Synopsis of ‘onychocellid’ cheilostome bryozoan genera

Genera assigned to the cheilostome bryozoan family Onychocellidae are revised based on the skeletal morphology of the type species and, when possible, the type material of these species. All genera are illustrated using scanning electron micrographs, some for the first time. Onychocellidae, which ranges from the Cenomanian stage of the Cretaceous to the Recent, has been a particularly troublesome family because of poorly defined generic concepts correlating at least in part with a paucity of morphological characters. Thirty-five genera are described in this review. Of these, two are recognised as subjective synonyms of other onychocellid genera (Rhebasia and Semieschara), one cannot be sufficiently characterised from the type material (Collura), and two are new: Aechmellina gen. nov. (type species Aechmella falcifera) and Kamilocella gen. nov. (type species Eschara latilabris). A neotype is chosen for Rhagasostoma hexagonum, the type species of Rhagasostoma. A key is provided to assist in the identification of onychocellid genera. Phylogenetic relationships between genera remain obscure and are unlikely to be fully resolved based on skeletal morphology alone. The family as an entity is loosely circumscribed and almost certainly paraphyletic, containing stem genera of other anascan familes such as Lunulitidae, Coscinopleuridae and Aspidostomatidae.

www.zoobank.org/urn:lsid:org:pub:63A31AD2-F049-42CB-A45B-557014DC286E     

The Huntington's disease candidate region exhibits many different haplotypes.

Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180.     

Acquired immunity and epidemiology of Schistosoma haematobium

Human immune responses to schistosome infection have been characterized in detail. But there has been controversy over the relative importance of ecological factors (variation in exposure to infection) and immunological factors (acquired immunity) in determining the relationships between levels of infection and age typically found in areas where infection is endemic. Independent effects of exposure and age on the rates of reinfection with Schistosoma haematobium after chemotherapy have been demonstrated in the Gambia and Zimbabwe. This age effect could be the result of acquired immunity to infection. Indeed, allowing for variation in exposure and age, low rates of reinfection in the Gambia are correlated with high amounts of specific IgE antibodies--human IgE can kill S. mansoni schistosomulae in vitro. Further, animals can acquire immunologically mediated resistance to S. mansoni infection, although nonimmunological factors could also be involved. Acquisition of this immunity seems to be related to the cumulative effects of repeated infection and provides only partial protection. These characteristics are consistent with immuno-epidemiological data for both S. mansoni and S. haematobium infections of humans. We have now analysed age-prevalence data for human infection with S. haematobium, and find patterns of variation that are indeed consistent with the epidemiological effects of acquired immunity predicted by mathematical models.     

Fibronectin peptide DRVPHSRNSIT and fibronectin receptor peptide DLYYLMDL arrest gastrulation ofRana pipiens

Gastrulation is characterized by dramatic cell migration which is thought to require the interaction of cell adhesion molecules with extracellular molecules. We have tested two novel peptides, a fibronectin peptide and a fibronectin receptor peptide, for their effects on gastrulation of the leopard frogRana pipiens. The fibronectin peptide DRVPHSRNSIT corresponds to residues 1373–1383 of the cell-binding domain of fibronectin; the receptor peptide DLYYLMDL corresponds to residues 124–131 of 1 subunit of a variety of integrins including 51. Either of these peptides significantly inhibited gastrulation after being microinjected into mid-blastulae. These results indicate that these sequences may correspond to the ligand/receptor interaction sites of fibronectin and its receptor(s).     

Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3

The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC₃, MC₄, and MC₅ receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r?/? mice. Fenoprofen displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology (allosterism) may lead to potential new therapeutics. In addition, MC₃ PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases.     

South-polar features on Venus similar to those near the north pole

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.     

HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS

A prominent feature of late-onset neurodegenerative diseases is accumulation of misfolded protein in vulnerable neurons. When levels of misfolded protein overwhelm degradative pathways, the result is cellular toxicity and neurodegeneration. Cellular mechanisms for degrading misfolded protein include the ubiquitin-proteasome system (UPS), the main non-lysosomal degradative pathway for ubiquitinated proteins, and autophagy, a lysosome-mediated degradative pathway. The UPS and autophagy have long been viewed as complementary degradation systems with no point of intersection. This view has been challenged by two observations suggesting an apparent interaction: impairment of the UPS induces autophagy in vitro, and conditional knockout of autophagy in the mouse brain leads to neurodegeneration with ubiquitin-positive pathology. It is not known whether autophagy is strictly a parallel degradation system, or whether it is a compensatory degradation system when the UPS is impaired; furthermore, if there is a compensatory interaction between these systems, the molecular link is not known. Here we show that autophagy acts as a compensatory degradation system when the UPS is impaired in Drosophila melanogaster, and that histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase that interacts with polyubiquitinated proteins, is an essential mechanistic link in this compensatory interaction. We found that compensatory autophagy was induced in response to mutations affecting the proteasome and in response to UPS impairment in a fly model of the neurodegenerative disease spinobulbar muscular atrophy. Autophagy compensated for impaired UPS function in an HDAC6-dependent manner. Furthermore, expression of HDAC6 was sufficient to rescue degeneration associated with UPS dysfunction in vivo in an autophagy-dependent manner. This study suggests that impairment of autophagy (for example, associated with ageing or genetic variation) might predispose to neurodegeneration. Morover, these findings suggest that it may be possible to intervene in neurodegeneration by augmenting HDAC6 to enhance autophagy.     

Evolution of cooperation in a finite homogeneous graph

Recent theoretical studies of selection in finite structured populations have worked with one of two measures of selective advantage of an allele: fixation probability and inclusive fitness. Each approach has its own analytical strengths, but given certain assumptions they provide equivalent results. In most instances the structure of the population can be specified by a network of nodes connected by edges (that is, a graph), and much of the work here has focused on a continuous-time model of evolution, first described by ref. 11. Working in this context, we provide an inclusive fitness analysis to derive a surprisingly simple analytical condition for the selective advantage of a cooperative allele in any graph for which the structure satisfies a general symmetry condition ('bi-transitivity'). Our results hold for a broad class of population structures, including most of those analysed previously, as well as some for which a direct calculation of fixation probability has appeared intractable. Notably, under some forms of population regulation, the ability of a cooperative allele to invade is seen to be independent of the nature of population structure (and in particular of how game partnerships are specified) and is identical to that for an unstructured population. For other types of population regulation our results reveal that cooperation can invade if players choose partners along relatively 'high-weight' edges.