There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

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

Melioidosis, caused by the gram-negative saprophyte Burkholderia pseudomallei, is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans. It has the potential for epidemic spread to areas where it is not endemic, and sporadic case reports elsewhere in the world suggest that as-yet-unrecognized foci of infection may exist. Environmental determinants of this infection, apart from a close association with rainfall, are yet to be elucidated. The sequencing of the genome of a strain of B. pseudomallei has recently been completed and will help in the further identification of virulence factors. The presence of specific risk factors for infection, such as diabetes, suggests that functional neutrophil defects are important in the pathogenesis of melioidosis; other studies have defined virulence factors (including a type III secretion system) that allow evasion of killing mechanisms by phagocytes. There is a possible role for cell-mediated immunity, but repeated environmental exposure does not elicit protective humoral or cellular immunity. A vaccine is under development, but economic constraints may make vaccination an unrealistic option for many regions of endemicity. Disease manifestations are protean, and no inexpensive, practical, and accurate rapid diagnostic tests are commercially available; diagnosis relies on culture of the organism. Despite the introduction of ceftazidime- and carbapenem-based intravenous treatments, melioidosis is still associated with a significant mortality attributable to severe sepsis and its complications. A long course of oral eradication therapy is required to prevent relapse. Studies exploring the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease.

https://ams.kku.ac.th/suchat/Mellioidosis/Melioidosis%20Epidemiology%20Pathophysiology,and%20Management.pdf

Melioidosis: Epidemiology, Pathophysiology, and Management

of antibiotics, whether there was an explicit note in the medical chart in which the physician diagnosed a true bacteremia, and the Centers for Disease Control surveillance criteria for primary bloodstream infection. Agreement between same-strain bacteremia and each definition was examined, based on the assumption that most true infections should be the result of a single strain. The study sample consisted of 42 patients and 106 isolates. Nineteen of the 42 bacteremias (45%) were the same strain. Classification of bacteremias as same-strain correlated poorly with all three clinical assessments (range of percentage agreement, 50%-57%; range of kappa statistic, 0.01-0.15). There were both false-positive and false-negative errors. Patients with three or more positive blood cultures were more likely to have same-strain bacteremia than those with only two positive cultures (11/15 [73%] vs 8/27 [30%], P=.006). Pulsed-field gel electrophoresis was more discriminating than AP PCR (percentage agreement, 83%; kappa, 0.67). The authors concluded that molecular typing correlated poorly with clinical criteria for true bacteremia, suggesting either that true bacteremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true bacteremia. Vancomycin treatment of clinically defined coagulase-negative staphylococcal bacteremia may frequently be unnecessary. FROM: Seo SK, Venkataraman L, DeGirolami PC, Samore MH. Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia. Am J Med 2000;109:697-704.

/pdf/nasal-carriage-as-a-source-of-staphylococcus-aureus-40zkf0m446.pdf

Nasal Carriage as a Source of Staphylococcus aureus Bacteremia

Cation-π interaction: its role and relevance in chemistry, biology, and material science.

Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities.

Abbreviations
ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - – Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - – Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.

/pdf/flavonoid-from-carica-papaya-inhibits-ns2b-ns3-protease-and-bceg2oeojl.pdf

Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly.

Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools.

The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures.

/pdf/computational-analysis-reveals-the-association-of-threonine-11qoltw071.pdf

Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A.

Background & objectives: Melioidosis and the causative organism Burkholderia 

pseudomallei are being recognized gradually in various centres in India. In the septicaemic form, 

melioidosis is a serious and life threatening condition which requires early detection and specific 

treatment to avoid case fatality. A review of patients with septicaemic melioidosis at a tertiary 

care hospital in south India was carried out with a view to define the clinical features, 

predisposing conditions, if any, and the outcome. Methods: A total of 28 patients with culture proven 

septicaemic melioidosis during December 1993 to December 2002 were included. Information on clinical 

details and outcome was obtained and antibiotic susceptibility of the isolates studied. Results: Of 

the 28 patients of blood culture proven septicaemic melioidosis, the organism was also isolated from 

pus in two patients. The presenting clinical features were varied, most presenting as pyrexia of 

unknown origin or visceral abscesses, or septic arthiritis. Associated/predisposing conditions were 

present in 50 per cent of the patients, and diabetes mellitus was the commonest one. The mortality 

was 58 per cent in our series. Interpretation & conclusion: Melioidosis is an emerging infection 

in India. The magnitude of the problem can only be assessed by increasing awareness, both of its 

existence in the clinical setting and its identification in the laboratory.

Septicaemic melioidosis in a tertiary care hospital in south India.

Bacterial resistance to β-lactam antibiotics poses a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pathogenic bacteria expressing drug insensitive PBPs rendering β-lactam antibiotics ineffective and (ii) production of β-lactamases along with alteration of their specificities. Thus, there is an urgent need to develop newer β-lactams to overcome the challenge of bacterial resistance. Therefore the present study aims to identify the binding affinity of β-lactam antibiotics with different types of PBPs and β-lactamases. In this study, cephalosporins and carbapenems are docked into PBP2a of Staphylococcus aureus, PBP2b and PBP2x of Streptococcus pneumoniae and SHV-1 β-lactamase of Escherichia coli. The results reveal that Ceftobiprole can efficiently bind to PBP2a, PBP2b and PBP2x and not strongly to SHV-1 β-lactamase. Furthermore, molecular dynamics (MD) simulations are performed to refine the binding mode of the docked complex structure and to observe the differences in the stability of free PBP2x and Ceftobiprole bound PBP2x. MD simulation supports the greater stability of the Ceftobiprole–PBP2x complex compared to free PBP2x. This work demonstrates that potential β-lactam antibiotics can efficiently bind to different types of PBPs for circumventing β-lactam resistance and opens avenues for the development of newer antibiotics that can target bacterial pathogens.

Anand Anbarasu

Papers

Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly.

Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools.

Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A.

Septicaemic melioidosis in a tertiary care hospital in south India.

Molecular docking and molecular dynamics studies on β-lactamases and penicillin binding proteins