Assessment of Psychiatric Illness among Pulmonary Tuberculosis Patients at a Tertiary Care Center in India.

INTRODUCTION: Tuberculosis (TB) is a chronic infectious multisystemic disease caused by Mycobacterium tuberculosis and is one of the leading causes of mortality worldwide. Both common mental disorders (CMD) and TB are global public health problems that have a considerable impact on human health. Moreover, TB and CMDs share common risk factors including poverty, drug addiction, and homelessness and the coexistence of CMD and TB leads to difficult management of TB. MATERIALS AND METHODS: This was a hospital-based longitudinal study, carried out between June 2021 and December 2022. In this study, 147 pulmonary TB patients were included as per inclusion and exclusion criteria, and psychiatric illness was evaluated by the Brief Psychiatric Rating Scale. RESULTS: The mean age of study participants was 37.59 ± 15.37 years, there were 99 (67.3%) were male and 48 (32.7%) were female. Psychiatric illness was found in 77 (52.38%) pulmonary TB patients. Among psychiatric illness, anxiety was found in 33 (22.4%) participants and 21 (14.3%) participants had depression. Mixed anxiety and depression were found in 20 (13.6%) patients and 03 (2%) participants had severe psychosis. The association of psychiatric illness with age group and gender was not significant ( P = 0.734, 0.203, respectively). There were 105 (71.40%) patients who had <12 standard education and 42 (28.60%) had >12 standard education and their association with psychiatric illness was statistically significant ( P = 0.044). Adverse drug reactions were found among 80 (54.42%) patients and the association between adverse drug reactions and psychiatric illness was significant ( P = 0.031). CONCLUSION: Psychiatric illness is one of the important domains to be evaluated in timely manner in TB patients and early intervention is needed for better management of the TB because the severity, social factors, and chronicity of the disease make them susceptible to develop psychiatric illness.

Résumé Introduction:La tuberculose (TB) est une maladie infectieuse multisystémique chronique causée par Mycobacterium tuberculosis et constitue l'une des principales causes de mortalité dans le monde. Les troubles mentaux courants (CMD) et la tuberculose sont des problèmes de santé publique mondiaux qui ont un impact considérable sur la santé humaine. De plus, la tuberculose et les troubles mentaux courants (CMD) partagent des facteurs de risque communs, notamment la pauvreté, la toxicomanie et l'itinérance, et la coexistence des CMD et de la tuberculose rend difficile la gestion de la tuberculose.Méthodes:Il s'agissait d'une étude longitudinale en milieu hospitalier, réalisée entre juin 2021 et décembre 2022. Dans cette étude, 147 patients atteints de tuberculose pulmonaire ont été inclus selon les critères d'inclusion et d'exclusion et la maladie psychiatrique a été évaluée par une brève échelle d'évaluation psychiatrique (BPRS).Résultats:L'âge moyen des participants à l'étude était de 37,59 ± 15,37 ans, il y avait 99 (67,3 %) hommes et 48 (32,7 %) femmes. Une maladie psychiatrique a été trouvée chez 77 (52,38 %) patients atteints de tuberculose pulmonaire. Parmi les maladies psychiatriques, l'anxiété a été constatée chez 33 (22,4 %) participants et 21 (14,3 %) participants souffraient de dépression. Une anxiété et une dépression mixtes ont été trouvées chez 20 (13,6 %) patients et 03 (2 %) participants souffraient d'une psychose sévère. L'association entre la maladie psychiatrique et le groupe d'âge et le sexe n'était pas significative (valeur P = 0,734, 0,203 respectivement). Il y avait 105 (71,40 %) patients ayant <12 niveaux d'éducation standard et 42 (28,60 %) avaient >12 niveaux d'éducation standard et leur association avec une maladie psychiatrique était statistiquement significative ( P = 0,044). Des effets indésirables du médicament ont été observés chez 80 (54,42 %) patients et l'association entre l'effet indésirable du médicament et la maladie psychiatrique était significative. ( P = 0,031).Conclusion:La maladie psychiatrique est l'un des domaines importants à évaluer en temps opportun chez les patients tuberculeux et une intervention précoce est nécessaire pour une meilleure prise en charge de la tuberculose car la gravité, les facteurs sociaux et la chronicité de la maladie les rendent susceptibles de développer une maladie psychiatrique.

Untangling the adaptive strategies of thermophilic bacterium Anoxybacillus rupiensis TPH1 under low temperature.

The present study investigates the low temperature tolerance strategies of thermophilic bacterium Anoxybacillus rupiensis TPH1, which grows optimally at 55 °C , by subjecting it to a temperature down-shift of 10 °C (45 °C) for 4 and 6 h followed by studying its growth, morphophysiological, molecular and proteomic responses. Results suggested that although TPH1 experienced increased growth inhibition, ROS production, protein oxidation and membrane disruption after 4 h of incubation at 45 °C yet maintained its DNA integrity and cellular structure through the increased expression of DNA damage repair and cell envelop synthesizing proteins and also progressively alleviated growth inhibition by 20% within two hours i.e., 6 h, by inducing the expression of antioxidative enzymes, production of unsaturated fatty acids, capsular and released exopolysaccharides and forming biofilm along with chemotaxis proteins. Conclusively, the adaptation of Anoxybacillus rupiensis TPH1 to lower temperature is mainly mediated by the synthesis of large numbers of defense proteins and exopolysaccharide rich biofilm formation.

Molecular pathways and therapeutic strategies in dermatofibrosarcoma protuberans (DFSP): unravelling the tumor's genetic landscape.

Dermatofibrosarcoma Protuberans (DFSP) is a rare soft tissue sarcoma distinguished by its infiltrative growth pattern and recurrence potential. Understanding the molecular characteristics of DFSP is essential for enhancing its diagnosis, prognosis, and treatment strategies. The paper provides an overview of DFSP, highlighting the significance of its molecular understanding. The gene expression profiling has uncovered unique molecular signatures in DFSP, highlighting its heterogeneity and potential therapeutic targets. The Platelet-Derived Growth Factor Receptors (PDGFRs) and Fibroblast Growth Factor Receptors (FGFRs) signaling pathways play essential roles in the progression and development of DFSP. The abnormal activation of these pathways presents opportunities for therapeutic interventions. Several emerging therapies, i.e., immunotherapies, immunomodulatory strategies, and immune checkpoint inhibitors, offer promising alternatives to surgical resection. In DFSP management, combination strategies, including rational combination therapies, aim to exploit the synergistic effects and overcome resistance. The article consisting future perspectives and challenges includes the discovery of prognostic and predictive biomarkers to improve risk stratification and treatment selection. Preclinical models, such as Patient-derived xenografts (PDX) and genetically engineered mouse models, help study the biology of DFSP and evaluate therapeutic interventions. The manuscript also covers small-molecule inhibitors, clinical trials, immune checkpoint inhibitors for DFSP treatment, combination therapies, rational therapies, and resistance mechanisms, which are unique and not broadly covered in recent pieces of literature. See also the graphical abstract(Fig. 1).

On the elephant trails: habitat suitability and connectivity for Asian elephants in eastern Indian landscape.

Identifying suitable habitats and conserving corridors are crucial to the long-term conservation of large and conflict-prone animals. Being a flagship species, survival of Asian elephants is threatened by human-induced mortality and habitat modification. We aimed to assess the habitat suitability and connectivity of the Asian elephant Elephas maximus Linnaeus, 1758 habitat in the state of Odisha in eastern India. We followed the ensemble of spatial prediction models using species presence data and five environmental variables. We used least-cost path and circuit theory approaches to identify the spatial connectivity between core habitats for Asian elephants. The results revealed that normalized difference vegetation index (NDVI; variable importance 42%) and terrain ruggedness (19%) are the most influential variables for predicting habitat suitability of species within the study area. Our habitat suitability map estimated 14.6% of Odisha's geographical area (c. 22,442 km2) as highly suitable and 13.3% (c. 20,464 km2) as moderate highly suitable. We identified 58 potential linkages to maintain the habitat connectivity across study area. Furthermore, we identified pinch points, bottlenecks, and high centrality links between core habitats. Our study offers management implications for long-term landscape conservation for Asian elephants in Odisha and highlights priority zones that can help maintain spatial links between elephant habitats.

Molecular targeted therapies for cutaneous squamous cell carcinoma: recent developments and clinical implications.

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.

Nitrogen and Redox Metabolism in Cyanobacterium Anabaena sp. PCC 7120 Exposed to Different Sulfate Regimes.

Sulfur is an important key nutrient required for the growth and development of cyanobacteria. Several reports showed the effect of sulfate limitation in unicellular and filamentous cyanobacteria, but such studies have not yet been reported in heterocytous cyanobacteria to ascribe the mechanisms of nitrogen and thiol metabolisms. Thus, the present work was carried out to appraise the impacts of sulfate limitation on nitrogen and thiol metabolisms in Anabaena sp. PCC 7120 by analyzing the contents as well as enzymes of nitrogen and thiol metabolisms. Cells of Anabaena sp. PCC 7120 were exposed to different regimes of sulfate, i.e., 300, 30, 3, and 0 µM. Application of reduced concentration of sulfate showed negative impact on the cyanobacterium. Sulfate-limiting conditions reduces nitrogen-containing compounds in the cells of Anabaena. Additionally, reduced activities of nitrogen metabolic enzymes represented the role of sulfate in nitrogen metabolism. However, decreased activities of thiol metabolic enzymes indicated that sulfate-limited cyanobacterial cells have lower amount of glutathione and total thiol contents. Reduced accumulation of thiol components in the stressed cells indicated that sulfate-limited cells have lower ability to withstand stressful condition. Hence, Anabaena displays differential response to different concentrations of sulfate, and thus, stipulated that sulfur plays an important role in nitrogen and thiol metabolisms. To the best of our knowledge, this is the first report demonstrating the impact of sulfate stress on nitrogen and redox metabolisms in heterocytous cyanobacteria. This preliminary study provides a baseline idea that may help improve the production of paddy.

Prospects of a hot spring-originated novel cyanobacterium, Scytonema ambikapurensis, for wastewater treatment and exopolysaccharide-enriched biomass production.

The present work performs the polyphasic characterization of a novel cyanobacterial species Scytonema ambikapurensis isolated from an Indian hot spring and evaluates its wastewater bioremediation potential. While the physicochemical analyses of the wastewater indicated high load of nutrients and metals, the wastewater bioremediation experiment performed using the test cyanobacterium denoted the removal of 70 and 86% phosphate, 49 and 66% sulfate, 96 and 98% nitrate, 91 and 92% nitrite, 95 and 96% ammonia, 66 and 72% chloride, 79 and 81% zinc, 68 and 80% nickel, 81 and 90% calcium, and 80 and 90% potassium from the autoclaved and un-autoclaved wastewater, respectively, after 20 days of culturing. The kinetics study of zinc and nickel removal from wastewater revealed that the cyanobacterium employed sequential biosorption (by following pseudo-second-order kinetics model) and bioaccumulation methods to remove these two metals. The quality of the autoclaved and un-autoclaved wastewater was further improved by the cyanobacterium through reduction of hardness by 74 and 81%, respectively. In wastewater, the cyanobacterium not only enhanced its biomass, chlorophyll and carbohydrate contents, but also produced small amount of released and high capsular exopolysaccharide (EPS). The FTIR and TGA analyses of capsular EPS unraveled that it was a negatively charged sulfated biomolecule having thermostability up to 240 °C, which suggested its possible use as excellent emulsifying, viscosifying, and biosorption agent. The credibility of this EPS as biosorption agent was ascertained by evaluating its metal chelating ability. Finally, the experimental data denoting the ability of S. ambikapurensis to bioremediate wastewater and simultaneously produce EPS was statistically validated by PCA1-pollutant removal model and the PCA2-cellular constituent model, respectively. Briefly, the study discloses that the cyanobacterium has huge biotechnological and industrial importance as it bioremediates wastewater and simultaneously produces thermostable exopolysaccharide.

Evaluation of Wound Healing Potential of Root Bark Extract of Berberis aristata and Molecular Docking Analysis of Berberis Phytoconstituents.

INTRODUCTION: The root bark of Berberis aristata has been utilized by indigenous peoples for wound treatment for centuries. The mature root barks are crushed into a paste and applied to the wound's surface. OBJECTIVE: The focus of this research is to analyse the wound healing activities of an ethanolic extract of Berberis aristata, as well as to use molecular docking to establish the likely mechanism of the potent phytochemical. There is no scientific evidence to support the usage of root bark extract of Berberis aristata. METHODS: The Herbal ointment, which comprises (1%, 2%, and 4% w/w) ethanolic extract of root bark, was developed to test the wound healing ability of incision and excision wounds, and the molecular mechanism was established using Auto-Dock software. RESULTS: Epithelization stage, wound index, % wound contraction area, hydroxyproline content, DNA estimate, and histopathological assessments were performed on the incision wound model. Tensile strength was assessed in an excision wound model. TLC was used to identify the samples after successive extractions with different solvents based on polarity. CONCLUSION: Berberine and tetrahydropalmatine were major active phytoconstituent found in root barks of Berberis aristata as secondary metabolites. Animals treated with 4% w/w formulation demonstrated considerable wound contraction, epithelization time, and wound index in the excision model. In contrast, to control and standardize the concentrations of hydroxyproline, total amino acids, and DNA in recovering tissue were higher. At 4% w/w extract formulation, the parameters studied indicated a substantial result. Berberine and tetrahydropalmatine, active metabolites which are present in the ethanolic extract of Berberis aristata, were found to be responsible for wound healing. Based on ligand interactions, the findings verified Berberis aristata ethnomedicinal claim in a wound healing capacity.

Decoding whole genome of Anoxybacillus rupiensis TPH1 isolated from tatapani hot spring, India and giving insight into bioremediation ability of TPH1 via heavy metals and azo dyes.

A moderately thermophilic, gram-positive genomospecies Anoxybacillus rupiensis TPH1 was isolated from Tatapani hot spring, Chhattisgarh, India. Genome of 3.70 Mb with 42.3% GC subsumed 4131 CDSs, 65 tRNA, 5 rRNA, 35 AMR and 19 drug target genes. Further, comparative genomics of 19 Anoxybacillus spp. exhibited an open pan genome of 13102 genes along with core (10.62%), unique (43.5%) and accessory (45.9%) genes. Moreover, phylogenomic tree displayed clustering of Anoxybacillus spp. into two distinct clades where clade A species harbored larger genomes, more unique genes, CDS and hypothetical proteins than clade B species. Further, distribution of azoreductases showed FMN-binding NADPH azoreductase (AzoRed1) presence in clade A species only and FMN-binding NADH azoreductase (AzoRed2) harboring by species of both clades. Heavy metal resistance genes distribution showed omnipresence of znuA, copZ and arsC in both clades, dispersed presence of cbiM, czcD, merA and feoB over both clades and harboring of nikA and acr3 by few species of clade A only. Additionally, molecular docking of AzoRed1, AzoRed2, ZnuA, CopZ, Acr3, CbiM, CzcD, MerA and NikA with their respective ligands indicated high affinity and stable binding. Conclusively, present study provided insight into gene repertoire of genus Anoxybacillus and a basis for the potential application of this thermophile in bioremediation of azo dyes and heavy metals.

Deciphering the mechanisms of zinc tolerance in the cyanobacterium Anabaena sphaerica and its zinc bioremediation potential.

Cyanobacteria adopt a variety of changes at proteomic and metabolic levels for surviving under harmful environmental conditions including heavy metal stress. The current study investigates the impact of zinc stress on the proteome of Anabaena sphaerica to get an insight into its molecular mechanisms of zinc tolerance. The study revealed three different aspects that were associated with the zinc tolerance in A. sphaerica: (i) the reduced expression of photosynthesis, nitrogen fixation, energy metabolism, respiratory, and transcriptional/translational proteins probably to conserve energy and utilizing it to sustain growth; (ii) the enhanced expression of metallothionein and ferritin domain protein All 3940 to chelate free zinc ions whereas upregulation of antioxidative proteins for detoxifying reactive oxygen species; and (iii) the expression of large numbers of hypothetical proteins to maintain the important cellular functions. Furthermore, over expressions of sulfate adenylyl transferase and cystathionine beta synthase along with the increased synthesis of peptidases and thiolated antioxidant proteins were also noticed which denoted cysteine synthesis under sulfur deprivation possibly by mobilizing the sulfur from dead cells and its channelization towards the production of thiolated antioxidants. Besides tolerating excess amount of zinc, A. sphaerica exhibited high zinc biosorption efficiency which confirmed its outstanding zinc bioremediation potential.

Agrobacterium-mediated gene transfer: recent advancements and layered immunity in plants.

MAIN CONCLUSION: Plant responds to Agrobacterium via three-layered immunity that determines its susceptibility or resistance to Agrobacterium infection. Agrobacterium tumefaciens is a soil-borne Gram-negative bacterium that causes crown gall disease in plants. The remarkable feat of interkingdom gene transfer has been extensively utilised in plant biotechnology to transform plant as well as non-host systems. In the past two decades, the molecular mode of the pathogenesis of A. tumefaciens has been extensively studied. Agrobacterium has also been utilised as a premier model to understand the defence response of plants during plant-Agrobacterium interaction. Nonetheless, the threat of Agrobacterium-mediated crown gall disease persists and is associated with a huge loss of plant vigour in agriculture. Understanding the molecular dialogues between these two interkingdom species might provide a cure for crown gall disease. Plants respond to A. tumefaciens by mounting a three-layered immune response, which is manipulated by Agrobacterium via its virulence effector proteins. Comparative studies on plant defence proteins versus the counter-defence of Agrobacterium have shed light on plant susceptibility and tolerance. It is possible to manipulate a plant's immune system to overcome the crown gall disease and increase its competence via A. tumefaciens-mediated transformation. This review summarises the recent advances in the molecular mode of Agrobacterium pathogenesis as well as the three-layered immune response of plants against Agrobacterium infection.

A tau class GST, OsGSTU5, interacts with VirE2 and modulates the Agrobacterium-mediated transformation in rice.

KEY MESSAGE: OsGSTU5 interacts and glutathionylates the VirE2 protein of Agrobacterium and its (OsGSTU5) overexpression and downregulation showed a low and high AMT efficiency in rice, respectively. During Agrobacterium-mediated transformation (AMT), T-DNA along with several virulence proteins such as VirD2, VirE2, VirE3, VirD5, and VirF enter the plant cytoplasm. VirE2 serves as a single-stranded DNA binding (SSB) protein that assists the cytoplasmic trafficking of T-DNA inside the host cell. Though the regulatory roles of VirE2 have been established, the cellular reaction of their host, especially in monocots, has not been characterized in detail. This study identified a cellular interactor of VirE2 from the cDNA library of rice. The identified plant protein encoded by the gene cloned from rice was designated OsGSTU5, it interacted specifically with VirE2 in the host cytoplasm. OsGSTU5 was upregulated during Agrobacterium infection and involved in the post-translational glutathionylation of VirE2 (gVirE2). Interestingly, the in silico analysis showed that the 'gVirE2 + ssDNA' complex was structurally less stable than the 'VirE2 + ssDNA' complex. The gel shift assay also confirmed the attenuated SSB property of gVirE2 over VirE2. Moreover, knock-down and overexpression of OsGSTU5 in rice showed increased and decreased T-DNA expression, respectively after Agrobacterium infection. The present finding establishes the role of OsGSTU5 as an important target for modulation of AMT efficiency in rice.

Induction of Iron Stress in Hepatocellular Carcinoma Cell Lines by Siderophore of Aspergillus nidulans Towards Promising Anticancer Effect.

Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide and needs efficient and feasible approach of treatment. Present study focuses on exploring the anticancer activity of a secondary metabolite called siderophore of Aspergillus nidulans against hepatocellular carcinoma cell line HepG2. These small peptides are produced by microorganisms including fungi for scavenging iron from its surroundings. Fungi including Aspergillus spp. are known to produce siderophores under iron-limited conditions. Siderophores have high affinity towards iron and are classified into various types. In the present study, siderophore isolated and purified from fungal cultures was confirmed to be of hydroxamate type by chrome azurol sulfonate and Atkin's assay. HPLC analysis confirmed purity while LC-ESI-MS revealed that the siderophore is triacetyl fusigen. Cancerous cells, HepG2, grown under siderophore treatment showed inhibition in growth and proliferation in a dose- and time-dependent manner. Reduction in viability and metabolic activity was evident upon treatment as seen in trypan blue, MTT and WST assay. Fluorescent staining using PI and DAPI confirmed the same while DCFDA staining revealed increased reactive oxygen species production which might have led to cell death and deterioration. Such increase in ROS has been correlated with iron accumulation by assessing intracellular iron level through ICP-MS. To assess the effect of siderophore treatment on normal cells, WRL-68, same assays were carried out but the effect was mostly non-significant up to 48 h. Thus, present work suggests that an optimum dose of siderophore purified from A. nidulans culture might prove a useful anticancer agent.

A tau class glutathione-S-transferase (OsGSTU5) confers tolerance against arsenic toxicity in rice by accumulating more arsenic in root.

Arsenic (As) considered as one of the hazardous metalloid that hampers various physiological activities in rice. To study the mechanism of As tolerance in rice, one differentially expressed tau class glutathione-S-transferase (OsGSTU5) has been selected and transgenic rice plants with knockdown (KD) and overexpressing (OE) OsGSTU5 were generated. Our results suggested that KD lines became less tolerant to As stress than WT plants, while OE lines showed enhanced tolerance to As. Under As toxicity, OE and KD lines showed enhanced and reduced antioxidant activities such as, SOD, PRX and catalase, respectively indicating its role in ROS homeostasis. In addition, higher malondialdehyde content, poor photosynthetic parameters and higher reactive oxygen species (ROS) in KD plant, suggests that knockdown of OsGSTU5 renders KD plants more susceptible to oxidative damage. Also, the relative expression profile of various transporters such as OsABCC1 (As sequestration), Lsi2 and Lsi6 (As translocaters) and GSH dependent activity of GSTU5 suggests that GSTU5 might help in chelation of As with GSH and sequester it into the root vacuole using OsABCC1 transporter and thus limits the upward translocation of As towards shoot. This study suggests the importance of GSTU5 as a good target to improve the As tolerance in rice.

Degrading ability and robust antioxidative defence system led to SDS tolerance in cyanobacterium Fischerella sp. lmga1.

To test the tolerance and degradation potential of the cyanobacterium Fischerella sp. lmga1 for surfactant, sodium dodecyl sulfate (SDS), different doses of SDS (10, 30, 40, 50, 70 and 100 µM) were used for the growth. The lower doses of SDS supported the growth of cyanobacterium whereas the higher doses were found to be inhibitory but the cyanobacterium somehow managed its survival up to 100 µM SDS. However, a significant reduction was observed in the pigment and protein content. A substantial accumulation of carbohydrate at 70 µM SDS may act as an osmoprotectant for the survival of the cyanobacterium. The higher doses of SDS also triggered the ROS generation and lipid peroxidation which showed negative impact on the PSII efficiency. Simultaneously, an efficient ROS mitigation system (SOD and CAT activity) has also been worked up to 70 µM SDS while APX was enhanced only up to 50 µM SDS. Furthermore, the SDS degrading potential was investigated and almost 80% of the SDS was degraded after 6th days of treatment in the cyanobacterium. Hence, the results suggested that due to robust antioxidative defence system and ability to degrade the surfactant this cyanobacterium showed significant tolerance toward SDS.

Insights Into the Phylogenetic Distribution, Diversity, Structural Attributes, and Substrate Specificity of Putative Cyanobacterial Orthocaspases.

The functionality of caspase homologs in prokaryotic cell execution has been perceived, yet the dimensions of their metabolic pertinence are still cryptic. Here, a detailed in silico study on putative cyanobacterial caspase homologs, termed orthocaspases, in a sequenced genome of 132 strains was performed. We observed that 473 putative orthocaspases were distributed among 62% cyanobacterial strains subsumed within all the taxonomical orders. However, high diversity among these orthocaspases was also evident as the conventional histidine-cysteine (HC) dyad was present only in 72.03% of orthocaspases (wild-type), whereas the rest 28.18% were pseudo-variants having substituted the catalytic dyad. Besides, the presence of various accessory functional domains with Peptidase C14 probably suggested the multifunctionality of the orthocaspases. Moreover, the early origin and emergence of wild-type orthocaspases were conferred by their presence in Gloeobacter; however, the complex phylogeny displayed by these caspase-homologs perhaps suggested horizontal a gene transfer for their acquisition. However, morpho-physiological advancements and larger genome size favored the acquisition of orthocaspases. Moreover, the conserved caspase hemoglobinase fold not only in the wild-type but also in the pseudo-orthocaspases in Nostoc sp. PCC 7120 ascertained the least effect of catalytic motifs in the protein tertiary structure. Further, the 100-ns molecular dynamic simulation and molecular mechanics/generalized born surface area exhibited stable binding of arginylarginine dipeptide with wild-type orthocaspase of Nostoc sp. PCC 7120, displaying arginine-P1 specificity of wild-type orthocaspases. This study deciphered the distribution, diversity, domain architecture, structure, and basic substrate specificity of putative cyanobacterial orthocaspases, which may aid in functional investigations in the future.

Bioinformatics analysis of enzymes involved in cysteine biosynthesis: first evidence for the formation of cysteine synthase complex in cyanobacteria.

The biosynthesis of cysteine is crucial and critically regulated by two enzymes. i.e., serine acetyl transferase (SAT) and O-acetyl serine (thiol) lyase (OAS-TL). A descriptive account on the activity and regulatory mechanism of the enzyme is available in bacteria and plants. But no such studies yet performed in cyanobacteria, to understand the evolutionary aspect of cysteine biosynthesis and its regulation. Therefore, in our study a detailed bioinformatic analysis has been performed to understand all the possible features of cyanobacterial SATs and OAS-TLs. The analysis of SAT and OAS-TL sequences from cyanobacteria depicted that the large genome and morphological complexities favoured acquisition of these genes. Besides, conserved function of these enzymes was presumed by their sequence similarity. Further, the phylogenetic tree consisted of distinct clusters for unicellular, filamentous, and heterocytous strains. Nevertheless, the specificity pocket, SVKDR for OAS-TL having K as catalytic residue was also identified. Additionally, in silico protein modelling of SAT (SrpG) and OAS-TL (SrpH) of Synechococcus elongatus PCC 7942 was performed to gain insight into the structural attributes of the proteins. Finally, here we showed the possibility of hetero-oligomeric bi-enzyme cysteine synthase complex formation upon interaction of SAT and OAS-TL through protein-protein docking analysis thus provides a way to understand the regulation of cysteine biosynthesis in cyanobacteria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02899-1.

Effects of zinc toxicity on the nitrogen-fixing cyanobacterium Anabaena sphaerica-ultastructural, physiological and biochemical analyses.

The current study describes the mechanisms of zinc toxicity in the cyanobacterium Anabaena sphaerica after eight days treatment with 10 mg L-1 ZnCl2. The application of zinc not only showed elevated accumulation of the metal inside the cells but also exhibited devastating impacts on the cell numbers, morphology, and ultrastructure of A. sphaerica. The effects of zinc on the pigments contents, oxygen evolution rate, Fv/Fm, electron transport rate, and carbohydrate content were also evaluated in A. sphaerica. Moreover, zinc adversely affected nutrient uptake and the cellular energy budget in the test cyanobacterium which in turn hampered heterocyst development and nitrogen fixation. Alongside, the cyanobacterium experienced zinc-mediated non-competitive inhibition of glutamine synthetase activity, curtailed synthesis of amino acids and proteins. Furthermore, drastically reduced total lipid and increased unsaturated lipid contents were also the prominent characteristics of zinc stressed A. sphaerica. Most importantly, zinc stress caused severe damages to the protein, lipid, and DNA by triggering hydrogen peroxide generation and accumulation of oxidized glutathione. Therefore, excess zinc is highly toxic to the cyanobacterium A. sphaerica, and the mechanisms of its toxicity followed a cascade of events including oxidative stress mediated geopardisation of growth and ultrastructure, metabolic derangements, and macromolecular damages.

Disentangling the Impact of Sulfur Limitation on Exopolysaccharide and Functionality of Alr2882 by In Silico Approaches in Anabaena sp. PCC 7120.

The wide applications, uniqueness, and high quality of cyanobacterial exopolysaccharides (EPSs) have attracted many biotechnologists. Despite it, the inducers and molecular determinants of EPS biosynthesis in cyanobacteria are lesser known. Although, studies revealed that environmental cues especially C/N ratio as the prime modulator, the factors like light, temperature, moisture, and nutrient availability, etc. have been overlooked. Due to this, the possibilities to modify cyanobacterial system for achieving higher quantity of EPS either by modifying growth medium or metabolic engineering are restricted to few optimisations. Therefore, the present work describes the impact of sulfate limitations on the EPS production and compositions in the cyanobacterium Anabaena sp. PCC 7120. Increased EPS production with enhanced expression of alr2882 was observed in lower sulfate supplementations; however, FTIR analysis depicted an altered composition of supramolecule. Furthermore, in silico analysis of Alr2882 depicted the presence of ExoD domain and three transmembrane regions, thereby indicating its membrane localisation and role in the EPS production. Additionally, the phylogeny and multiple sequence alignment showed vertical inheritance of exoD and conservation among cyanobacteria. The meta-threading template-based modelling and ab initio full atomic relaxation by LOMET and ModRefiner servers, respectively, also exhibited helical topology of Alr2882, with nine α-helices arranged antiparallel to the preceding one. Moreover, post-translational modifications predicted in Alr2882 indicated high order of molecular regulation underlining EPS production in Anabaena sp. PCC 7120. This study provides a foundation for understanding the EPS biosynthesis mechanism under sulfur limitation and the possible role of ExoD in cyanobacteria.

Advancement in Pharmacological Activities of Benzothiazole and its Derivatives: An Up to Date Review.

Benzothiazole is a heterocyclic aromatic and bicyclic compound in which, benzene ring is attached with thiazole ring. This nucleus is established in marine as well as terrestrial natural compounds. The benzothiazole skeleton is established in a broad variety of bioactive heterocycles and natural products. The benzothiazole nucleus is considered as the principle moiety in several biologically active compounds. Over the decade, chemists are paying more attention towards the revision of the biological and therapeutic activities such as antimicrobial, analgesic, antiinflammatory, antitubercular, antiviral and antioxidant of benzothiazole containing compounds. The molecular structures of a number of potent drugs including Frentizole, Pramipexole, Thioflavin T and Riluzole etc., are based on benzothiazole skeleton. The present work is the compilation and presentation of all available information in a systematic manner with an aim to present the findings in a way, which may be beneficial for future research.