Utilization of dietary mixed-linkage ß-glucans by the Firmicute Blautia producta.

The ß-glucans are structurally varied, naturally occurring components of the cell walls, and storage materials of a variety of plant and microbial species. In the human diet, mixed-linkage glucans [MLG - ß-(1,3/4)-glucans] influence the gut microbiome and the host immune system. Although consumed daily, the molecular mechanism by which human gut Gram-positive bacteria utilize MLG largely remains unknown. In this study, we used Blautia producta ATCC 27340 as a model organism to develop an understanding of MLG utilization. B. producta encodes a gene locus comprising a multi-modular cell-anchored endo-glucanase (BpGH16MLG), an ABC transporter, and a glycoside phosphorylase (BpGH94MLG) for utilizing MLG, as evidenced by the upregulation of expression of the enzyme- and solute binding protein (SBP)-encoding genes in this cluster when the organism is grown on MLG. We determined that recombinant BpGH16MLG cleaved various types of ß-glucan, generating oligosaccharides suitable for cellular uptake by B. producta. Cytoplasmic digestion of these oligosaccharides is then performed by recombinant BpGH94MLG and ß-glucosidases (BpGH3-AR8MLG and BpGH3-X62MLG). Using targeted deletion, we demonstrated BpSBPMLG is essential for B. producta growth on barley ß-glucan. Furthermore, we revealed that beneficial bacteria, such as Roseburia faecis JCM 17581T, Bifidobacterium pseudocatenulatum JCM 1200T, Bifidobacterium adolescentis JCM 1275T, and Bifidobacterium bifidum JCM 1254, can also utilize oligosaccharides resulting from the action of BpGH16MLG. Disentangling the ß-glucan utilizing the capability of B. producta provides a rational basis on which to consider the probiotic potential of this class of organism.

Synthesis and site selective C-H functionalization of imidazo-[1,2-a]pyridines.

Imidazo[1,2-a]pyridine has attracted much interest in drug development because of its potent medicinal properties, therefore the discovery of novel methods for its synthesis and functionalization continues to be an exciting area of research. Although transition metal catalysis has fuelled the most significant developments, extremely beneficial metal-free approaches have also been identified. Even though pertinent reviews focused on imidazo[1,2-a]pyridine synthesis, properties (physicochemical and medicinal), and functionalization at the C3 position have been published, none of these reviews has focused on the outcomes obtained in the field of global ring functionalization. We wish here to describe a brief synthesis and an overview of all the functionalization reactions at each carbon atom, viz, C2, C3, C5, C6, C7 and C8 of this scaffold, divided into sections based on site-selectivity and the type of functionalization methods used.

WSSV susceptibility in the early life stages of Penaeus vannamei shows relationship with bodyweight.

White Spot Syndrome Virus (WSSV) continues to cause considerable loss to shrimp farmers globally with frequent outbreaks even in specific pathogen free Peneaus vannamei. Our studies showed that the bodyweight (BW) of PL has a bearing on their susceptibility to the virus. To test this hypothesis, PL of the same age group and family were grouped according to BW (10-20, 30-40, and 50-60 mg) and challenged through immersion route with two viral doses (106 and 107 virus copies/L of water). It was observed that the PL became susceptible to WSSV at ≥50 mg BW. In the 50-60 mg PL group, the higher challenge dose shows a sharp mortality curve with 100% mortality at 10 days post immersion, while the lower dose shows a steady increase in cumulative mortality that reaches 100% on the 13th day post immersion. The study also brings out that an in vivo viral load of approximately 3.5 to 4.5 × 107WSSV copies/100 ng shrimp DNA results in mortality. This is the first report on the relationship between BW and WSSV susceptibility in shrimp PL. Also reported here is a quantitative assessment of WSSV infection in P. vannamei PL and an optimized challenge protocol.

Encapsulation-Led Adsorption of Neutral Dyes and Complete Photodegradation of Cationic Dyes and Antipsychotic Drugs by Lanthanide-Based Macrocycles.

Molecular architectures offering large cavities can accommodate guest molecules, while their compositional engineering allows tunability of the band gap to support photocatalysis using visible light. In this work, two lanthanide (Ln)-based macrocycles, synthesized using a cobalt-based metalloligand and offering large rectangular cavities, exhibited selective adsorption of neutral dyes over both anionic and cationic dyes. Both Ln macrocycles illustrated complete photodegradation of cationic dyes using visible light without the use of any oxidant. Both Ln macrocycles exhibited complete photodegradation of not only cationic dyes but also a few phenothiazine-based antipsychotic drugs. Photocatalysis involved the generation of reactive oxygen species (ROS), which was corroborated with the band gap of two Ln macrocycles. These results were supported by radical scavenger studies and the quantitative estimation of superoxide and hydroxyl radicals. Complete photodegradation of both dyes and drugs was confirmed by spectral studies, while the generation of CO2 and N2 gases was established by gas chromatography. Importantly, Ln macrocycles were able to distinguish between the neutral dyes that were quantitatively adsorbed and the cationic dyes/drugs that were completely photodegraded.

Gain of function studies on predicted host receptors for white spot virus.

Three decades after its first outbreak, the shrimp white spot virus (WSV) is still a global cause of concern due to considerable losses and lack of effective control measures. Several candidate host receptor proteins have been identified, but the pathogenesis is not clearly understood, although the key role of the WSV envelope protein VP28 in virus internalization is established. Here, protein-protein docking is applied to evaluate the interaction of VP28 trimeric extracellular region with four host (Penaeus monodon) receptors reported earlier, Rab7 GTPase (PmRab7), glucose transporter 1 (PmGLUT1), C-type lectin (PmCTL) and calreticulin (PmCRT). The stability of predicted complexes evaluated in terms of binding energy per unit buried surface area ranged from -8.46 to -11.82 cal mol-1/Å2, which is not sufficient for functional interaction. Nevertheless, each of these host proteins was tested by a gain-of-function approach by observing their ability to make a fish cell line permissive to the shrimp WSV. Full-length expression constructs of the four receptors were transfected into SSN1 snakehead fish cells that are non-permissive to WSV. Transfected SSN1 cells and WSV permissive insect Sf9 cells were challenged with purified WSV. After 24 h, the presence of receptor transcripts was confirmed in the treated SSN1 cells, and not in the non-transfected SSN1 cells. Further, vp28 transcript was detected in Sf9 cells, but not in any of the treated SSN1 cells, indicating that none of the receptors were singly sufficient to make SSN1 cells permissive to WSV, even though PmRab7 was a strong candidate that alone showed >85% protection in virus neutralization experiments. For the other 3 candidates, previous reports predicted the involvement of co-receptors, which is confirmed here by their inability to act singly.

Organocatalyzed umpolung addition for synthesis of heterocyclic-fused arylidene-imidazolones as anticancer agents.

A strategy of "Nature-to-new" with iterative scaffold-hopping was considered for investigation of privileged ring/functional motif-elaborated analogs of natural aurones. An organocatalyzed umpolung chemistry based method was established for molecular-diversity feasible synthesis of title class of chemotypes i.e. (Z)-2-Arylideneimidazo[1,2-a]pyridinones and (Z)-2-Arylidenebenzo[d]imidazo[2,1-b]thiazol-3-ones. Various biophysical experiments indicated their important biological properties. The analogs showed characteristic anticancer activities with efficiency more than an anticancer drug. The compounds induced apoptosis with arrest in the S phase of the cell cycle regulation. The compounds' significant effect in up/down-regulation of various apoptotic proteins, an apoptosis cascade, and the inhibition of topoisomerases-mediated DNA relaxation process was identified. The analysis of the structure-activity relationship, interference with biological events and the drug-likeness physicochemical properties of the compounds in the acceptable window indicated distinctive medicinal molecule-to-properties of the investigated chemotypes.

Synthesis of 3-N-/O-/S-methyl-imidazo[1,2-a] pyridine derivatives for caspase-3 mediated apoptosis induced anticancer activity.

A library of 49 analogs of imidazo[1,2-a]pyridine with 2-halo, aryl, styryl and phenylethynyl-substitution at C-2 position and N-/O-/S-methyl linkage at C-3 position, have been synthesized and evaluated for their anti-proliferative activity against breast (MCF-7, MDA-MB-231), pancreatic (MiaPaca-2), lung (A549), prostate (PC-3) and colon (HCT-116) cancer cell lines and normal cells (HEK-293). Among the screened compounds, 5b exhibited best anticancer potential in all tested cancer cells with IC50 ranging from 3.5 to 61.1 µM and no toxicity in normal cells. Further, mechanistic study of 5b revealed concentration dependent increased generation of ROS, reduced mitochondrial membrane potential (MMP), surface and nuclear morphological alterations and inhibition of colony formation in HCT-116 cells. Western blot results had shown that the cell death in HCT-116 colon cancer cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and downregulation of AKT pathway. Similarly, 5b treatment induced caspase-3 cleavage which is a hallmark of apoptosis. Molecular docking and binding energy (ΔG) studies of hit 5b with respect to three important cancer targets (EGFR, mTOR and PI3Kα) revealed strong binding of inhibitor with PI3Kα (docking score -6.932 and ΔG -56.297).

Study of Correlation of Serum Calcium Level with Disease Severity in Dengue Patients.

Dengue fever is the world's fastest growing vector borne viral disease. Dengue infection has high morbidity and mortality unless managed promptly and appropriately. Calcium regulates many physiological processes such as neuromuscular transmission, heart contractility, hormonal release, blood coagulation and is essential for cell function. Low calcium level is present in almost 80% of dengue cases and is more associated with severe cases. Hypocalcemia enhances the binding of the dengue virus to monocyte macrophages and cells of T cell and B cell lineages in dengue infection. However, there is scarcity of literature on calcium homeostasis in dengue infection, and current guidelines do not address the necessity to monitor or correct blood calcium levels in dengue patients. In present study, we evaluated serum calcium level in dengue patients and correlated it with disease severity. MATERIAL: The present observational cross-sectional study conducted in the Department of Medicine and Biochemistry, VMMC and Safdarjung Hospital, New Delhi, included 60 patients of dengue infection, satisfying the inclusion and exclusion criteria over a period of 18 months. Inclusion criteria were patients with age above 12 years, any gender, and diagnosed as having dengue infection, either by NS1Ag or by IgM ELISA for dengue antibodies, were clinically classified as Dengue Fever (DF), Dengue Haemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) as per National Guidelines for Clinical Management of Dengue Fever developed by NVBDCP. Exclusion criteria were patients with diseases like hypertension, diabetes, cardiac disease, liver disease, malabsorption syndrome, renal dysfunction and patients taking drugs causing hypocalcemia and oral calcium and vitamin D supplements. In present study, serum calcium level used was corrected for hypoalbuminemia. OBSERVATION: The mean age was 27 years with a male and female ratio of approximately 3:2. The present study shows that the mean serum calcium level (mg/dL) of patients in Dengue Fever, Dengue Haemorrhagic Fever and Dengue Shock Syndrome was 8.85, 8.27 and 7.95 respectively(p<0.0001). Serum calcium level was lower in DSS and DHF patients than DF patients. Negative correlation between severity of dengue infection and serum calcium level was found with correlation coefficient of -0.892. CONCLUSION: The present study revealed significant negative correlation between Serum calcium level and severity of dengue infection. Therefore, it can be considered to use serum calcium level as a potential biomarker in order to identify severe dengue patients and this investigation will help in early identification, diagnosis and management of dengue infection but further studies are required to support this.

Exploration of Benzo[b]carbazole-6,11-diones as anticancer agents: Synthesis and studies of hTopoIIα inhibition and apoptotic effects.

Two series of (hetero)arylamino-naphthoquinones and benzo-fused carbazolequinones were considered for study with the rationale that related structural motifs are present in numerous drugs, clinical trial agents, natural products and hTopoIIα inhibitors. Total 42 compounds were synthesized by reactions including dehydrogenative CN and Pd-catalyzed CC bond forming transformations. These compounds were screened against numerous cancer cells including highly metastatic one (MCF-7, MDA-MB-231, H-357 and HEK293T), and normal cells (MCF 10A). Some of the active compounds were evaluated for clonogenic cell survival and apoptotic effects in cancer cells (DAPI nuclear staining, Comet assay, Annexin-V-FITC/PI dual staining, flow cytometry, and western blot analysis with relevant proteins). All compounds were tested for hTopoIIα inhibitory activity. The investigated series compounds showed important properties like significant apoptotic antiproliferation in cancer cells with cell cycle arrest at S-phase and downregulation of NF- κß signaling cascade, relatively less cytotoxicity to normal cells, and hTopoIIα inhibition with more efficiency compared to an anticancer drug etoposide.

Role of transporters in plant disease resistance.

Plants being sessile have evolved numerous mechanisms to meet the changing environmental and growth conditions. Plant pathogens are responsible for devastating disease epidemics in many species. Transporter proteins are an integral part of plant growth and development, and several studies have documented their role in pathogen disease resistance. In this review, we analyze the studies on genome-wide identifications of plant transporters like sugars will eventually be exported transporters (SWEET), multidrug and toxic compound extrusion (MATE) transporters, ATP-binding cassette (ABC) transporters, natural resistance-associated macrophage proteins (NRAMP), and sugar transport proteins (STPs), all having a significant role in plant disease resistance. The mechanism of action of these transporters, their solute specificity, and the potential application of recent molecular biology approaches deploying these transporters for the development of disease-resistant plants are also discussed. The applications of genome editing tools, such as CRIPSR/Cas9, are also presented. Altogether the information included in this article gives a better understanding of the role of transporter proteins during plant-pathogen interaction.

Palladium(II) catalyzed site-selective C-H olefination of imidazo[1,2-a]pyridines.

Herein, we disclose an efficient Pd(II)-catalyzed site selective C8 alkenylation of imidazo[1,2-a]pyridines with electronically biased olefinic substrates. Notably, besides the presence of four C-H sites available, selective mono-alkenylation was achieved by N-chelation overriding O-chelation. The versatility and scalability of the catalysis enabled the selective late-stage functionalization of a marketed drug, zolimidine. Various substituted heteroaryl alkenes can be afforded with moderate to good yields with high C8 regioselectivity.

Ontogenetic and tissue-specific expression of gonadotropin-inhibitory hormone (GnIH) and its receptors in Catla catla.

Gonadotropin-inhibitory hormone (GnIH) is an RFamide peptide, and its role in reproduction is well studied from fish to mammals, but very few reports are available about the function of GnIH during larval development. In this study, we examined the GnIH and GnIH receptors (GnIHRs) expression from embryogenesis to adult stage and tissue-specific expression in adult Catla catla using quantitative real-time (qRT) PCR. The qRT PCR analysis of GnIH mRNA during ontogenetic development showed the increasing trend from early developmental stages to the adult stage with the highest expression in 24 months fish. However, the expression of two GnIH receptors, GnIHR1 and GnIHR2 also increased from larval stages to the adults with a peak at 17 days post-hatching, while GnIHR3 showed the higher mRNA expression during embryogenesis and then decreasing gradually. Tissue distribution analysis of GnIH showed the highest mRNA expression of GnIH in the brain, followed by gonads of both the sexes. GnIHR1 and GnIHR2 were also highly expressed in the brain and gonads of both the sexes, while GnIHR3 showed the highest expression in gonads of both the sexes without any expression in the brain. These results suggest that the brain is the primary site of action for GnIH, GnIHR1 and GnIHR2, while gonads for GnIHR3.

Video-assisted smart health monitoring for affliction determination based on fog analytics.

Satisfying the expectations of quality living is essential for smart healthcare. Therefore, the determination of health afflictions in real-time has been considered as one of the most necessary parts of medical or assistive-care domain. In this article, a novel fog analytic-assisted deep learning-enabled physical stance-based irregularity recognition framework is presented to enhance personal living satisfaction of an individual. To increase the utility of the proposed framework for assistive-care, an attempt has been made to record predicted activity scores on cloud by following the continuous time series policy to provide future health references to authorized medical specialist. Furthermore, a smart two-phased decision generation mechanism is proposed to intimate medical specialist and caretakers about the current physical status of an individual in real-time. The generation of the alert is directly proportional to the predicted physical irregularity and the scale of health severity. The experimental results highlight the advantages of fog analytics that helps to increase the recognition rate up to 46.45% for 40 FPS and 45.72% for 30 FPS against cloud-based monitoring solutions. The calculated outcomes justify the superiority of the proposed fog analytics monitoring solution over the conventional cloud-based monitoring solutions by achieving high activity prediction accuracy and less latency rate in decision making.

Andrographolide: Chemical modification and its effect on biological activities.

The major natural bioactive constituent of Andrographis paniculata (AP) (Burm. f.) Nees Andrographolide (1) and its derivatives are well acknowledged in literature for its biological activities such as anti-cancer, anti-diabetic, anti-inflammatory, anti-bacterial, anti-malarial, antihepatitis, anti-HIV, anti-atherosclerosis, hepatoprotective, FXR antagonist, and α-glucosidase inhibition. Many reports are available related to Andrographolide (1) but a consolidated review on the chemical modification of andrographolide with special emphasis on its different functional groups with respect to their biological activities is still missing from the previous literature. Therefore, herein we have collected a literature for the period 2009 onwards in relation to chemistry on andrographolide (1) and its effect on respective biological activity. Also, special attempt on increasing the bioavailability of andrographolide (1) has been given for the designing of various targeted drug delivery systems.

District level inequality in reproductive, maternal, neonatal and child health coverage in India.

BACKGROUND: As India already missed maternal and child health related millennium development goals, the maternal and child health outcomes are a matter of concern to achieve sustainable development goals (SDGs). This study is focused to assess the gap in coverage and inequality of various reproductive, maternal, neonatal and child health (RMNCH) indicators in 640 districts of India, using data from most recent round of National Family Health Survey. METHODS: A composite index named Coverage Gap Index (CGI) was calculated, as the weighted average of eight preventive maternal and child care interventions at different administrative levels. Bivariate and spatial analysis were used to understand the geographical diversity and spatial clustering in districts of India. A socio-economic development index (SDI) was also derived and used to assess the interlinkages between CGI and development. The ratio method was used to assess the socio-economic inequality in CGI and its component at the national level. RESULTS: The average national CGI was 26.23% with the lowest in Kerala (10.48%) and highest in Nagaland (55.07%). Almost half of the Indian districts had CGI above the national average and mainly concentrated in high focus states and north-eastern part. From the geospatial analysis of CGI, 122 districts formed hotspots and 164 districts were in cold spot. The poorest households had 2.5 times higher CGI in comparison to the richest households and rural households have 1.5 times higher CGI as compared to urban households. CONCLUSION: Evidence from the study suggests that many districts in India are lagging in terms of CGI and prioritize to achieve the desired level of maternal and child health outcomes. Efforts are needed to reduce the CGI among the poorest and rural resident which may curtail the inequality.

Serovar diversity of Salmonella among poultry.

Background & objectives: Salmonellosis due to the consumption of contaminated poultry products is a well-known public health concern, and assessing the distribution of Salmonella serovars among poultry becomes important for better prevention and control. The objective of the present study was to assess the distribution of Salmonella serovars among poultry. Methods: The isolates received at National Salmonella and Escherichia Centre during 2011-2016 were subjected to biochemical identification, followed by serological characterization to identify the Salmonella serovars, and the data were presented to exhibit the distribution of Salmonella serovars among poultry. Results: Salmonella was found to be present in poultry in all the regions included in the study. Salmonella Typhimurium, S. Gallinarum and S. Enteritidis were the most prevalent serovars accounting for 96.2 per cent of isolates. Salmonella was identified in poultry from all major egg-producing and egg-consuming States. Other serovars which were scantly identified included S. Infantis (2.7%), S. Montevideo (0.64%), S. Newport (0.26%) and S. Pullorum (0.13%). Interpretation & conclusions: Diverse distribution of Salmonella serovars in poultry in India, with known potential to infect human population and/or other poultry flocks, requires urgent nationwide stringent control measures.

Energy Efficient Range-Free Localization Algorithm for Wireless Sensor Networks.

In this paper, an energy-efficient localization algorithm is proposed for precise localization in wireless sensor networks (WSNs) and the process is accomplished in three steps. Firstly, the beacon nodes discover their one-hop neighbor nodes with additional tone requests and reply packets over the media access control (MAC) layer to avoid collision of packets. Secondly, the discovered one-hop unknown nodes are divided into two sets, i.e. unknown nodes with direct communication, and with indirect communication for energy efficiency. In direct communication, source beacon nodes forward the information directly to the unknown nodes, but a common beacon node is selected for communication which reduces overall energy consumption during transmission in indirect communication. Finally, a correction factor is also introduced, and localized unknown nodes are upgraded into helper nodes for reducing the localization error. To analyze the efficiency and effectiveness of the proposed algorithm, various simulations are conducted and compared with the existing algorithms.

Improved Location Estimation in Wireless Sensor Networks Using a Vector-Based Swarm Optimized Connected Dominating Set.

Location estimation in wireless sensor networks (WSNs) has received tremendous attention in recent times. Improved technology and efficient algorithms systematically empower WSNs with precise location identification. However, while algorithms are efficient in improving the location estimation error, the factor of the network lifetime has not been researched thoroughly. In addition, algorithms are not optimized in balancing the load among nodes, which reduces the overall network lifetime. In this paper, we have proposed an algorithm that balances the load of computation for location estimation among the anchor nodes. We have used vector-based swarm optimization on the connected dominating set (CDS), consisting of anchor nodes for that purpose. In this algorithm, major tasks are performed by the base station with a minimum number of messages exchanged by anchor nodes and unknown nodes. The simulation results showed that the proposed algorithm significantly improves the network lifetime and reduces the location estimation error. Furthermore, the proposed optimized CDS is capable of providing a global optimum solution with a minimum number of iterations.

Beyond Hypnograms: Assessing Sleep Stability Using Acoustic and Electrical Stimulation.

OBJECTIVE: Conventional polysomnographic recordings reflect brain dynamics associated with sleep architecture. We hypothesized that noninvasive tools like transcranial alternating current stimulation (tACS) and acoustic stimulation (for generating event related potentials [ERPs]) would help to predict sleep stability and provide a window to actively assess brain activity during sleep. MATERIALS AND METHODS: Twelve healthy male volunteers participated in the multiple whole-night polysomnography (PSG) recording protocol. Acoustic tones (100 msec duration) were presented throughout night to evaluate ERP during sleep. Furthermore, 30 sec tACS were presented during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep on subsequent two nights without disturbing the subject's sleep. For ERP analysis, event-locked artifact-free epochs from each sleep stage were averaged separately. For tACS analysis, 30 sec prestimulus and poststimulus artifact-free EEG epochs were subjected to bootstrapping-based comparison of power spectral values. RESULTS: Acoustic stimulation generated sleep stage-dependent ERP components (N350, N550, and P900) in all participants. The tACS stimulation during NREM sleep (0.75 Hz) increased parietal delta power but decreased frontocentral theta and increased frontal gamma power when delivered during REM sleep (40Hz). These interventions provide details on sleep stability as larger N550-P900 ERP-complex correlated with lower NREM disruptions (Spearman's rho = -0.553; p = 0.049; n = 10) and tACS-related theta power perturbation with higher REM disruptions (Spearman's rho = 0.734; p = 0.030; n = 7). CONCLUSIONS: Noninvasive brain stimulation approaches such as sleep ERP and sleep tACS are reliable tools to evaluate sleep stability during NREM and REM sleep, respectively, but more large-sample studies are warranted.

Synthesis of Polyfunctionalized Pyrroles via a Tandem Reaction of Michael Addition and Intramolecular Cyanide-Mediated Nitrile-to-Nitrile Condensation.

A new approach for the synthesis of tetrasubstituted/functionalized NH-pyrroles from gem-diactivated acrylonitriles and TMSCN has been developed. The strategy utilizes the generation of vic-dinitrile via Michael addition and cyanide-mediated nitrile-to-nitrile cyclocondensation, which proceed in tandem guided by manifold roles of "CN". An extended application to the production of fused pyrrole has also been realized.