Characterization of heat, salt, acid, alkaline, and antibiotic stress response in soil isolate Bacillus subtilis strain PSK.A2.

Microbes play an essential role in soil fertility by replenishing the nutrients; they encounter various biotic and abiotic stresses disrupting their cellular homeostasis, which expedites activating a conserved signaling pathway for transient over-expression of heat shock proteins (HSPs). In the present study, a versatile soil bacterium Bacillus subtilis strain PSK.A2 was isolated and characterized. Further, the isolated bacterium was exposed with several stresses, viz., heat, salt, acid, alkaline, and antibiotics. Stress-attributed cellular morphological modifications such as swelling, shrinkage, and clump formation were observed under the scanning electron microscope. The comparative protein expression pattern was studied by SDS-PAGE, relative protein stabilization was assessed by protein aggregation assay, and relative survival was mapped by single spot dilution and colony-counting method under control, stressed, lethal, and stressed lethal conditions of the isolate. The findings demonstrated that bacterial stress tolerance was maintained via the activation of various HSPs of molecular weight ranging from 17 to 115 kD to respective stimuli. The treatment of subinhibitory dose of antibiotics not interfering protein synthesis (amoxicillin and ciprofloxacin) resulted in the expression of eight HSPs of molecular weight ranging from 18 to 71 kD. The pre-treatment of short stress dosage showed endured overall tolerance of bacterium to lethal conditions, as evidenced by moderately enhanced total soluble intracellular protein content, better protein stabilization, comparatively over-expressed HSPs, and relatively enhanced cell survival. These findings hold an opportunity for developing novel approaches towards enhancing microbial resilience in a variety of conditions, including industrial bioprocessing, environmental remediation, and infectious disease management.

Synthesis and characterization of Pyrus communis fruit extract synthesized ZnO NPs and assessed their anti-diabetic and anti-microbial potential.

The fruit Pyrus communis, owing to its presence of phenolics and flavonoids, was chosen for its nanoparticle's reducing and stabilizing properties. Furthermore, the zinc metal may be nano-absorbed by the human body. As a result, the study involves synthesizing zinc oxide nanoparticles (ZnO NPs) from P. communis fruit extract using the green method. The synthesized nanoparticle was examined with a UV-visible spectrophotometer, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS). When absorption studies were performed with a UV-visible spectrophotometer, the nanoparticle exhibited a blue shift. The FTIR spectrum revealed the molecular groups present in both the fruit extract and metal. In the SEM analysis, the ZnO NPs appeared as spherical particles, agglomerated together, and of nano-size. The larger size of the ZnO NPs in DLS can be attributed to their ability to absorb water. After characterization, nanoparticles were tested for anti-diabetic (α-amylase and yeast glucose uptake activity) and anti-microbial properties. The α-amylase inhibition percentage was 46.46 ± 0.15% for 100 µg/mL, which was comparable to the acarbose inhibition percentage of 50.58 ± 0.67% at the same concentration. The yeast glucose uptake activity was 64.24 ± 0.80% at 20 mM glucose concentration, which was comparable to the standard of 78.03 ± 0.80. The nanoparticle was more effective against Gram-negative bacteria Shigella sp. and Salmonella typhi than against Gram-positive bacteria Bacillus cereus and Streptococcus pneumoniae.

Distribution and Uniqueness in the Pattern of Lip Prints.

Introduction Lip prints are the characteristic pattern of wrinkles and grooves on the labial mucosa. Lip prints can be classified into various patterns and can be used for personal identification as they are unique and do not change during the life of a person. Cheiloscopy is a forensic investigation technique that deals with the identification of humans based on lip traces. Objectives This study aimed to investigate the distribution of lip print patterns, to assess gender differences, and to calculate the lip score using a weighted value scoring system. Material and methods A cross-sectional study was carried out in the Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Guwahati, India, from May to October 2023, after getting approval from the Institutional Ethics Committee (IEC). A total of 200 individuals (100 males and 100 females) were included in the study. Each lip print was divided into four quadrants. In each quadrant, up to 14 grooves were marked from the midline, and the pattern of each groove was observed. Each pattern was given an Arabic numeral score. Weighted values were given for the grooves in descending order from 15 to 1 with reference to their position from the midline of the lip print. The product of the Arabic numeral score of the groove and the weighted value of the groove is the lip line score. The sum of the lip line scores was calculated. Results The most common pattern observed in the present study is type II, with 3,816/12,000 (31.8%), followed by type I' with 3,146/12,000 (26.21%), type I with 1,865/12000 (15.54%), type III with 1,491/12,000 (12.42%), type IV with 1,133/12,000 (9.44%), and type V with 549/12,000 (4.5%). The mean total lip score is 1,467.68 (1,486.41 in males and 1448.96 in females). Conclusion Lip prints are unique and useful for personal identification, as the lip score in various quadrants and the total lip score are different for different individuals.

Benign paraspinal ganglioneuroma with paraneoplastic opsoclonus myoclonus syndrome.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare immune-mediated movement disorder occurring as a paraneoplastic manifestation of neuroblastic tumours (NTs), especially neuroblastoma in infancy. Ganglioneuroma (GN), the benign tumour in the spectrum, is rarely associated with OMAS. We report the case of a child in her second year of life presenting with acute onset of progressive paraplegia and OMAS. MRI showed diffuse and infiltrating left paraspinal mass from T3-T9 levels with differentials of neuroblastoma or ganglioneuroblastoma. Histopathological and immunohistochemistry examination of the excised tumour showed maturing GN. The OMAS was managed with intravenous immunoglobulin and steroids. In the 6-month follow-up, the child has a residual motor weakness with myelomalacia in neuroimaging. The case report substantiates the occurrence of OMAS as paraneoplastic manifestation in NTs, including benign, in children younger than 2 years with a female predilection.

Molecular data reveals a new genus of blindsnakes within Asiatyphlopinae from India.

The genus Indotyphlops has a widespread distribution in the Indian landmass and Southeast Asia, with 20 reported species. The current classification within the genus is based on morphology. In this study, we sampled all the reported Indotyphlops species from subcontinental India, to resolve relationships within this genus and to understand biogeographic patterns that resulted in the widespread distribution. We generated sequences for five nuclear markers which were used in the global typhlopoid phylogeny and built phylogenetic trees of the superfamily Typhlopoidea. We also carried out divergence time analysis and biogeographic analysis to understand the time and modes of dispersal and diversification of these species. The results show Indotyphlops sensu lato to be polyphyletic, with the clade consisting of I. porrectus and I. exiguus sister to a clade consisting of the southeast Asian typhlopid genera Ramphotyphlops, Anilios, Malayotyphlops, Acutotyphlops, Sundatyphlops, and Indotyphlops sensu stricto. The other clade consists of I. pammeces and I. braminus from the Indian subcontinent and I. albiceps from Southeast Asia. Biogeographical analysis suggests two dispersals from Asia to the Indian landmass-an earlier dispersal from Eurasia into India led to the lineage consisting of I. porrectus and I. exiguus, followed by a later dispersal that evolved into I. pammeces and I. braminus. These results necessitate a taxonomic revision. We propose the genus Pseudoindotyphlops gen. nov. for the clade currently consisting of the most recent common ancestor (MRCA) of I. porrectus and I. exiguus, and all descendants thereof.

All about being old and shooting hairs: clade age and urticating hair explain the patterns of diversification in tarantulas.

The extreme asymmetry of species richness distribution across the tree of life has always intrigued evolutionary biologists. Two competing explanations have been proposed to explain this pattern-the clade age hypothesis and diversification rate variation. While these two scenarios may not be mutually exclusive, to what extent time and diversification rates interact to explain species richness patterns remains understudied. Here, we investigate the relative influence of these two scenarios using tarantulas (Family: Theraphosidae) as a model. Tarantulas represent a speciose group of spiders found worldwide but exceptionally diverse in South America. These spiders show two distinct patterns of microhabitat use (ground-dwelling or arboreal) and defense strategies (presence or absence of urticating hairs). Using various trait-independent and dependent diversification models, we test the clade age hypothesis, the role of microhabitat, antipredator defense strategy, and geography in influencing diversification rates. Our results suggest that clade age is the primary predictor of species richness distribution across the tarantula subfamilies. However, the presence of urticating hair probably disrupted this pattern in some clades by increasing the net diversification rates, not by increasing the speciation rate but by reducing the extinction rate.

Physicochemical and antioxidant properties of tannic acid crosslinked cationic starch/chitosan based active films for ladyfinger packaging application.

In the present study, cationic starch (CS)/chitosan (CH) incorporated with tannic acid (TA)(CSCT) eco-friendly films were prepared by employing an inexpensive solvent casting technique. Influence of TA on the physicochemical and antimicrobial properties of CS/CH polymer matrix were studied. The FTIR findings and homogeneous, dense SEM micrographs confirms the effective interaction of TA with CS/CH polymer matrix. CSCT-3 active film displayed tensile strength of 26.99±1.91 MPa, which is more substantial than commercially available polyethylene (PE) (12-16 MPa) films. The active films exhibited excellent barrier properties against moisture and water, supported by increased water contact angle values (86.97±0.29°). Overall migration rate of active films was found to be below the permitted limit of 10mg/dm2. The active films showed around 56% of degradation in soil within 15 days. Besides, the active films showed concurring impact against food borne pathogens like E. coli, S. aureus and C. albicans. The CSCT-3 active film presented 90.83% of antioxidant capacity, demonstrating the effective prevention of food oxidation related deterioration. Ladyfinger packaging was inspected to examine the ability of active films as packaging material resulted in effectively resisting deterioration and extending shelf life in comparison with traditional PE packaging.

Exploring the role of natural bioactive molecules in genitourinary cancers: how far has research progressed?

The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard.

Fluorescent-Nanoparticle-Impregnated Nanocomposite Polymeric Gels for Biosensing and Drug Delivery Applications.

Nanocomposite polymeric gels infused with fluorescent nanoparticles have surfaced as a propitious category of substances for biomedical purposes owing to their exceptional characteristics. The aforementioned materials possess a blend of desirable characteristics, including biocompatibility, biodegradability, drug encapsulation, controlled release capabilities, and optical properties that are conducive to imaging and tracking. This paper presents a comprehensive analysis of the synthesis and characterization of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels, as well as their biomedical applications, such as drug delivery, imaging, and tissue engineering. In this discourse, we deliberate upon the merits and obstacles linked to these substances, encompassing biocompatibility, drug encapsulation, optical characteristics, and scalability. The present study aims to provide an overall evaluation of the potential of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels for biomedical applications. Additionally, emerging trends and future directions for research in this area are highlighted.

Evaluation of mechanical, antimicrobial, and antioxidant properties of vanillic acid induced chitosan/poly (vinyl alcohol) active films to prolong the shelf life of green chilli.

Vanillic acid incorporated chitosan/poly(vinyl alcohol) active films were prepared by employing a cost-effective solvent casting technique. FTIR investigation validated the intermolecular interaction and formation of Schiff's base (C=N) between functional groups of vanillic acid, chitosan, and poly(vinyl alcohol). The addition of vanillic acid resulted in homogenous and dense morphology, as confirmed by SEM micrographs. The tensile strength of active films increased from 32 to 59 MPa as the amount of vanillic acid increased and the obtained values are more significant than reported polyethylene (2231 MPa) and polypropylene (31-38 MPa) films, widely utilized in food packaging. Active film's UV, water, and oxygen barrier properties exhibited excellent results with the incorporation of vanillic acid. Around 40 % of degradation commences within 15 days. Synergistic impact against S. aureus, E. coli, and C. albicans pathogens caused the expansion of the inhibition zone, evidenced by the excellent antimicrobial activity. The highest antioxidant capacity, 73.65 % of CPV-4 active film, proved that active films could prevent the spoilage of food from oxidation. Green chillies packaging was carried out to examine the potential of prepared active films as packaging material results in successfully sustaining carotenoid accumulation and prolonging the shelf life compared to conventional polyethylene (PE) packaging.

The COSPAR Planetary Protection Policy for robotic missions to Mars: A review of current scientific knowledge and future perspectives.

Planetary protection guidance for martian exploration has become a notable point of discussion over the last decade. This is due to increased scientific interest in the habitability of the red planet with updated techniques, missions becoming more attainable by smaller space agencies, and both the private sector and governments engaging in activities to facilitate commercial opportunities and human-crewed missions. The international standards for planetary protection have been developed through consultation with the scientific community and the space agencies by the Committee on Space Research's (COSPAR) Panel on Planetary Protection, which provides guidance for compliance with the Outer Space Treaty of 1967. In 2021, the Panel evaluated recent scientific data and literature regarding the planetary protection requirements for Mars and the implications of this on the guidelines. In this paper, we discuss the COSPAR Planetary Protection Policy for Mars, review the new scientific findings and discuss the next steps required to enable the next generation of robotic missions to Mars.

Risk factors, clinical indicators, and pathological findings of abomasal ulcers in tropical dairy buffaloes.

The current study aimed at identifying the risk factors and initial diagnostic aids for abomasal ulcers. The risk factor analysis confirmed a significant association (P < 0.05) of abomasal ulcers with concentrate-rich diets (OR, 4.795; CI, 1.212-15.974) and concurrent disorders (OR, 2.978; CI, 0.987-8.980), while the buffaloes in early lactation (OR, 2.777; CI, 0.703-10.972) showed a higher tendency (P = 0.078) for the disorder. The depressed demeanour, dark or black manure (melena), anemia, tachycardia, decreased milk production, anorexia, tachypnea, absence of rumination, abdominal guarding, kyphosis, and tachypnea were the most frequent clinical signs. Subjecting the abomasal fluid for cultural isolation, gram staining, and stormy clot fermentation test identified the presence of clostridium perfringes, while screening through uniplex PCR detected cpa toxin. The buffaloes affected with type-3 and 4 abomasal ulcers exhibited a higher peritoneal fluid to serum ratio of total protein, albumin, and glucose with a low (P < 0.01) serum-ascites albumin gradient (SAAG) concentration compared to reference values of healthy buffaloes. The first two principal components of PCA explained 54.50% of the total variances with lymphocytes, creatine kinase, and rumen chloride levels as the top contributors to dimension I, and albumin, total protein, sodium, and methylene blue reduction time (MBRT) for rumen liquor as the major contributors to dimension II. The vector plot revealed lymphocytopenia, decreased hemoglobin, hypoalbuminemia, hypokalemia, decreased rumen pH, neutrophilia, eosinophilia, leucocytosis, greater MBRT, and higher rumen chloride, serum creatine kinase, and blood urea nitrogen as the major indicators for abomasal ulcers. Histopathological studies revealed infiltration of inflammatory cells in the mucosa along with multifocal areas of necrosis, degeneration, and eroded muscle structure. The study projected a few high-scored clinical signs and extremely variable clinical indicators as initial diagnostic aids of abomasal ulcers, which can be confirmed by ultrasonography and peritoneal fluid examination.

Role of paleoclimatic and paleohydrological processes in lineage divergence in freshwater organisms: A snippet from lentic genus Pila.

The Indian subcontinent is extremely diverse in terms of its flora and fauna. However, only a handful of studies have aimed to understand the diversity of freshwater invertebrates using multiple lines of evidence in recent times. Here we aimed to estimate the cryptic diversity of two widespread freshwater snail species within the genus Pila (Röding, 1798) and uncover the processes behind lineage diversification in these species. We sequenced mitochondrial and nuclear markers from a comprehensive sampling of specimens from different river basins in India. We implemented an integrative taxonomy approach to delimit the lineages in these groups, employing phylogenetic, geometric morphometric and niche modelling-based methods. Then, we investigated the drivers of lineage divergence in these species using population genetic tools in conjunction with divergence time estimation. We found that both species consist of several genetically and ecologically distinct lineages. The genetic data showed that several of these lineages are restricted to a single or a few river basins. The divergence time estimation analyses indicated that the time frame of divergence within the species coincided with paleohydrological and paleoclimatic events in the Miocene. The diversification was primarily driven by allopatric isolation into different river basins. To conclude, the study sheds light on the complex interaction between the habitat preference of the species and the environment in shaping the diversification patterns in this group.

Abomasal impaction in buffaloes: Risk factors, clinical indicators, necropsy findings, and histology studies.

The present study aims to identify potential risk factors and most possible clinical indicators of abomasal impaction in buffaloes. Among the screened buffaloes (n = 636), the logistic model was fitted for 491 buffaloes because of the non-availability of parity-related data for 145 buffaloes. Third-trimester pregnancy, feeding paddy straw alone, and concurrent disorders were identified as the potential risk factors using multivariate regression analysis. The buffaloes reared by farmers devoid of land tended to have a higher incidence of abomasal impaction. Depressed demeanour, absence of rumination, abdominal guarding, scleral congestion, sunken eyeballs, anorexia, reduced dung output, abacus beads-like faeces, colic signs (straining to defecate, frequent lying down, and kicking at abdomen), tachypnea, and tachycardia were the most repeatedly noticed clinical signs in buffaloes diagnosed with abomasal impaction. Further, the principal component analysis revealed increased rumen fluid sedimentation time and chloride content, serum creatine phosphokinase, and blood neutrophil and eosinophil content along with decreased blood lymphocytes proportion, potassium, and chloride as the greatest indicators for abomasal impaction. Next to them, a higher rumen fluid methylene blue reduction time, serum urea nitrogen, and blood total leucocyte count, along with a lower serum albumin and blood haemoglobin were the best possible indicators for diagnosis. The necropsy findings of the buffaloes that died with abomasal disorders revealed an abomasum with increased dimensions and constant pitting on pressure. Furthermore, the histopathological studies showed degeneration and necrosis of the abomasal wall with infiltrated mononuclear cells. The results of the study help in designing a comprehensive evaluation mechanism for diagnosing abomasal impaction in buffaloes.

A novel family of small molecule HIF-1 alpha stabilizers for the treatment of diabetic wounds; an integrated in silico, in vitro, and in vivo strategy.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a crucial regulator of wound healing, which includes epithelialization, angiogenesis, granulation, tissue development, and wound contraction. Even though diabetic wounds are hypoxic, HIF-1α levels are decreased during healing. Diabetic wound healing necessitates the modulation of hypoxia-induced responses by VHL-HIF-1α protein-protein inhibition. Our proposed hypothesis is to increase HIF-1α levels by inhibiting VHL and HIF-1α interactions by novel small bioactive molecules, accelerating diabetic wound healing. A three features (two aromatic rings and one hydrogen bond acceptor) pharmacophore hypothesis was generated from the existing HIF-1α modulators. Virtual screening was done based on the generated pharmacophore, and a library consisting of the top 20 out of 3728 compounds was selected using ZINCPharmer. Of the top 20 molecules, the pyrazole moiety was identified as the top "HIT". Five analogues of pyrazole were designed, and Scifinder ascertained the novelty. The designed compounds were synthesized and characterized by IR, Mass, and NMR. Preliminarily, we have carried out a scratch wound assay using 3T3L1 cell lines. All the synthesized compounds showed significant wound healing activity. Further, to validate the in vitro assay, the compound CI, which showed effective in vitro results was used for in vivo study. Using the diabetes mouse model, comprising streptozotocin-induced (STZ) diabetic mice and scratch wound assay, we demonstrated that inhibiting the VHL and HIF-1α connection is a promising strategy for treating diabetic ulcers. Molecules CI and CP were found to have substantial in silico, in vitro, and in vivo outcomes.

Technology, Megatrends and Work: Thoughts on the Future of Business Ethics.

To commemorate 40 years since the founding of the Journal of Business Ethics, the editors in chief of the journal have invited the editors to provide commentaries on the future of business ethics. This essay comprises a selection of commentaries aimed at creating dialogue around the theme Technology, Megatrends and Work. Of all the profound changes in business, technology is perhaps the most ubiquitous. There is not a facet of our lives unaffected by internet technologies and artificial intelligence. The Journal of Business Ethics established a dedicated section that focuses on Technology and Business Ethics, yet issues related to this phenomenon run right through all the sections. Kirsten Martin, editor of the Technology and Business Ethics section, joins our interim social media editor, Hannah Trittin-UIbrich, to advance a human-centric approach to the development and application of digital technologies that places Business Ethics at centre of the analysis. For Shuili Du, technology is the defining condition for a new era of Corporate Social Responsibility-CSR 3.0-which she defines as "a company's socially responsible strategies and practices that deal with key ethical and socio-technical issues associated with AI and related technologies on the one hand and leverage the power of AI and related technologies to tackle social and environmental problems on the other hand." It is not just technologies that are a determining feature of our lives but technology companies, an argument made by Glen Whelan as he examines Big Business and the need for a Big Business Ethics as we try to understand the impact of Big Tech on our post-work world. Indeed, as noted by Ernesto Noronha and Premilla D'Cruz, megatrends in addition to advancement in technologies, namely globalization, the greening of economies, and changes in demographics and migration, are shaping the future for workers in ways previously unimaginable. Contributing to this important debate, Praveen Parboteeah considers the influence of another longstanding but oft overlooked megatrend, the role of religion in the workplace. Given the enormity of the influence of technology and other megatrends in our world, it is not surprising that this essay introduces ground-breaking ideas that speak to the future of business ethics research.

Comparative assessment of cognitive impairment and oxidative stress markers among vitamin D insufficient elderly patients with and without type 2 diabetes mellitus (T2DM).

BACKGROUND: Disorders of mental health are known to affect cognitive functions, hence called as cognitive disorders. Impaired glucose metabolism, insulin resistance, vitamin-D deficiency and oxidative stress are some of the key early events reported to be involved in the pathogenesis of most common cognitive disorders, which include Alzheimer's disease. Type-2 diabetes mellitus (T2DM) is one of the known contributing factors of cognitive impairment and dementia. METHODS: A cross sectional study was carried out in 145 subjects, who were assessed for cognitive function by modified mini mental status examination (3MS). In addition, measurement of fasting blood sugar (FBS), fasting insulin, HbA1c, lipid profile, vitamin D and oxidative markers was performed. Participants were divided into different groups based on (a) vitamin D insufficiency and sufficiency; (b) diabetic and non-diabetic with and without cognitive impairment. RESULTS: The study included a total of 145 subjects; 51 males and 94 females and the mean age was 68.24±9.70 years. Among diabetics with vitamin D insufficiency, 35 subjects (71.43%) had cognitive impairment, but, among non-diabetics with vitamin D insufficiency, 27 subjects (62.79%) had cognitive impairment. Chi square test showed no significant association between diabetes, vitamin D insufficiency and cognitive impairment. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels were non-significantly lower in cognition-impaired subjects, when compared to cognition normal subjects in diabetics with vitamin D insufficiency. CONCLUSION: Our study showed that cognitive impairment is more predominant in individuals with diabetes. However, our study did not find any significant relationship between T2DM, vitamin D deficiency, cognitive impairment, and oxidative stress. A significant association was found only with GPx and 3MSE score in vitamin D insufficient non-diabetics.

Multi-staged gene expression profiling reveals potential genes and the critical pathways in kidney cancer.

Cancer is among the highly complex disease and renal cell carcinoma is the sixth-leading cause of cancer death. In order to understand complex diseases such as cancer, diabetes and kidney diseases, high-throughput data are generated at large scale and it has helped in the research and diagnostic advancement. However, to unravel the meaningful information from such large datasets for comprehensive and minute understanding of cell phenotypes and disease pathophysiology remains a trivial challenge and also the molecular events leading to disease onset and progression are not well understood. With this goal, we have collected gene expression datasets from publicly available dataset which are for two different stages (I and II) for renal cell carcinoma and furthermore, the TCGA and cBioPortal database have been utilized for clinical relevance understanding. In this work, we have applied computational approach to unravel the differentially expressed genes, their networks for the enriched pathways. Based on our results, we conclude that among the most dominantly altered pathways for renal cell carcinoma, are PI3K-Akt, Foxo, endocytosis, MAPK, Tight junction, cytokine-cytokine receptor interaction pathways and the major source of alteration for these pathways are MAP3K13, CHAF1A, FDX1, ARHGAP26, ITGBL1, C10orf118, MTO1, LAMP2, STAMBP, DLC1, NSMAF, YY1, TPGS2, SCARB2, PRSS23, SYNJ1, CNPPD1, PPP2R5E. In terms of clinical significance, there are large number of differentially expressed genes which appears to be playing critical roles in survival.

Discovery of potential inhibitors for stat3: ligand based 3D pharmacophore, virtual screening, molecular docking, dynamic studies and in vitro evaluation.

A large analysis of the signal transducer and activator of transcription (STAT3) in cancer is currently being carried out. It regulates gene expression, which is required for normal cellular functions such as differentiation, cell growth, proliferation, survival, maturation, and immunity. A ligand-based pharmacophore model was created using 3 D QSAR pharmacophore generation methodology in Discovery studio 4.1 clients to imagine structurally diverse novel chemical entities as STAT3 inhibitors with improved efficacy. Chemical properties of 48 different derivatives were included in the training package. Hypo1 was chosen as the query model for screening 1,45,000 drug-like molecules from the SPECS database, with these molecules subjected to the Lipinski rule of 5, Verber's rule, and SMART filtration. After filtration, the molecule was examined further using molecular docking analysis on the active site of STAT3. The binding interaction(s) and pharmacophore mapping were used to select the 19 possible inhibitory molecules. These 19 hits were then tested for toxicity using the TOPKAT software. In MD simulations and MM-PBSA calculations, the tested compound specs 28 provided the best results, suggesting that this ligand has the ability to inhibit more effectively. Based in-silico finding 19 compounds are subjected to in vitro anticancer activity against MDA-MB-231 and MCF-7 cell lines. Based on results compounds specs 11 and specs 13 shows significant activity compared to other compounds and these compounds were subjected to apoptosis assay. The tested compounds induced morphologic changes were dose and time dependent by which all the tested compound exhibits stronger anti-tumor effects.Communicated by Ramaswamy H. Sarma.

Spatial patterns of phylogenetic diversity and endemism in the Western Ghats, India: A case study using ancient predatory arthropods.

The Western Ghats (WG) mountain chain in peninsular India is a global biodiversity hotspot, one in which patterns of phylogenetic diversity and endemism remain to be documented across taxa. We used a well-characterized community of ancient soil predatory arthropods from the WG to understand diversity gradients, identify hotspots of endemism and conservation importance, and highlight poorly studied areas with unique biodiversity. We compiled an occurrence dataset for 19 species of scolopendrid centipedes, which was used to predict areas of habitat suitability using bioclimatic and geomorphological variables in Maxent. We used predicted distributions and a time-calibrated species phylogeny to calculate taxonomic and phylogenetic indices of diversity, endemism, and turnover. We observed a decreasing latitudinal gradient in taxonomic and phylogenetic diversity in the WG, which supports expectations from the latitudinal diversity gradient. The southern WG had the highest phylogenetic diversity and endemism, and was represented by lineages with long branch lengths as observed from relative phylogenetic diversity/endemism. These results indicate the persistence of lineages over evolutionary time in the southern WG and are consistent with predictions from the southern WG refuge hypothesis. The northern WG, despite having low phylogenetic diversity, had high values of phylogenetic endemism represented by distinct lineages as inferred from relative phylogenetic endemism. The distinct endemic lineages in this subregion might be adapted to life in lateritic plateaus characterized by poor soil conditions and high seasonality. Sites across an important biogeographic break, the Palghat Gap, broadly grouped separately in comparisons of species turnover along the WG. The southern WG and Nilgiris, adjoining the Palghat Gap, harbor unique centipede communities, where the causal role of climate or dispersal barriers in shaping diversity remains to be investigated. Our results highlight the need to use phylogeny and distribution data while assessing diversity and endemism patterns in the WG.