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Bulk foam analysis (static test) is simple and fast, which makes it a cost-effective method for screening and ranking hundreds of surfactants being considered for foam applications. Coreflood tests (dynamic test) can also be used, but it is quite laborious and costly. However, previous reports show that ranking based on static tests sometimes differs from ranking based on dynamic tests. To date, the reason for such a discrepancy is not well understood. Some believe that it may be due to faulty experimental design while some others believe that there is no discrepancy if the right foam performance indices are used to describe and compare the results from both methods. For the first time, this study reports a systematic series of static tests conducted on different foaming solutions (with surfactant concentration ranging from 0.025 to 5 wt%) and duplicated in dynamic tests using the same core sample for all the surfactant solutions. The dynamic test was also repeated on three different rocks of a wide permeability range (26–5000 mD) for each of the surfactant solutions. Unlike previous studies, here multiple dynamic foam indices (limiting capillary pressure, apparent viscosity, trapped foam, and trapped to mobile foam ratio) were measured and compared with the performance indices measured from the static tests (foam texture and foam half-life). Dynamic tests were in total agreement with static tests for all the foam formulations. However, it was observed that the pore size of the base filter disk used in the static foam analyzer can be a potential source of conflicting results when comparing with dynamic test. This is because a threshold pore size exists above which some foam properties (apparent viscosity and trapped foam) significantly decreased compared to the properties before that threshold. Foam limiting capillary pressure is the only foam property that does not show such a trend. It also appears that such threshold occurs above a certain surfactant concentration (0.025 wt%). Apparently, it becomes imperative that the pore size of the filter disk used in the static test and the porous medium used in dynamic tests must be on the same side of the threshold point, otherwise there may be disparity in their results. The threshold surfactant concentration should also be determined. The role of these two factors (pore size and surfactant concentration) requires further investigation.

As an alternate for the conventional glass-based pH sensor which is associated with problems like fragile nature, alkaline error, and potential drift, the development of a new redox-sensitive pH probe-modified electrode that could show potential, current-drift and surface-fouling free voltammetric pH sensing is a demanding research interest, recently. Herein, we report a substituted carbazole-quinone (Car-HQ) based new redox-active pH-sensitive probe that contains benzyl and bromo-substituents, immobilized multiwalled carbon nanotube modified glassy carbon (GCE/MWCNT@Car-HQ) and screen-printed three-in-one (SPE/MWCNT@Car-HQ) electrodes for selective, surface-fouling free pH sensor application. This new system showed a well-defined surface-confined redox peak at an apparent standard electrode potential, Eo′ = − 0.160 V versus Ag/AgCl with surface-excess value, Γ = 47 n mol cm−2 in pH 7 phosphate buffer solution. When tested with various electroactive chemicals and biochemicals such as cysteine, hydrazine, NADH, uric acid, and ascorbic acid, MWCNT@Car-HQ showed an unaltered redox-peak potential and current values without mediated oxidation/reduction behavior unlike the conventional hydroquinone, anthraquinone and other redox mediators based voltammetry sensors with serious electrocatalytic effects and in turn potential and current drifts. A strong π–π interaction, nitrogen-atom assisted surface orientation and C–C bond formation on the graphitic structure of MWCNT are the plausible reasons for stable and selective voltammetric pH sensing application of MWCNT@Car-HQ system. Using a programed/in-built three-in-one screen printed compatible potentiostat system, voltammetric pH sensing of 3 μL sample of urine, saliva, and orange juice samples with pH values comparable to that of milliliter volume-based pH-glass electrode measurements has been demonstrated.

The milk and milk products from cows reared under grazing system are believed to be healthier and hence have high demand compared to milk from cows reared in the non-grazing system. However, the effect of grazing on milk metabolites, specifically lipids has not been fully understood. In this study, we used acetonitrile precipitation and methanol:chloroform methods for extracting the milk metabolites followed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) run to identify the different metabolites between the milk of grazing and non-grazing early lactating Malnad Gidda cows. Various carbohydrates, amino acids, nucleosides and vitamin derivatives were found to be differentially abundant in grazing cows. A total of 35 metabolites were differentially regulated (fold change above 1.5) between the two groups. Tyrosyl-threonine, histidinyl-cysteine, 1-methyladenine, l-cysteine and selenocysteine showed fold change above 3 in grazing cows. The lipid profile of milk showed a lesser difference between grazing and non-grazing cows as compared to polar metabolites. To the best of our knowledge, this is the largest inventory of milk metabolomics data of an Indian cattle (Bos indicus) breed. We believe that our study would help to emerge a field of Nutri-metabolomics and veterinary omics research.

Dragon fruit (Hylocereus spp.), an important tropical fruit belonging to the family Cactaceae, is rich in essential nutrients such as vitamins, minerals, complex carbohydrates, dietary fibres and antioxidants. This study aims to distinguish three dragon fruit species well adapted to Andaman and Nicobar Island through morphological (34 quantitative and 26 qualitative traits), biochemical (5 traits) and molecular (14 ISSR primers) characterization. Morphological characterization revealed that presence of considerable amount of genetic variations among them especially for fruit characters viz., colour of peel and pulp. Cladode characters such as number of spines (3–5), length of areoles (mm) as 1–4, margin ribs of cladode (convex or concave) and its waxiness (weak or strong white waxy or light waxy) could be used for identification of three Hylocereus spp. under present study. Highest co-efficient of variation (%) obtained for pulp weight (88.7), whereas, lowest in distance of anthers belowstigma (3.3). Fruit and pulp weight (g) ranged from 26.5–419.3 and 10.3–258.8 with mean value of 204.8 and 125.3, respectively. Comparatively, high phenol (71.3–161.3) and flavonoid (26.6–508.2) content observed in peels than pulp (32.5–130.0 and 45.0–258.2) of fruit indicating higher antioxidant potential. Highest total carotenoids (µg 100 g−1), β-carotene (µg 100 g−1) and xanthophyll (µg g−1) content obtained in pulp on DGF3 (33.8), DGF4 (55.9) and DGF3 (32.7), whereas, in peel on DGF2 (24.3), DGF4 (18.5) and DGF2 (24.1), respectively. DPPH-based scavenging activity (%) revealed higher scavenging activity of peels (55.6–81.2) than pulp (36.0–75.3) extracts. Comparatively, ABTS-based scavenging activity (%) was found more than DPPH-based one. Sixteen ISSR primers screened, 14 were produced 178 reproducible amplified bands. Number of amplified bands varied from 5 in UBC887 to 19 in UBC811 with an average of 12.71 bands per primer. Range of polymorphic bands and % polymorphism observed were 1–13 and 20.0–92.8, respectively. The polymorphic information content value of ISSR marker ranged from 0.42 (UBC895) to 0.91 (UBC 856). Cluster analysis distinguished three different Hylocereus species on the basis of geographic origin and pulp colour by forming separate groups and two genotypes each showed 52% (DGF1 and DGF3) and 76% (DGF2 and DGF4) genetic similarity. Key traits identified for distinguishing three different Hylocereus species were: Pulp/ peel colour of fruits, number of spines and length of areoles in cladode. Genotypes with high carotenoid and xanthophylls content (DGF4 and DGF2) identified under present study may be of industrial importance for development of nutraceutical products to meet out the vitamin-A deficiency among humans in tropical regions needed future focus.

Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions. The common C677T variant of the MTHFR gene was also screened by restriction fragment length polymorphism. Fifteen children were clinically suspected of having classical homocystinuria and one asymptomatic child with positive family history. Only seven children had biochemical features of classical homocystinuria. Sanger sequencing of the CBS gene confirmed 15 different pathogenic or likely pathogenic variants in 14 cases. Of these, seven variants were novel (three frameshift deletions, two nonsense, one missense, one splice site variant) and were predicted to be deleterious by Mutation Taster software. Seven cases were homozygous, another six were compound heterozygous, and one case was single heterozygous in the study. None of the three most frequent mutations reported worldwide viz., I278T, G307S, and IVS 11-2A>C were found in our cohort. No variants were detected in the exons 2, 8, 12, and 14 as compared to reported literature. Eleven out of 15 variants were associated with the conserved catalytic domain of the CBS polypeptide. The MTHFR polymorphism C677T was observed in heterozygous state in six cases. Our study reports the detailed genotype and seven novel variants in the CBS gene, causing classical homocystinuria in Indian children. The genetic analysis will help to offer accurate genetic counseling, prenatal diagnosis, and development of mutation-based novel therapeutic strategies.

Muscle contraction, which is initiated by Ca2+, results in precise sliding of myosin-based thick and actin-based thin filament contractile proteins. The interactions between myosin and actin are finely tuned by three isoforms of myosin binding protein-C (MyBP-C): slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C and cMyBP-C, respectively), each with distinct N-terminal regulatory regions. The skeletal MyBP-C isoforms are conditionally coexpressed in cardiac muscle, but little is known about their function. Therefore, to characterize the functional differences and regulatory mechanisms among these three isoforms, we expressed recombinant N-terminal fragments and examined their effect on contractile properties in biophysical assays. Addition of the fragments to in vitro motility assays demonstrated that ssMyBP-C and cMyBP-C activate thin filament sliding at low Ca2+. Corresponding 3D electron microscopy reconstructions of native thin filaments suggest that graded shifts of tropomyosin on actin are responsible for this activation (cardiac > slow-skeletal > fast-skeletal). Conversely, at higher Ca2+, addition of fsMyBP-C and cMyBP-C fragments reduced sliding velocities in the in vitro motility assays and increased force production in cardiac muscle fibers. We conclude that due to the high frequency of Ca2+ cycling in cardiac muscle, cardiac MyBP-C may play dual roles at both low and high Ca2+. However, skeletal MyBP-C isoforms may be tuned to meet the needs of specific skeletal muscles.

Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70–80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families. Since defects in DNA mismatch repair genes generate frame-shift mutations giving rise to highly immunogenic neoepitopes, we postulated that vaccination with these mutant peptide antigens could offer promising treatment options to LS patients. To this end we performed whole-exome and RNA seq analysis on the blood and tumour samples from an LS-CRC patient, and used our proprietary neoepitope prioritization pipeline OncoPeptVAC to select peptides, and confirm their immunogenicity in an ex vivo CD8+ T cell activation assay. Three neoepitopes derived from the tumour of this patient elicited a potent CD8+ T cell response. Furthermore, analysis of the tumour-associated immune infiltrate revealed CD8+ T cells expressing low levels of activation markers, suggesting mechanisms of immune suppression at play in this relapsed tumour. Taken together, our study paves the way towards development of a cancer vaccine to treat or delay the onset/relapse of LS-CRC.

Efficient, fast and new micro-analytical methods for characterization of ultrastructures of fungal spores with electron microscopy are very much required and essential. SEM analysis of biological materials, especially fungi, requires optimal preparation of the specimen and often requires the usage of dried samples which demands a challenging sample preparation. In the present investigation, we described a fast and improved method for the preparation of fungal specimen for scanning electron microscopy (SEM). The fungus, Curvularia lunata was grown on the surface of sterile Whatman No.1 filter paper which was overlaid on Potato Dextrose Agar (PDA) medium, gold coated immediately after removal from the growth medium and subjected to imaging. Generally, SEM imaging is done with samples that were fixed with chemical fixatives, dehydrated and gold coated specimens, but here we describe an easy and more efficient sample preparation for SEM which enabled enhanced image quality and precision visualization of fungal cells, especially the spores. The developed method has enabled the analysis of even the robust samples like fungal spores that to eliminating special temperature requirement. The ultimate goal was to develop an improved protocol/method applied to analysis of fungal spores with greater coverage about fungal specimen preparation. This method permits the use of rapid sample preparation and will allow us to imaging of individual spore or conidia structures in the context of fungal cell architecture which clarifies our understanding in fungal taxonomy/biology.

We report a simple hydrothermal method used for the synthesis of Cr2Se3 hexagons (h-Cr2Se3) and its application towards electrochemical sensing of 4-nitrophenol (4-NP). The formation of h-Cr2Se3 was confirmed by using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The electrochemical activity of the h-Cr2Se3 modified screen-printed carbon electrode (SPCE) towards 4-NP was studied using cyclic voltammetry (CV) and amperometric i-t techniques. Typically, the obtained results were compared with those for a bare SPCE. The CV result clearly reveals that h-Cr2Se3 modified SPCE has higher catalytic activity towards reduction of 4-NP than bare SPCE. Hence, h-Cr2Se3 modified SPCE was concluded as a viable sensor for sensitive determination of 4-NP. Under optimized conditions, h-Cr2Se3 modified SPCE demonstrates the excellent capacity to detect the 4-NP in a linear range from 0.05 µM to 908.0 µM. The LOD and sensitivity in detection of 4-NP were determined at 0.01 µM and 1.24 µAµM−1 cm−2 respectively. The sensor is highly selective and stable and shows reproducible recovery of 4-NP in domestic supply and river water samples.

Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.

The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.

We report a class of amorphous thin film material comprising of transition (Fe) and Lanthanide metals (Dy and Tb) that show unique combination of functional properties. Films were deposited with different atomic weight ratio (R) of Fe to Lanthanide (Dy + Tb) using electron beam co-evaporation at room temperature. The films were found to be amorphous, with grazing incidence x-ray diffraction and x-ray photoelectron spectroscopy studies indicating that the films were largely oxidized with a majority of the metal being in higher oxidation states. Films with R = 0.6 were semiconducting with visible light transmission due to a direct optical band-gap (2.49 eV), had low resistivity and sheet resistance (7.15 × 10−4 Ω-cm and ~200 Ω/sq respectively) and showed room temperature ferromagnetism. A metal to semiconductor transition with composition (for R 0 oxidation state in the R = 0.6 case as well as a significantly higher fraction of oxidized Dy. The combination of amorphous microstructure and room temperature electronic and magnetic properties could lead to the use of the material in multiple applications, including as a transparent conductor, active material in thin film transistors for display devices and in spin-dependent electronics.

The Sec13 protein functions in various intracellular compartments including the nuclear pore complex, COPII-coated vesicles and inside the nucleus as a transcription regulator. Here we developed a mouse model that expresses low levels of Sec13 (Sec13H/−) to assess its functions in vivo, as Sec13 knockout is lethal. These Sec13 mutant mice did not present gross defects in anatomy and physiology. However, the reduced levels of Sec13 in vivo yielded specific immunological defects. In particular, these Sec13 mutant mice showed low levels of MHC I and II expressed by macrophages, low levels of INF-γ and IL-6 expressed by stimulated T cells and low frequencies of splenic IFN-γ+CD8+ T cells. In contrast, the levels of soluble and membrane-bound TGF-β as well as serum immunoglobulin production are high in these mice. Furthermore, frequencies of CD19+CD5-CD95+ and CD19+CD5-IL-4+ B cells were diminished in Sec13H/− mice. Upon stimulation or immunization, some of the defects observed in the naïve mutant mice were compensated. However, TGF-β expression remained high suggesting that Sec13 is a negative modulator of TGF-β expression and of its immunosuppressive functions on certain immune cells. In sum, Sec13 regulates specific expression of immune factors with key functions in inflammation.

Elevated protein kinase C βII (PKCβII) expression develops during heart failure and yet the role of this isoform in modulating contractile function remains controversial. The present study examines the impact of agonist-induced PKCβII activation on contractile function in adult cardiac myocytes. Diminished contractile function develops in response to low dose phenylephrine (PHE, 100 nM) in controls, while function is preserved in response to PHE in PKCβII-expressing myocytes. PHE also caused PKCβII translocation and a punctate distribution pattern in myocytes expressing this isoform. The preserved contractile function and translocation responses to PHE are blocked by the inhibitor, LY379196 (30 nM) in PKCβII-expressing myocytes. Further analysis showed downstream protein kinase D (PKD) phosphorylation and phosphatase activation are associated with the LY379196-sensitive contractile response. PHE also triggered a complex pattern of end-target phosphorylation in PKCβII-expressing myocytes. These patterns are consistent with bifurcated activation of downstream signaling activity by PKCβII.