Impact of barrages on assemblage pattern of phytoplankton in tropical river Ganga, India.

The occurrence, abundance, and distribution of phytoplankton have been investigated upstream and downstream of three barrages on the river Ganga at Bijnor, Narora, and Kanpur in Uttar Pradesh, India. A total of 104 phytoplankton species belonging to eight phyla (Bacillariophyta, Charophyta, Chlorophyta, Cryptophyta, Cyanophyta, Euglenophyta, Miozoa, and Ochrophyta) were identified during the sampling period. During the summer, monsoon, and post-monsoon seasons, the density of phytoplankton (Ind. L-1) ranged from 9.6 × 104 to 2.03 × 107, 9.6 × 104 to 4.5 × 105, and 2.2 × 105 to 2.17 × 106, respectively. The species abundance and the relative abundance showed an increasing trend from the first (Bijnor) to the third (Kanpur) barrage, suggesting a gradual decrease in river flow and an increase in residence time. Phytoplankton cell density in Kanpur, however, was unexpectedly higher and showed eutrophic conditions attributable to elevated organic load and surplus nutrients from the land runoff. One-way ANOVA (post-hoc Tukey test) showed statistically significant (p < 0.05) seasonal variation in temperature, transparency, free CO2, PO43-, and dissolved organic matter. Analysis of Pearson's correlation coefficient suggested a statistically significant correlation (p < 0.05) of mostly phytoplanktonic groups with free CO2, CO32-, HCO3-, Cl-, specific conductivity, total dissolved solids, total hardness, Mg2+, PO43-, and SiO44-. The minimum species diversity was recorded during the monsoon season, while the maximum diversity was reported during the post-monsoon season which might be due to high nutrient load and a high concentration of PO43- post-monsoon. We concluded that aquatic biodiversity and ecological structure could be adversely influenced by a series of obstructed barrages and dams, which influenced the assemblage pattern of phytoplankton communities.

Clinical profile and risk factors for mortality among COVID-19 inpatients at a tertiary care centre in Bengaluru, India.

COVID-19 is an emerging viral disease affecting more than 200 countries worldwide and it present with varied clinical profile throughout the world. Without effective drugs to cure COVID-19, early identification and control of risk factors are important measures to combat COVID-19.  This study was conducted to determine the clinical profile and risk factors associated with mortality among COVID-19 patients in a tertiary care hospital in South India. This record-based longitudinal study was conducted by reviewing the case records of COVID-19 patients admitted for treatment from June 2020 to September 2020 in a tertiary care centre in South India. The clinical details, discharge/death details, were collected and entered in MS Excel. Potential risk factors for COVID-19 mortality were analysed using univariate binomial logistic regression, generalized linear models (GLM) with Poisson distribution. Survival curves were made using the Kaplan-Meier method. Log-rank test was used to test the equality of survivor functions between the groups. Out of 854 COVID-19 patients, 56.6% were men and the mean (standard deviation) age was 45.3(17.2) years. The median survival time was significantly lesser in male COVID-19 patients (16 days) as compared to female patients (20 days). Increasing age, male gender, patients presenting with symptoms of fever, cough, breathlessness, smoking, alcohol consumption, comorbidities were significantly associated with mortality among COVID-19 patients. Patients with older age, male gender, breathlessness, fever, cough, smoking and alcohol and comorbidities need careful observation and early intervention.  Public health campaigns aimed at reducing the prevalence of risk factors like diabetes, hypertension, smoking and alcohol use are also needed.

Pediatric tolerogenic DCs expressing CD4 and immunoglobulin-like transcript receptor (ILT)-4 secrete IL-10 in response to Fc and adenosine.

We characterized a novel population of tolerogenic myeloid dendritic cells (tmDCs) defined as CD11c+ CD11b+ CD14+ CD4+ and immunoglobulin-like transcript receptor (ILT)-4+ that are significantly more abundant in the circulation of infants and young children than in adults. TmDCs secrete the immunosuppressive lymphokine interleukin (IL)-10 when stimulated with the heavy constant region of immunoglobulins (Fc) and express high levels of the adenosine A2A receptor (A2A R), which, when activated by adenosine, inhibits the release of pro-inflammatory cytokines from most immune cells. Here we show that stimulation of the A2A R on tmDCs by regadenoson or N-ethylcarboxamidoadenosine (NECA) rapidly increases cyclic AMP accumulation and enhances IL-10 production under Fc stimulatory conditions. In co-culture experiments, tmDCs inhibit the differentiation of naïve T cells to a pro-inflammatory phenotype. In conclusion, although DCs are classically viewed as antigen presenting cells that activate T cells, we show an independent role of tmDCs in pediatric immune regulation that may be important for suppressing T cell responses to neoantigens in infants and young children.

Ecological and human health risk from exposure to metal contaminated sediments in a subtropical river affected by anthropogenic activities: A case study from river Yamuna.

Heavy metal enrichment in river sediments poses a significant risk to human and aquatic health. The Yamuna River faces severe challenges due to untreated industrial and domestic wastewater discharge. The study evaluates sediment metal content, ecological and human health risks, and potential sources. Results showed Cd and Pb exhibited moderate to severe contamination and displayed ecological risk based on contamination factor, enrichment factor, and potential ecological risk. According to synergistic indices (pollution load index, PINemerow, toxic risk index, contamination security index, mean probable effects level quotients, and probability of toxicity), the sediment in the Yamuna River doesn't seem to have a risk or enrichment from combined metals. Cd and Pb mainly originate from anthropogenic sources. Hazard index (< 1) and carcinogenic risk (2.2 × 10-7 to 4.7 × 10-5) assessments suggest metal didn't pose any risk to humans exposed to sediment. The present study aids in developing pollution control strategies for the Yamuna River.

Carbon sequestration and credit potential of gamhar (Gmelina arborea Roxb.) based agroforestry system for zero carbon emission of India.

The agroforestry system is the best option to achieve the net zero carbon emissions target for India. Keeping this view, carbon sequestration and credit potential of gamhar based agroforestry system has been assessed. The experiment was carried out in randomized block design in seven different treatments with five replications. Gamhar tree biomass accumulation was higher in gamhar based agroforestry system compared to sole gamhar. Among different tree components, stem contributed a maximum to total gamhar tree biomass followed by roots, leaves and branches. The average contributions of stems, roots, leaves and branches in total tree biomass in two annual cycles (2016-17 and 2017-18) varied between 50 and 60, 19.8 and 20, 19.2 and 20, and 10.7 and 12.7 percent, respectively. In case of crops, above ground, below ground and total biomass was significantly higher in sole intercrops than gamhar based agroforestry system. Total (Tree + interrops + Soil) carbon stock, carbon sequestration, carbon credit and carbon price were significantly affected by treatments, and was maximum in Sole Greengram-Mustard. Net carbon emission was also recorded lowest in Sole Greengram-Mustard for which the values were 811.55% and 725.24% and 760.69% lower than Sole Gamhar in 2016-17, 2017-18 and in pooled data, respectively.

Ecosystem-based fishery enhancement through pen culture of Indian major carp Labeo catla in a tropical floodplain wetland of North Eastern Region, India, during COVID pandemic.

The present study was conducted with the objective of developing ecologically and economically feasible pen culture protocols for Labeo catla as an alternate income source for wetland fishers in the context of the COVID-19 pandemic. Yearlings of L. catla (12.33 ± 1.99 cm mean total length and 26.05 ± 6.57 g mean weight) were reared in HDPE pens (500 m2 area each) at three different stocking densities of 3 (SD3), 6 (SD6) and 9 (SD9) no. m-2 in triplicates. Fishes were fed with floating pelleted feed containing 28% crude protein and 5% crude lipid two times daily at 1.5-3% of body weight. During the culture period, fish grew from 26.05 ± 6.57 to 434.61 ± 30.63 g, 306.13 ± 10.68 g and 221.13 ± 14.92 g, respectively, at stocking densities of 3, 6 and 9 no. m-2 respectively. Weight gain percentage and specific growth rate declined with increase in stocking density. Gross fish yield increased with increase in stocking density and was highest at SD9 (657.92 ± 53.55 kg pen-1), while net fish yield increased initially from SD3 to SD6 (594.31 ± 29.72 kg pen-1) and then declined with further increase in stocking density. Important water quality parameters influencing fish growth were measured, and significant difference (p > 0.05) was not observed between treatments (inside pens) and reference site (outside pen at 10-m distance). Weight gain was positively correlated (p < 0.05) to water temperature (r = 0.989) and total phosphorus (r = 0.81). Benefit cost ratio and net return was highest at SD3 (1.61; US $518.88, respectively). Stocking density of 3 no. m-2 can be considered economically feasible for table fish production of L. catla in pens. Post pen culture, monthly income of fishers increased by 10.76-179.11%, with a mean increase of 90.57%, compared to the period of first COVID-19 wave in India. The present findings can provide an impetus for effective utilization of pen enclosures for income generation and livelihood enhancement of small-scale wetland fishers during pandemic.

Influence of barrages on hydrological parameters and functional groups of phytoplankton of a subtropical river Ganga, India.

The current study used phytoplankton functional groups (FGs) to assess the impact of barrages on the ecological function of subtropical river Ganga. A total of 101 phytoplankton species were identified, including 20 phytoplankton FGs with MP and D having the highest prevalence rates of more than 50%. Other FGs with higher occurrence rates, such as N, A, and J, displayed seasonal and spatial advantages on occasion, indicating the randomness of exogenous influx from catchment areas. Based on phytoplankton FGs similarities, a non-metric multidimensional scaling analysis (NMDS) revealed geographical and seasonal discrepancies. The higher concentration of chemical components in Kanpur was linked to decreased water discharged from preceding reservoirs, resulting in a highly polluted stretch in terms of spatial variation, according to our findings. During the monsoon season, however, the diluting process caused by precipitation and surface runoff significantly improved water quality. As a result, we hypothesized that a sequence of barrages alters the hydrological characteristics of cascading reservoirs, which was related to spatial and seasonal fluctuation in FG diversity and phytoplankton FGs could be useful bioindicators of water quality. In conclusion, the phytoplankton FGs approach is useful for identifying the geographical and seasonal aspects of aquatic ecosystems that are heavily influenced by human activities, but its sensitivity to changes in spatial and seasonal water quality warrants more exploration.

Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma.

Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS. The 3A11 CAR T cells induced robust cytokine production and cytotoxicity against RMS cell lines in vitro. In contrast, a panel of healthy human primary cells failed to activate 3A11 CAR T cells, confirming the selectivity of 3A11 CAR T cells against tumors with high FGFR4 expression. Finally, we demonstrate that 3A11 CAR T cells are persistent in vivo and can effectively eliminate RMS tumors in two metastatic and two orthotopic models. Therefore, our study credentials CAR T cell therapy targeting FGFR4 to treat patients with RMS.

Clinical presentation and mortality risk factors for COVID-19 among diabetic patients in a tertiary care center in South India.

BACKGROUND: Non-communicable diseases (NCD) like hypertension, diabetes, cardiovascular and cerebrovascular diseases are the most common comorbidities among COVID-19 patients. The clinical presentation and mortality pattern of COVID-19 are different for patients with comorbidities and without comorbidities. OBJECTIVE: To determine the clinical presentation of COVID-19 and risk factors for COVID-19 mortality among diabetic patients in a tertiary care hospital in South India. METHODS: A record-based cross-sectional study was conducted by reviewing the case records of COVID-19 patients admitted for treatment from June 2020 to September 2020 in a tertiary care centre in South India. Potential risk factors for COVID-19 mortality were analysed using univariate binomial logistic regression, generalized linear models (GLM) with the Poisson distribution. Survival curves were made using the Kaplan-Meier method. RESULTS: Out of 200 COVID-19 patients with diabetes with a mean (SD) age of 56.1 (11.8) years, 61% were men. The median survival time was slightly lesser in male COVID-19 patients (15 days) as compared to female patients (16 days). The risk of mortality among COVID-19 patients with diabetes is increased for patients who presented with breathlessness (aRR = 4.5 (95% CI: 2.3-8.8)), had positive history of smoking (aRR = 1.9 (95% CI: 1.1-3.8)), who had CKD (aRR = 1.8 (95% CI: 1.1-2.8)) and who had cardiac illness (aRR = 1.6 (95% CI: 0.9-2.7)). CONCLUSION: Diabetes patients with COVID-19 need to be given additional care and monitoring especially if they present with breathlessness, positive history of smoking, cardiac illness and, CKD. Public health campaigns and health education activities to control smoking is needed to reduce the COVID-19 mortality in diabetes patients.

Co-Prevalence of Virulence and Pathogenic Potential in Multiple Antibiotic Resistant Aeromonas spp. from Diseased Fishes with In Silico Insight on the Virulent Protein Network.

Aeromonas species exhibit widespread presence in food, poultry, and aquaculture. They are major multi-drug-resistant fish pathogens. This study aims to identify Aeromonas species harbouring virulence genes aerolysin, flagellin, and lipase from diseased fishes of Assam wetlands with association with antibiotic resistance and in vivo pathogenicity. One hundred and thirty-four Aeromonas strains were isolated and thirty representative species identified using genus-specific 16S rRNA gene amplification. A. veronii was most prevalent (53.7%) followed by A. hydrophila (40.2%), A. caviae (4.47%), and A. dhakensis (1.49%). Ninety percent (90%) of strains harboured at least one of the studied virulence genes: aerA (73.3%), lip (46.6%), and flaA (26.6%). The highest multiple antibiotic resistance (MAR) index 0.8 corresponded to A. hydrophila DBTNE1 (MZ723069), containing all the studied genes. The lowest LD50 values (1.6 × 106 CFU/fish) corresponded to isolates having both aerA and lip. ß-lactams showed utmost resistance and lowest for aminoglycosides. There was a significant (p < 0.05) Pearson chi-square test of association between the occurrence of virulence and antibiotic resistance. The in silico protein−protein interaction revealed important drug targets, such as σ28 transcription factor, aminoacyl-tRNA synthetase, and diacylglycerol kinase, with significant (p < 0.05) enrichment. This study suggests that fish-isolate Aeromonas strains represent potential threat to aquaculture with subsequent risk of transferring antibiotic resistance to human pathogens.

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches.

Umbilical cord blood-derived CD11c(+) dendritic cells could serve as an alternative allogeneic source of dendritic cells for cancer immunotherapy.

INTRODUCTION: Allogenic dendritic cells (DCs) generated from healthy donors, who are complete or partially HLA-matched, have been used for clinical trials. One of the sources for allogenic DCs is umbilical cord blood (UCB) cells. However, as far as cord blood cells are concerned, looking at their naïve nature, there is a concern as to whether the DCs generated from them will have enough potential to elicit a proper T cell response. For this, we compared CD11c(+) UCB-DCs/ Cytotoxic T lymphocytes (CTLs) with the conventional source, i.e. peripheral blood (PBL) monocyte DCs/CTLs, using various parameters. METHODS: CD11c(+) DCs generated from the two sources were compared morphologically, phenotypically and functionally. Functional assays included antigen uptake, chemotactic migration and MLR (mixed lymphocyte reaction). The CTLs generated were examined for the activation markers, granzyme A & granzyme B, and IFN-γ secretion. MUC1 (STAPPVHNV) peptide-specific CTLs were quantified by Streptamer staining. In vitro CTL activity was assessed by their efficiency in killing MCF-7 cells. For in vivo CTL assay, a xenograft of MCF-7-luc-F5 cells in female NOD/SCID mice was employed. Regression of tumors in mice was monitored using an in vivo imaging system before and after ten days of CTL infusion. Statistical analysis of all the experiments between the two groups was evaluated by one-way ANOVA. RESULTS: The CD11c(+) DCs from the two sources were morphologically and phenotypically similar. Their capacity to uptake antigen, migration towards CCL-19 and MLR activity were equivalent. UCB-CTLs had significantly higher levels of activation markers, number of MUC1 specific CTLs, IFN-γ secretion and IL-12p70/IL-10 ratio than that of PBL-CTLs. Hematoxylin and Eosin-stained tumor sections showed T cell infiltration, which was further confirmed by immunofluorescence staining. In vivo CTL activity was found to be similar with the two sources. CONCLUSIONS: Our data demonstrate that CD11c(+) UCB-DCs/CTLs are as potent as standard CD11c(+) PBL-DC/CTLs and could therefore be used as an allogenic source for therapeutic purposes. The findings of this study could help in taking us one step closer towards the personalized therapy using DC based cancer vaccines.

Exogenous addition of arachidonic acid to the culture media enhances the functionality of dendritic cells for their possible use in cancer immunotherapy.

The development of dendritic cell based vaccines is a promising approach in cancer immunotherapy. For their successful use in the clinics, the propagation and functionality of DCs is crucial. We earlier established a two-step method for the large scale generation of DCs from umbilical cord blood derived MNCs/CD34(+) cells. This work aims at improving their functionality based on the following observations: in vitro generated DCs can be less efficient in migration and other functional activities due to lower eicosanoid levels. The production of eicosanoids from Arachidonic Acid (AA) can be hampered due to suppression of the enzyme phospholipase A2 by IL-4, an essential cytokine required for the differentiation of DCs. We hypothesized that exogenous addition of AA to the culture media during DC generation may result in DCs with improved functionality. DCs were generated with and without AA. The two DC sets were compared by phenotypic analysis, morphology and functional assays like antigen uptake, MLR, CTL assay and in vitro and in vivo migration. Though there were no differences between the two types of DCs in terms of morphology, phenotype and antigen uptake, AA(+) DCs exhibited an enhanced in vitro and in vivo migration, T cell stimulatory capacity, CTL activity and significantly higher transcript levels of COX-2. AA(+) DCs also show a favorable Th1 cytokine profile than AA- DCs. Thus addition of AA to the culture media is skewing the DCs towards the secretion of more IL-12 and less of IL-10 along with the restoration of eicosanoids levels in a COX-2 mediated pathway thereby enhancing the functionality of these cells to be used as a potent cellular vaccine. Taken together, these findings will be helpful in the better contriving of DC based vaccines for cancer immunotherapy.