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.

Impact of Nanoencapsulated Rosemary Essential Oil as a Novel Feed Additive on Growth Performance, Nutrient Utilization, Carcass Traits, Meat Quality and Gene Expression of Broiler Chicken.

This study evaluated the effect of free and nanoencapsulated rosemary essential oil (REO) as an antibiotic alternative in broiler diets on growth performance, nutrient digestibility, carcass traits, meat quality and gene expression. Four hundred twenty day-old commercial broiler chicks (VENCOBB) were randomly allocated to seven dietary treatments, each having four replicates of fifteen chicks. The dietary treatments comprised control (CON) fed a basal diet only, AB (basal diet + 10 mg enramycin/kg), CS (basal diet + 150 mg chitosan nanoparticles/kg), REOF100 and REOF200 (basal diet + 100 mg and 200 mg free REO/kg, respectively), and REON100 and REON200 (basal diet + 100 mg and 200 mg nanoencapsulated REO/kg, respectively). Overall (7-42 d), REON200 showed the highest (p < 0.001) body weight gain (1899 g/bird) and CON had the lowest gain (1742 g/bird), while the CS, REOF100 and REOF200 groups had a similar gain, but lower than that of the AB and REON100 groups. Feed intake was not affected by dietary treatments. Overall, the feed efficiency increased (p = 0.001) by 8.47% in the REON200 group and 6.21% in the AB and REON100 groups compared with the CON. Supplementation of REO improved (p < 0.05) dry matter and crude protein digestibility, with the highest values in REON100 and REON200. Ether extract, crude fiber, calcium and phosphorus digestibility values showed no difference among the groups. The dressing, breast, thigh % increased (p < 0.05) and abdominal fat % decreased (p < 0.001) more in the REON200 group than with other treatments and CON. In breast meat quality, water holding capacity and extract reserve volume increased (p < 0.05) while drip loss and cholesterol content decreased (p < 0.05) in REON100 and REON200. No change was observed in the breast meat color among dietary treatments and CON. The REON100 and REON200 groups had reduced (p < 0.05) meat lipid peroxidation as depicted by the decreased levels of TBARS, free fatty acids and peroxide value compared to other treatments and CON. The expression of the Mucin 2, PepT1 and IL-10 genes was upregulated (p < 0.001) and TNF-α downregulated (p < 0.001) by dietary addition of REO particularly in the nanoencapsulated form compared with the CON. In conclusion, nanoencapsulated REO, especially at 200 mg/kg diet, showed promising results as an antibiotic alternative in improving the performance, nutrient digestibility, carcass traits, meat quality and upregulation of growth and anti-inflammatory genes.

Microglia, Trem2, and Neurodegeneration.

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. Microglia express Trem2, which serves as a receptor for a multitude of ligands enhancing their phagocytic activity. Trem2 has emerged as a critical modulator of microglial activity, especially in many neurodegenerative disorders. Human TREM2 mutations are associated with an increased risk of developing Alzheimer disease (AD) and other neurodegenerative diseases. Trem2 plays dual roles in neuroinflammation and more specifically in disease-associated microglia. Most recent developments on the molecular mechanisms of Trem2, emphasizing its role in uptake and clearance of amyloid ß (Aß) aggregates and other tissue debris to help protect and preserve the brain, are encouraging. Although Trem2 normally stimulates defense mechanisms, its dysregulation can intensify inflammation, which poses major therapeutic challenges. Recent therapeutic approaches targeting Trem2 via agonistic antibodies and gene therapy methodologies present possible avenues for reducing the burden of neurodegenerative diseases. This review highlights the promise of Trem2 as a therapeutic target, especially for Aß-associated AD, and calls for more mechanistic investigations to understand the context-specific role of microglial Trem2 in developing effective therapies against neurodegenerative diseases.

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.

Protocol for isolating and processing mouse sciatic nerve fibers for confocal immunohistochemistry.

Many motor and neurodegenerative diseases affect the peripheral nervous system (PNS). The myelinated axons in the sciatic nerves offer valuable insights into the pathology of these diseases. Here, we present a protocol for isolating and processing mouse sciatic nerves for confocal immunohistochemistry. We describe steps for mouse perfusion, removing and fixing the sciatic nerve, transferring nerves onto slides, staining, and imaging. This protocol can assist in characterizing pathologies of myelinated fibers resulting from diseases affecting the PNS. For complete details on the use and execution of this protocol, please refer to Chang et al. (2023).1.

Deciphering the chemical constituents and antimicrobial activity of Prangos pabularia Lindl. using LC-MS/MS in combination with experimental evaluation and computational studies.

This study meticulously explores the antimicrobial potential of Prangos pabularia Lindl.'s aerial parts through a comprehensive blend of in vitro and in silico analysis. Extracts with varying polarities underwent LC-MS/MS identification of active components, followed by in vitro and in silico assessments of antimicrobial efficacy against Escherichia coli, Bacillus cereus, Candida albicans, Candida glabrata, and Candida paropsilosis. The methanolic extract exhibited significant antimicrobial activity with a MIC value of 48 µg/mL against all tested strains. Molecular docking revealed the compound 9-(3-methylbut-2-enoxy)-furo-(3,2-g)-chromen-7-one's highest binding affinity against the penicillin-binding protein (PBP) bacterial drug target molecule. Other compounds also displayed substantial interactions with key antimicrobial drug target proteins. Further, Molecular dynamics simulations affirmed the stability of protein and ligand conformations. Collectively, these results underscore Prangos pabularia Lindl.'s aerial parts as a promising botanical resource in combating diverse microbial infections. This comprehensive approach not only validates it's in vitro antimicrobial properties but also provides molecular insights into interaction mechanisms, advancing our comprehension of the plant's therapeutic potential.

Species composition of root-associated mycobiome of ruderal invasive Anthemis cotula L. varies with elevation in Kashmir Himalaya / La composición de especies del micobioma asociado a las raíces de la invasora ruderal Anthemis cotula L. varía con la elevación en Cachemira 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 β-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.(AU)

Mouse models of human CNTNAP1-associated congenital hypomyelinating neuropathy and genetic restoration of murine neurological deficits.

The Contactin-associated protein 1 (Cntnap1) mouse mutants fail to establish proper axonal domains in myelinated axons. Human CNTNAP1 mutations are linked to hypomyelinating neuropathy-3, which causes severe neurological deficits. To understand the human neuropathology and to model human CNTNAP1C323R and CNTNAP1R764C mutations, we generated Cntnap1C324R and Cntnap1R765C mouse mutants, respectively. Both Cntnap1 mutants show weight loss, reduced nerve conduction, and progressive motor dysfunction. The paranodal ultrastructure shows everted myelin loops and the absence of axo-glial junctions. Biochemical analysis reveals that these Cntnap1 mutant proteins are nearly undetectable in the paranodes, have reduced surface expression and stability, and are retained in the neuronal soma. Postnatal transgenic expression of Cntnap1 in the mutant backgrounds rescues the phenotypes and restores the organization of axonal domains with improved motor function. This study uncovers the mechanistic impact of two human CNTNAP1 mutations in a mouse model and provides proof of concept for gene therapy for CNTNAP1 patients.

Retromandibular Vein, Digastric Muscle, and Greater Auricular Nerve in Superficial Parotidectomies for Patients with Pleomorphic Adenoma-A Surgical Experience.

Retromandibular vein (RMV) and posterior belly of digastric muscle are among the landmarks used to identify facial nerve in parotid surgery. This observational cross-sectional study was done in the Department of ENT &HNS at a tertiary care teaching hospital for a period of 8 years with the aim to aware young otorhinolaryngologist about the relationship of posterior belly of digastric muscle & retromandibular vein with facial nerve and share our experience about preservation of posterior branch of greater auricular nerve. A total of 34 cases of superficial parotidectomies done for pleomorphic adenoma were included in this study. Relationship of facial nerve with retromandibular vein and posterior belly of digastric muscle was noted. Greater auricular nerve was identified, and every attempt was made to preserve its posterior branch. Retromandibular vein was medial to the trunks of facial nerve in 33 (97%) patients. It was lateral to lower division and medial to upper division in one case. Greater auricular nerve was seen to bifurcate into two branches (Anterior and posterior) in 21 (62%) cases while in one case(3%) three branches were seen emerging from main trunk and in another case(3%) first two branches were seen emerging and then anterior branch was further dividing into two. Preservation of posterior branch of greater auricular nerve was possible in 23 (68%) of patients. Posterior belly of digastric muscle was seen as a reliable and constant landmark. Facial nerve was seen superior to upper border of posterior belly of digastric muscle in all cases (100%). No anatomical variation of posterior belly was seen. Retromandibular vein is invariably seen medial to the trunks of facial nerve. Facial nerve is always seen superior to upper border of posterior belly of digastric muscle in almost all cases. Preservation of posterior branch of greater auricular nerve is possible in majority of the cases.

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.

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.

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.

Increasing the Safety Profile of Follicular Unit Extraction by Eliminating the Use of Bupivacaine and Nerve Block: Experience from a Tertiary Care Center of North India.

Introduction: Follicular unit extraction (FUE) is a safe and effective procedure in the hands of an expert. Side effects, particularly those which can lead to significant morbidity or mortality, are unacceptable as the procedure is done purely for cosmetic reasons. Any modification that decreases the risk associated with the procedure should be promoted. Aim and Objective: The study was conducted to determine whether FUE can be carried out effectively with the elimination of nerve blocks and bupivacaine from the procedure. Materials and Methods: The study was conducted in 30 patients suffering from androgenetic alopecia. The donor areas was anesthetized using lignocaine with adrenaline just below the area to be harvested. The anesthetic was injected intradermally resulting in the development of wheals in continuity, forming a linear line. From our previous experience, we found intradermal administration of lignocaine to give better anesthetic effect as compared to subcutaneous administration, although the former is more painful. This was followed by injection of tumescent into the donor area and donor harvesting, which lasted for a couple of hours. The recipient area was anesthetized using a similar technique of linear injection of anesthetic just ahead of the proposed hair line. Results: The total amount of lignocaine with adrenaline consumed during the surgery ranged from a minimum of 6.1 ml to 8.5 ml, with an average of 7.6 ml. The average duration of the entire surgery was 6.5 h, ranging from 4.5 to 8.5 h. None of the patients experienced any pain during the entire surgery, and there were no significant side effects related to anesthetic administration in any patient. Discussion: We found lignocaine with adrenaline to be a very safe and effective anesthetic agent for field block anesthesia in FUE. The exclusion of bupivacaine and nerve blocks from the procedure of FUE can further increase the safety of the procedure, particularly for beginners and in cases where the area to be covered is not extensive (Norwood-Hamilton grades 3, 4, and 5).

Reticular Oral Lichen Planus: A Clinical Experience of ENT Surgeons.

Reticular Oral lichen planus (OLP) is a chronic autoimmune disease that presents as fine, white, linear and lace like lesions of the oral cavity referred to as Wickham striae. The clinical characteristics of 30 patients with reticular oral lichen planus is presented so that cases are not missed/misdiagnosed by ENT surgeons. The clinical records noted for each patient were gender, age and clinical presentation of reticular OLP (site affected, presence of symptoms and extraoral manifestations of the disease, smoking habit, and consumption of alcoholic beverages). Twenty patients were females (66.7%) and 10 (33.3%) were males giving a female to male ratio of 2:1. Majority of patients (50%) among both males and females were in the age group of 31-40 years followed by 41-50 years (20%). Oral discomfort/burning sensation was the chief symptom in 24 (80%) patients followed by asymptomatic oral white patches in 5 (16.6%).The buccal (cheek) mucosa was the site most affected (76.8%) followed by the buccal mucosa plus retromolar trigone mucosa (10%) and tongue (6.6%), Extraoral lesions were observed in 2 (6.6%) of patients at presentation with oral lesions and were on the nails in 1 patient and wrist in 1 patient. Tobacco smoking, alcohol use, diabetes and hypertension were reported in 3 (10%), 0%, 2 (6.7%) and 4 (13.3%) patients respectively. ENT surgeons routinely see patients with oral discomfort/oral ulcerations and as such they should be well versed with classical clinical characteristics of reticular oral lichen planus.

A network pharmacology-based investigation of brugine reveals its multi-target molecular mechanism against Breast Cancer.

Breast cancer represents the leading cause of mortality among women worldwide. Since the complexity of breast cancer as a disease resides in its heterogeneity as it consists of several subtypes such as hormone receptor-positive subtypes: Luminal A, Luminal B, Her2- overexpressed, basal-like and hormone receptor-negative subtype: TNBC. Among all the subtypes, triple negative breast cancer (TNBC) is the most lethal and complex subtype. Moreover, the available treatment options like surgery, radiation therapy, and chemotherapy are not sufficient because of the associated side effects and drug resistance development. Therefore, discovery of new effective natural compounds with anti-tumor activity is required. In this pursuit, marine organisms provide a plentiful supply of such chemicals compounds. A marine compound Brugine found in the bark and stem of mangrove species Bruguiera sexangula is a potential anti-cancer compound. It has shown its cytotoxic activity against sarcoma 180 and lewis lung cancer. The molecular processes, however, are currently unknown. So, in order to research the molecular pathways this compound utilizes, we sought to apply a network pharmacology approach. The network pharmacology strategy we used in this investigation to identify and evaluate possible molecular pathways involved in the treatment of breast cancer with brugine was supported by simulation and molecular docking experiments. The study was conducted using various databases such as the cancer genome atlas (TCGA) for the genetic profile study of breast cancer, Swiss ADME for studying the pharmacodynamic study of brugine, Gene cards for collection of information of genes, STRING was used to study the interaction among proteins, AutoDock vina was to study the binding efficacy of brugine with the best fit protein. The results showed that the compound and breast cancer target network shared 90 common targets. According to the functional enrichment analysis brugine exhibited its effects in breast cancer via modulating certain pathways such as cAMP signaling pathway, JAK/STAT pathway, HIF-1 signaling pathway PI3K-Akt pathway, calcium signaling pathway, and Necroptosis. Molecular docking investigations demonstrated that the investigated marine compound has a high affinity for the key target, protein kinase A (PKA). A stable protein-ligand combination was created by the best hit molecule, according to molecular dynamics modeling. The purpose of this research was to examine the importance of brugine as a potentially effective treatment for breast cancer and to obtain knowledge of the molecular mechanism used by this substance in breast cancer.

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.

Targeting tumor microenvironment using tumor-infiltrating lymphocytes as therapeutics against tumorigenesis.

The immune system plays a vital role in suppressing tumor cell progression. The tumor microenvironment augmented with significant levels of tumor-infiltrating lymphocytes has been widely investigated and it is suggested that tumor-infiltrating lymphocytes have shown a significant role in the prognosis of cancer patients. Compared to ordinary non-infiltrating lymphocytes, tumor-infiltrating lymphocytes (TILs) are a significant population of lymphocytes that infiltrate tumor tissue and have a higher level of specific immunological reactivity against tumor cells. They serve as an effective immunological defense against various malignancies. TILs are a diverse group of immune cells that are divided into immune subsets based on the pathological and physiological impact they have on the immune system. TILs mainly consist of B-cells, T-cells, or natural killer cells with diverse phenotypic and functional properties. TILs are known to be superior to other immune cells in that they can recognize a wide range of heterogeneous tumor antigens by producing many clones of T cell receptors (TCRs), outperforming treatments like TCR-T cell and CAR-T therapy. With the introduction of genetic engineering technologies, tumor-infiltrating lymphocytes (TILs) have become a ground-breaking therapeutic option for malignancies, but because of the hindrances opposed by the immune microenvironment and the mutation of antigens, the development of TILs as therapeutic has been hindered. By giving some insight into the many variables, such as the various barriers inhibiting its usage as a potential therapeutic agent, we have examined various aspects of TILs in this work.

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.

Extranuclear DNA Variations in the Susceptibility of Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide which affects all age groups. It is often identified by high intraocular pressure, characteristic optic neuropathy, and vision loss. Due to multifactorial nature of glaucoma pathogenesis, the molecular events responsible for its precipitation are currently poorly understood. Mitochondrial DNA (mtDNA) variations which are inherited maternally are being closely studied in recent times to elucidate the effect on glaucoma. Mitochondrial genetic studies till date have found a possible link between Leber hereditary optic neuropathy loci and glaucoma but with conflicting views. Furthermore, whole mtDNA studies in glaucoma points at the involvement of oxidative phosphorylation complex I and specifically the NADH dehydrogenase 5 gene in glaucoma. This review focuses on identifying the potential genes and variations in the maternally inherited mtDNA which might be involved in glaucoma pathogenesis.

Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis.

Cancer continues to be a major global public health concern and one of the foremost causes of death. Delays in the diagnosis and cure may cause an increase in advanced stage disease and mortality. The most common cancer found in women currently is breast carcinoma. Breast carcinoma has surpassed lung carcinoma and currently represents the chief type of cancer diagnosed (2.3 million new cases, which amount to 11.7% of all cancer cases). In addition, by 2040, the incidence will increase by more than 46% as per the estimates of GLOBOCAN. Triple-negative breast cancer (TNBC) represents a highly aggressive and invasive subtype of breast cancer, characterized by rapid progression, short response time to the available treatment, and poor clinical results. Thus, it is very crucial to develop novel diagnostic tools and therapeutics with good efficacy. A majority of cancers display malfunction along the p53 pathway. Moreover, p53 not only loses its function but is also prone to misfolding and aggregation, leading to formation of amyloid aggregates as well. Research is being carried out to find ways to restore the normal action and expression of p53. Here, we have explored PhiKan-083 for its possible stabilizing effect on p53 in order to address the problem with its misfolding. Thus, examining the analogs of PhiKan-083 that have a role in p53 stability will help update our understanding of cancer progression and may expedite the progress of new anticancer treatments. We anticipate that the drug molecules and their analogs targeting p53 aggregation may be used in combination with other anticancer compounds to solve the problem with p53 aggregation. In this study, by employing ADMET analysis, the compounds were screened, and we further examined the chosen compounds with the help of molecular docking. By using databases like UALCAN, TIMER, GEPIA, and PredictProtein, we investigated TP53's expression pattern and prognostic relevance in various cancer settings.