Cardiomyocyte growth and sarcomerogenesis at the intercalated disc

Cardiomyocytes grow during heart maturation or disease-related cardiac remodeling. We present evidence that the intercalated disc (ID) is integral to both longitudinal and lateral growth: increases in width are accommodated by lateral extension of the plicate tread regions and increases in length by sarcomere insertion within the ID. At the margin between myofibril and the folded membrane of the ID lies a transitional junction through which the thin filaments from the last sarcomere run to the ID membrane and it has been suggested that this junction acts as a proto Z-disc for sarcomere addition. In support of this hypothesis, we have investigated the ultrastructure of the ID in mouse hearts from control and dilated cardiomyopathy (DCM) models, the MLP-null and a cardiac-specific β-catenin mutant, cΔex3, as well as in human left ventricle from normal and DCM samples. We find that the ID amplitude can vary tenfold from 0.2 μm up to a maximum of ~2 μm allowing gradual expansion during heart growth. At the greatest amplitude, equivalent to a sarcomere length, A-bands and thick filaments are found within the ID membrane loops together with a Z-disc, which develops at the transitional junction position. Here, also, the tops of the membrane folds, which are rich in αII spectrin, become enlarged and associated with junctional sarcoplasmic reticulum. Systematically larger ID amplitudes are found in DCM samples. Other morphological differences between mouse DCM and normal hearts suggest that sarcomere inclusion is compromised in the diseased hearts.     

Broad neutralization coverage of HIV by multiple highly potent antibodies

Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.     

拉兹蝎属——中国新纪录属及1新种记述(蝎目:钳蝎科)

描述了采自中国新疆喀什地区钳蝎科1中国新纪录属(拉兹蝎属Razianus Farzanpay,1987)及1新种(新疆拉兹蝎,新种Razianus xinjianganus sp. nov.).新种的模式标本保存于河北大学博物馆.     

Small mammals within riparian habitats of a regulated and unregulated arid land river

In northwestern Colorado, flow regulation on the Green River has created a transitional plant community that features encroachment by upland vegetation into cottonwood ( Populus fremontii )-dominated, riparian forest on topographically high floodplain sites and reduced cottonwood regeneration on low floodplain sites. To assess how these changes might have affected small mammal distributions, in 1994 and 1995 we live-trapped during periods surrounding spring flooding at 3 sites: above and below the confluence of the regulated Green River and at the ecologically similar, but unregulated, Yampa River (reference site). More species were captured at the most regulated site along the Green River above its confluence with the Yampa River. Within sites, more species were captured in riparian habitats than adjacent upland habitats. Despite river regulation-induced habitat changes, we did not detect changes in species distributions within low and high floodplain habitat for Peromyscus maniculatus or Microtus montanus , but changes may have occurred for Dipodomys ordii . The total effect of regulation-induced habitat change on small mammal populations may not be fully revealed until current, mature cottonwood forests disappear and associated woody debris decomposes.     

Naturalization of plains cottonwood ( Populus deltoides subsp. monilifera ) along river drainages west of the Rocky Mountains

Historic botanical surveys documented that the natural distribution of the plains cottonwood ( Populus deltoides subsp. monilifera ) was limited to semiarid drainages east of the Rocky Mountains. Recently, a number of isolated populations of plains cottonwood have been found along the Kootenai, lower Snake, and Columbia Rivers and their tributaries. We used isozyme analysis to assess the genetic structure of these Pacific Northwest (PNW) populations in relation to native cottonwood populations east of the Rocky Mountains. These genetic data along with field surveys (dbh, age estimates) and cadastral field survey notes (mid-1800s) were used to understand the origin of these disjunct populations (i.e., relictual natives versus naturalized introductions). Genetic analyses revealed high levels of genetic diversity within and among PNW populations as well as hybridization with black cottonwood ( P. trichocarpa ). The observed range of genetic variation for PNW populations was similar to that of native cottonwood populations. Collectively, these data confirm that these scattered populations are plains cottonwood ( Populus deltoides subsp. monilifera ). Age estimates of the largest individuals found within study populations ranged from 27 to 51 years. Cadastral field surveys also noted the absence of woody vegetation along the lower Snake and Columbia Rivers. Considered together, the data suggest that these populations are of recent origin. The high levels of observed genetic variation are consistent with the reproductive biology of Populus spp. (i.e., obligate outcrossing and widespread dispersal of pollen and seed by wind and water) and a recurrent introduction of plains cottonwood throughout the study area.     

Natural history of the fireflies of the Serra dos Órgãos mountain range (Brazil: Rio de Janeiro) – one of the ‘hottest’ firefly spots on Earth,with a key to genera (Coleoptera: Lampyridae)

ABSTRACT

Fireflies (Coleoptera: Lampyridae) are charismatic insects that have been fruitful model systems in biotechnology. However, lack of information about firefly taxonomy and ecology renders species identification a hard task, especially in the Neotropical region, where fireflies are most diverse. A major gap in the literature on Neotropical fireflies is the lack of knowledge on species’ ecological niches and habitats, which are fundamental aspects for understanding their biology. Here, we provide an annotated checklist of the firefly fauna of the Serra dos Órgãos mountain range (Rio de Janeiro State, Southeastern Brazil), with information on the natural history of each species. We assembled data in three ways: monthly sampling with Malaise traps and active search along an elevational transect from 130 to 2,170 m, over 2 years (2014–2016), extensive field observations, and extracted from historical species records for the Serra dos Órgãos from museum specimens in key collections in Brazil and Europe. We provide a taxonomic key to the genera recorded in the region, and a differential diagnosis for each species, highlighting key references for each taxon. We report 58 species representing 21 genera, making the Serra dos Órgãos one of the richest firefly hotspots on Earth. Most species are restricted to one or two habitat types and/or just one of the regional seasons (warm or cool), and many were only collected either by malaise traps or active search, underlining the importance of sampling different habitat types and seasons, and using different sampling methods when surveying fireflies. Out of the 51 species observed in the field, 49 were active either during the day or the night, although two species – Photuris elliptica and Pyrogaster nigrolineatus – were active in both periods, which is rare in fireflies.     

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.