Membrane-shed vesicles from the parasite <Emphasis Type="Italic">Trichomonas vaginalis</Emphasis>: characterization and their association with cell interaction

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor–ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions.     

A copy number variation morbidity map of developmental delay

To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ～14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.     

Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1

Although thoracic aortic aneurysms and dissections (TAAD) can be inherited as a single-gene disorder, the genetic predisposition in the majority of affected people is poorly understood. In a multistage genome-wide association study (GWAS), we compared 765 individuals who had sporadic TAAD (STAAD) with 874 controls and identified common SNPs at a 15q21.1 locus that were associated with STAAD, with odds ratios of 1.6-1.8 that achieved genome-wide significance. We followed up 107 SNPs associated with STAAD with P < 1 × 10(-5) in the region, in two separate STAAD cohorts. The associated SNPs fall into a large region of linkage disequilibrium encompassing FBN1, which encodes fibrillin-1. FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD. This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD.     

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.     

Seed bank dynamics and habitat indicators of Arctomecon californica, a rare plant in a fragmented desert environment

Protection of endangered desert plant species is frequently complicated by a lack of information about seeds, the most stress-resistant and populous life stage. We studied the relative locations of seeds and plants of a rare endangered herbaceous perennial, the Las Vegas bearpoppy ( Arctomecon californica ) in seven 1-ha sites randomly located within a 100-ha study area that was slated for development in Las Vegas, Nevada. We also measured the physical and biological attributes of the environment supporting the seeds and plants, including soil hardness, rock cover, cryptogamic crust cover, and associated vegetation. Arctomecon californica seed density was 0.651 seeds &middot; m &ndash;2 , and seeds were found throughout the top 4 cm of soil. Seed viability among sites ranged from 26% to 79%; however, no significant changes between depths were detected. The spatial distribution of the seed bank coincided with the current A. californica adult distribution only in sites with both a high plant density and high numbers of seeds. Arctomecon californica adults occupied open areas within the gypsum environment that supported significantly less vegetative cover than the surrounding area. We observed a positive association between A. californica adults and shadscale ( Atriplex confertifolia ) and a negative association with 7 other plant species among sites. Sites with an indurated abiotic crust hosted higher numbers of A. californica adults than sites with softer soils. However, rock cover, cryptogamic crust cover, and soil hardness were poor explanatory factors for characterizing A. californica presence. We suggest that land managers should incorporate seed bank census into monitoring programs due to the extreme year-to-year fluctuations in A. californica plant population densities. A menudo la protecci&oacute;n de especies de plantas des&eacute;rticas en peligro de extinci&oacute;n se ve complicada por la falta de informaci&oacute;n sobre las semillas, la etapa de vida m&aacute;s abundante y resistente al estr&eacute;s. Estudiamos la ubicaci&oacute;n relativa de semillas y plantas de &ldquo;Las Vegas bearpoppy&rdquo; ( Arctomecon californica ), una planta perenne en peligro de extinci&oacute;n, en 7 sitios de 1 ha. localizados al azar dentro de un &aacute;rea de estudio de 100 ha que estaba destinada a la urbanizaci&oacute;n en Las Vegas, Nevada (E.U.A.). Tambi&eacute;n medimos los atributos f&iacute;sicos y biol&oacute;gicos del ambiente que sostiene las semillas y plantas, tales como dureza del suelo, rocosidad, cobertura de costra crypt&oacute;gama y vegetaci&oacute;n asociada. La densidad de semillas de A. californica fue 0.651 semillas &middot; m &ndash;2 y se observ&oacute; en los 4 cm superiores del suelo. La viabilidad de las semillas vari&oacute; del 26% al 79% entre los sitios; sin embargo, no detectamos cambios significativos entre profundidades. La distribuci&oacute;n espacial del banco de semillas coincidi&oacute; con la distribuci&oacute;n actual de adultos de A. californica, s&oacute;lo en sitios que tuvieron una alta densidad de plantas y altos n&uacute;meros de semillas. Los adultos de A. californica ocuparon &aacute;reas abiertas dentro del ambiente de yeso que sosten&iacute;a significativamente menos cobertura vegetal que las &aacute;reas circunvecinas. Observamos una asociaci&oacute;n positiva entre los adultos de A. californica y el chamizo ( Atriplex confertifolia ) y una asociaci&oacute;n negativa con siete otras especies de plantas entre sitios. Los sitios con una costra abi&oacute;tica endurecida albergaron m&aacute;s adultos de A. californica que los sitios con suelos m&aacute;s blandos. No obstante, la cubierta rocosa, la costra crypt&oacute;gama y la dureza del suelo fueron inadecuadas como factores para caracterizar la presencia de A. californica. Sugerimos que los manejadores de tierras deben incorporar censos de bancos de semillas en los programas de monitoreo, debido a las fluctuaciones extremas de un a&ntilde;o a otro en la densidad poblacional de A. californica. Normal 0 MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman";}     

Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk

To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights.     

Molecular cloning of cDNA for murine interleukin-3

The cDNA sequence for murine interleukin-3, one of the colony stimulating factors that regulate haematopoiesis, codes for a polypeptide of 166 amino acids including a putative signal peptide. The predicted amino acid sequence indicates that formation of mature interleukin-3 involves proteolytic removal of not only the signal peptide but additional amino-terminal amino acids.