Suppression of Charcoal Rot of Chickpea by Fluorescent <Emphasis Type="Italic">Pseudomonas</Emphasis> Under Saline Stress Condition

The ability of fluorescent Pseudomonas strain EKi, in production of biocontrol and plant growth promotory (PGP) metabolites under saline stress was evaluated. Strain EKi could tolerate NaCl up to 1,550 mM and showed biocontrol of Macrophomina phaseolina (76.19%) in the presence of up to 400 mM NaCl. Strain EKi was able to produce IAA, siderophore and pyocyanin with gradual reduction of up to 76.31, 45.46, and 48.99%, respectively, as NaCl concentration increased from 0 to 500 mM. Reduced growth rate resulted in delayed induction of IAA, siderophore and pyocyanin by the PGPR. Thin layer chromatography of chloroform extract from non-stressed and salt stressed EKi, and inhibition of M. phaseolina by purified pyocyanin clearly indicated its role in biocontrol. In vitro and in vivo results showed the growth promotion and charcoal rot disease suppression of chickpea by strain EKi under both non-stressed and saline stress. There was 76.75 and 65.25% reduction of disease incidence in non-saline and saline conditions, respectively, in vitro conditions. In presence of M. phaseolina strain EKi brought about 67.65 and 58.45% reduction of disease incidence in non-saline and saline soil, respectively.     

High fat diet alters lactation outcomes: possible involvement of inflammatory and serotonergic pathways

Delay in the onset of lactogenesis has been shown to occur in women who are obese, however the mechanism altered within the mammary gland causing the delay remains unknown. Consumption of high fat diets (HFD) has been previously determined to result decreased litters and litter numbers in rodent models due to a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from fat) diet versus a low-fat diet (LFD; 10% kcal from fat) to female Wistar rats on lactation outcomes. Feeding of HFD diet resulted in increased pup weights compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed in mothers on HFD but they began to produce copious milk volumes beginning 2 d post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected from lactating animals on HFD diet, displayed a disrupted morphologies, with very few and small alveoli. Consistently, there was a significant decrease in the mRNA expression of milk protein genes, glucose transporter 1 (GLUT1) and keratin 5 (K5), a luminobasal cell marker in the mammary glands of HFD lactating animals. Expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and the 5-HT(7) receptor (HTR7), which regulates mammary gland involution, were significantly increased in mammary glands of HFD animals. Additionally, we saw elevation of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). These results indicate that consumption of HFD impairs mammary parenchymal tissue and impedes its ability to synthesize and secrete milk, possibly through an increase in 5-HT production within the mammary gland leading to an inflammatory process.     

Clearance of extractables and leachables from single‐use technologies via ultrafiltration/diafiltration operations

Quantifying the clearance of extractables and leachables (E/L) throughout ultrafiltration/diafiltration (UFDF) operations allows for greater flexibility in the implementation of single‐use technologies in steps upstream of the UFDF process. A proof‐of‐concept study was completed in which the clearance of 7 E/L from single‐use technologies (trimethylsilanol, hexanoic acid, butyrolactone, t‐butyl alcohol, caprolactam, acetonitrile, and benzyl alcohol) in four representative proteins were measured and monitored during the UFDF process using quantitative NMR. This study demonstrated that the defined E/L spiked into a variety of protein solutions can be cleared to <1 ppm by 9 diavolumes from a maximum initial load concentration of 1,000 ppm. However, in some cases a rebound effect was observed in the recovered pool to >1 ppm, which is explained in detail. The overall clearance trend observed for both buffer control and protein‐containing solutions resembled the ideal clearance trend where no apparent interactions were observed between E/L with the protein, UFDF system, or with other defined E/L which may be present in the system. Additionally, the UFDF system is capable of clearing these potential E/L from single‐use technologies below 1 ppm irrespective of initial concentrations in the load (1,000 or 100 ppm), independently from the type of protein. In general, mass recoveries were within ±15% of each spiked compound in protein solutions and their respective buffer controls, suggesting spiked E/L do not interact strongly with protein. By demonstrating the product independent clearance trends of the spiked E/L across UFDF, these results will contribute to the simplification of the E/L toxicology assessment and allow modular manufacturing approach for single‐use technologies in biopharmaceutical manufacturing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:718–724, 2016     

The many faces of actin: matching assembly factors with cellular structures

Actin filaments are major components of at least 15 distinct structures in metazoan cells. These filaments assemble from a common pool of actin monomers, but do so at different times and places, and in response to different stimuli. All of these structures require actin-filament assembly factors. To date, many assembly factors have been identified, including Arp2/3 complex, multiple formin isoforms and spire. Now, a major task is to figure out which factors assemble which actin-based structures. Here, we focus on structures at the plasma membrane, including both sheet-like protrusive structures (such as lamellipodia and ruffles) and finger-like protrusions (such as filopodia and microvilli). Insights gained from studies of adherens junctions and the immunological synapse are also considered.     

Comparison of the prevention of aflatoxin b(1)-induced genotoxicity by quercetin and quercetin pentaacetate

Earlier work carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins in preventing the genotoxicity of aflatoxin B(1) (AFB(1)). We have in this report extended the observations to quercetin pentaacetate (QPA), which unlike quercetin (Q) has demonstrated time-dependent inhibition of liver microsome catalysed AFB(1) epoxidation as measured by AFB(1) binding to DNA. The action of QPA is similar to that of the acetoxy 4-methylcoumarins in that they are acted upon by microsomal transacetylase leading to modulation of catalytic activities of certain enzymes (such as P-450 enzymes, NADPH cytochrome C reductase and glutathione S-transferase) possibly by way of protein acetylation. In the present work, we have documented the transacetylase-mediated action of QPA in preventing genotoxicity due to AFB(1).     

Cell survival and metastasis regulation by Akt signaling in colorectal cancer

Dissemination of cancer cells to distant organ sites is the leading cause of death due to treatment failure in different types of cancer. Mehlen and Puisieux have reviewed the importance of the development of inappropriate cell survival signaling for various steps in the metastatic process and have noted the particular importance of aberrant cell survival to successful colonization at the metastatic site. Therefore, the understanding of mechanisms that govern cell survival fate of these metastatic cells could lead to the understanding of a new paradigm for the control of metastatic potential and could provide the basis for developing novel strategies for the treatment of metastases. Numerous studies have documented the widespread role of Akt in cell survival and metastasis in colorectal cancer, as well as many other types of cancer. Akt acts as a key signaling node that bridges the link between oncogenic receptors to many essential pro-survival cellular functions, and is perhaps the most commonly activated signaling pathway in human cancer. In recent years, Akt2 and Akt3 have emerged as significant contributors to malignancy alongside the well-characterized Akt1 isoform, with distinct non-overlapping functions. This review is aimed at gaining a better understanding of the Akt-driven cell survival mechanisms that contribute to cancer progression and metastasis and the pharmacological inhibitors in clinical trials designed to counter the Akt-driven cell survival responses in cancer.     

PGC-1α Thr394Thr and Gly482Ser variants are significantly associated with T2DM in two North Indian populations: a replicate case-control study

The recent observations that Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1A) is responsible for the induction of reactive oxygen species (ROS) detoxifying agents and that ROS triggers insulin resistance, support the role that this gene could play in the onset of Type 2 diabetes mellitus (T2DM). Two PGC1A variants Thr394Thr (rs2970847) and Gly482Ser (rs8192673) were genotyped in 822 subjects (351 T2DM cases and 471 controls) from two North Indian populations, represented as Group 1 (Kashmir population) and Group 2 (Punjab and Jammu population). Both Groups 1 and 2 showed a significant association of Thr394Thr variant with T2DM after applying Bonferroni corrections (P = 0.001 and 0.012, respectively). Logistic regression analysis for Thr394Thr susceptible genotypes together (rs2970847 G/A and A/A) conferred a 1.89-(95%CI 1.25–2.85) fold higher risk for T2DM in Group 1 and 1.81-(95%CI 1.19–2.78) fold risk in Group 2. The susceptible, Ser482 (rs8192673 G/A and A/A) genotypes, gave a 2.04 (95%CI 1.47–3.03) fold higher risk for T2DM in Group 1. Mitochondrial genotype backgrounds observed in association with T2DM (Bhat et al. 2007), when studied in combination with PGC1A variants, showed an increased prevalence in controls with mt10398G and 16189T along with G/G genotype background at the two polymorphic loci of PGC1A. These observations suggest that the two genotype backgrounds together could provide protection against T2DM. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article is available at .