MOTIVATION: Molecular dynamics (MD) is a computational experiment that is crucial for understanding the structure of biological macro and micro molecules, their folding, and the inter-molecular interactions. Accurate knowledge of these structural features is the cornerstone in drug development and elucidating macromoolecules functions. The open-source GROMACS biomolecular MD simulation program is recognized as a reliable and frequently used simulation program for its precision. However, the user requires expertise, and scripting skills to carrying out MD simulations. RESULTS: We have developed an end-to-end interactive MD simulation application, MolDy for Gromacs. This front-end application provides a customizable user interface integrated with the Python and Perl-based logical backend connecting the Linux shell and Gromacs software. The tool performs analysis and provides the user with simulation trajectories and graphical representations of relevant biophysical parameters. The advantages of MolDy are (1) user-friendly, does not requiring the researcher to have prior knowledge of Linux; (2) easy installation by a single command; (3) freely available for academic research; (4) can run with minimum configuration of operating systems; (5) has valid default prefilled parameters for beginners, and at the same time provides scope for modifications for expert users. AVAILABILITY: MolDy is available freely as compressed source code files with user manual for installation and operation on GitHub: https://github.com/AIBResearchMolDy/Moldyv01.git and on https://aibresearch.com/innovations. SUPPLEMENTARY INFORMATION: Supplementary data is available at Bioinformatics online.
Recent research has provided crucial insights on regional heatwaves, including their causal mechanisms and changes under global warming. However, detailed research on global-scale spatially compound heatwaves (SCHs) (concurrent heatwaves over multiple regions) is lacking. Here, we find statistically significant teleconnections in heatwaves and show that the frequency of global-scale SCHs and their areal extent have increased significantly, which has led to 50 % increase in the population exposed to extreme heat stresses in the two most recent decades. Crop yields were reduced in most of the years of anomalous heatwaves, which often happen during El-Niños. The internal climate variability appears to significantly influence the inter-annual variability of regional and global heatwave extents. Insights gained here are critical in better quantifying heat stress risks inflicted on socioecological systems.
Extreme Heat , Global Warming , Climate Change , Crop Production/methods , Humans , Hot Temperature , Crops, Agricultural/growth & development
This paper reports the effect of incorporation of Yb3+ions on the frequency downconversion luminescence and thermal properties of triply ionised Ho3+doped zinc tellurite (TZ) glasses. The photoluminescence spectra of both the Ho3+/Yb3+doped and codoped glasses have been recorded and observed a green emission band corresponding to the5F4,5S2â5I8(â¼550 nm) transition upon various excitations. In the downconversion (DC) emission process, the back energy transfer (BET) mechanism from Ho3+ions to Yb3+ions has also been explored. The colour emitted in the downconversion process is found to be non-tunable at different excitations. Thus, the Ho3+:TZ glass can be utilised for non-colour tunable optical devices under various UV excitations. Also the glass transition (Tg) and crystallisation (Tc) temperatures have been measured for both the doped and codoped glasses and found to be increased in the codoped glass. The singly Ho3+ions doped TZ glass shows better optical downconversion and glass forming ability.
The Enterobacterales order is a massive group of Gram-negative bacteria comprised of pathogenic and nonpathogenic members, including beneficial commensal gut microbiota. The pathogenic members produce several pathogenic or virulence factors that enhance their pathogenic properties and increase the severity of the infection. The members of Enterobacterales can also develop resistance against the common antimicrobial agents, a phenomenon called antimicrobial resistance (AMR). Many pathogenic Enterobacterales members are known to possess antimicrobial resistance. This review discusses the virulence factors, pathogenicity, and infections caused by multidrug-resistant Enterobacterales, especially E. coli and some other bacterial species sharing similarities with the Enterobacterales members. We also discuss both conventional and modern approaches used to combat the infections caused by them. Understanding the virulence factors produced by the pathogenic bacteria will help develop novel strategies and methods to treat infections caused by them.
An important public health problem in India is dengue infection, with every year seeing an increase in cases of dengue fever. Dengue affects all individuals irrespective of their gender and age, although the infection rate is higher among males and younger people. Despite low severity in general, dengue virus can cause severe health conditions in some individuals. Genetic characterization of circulating endemic dengue virus (DENV) serotypes plays a significant role in providing epidemiological knowledge and subsequent vaccine development. In the present study, over a 4 year period, we assessed DENV transmission dynamics in major regions of western Uttar Pradesh in North India. ELISA tests were used to diagnose dengue, and PCRs were used to determine the circulating serotype. We found that dengue infection peaks after the rainy season and affects all sexes and ages. A total of 1277 individuals were found positive for dengue; among them, 61.7â% were male and 38.3â% were female. DEN-1 was found in 23.12â%, DEN-2 in 45â%, DEN-3 in 29.06â% and DEN-4 in 1.5â% of the dengue-infected individuals. All four DENV serotypes were circulating in the study area, and DENV serotype-2 (DEN-2) was the most prevalent serotype.
Inflammation and oxidative stress are interrelated processes that represent the underlying causes of several chronic inflammatory diseases that include asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), allergies, diabetes, and cardiovascular diseases. Macrophages are key initiators of inflammatory processes in the body. When triggered by a stimulus such as bacterial lipopolysaccharides (LPS), these cells secrete inflammatory cytokines namely TNF-α that orchestrate the cellular inflammatory process. Simultaneously, pro-inflammatory stimuli induce the upregulation of inducible nitric oxide synthase (iNOS) which catalyzes the generation of high levels of nitric oxide (NO). This, together with high concentrations of reactive oxygen species (ROS) produced by macrophages, mediate oxidative stress which, in turn, exacerbates inflammation in a feedback loop, resulting in the pathogenesis of several chronic inflammatory diseases. Berberine is a phytochemical embedded with potent in vitro anti-inflammatory and antioxidant properties, whose therapeutic application is hindered by poor solubility and bioavailability. For this reason, large doses of berberine need to be administered to achieve the desired pharmacological effect, which may result in toxicity. Encapsulation of such a drug in liquid crystalline nanoparticles (LCNs) represents a viable strategy to overcome these limitations. We encapsulated berberine in phytantriol-based LCNs (BP-LCNs) and tested the antioxidant and anti-inflammatory activities of BP-LCNs in vitro on LPS-induced mouse RAW264.7 macrophages. BP-LCNs showed potent anti-inflammatory and antioxidant activities, with significant reduction in the gene expressions of TNF-α and iNOS, followed by concomitant reduction of ROS and NO production at a concentration of 2.5 µM, which is lower than the concentration of free berberine concentration required to achieve similar effects as reported elsewhere. Furthermore, we provide evidence for the suitability for BP-LCNs both as an antioxidant and as an anti-inflammatory agent with potential application in the therapy of chronic inflammatory diseases.
Since their discovery, MXenes have conferred various intriguing features because of their distinctive structures. Focus has been placed on using MXenes in electrochemical energy storage including a supercapacitor showing significant and promising development. However, like other 2D materials, MXene layers unavoidably experience stacking agglomeration because of its great van der Waals forces, which causes a significant loss of electrochemically active sites. With the help of MoS2, a better MXene-based electrodecan is planned to fabricate supercapacitors with the remarkable electrochemical performance. The synthesis of MXene/MoS2 and the ground effects of supercapacitors are currently being analysed by many researchers internationally. The performance of commercial supercapacitors might be improved via electrode architecture. This analysis will support the design of MXene and MoS2 hybrid electrodes for highly effective supercapacitors. Improved electrode capacitance, voltage window and energy density are discussed in this literature study. With a focus on the most recent electrochemical performance of both MXene and MoS2-based electrodes and devices, this review summarises recent developments in materials synthesis and its characterisation. It also helps to identify the difficulties and fresh possibilities MXenes MoS2 and its hybrid heterostructure in this developing field of energy storage. Future choices for constructing supercapacitors will benefit from this review. This review examines the newest developments in MXene/MoS2 supercapacitors, primarily focusing on compiling literature from 2017 through 2022. This review also presents an overview of the design (structures), recent developments, and challenges of the emerging electrode materials, with thoughts on how well such materials function electrochemically in supercapacitors.
Background: Biofilm formation is a complex phenomenon, and it is the causative agent of several human infections. Bacterial amyloids are involved in biofilm formation leading to infection persistence. Due to antibiotic resistance, their treatment is a great challenge for physicians. Probiotics, especially E. coli Nissle 1917 (EcN), are used to treat human intestinal disorders and ulcerative colitis. It also expresses virulence factors associated with biofilm and amyloid formation. EcN produces biofilm equivalent to the pathogenic UPEC strains. Methods: CRISPRi was used to create the knockdown mutants of the csgD gene (csgD-KD). The qRT-PCR was performed to assess the expression of the csgD gene in csgD-KD cells. The csgD-KD cells were also evaluated for the expression of csgA, csgB, fimA, fimH, ompR, luxS, and bolA genes. The gene expression data obtained was further confirmed by spectroscopic, microscopic, and other assays to validate our study. Results: CRISPRi-mediated knockdown of csgD gene shows reduction in curli amyloid formation, biofilm formation, and suppression of genes (csgA, csgB, fimA, fimH, ompR, bolA, and luxS) involved in virulence factors production. Conclusion: Curli amyloid fibers and fimbriae fibers play a critical role in biofilm formation leading to pathogenicity. CsgD protein is the master regulator of curli synthesis in E. coli. Hence, curli amyloid inhibition through the csgD gene may be used to improve the EcN and different probiotic strains by suppressing virulence factors.
Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, which is a leading cause of cancer-related deaths worldwide. Berberine is an isoquinoline alkaloid that is commercially available for use as a supplement for the treatment of diabetes and cardiovascular diseases. However, the therapeutic benefits of berberine are limited by its extremely low bioavailability and toxicity at higher doses. Increasing evidence suggests that the incorporation of drug compounds in liquid crystal nanoparticles provides a new platform for the safe, effective, stable, and controlled delivery of the drug molecules. This study aimed to formulate an optimized formulation of berberine-phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line. The BP-LCN formulation possessing optimal characteristics that was used in this study had a favorable particle size and entrapment efficiency rate (75.31%) and a superior drug release profile. The potential mechanism of action of the formulation was determined by measuring the mRNA levels of the tumor-associated genes PTEN, P53, and KRT18 and the protein expression levels with a human oncology protein array. BP-LCNs decreased the proliferation, migration, and colony-forming activity of A549 cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18. Similarly, BP-LCNs also decreased the expression of proteins related to cancer cell proliferation and migration. This study highlights the utility of phytantriol-based LCNs in incorporating drug molecules with low GI absorption and bioavailability to increase their pharmacological effectiveness and potency in NSCLC.
Biofilm plays an important role in the community and hospital-acquired infections. Especially E. coli biofilm that contributes towards the significant part of medical devices associated with microbial infections. OmpR/EnvZ, a two-component system, is one of the regulatory mechanisms involved in transcription regulation in response to environmental osmolarity changes. The main objective of this study was to elucidate the role of the OmpR/EnvZ two-component system in regulating the biofilm through curli and fimbriae (FimH gene), a contrary approach towards biofilm inhibition. In this study, the CRISPRi technique was used to suppress the expression of the OmpR gene. The RT-PCR assay was performed to quantify mRNA gene expression of curli and biofilm producing genes, and the data were further confirmed by different microscopic, spectroscopic and biofilm quantification assay (Crystal Violet). It is the first time we have shown downregulation of the OmpR gene in biofilm causing clinical isolates of E. coli, which further suppressed the FimH gene, leading to biofilm reduction. The crystal violet assay and microscopic studies also confirmed the biofilm reduction. We conclude that the OmpR gene of the OmpR/EnvZ two-component system could be one of the targets for biofilm mediated infection intervention. Our findings open new vistas to explore the pathways and targets to control biofilm mediated infections.
Escherichia coli Proteins , Escherichia coli , Bacterial Proteins/genetics , Biofilms , Clustered Regularly Interspaced Short Palindromic Repeats , Escherichia coli/genetics , Escherichia coli Proteins/genetics
BACKGROUND: Reverse transcriptase is an important therapeutic target to treat AIDS caused by the Human Immunodeficiency Virus (HIV). Despite many effective anti-HIV drugs, reverse transcriptase (RT) inhibitors remain the cornerstone of the drug regimen to treat AIDS. In the present work, we have expedited the use of different computational modules and presented an easy, costeffective, and high throughput screening method to identify potential reverse transcriptase inhibitors. METHODS: A congeneric series of 4-Arylthio & 4-Aryloxy-3- Iodopyridine-2(1H)-one analogs having anti-HIV activity were subjected to structure-based 2D, 3D QSAR, Pharmacophore Modeling, and Molecular Docking to elucidate the structural properties required for the design of potent HIV-RT inhibitors. Prediction of preliminary Pharmacokinetic and the Drug Likeliness profile was performed for these compounds by in silico ADME study. RESULTS: The 2D and 3D- QSAR models were developed by correlating two and three-dimensional descriptors with activity (pIC50) by sphere exclusion method and k-nearest neighbor molecular field analysis approach, respectively. The significant 2D- QSAR model developed by Partial Least Square is associated with the Sphere Exclusion method (PLS-SE), having r2 and q2 values 0.9509 and 0.8038, respectively. The 3D-QSAR model by Step Wise variable selection method (SW-kNN MFA) is more significant, which has a cross-validated squared correlation coefficient q2= 0.8509 and a non-crossvalidated correlation coefficient pred_r2= 0.8102. The pharmacophore hypothesis was developed, which comprised 5 features includes 3 aliphatic regions (Ala), 1 H-bond donor (HDr) and 1 H-bond acceptor (HAc). Docking studies of the selected inhibitors with the active site of reverse transcriptase enzyme showed hydrogen bond and π - π interaction with LYS-101, LYS-103, TYR- 181, TYR-188 and TRP-229 residues present at the active site. All the candidates with good bioavailability and ADMET drug likeliness properties. CONCLUSION: The results of the present work provide more useful information and important structural insights for the discovery, design of novel and potent reverse transcriptase inhibitors with high therapeutic windows in the future.
Anti-HIV Agents , Reverse Transcriptase Inhibitors , Anti-HIV Agents/pharmacology , HIV Reverse Transcriptase , Humans , Molecular Docking Simulation , Quantitative Structure-Activity Relationship , Reverse Transcriptase Inhibitors/pharmacology
Cryptococcus neoformans infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in the treatment of C. neoformans in cyclophosphamide injected leukopenic mice. A liposomal formulation of ellagic acid (Lip-EA) was prepared and characterized, and its antifungal activity was assessed in comparison to fluconazole (FLZ). The efficacy of the drug treatment was tested by assessing survival rate, fungal burden, and histological analysis in lung tissues. The safety of the drug formulations was tested by investigating hepatic, renal function, and antioxidant levels. The results of the present work demonstrated that Lip-EA, not FLZ, effectively eliminated C. neoformans infection in the leukopenic mice. Mice treated with Lip-EA (40 mg/kg) showed 70% survival rate and highly reduced fungal burden in their lung tissues, whereas the mice treated with FLZ (40 mg/kg) had 20% survival rate and greater fungal load in their lungs. Noteworthy, Lip-EA treatment alleviated cyclophosphamide-induced toxicity and restored hepatic and renal function parameters. Moreover, Lip-EA treatment restored the levels of superoxide dismutase and reduced glutathione and catalase in the lung tissues. The effect of FLZ or EA or Lip-EA against C. neoformans infection was assessed by the histological analysis of lung tissues. Lip-EA effectively reduced influx of inflammatory cells, thickening of alveolar walls, congestion, and hemorrhage. The findings of the present study suggest that Lip-EA may prove to be a promising therapeutic formulation against C. neoformans in immunocompromised persons.
Understanding the response of Himalayan-Karakoram (HK) rivers to climate change is crucial for ~1 billion people who partly depend on these water resources. Policy-makers tasked with sustainable water resources management require an assessment of the rivers' current status and potential future changes. We show that glacier and snow melt are important components of HK rivers, with greater hydrological importance for the Indus basin than for the Ganges and Brahmaputra basins. Total river runoff, glacier melt, and seasonality of flow are projected to increase until the 2050s, with some exceptions and large uncertainties. Critical knowledge gaps severely affect modeled contributions of different runoff components, future runoff volumes, and seasonality. Therefore, comprehensive field observation-based and remote sensing-based methods and models are needed.
BACKGROUND: Azoles are the most common antifungal drugs used in the treatment of vulvovaginal candidiasis (VVC). The frequency of azole-resistant Candida isolates has increased dramatically in the last two decades. Here, we assessed the antifungal activity of a combination of fluconazole (FLZ) and methanolic extract of ginger (Meth-Gin) against drug-resistant vulvovaginal candidiasis (VVC) in a murine model. METHODS: The in vitro activity of FLZ or a combination of FLZ and Meth-Gin was determined against Candida albicans by the agar well diffusion, macrodilution, time-kill and the biofilm eradication methods. The therapeutic efficacy of the formulations was assessed by analyzing the fungal load, pro-inflammatory cytokines, percent apoptotic cells and the histological changes in the vaginal tissues of the mice. Moreover, the renal toxicity the drug formulation was evaluated by analyzing the levels of the blood urea nitrogen (BUN) and creatinine. RESULTS: The results of in vitro study demonstrated that FLZ did not show any activity against C. albicans, whereas a combination of FLZ and Meth-Gin demonstrated greater activity as shown by the data of the zone of growth inhibition, MIC and time-kill assay. FLZ or Meth-Gin treatment could not completely cure VVC, whereas a combination of FLZ and Meth-Gin was greatly effective in the treatment of VVC. The vaginal tissue from mice of the infected control group had the highest fungal load of 155370 ± 20617 CFUs. Treatment with FLZ at a dose of 40 mg/kg reduced the fungal load to 120863 ± 10723 CFUs. Interestingly, the mice treated with a combination of FLZ (40 mg/kg) and Meth-Gin (200 mg/kg) had a fungal load of 256 ± 152 CFUs. Besides, FLZ and Meth-Gin combination effectively reduced the pro-inflammatory cytokines (IL-1ß, TNF-α and IL-17) and the percentage of apoptotic cells in the vaginal tissues. Likewise, the histological analysis revealed the epithelial necrosis, shedding and ulceration in the vaginal tissue, whereas treatment with FLZ and Meth-Gin combination reversed the histopathological changes in the vaginal epithelium and lamina propria. CONCLUSION: The findings of the current study suggest that the co-administration of Meth-Gin and FLZ may have a potential therapeutic effect in the treatment of azole-resistant candidiasis.
Dengue fever is a mosquito-borne disease that affects nearly 3.9 billion people globally. Dengue remains endemic in Malaysia since its outbreak in the 1980's, with its highest concentration of cases in the state of Selangor. Predictors of dengue fever outbreaks could provide timely information for health officials to implement preventative actions. In this study, five districts in Selangor, Malaysia, that demonstrated the highest incidence of dengue fever from 2013 to 2017 were evaluated for the best machine learning model to predict Dengue outbreaks. Climate variables such as temperature, wind speed, humidity and rainfall were used in each model. Based on results, the SVM (linear kernel) exhibited the best prediction performance (Accuracy = 70%, Sensitivity = 14%, Specificity = 95%, Precision = 56%). However, the sensitivity for SVM (linear) for the testing sample increased up to 63.54% compared to 14.4% for imbalanced data (original data). The week-of-the-year was the most important predictor in the SVM model. This study exemplifies that machine learning has respectable potential for the prediction of dengue outbreaks. Future research should consider boosting, or using, nature inspired algorithms to develop a dengue prediction model.
Dengue/epidemiology , Disease Outbreaks/prevention & control , Forecasting/methods , Aedes , Algorithms , Animals , Climate , Humans , Incidence , Machine Learning , Malaysia/epidemiology , Mosquito Vectors/pathogenicity , Seasons , Temperature , Vector Borne Diseases/prevention & control
In this study, we investigated the therapeutic efficacy of a combination of liposomal amphotericin B (Lip-Amp B) and Methylglyoxal (Lip-MG) against Candida albicans in the leukopoenic mice. The antifungal efficacy of Lip-Amp B or Lip-MG or a combination of Lip-Amp B and Lip-MG was evaluated by the analysis of the survival rate and the fungal load in the treated mice. The immune-stimulatory effect of Lip-MG on macrophages was evaluated by analysing the secretion of proinflammatory cytokines. C. albicans infected mice treated at the doses of 1 and 2 mg/kg of Lip-Amp B showed 20% and 50% survival rates, respectively. Whereas the mice treated with free Amp B at the same doses died within 40 days of treatment. Interestingly, C. albicans infected mice treated with a combination of Lip-Amp B and Lip-MG had 70% survival rate on day 40 postinfection. Moreover, treatment of macrophages with Lip-MG increased their fungicidal activity and the secretion of proinflammatory cytokines, including TNF-α and IL-1ß. These findings suggested that co-treatment with Lip-Amp B and Lip-MG had a synergistic effect and could be effective against C. albicans in immunocompromised subjects.
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Candida albicans/drug effects , Leukopenia/drug therapy , Pyruvaldehyde/administration & dosage , Animals , Candida albicans/physiology , Drug Therapy, Combination , Female , Leukopenia/immunology , Leukopenia/pathology , Liposomes , Mice , Mice, Inbred BALB C
BACKGROUND: Biofilm formation is a complex phenomenon of bacterial cells, involved in several human infections. Its formation is regulated and controlled by several protein factors. The BolA-like proteins (bolA gene) are conserved in both prokaryotes and eukaryotes. The BolA protein is a transcription factor involved in bacterial cell motility and biofilm formation. This study was initiated to elucidate the role of the bolA gene in the curli biogenesis and amyloid production as well as to observe changes in the expression of fimH, a fimbriae gene. METHODS: Knockdown mutants of Escherichia coli MG1655 bolA gene (bolA-KD) were generated using CRISPR interference. The results obtained, were validated through gene expression using RT-PCR, microscopic analysis and different biofilm and amyloid assays. RESULTS: The bolA knockdown mutants showed a decrement in curli amyloid fibers, in fimbriae production and biofilm formation. We have also observed a reduction in EPS formation, eDNA production and extracellular protein content. Gene expression data showed that bolA downregulation caused the suppression of csgA and csgD of curli that led to the reduction in curli fiber and the amyloid formation and also the suppression of fimH, leading to the loss of fimbriae. CONCLUSIONS: Curli fibers and fimbriae are found to be involved in biofilm formation leading to the pathogenicity of the bacterial cell. BolA is a conserved protein and is found to play a significant role in curli and fimbriae formation in E. coli. This study further proved that CRISPRi mediated suppression of the bolA gene leads to inhibition of biofilm formation through curli and fimbriae inhibition. Hence, it may be proposed as a possible target for intervention of biofilm mediated infections.
Antimicrobial resistance is becoming a growing health problem, which has become a challenge for the physicians to control infection and also an economic burden on the healthcare. This increase in resistance to the present antimicrobial agents led the researchers to find some alternative and more efficient drugs which can fight with the resistant microorganisms more effectively. Hence, in silico approach is used to design some novel drugs against various targets of microorganisms. For effective virtual screening of the drugs, there is a need to know about the chemical structure and properties of the antimicrobial agents. Therefore, we have prepared a comprehensive database as a platform for the researcher to search for possible lead molecules. Antimicrobial chemotherapeutics database (ACD) is comprised of ~4100 synthetic antimicrobial compounds as well as ~1030 active antimicrobial peptides. The Antimicrobial peptides are mainly from biological sources but some of them are synthetic in nature. Only those compounds, which are found to be active against either bacteria (both Gram-positive and negative) or fungus, are selected for this database.The ACD database is freely available at URL: http://amdr.amu.ac.in/acd, and it is compatible with desktops, smartphones, and tablets.
Anti-Infective Agents , Computer Simulation , Databases, Pharmaceutical , Gram-Negative Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/drug therapy , Mycoses/drug therapy , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/therapeutic use , Drug Evaluation, Preclinical , Fungi , Gram-Negative Bacteria , Gram-Positive Bacteria , Humans
Melting snow and glacier ice in the Himalaya forms an important source of water for people downstream. Incoming longwave radiation (LWin) is an important energy source for melt, but there are only few measurements of LWin at high elevation. For the modelling of snow and glacier melt, the LWin is therefore often represented by parameterizations that were originally developed for lower elevation environments. With LWin measurements at eight stations in three catchments in the Himalaya, with elevations between 3,980 and 6,352 m.a.s.l., we test existing LWin parameterizations. We find that these parameterizations generally underestimate the LWin, especially in wet (monsoon) conditions, where clouds are abundant and locally formed. We present a new parameterization based only on near-surface temperature and relative humidity, both of which are easy and inexpensive to measure accurately. The new parameterization performs better than the parameterizations available in literature, in some cases halving the root-mean-squared error. The new parameterization is especially improving existing parameterizations in cloudy conditions. We also show that the choice of longwave parameterization strongly affects melt calculations of snow and ice.
Leptospirosis is identified as an important reemerging zoonotic disease distributed worldwide, caused by Leptospira. This study was carried out to explore the genetic characterization and its phylogenetic analysis of circulating Leptospira species, among the Aligarh region of western Uttar Pradesh in India, utilizing secY gene-based nucleotide sequence. A total of 190 human samples were included in the study. Positive samples were identified by ELISA, MAT and PCR. MAT was carried out utilizing local circulating Leptospira serovars. Four positive samples including two MAT positive samples were subjected to DNA sequencing for further confirmation and phylogenetic tree was constructed. Out of the total of 190 samples, 24 patients were found positive by ELISA and 29 by PCR. Two samples were found reactive in MAT with L. interrogans serovars like hebdomadis and copenhageni. Phylogenetic analysis of four isolates based on partial secY gene nucleotide sequences revealed that species obtained from the Aligarh region clustered with the several published pathogenic Leptospira interrogans, while some of our isolates nucleotide sequences also clustered with the published sequence of intermediate and saprophytic Leptospira serovars like Leptospira inadai and Leptospira meyeri. This pilot study will help us to decipher the present scenario of circulating serovars of leptospira as well as to identify the nucleotide changes in secY gene, in this region.
Leptospira/classification , Leptospira/isolation & purification , Leptospirosis/microbiology , Phylogeny , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Humans , India , Leptospira/chemistry , Leptospira/genetics , Sequence Alignment , Sequence Analysis, DNA , Tertiary Care Centers/statistics & numerical data
