Birth and death of gene overlaps in vertebrates

<p>Abstract</p> <p>Background</p> <p>Between five and fourteen per cent of genes in the vertebrate genomes do overlap sharing some intronic and/or exonic sequence. It was observed that majority of these overlaps are not conserved among vertebrate lineages. Although several mechanisms have been proposed to explain gene overlap origination the evolutionary basis of these phenomenon are still not well understood. Here, we present results of the comparative analysis of several vertebrate genomes. The purpose of this study was to examine overlapping genes in the context of their evolution and mechanisms leading to their origin.</p> <p>Results</p> <p>Based on the presence and arrangement of human overlapping genes orthologs in rodent and fish genomes we developed 15 theoretical scenarios of overlapping genes evolution. Analysis of these theoretical scenarios and close examination of genomic sequences revealed new mechanisms leading to the overlaps evolution and confirmed that many of the vertebrate gene overlaps are not conserved. This study also demonstrates that repetitive elements contribute to the overlapping genes origination and, for the first time, that evolutionary events could lead to the loss of an ancient overlap.</p> <p>Conclusion</p> <p>Birth as well as most probably death of gene overlaps occurred over the entire time of vertebrate evolution and there wasn't any rapid origin or 'big bang' in the course of overlapping genes evolution. The major forces in the gene overlaps origination are transposition and exaptation. Our results also imply that origin of overlapping genes is not an issue of saving space and contracting genomes size.</p

Evolutionary dynamics of U12-type spliceosomal introns

<p>Abstract</p> <p>Background</p> <p>Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.</p> <p>Results</p> <p>We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in <it>Drosophila melanogaster</it>, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.</p> <p>Conclusions</p> <p>Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.</p

Alcohol Use, HIV Treatment Adherence, and Sexual Risk Among People with a History of Injecting Drug Use in Vietnam.

Alcohol use can limit the effectiveness of antiretroviral therapy (ART) for people living with HIV (PLH) who have a history of injecting drug use. This study described the patterns of alcohol use among PLH with a history of injecting drug use in Vietnam and examined the relationships between alcohol use, adherence to ART, and sexual risks. We utilized cross-sectional data of 109 PLH on ART collected from a randomized controlled intervention trial in Vietnam. Approximately 30 and 46% of the participants were frequent and occasional drinkers, respectively. Frequent drinkers reported the highest number of missed medication days. About 61% of frequent drinkers reported having sex after using alcohol. Additionally, 23, 34, and 24% of nondrinkers, occasional drinkers, and frequent drinkers, respectively, reported inconsistent condom use during sex. Future intervention programs should address the issues of alcohol use and sexual risks to maximize the effectiveness of HIV treatment programs in Vietnam

U12-type Spliceosomal Introns of Insecta

Most of eukaryotic genes are interrupted by introns that need to be removed from pre-mRNAs before they can perform their function. This is done by complex machinery called spliceosome. Many eukaryotes possess two separate spliceosomal systems that process separate sets of introns. The major (U2) spliceosome removes majority of introns, while minute fraction of intron repertoire is processed by the minor (U12) spliceosome. These two populations of introns are called U2-type and U12-type, respectively. The latter fall into two subtypes based on the terminal dinucleotides. The minor spliceosomal system has been lost independently in some lineages, while in some others few U12-type introns persist. We investigated twenty insect genomes in order to better understand the evolutionary dynamics of U12-type introns. Our work confirms dramatic drop of U12-type introns in Diptera, leaving these genomes just with a handful cases. This is mostly the result of intron deletion, but in a number of dipteral cases, minor type introns were switched to a major type, as well. Insect genes that harbor U12-type introns belong to several functional categories among which proteins binding ions and nucleic acids are enriched and these few categories are also overrepresented among these genes that preserved minor type introns in Diptera

Magnetowave Induced Plasma Wakefield Acceleration for Ultra High Energy Cosmic Rays

Magnetowave induced plasma wakefield acceleration (MPWA) in a relativistic astrophysical outflow has been proposed as a viable mechanism for the acceleration of cosmic particles to ultra high energies. Here we present simulation results that clearly demonstrate the viability of this mechanism for the first time. We invoke the high frequency and high speed whistler mode for the driving pulse. The plasma wakefield so induced validates precisely the theoretical prediction. We show that under appropriate conditions, the plasma wakefield maintains very high coherence and can sustain high-gradient acceleration over a macroscopic distance. Invoking gamma ray burst (GRB) as the source, we show that MPWA production of ultra high energy cosmic rays (UHECR) beyond ZeV 10^21 eV is possible.Comment: 4 pages, 4 figure

Learning a Complete Image Indexing Pipeline

To work at scale, a complete image indexing system comprises two components: An inverted file index to restrict the actual search to only a subset that should contain most of the items relevant to the query; An approximate distance computation mechanism to rapidly scan these lists. While supervised deep learning has recently enabled improvements to the latter, the former continues to be based on unsupervised clustering in the literature. In this work, we propose a first system that learns both components within a unifying neural framework of structured binary encoding

A 78-Year-Old Woman with Fecaloid Vaginal Discharge

A 78-year-old woman with a history of colon cancer with metastasis to the liver was presented to our emergency department because of bilateral groin pain and difficulty in walking, which had gradually increased during the previous 5 days. The pain was of sudden onset, radiating to the back, without aggravating or relieving factors. It was associated with constipation, dysuria and vaginal discharge. She reported passing fecal matter from the vagina one month ago. On physical examination, she appeared malnourished. Her blood pressure was 98/65 mmHg, with a 108 beats/min heart rate and 28 breaths/min respiratory rate. She was afebrile. Physical examinations were unremarkable, except for pale conjunctiva, abdominal distention, and diffuse tenderness especially over the umbilicus with guarding tenderness. Bowel sounds were decreased. Pelvic examination showed a yellowish odorous vaginal discharge from the external orifice of uterus. A complete blood cell count showed the following: leukocyte count, 34,200/mm3; segmented neutrophils, 87.5%; hemoglobin level of 7.4 mg/dl; hematocrit, 18.8%; and platelet, 180000/uL. Other laboratory studies included: glucose, 86 mg/dL; serum urea nitrogen, 28 mg/dL; serum creatinine, 0.87 mg/dL; sodium, 142 mEq/L; potassium, 4.8 mEq/L; albumin, 2.5g/dL; a carbohydrate antigen 19-9 level of 3,244 U/ml, and a carcinoembryonic antigen (CEA) level of 64.6 ng/ml. Coronal and axial cuts of patient’s abdominopelvic computed Tomography (CT) are shown in figures 1 and 2

Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways

Histone deacetylase (HDAC) inhibitors are a new class of chemotherapeutic agents. Our laboratory has recently reported that phenylhexyl isothiocyanate (PHI), a synthetic isothiocyanate, is an inhibitor of HDAC. In this study we examined whether PHI is a hypomethylating agent and its effects on myeloma cells. RPMI8226, a myeloma cell line, was treated with PHI. PHI inhibited the proliferation of the myeloma cells and induced apoptosis in a concentration as low as 0.5 μM. Cell proliferation was reduced to 50% of control with PHI concentration of 0.5 μM. Cell cycle analysis revealed that PHI caused G1-phase arrest of RPMI8226 cells. PHI induced p16 hypomethylation in a concentration- dependent manner. PHI was further shown to induce histone H3 hyperacetylation in a concentration-dependent manner. It was also demonstrated that PHI inhibited IL-6 receptor expression and VEGF production in the RPMI8226 cells, and reactivated p21 expression. It was found that PHI induced apoptosis through disruption of mitochondrial membrane potential. For the first time we show that PHI can induce both p16 hypomethylation and histone H3 hyperacetylation. We conclude that PHI has dual epigenetic effects on p16 hypomethylation and histone hyperacetylation in myeloma cells and targets several critical processes of myeloma proliferation

Bioinformatics Workflow for Clinical Whole Genome Sequencing at Partners HealthCare Personalized Medicine

Effective implementation of precision medicine will be enhanced by a thorough understanding of each patient’s genetic composition to better treat his or her presenting symptoms or mitigate the onset of disease. This ideally includes the sequence information of a complete genome for each individual. At Partners HealthCare Personalized Medicine, we have developed a clinical process for whole genome sequencing (WGS) with application in both healthy individuals and those with disease. In this manuscript, we will describe our bioinformatics strategy to efficiently process and deliver genomic data to geneticists for clinical interpretation. We describe the handling of data from FASTQ to the final variant list for clinical review for the final report. We will also discuss our methodology for validating this workflow and the cost implications of running WGS