Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy

Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei.     

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 enteric nervous system in gastrointestinal disease etiology

A highly conserved but convoluted network of neurons and glial cells, the enteric nervous system (ENS), is positioned along the wall of the gut to coordinate digestive processes and gastrointestinal homeostasis. Because ENS components are in charge of the autonomous regulation of gut function, it is inevitable that their dysfunction is central to the pathophysiology and symptom generation of gastrointestinal disease. While for neurodevelopmental disorders such as Hirschsprung, ENS pathogenesis appears to be clear-cut, the role for impaired ENS activity in the etiology of other gastrointestinal disorders is less established and is often deemed secondary to other insults like intestinal inflammation. However, mounting experimental evidence in recent years indicates that gastrointestinal homeostasis hinges on multifaceted connections between the ENS, and other cellular networks such as the intestinal epithelium, the immune system, and the intestinal microbiome. Derangement of these interactions could underlie gastrointestinal disease onset and elicit variable degrees of abnormal gut function, pinpointing, perhaps unexpectedly, the ENS as a diligent participant in idiopathic but also in inflammatory and cancerous diseases of the gut. In this review, we discuss the latest evidence on the role of the ENS in the pathogenesis of enteric neuropathies, disorders of gut–brain interaction, inflammatory bowel diseases, and colorectal cancer.

     

Habitat use of leatherside chub ( Gila copei ) in the presence of predatory brown trout ( Salmo trutta )

The objectives of this study were to (1) examine distribution and habitat use of leatherside chub ( Gila copei ) in a creek with high densities of predatory brown trout ( Salmo trutta ), and (2) compare study results with published accounts of leatherside chub habitat use in streams with few or no brown trout. A 14-km section of Diamond Fork Creek, Utah, was point-shocked to determine macrohabitat (main channel and lateral habitat) and microhabitat (current, depth, substrate, and cover) use of leatherside chug. At the macrohabitat level, leatherside chub were most common in lower reaches of Diamond Fork Creek where the channel was braided and lateral habitats (cutoff pools and backwaters) were abundant. Only a single leatherside chub was found in the main channel of Diamond Fork. Investigations in other systems lacking brown trout indicated that leatherside chub occupy main channel habitats. At the microhabitat level, we found significant positive associations between presence of leatherside chub and both habitat depth and silt. In addition, we found a significant negative association between presence of leatherside chub and number of brown trout. Our results suggest predation by brown trout may limit leatherside chub to lateral habitats that could provide refugia against predation. The introduction of brown trout to systems with little lateral habitat could have serious effects on persistence of resident leatherside chub populations.     

Inflammation and therapeutic vaccination in CNS diseases

The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit.     

Mass march of termites into the deadly trap.

Carnivorous pitcher plants of the genus Nepenthes are not usually very selective about their prey, catching anything that is careless enough to walk on their slippery peristome, but Nepenthes albomarginata is an exception. We show here that this plant uses a fringe of edible white hairs to lure and then trap its prey, which consists exclusively of termites in enormous numbers. This singular feature accounts for the specialization of N. albomarginata for one prey taxon, unique so far among carnivorous plants.