On supersymmetric quantum mechanics

This paper constitutes a review on N=2 fractional supersymmetric Quantum Mechanics of order k. The presentation is based on the introduction of a generalized Weyl-Heisenberg algebra W_k. It is shown how a general Hamiltonian can be associated with the algebra W_k. This general Hamiltonian covers various supersymmetrical versions of dynamical systems (Morse system, Poschl-Teller system, fractional supersymmetric oscillator of order k, etc.). The case of ordinary supersymmetric Quantum Mechanics corresponds to k=2. A connection between fractional supersymmetric Quantum Mechanics and ordinary supersymmetric Quantum Mechanics is briefly described. A realization of the algebra W_k, of the N=2 supercharges and of the corresponding Hamiltonian is given in terms of deformed-bosons and k-fermions as well as in terms of differential operators.Comment: Review paper (31 pages) to be published in: Fundamental World of Quantum Chemistry, A Tribute to the Memory of Per-Olov Lowdin, Volume 3, E. Brandas and E.S. Kryachko (Eds.), Springer-Verlag, Berlin, 200

The Interplay between Protein L-Isoaspartyl Methyltransferase Activity and Insulin-Like Signaling to Extend Lifespan in Caenorhabditis elegans

The protein L-isoaspartyl-O-methyltransferase functions to initiate the repair of isomerized aspartyl and asparaginyl residues that spontaneously accumulate with age in a variety of organisms. Caenorhabditis elegans nematodes lacking the pcm-1 gene encoding this enzyme display a normal lifespan and phenotype under standard laboratory growth conditions. However, significant defects in development, egg laying, dauer survival, and autophagy have been observed in pcm-1 mutant nematodes when deprived of food and when exposed to oxidative stress. Interestingly, overexpression of this repair enzyme in both Drosophila and C. elegans extends adult lifespan under thermal stress. In this work, we show the involvement of the insulin/insulin-like growth factor-1 signaling (IIS) pathway in PCM-1-dependent lifespan extension in C. elegans. We demonstrate that reducing the levels of the DAF-16 downstream transcriptional effector of the IIS pathway by RNA interference reduces the lifespan extension resulting from PCM-1 overexpression. Using quantitative real-time PCR analysis, we show the up-regulation of DAF-16-dependent stress response genes in the PCM-1 overexpressor animals compared to wild-type and pcm-1 mutant nematodes under mild thermal stress conditions. Additionally, similar to other long-lived C. elegans mutants in the IIS pathway, including daf-2 and age-1 mutants, PCM-1 overexpressor adult animals display increased resistance to severe thermal stress, whereas pcm-1 mutant animals survive less long under these conditions. Although we observe a higher accumulation of damaged proteins in pcm-1 mutant nematodes, the basal level of isoaspartyl residues detected in wild-type animals was not reduced by PCM-1 overexpression. Our results support a signaling role for the protein L-isoaspartyl methyltransferase in lifespan extension that involves the IIS pathway, but that may be independent of its function in overall protein repair

Radial Corrugations of Multi-Walled Carbon Nanotubes Driven by Inter-Wall Nonbonding Interactions

We perform large-scale quasi-continuum simulations to determine the stable cross-sectional configurations of free-standing multi-walled carbon nanotubes (MWCNTs). We show that at an inter-wall spacing larger than the equilibrium distance set by the inter-wall van der Waals (vdW) interactions, the initial circular cross-sections of the MWCNTs are transformed into symmetric polygonal shapes or asymmetric water-drop-like shapes. Our simulations also show that removing several innermost walls causes even more drastic cross-sectional polygonization of the MWCNTs. The predicted cross-sectional configurations agree with prior experimental observations. We attribute the radial corrugations to the compressive stresses induced by the excessive inter-wall vdW energy release of the MWCNTs. The stable cross-sectional configurations provide fundamental guidance to the design of single MWCNT-based devices and shed lights on the mechanical control of electrical properties

Comparative Assessment of Copper, Iron, and Zinc Contents in Selected Indian (Assam) and South African (Thohoyandou) Tea (Camellia sinensis L.) Samples and Their Infusion: A Quest for Health Risks to Consumer

The current study aims to assess the infusion pattern of three important micronutrients namely copper (Cu), iron (Fe), and zinc (Zn) contents from black tea samples produced in Assam (India) and Thohoyandou (South Africa). Average daily intakes and hazardous quotient were reported for these micronutrients. Total content for Cu, Fe, and Zn varied from 2.25 to 48.82 mg kg−1, 14.75 to 148.18 mg kg−1, and 28.48 to 106.68 mg kg−1, respectively. The average contents of each of the three micronutrients were higher in tea leaves samples collected from South Africa than those from India while the contents in tea infusions in Indian samples were higher than in South African tea samples. Results of this study revealed that the consumption of 600 mL tea infusion produced from 24 g of made tea per day may be beneficial to human in terms of these micronutrients content. Application of nonparametric tests revealed that most of the data sets do not satisfy the normality assumptions. Hence, the use of both parametric and nonparametric statistical analysis that subsequently revealed significant differences in elemental contents among Indian and South African tea

Depletion of somatic mutations in splicing-associated sequences in cancer genomes

Abstract Background An important goal of cancer genomics is to identify systematically cancer-causing mutations. A common approach is to identify sites with high ratios of non-synonymous to synonymous mutations; however, if synonymous mutations are under purifying selection, this methodology leads to identification of false-positive mutations. Here, using synonymous somatic mutations (SSMs) identified in over 4000 tumours across 15 different cancer types, we sought to test this assumption by focusing on coding regions required for splicing. Results Exon flanks, which are enriched for sequences required for splicing fidelity, have ~ 17% lower SSM density compared to exonic cores, even after excluding canonical splice sites. While it is impossible to eliminate a mutation bias of unknown cause, multiple lines of evidence support a purifying selection model above a mutational bias explanation. The flank/core difference is not explained by skewed nucleotide content, replication timing, nucleosome occupancy or deficiency in mismatch repair. The depletion is not seen in tumour suppressors, consistent with their role in positive tumour selection, but is otherwise observed in cancer-associated and non-cancer genes, both essential and non-essential. Consistent with a role in splicing modulation, exonic splice enhancers have a lower SSM density before and after controlling for nucleotide composition; moreover, flanks at the 5’ end of the exons have significantly lower SSM density than at the 3’ end. Conclusions These results suggest that the observable mutational spectrum of cancer genomes is not simply a product of various mutational processes and positive selection, but might also be shaped by negative selection

A review of data needed to parameterize a dynamic model of measles in developing countries

<p>Abstract</p> <p>Background</p> <p>Dynamic models of infection transmission can project future disease burden within a population. Few dynamic measles models have been developed for low-income countries, where measles disease burden is highest. Our objective was to review the literature on measles epidemiology in low-income countries, with a particular focus on data that are needed to parameterize dynamic models.</p> <p>Methods</p> <p>We included age-stratified case reporting and seroprevalence studies with fair to good sample sizes for mostly urban African and Indian populations. We emphasized studies conducted before widespread immunization. We summarized age-stratified attack rates and seroprevalence profiles across these populations. Using the study data, we fitted a "representative" seroprevalence profile for African and Indian settings. We also used a catalytic model to estimate the age-dependent force of infection for individual African and Indian studies where seroprevalence was surveyed. We used these data to quantify the effects of population density on the basic reproductive number <it>R</it>₀.</p> <p>Results</p> <p>The peak attack rate usually occurred at age 1 year in Africa, and 1 to 2 years in India, which is earlier than in developed countries before mass vaccination. Approximately 60% of children were seropositive for measles antibody by age 2 in Africa and India, according to the representative seroprevalence profiles. A statistically significant decline in the force of infection with age was found in 4 of 6 Indian seroprevalence studies, but not in 2 African studies. This implies that the classic threshold result describing the critical proportion immune (<it>p</it>_c) required to eradicate an infectious disease, <it>p</it>_c= 1-1/<it>R</it>₀, may overestimate the required proportion immune to eradicate measles in some developing country populations. A possible, though not statistically significant, positive relation between population density and <it>R</it>₀for various Indian and African populations was also found. These populations also showed a similar pattern of waning of maternal antibodies. Attack rates in rural Indian populations show little dependence on vaccine coverage or population density compared to urban Indian populations. Estimated <it>R</it>₀values varied widely across populations which has further implications for measles elimination.</p> <p>Conclusions</p> <p>It is possible to develop a broadly informative dynamic model of measles transmission in low-income country settings based on existing literature, though it may be difficult to develop a model that is closely tailored to any given country. Greater efforts to collect data specific to low-income countries would aid in control efforts by allowing highly population-specific models to be developed.</p

The multicellularity genes of dictyostelid social amoebas

The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives. This set is enriched in cytosolic and nuclear proteins, and protein kinases. The remaining 20%, unique to Dictyostelia, mostly consists of extracellularly exposed and secreted proteins, with roles in sensing and recognition, while several genes for synthesis of signals that induce cell-type specialization were acquired by lateral gene transfer. Across Dictyostelia, changes in gene expression correspond more strongly with phenotypic innovation than changes in protein functional domains. We conclude that the transition to multicellularity required novel signals and sensors rather than novel signal processing mechanisms

Polyglutamine Induced Misfolding of Huntingtin Exon1 is Modulated by the Flanking Sequences

Polyglutamine (polyQ) expansion in exon1 (XN1) of the huntingtin protein is linked to Huntington's disease. When the number of glutamines exceeds a threshold of approximately 36–40 repeats, XN1 can readily form amyloid aggregates similar to those associated with disease. Many experiments suggest that misfolding of monomeric XN1 plays an important role in the length-dependent aggregation. Elucidating the misfolding of a XN1 monomer can help determine the molecular mechanism of XN1 aggregation and potentially help develop strategies to inhibit XN1 aggregation. The flanking sequences surrounding the polyQ region can play a critical role in determining the structural rearrangement and aggregation mechanism of XN1. Few experiments have studied XN1 in its entirety, with all flanking regions. To obtain structural insights into the misfolding of XN1 toward amyloid aggregation, we perform molecular dynamics simulations on monomeric XN1 with full flanking regions, a variant missing the polyproline regions, which are hypothesized to prevent aggregation, and an isolated polyQ peptide (Qn). For each of these three constructs, we study glutamine repeat lengths of 23, 36, 40 and 47. We find that polyQ peptides have a positive correlation between their probability to form a β-rich misfolded state and their expansion length. We also find that the flanking regions of XN1 affect its probability to^x_page_count=28 form a β-rich state compared to the isolated polyQ. Particularly, the polyproline regions form polyproline type II helices and decrease the probability of the polyQ region to form a β-rich state. Additionally, by lengthening polyQ, the first N-terminal 17 residues are more likely to adopt a β-sheet conformation rather than an α-helix conformation. Therefore, our molecular dynamics study provides a structural insight of XN1 misfolding and elucidates the possible role of the flanking sequences in XN1 aggregation

Extent of Structural Asymmetry in Homodimeric Proteins: Prevalence and Relevance

Most homodimeric proteins have symmetric structure. Although symmetry is known to confer structural and functional advantage, asymmetric organization is also observed. Using a non-redundant dataset of 223 high-resolution crystal structures of biologically relevant homodimers, we address questions on the prevalence and significance of asymmetry. We used two measures to quantify global and interface asymmetry, and assess the correlation of several molecular and structural parameters with asymmetry. We have identified rare cases (11/223) of biologically relevant homodimers with pronounced global asymmetry. Asymmetry serves as a means to bring about 2∶1 binding between the homodimer and another molecule; it also enables cellular signalling arising from asymmetric macromolecular ligands such as DNA. Analysis of these cases reveals two possible mechanisms by which possible infinite array formation is prevented. In case of homodimers associating via non-topologically equivalent surfaces in their tertiary structures, ligand-dependent mechanisms are used. For stable dimers binding via large surfaces, ligand-dependent structural change regulates polymerisation/depolymerisation; for unstable dimers binding via smaller surfaces that are not evolutionarily well conserved, dimerisation occurs only in the presence of the ligand. In case of homodimers associating via interaction surfaces with parts of the surfaces topologically equivalent in the tertiary structures, steric hindrance serves as the preventive mechanism of infinite array. We also find that homodimers exhibiting grossly symmetric organization rarely exhibit either perfect local symmetry or high local asymmetry. Binding of small ligands at the interface does not cause any significant variation in interface asymmetry. However, identification of biologically relevant interface asymmetry in grossly symmetric homodimers is confounded by the presence of similar small magnitude changes caused due to artefacts of crystallisation. Our study provides new insights regarding accommodation of asymmetry in homodimers

Changes in Lysozyme Flexibility upon Mutation Are Frequent, Large and Long-Ranged

We investigate changes in human c-type lysozyme flexibility upon mutation via a Distance Constraint Model, which gives a statistical mechanical treatment of network rigidity. Specifically, two dynamical metrics are tracked. Changes in flexibility index quantify differences within backbone flexibility, whereas changes in the cooperativity correlation quantify differences within pairwise mechanical couplings. Regardless of metric, the same general conclusions are drawn. That is, small structural perturbations introduced by single point mutations have a frequent and pronounced affect on lysozyme flexibility that can extend over long distances. Specifically, an appreciable change occurs in backbone flexibility for 48% of the residues, and a change in cooperativity occurs in 42% of residue pairs. The average distance from mutation to a site with a change in flexibility is 17–20 Å. Interestingly, the frequency and scale of the changes within single point mutant structures are generally larger than those observed in the hen egg white lysozyme (HEWL) ortholog, which shares 61% sequence identity with human lysozyme. For example, point mutations often lead to substantial flexibility increases within the β-subdomain, which is consistent with experimental results indicating that it is the nucleation site for amyloid formation. However, β-subdomain flexibility within the human and HEWL orthologs is more similar despite the lowered sequence identity. These results suggest compensating mutations in HEWL reestablish desired properties