Uncovering Genes with Divergent mRNA-Protein Dynamics in Streptomyces coelicolor

Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ™) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level

A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants.

Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011

UNDERSTANDING THE MOLECULAR BASIS OF CELL DEATH MEDIATED BY ONCOSIS-INDUCING CYTOTOXIC ANTIBODIES

Ph.DDOCTOR OF PHILOSOPH

COMMON NECROSIS-APOPTOSIS COMMITMENT

Master'sMASTER OF SCIENC

miRNA in Ischemic Heart Disease and Its Potential as Biomarkers:A Comprehensive Review

Ischemic heart disease (IHD) constitutes the leading global cause of mortality and morbidity. Although significant progress has been achieved in the diagnosis, treatment, and prognosis of IHD, more robust diagnostic biomarkers and therapeutic interventions are still needed to circumvent the increasing incidence of IHD. MicroRNAs (miRNAs) are critical regulators of cardiovascular function and are involved in various facets of cardiovascular biology. While the knowledge of the role of miRNAs in IHD as diagnostic biomarkers has improved, research emphasis on how miRNAs can be effectively used for diagnosis and prognosis of IHD is crucial. This review provides an overview of the biology, therapeutic and diagnostic potential, as well as the caveats of using miRNAs in IHD based on existing research

Oxidative stress parameters as biomarkers of cardiovascular disease towards the development and progression

Cardiovascular disease (CVD) remains the leading cause of death globally, with unhealthy lifestyles today greatly increasing the risk. Over the decades, scientific investigation has been carried out on reactive oxygen species (ROS) and their resultant oxidative stress based on their changes made on biological targets such as lipids, proteins, and DNA. Since the existing clinical studies with antioxidants failed to provide relevant findings on CVD prediction, the focus has shifted towards recognition of oxidised targets as biomarkers to predict prognosis and response to accurate treatment. The identification of redox markers could help clinicians in providing risk stratification for CVD events beyond the traditional prognostic and diagnostic targets. This review will focus on how oxidant-related parameters can be applied as biomarkers for CVD based on recent clinical evidence

Proteomics Profiling of Cellular Reprogramming: Are Human Induced Pluripotent Stem Cells (hiPSCs) Indistinguishable from Human Embryonic Stem Cells (hESCs)?

<p><em>presented in: ASMS 2010 in Salt Lake City, Utah</em></p> <p> </p> <p>“Are iPS cells indistinguishable from ES cells?”<br>We prole the proteomes of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) with quantitative dimethyllabeling developed in-house to unravel the similarities and dierences between the two cell lines. Our results show that both pluripotent cell lines are nearly indistinguishable at the proteome level.</p> <p>Being self-renewing and pluripotent, hESCs hold great promise for cell transplantation therapies to cure degenerative diseases such as Parkinson’s disease or heart failures. However, this technology is limited by ethical issues since embryos are inevitably destroyed upon derivation of hESCs. Besides, potential risks do exist for immune rejection posttransplantion. These issues can probably be addressed now by the reprogramming<br>technology where adult somatic cells are induced to become hESC-like by the ectopic expression of dened transcription factors. These induced pluripotent stem cells (hiPSCs) closely resemble hESCs in many aspects, such as the expression of certain stem cell markers. More importantly, they are also capable of pluripotency and self-renewal.</p> <p>Being patient-derived and thus patient-specic, hiPSCs are ideal replacements for hESCs in cell transplantation therapies. However, before any clinical applications, they need to be characterized extensively so as to evaluate their abilities for replication and dierentiation in comparison to the actual hESCs.</p> <p>More recently, transcriptomic approaches have been used to assess the gene expression proles of both cell types. We argue that mRNA levels are not truly representative of the true character of a cell as proteins are the actual functional entities. Therefore, we used “proteomics profiling” instead and ask “Are iPS cells indistinguishable from ES cells?”</p> <p> </p> <p> </p> <p> </p

A metal-containing NP approach to treat methicillin-resistant <i>Staphylococcus aureus</i> (MRSA):Prospects and challenges

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in humans, and it is associated with high morbidity and mortality rates, especially in immunocompromised patients. Its high rate of multidrug resistance led to an exploration of novel antimicrobials. Metal nanoparticles have shown potent antibacterial activity, thus instigating their application in MRSA. This review summarizes current insights of Metal-Containing NPs in treating MRSA. This review also provides an in-depth appraisal of opportunities and challenges in utilizing metal-NPs to treat MRSA

Effect of lignosulphonates on Vanilla planifolia shoot multiplication, regeneration and metabolism

Vanilla planifolia (V. planifolia) is a valuable orchidaceous plant, commonly grown for its pods that are used to produce the flavouring vanilla extract. Here, we evaluated the effect of calcium lignosulphonate (Ca-LIGN) and sodium lignosulphonate (Na-LIGN) on multiplication and regeneration of V. planifolia shoot tip culture. In 150 mg L−1 Ca-LIGN medium, the most number of shoots per explant (5.78 ± 0.63) was successfully obtained. Besides, Ca-LIGN also enhanced the shoot bud and primordial formation rate, as seen under scanning electron microscopy. In contrast, medium containing 150 mg L−1 Na-LIGN recorded the highest average of shoot length (4.72 ± 0.30 cm). Meanwhile, the best growth of root length (1.8 ± 0.32 cm) and root induction (96.67 ± 5.16%) were recorded on the explants treated with 150 mg L−1 Na-LIGN rooting medium. All rooted plantlets successfully acclimatized in the greenhouse (100.00% survival rate). Further biochemical analysis revealed that Ca-LIGN increased the total protein, chlorophyll, sugar, flavonoid and phenolic contents of V. planifolia. Notably, expression of both ribulose-1,5-bisphosphate carboxylase (Rubisco) and phosphoenolpyruvate carboxylase (PEPC) genes were also elevated under the treatment of Ca-LIGN, implying a positive role in the photosynthetic process. Taken together, LIGN being an environmental friendly product could be used to enhance the growth and micropropagation of V. planifolia