Synaptotagmins I and IV promote transmitter release independently of Ca(2+) binding in the C(2)A domain

At nerve terminals, a focal and transient increase in intracellular Ca(2+) triggers the fusion of neurotransmitter-filled vesicles with the plasma membrane. The most extensively studied candidate for the Ca(2+)-sensing trigger is synaptotagmin I, whose Ca(2+)-dependent interactions with acidic phospholipids and syntaxin have largely been ascribed to its C(2)A domain, although the C(2)B domain also binds Ca(2+) (refs 7, 8). Genetic tests of synaptotagmin I have been equivocal as to whether it is the Ca(2+)-sensing trigger of fusion. Synaptotagmin IV, a related isoform that does not bind Ca(2+) in the C(2)A domain, might be an inhibitor of release. We mutated an essential aspartate of the Ca(2+)-binding site of the synaptotagmin I C(2)A domain and expressed it in Drosophila lacking synaptotagmin I. Here we show that, despite the disruption of the binding site, the Ca(2+)-dependent properties of transmission were not altered. Similarly, we found that synaptotagmin IV could substitute for synaptotagmin I. We conclude that the C(2)A domain of synaptotagmin is not required for Ca(2+)-dependent synaptic transmission, and that synaptotagmin IV promotes rather than inhibits transmission.     

Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture

Manipulation or non-physiological embryo culture environments can lead to defective fetal programming in livestock. Our demonstration of reduced fetal methylation and expression of ovine IGF2R suggests pre-implantation embryo procedures may be vulnerable to epigenetic alterations in imprinted genes. This highlights the potential benefits of epigenetic diagnostic screening in developing embryo procedures.     

Human Genome and Diseases:¶The molecular pathogenesis of the Marfan syndrome

The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue with highly variable clinical manifestations including aortic dilatation and dissection, ectopia lentis, and a range of skeletal anomalies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS and other related disorders of connective tissue collectively termed type-1 fibrillinopathies. Fibrillin-1 is a main component of the 10- to 12-nm extracellular microfibrils that are important for elastogenesis, elasticity, and homeostasis of elastic fibers. Mutations in fibrillin-1 are hypothesized to exert their effects by dominant negative mechanisms, but recent work has also emphasized the potential role of proteases and disturbances in tissue homeostasis in the pathogenesis of the MFS. This article provides an overview of the clinical aspects of the MFS and current thinking on the pathogenesis of this disorder.     

Survey indicators for pygmy rabbits: temporal trends of burrow systems and pellets

Obtaining estimates of absolute abundance for rare or cryptic species can be challenging. In these cases,methods using indirect indicators such as sign might offer useful indices of population size. Pygmy rabbits ( Brachylagus idahoensis ) are small, burrowing lagomorphs for which methods for population assessment and monitoring are needed. Current tools for estimating relative abundance rely on detecting and assessing fecal pellets and burrow systems. We evaluated temporal changes in each of these indicators to gauge their potential usefulness as indicators of relative and absolute abundance of pygmy rabbits. Pellet persistence was strongly influenced by environmental exposure, and based on our data, we estimated that maximum persistence of fecal pellets would be 24–34 months. Pellet appearance (color) was affected by both time and exposure. Burrow systems were remarkably resilient over the course of the study. Probability of burrow systems transitioning between activity classes (active, recent, and old) did not vary detectably by study site, season, or year. We suggest that 2 protocols currently used for classification of pygmy rabbit burrow systems are most useful for different applications. Further work is needed, however, to link such assessments to quantitative estimates of population size.     

Asian tapeworm ( Bothriocephalus acheilognathi ) in native fishes from the Little Colorado River, Grand Canyon, Arizona

Examination of gastrointestinal tracts of native cyprinids from the Little Colorado River (LCR) in Grand Canyon, Arizona, 1990-1994, revealed varying rates of prevalence and infrapopulation levels of Asian tapeworm ( Bothriocephalus acheilognathi ). Mean prevalence was 28% (range 0-78%) in humpback chub ( Gila cypha ) and 8% (range 0-46%) in speckled dace ( Rhinichthys osculus ), with infrapopulations as high as 46 and 28, respectively. We also note Asian tapeworm infection of nonnatives common carp ( Cyprinus carpio ), fathead minnow ( Pimephales promelas ), and plains killifish ( Fundulus zebrinus ) from the LCR. Reported pathogenic and chronic effects of this cestode to its definitive hosts add concern for the status of the Grand Canyon population of the federally endangered humpback chub. The rapidity which Asian tapeworm has spread to different drainages of the Colorado River Basin likely portends an eventual cosmopolitan basin distribution in lower elevations suitable to the parasite's thermophilic life history. Such biotic changes must be considered among the most serious threats to conservation and recovery of native fish populations.     

Kin selection and eusociality

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Hamilton described a selective process in which individuals affect kin (kin selection), developed a novel modelling strategy for it (inclusive fitness), and derived a rule to describe it (Hamilton's rule). Nowak et al. assert that inclusive fitness is not the best modelling strategy, and also that its production has been "meagre". The former may be debated by theoreticians, but the latter is simply incorrect. There is abundant evidence to demonstrate that inclusive fitness, kin selection and Hamilton's rule have been extraordinarily productive for understanding the evolution of sociality.     

Persistence of added retinoids in organ culture media during induction of mucous metaplasia and glandular morphogenesis in hamster cheek pouches

The retinoid concentration (determined colorimetrically) did not change significantly in retinyl acetate-supplemented (6 micrograms/ml) Eagle's Minimal Essential Medium containing 10% fetal calf serum when stored at -20 or 4 degrees C over 7 days. After the medium was incubated at 37 degrees C for 48 h, 37-49% of the retinoid remained, whether or not tissue (neonatal Syrian hamster cheek pouch) was present, and irrespective of explant age. The normal retinoid level in the tissue was approximately 0.25 micrograms per gram. Therefore, neonatal hamster cheek pouches, incubated in medium with the addition of 6 micrograms of retinyl acetate per ml of medium and undergoing mucous metaplasia and some mucous gland morphogenesis, were continually being exposed to retinoid levels which, though gradually decreasing, remained well above their normal physiological level.