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Manish Kumar

Publications and source records attributed to Manish Kumar.

At least 19 recordsLinked to original sources
PubMed2026

The Network of National COVID-19 Data Portals: public health equity through collaboration.

The network of the national COVID-19 Data Portals was developed and linked to the COVID-19 Data Portal (https://www.covid19dataportal.org/)inresponsetothe need for rapid data sharing and analysis during the 2020-2022 SARS-CoV-2 pandemic. Built on open-source code developed by the Swedish COVID-19 Data Portal (now the Swedish Pathogens Portal, www.pathogens.se) the network included 12 national portals addressing demand for local open data sharing and access, across data types and resources. It provides a robust case study of national initiatives for FAIR (Findable, Accessible, Interoperable and Reusable) resources and a foundation for future pandemic preparedness across pathogens globally. In this paper we outline the structure of the origins of the network of National COVID-19 Datal Portals, the technical aspects and code originating from the Swedish Portal and provide an overview of the services and tools offered by each Portal. The paper showcases the process and operation of four Portals: Sweden, Poland, Spain, Norway and The Netherlands. In this study, we observe that pandemic response greatly benefits from an established infrastructure that can be quickly mobilised, developed and extended. Collaborations and preparation built on solid foundations over several years, supported by investment in the form of national and international research grants, is key for sustainability, continuation and readiness to deploy such efforts.

COVID-19↗
PubMed2025

Metabolism and gene expression models for the microbiome reveal how diet and metabolic dysbiosis impact disease.

The gut microbiome plays a critical role in human health, spurring extensive research using multi-omic technologies. Although these tools offer valuable insights, they often fall short in capturing the complexity of microbial interactions that associate with disease onset, progression, and treatment. Thus, integration of multi-omics datasets with metabolic models is needed to predict associations between microbial activity and disease. Here, we automated the reconstruction of 495 metabolic and gene expression models (ME-models), overcoming the main limitation preventing the wide use of this approach. We integrated them with multi-omics data from patients with inflammatory bowel disease (IBD), identifying taxa associated with variations in amino acids, short-chain fatty acids, and pH in the gut of IBD patients. In general, this approach provides testable hypotheses of the metabolic activity of the gut microbiota, and the automated pipeline opens the opportunity to study microbial interactions in other biologically relevant settings using ME-models.

Humans↗
PubMed2006

Naphtho[2,3-b][1,4]-thiazine-5,10-diones and 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thioalkanoate derivatives: synthesis and biological evaluation as potential antibacterial and antifungal agents.

A series of 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thio-alkanoate derivatives 3-21 and naphtho[2,3-b][1,4]-thiazine-5,10-diones 24 were synthesized and evaluated for their antibacterial and antifungal activities. The structure-activity relationships of these compounds were studied and the results show that the compound 24a exhibited better antibacterial activity than Gentamycin in vitro against Staphylococcus aureus. In addition 24a also imparted marked antifungal activity in vitro against Cryptococcus neoformans, Sporothrix schenckii, and Trichophyton mentagraphytes when compared with Fluconazole. Compounds 15, 18, 19, and 21 also exhibited significant antibacterial activity in vitro against S. aureus.

Anti-Bacterial Agents↗
PubMed2006

Synthesis of benzenepropanamine analogues as non-detergent spermicides with antitrichomonas and anticandida activities.

Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as well as microbicidal activities against Trichomonas vaginalis and Candida spp. Several compounds showed appreciable dual activities. Compound 12 exhibited good spermicidal (MEC=0.1%) along with substantial anticandidal (MIC=0.05%) activities, while compounds 3 and 6 showed significant microbicidal activities with moderate spermicidal effect. The SAR of these structures is being discussed here in this communication. It is concluded that suitable structural modifications in this class of compounds at 3-amino position may lead to a potent spermicide with associated microbicidal activity.

Adult↗
PubMed2006

Synthesis and antibacterial evaluation of ureides of Baylis-Hillman derivatives.

The synthesis of several 1-(2-cyano-3-aryl-allyl)-3-aryl-urea(thiourea) constructed from the reaction between allylamines generated from Baylis-Hillman acetates and substituted isocyanates and isothiocyanates has been described. Further, their cyclization in the presence of a base led to the formation of 5-arylmethyl-4-imino-3-aryl-3,4-dihydro-1H-pyrimidin-2-ones. All compounds were tested for their antibacterial activity. Few of the compounds showed superior activity or were equipotent to the standard antibacterial agents.

Acetates↗
PubMed2006

Single-stranded conformation polymorphism of large subunit of ribosomal RNA is best suited to diagnosing fungal infections and differentiating fungi at species level.

In the last decade, various polymerase chain reaction (PCR)-based methods have been developed using ribosomal RNA (rRNA) for the identification of medically important fungi. In the present study, large subunit (LSU) and small subunit (SSU) of fungal rRNA were amplified and analyzed by single-stranded conformation polymorphism (SSCP) of nested PCR, restriction digestion, and SSCP of digested products. The relationship between several clinical isolates of patients suffering from aspergillosis, candidiasis, cryptococcosis, keratitis, and skin and nail infections has been established with standard fungal cultures using the SSU- and LSU-specific primers. Single-stranded conformation polymorphism of restriction profile of amplified products of LSU-specific primers was successfully used to differentiate fungi up to genus and species level.

Classification↗
PubMed2006

Investigation of seawater reverse osmosis fouling and its relationship to pretreatment type.

Desalination of seawater using reverse osmosis (RO) technology is an important option available to water-scarce coastal regions. A major challenge to seawater reverse osmosis (SWRO) is membrane productivity decline due to fouling. Systematic studies in the area of SWRO fouling are lacking as compared to RO fouling by freshwater. The effect of the type of pretreatment employed ahead of the SWRO process has been recognized to be of critical importance in SWRO fouling. The objective of this study was to evaluate the effect of pretreatment on SWRO performance using bench scale experiments. The effect of different pretreatment strategies on SWRO flux decline was simulated using prefiltration of the SWRO feedwater using different filtration size ranges. The prefiltration size ranges used were selected to mimic the size fractions associated with different SWRO pretreatment processes. It was found that particulate matter greater than 1 microm (representing media filtration) caused most of the RO fouling. On the other hand, significant reduction in fouling was observed when membrane filtration was used (microfiltration represented by 0.1 microm prefiltration and ultrafiltration represented by 100 kDa prefiltration). There was no significant difference in flux decline between these two membrane filtration types. The lowest RO flux decline was observed when a tight ultrafiltration membrane (20 kDa) was used as prefiltration. The RO fouling observed was modeled using the gel layertheory, which could be used to satisfactorily describe fouling by different dissolved fractions of seawater. The observed SWRO fouling trends were confirmed using specially adapted attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy of the fouled membrane surface.

Equipment Failure↗
PubMed2006

ppGpp: stringent response and survival.

Adaptation to any undesirable change in the environment dictates the survivability of many microorganisms, with such changes generating a quick and suitable response, which guides the physiology of bacteria. During nutritional deprivation, bacteria show a stringent response, as characterized by the accumulation of (p)ppGpp, resulting in the repression of stable RNA species, such as rRNA and tRNA, with a concomitant change in colony morphology. However, genes involved in amino acid biosynthesis become over-expressed to help bacteria survive under such conditions. The survivability of pathogenic bacteria inside a host cell also depends upon the stringent response demonstrated. Therefore, an understanding of the physiology of stringent conditions becomes very interesting in regulation of the growth and persistence of such invading pathogens.

Amino Acid Sequence↗
PubMed2005

Chemical denitrification of water by zero-valent magnesium powder.

A laboratory-scale study was conducted in batch mode to investigate the feasibility of using zero-valent magnesium (Mg(0)), for removal of nitrate from aqueous solution. Reaction pH, dose of Mg(0), initial nitrate concentration and temperature were considered variable parameters during the study. Strong acidic condition enhanced nitrate reduction and in absence of external proton addition, reaction pH increased rapidly above ten and insignificant nitrate removal (7-16%) was achieved. At Mg(0):NO(3)(-)-N molar ratio of 5.8 and controlled reaction pH of 2, 84% denitrification efficiency was achieved (initial NO(3)(-)-N 50 mg/L) under ambient temperature and pressure and total nitrogen removal was 70% with 3.2% and 10% conversion of initial NO(3)(-)-N to NO(2)(-)-N and NH(4)(+)-N, respectively. The reaction was first order with respect to nitrate concentration. Nitrate removal rate decreased with solution pH and increased linearly with Mg(0) dose. Nitrate removal was coupled with 96-100% removal of dissolved oxygen and 85-90% generation of soluble Mg(2+) ion. An activation energy (E(a)) of nitrate reduction over the temperature range of 10-50 degrees C was observed as 17.7 kJ mol(-1).

Hydrogen-Ion Concentration↗
PubMed2005

Prediction of mitochondrial proteins using support vector machine and hidden Markov model.

Mitochondria are considered as one of the core organelles of eukaryotic cells hence prediction of mitochondrial proteins is one of the major challenges in the field of genome annotation. This study describes a method, MitPred, developed for predicting mitochondrial proteins with high accuracy. The data set used in this study was obtained from Guda, C., Fahy, E. & Subramaniam, S. (2004) Bioinformatics 20, 1785-1794. First support vector machine-based modules/methods were developed using amino acid and dipeptide composition of proteins and achieved accuracy of 78.37 and 79.38%, respectively. The accuracy of prediction further improved to 83.74% when split amino acid composition (25 N-terminal, 25 C-terminal, and remaining residues) of proteins was used. Then BLAST search and support vector machine-based method were combined to get 88.22% accuracy. Finally we developed a hybrid approach that combined hidden Markov model profiles of domains (exclusively found in mitochondrial proteins) and the support vector machine-based method. We were able to predict mitochondrial protein with 100% specificity at a 56.36% sensitivity rate and with 80.50% specificity at 98.95% sensitivity. The method estimated 9.01, 6.35, 4.84, 3.95, and 4.25% of proteins as mitochondrial in Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, mouse, and human proteomes, respectively. MitPred was developed on the above hybrid approach.

Algorithms↗
PubMed2005

Heat shock protein 40 is necessary for human immunodeficiency virus-1 Nef-mediated enhancement of viral gene expression and replication.

The human immunodeficiency virus-1 (HIV-1) Nef protein, originally identified as a negative factor, has now emerged as one of the most important viral proteins necessary for viral pathogenesis and disease progression. Nef has been also implicated in viral infectivity and replication, however, the molecular mechanism of Nef-induced viral gene expression and replication is not clearly understood. Although involvement of heat shock proteins in viral pathogenesis has been reported earlier, a clear understanding of their role remains to be elucidated. Here we report for the first time that Nef not only interacts with heat shock protein 40 (Hsp40) but it also induces the expression of Hsp40 in HIV-1-infected cells. The interaction between Nef and Hsp40 is important for increased Hsp40 translocation into the nucleus of infected cells, which seems to facilitate viral gene expression by becoming part of the cyclin-dependent kinase 9-associated transcription complex regulating long terminal repeat-mediated gene expression. The finding is consistent with the failure of the nef-deleted virus to induce Hsp40, resulting in reduced virus production. Our data further shows that, whereas, Hsp40 overexpression induces viral gene expression, silencing of Hsp40 reduces the gene expression in a Nef-dependent manner. Thus our results clearly indicate that Hsp40 is crucial for Nef-mediated enhancement of viral gene expression and replication.

Amino Acid Sequence↗
PubMed2005

BhairPred: prediction of beta-hairpins in a protein from multiple alignment information using ANN and SVM techniques.

This paper describes a method for predicting a supersecondary structural motif, beta-hairpins, in a protein sequence. The method was trained and tested on a set of 5102 hairpins and 5131 non-hairpins, obtained from a non-redundant dataset of 2880 proteins using the DSSP and PROMOTIF programs. Two machine-learning techniques, an artificial neural network (ANN) and a support vector machine (SVM), were used to predict beta-hairpins. An accuracy of 65.5% was achieved using ANN when an amino acid sequence was used as the input. The accuracy improved from 65.5 to 69.1% when evolutionary information (PSI-BLAST profile), observed secondary structure and surface accessibility were used as the inputs. The accuracy of the method further improved from 69.1 to 79.2% when the SVM was used for classification instead of the ANN. The performances of the methods developed were assessed in a test case, where predicted secondary structure and surface accessibility were used instead of the observed structure. The highest accuracy achieved by the SVM based method in the test case was 77.9%. A maximum accuracy of 71.1% with Matthew's correlation coefficient of 0.41 in the test case was obtained on a dataset previously used by X. Cruz, E. G. Hutchinson, A. Shephard and J. M. Thornton (2002) Proc. Natl Acad. Sci. USA, 99, 11157-11162. The performance of the method was also evaluated on proteins used in the '6th community-wide experiment on the critical assessment of techniques for protein structure prediction (CASP6)'. Based on the algorithm described, a web server, BhairPred (http://www.imtech.res.in/raghava/bhairpred/), has been developed, which can be used to predict beta-hairpins in a protein using the SVM approach.

Algorithms↗
PubMed2005

Enhanced biodegradation of beta- and delta-hexachlorocyclohexane in the presence of alpha- and gamma-isomers in contaminated soils.

The chlorinated insecticide hexachlorocyclohexane (HCH) has been used extensively in the past, and contaminated sites are present throughout the world. Toward their bioremediation, we isolated a bacterium Pseudomonas aeruginosa ITRC-5 that mediates the degradation of all the four major isomers of HCH under aerobic conditions, both in liquid-culture and contaminated soils. In liquid-culture, the degradation of alpha- and gamma-HCH is rapid and is accompanied with the release of 5.6 micromole chloride ions and 4.1 micromole CO2 micromole(-1) HCH-isomer. The degradation of beta- and delta-isomers is slow, accompanied with the release of 0.9 micromole chloride ions micromole(-1) HCH-isomer, and results in a transient metabolite 2,3,4,5,6-pentachlorocyclohexan-1-ol. The strain ITRC-5 also mediates the degradation of alpha-, beta-, gamma-, and delta-isomers in contaminated soils, where degradation of otherwise persistent beta- and delta-HCH is enhanced severalfold in the presence of alpha- or gamma-HCH. The degradation of soil-applied beta- and delta-HCH under aerobic conditions has not been reported earlier. The isolate ITRC-5 therefore demonstrates potential for the bioremediation of HCH-wastes and contaminated soils.

Aerobiosis↗
PubMed2005

Sensitive and rapid polymerase chain reaction based diagnosis of mycotic keratitis through single stranded conformation polymorphism.

PURPOSE: To report a method for early and correct diagnosis of mycotic keratitis. DESIGN: Clinical laboratory diagnostic study. METHODS: Corneal scraping of all the four patients were processed for DNA extraction which were amplified by fungal specific primers of internal transcribed spacer region I (ITS1). These products were sequenced and analyzed by single stranded conformation polymorphism (SSCP) for species identification. RESULTS: The DNA samples from corneal scrapings of all the four patients were successfully amplified by the primer pair ITS1 and ITS2 and similarity/dissimilarity were established by Jaccard's coefficient. Patient isolate 1 was identified as Nectria hematococca, isolate 2 as Candida albicans, and isolates 3 and 4 were identified as Bipolaris papendorfii. This led to prompt initiation of antifungal therapy in all the four cases where useful vision could be restored. CONCLUSIONS: Early and correct diagnosis of mycotic keratitis by polymerase chain reaction could be obtained in all the four cases compared with conventional methods, which helped in the prompt initiation of antifungal therapy in patients.

Adolescent↗
PubMed2005

Identification of a novel antifungal nonapeptide generated by combinatorial approach.

It is becoming clear that antimicrobial peptides are important components of the innate defences of all species of life. They kill very rapidly, do not easily select resistant mutants and are synergistic with potentially toxic conventional therapeutic agents against microbes. This paper describes an attempt to expand a lead hexapeptide motif synthesized through combinatorial approach. A cationic peptide H-Arg-Trp-Trp-Arg-D-Trp-D-Phe-Ile-D-Phe-His-NH2 was found to be active with a therapeutic index of >17. I was proposed that the combination of peptide with known antifungal agents may identify synergistic combinations that would ideally reduce the dosage of conventional antifungals as well as their associated toxicity. Nine different pathogenic strains and species of Candida and two of Cryptococcus neoformans were employed in chequerboard method and in time kill assays to evaluate the synergistic effect of the lead peptide in combination with amphotericin B, 5-flucytosine, ketoconazole and fluconazole. We found synergistic interaction between the peptide and all four drugs against Cryptococcus isolates whilst both synergistic and additive combinations occurred when Candida isolates were used.

Amino Acid Motifs↗
PubMed2005

Use of PCR targeting of internal transcribed spacer regions and single-stranded conformation polymorphism analysis of sequence variation in different regions of rrna genes in fungi for rapid diagnosis of mycotic keratitis.

The increased incidence of fungal infections in the recent past has been attributed to the increase in the number of human immunodeficiency virus-positive and AIDS patients. Early diagnosis of mycoses in patients is crucial for prompt antifungal therapy. Immunological methods of diagnosis have not been found to be satisfactory, and recent research has been diverted to the use of PCR for the sensitive and early diagnosis at the molecular level. In the present study we targeted different regions of the rRNA gene to diagnose cases of mycotic keratitis and identify the causal agents. Six fungus-specific primers (primers ITS1, ITS2, ITS3, ITS4, invSR1R, and LR12R) were used, and the amplified products were analyzed by single-stranded conformation polymorphism (SSCP) analysis. Dendrograms of these SSCP patterns, prepared on the basis of Jaccard's coefficient, indicated that the PCR products obtained with primer pair ITS1 and ITS2 were the best for the identification of fungi. The results were confirmed by sequencing of the PCR products, and the approach was successfully tested experimentally for the detection of mycotic keratitis caused by Aspergillus fumigatus and was used for the diagnosis of fungal corneal ulcers in patients.

Animals↗