BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

The majority of described plant viruses are transmitted by insects of the Hemipteroid assemblage that includes aphids, whiteflies, leafhoppers, planthoppers, and thrips. In this review we highlight progress made in research on vector interactions of the more than 200 plant viruses that are transmitted by hemipteroid insects beginning a few hours or days after acquisition and for up to the life of the insect, i.e., in a persistentcirculative or persistent-propagative mode. These plant viruses move through the insect vector, from the gut lumen into the hemolymph or other tissues and finally into the salivary glands, from which these viruses are introduced back into the plant host during insect feeding. The movement and/or replication of the viruses in the insect vectors require specific interactions between virus and vector components. Recent investigations have resulted in a better understanding of the replication sites and tissue tropism of several plant viruses that propagate in insect vectors. Furthermore, virus and insect proteins involved in overcoming transmission barriers in the vector have been identified for some virus-vector combinations.

Insect Vector Interactions with Persistently Transmitted Viruses

Halophytes are defined as plants that are adapted to live in soils containing high concentrations of salt and benefiting from it, and thus represent an ideal model to understand complex physiological and genetic mechanisms of salinity stress tolerance. It is also known that oxidative stress signalling and reactive oxygen species (ROS) detoxification are both essential components of salinity stress tolerance mechanisms. This paper comprehensively reviews the differences in ROS homeostasis between halophytes and glycophytes in an attempt to answer the questions of whether stress-induced ROS production is similar between halophytes and glycophytes; is the superior salinity tolerance in halophytes attributed to higher antioxidant activity; and is there something special about the specific ‘pool’ of enzymatic and non-enzymatic antioxidants in halophytes. We argue that truly salt-tolerant species possessing efficient mechanisms for Na + exclusion from the cytosol may not require a high level of antioxidant activity, as they simply do not allow excessive ROS production in the first instance. We also suggest that H 2O2 ‘signatures’ may operate in plant signalling networks, in addition to well-known cytosolic calcium ‘signatures’. According to the suggested concept, the intrinsically higher superoxide dismutase (SOD) levels in halophytes are required for rapid induction of the H2O2 ‘signature’, and to trigger a cascade of adaptive responses (both genetic and physiological), while the role of other enzymatic antioxidants may be in decreasing the basal levels of H2O2, once the signalling has been processed. Finally, we emphasize the importance of non-enzymatic antioxidants as the only effective means to prevent detrimental effects of hydroxyl radicals on cellular structures.

ROS homeostasis in halophytes in the context of salinity stress tolerance

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorders in the world. Studying PD from systems biology perspective involving genes and their regulators might provide deeper insights into the complex molecular interactions associated with this disease. We have studied gene co-expression network obtained from a PD-specific microarray data. The co-expression network identified 11 hub genes, of which eight genes are not previously known to be associated with PD. Further study on the functionality of these eight novel hub genes revealed that these genes play important roles in several neurodegenerative diseases. Furthermore, we have studied the tissue-specific expression and histone modification patterns of the novel hub genes. Most of these genes possess several histone modification sites those are already known to be associated with neurodegenerative diseases. Regulatory network namely mTF-miRNA-gene-gTF involves microRNA Transcription Factor (mTF), microRNA (miRNA), gene and gene Transcription Factor (gTF). Whereas long noncoding RNA (lncRNA) mediated regulatory network involves miRNA, gene, mTF and lncRNA. mTF-miRNA-gene-gTF regulatory network identified a novel feed-forward loop. lncRNA-mediated regulatory network identified novel lncRNAs of PD and revealed the two-way regulatory pattern of PD-specific miRNAs where miRNAs can be regulated by both the TFs and lncRNAs. SNP analysis of the most significant genes of the co-expression network identified 20 SNPs. These SNPs are present in the 3′ UTR of known PD genes and are controlled by those miRNAs which are also involved in PD. Our study identified eight novel hub genes which can be considered as possible candidates for future biomarker identification studies for PD. The two regulatory networks studied in our work provide a detailed overview of the cellular regulatory mechanisms where the non-coding RNAs namely miRNA and lncRNA, can act as epigenetic regulators of PD. SNPs identified in our study can be helpful for identifying PD at an earlier stage. Overall, this study may impart a better comprehension of the complex molecular interactions associated with PD from systems biology perspective.

/pdf/biological-networks-in-parkinson-s-disease-an-insight-into-31gq25b0p9.pdf

Biological networks in Parkinson’s disease: an insight into the epigenetic mechanisms associated with this disease

Comparative molecular dynamics simulations of psychrophilic type III antifreeze protein from the North-Atlantic ocean-pout Macrozoarces americanus and its corresponding mesophilic counterpart, the antifreeze-like domain of human sialic acid synthase, have been performed for 10 ns each at five different temperatures. Analyses of trajectories in terms of secondary structure content, solvent accessibility, intramolecular hydrogen bonds and protein–solvent interactions indicate distinct differences in these two proteins. The two proteins also follow dissimilar unfolding pathways. The overall flexibility calculated by the trace of the diagonalized covariance matrix displays similar flexibility of both the proteins near their growth temperatures. However at higher temperatures psychrophilic protein shows increased overall flexibility than its mesophilic counterpart. Principal component analysis also indicates that the essential subspaces explored by the simulations of two proteins at different temperatures are non-overlapping and they show significantly different directions of motion. However, there are significant overlaps within the trajectories and similar directions of motion of each protein especially at 298 K, 310 K and 373 K. Overall, the psychrophilic protein leads to increased conformational sampling of the phase space than its mesophilic counterpart. Our study may help in elucidating the molecular basis of thermostability of homologous proteins from two organisms living at different temperature conditions. Such an understanding is required for designing efficient proteins with characteristics for a particular application at desired working temperatures.

Comparative structural studies of psychrophilic and mesophilic protein homologues by molecular dynamics simulation.

HspR is a repressor known to control expression of heat shock operons in a number of Eubacteria. In mycobacteria and in several other actinobacteria, this protein is synthesized from the dnaKJE-hspR operon. Previous investigations revealed that HspR binds to the operon promoter, thereby controlling its expression in an autoregulatory manner. DnaK, which is a product of the same operon, further aids this autoregulatory process by stimulating the operator binding activity of HspR. The molecular mechanism by which DnaK assists HspR in executing its function is not clearly understood. In this study, it has been shown that DnaK can augment DNA binding activity of HspR by two mechanisms: (i) DnaK can restore the activity of completely denatured HspR by forming a complex with it, and (ii) DnaK can prevent thermal instability of HspR renatured by other means. Unlike the first mechanism, the latter function does not involve complex formation. The C-terminal hydrophobic tail of HspR was found to play a significant role in determining its thermal stability and DnaK dependence properties. A deletion mutant in which this region is removed does not respond to thermal stress and functions independent of DnaK. The hydrophobic C-terminal tails of HspRs of Mycobacterium tuberculosis and related Actinomycetales therefore may have evolved to make these HspRs more sensitive to thermal stress and, at the same time, subject to regulation by DnaK.

DnaK Dependence of the Mycobacterial Stress-Responsive Regulator HspR Is Mediated through Its Hydrophobic C-Terminal Tail

Background 
Parkinson's Disease (PD) is a progressive neurologic disorder that affects movement and balance. Recent studies have revealed the importance of microRNA (miR) in PD. However, the detailed role of miR and its regulation by Transcription Factor (TF) remain unexplored. In this work for the first time we have studied TF-miR-mRNA regulatory network as well as miR co-expression network in PD.


Result 
We compared the 204 differentially expressed miRs from microarray data with 73 PD related miRs obtained from literature, Human MicroRNA Disease Database and found a significant overlap of 47 PD related miRs (p-value<0.05). Functional enrichment analyses of these 47 common (Group1) miRs and the remaining 157 (Group2) miRs revealed similar kinds of over-representative GO Biological Processes and KEGG pathways. This strengthens the possibility that some of the Group 2 miRs can have functional roles in PD progression, hitherto unidentified in any study. In order to explore the cross talk between TF, miR and target mRNA, regulatory networks were constructed. Study of these networks resulted in 14 Inter-Regulatory hub miRs whereas miR co-expression network revealed 18 co-expressed hub miRs. Of these 32 hub miRs, 23 miRs were previously unidentified with respect to their association with PD. Hierarchical clustering analysis further strengthens the roles of these novel miRs in different PD pathways. Furthermore hsa-miR-92a appeared as novel hub miR in both regulatory and co-expression network indicating its strong functional role in PD. High conservation patterns were observed for most of these 23 novel hub miRs across different species including human. Thus these 23 novel hub miRs can be considered as potential biomarkers for PD.


Conclusion 
Our study identified 23 novel miR markers which can open up new avenues for future studies and shed lights on potential therapeutic targets for PD.

/pdf/studying-the-system-level-involvement-of-micrornas-in-okbmr07zqr.pdf

Debjani Roy

Papers

Biological networks in Parkinson’s disease: an insight into the epigenetic mechanisms associated with this disease

Comparative structural studies of psychrophilic and mesophilic protein homologues by molecular dynamics simulation.

DnaK Dependence of the Mycobacterial Stress-Responsive Regulator HspR Is Mediated through Its Hydrophobic C-Terminal Tail

Studying the System-Level Involvement of MicroRNAs in Parkinson's Disease

Comparative analysis of RNA-Seq data from brain and blood samples of Parkinson's disease.