The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Aerobic fitness is a potential crucial factor in protecting paralympic athletes with locomotor impairments from atherosclerotic cardiovascular risk

PurposeTo test the hypothesis that aerobic fitness is inversely related to the risk of atherosclerotic cardiovascular disease (ACVD) in athletes with locomotor impairments deriving from health conditions, such as spinal cord injury (SCI), lower limb amputation, cerebral palsy, poliomyelitis, and other health conditions different from the previous ones.MethodsA total of 68 male athletes who competed in either summer or winter Paralympic games were divided in two health conditions groups (35 with SCI, mean age 37.28.0 years, and 33 with different health conditions, mean age 37.89.9 years) and in four sport type groups (skill, power, intermittent-mixed metabolism-and endurance). They were evaluated through anthropometric and blood pressure measurements, laboratory blood tests, and graded cardiopulmonary maximal arm cranking exercise test, with oxygen uptake peak (VO2peak) measurement. Cardiovascular risk profile was assessed in each athlete.ResultsThe prevalence of ACVD-risk factors in the overall population was 20.6% for hypertension; 47% and 55.9% for high values of total and LDL cholesterol, respectively; 22.1% for reduce glucose tolerance; and 8.8% for obesity. No difference was found between athletes with and without SCI, while the prevalence of obesity was significantly higher in those practicing skill sports (22.7%, p=0.035), which was the sport type group with Paralympic athletes with the lowest VO2peak (22.5 +/- 5.70 ml kg(-1) min(-1)). VO2peak was lower in athletes with SCI than those with different health conditions (28.6 +/- 10.0 vs 33.6 +/- 8.9 ml kg(-1) min(-1)p=0.03), and in those with 3-4 risk factors (19.09 +/- 5.34 ml kg(-1) min(-1)) than those with 2 risk factors (27.1 +/- 5.50 ml kg(-1) min(-1)), 1 risk factor (31.6 +/- 8.55 ml kg(-1) min(-1)), or none (36.4 +/- 8.76 ml kg(-1) min(-1)) (p<0.001).ConclusionsThe present study suggests that having higher VO2peak seems to offer greater protection against ACVD in individuals with a locomotor impairment. Prescribing physical exercise at an intensity similar to that of endurance and intermittent sports should become a fundamental tool to promote health among people with a locomotor impairment.Open access funding provided by Universita degli Studi dell'Aquila within the CRUI-CARE Agreement

Zebrafish as a model for kidney function and disease

Kidney disease is a global problem with around three million people diagnosed in the UK alone and the incidence is rising. Research is critical to develop better treatments. Animal models can help to better understand the pathophysiology behind the various kidney diseases and to screen for therapeutic compounds, but the use especially of mammalian models should be minimised in the interest of animal welfare. Zebrafish are increasingly used, as they are genetically tractable and have a basic renal anatomy comparable to mammalian kidneys with glomerular filtration and tubular filtration processing. Here, we discuss how zebrafish have advanced the study of nephrology and the mechanisms underlying kidney disease

Zebrafish: a vertebrate tool for studying basal body biogenesis, structure, and function.

Understanding the role of basal bodies (BBs) during development and disease has been largely overshadowed by research into the function of the cilium. Although these two organelles are closely associated, they have specific roles to complete for successful cellular development. Appropriate development and function of the BB are fundamental for cilia function. Indeed, there are a growing number of human genetic diseases affecting ciliary development, known collectively as the ciliopathies. Accumulating evidence suggests that BBs establish cell polarity, direct ciliogenesis, and provide docking sites for proteins required within the ciliary axoneme. Major contributions to our knowledge of BB structure and function have been provided by studies in flagellated or ciliated unicellular eukaryotic organisms, specifically Tetrahymena and Chlamydomonas. Reproducing these and other findings in vertebrates has required animal in vivo models. Zebrafish have fast become one of the primary organisms of choice for modeling vertebrate functional genetics. Rapid ex-utero development, proficient egg laying, ease of genetic manipulation, and affordability make zebrafish an attractive vertebrate research tool. Furthermore, zebrafish share over 80 % of disease causing genes with humans. In this article, we discuss the merits of using zebrafish to study BB functional genetics, review current knowledge of zebrafish BB ultrastructure and mechanisms of function, and consider the outlook for future zebrafish-based BB studies

The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity

Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Functional Assessment of Disease-Associated Regulatory Variants <i>In Vivo</i> Using a Versatile Dual Colour Transgenesis Strategy in Zebrafish

Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function

Radar imaging and characterization of the binary near-Earth asteroid (185851) 2000 DP107

The potentially hazardous asteroid (185851) 2000 DP107 was the first binary near-Earth asteroid to be imaged. Radar observations in 2000 provided images at 75m resolution that revealed the shape, orbit, and spin-up formation mechanism of the binary. The asteroid made a more favorable flyby of the Earth in 2008, yielding images at 30m resolution. We used these data to obtain shape models for the two components and to improve the estimates of the mutual orbit, component masses, and spin periods. The primary has a sidereal spin period of 2.7745 ± 0.0007 hr and is roughly spheroidal with an equivalent diameter of 863m ± 5%. It has a mass of 4.656 ± 0.43 × 1011 kg and a density of 1381 ± 244 kgm.3. It exhibits an equatorial ridge similar to the (66391) 1999 KW4 primary; however, the equatorial ridge in this case is not as regular and has a .300 m diameter concavity on one side. The secondary has a sidereal spin period of 1.77 ± 0.02 days commensurate with the orbital period. The secondary is slightly elongated and has overall dimensions of 377 × 314 × 268 m (6% uncertainties). Its mass is 0.178 ± 0.021 × 1011 kg and its density is 1047 ± 230 kgm.3. The mutual orbit has a semimajor axis of 2.659 ± 0.08 km, an eccentricity of 0.019 ± 0.01, and a period of 1.7556 ± 0.0015 days. The normalized total angular momentum of this system exceeds the amount required for the expected spin-up formation mechanism. An increase of angular momentum from nongravitational forces after binary formation is a possible explanation. The two components have similar radar reflectivity, suggesting a similar composition consistent with formation by spin-up. The secondary appears to exhibit a larger circular polarization ratio than the primary, suggesting a rougher surface or subsurface at radar wavelength scales

Radar imaging and characterization of the binary near-Earth asteroid (185851) 2000 DP107

The potentially hazardous asteroid (185851) 2000 DP107 was the first binary near-Earth asteroid to be imaged. Radar observations in 2000 provided images at 75m resolution that revealed the shape, orbit, and spin-up formation mechanism of the binary. The asteroid made a more favorable flyby of the Earth in 2008, yielding images at 30m resolution. We used these data to obtain shape models for the two components and to improve the estimates of the mutual orbit, component masses, and spin periods. The primary has a sidereal spin period of 2.7745 ± 0.0007 hr and is roughly spheroidal with an equivalent diameter of 863m ± 5%. It has a mass of 4.656 ± 0.43 × 1011 kg and a density of 1381 ± 244 kgm.3. It exhibits an equatorial ridge similar to the (66391) 1999 KW4 primary; however, the equatorial ridge in this case is not as regular and has a .300 m diameter concavity on one side. The secondary has a sidereal spin period of 1.77 ± 0.02 days commensurate with the orbital period. The secondary is slightly elongated and has overall dimensions of 377 × 314 × 268 m (6% uncertainties). Its mass is 0.178 ± 0.021 × 1011 kg and its density is 1047 ± 230 kgm.3. The mutual orbit has a semimajor axis of 2.659 ± 0.08 km, an eccentricity of 0.019 ± 0.01, and a period of 1.7556 ± 0.0015 days. The normalized total angular momentum of this system exceeds the amount required for the expected spin-up formation mechanism. An increase of angular momentum from nongravitational forces after binary formation is a possible explanation. The two components have similar radar reflectivity, suggesting a similar composition consistent with formation by spin-up. The secondary appears to exhibit a larger circular polarization ratio than the primary, suggesting a rougher surface or subsurface at radar wavelength scales