Kinetics of Decomposition of Nitramine Propellant by Differential Scanning Calorimetry

The paper describes an experimental procedure for the determination of overall kinetic parameters for the exothermic decomposition reaction of nitramine propellant. The kinetic parameters can be obtained through the use of differential thermal analysis (DTA), differential scanning calorimetry (DSC) or thermogravimetric analysis (TGA) methods. The procedure is applicable to reactions whose behaviour can be described by the Arrhenius equation and the general rate law. In the present work, DSC technique has been used for the evaluation of Arrehenius activation parameters and specific rate constants for thermal decomposition of a typical nitramine propellant. The kinetic parameters were computed by Ozawa and Kissinger methods for comparison. The activation energy value obtained from the Ozawa method is refined by an iteration procedure using Doyle approximation for the Arrhenius temperature integral p(x)

Evaluation of Anti-inflammatory property of Melanin from marine Bacillus sp BTCZ31

 Objectives: To evaluate the anti-inflammatory property of melanin from marine Bacillus spp. BTCZ31.Methods: Radical scavenging property of melanin was determined by 2,2-Diphenyl-1-picrylhydrazyl and metal chelation assays, which was furtherconfirmed by electron paramagnetic resonance (EPR) spectroscopy. Anti-inflammatory property of melanin was explored in vitro in RAW264.7cell line using cyclooxygenase (COX), Lipoxygenase (LOX), Myleoperoxidase (MPO), cellular nitrite inhibitory assays. Cytotoxicity of melanin wasdetermined using 3-(4,5 dimethythiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay.Results: BTCZ31 melanin showed radical scavenging activity of 67.55% and ferrous ion chelating activity of 97.88%. EPR spectrum showed sharppeaks indicating the presence of unpaired electrons. Melanin inhibited the activity of COX and LOX enzyme with IC50 values of 104.34 μg/mL and10.5 μg/mL, respectively. It also reduced the activity of MPO and cellular nitrite levels. Cytotoxic concentration of melanin was found to be 105.4 μg/mL(IC50).Conclusion: Bacillus spp. BTCZ10 melanin can be a potential anti-inflammatory agent. Further in vivo evaluations are needed for confirming theactivity, leading to therapeutic applications.Keywords: Anti-inflammatory, Antioxidant, Bacillus spp., Bacteria, Marine, Melanin

Multiplex ligation-dependent probe amplification (MLPA) analysis is an effective tool for the detection of novel intragenic PLA2G6 mutations: Implications for molecular diagnosis

Phospholipase associated neurodegeneration (PLAN) comprises a heterogeneous group of autosomal recessive neurological disorders caused by mutations in the PLA2G6 gene. Direct gene sequencing detects 85% mutations in infantile neuroaxonal dystrophy. We report the novel use of multiplex ligation-dependent probe amplification (MLPA) analysis to detect novel PLA2G6 duplications and deletions. The identification of such copy number variants (CNVs) expands the PLAN mutation spectrum and may account for up to 12.5% of PLA2G6 mutations. MLPA should thus be employed to detect CNVs of PLA2G6 in patients who show clinical features of PLAN but in whom both disease-causing mutations cannot be identified on routine sequencin

HPLC-LIF for early detection of oral cancer

At present, the diagnosis of many cancers relies on the subjective interpretation of morphological changes in biopsy samples. This usually provides only late diagnosis. Early detection, which can provide more successful therapy, is expected to be possible by identification of tumour markers in physiological samples. Immunoassay used at present for this purpose has several drawbacks. It is applicable only for known markers, can usually detect only one marker at a time, and may also fail to detect a marker when there exist conditions, which may mask or prevent the interaction between antigen and the antibody. We have developed a high performance liquid chromatography- laser induced fluorescence (HPLC-LIF) technique to detect and record simultaneously spectra and chromatograms of physiological samples, which will enable the detection of multiple 'markers' in a single physiological sample in a short time. Samples of saliva and serum from normal and oral cancer subjects have been studied with the set up. The present studies show that body fluids like saliva and serum of normal, premalignant and malignant subjects have substantially different protein profiles. By simultaneous recording of the chromatographic peaks and corresponding fluorescence spectra, it is possible to carry out unambiguous discrimination between normal, premalignant and malignant cases even when markers are present in femto/subfemtomole quantities, which should assist in early diagnosis of neoplasia

Studies on development of instant pumpkin soup tablets and evaluation of storage stability

486-491A study was carried out to develop pumpkin soup tablet with enriched β-carotene which can be instantly reconstituted in hot water. Ingredients of pumpkin soup tablet namely pumpkin flour (32.5%), corn flour (19.4%), milk powder (14.5%), onion powder (3.2%), pepper powder (3.2%), coriander (1.3%), garlic (1.3%), saturated fat (6.5%) and salt (13.9%) were optimised. Maltodextrin and xanthan gum were used as emulsifier to prepare two variants of the soup cube formulations. Proximate composition, β-carotene, textural attributes and microbiological quality of the developed product were determined during storage at room temperature. Sensory acceptability of the product was evaluated by reconstituting the soup cube in hot water. The study revealed that the product was acceptable and could be reconstituted instantly in hot water. Soup tablets prepared with xanthan gum as emulsifier were superior in colour, texture and retention of β-carotene. The incorporation of pumpkin flour in soup cube enhanced its nutritional value to an extent of 50% of RDI for β-carotene. The product could be a convenient alternative for preparing an organoleptically acceptable soup instantly and thereby saving packaging cost and space

Aromatic l-amino acid decarboxylase deficiency: a patient-derived neuronal model for precision therapies

Aromatic l-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. The majority of affected individuals have variable, though often severe cognitive and motor delay, with a complex movement disorder and high risk of premature mortality. For most, standard pharmacological treatment provides only limited clinical benefit. Promising gene therapy approaches are emerging, though may not be either suitable or easily accessible for all patients. To characterize the underlying disease pathophysiology and guide precision therapies, we generated a patient-derived midbrain dopaminergic neuronal model of AADC deficiency from induced pluripotent stem cells. The neuronal model recapitulates key disease features, including absent AADC enzyme activity and dysregulated dopamine metabolism. We observed developmental defects affecting synaptic maturation and neuronal electrical properties, which were improved by lentiviral gene therapy. Bioinformatic and biochemical analyses on recombinant AADC predicted that the activity of one variant could be improved by l-3,4-dihydroxyphenylalanine (l-DOPA) administration; this hypothesis was corroborated in the patient-derived neuronal model, where l-DOPA treatment leads to amelioration of dopamine metabolites. Our study has shown that patient-derived disease modelling provides further insight into the neurodevelopmental sequelae of AADC deficiency, as well as a robust platform to investigate and develop personalized therapeutic approaches

Aromatic L-amino acid decarboxylase deficiency: a patient-derived neuronal model for precision therapies

Aromatic L-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. The majority of affected individuals have variable, though often severe cognitive and motor delay, with a complex movement disorder and high risk of premature mortality. For most, standard pharmacological treatment provides only limited clinical benefit. Promising gene therapy approaches are emerging, though may not be either suitable or easily accessible for all patients. In order to better characterize the underlying disease pathophysiology and guide precision therapies, we generated a patient-derived midbrain dopaminergic (mDA) neuronal model of AADC deficiency from induced pluripotent stem cells (iPSCs). The neuronal model recapitulates key disease features, including absent AADC enzyme activity and dysregulated dopamine metabolism. We observed developmental defects affecting synaptic maturation and neuronal electrical properties, which were improved by lentiviral gene therapy. Bioinformatic and biochemical analyses on recombinant AADC predicted that the activity of one variant could be improved by L-3,4-dihydroxyphenylalanine (L-DOPA) administration; this hypothesis was corroborated in the patient-derived neuronal model, where L-DOPA treatment leads to amelioration of dopamine metabolites. Our study has shown that patient-derived disease modelling provides further insight into the neurodevelopmental sequelae of AADC deficiency, as well as a robust platform to investigate and develop personalised therapeutic approaches

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches

© 2019 H. P. Ellis et al. Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel. Copy number variations (CNVs) and single nucleotide variants (SNVs) were examined, and potentially pathogenic variants and clinically actionable mutations were identified. The results revealed that glioblastomas were IDH-wildtype (IDHWT; n = 38) and IDH-mutant (IDHMUT; n = 3). SNVs in TSC2, MSH6, TP53, CREBBP, and IDH1 were variants of unknown significance (VUS) that were predicted to be pathogenic in both subtypes. IDHWT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein pathways. Many tumours had BRCA1/2 (18%) variants, including confirmed somatic mutations in haemangioblastoma. IDHWT recurrent tumours had fewer pathways impacted (RTK/Ras/PI(3)K, p53, WNT, and G-protein) and CNV gains (BRCA2, GNAS, and EGFR) and losses (TERT and SMARCA4). IDHMUT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, and WNT pathways. VUS in KLK1 was possibly pathogenic in IDHMUT. Recurrent tumours also had fewer pathways (p53, WNT, and G-protein) impacted by genetic alterations. Public datasets (TCGA and GDC) confirmed the clinical significance of findings in both subtypes. Overall in this cohort, potentially actionable variation was most often identified in EGFR, PTEN, BRCA1/2, and ATM. This study underlines the need for detailed molecular profiling to identify individual GBM patients who may be eligible for novel treatment approaches. This information is also crucial for patient recruitment to clinical trials

Variation of biogenic sulphur compounds in the estuarine and coastal waters of Goa, West coast of India

Dimethylsulphide (DMS) originates predominantly from dimethylsulphoniopropionate (DMSP), a metabolite produced by phytoplankton. Through its contribution to the production of new aerosols and cloud condensation nuclei, a high concentration of DMS has the potential to influence the radiation budget of the earth. Estuaries and coastal regions being dynamic may produce significantly high concentrations of DMS and DMSP. The present study aimed to investigate the spatial variation of DMS, its precursor total dimethylsulphoniopropionate (DMSPt), and its sink total dimethylsulphoxide (DMSOt) at 7 estuarine locations in 4 rivers and a coastal station in Goa during the North East Monsoon (NEM). Generally, higher concentrations of DMS and DMSPt were observed at the near mouth stations and the coastal station compared to upstream stations. Though a positive correlation was observed between salinity and DMSPt, it was not significant, indicating the involvement of other factors influencing DMSP and DMS concentrations. Diatoms were the most abundant group accounting for > 90 % of the phytoplankton. However, higher fractions of dinoflagellates, nano- and picoplankton probably contributed to the DMSPt, DMS and DMSOt production at the coastal and near mouth stations. As the wind speeds were low, DMS flux was governed by surface DMS concentrations and varied between 0.07 and 2.11 µmoles S m-2 D-1 with an average of 0.92±0.80 µmoles S m-2 D-1. In comparison to DMSPt and DMS, a relatively higher concentration of DMSOt was observed in the study area. While the high DMSOt concentration at the estuarine mouths may be attributed to the photo- or biological oxidation of DMS, those in the upper reaches point to an unknown source and warrants further investigation