Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children

Gut bacteria contribute to energy conservation in man through their ability to ferment unabsorbed carbohydrate. The present study examined the composition of predominant faecal microbiota in obese and non-obese children. The participants (n 28) aged 11-14 years provided fresh faecal samples and completed a dietary survey consisting of 24 h diet recall and a FFQ of commonly used foods taken over the previous 3 months. Faecal bacteria were quantitated by real-time PCR using primers targeted at 16S rDNA. Of the participants, fifteen (seven female) were obese, with median BMI-for-age at the 99th percentile (range 97 to<99) while thirteen participants (seven female) were normal weight, with median BMI-for age being at the 50th percentile (range 1-85). Consumption of energy, carbohydrates, fat and protein was not significantly different between the obese and non-obese participants. There was no significant difference between the two groups in faecal levels of Bacteroides-Prevotella, Bifidobacterium species, Lactobacillus acidophilus group or Eubacterium rectale. Levels of Faecalibacterium prausnitzii were significantly higher in obese children than in non-obese participants (P = 0.0253). We concluded that the finding of increased numbers of F. prausnitzii in the faeces of obese children in south India adds to the growing information on alterations in faecal microbiota in obesity

Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

<p>Abstract</p> <p>Background</p> <p>Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet.</p> <p>Findings</p> <p>26 women aged 18-21 (median 19) years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing <it>Bifidobacterium lactis </it>Bb12^®(10⁹in 200 ml) for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184) and returned to normal after cessation of probiotic yoghurt intake.</p> <p>Conclusions</p> <p><it>Bifidobacterium lactis </it>Bb12^®increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.</p

ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms

<p>Abstract</p> <p>Background</p> <p>Zinc Finger Nucleases (ZFNs) have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN) method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms.</p> <p>Description</p> <p>ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; <it>S. cerevisiae, C. reinhardtii, A. thaliana</it>, <it>D. melanogaster, D. rerio, C. elegans</it>, and <it>H. sapiens </it>and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s). Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence). Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter) "confidence" scores that estimate the likelihood that a chosen ZFN target site will function <it>in vivo</it>. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the effectiveness of a given ZFN in creating double-stranded breaks.</p> <p>Conclusions</p> <p>ZFNGenome provides a user-friendly interface that allows researchers to access resources and information regarding genomic target sites for engineered ZFNs in seven model organisms. This genome-wide database of potential ZFN target sites should greatly facilitate the utilization of ZFNs in both basic and clinical research.</p> <p>ZFNGenome is freely available at: <url>http://bindr.gdcb.iastate.edu/ZFNGenome</url> or at the Zinc Finger Consortium website: <url>http://www.zincfingers.org/</url>.</p

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

Novel Allosteric Sites on Ras for Lead Generation

Aberrant Ras activity is a hallmark of diverse cancers and developmental diseases. Unfortunately, conventional efforts to develop effective small molecule Ras inhibitors have met with limited success. We have developed a novel multi-level computational approach to discover potential inhibitors of previously uncharacterized allosteric sites. Our approach couples bioinformatics analysis, advanced molecular simulations, ensemble docking and initial experimental testing of potential inhibitors. Molecular dynamics simulation highlighted conserved allosteric coupling of the nucleotide-binding switch region with distal regions, including loop 7 and helix 5. Bioinformatics methods identified novel transient small molecule binding pockets close to these regions and in the vicinity of the conformationally responsive switch region. Candidate binders for these pockets were selected through ensemble docking of ZINC and NCI compound libraries. Finally, cell-based assays confirmed our hypothesis that the chosen binders can inhibit the downstream signaling activity of Ras. We thus propose that the predicted allosteric sites are viable targets for the development and optimization of new drugs

Malicious Attack Detector

ABSTRAC

Single nucleotide polymorphisms in the human ATP7B gene modify the properties of the ATP7B protein

Single nucleotide polymorphisms (SNPs) are the largest source of sequence variation in the human genome. However, their functional significance is not well understood. We show that SNPs in the Wilson disease gene, ATP7B, that produce amino-acid substitutions K832R and R952K, modulate ATP7B properties in vitro and influence serum copper (Cu) status in vivo. The presence of R832 is associated with a lower ATP7B abundance and a diminished trafficking in response to elevated Cu. The K832R substitution alters surface exposure of amino acid residues in the actuator domain and increases its conformational flexibility. All SNP-related ATP7B variants (R832/R952, R832/K952, K832/K952, and K832/R952) have Cu-transport activity. However, the activity of ATP7B-K832/K952 is lower compared to other variants. In humans, the presence of K952 is associated with a higher fraction of exchangeable Cu in serum. Thus, SNPs may modulate the properties of ATP7B and the organism Cu status

Physiological Role of Nutrient Consortium for Improving the Yield in Cotton

The present investigation was carried out to study the impact of nutrients and PGRs (Plant Growth Regulators) on morphological, physiological and yield attributes of the cotton crop. The statistical design used for the study was Factorial Completely Randomized Design (FCRD) with four replications. The pot culture experiment was conducted in the Glass house, Department of Crop Physiology, Tamil Nadu Agricultural University (TNAU) during February 2023 – June 2023. The study was carried out using two cotton varieties (CO 17 and MCU 5) with the treatments containing 1% foliar spray of Nutrio-hormonal consortia Ⅰ, Nutrio-hormonal consortia Ⅱ, Cotton Booster Ⅰ, Cotton Booster Ⅱ and control. The treatments were imposed during flowering and boll development stages. The morphological, physiological and yield attributes viz., plant height (in cm), chlorophyll index, total dry matter production (g/plant), number of sympodial branches per plant, number of bolls per plant, boll weight (g/boll) and seed cotton yield (g/plant) were recorded. Foliar application of the Cotton booster Ⅱ resulted in significant increase in the plant height (58.35 cm), total dry matter production (38.65 g/plant), number of sympodial branches per plant (17.8), number of bolls per plant (15.60), boll weight (3.88 g/boll) and seed cotton yield (42.79 g/plant) followed by Cotton booster Ⅰ in CO 17 variety. Similarly, in MCU 5 cotton variety, significant difference was observed in plant height (69.37 cm), total dry matter production (45.60 g/plant), number of sympodial branches per plant (19.6), number of bolls per plant (20.0), boll weight(4.39 g/boll) and seed cotton yield (48.77 g/plant). In conclusion, foliar application of 1% Cotton Booster Ⅱ exhibited better growth and yield attributes in cotton

Methyl Eugenol (Parapheromone) Trapping System on Diversity of Fruit Flies and Influence of Weather Parameters on Trap Catches in Mango and Guava Cropping Systems

Studies on species diversity and influence of weather parameters on methyl eugenol (parapheromone) trap catches were carried out in mango and guava orchards at Coimbatore and Dindigul Districts of Tamil Nadu from Standard Meteorological Week (SMW) 16th to SMW 25th. Species diversity indices were calculated, and the methyl eugenol trap catches were correlated with the weather parameters. The results revealed that four fruit fly species viz., Oriental fruit fly, Bactrocera dorsalis (Hendel), Guava fruit fly, B. correcta (Bezii), B. caryeae (Kapoor), and Peach fruit fly, B. zonata (Saunders), were attracted to the parapheromone methyl eugenol traps. Among them the population of B. dorsalis was higher in both mango and guava orchards of Coimbatore and Dindigul Districts. The highest species diversity indices for fruit flies viz., Shannon H’ (0.936) and Simpsons D’ (0.593), evenness (0.468), and richness (0.482) were observed in guava orchard located in Coimbatore District, and the minimum diversity indices Shannon H’ (0.254), Simpsons D’ (0.921), evenness (0.160), and richness (0.291), were observed in mango orchard located in Dindigul District. The maximum number of fruit flies were trapped in 19th SMW in mango orchards in both Districts 134 and 145 flies/three traps, respectively. In Coimbatore District’s guava orchard and Dindigul District's mango orchard, trap catches revealed a significant positive correlation with rainfall. The subsequent weather parameters like max. temperature, min. temperature, wind speed, and relative humidity, were either positively or negatively correlated with trap catches in mango and guava orchards. In multiple regression analysis, the maximum predictability was seen in mango orchard (75.54%) located in Coimbatore District and the minimum (66.68%) in mango orchard located in Dindigul District