and may be contributing to its spread into higher elevations. This study highlights the importance of understanding the role of root-associated fungi in invasion dynamics and the potential use of mycobiome management strategies to control invasive species.

Risk analysis of fast spreading species in a Kashmir Himalayan National Park (Dachigam) for better monitoring and management.

Huge economic costs and ecological impacts of invasive alien species (IAS) in the protected areas (PAs) worldwide make their timely prediction and potential risk assessment of central importance for effective management. While the preborder weed risk assessment framework has been extensively evaluated and implemented, the postborder species risk assessment framework has not been subjected to the same degree of scrutiny. Here we used a rather more realistic modified version of the Australian Weed Risk framework (AWRM) for Dachigam National Park (DNP) in Kashmir Himalaya against 84 plant species, including 55 alien species and 29 fast spreading native species, for risk analysis. We found two very high-risk species, three high-risk species, 10 medium-risk species, 29 low-risk species, and 40 negligible-risk species in the DNP. The containment scores accordingly ranged from 14.4 to 293.5 comprising of 27 species that can be contained with very high feasibility, 23 species with high feasibility, 14 species with medium feasibility, and 12 species which cannot be contained easily thereby having low feasibility of containment (FOC) score. However, eight species which have a negligible FOC score are difficult to contain within their infestation sites. Our results demonstrate the merit of the AWRM with a caution that the necessary region-specific modifications may help in its better implementation. Overall, these results provide quite a promising tool in the hands of protected area managers to timely and effectively deal with the problem of plant invasions.

Integrating human footprint with ensemble modelling identifies priority habitats for conservation: a case study in the distributional range of Arnebia euchroma, a vulnerable species.

Climate change-driven rapid alteration of ecosystems globally is further complicated by growing anthropogenic pressures, especially in the ecologically sensitive mountainous regions. However, these two major drivers of change have largely been considered separately in species distribution models, thus compromising their reliability. Here, we integrated ensemble modelling with the human pressure index for predicting distribution and mapping priority regions across a whole range of occurrences for vulnerable species, Arnebia euchroma. Our results identified 3.08% of the study area as 'highly suitable', 2.45% as 'moderately suitable', and 94.45% as 'not suitable' or 'least suitable'. Compared to current climatic conditions, future RCP scenarios of 2050 and 2070 showed a significant loss in habitat suitability and a slight shift in the distribution pattern of the target species. By excluding the high-pressure areas of the human footprint from the predicted suitable habitats, we were able to identify the unique areas (70% of the predicted suitable area) that need special attention for conservation and restoration. Such models, if well implemented, may play a pivotal role in achieving the effective targets under the aegis of the current UN decade on ecological restoration (2021-2030) in accordance with SDG 15.4.

Functional traits influence patterns in vegetative and reproductive plant phenology - a multi-botanical garden study.

Phenology has emerged as key indicator of the biological impacts of climate change, yet the role of functional traits constraining variation in herbaceous species' phenology has received little attention. Botanical gardens are ideal places in which to investigate large numbers of species growing under common climate conditions. We ask whether interspecific variation in plant phenology is influenced by differences in functional traits. We recorded onset, end, duration and intensity of initial growth, leafing out, leaf senescence, flowering and fruiting for 212 species across five botanical gardens in Germany. We measured functional traits, including plant height, absolute and specific leaf area, leaf dry matter content, leaf carbon and nitrogen content and seed mass and accounted for species' relatedness. Closely related species showed greater similarities in timing of phenological events than expected by chance, but species' traits had a high degree of explanatory power, pointing to paramount importance of species' life-history strategies. Taller plants showed later timing of initial growth, and flowered, fruited and underwent leaf senescence later. Large-leaved species had shorter flowering and fruiting durations. Taller, large-leaved species differ in their phenology and are more competitive than smaller, small-leaved species. We assume climate warming will change plant communities' competitive hierarchies with consequences for biodiversity.

Plant based natural products as potential ecofriendly and safer biopesticides: A comprehensive overview of their advantages over conventional pesticides, limitations and regulatory aspects.

The commercially used synthetic pesticides have been proven to be toxic not only to humans and other animals, but also to non-target plant, the surrounding organisms around the plant, and the environment. There are also increased concerns regarding the development of pest resistance towards these synthetic pesticides. As such, biopesticides, which are defined as the certain kinds of pesticides derived from natural sources such as plants, bacteria, fungi, animals and some minerals, are potential alternative pesticides and are gaining increasing attention. Biopesticides are safer and eco-friendly pesticides used for pest management. Among these, plant-based biopesticides constitute a small but important group of biopesticides. Plant based extracts and essential oils have been particularly used in the management of insects exhibiting a variety of anti-insecticidal mechanisms. Their chemical compositions are very complex and as such acquiring resistance by the pest against such biopesticide is very difficult. As far as their mechanism of action is concerned, these can act as insect repellants, insect attractants, or anti-feedants. They can also inhibit respiration or they can obstruct the host plant identification. These insecticides can inhibit oviposition and decrease adult emergence by ovicidal and larvicidal effects. Some of the essential oil based insecticides have even been commercialized for use. However, there are some limitations that restrict the widespread use of such biopesticides. These limitations include cost, difficulties in production, gentle action, and dearth of appropriate biopesticide formulations. As far as their regulations are concerned, it is still a problem in many countries further halting biopesticide use. But one thing is clear that biopesticides do have a promising future due to their eco-friendly nature and unique chemical compositions and unique mode of action.

Gas chromatographic-mass spectrometric analysis, antioxidant, antiproliferative and antibacterial activities of the essential oil of Prangospabularia.

The essential oil composition of the shoot parts of Prangos pabularia, growing in Drass area of Ladakh, India, along with its antioxidant, antibacterial and anticancer activity, is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 31 constituents, representing 97.342% of the total essential oil. The major constituents of essential oil were Durylaldehyde (62.161%), Bicyclo [3.1.1] hept-2-en-4-ol (8.846%), Chrysanthenyl acetate (5.120%) followed by unknown (3.420%), (-)-Spathulenol (3.028%), Mesityl aldehyde (2.402%) and Hexahydro farnesyl acetone (1.683%. Cytotoxic activity of the essential oil by MTT assay against human breast adenocarcinoma (MCF7), human breast (HBL-100), human cervical cancer (HELA) and human lung adenocarcinoma epithelial (A549) cells, at four different concentrations (20, 30, 50 & 100 µg/mL) revealed that the activity of 56.12% against A549 (human lung) cell line at 20 µg/mL concentration was the highest. The Essential oil displayed a significant free radical scavenging activity with DPPH. Antibacterial activity was carried out against 3 g positive and 2-g negative bacteria at four different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The essential oil displayed significant and broad-spectrum antibacterial activity against different bacteria used. The MIC of the oil ranged from 2.06 to 5.00 µg/mL. The zones of inhibition were lesser for Micrococcus and Escherichia coli compared to other strains of bacteria.

Expression of nutrient transporter genes in response to dietary rice gluten meal and protease enzyme supplementation and the consequent effects on growth, nutrient digestibility, immunity and jejunum histomorphometry in chicken.

The objective of this study was to investigate the effects of feeding rice gluten meal (RGM) as an alternative protein source along with protease enzyme supplementation on growth performance, expression of nutrient transporter genes, nutrient digestibility, immune response and gut histomorphometry of broiler chicken. Proximate analysis of RGM revealed 923 g dry matter (DM), 500 g crude protein (CP), 69.2 g ether extract, 94.7 g crude fiber, 215.4 g nitrogen-free extract, 43.7 g ash, 6.20 g calcium, 7.80 g total phosphorus, 18.99 MJ gross energy and 12.68 MJ metabolizable energy per kg diet. Significant upregulation of nutrient transporter genes (PepT1, EAAT3 and mucin) and better growth performance was observed in the birds fed control diet which was statistically similar to the birds fed 150 g RGM compared to birds fed higher RGM levels. Histomorphometry of jejunum, nutrient digestibility, and immune response of birds did not reveal any significant effect of RGM or protease enzyme supplementation. However, the inclusion of RGM up to 150 g/kg diet resulted in significant decline of feed cost/kg live weight gain, dressed meat yield and eviscerated meat yield by 13.13%, 12.99% and 13.36%, respectively compared to control. Thus, it was concluded that the inclusion of 150 g RGM/kg diet in broiler chicken ration has no adverse effects on the growth pattern of birds and can be used for least-cost feed formulation for chicken.

Risk assessment and management framework for rapidly spreading species in a Kashmir Himalayan Ramsar site.

In view of huge ecological impacts and exorbitantly high economic costs of biological invasions, the risk assessment for timely prediction of potential invaders and their effective management assumes central importance, yet having been little addressed. Hence, we did the risk analysis of 39 plant species, including both alien and fast-spreading native species, in Hokera wetland, an important Ramsar site in Kashmir Himalaya, using the post-border Australian Weed Risk Management (AWRM) framework. Based on the AWRM scores, we listed these species into different categories, such as alert, destroy infestation, contain spread, manage weed, manage sites and monitor, with management implications. Out of the eight decisions created for Hokera wetland, alien Alternanthera philoxeroides was identified as 'alert species', while Typha angustifolia, Typha latifolia, Phragmites australis, Sparganium ramosum and Myriophyllum aquaticum were placed under the 'manage weed' category of the management priorities. To check the predictability and reliability of the AWRM scheme, we developed the receiver operating characteristic (ROC) curve that yielded a positive diagonal value of above 0.5, with 88.6% and 83.1% area under the curve for comparative weed risk (CWR) score and the feasibility of coordinated control (FOC) score, respectively. The outcomes of the ROC analysis were compared with the results of the WRM evaluation of other regions across the globe. Our results indicate that the risk assessment using the AWRM model is quite efficient at discriminating and flagging the most troublesome plant species and offsetting their impacts on native biodiversity and ecosystem functioning in wetland ecosystems. Given the growing threat of biological invasions in the protected areas, we recommend an integrated and strategic approach, well informed by the data on the species biology and ecology, in the form of the AWRM management system to effectively deal with the alarmingly spreading species.

Molecular scaffolds from mother nature as possible lead compounds in drug design and discovery against coronaviruses: A landscape analysis of published literature and molecular docking studies.

The recent outbreak of viral infection and its transmission has highlighted the importance of its slowdown for the safeguard of public health, globally. The identification of novel drugs and efficient therapies against these infectious viruses is need of the hour. The eruption of COVID-19 is caused by a novel acute respiratory syndrome virus SARS-CoV-2 which has taken the whole world by storm as it has transformed into a global pandemic. This lethal syndrome is a global health threat to general public which has already affected millions of people. Despite the development of some potential vaccines and repurposed drugs by some Pharma companies, this health emergency needs more attention due to the less efficacy of these vaccines coupled with the emergence of novel and resistant strains of SARS-CoV-2. Due to enormous structural diversity and biological applications, natural products are considered as a wonderful source of drugs for such diseases. Natural product based drugs constitute a substantial proportion of the pharmaceutical market particularly in the therapeutic areas of infectious diseases and oncology. The naturally occurring bioactive antiviral phytochemicals including alkaloids, flavonoids and peptides have been subjected to virtual screening against COVID-19. Since there is no specific medicine available for the treatment of Covid-19, designing new drugs using in silico methods plays an all important role to find that magic bullet which can target this lethal virus. The in silico method is not only quick but economical also when compared to the other conventional methods which are hit and trial methods. Based on this in silico approach, various natural products have been recently identified which might have a potential to inhibit COVID-19 outbreak. These natural products have been shown by these docking studies to interact with the spike protein of the novel coronavirus. This spike protein has been shown to bind to a transmembrane protein called Angiotensin converting enzyme 2 (ACE2), this protein acts as a receptor for the viral spike protein. This comprehensive review article anticipates providing a summary of the authentic and peer reviewed published literature about the potential of natural metabolites that can be developed into possible lead compounds against this new threat of Covid-19. Main focus of the article will be to highlight natural sources of potential anti-coronavirus molecules, mechanism of action, docking studies and the target proteins as well as their toxicity profiles. This review article intends to provide a starting point for the research endeavors that are needed for the design and development of drugs based on pure natural products, their synthetic or semi-synthetic derivatives and standardized plant extracts. This review article will be highly helpful for scientists who are working or intend to work on antiviral drugs from natural sources.

Gas Chromatographic-Mass Spectrometric Analysis, Antibacterial, Antioxidant and Antiproliferative Activities of the Needle Essential Oil of Abies pindrow growing wild in Kashmir, India.

The essential oil composition of the leaves of Abies pindrow, growing in Kashmir, India, along with its antioxidant, antibacterial and anticancer activity is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 12 constituents, representing 99.9% of the total oil. The major constituents of the oil were limonene (38.9%), α-pinene (36.5%), ß-pinene (6.9%), and α-selinene (4.4%). The essential oil was dominated by the presence of monoterpene hydrocarbons (90.2%), followed by sesquiterpene hydrocarbons (6.761%), oxygenated sesquiterpenes (2.096%) and oxygenated monoterpenes (0.942%). The monoterpene rich essential oil was subjected to antibacterial activity against 4 Gram negative bacteria and 2 Gram positive bacteria at three different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The oil displayed significant and broad spectrum antibacterial activity against different bacteria used. The minimum inhibitory concentration (MIC) of the active essential oil was determined using Agar Dilution Method. Highest antibacterial activity was shown by the oil against E. Coli (25 mm), and the lowest by Bacillus subtilis (14 mm) and Pseudomonas aeruginosa (14 mm). The oil was subjected to cytotoxic activity by MTT assay against human mammary carcinoma (MCF), human ductal breast epithelial tumour (T47D), human lung adeno-carcinoma epithelial (A549) and rat glial (C6) cell lines at three different concentrations. The results revealed significant sensitization of the cell lines with highest inhibition against human ductal breast epithelial cell line (51%) and the lowest against rat glial cell line (33%) at a concentartion of 50 µg/mL. The oil displayed a significant free radical scavenging activity with DPPH.

An insight into the cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most complex, aggressive and fatal subtype of breast cancer. Owing to the lack of targeted therapy and heterogenic nature of TNBC, chemotherapy remains the sole treatment option for TNBC, with taxanes and anthracyclines representing the general chemotherapeutic regimen in TNBC therapy. But unfortunately, patients develop resistance to the existing chemotherapeutic regimen, resulting in approximately 90% treatment failure. Breast cancer stem cells (BCSCs) are one of the major causes for the development of chemoresistance in TNBC patients. After surviving the chemotherapy damage, the presence of BCSCs results in relapse and recurrence of TNBC. Several pathways are known to regulate BCSCs' survival, such as the Wnt/ß-catenin, Hedgehog, JAK/STAT and HIPPO pathways. Therefore it is imperative to target these pathways in the context of eliminating chemoresistance. In this review we will discuss the novel strategies and various preclinical and clinical studies to give an insight into overcoming TNBC chemoresistance. We present a detailed account of recent studies carried out that open an exciting perspective in relation to the mechanisms of chemoresistance.

Next Generation High Throughput Sequencing to Assess Microbial Communities: An Application Based on Water Quality.

Traditional techniques to identify different contaminants (biological or chemical) in the waters are slow, laborious, and can require specialized expertise. Hence, the rapid determination of water quality using more sensitive and reliable metagenomic based approaches attains special importance. Metagenomics deals with the study of genetic material that is recovered from microbial communities present in environmental samples. In traditional techniques cultivation-based methodologies were used to describe the diversity of microorganisms in environmental samples. It has failed to function as a robust marker because of limited taxonomic and phylogenetic implications. In this backdrop, high-throughput DNA sequencing approaches have proven very powerful in microbial source tracking because of investigating the full variety of genome-based analysis such as microbial genetic diversity and population structure played by them. Next generation sequencing technologies can reveal a greater proportion of microbial communities that have not been reported earlier by traditional techniques. The present review highlights the shift from traditional techniques for the basic study of community composition to next-generation sequencing (NGS) platforms and their potential applications to the biomonitoring of water quality in relation to human health.