Lipoproteins in the DCCT/EDIC cohort:associations with diabetic nephropathy

Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients.

Identification of putative markers of triclabendazole resistance by a genome-wide analysis of genetically recombinant Fasciola hepatica

Despite years of investigation into triclabendazole (TCBZ) resistance in Fasciola hepatica, the genetic mechanisms responsible remain unknown. Extensive analysis of multiple triclabendazole-susceptible and -resistant isolates using a combination of experimental in vivo and in vitro approaches has been carried out, yet few, if any, genes have been demonstrated experimentally to be associated with resistance phenotypes in the field. In this review we summarize the current understanding of TCBZ resistance from the approaches employed to date. We report the current genomic and genetic resources for F. hepatica that are available to facilitate novel functional genomics and genetic experiments for this parasite in the future. Finally, we describe our own non-biased approach to mapping the major genetic loci involved in conferring TCBZ resistance in F. hepatica.

PESSTO monitoring of SN 2012hn: further heterogeneity among faint Type I supernovae

We present optical and infrared monitoring data of SN 2012hn collectedby the Public European Southern Observatory Spectroscopic Survey forTransient Objects. We show that SN 2012hn has a faint peak magnitude(MR ˜ -15.65) and shows no hydrogen and no clearevidence for helium in its spectral evolution. Instead, we detectprominent Ca II lines at all epochs, which relates this transient topreviously described `Ca-rich' or `gap' transients. However, thephotospheric spectra (from -3 to +32 d with respect to peak) of SN2012hn show a series of absorption lines which are unique and a redcontinuum that is likely intrinsic rather than due to extinction. Linesof Ti II and Cr II are visible. This may be a temperature effect, whichcould also explain the red photospheric colour. A nebular spectrum at+150 d shows prominent Ca II, O I, C I and possibly Mg I lines whichappear similar in strength to those displayed by core-collapsesupernovae (SNe). To add to the puzzle, SN 2012hn is located at aprojected distance of 6 kpc from an E/S0 host and is not close to anyobvious star-forming region. Overall SN 2012hn resembles a group offaint H-poor SNe that have been discovered recently and for which aconvincing and consistent physical explanation is still missing. Theyall appear to explode preferentially in remote locations offset from amassive host galaxy with deep limits on any dwarf host galaxies,favouring old progenitor systems. SN 2012hn adds heterogeneity to thissample of objects. We discuss potential explosion channels includingHe-shell detonations and double detonations of white dwarfs as well aspeculiar core-collapse SNe.

Intersectin is a negative regulator of dynamin recruitment to the synaptic endocytic zone in the central synapse

Intersectin is a multidomain dynamin-binding protein implicated in numerous functions in the nervous system, including synapse formation and endocytosis. Here, we demonstrate that during neurotransmitter release in the central synapse, intersectin, like its binding partner dynamin, is redistributed from the synaptic vesicle pool to the periactive zone. Acute perturbation of the intersectin-dynamin interaction by microinjection of either intersectin antibodies or Src homology 3 (SH3) domains inhibited endocytosis at the fission step. Although the morphological effects induced by the different reagents were similar, antibody injections resulted in a dramatic increase in dynamin immunoreactivity around coated pits and at constricted necks, whereas synapses microinjected with the GST (glutathione S-transferase)-SH3C domain displayed reduced amounts of dynamin in the neck region. Our data suggest that intersectin controls the amount of dynamin released from the synaptic vesicle cluster to the periactive zone and that it may regulate fission of clathrin-coated intermediates.