A supercooled study of nucleation and symmetries

Nucleation is the process by which a metastable phase decays into a stable phase. It is widely observed in nature, and is responsible for many phenomena such as the formation clouds and domains in crystalline solids. The classical theory of nucleation predicts that the objects that initiate the decay from the metastable to the stable phase are compact droplets whose interior has the structure of the stable phase. For quenches deep into the metastable phase, however, the droplets may be ramified, with a structure very different from the stable phase. This difference has profound implications for material properties, especially because predicting the onset of structure early enough is useful for manipulating and controlling nucleation processes. I used molecular dynamics to simulate nucleation in Lennard-Jonesium, a model system for liquid-solid transformations. The system is quenched from a high temperature, where the liquid is stable, to a temperature where the liquid is metastable, and is allowed to nucleate via fluctuation-driven clusters referred to as critical droplets. I determined the occurrence of critical droplets by the intervention method, but found a non-monotonic variation in droplet survival rates near the saddle point. I determined the structure of the critical droplet and found evidence for a core consisting of mostly solid-like particles with hcp symmetry and a previously unknown planar structure around it. Using perturbative techniques, I showed that the planar particles have a significant influence on the nucleation and growth of critical droplets. I also introduced a novel method of learning symmetries to predict the structure and appearance of precursors to the critical nucleus. My results give added evidence for the presence of spinodal nucleation at deep quenches

Metabolic Network Modeling for Rational Drug Design against <em>Candida albicans</em>

The growing evidences of Candida albicans (C. albicans) infections are slowly becoming a threat to public health. Moreover, prevalence of antifungal resistant strains of C. albicans has emphasized the need for identification of potent targets for rational drug designing. In this aspect, traditional methods for target identification with validation have been found to be expensive and time-consuming. To overcome the concern, genome scale metabolic model construction provides a promising platform that allows novel target identification in combination with subtractive genome analysis. Thus, the chapter details current advancement in model construction, target identification and validation. In brief, it elucidates the overall strategies of C. albicans metabolome draft preparation, gap filling, curation of model, simulation followed by model validation, target identification and host pathogen interaction analysis. Finally, several examples of successful metabolic model construction and their utility in rational drug designing also have been discussed

Quadruplex-single nucleotide polymorphisms (Quad-SNP) influence gene expression difference among individuals

Non-canonical guanine quadruplex structures are not only predominant but also conserved among bacterial and mammalian promoters. Moreover recent findings directly implicate quadruplex structures in transcription. These argue for an intrinsic role of the structural motif and thereby posit that single nucleotide polymorphisms (SNP) that compromise the quadruplex architecture could influence function. To test this, we analysed SNPs within quadruplex motifs (Quad-SNP) and gene expression in 270 individuals across four populations (HapMap) representing more than 14 500 genotypes. Findings reveal significant association between quadruplex-SNPs and expression of the corresponding gene in individuals (P < 0.0001). Furthermore, analysis of Quad-SNPs obtained from population-scale sequencing of 1000 human genomes showed relative selection bias against alteration of the structural motif. To directly test the quadruplex-SNP-transcription connection, we constructed a reporter system using the RPS3 promoter—remarkable difference in promoter activity in the ‘quadruplex-destabilized’ versus ‘quadruplex-intact’ promoter was noticed. As a further test, we incorporated a quadruplex motif or its disrupted counterpart within a synthetic promoter reporter construct. The quadruplex motif, and not the disrupted-motif, enhanced transcription in human cell lines of different origin. Together, these findings build direct support for quadruplex-mediated transcription and suggest quadruplex-SNPs may play significant role in mechanistically understanding variations in gene expression among individuals

Genome-wide computational and expression analyses reveal G-quadruplex DNA motifs as conserved cis-regulatory elements in human and related species

Using a combination of in silico and experimental approaches, we present evidence that the G-quadruplex (G4) motif (an alternative higher-order DNA conformation) has regulatory potential. Genome-wide analyses of 99980 human, chimpanzee, mouse and rat promoters showed enrichment of sequence with potential to adopt G4 (potential G4 or PG4) motifs near transcription start sites (TSS; P&#60;0.0001), supporting earlier findings. Interestingly, we found &#62;700 orthologously related promoters in human, mouse and rat conserve PG4 motif(s). The corresponding genes have enriched (z score &#62;4.0) tissue-specific expression in 75 of 79 human tissues and are significantly overrepresented in signaling and regulation of cell-cycle (P&#60;10(−05)). This is supported by results from whole genome expression experiments in human HeLa S3 cells following treatment with TMPyP4 [5,10,15,20-tetra(N-methyl-4-pyridyl) porphine chloride], which is known to bind the G4 motif inside cells. Our results implicate G4-motif mediated regulation as a more general mode of transcription control than currently appreciated

The Tactical Strategy, Readiness, Epidemiology and Reaction to Potential Treatments for the Possibly Lethal Ebola Virus: A Review

Over the preceding 38 years, a few outbreaks have been brought on by the Ebola virus, which produces the Ebola illness. No specific treatment has been approved for EVD. Problem management and supportive care are the cornerstones of treatment. Effective outbreak control requires a multidisciplinary team effort that includes case care, infection prevention and control protocols, contact tracing and surveillance, a high-quality laboratory service, dignified and safe funerals, and social and community mobilization. The 2014 Ebola outbreak started in Africa and swiftly spread to other continents before turning into a pandemic. The illness gained international interest because to its relatively peculiar design, lethality and contagiousness, difficulty in containing its spread, and absence of a reliable treatment. Two medications have received FDA approval to treat EVD. Ebanga is a single monoclonal antibody, whereas Inmazeb is a mixture of three monoclonal antibodies.&nbsp; Individuals utilizing any of the two FDA-approved treatments had a significantly greater overall survival rate. In this article, the known history of the Ebola virus, its mode of infection, epidemiology, lifecycle, and possible treatments are briefly reviewed