In silico design and evaluation of a multiepitope vaccine targeting the nucleoprotein of Puumala orthohantavirus.

The Puumala orthohantavirus is present in the body of the bank vole (Myodes glareolus). Humans infected with this virus may develop hemorrhagic fever accompanying renal syndrome. In addition, the infection may further lead to the failure of an immune system completely. The present study aimed to propose a possible vaccine by employing bioinformatics techniques to identify B and T-cell antigens. The best multi-epitope of potential immunogenicity was generated by combining epitopes. Additionally, the linkers EAAAK, AAY, and GPGPG were utilized in order to link the epitopes successfully. Further, C-ImmSim was used to perform in silico immunological simulations upon the vaccine. For the purpose of conducting expression tests in Escherichia coli, the chimeric protein construct was cloned using Snapgene into the pET-9c vector. The designed vaccine showed adequate results, evidenced by the global population coverage and favorable immune response. The developed vaccine was found to be highly effective and to have excellent population coverage in a number of computer-based assessments. This work is fully dependent on the development of nucleoprotein-based vaccines, which would constitute a significant step forward if our findings were used in developing a global vaccination to combat the Puumala virus.

Recent Advances in the Detection of Food Toxins Using Mass Spectrometry.

Edibles are the only source of nutrients and energy for humans. However, ingredients of edibles have undergone many physicochemical changes during preparation and storage. Aging, hydrolysis, oxidation, and rancidity are some of the major changes that not only change the native flavor, texture, and taste of food but also destroy the nutritive value and jeopardize public health. The major reasons for the production of harmful metabolites, chemicals, and toxins are poor processing, inappropriate storage, and microbial spoilage, which are lethal to consumers. In addition, the emergence of new pollutants has intensified the need for advanced and rapid food analysis techniques to detect such toxins. The issue with the detection of toxins in food samples is the nonvolatile nature and absence of detectable chromophores; hence, normal conventional techniques need additional derivatization. Mass spectrometry (MS) offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. Recent technological advancements, such as high-resolution MS and tandem mass spectrometry (MS/MS), have significantly improved sensitivity, enabling the detection of food toxins at ultralow levels. Moreover, the emergence of ambient ionization techniques has facilitated rapid in situ analysis of samples with lower time and resources. Despite numerous advantages, the widespread adoption of MS in routine food safety monitoring faces certain challenges such as instrument cost, complexity, data analysis, and standardization of methods. Nevertheless, the continuous advancements in MS-technology and its integration with complementary techniques hold promising prospects for revolutionizing food safety monitoring. This review discusses the application of MS in detecting various food toxins including mycotoxins, marine biotoxins, and plant-derived toxins. It also explores the implementation of untargeted approaches, such as metabolomics and proteomics, for the discovery of novel and emerging food toxins, enhancing our understanding of potential hazards in the food supply chain.

Clinical profile of children with acute post-streptococcal glomerulonephritis.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is common in developing countries with a high hospitalization rate. Most patients have acute nephritic syndrome features, although some occasionally present with unusual clinical features. This study aims to describe and analyze clinical features, complications, and laboratory parameters in children diagnosed with APSGN at presentation, 4 and 12 weeks later, in a resource-limited setting. METHODS: This cross-sectional study was conducted among children < 16 years with APSGN between January 2015 and July 2022. Hospital medical records and outpatient cards were reviewed for clinical findings, laboratory parameters, and kidney biopsy results. Descriptive analysis of multiple categorical variables was performed using SPSS version 16.0 and presented as frequencies and percentages. RESULTS: The study included 77 patients. Most (94.8%) were older than five years, and age group 5-12 years had highest prevalence (72.7%). Boys were affected more frequently than girls (66.2% vs. 33.8%). Edema (93.5%), hypertension (87%), and gross hematuria (67.5%) were the most frequent presenting symptoms, and pulmonary edema (23.4%) was the most common severe complication. Anti-DNase B and anti-streptolysin O titers were positive in 86.9% and 72.7%, respectively, and 96.1% had C3 hypocomplementemia. Most clinical features resolved in three months. However, at 3 months, 6.5% of patients had persistent hypertension, impaired kidney function, and proteinuria alone or in combination. Most patients (84.4%) had an uncomplicated course; 12 underwent kidney biopsy, 9 required corticosteroids, and 1 required kidney replacement therapy. There was no mortality during the study period. CONCLUSION: Generalized swelling, hypertension, and hematuria were most common presenting features. Persistent hypertension, impaired kidney function, and proteinuria persisted in a small proportion who had a significant clinical course and required kidney biopsy. A higher resolution version of the Graphical abstract is available as Supplementary information.

A Comprehensive review on Pharmacokinetic Studies of Vaccines: Impact of delivery route, carrier-and its modulation on immune response.

The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes former biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced.. Thus, understanding vaccine ADME and its effects on immunization effectiveness could result in a more logical vaccine design in terms of formulation, method of administration, and dosing regimens. Herein, we will cover the information available on vaccine pharmacokinetics, impacts of delivery routes and carriers on ADME, utilization and efficiency of nanoparticulate delivery vehicles, impact of dose level and dosing schedule on the therapeutic efficacy of vaccines, intracellular and endosomal trafficking and in vivo fate, perspective on DNA and mRNA vaccines, new generation sequencing and mathematical models to improve cancer vaccination and pharmacology, and the reported toxicological study of COVID-19 vaccines. Altogether, this review will enhance the reader's understanding of the pharmacokinetics of vaccines and methods that can be implied in delivery vehicle design to improve the absorption and distribution of immunizing agents and estimate the appropriate dose to achieve better immunogenic responses and prevent toxicities.

Advanced targeted drug delivery by bioengineered white blood cell-membrane camouflaged nanoparticulate delivery nanostructures.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Leukocyte membrane coated nanoparticles (NPs) have attracted a lot of interest as an effective approach for delivering targeted drugs, capitalizing on the natural attributes of leukocytes to achieve site-specific accumulation, and heightened therapeutic outcomes. An overview of the present state of the targeted medication delivery research is given in this review. Notably, Leukocyte membrane-coated NPs offer inherent advantages such as immune evasion, extended circulation half-life, and precise homing to inflamed or diseased tissues through specific interactions with adhesion molecules. leukocyte membrane-coated NPs hold significant promise in advancing targeted drug delivery for precision medicine. As research progresses, they are anticipated to contribute to improved therapeutic outcomes, enabling personalized and effective treatments for a wide range of diseases and conditions. The review covers the method of preparation, characterization, and biological applications of leucocytic membrane coated NPs. Further, patents related factors, gap of translation from laboratory to clinic, and future prospective were discussed in detail. Overall, the review covers extensive literature to establish leucocytic membrane NPs for targeted drug delivery.

Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer.

Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds' anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid-lipid and liquid-lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies.

Altitudinal and seasonal distribution of benthic macroinvertebrates in River Tons - a tributary of Yamuna River, Uttarakhand, India.

The main tributary of the Yamuna, the Tons River, exhibits altitudinal changes in its macroinvertebrate community's diversity, abundance, and composition. Between May 2019 and April 2021, the study was conducted in the upper section of the river. A total of 48 numbers of taxa from 34 families and ten orders were recorded during the investigation. At this elevation of 1150 to 1287 m, the two most predominant orders are Ephemeroptera (32.9%) and Trichoptera (29.5%). During the premonsoon season, they had the lowest macroinvertebrate density (250-290 individuals/m2), and the post-monsoon season had the highest density (600-640 individuals/m2). During the post-monsoon season, the maximum larval forms (60%) of various insect orders were predominant. The findings indicated that lower altitudes (1150-1232 m) have higher macroinvertebrate abundance than higher ones. The diversity of dominance is shallow at site-I (0.0738) and strong at the site-IV during the premonsoon season (0.03837). Taxa richness, as measured by the Margalef index (D), peaked in the spring season (January to March) at 6.9 and reached its lowest point (5.74) in the premonsoon season (April to May). Only 16 taxa were discovered in site-I and site-II, but 39 taxa were discovered at low altitudes (site-IV, 1100 m) (1277-1287 m). The Tons River contains a total of 12 and 13 genera, respectively, that belong to the orders Ephemeroptera and Trichoptera, according to qualitative study of the macroinvertebrates. The current study supports the use of macroinvertebrates as bioindicator species for monitoring biodiversity and assessing the health of ecosystems.

New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency.

Scytophycins, including tolytoxin, represent a class of actin disrupting macrolides with strong antiproliferative effects on human cells. Despite intense research, little attention has been paid to scytophycin-induced cell death or the structural features affecting its potency. We show that tolytoxin and its natural analogue, 7-O-methylscytophycin B, lacking the hydroxyl substitution in its macrolactone ring, differ substantially in their cytotoxic effect. Both compounds increase the level of caspases 3/7, which are the main executioner proteases during apoptosis, in HeLa wild-type (WT) cells. However, no caspase activity was detected in HeLa cells lacking Bax/Bak proteins crucial for caspase activation via the mitochondrial pathway. Obtained data strongly suggests that scytophycins are capable of inducing mitochondria-dependent apoptosis. These findings encourage further research in structure-activity relationships in scytophycins and highlight the potential of these compounds in targeted drug delivery.

Silver Nanoparticles and Its Mechanistic Insight for Chronic Wound Healing: Review on Recent Progress.

Wounds are structural and functional disruptions of skin that occur because of trauma, surgery, acute illness, or chronic disease conditions. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase, and finally the tissue remodeling. Therefore, these processes are extensively studied to develop novel therapeutics in order to achieve maximum recovery with minimum scarring. Several growth hormones and cytokines secreted at the site of lesions tightly regulates the healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold and zinc) are increasingly being employed in dermatology due to their favorable effects on healing, as well as in treating and preventing secondary bacterial infections. In the current review, a brief introduction on traditional would healing approach is provided, followed by focus on the potential of wound dressing therapeutic techniques functionalized with Ag-NPs.

Comparative Evaluation of Ridge Width for Implant Placement Using Ridge Mapping on the Diagnostic Cast, Cone-beam Computed Tomography, and Direct Surgical Measurements.

AIM: This study was undertaken with an objective to find out the accuracy and reliability of presurgical ridge mapping (RM) on a diagnostic cast for linear measurements in the horizontal direction on cone-beam computed tomography (CBCT) and direct surgical assessment. MATERIALS AND METHODS: In total, 25 patients based on inclusion and exclusion criteria were selected. An acrylic stent with two points marked at 3 mm and 6 mm from the soft tissue summit of the alveolar ridge was fabricated. Linear measurements at these points were estimated with three techniques viz. RM on the diagnostic cast, CBCT, and direct surgical in situ measurements after flap reflection. RESULTS: Considering direct in situ surgical measurements as the gold standard with an accuracy of 100%, the accuracy for CBCT and RM on the diagnostic cast was 95.5% and 87.4%, respectively, for the maxillary arch. Whereas the accuracy for CBCT and RM on the diagnostic cast was 88.6% and 92.2%, respectively, for mandibular arch. CONCLUSION: The three approaches discussed are reliable for the assessment of ridge dimensions in the horizontal direction. Ridge mapping on the diagnostic cast is a simple, precise, noninvasive technique without any radiographic exposure. CLINICAL SIGNIFICANCE: Ridge mapping on a diagnostic cast along with two-dimensional (2D) radiography can be used as a valuable chairside diagnostic tool in the treatment planning prior to dental implant placement in the cases of a regular alveolar ridge and even mucosal lining. This clinical technique provides zero radiation exposure and is also cost-effective.

Reaching Out: How the Pandemic Impacted Knowledge Production and Dissemination in India.

The unprecedented spread of the COVID-19 pandemic compelled academic institutions and public repositories worldwide to come up with novel ideas in order to keep themselves functional. Adoption of new technology often constituted the fulcrum of such institutional responses. This article delves into some of the measures adopted by the Nehru Memorial Museum and Library, one of India's premier research institutes in social sciences. While doing so, it delineates a few anecdotal references from the past as well. The article emphasizes that the technological shifts in the wake of COVID-19 have far-reaching consequences so far as dissemination of knowledge through seminars and access to primary sources are concerned.

Cyanochelins, an Overlooked Class of Widely Distributed Cyanobacterial Siderophores, Discovered by Silent Gene Cluster Awakening.

Cyanobacteria require iron for growth and often inhabit iron-limited habitats, yet only a few siderophores are known to be produced by them. We report that cyanobacterial genomes frequently encode polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) biosynthetic pathways for synthesis of lipopeptides featuring ß-hydroxyaspartate (ß-OH-Asp), a residue known to be involved in iron chelation. Iron starvation triggered the synthesis of ß-OH-Asp lipopeptides in the cyanobacteria Rivularia sp. strain PCC 7116, Leptolyngbya sp. strain NIES-3755, and Rubidibacter lacunae strain KORDI 51-2. The induced compounds were confirmed to bind iron by mass spectrometry (MS) and were capable of Fe3+ to Fe2+ photoreduction, accompanied by their cleavage, when exposed to sunlight. The siderophore from Rivularia, named cyanochelin A, was structurally characterized by MS and nuclear magnetic resonance (NMR) and found to contain a hydrophobic tail bound to phenolate and oxazole moieties followed by five amino acids, including two modified aspartate residues for iron chelation. Phylogenomic analysis revealed 26 additional cyanochelin-like gene clusters across a broad range of cyanobacterial lineages. Our data suggest that cyanochelins and related compounds are widespread ß-OH-Asp-featuring cyanobacterial siderophores produced by phylogenetically distant species upon iron starvation. Production of photolabile siderophores by phototrophic cyanobacteria raises questions about whether the compounds facilitate iron monopolization by the producer or, rather, provide Fe2+ for the whole microbial community via photoreduction. IMPORTANCE All living organisms depend on iron as an essential cofactor for indispensable enzymes. However, the sources of bioavailable iron are often limited. To face this problem, microorganisms synthesize low-molecular-weight metabolites capable of iron scavenging, i.e., the siderophores. Although cyanobacteria inhabit the majority of the Earth's ecosystems, their repertoire of known siderophores is remarkably poor. Their genomes are known to harbor a rich variety of gene clusters with unknown function. Here, we report the awakening of a widely distributed class of silent gene clusters by iron starvation to yield cyanochelins, ß-hydroxy aspartate lipopeptides involved in iron acquisition. Our results expand the limited arsenal of known cyanobacterial siderophores and propose products with ecological function for a number of previously orphan gene clusters.

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study.

OBJECTIVE: To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI). METHODS: This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline. RESULTS: A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 ml to 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 h to 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H2 O to 41 cm H2 O (p = .005) at 6 weeks. Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment. CONCLUSION: Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies.

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein-protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

3D direct laser writing of microstructured optical fiber tapers on single-mode fibers for mode-field conversion.

We present a design and fabrication approach for 3D printed polymer microstructured optical fiber tapers on standard single-mode glass fibers for efficient and compact mode-field conversion. This paves the way towards complex functionalized fiber tips for various applications, like sensors and beam shaping components, currently limited by the mode-field size and distribution of standard optical fibers. In this paper, we demonstrate the potential of mode-field converting tapers for relaxing the misalignment tolerance in fiber-to-fiber connections and maximizing the coupling efficiency in fiber-to-chip connections. We demonstrate a mode-field diameter expansion ratio of 1.7 and reduction ratio of 3 and show that our microstructured tapers achieve a comparable performance in coupling efficiency as their step-index counterparts, while providing greater robustness.

Identification of Quorum Sensing Activators and Inhibitors in The Marine Sponge Sarcotragus spinosulus.

Marine sponges, a well-documented prolific source of natural products, harbor highly diverse microbial communities. Their extracts were previously shown to contain quorum sensing (QS) signal molecules of the N-acyl homoserine lactone (AHL) type, known to orchestrate bacterial gene regulation. Some bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the production of both QS signal molecules as well as QS inhibitory (QSI) molecules in the sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six unsaturated acyl chain AHLs. Bioassay-guided purification led to the isolation of two brominated metabolites with QSI activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and were identified as 3-bromo-4-methoxyphenethylamine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 was evaluated using reporter gene assays for long- and short-chain AHL signals (Escherichia coli pSB1075 and E. coli pSB401, respectively). QSI activity was further confirmed by measuring dose-dependent inhibition of proteolytic activity and pyocyanin production in Pseudomonas aeruginosa PAO1. The obtained results show the coexistence of QS and QSI in S. spinosulus, a complex signal network that may mediate the orchestrated function of the microbiome within the sponge holobiont.

Efficacy and safety of mirabegron for the treatment of low compliance bladder resulting from sacral/infrasacral lesions: A prospective study.

OBJECTIVE: To assess the efficacy and safety of mirabegron in patients with sacral/infrasacral lesions who have an acontractile detrusor and develop a low compliance bladder. METHODS: This prospective study included adult patients with acontractile detrusor as a result of sacral/infrasacral lesions who develop a low compliance bladder (compliance <20 mL/cmH2 O). All patients were asked to make a 48-h clean intermittent catheterization diary and underwent invasive urodynamics evaluation at the baseline, and were started on mirabegron 50 mg once daily. Patients were re-evaluated at 6 weeks with a repeat clean intermittent catheterization diary and invasive urodynamics, and the efficacy and safety of mirabegron was assessed. RESULTS: A total of 17 patients were included. After 6 weeks of mirabegron therapy, the number of patients reporting leakage in between clean intermittent catheterization reduced from seven to two (P = 0.02), the end filling pressures reduced from 41.4 to 15.1 cmH2 O (P = 0.003), the compliance increased from 9.8 to 99.9 mL/cmH2 O (P = 0.000), and the number of patients where the end filling pressure was >40 cmH2 O reduced from eight to one (P = 0.02). The cystometric bladder capacity did not change significantly. Similar effects were noted in patients who were already on clean intermittent catheterization or were started on clean intermittent catheterization at inclusion in the study. Mirabegron was well tolerated, none of the patients discontinued therapy or reported major side-effects. CONCLUSIONS: Mirabegron reduces end filling pressure, improves compliance and is safe in patients with a low compliance bladder resulting from a sacral/infrasacral lesion.

Discovery of Unusual Cyanobacterial Tryptophan-Containing Anabaenopeptins by MS/MS-Based Molecular Networking.

Heterocytous cyanobacteria are among the most prolific sources of bioactive secondary metabolites, including anabaenopeptins (APTs). A terrestrial filamentous Brasilonema sp. CT11 collected in Costa Rica bamboo forest as a black mat, was studied using a multidisciplinary approach: genome mining and HPLC-HRMS/MS coupled with bioinformatic analyses. Herein, we report the nearly complete genome consisting of 8.79 Mbp with a GC content of 42.4%. Moreover, we report on three novel tryptophan-containing APTs; anabaenopeptin 788 (1), anabaenopeptin 802 (2), and anabaenopeptin 816 (3). Furthermore, the structure of two homologues, i.e., anabaenopeptin 802 (2a) and anabaenopeptin 802 (2b), was determined by spectroscopic analysis (NMR and MS). Both compounds were shown to exert weak to moderate antiproliferative activity against HeLa cell lines. This study also provides the unique and diverse potential of biosynthetic gene clusters and an assessment of the predicted chemical space yet to be discovered from this genus.

Alternative Biosynthetic Starter Units Enhance the Structural Diversity of Cyanobacterial Lipopeptides.

Puwainaphycins (PUWs) and minutissamides (MINs) are structurally analogous cyclic lipopeptides possessing cytotoxic activity. Both types of compound exhibit high structural variability, particularly in the fatty acid (FA) moiety. Although a biosynthetic gene cluster responsible for synthesis of several PUW variants has been proposed in a cyanobacterial strain, the genetic background for MINs remains unexplored. Herein, we report PUW/MIN biosynthetic gene clusters and structural variants from six cyanobacterial strains. Comparison of biosynthetic gene clusters indicates a common origin of the PUW/MIN hybrid nonribosomal peptide synthetase and polyketide synthase. Surprisingly, the biosynthetic gene clusters encode two alternative biosynthetic starter modules, and analysis of structural variants suggests that initiation by each of the starter modules results in lipopeptides of differing lengths and FA substitutions. Among additional modifications of the FA chain, chlorination of minutissamide D was explained by the presence of a putative halogenase gene in the PUW/MIN gene cluster of Anabaena minutissima strain UTEX B 1613. We detected PUW variants bearing an acetyl substitution in Symplocastrum muelleri strain NIVA-CYA 644, consistent with an O-acetyltransferase gene in its biosynthetic gene cluster. The major lipopeptide variants did not exhibit any significant antibacterial activity, and only the PUW F variant was moderately active against yeast, consistent with previously published data suggesting that PUWs/MINs interact preferentially with eukaryotic plasma membranes.IMPORTANCE Herein, we deciphered the most important biosynthetic traits of a prominent group of bioactive lipopeptides. We reveal evidence for initiation of biosynthesis by two alternative starter units hardwired directly in the same gene cluster, eventually resulting in the production of a remarkable range of lipopeptide variants. We identified several unusual tailoring genes potentially involved in modifying the fatty acid chain. Careful characterization of these biosynthetic gene clusters and their diverse products could provide important insight into lipopeptide biosynthesis in prokaryotes. Some of the variants identified exhibit cytotoxic and antifungal properties, and some are associated with a toxigenic biofilm-forming strain. The findings may prove valuable to researchers in the fields of natural product discovery and toxicology.

Climato-environmental influence on breeding phenology of native catfishes in River Ganga and modeling species response to climatic variability for their conservation.

The main objectives of the present study were to quantify the environmental, especially temperature and rainfall, effects on breeding phenology of selected catfish species and to predict changes in breeding phenology of the selected species in relation to climatic variability for the Ganga River Basin. The study showed that changes in rainfall pattern may have the most profound effect on gonad maturation and breeding of Mystus tengara and Mystus cavasius followed by the effect of increased water temperature due to rising air temperature. Indication of region-specific adaptation was noticed in reproductive phenology of Eutropiichthys vacha based on local trends of warming climate. The other habitat parameters, such as dissolved oxygen, alkalinity, nitrate, and phosphate, were correlated with gonad maturity and spawning. Climatic variability may bring region-specific changes in breeding phenology of fish species in the Ganga River. Under a warming climate, changes in precipitation pattern manifested into riverine flow pulse may be the key driver in dictating breeding phenology. Our study indicates E. vacha as a climate sensitive species that may be selected as a target species for climate change impact studies.