MicroRNAs in a hypertrophic heart: from foetal life to adulthood

The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non‐coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.     

Metabolism-mediated induction of zinc tolerance in <Emphasis Type="Italic">Brassica rapa</Emphasis> by <Emphasis Type="Italic">Burkholderia cepacia</Emphasis> CS2-1

Brassica rapa (Chinese cabbage) is an essential component of traditional Korean food. However, the crop is often subject to zinc (Zn⁺) toxicity from contaminated irrigation water, which, as a result, compromises plant growth and production, as well as the health of human consumers. The present study investigated the bioaccumulation of Zn⁺ by Burkholderia cepacia CS2-1 and its effect on the heavy metal tolerance of Chinese cabbage. Strain CS2-1 was identified and characterized on the basis of 16S rRNA sequences and phylogenetic analysis. The strain actively produced indole-3-acetic acid (3.08 ± 0.21 μg/ml) and was also able to produce siderophore, solubilize minerals, and tolerate various concentrations of Zn⁺. The heavy metal tolerance of B. rapa plants was enhanced by CS2-1 inoculation, as indicated by growth attributes, Zn⁺ uptake, amino acid synthesis, antioxidant levels, and endogenous hormone (ABA and SA) synthesis. Without inoculation, the application of Zn⁺ negatively affected the growth and physiology of B. rapa plants. However, CS2-1 inoculation improved plant growth, lowered Zn⁺ uptake, altered both amino acid regulation and levels of flavonoids and phenolics, and significantly decreased levels of superoxide dismutase, endogenous abscisic acid, and salicylic acid. These findings indicate that B. cepacia CS2-1 is suitable for bioremediation against Zn⁺-induced oxidative stress.     

Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta)

AIMS: In primates, changes in nutritional status affect the hypothalamic-pituitary-gonadal (HPG) axis by still poorly understood mechanisms. Recently, hypothalamic kisspeptin-GPR54 signaling has emerged as a significant regulator of this neuroendocrine axis. The present study was designed to examine whether suppression of the reproductive function by acute food-restriction in a non-human primate is mediated by decreased responsiveness of the HPG axis to endogenous kisspeptin drive. MAIN METHODS: Five intact adult male rhesus monkeys habituated to chair-restraint, received intravenous boli of human kisspeptin-10 (KP10, 50 microg), hCG (50 IU), and vehicle (1 ml) in both fed and 48-h fasting conditions. Plasma concentrations of glucose, cortisol and testosterone (T) were measured by using enzymatic and specific RIAs, respectively. KEY FINDINGS: The acute 48-h fasting decreased plasma glucose (P<0.01) and T (P<0.005) levels, and increased cortisol levels (P<0.05). KP10 administration caused a robust stimulation of T secretion in both fed and fasted monkeys. However, mean T concentration and T AUC after KP10 administration were significantly (P<0.01-0.005) reduced in fasted monkeys. Likewise, the time of the first significant increase in post-KP10 T levels was also significantly (P<0.01) delayed. T response to hCG stimulation was similar in fed and fasted monkeys. SIGNIFICANCE: The present results indicate that under fasting conditions the KP10 induced T response is delayed and suppressed. These data support the notion that fasting-induced suppression of the HPG axis in the adult male rhesus monkey may involve, at least in part, a reduction in the sensitivity of the GnRH neuronal network to endogenous kisspeptin stimulation.     

Ross operation in children and young adults: the Alder Hey case series

Background

Plasma levels of tumor necrosis factor (TNF)-α and of C-reactive protein (CRP) are elevated in smokers. Previous studies failed to show an association between the G-308A polymorphism in the promoter region of the TNF-α gene and coronary artery disease (CAD). We investigated whether smoking would interact with the TNF-α G-308A polymorphism in determining plasma levels of TNF-α and CRP.

Methods

Study participants with a complete data set in terms of smoking and the TNF-α G-308A polymorphism were 300 middle-aged male and female industrial employees. After excluding 24 irregular smokers, analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects currently smoking >3 cigarettes/day). All subjects had a fasting morning blood draw to measure plasma levels of TNF-α and CRP by high-sensitive enzyme-linked immunosorbent assays.

Results

The cardiovascular risk factor adjusted analysis regressing log-transformed CRP levels against smoking status, genotype, and smoking-status-genotype interaction revealed a significant main effect for smoking status (F_1,250 = 5.67, p = .018) but not for genotype (F_1,250 = 0.33, p = .57). The interaction-term between genotype and smoking status was not significant (F_1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF-α failed to show significant main effects for smoking and genotype, as well as for the smoking-status-genotype interaction.

Conclusions

The findings suggest that the TNF-α G-308A polymorphism does not mediate the effect of smoking on plasma CRP levels. It remains to be seen whether other genetic polymorphisms along the inflammatory pathway may modulate vascular risk in smokers.     

Influence of Plant Growth Promoting Rhizobacterial Inoculation on Wheat Productivity Under Soil Salinity Stress

Soil salinity affects the growth and yield of crops. The stress of soil salinity on plants can be mitigated by inoculation of plant growth promoting bacteria (PGPR). The influence of PGPR inoculation on wheat (Triticum aestivum L.) crop productivity under salinity stress has not been properly addressed so far. Therefore, the present study was conducted to investigate the effects of various PGPR strains (W14, W10 and 6K; alone and combined) at several growth attributes of wheat plant under different soil salinity gradients (3, 6 and 9 dS m-1). The growth attributes of wheat (height, roots, shoots, spikes, grains quality, biological and economical yield, nutrients nitrogen, phosphorus and potassium in grains) were highly affected by salinity and decreased with increasing salinity level. The PGPR inoculation substantially promoted growth attributes of wheat and prominent results were observed in W14 × W10 × 6K treatment at all salinity levels. The results suggest that inoculation of PGPR is a potential strategy to mitigate salinity stress for improving wheat growth and yield.     

Pollination biology of Albizia lebbeck (L.) Benth. (Fabaceae: Mimosoideae) with reference to insect floral visitors

Indian siris, Albizia lebbeck (L.) Benth. (Fabaceae: Mimosoideae) has significant importance to human beings for its multipurpose use. Insects play a crucial role in the pollination biology of flowering plants. In the current study, we studied the pollination biology of A. lebbeck with special reference to insect floral visitors. The effectiveness of floral visitors was investigated in term of visitation frequency, visitation rate and pollen load during 2012 and 2013. In the second experiment, effect of pollinators on yield of A. lebbeck was studied in open and cage pollination experiments. Floral visitor fauna of A. lebbeck included eight-bees, two wasps, two flies, and two butterflies species. Among them, Apis dorsata, Apis florea, Amegilla cingulata, and Nomia oxybeloides had maximum abundance ranging from 349–492, 339–428, 291–342 and 235–255 numbers of individuals, respectively during two flowering seasons. A. dorsata had the highest visitation frequency (6.44 ± 0.49–8.78 ± 0.48 visits/flower/5min) followed by Amegilla cingulata (6.03 ± 0.43–7.99 ± 0.33 visits/flower/5min) and A. florea (3.61 ± 0.31–4.44 ± 0.18 visits/flower/5min). A. dorsata, N. oxybeloides, and Amegilla cingulata had the highest visitation rates (18.904 ± 1.53–11.43 ± 1.17 flower visited/min) and pollen load (15333 ± 336.22–19243 ± 648.45 pollen grains). The open pollinated flowers had significantly higher capsule weight (4.97 ± 0.21 g), seed weight (1.04 ± 0.05 g), seed numbers per pod (9.80 ± 0.34) and seed germination percentage (84.0 ± 1.78%) as compared to caged flowers. The results suggested bees especially A. dorsata, N. oxybeloides and Amegilla cingulata could be effective pollinators of A. lebbeck.     

Interference of phosphane copper (I) complexes of β-carboline with quorum sensing regulated virulence functions and biofilm in foodborne pathogenic bacteria: A first report

Foodborne pathogens are one of the major cause of food-related diseases and food poisoning. Bacterial biofilms and quorum sensing (QS) mechanism of cell–cell communication have also been found to be associated with several outbreaks of foodborne diseases and are great threat to food safety. Therefore, In the present study, we investigated the activity of three tetrahedrally coordinated copper(I) complexes against quorum sensing and biofilms of foodborne bacteria. All the three complexes demonstrated similar antimicrobial properties against the selected pathogens. Concentration below the MIC i.e. at sub-MICs all the three complexes interfered significantly with the quorum sensing regulated functions in C. violaceum (violacein), P. aeruginosa (elastase, pyocyanin and alginate production) and S. marcescens (prodigiosin). The complexes demonstrated potent broad-spectrum biofilm inhibition in Pseudomonas aeruginosa, E. coli, Chromobacterium violaceum, Serratia marcescens, Klebsiella pneumoniae and Listeria monocytogenes. Biofilm inhibition was visualized using SEM and CLSM images. Action of the copper(I) complexes on two key QS regulated functions contributing to biofilm formation i.e. EPS production and swarming motility was also studied and statistically significant reduction was recorded. These results could form the basis for development of safe anti-QS and anti-biofilm agents that can be utilized in the food industry as well as healthcare sector to prevent food-associated diseases.     

Circulating liver-specific microRNAs as noninvasive diagnostic biomarkers of hepatic diseases in human

Context: Hepatitis is an endemic disease worldwide leading to chronic and debilitating cancers. The viral agents and hepatotoxic substances lead to damage of hepatocytes and release of damage associated molecules in circulation. The lack of timely and rapid diagnosis of hepatitis results in chronic disease.

Objective: The present review aimed to describe regulation, release and functions of microRNAs (miR) during human liver pathology and insights into their promising use as noninvasive biomarkers of hepatitis.

Methods: Comprehensive data were collected from PubMed, ScienceDirect and the Web of Science databases utilizing the keywords “biomarkers”, “microRNAs” and “hepatic diseases”.

Results: The miRs are readily released in the body fluids and blood during HBV/HCV associated hepatitis as well as metabolic, alcoholic, drug induced and autoimmune hepatitis. The liver-specific microRNAs including miR-122, miR-130, miR-183, miR-196, miR-209 and miR-96 are potential indicators of liver injury (mainly via apoptosis, necrosis and necroptosis) or hepatitis with their varied expression during acute/fulminant, chronic, liver fibrosis/cirrhosis and hepato-cellular carcinoma.

Conclusions: The liver-specific miRs can be used as rapid and noninvasive biomarkers of hepatitis to discern different stages of hepatitis. Blocking or stimulating pathways associated with miR regulation in liver could unveil novel therapeutic strategies in the management of liver diseases.

• Clinical significance

• Liver specific microRNAs interact with cellular proteins and signaling molecules to regulate the expression of various genes controlling biological processes.

• The circulatory level of liver specific microRNAs is indicator of severity of HBV and HCV infections as well as prognostic and therapeutic candidates.

• The expression of liver specific microRNAs is strongly associated with infectious, drug-induced, hepatotoxic, nonalcoholic steatohepatitis and nonalcoholic fatty liver diseases.

     

Adsorption Evaluation of Herbicide Iodosulfuron Followed by Cedrus deodora Sawdust-Derived Activated Carbon Removal

The paucity of sorption studies of sulfonylurea herbicide Iodosulfuron has led to the current research for investigation of this imperative phenomena. Iodosulfuron adsorption capacity was evaluated through batch equilibrium experiments in six soil samples collected from distinct geographical regions of Pakistan. Activated carbon prepared from sawdust (Cedrus deodara) was investigated as an economical and sustainable adsorbent for the removal of Iodosulfuron from selected soils. Removal efficiency was studied as a function of contact time and pesticide concentration. Results exhibited a good adsorption capability of Iodosulfuron in different soils. Adsorption coefficient values ranged from 8.9 to 26 mL/g. Soil pH and organic matter greatly influenced the rate of adsorption. The linear adsorption model fitted best with the experimental results. Gibbs free energy values (?17 to ?20 kJ/mol) proposed physisorption and exothermic interaction of Iodosulfuron with selected soils. Analysis of variance and regression displayed a negative correlation of soil pH and K_d (R² = ?0.91) and positive correlation with organic matter (R² = 0.87). A good removal rate for was observed in soils by sawdust-derived activated carbon. Soil properties mainly; pH, organic matter and sand content greatly influenced Iodosulfuron removal phenomena. Biomass-derived activated carbon can thus be utilized as a sustainable remediation tool.     

Molecular genetics of <Emphasis Type="Italic">MARVELD2</Emphasis> and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss

Pathogenic mutations of MARVELD2, encoding tricellulin, a tricelluar tight junction protein, cause autosomal recessive non-syndromic hearing loss (DFNB49) in families of Pakistan and Czech Roma origin. In fact, they are a significant cause of prelingual hearing loss in the Czech Roma, second only to GJB2 variants. Previously, we reported that mice homozygous for p.Arg497* variant of Marveld2 had a broad phenotypic spectrum, where defects were observed in the inner ear, heart, mandibular salivary gland, thyroid gland and olfactory epithelium. The current study describes the types and frequencies of MARVELD2 alleles and clinically reexamines members of DFNB49 families. We found that MARVELD2 variants are responsible for about 1.5 % (95 % CI 0.8–2.6) of non-syndromic hearing loss in our cohort of 800 Pakistani families. The c.1331+2T>C allele is recurrent. In addition, we identified a novel large deletion in a single family, which appears to have resulted from non-allelic homologous recombination between two similar Alu short interspersed elements. Finally, we observed no other clinical manifestations co-segregating with hearing loss in DFNB49 human families, and hypothesize that the additional abnormalities in the Marveld2 mutant mouse indicates a critical non-redundant function for tricellulin in other organ systems.