Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

The Architectural Design Rules of Solar Systems based on the New Perspective

On the basis of the Lunar Laser Ranging Data released by NASA on the Silver Jubilee Celebration of Man Landing on Moon on 21st July 1969-1994, theoretical formulation of Earth-Moon tidal interaction was carried out and Planetary Satellite Dynamics was established. It was found that this mathematical analysis could as well be applied to Star and Planets system and since every star could potentially contain an extra-solar system, hence we have a large ensemble of exoplanets to test our new perspective on the birth and evolution of solar systems. Till date 403 exoplanets have been discovered in 390 extra-solar systems. I have taken 12 single planet systems, 4 Brown Dwarf - Star systems and 2 Brown Dwarf pairs. Following architectural design rules are corroborated through this study of exoplanets. All planets are born at inner Clarke Orbit what we refer to as inner geo-synchronous orbit in case of Earth-Moon System. By any perturbative force such as cosmic particles or radiation pressure, the planet gets tipped long of aG1 or short of aG1. Here aG1 is inner Clarke Orbit. The exoplanet can either be launched on death spiral as CLOSE HOT JUPITERS or can be launched on an expanding spiral path as the planets in our Solar System are. It was also found that if the exo-planet are significant fraction of the host star then those exo-planets rapidly migrate from aG1 to aG2 and have very short Time Constant of Evolution as Brown Dwarfs have. This vindicates our basic premise that planets are always born at inner Clarke Orbit. This study vindicates the design rules which had been postulated at 35th COSPAR Scientific Assembly in 2004 at Paris, France, under the title ,New Perspective on the Birth & Evolution of Solar Systems.Comment: This paper has been reported to Earth,Moon and Planets Journal as MOON-S-09-0007

Magnetic Fluffy Dark Matter

We explore extensions of inelastic Dark Matter and Magnetic inelastic Dark Matter where the WIMP can scatter to a tower of heavier states. We assume a WIMP mass $m_\chi \sim \mathcal{O}(1-100)$ GeV and a constant splitting between successive states $\delta \sim\mathcal{O}(1 - 100)$ keV. For the spin-independent scattering scenario we find that the direct experiments CDMS and XENON strongly constrain most of the DAMA/LIBRA preferred parameter space, while for WIMPs that interact with nuclei via their magnetic moment a region of parameter space corresponding to $m_{\chi}\sim 11$ GeV and $\delta < 15$ keV is allowed by all the present direct detection constraints.Comment: 16 pages, 6 figures, added comments about magnetic moment form factor to Sec 3.1.2 and results to Sec 3.2.2, final version to be published in JHE

Probing top charged-Higgs production using top polarization at the Large Hadron Collider

We study single top production in association with a charged Higgs in the type II two Higgs doublet model at the Large Hadron Collider. The polarization of the top, reflected in the angular distributions of its decay products, can be a sensitive probe of new physics in its production. We present theoretically expected polarizations of the top for top charged-Higgs production, which is significantly different from that in the closely related process of t-W production in the Standard Model. We then show that an azimuthal symmetry, constructed from the decay lepton angular distribution in the laboratory frame, is a sensitive probe of top polarization and can be used to constrain parameters involved in top charged-Higgs production.Comment: 22 pages, 18 Figures, Discussions about backgrounds and NLO corrections added, figures modified, references added, Version published in JHE

The Dark Side of the Electroweak Phase Transition

Recent data from cosmic ray experiments may be explained by a new GeV scale of physics. In addition the fine-tuning of supersymmetric models may be alleviated by new O(GeV) states into which the Higgs boson could decay. The presence of these new, light states can affect early universe cosmology. We explore the consequences of a light (~ GeV) scalar on the electroweak phase transition. We find that trilinear interactions between the light state and the Higgs can allow a first order electroweak phase transition and a Higgs mass consistent with experimental bounds, which may allow electroweak baryogenesis to explain the cosmological baryon asymmetry. We show, within the context of a specific supersymmetric model, how the physics responsible for the first order phase transition may also be responsible for the recent cosmic ray excesses of PAMELA, FERMI etc. We consider the production of gravity waves from this transition and the possible detectability at LISA and BBO

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST