Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2)

Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay.     

Rediscovery of the southern California endemic American Keeled Slug Anadenulus cockerelli (Hemphill, 1890) after a 68-year hiatus

ABSTRACT

We report the first records of the southern California endemic American Keeled Slug Anadenulus cockerelli (Hemphill, 1890) in 68 years. Due to the restricted range of this species and lack of recent detection, it has received a NatureServe conservation status of Critically Imperilled or Imperilled. This species has always been difficult to detect, and will likely continue to be. This may be the result of genuine rarity, or may be the result of being cryptic and occurring in a microhabitat only ephemerally accessible to humans. We created a Species Distribution Model for A. cockerelli, which strongly predicts its occurrence where it is known, as well as some locations where it is currently unknown, such as in the northern Peninsular Ranges and in the San Bernardino Mountains in California. Threats to the continued existence of this species in southern California include human encroachment and resulting habitat loss, the climate changing to be hotter and drier, increased fire frequency, oak death due to beetle infestation, and other introduced species. Anadenulus cockerelli should continue to be surveyed and monitored into the future in order to better understand its distribution and level of conservation concern.     

Prairie dog colony attributes and associated vertebrate species

A survey of colony attributes and associated vertebrates on black - tail ( Cynomys ludovicianus ), Gunnison's ( C. gunnisoni ), and white - tail ( C. leucurus ) prairie dogs was made. A belt transect 1.6 km wide and 13,334 km long from Hobbs, New Mexico, to the Utah - Wyoming state line was surveyed. There were 47 colonies located (4760 ha comprising 2.2 percent) in the belt. Intercolony distances varied significantly. Three black - tail towns averaged 33 ha in area (SD = 26, range 10 – 61), II Gunnison's averaged 46 ha (SD = 43, range 16 – 150), and 33 white - tail towns averaged 125 ha (SD = 200, range 0.2 – 958). Badger activity was positively and significantly correlated to colony size and number of burrow openings on Gunnison's and white - tail towns. There were 107 vertebrate species and subspecies (one amphibian, 25 reptiles, 51 birds, 30 mammals) observed on prairie dog colonies. Results of our surveys are compared with prairie dog studies elsewhere. The role of prairie dogs and relationships to some vertebrates species are discussed.     

Memory CD4 T cells emerge from effector T-cell progenitors

A hallmark of adaptive immunity is the generation of memory T cells that confer long-lived, antigen-specific protection against repeat challenges by pathogens. Understanding the mechanisms by which memory T cells arise is important for rational vaccination strategies and improved therapeutic interventions for chronic infections and autoimmune disorders. The large clonal expansion of CD8 T cells in response to some infections has made the development of CD8 T-cell memory more amenable to study, giving rise to a model of memory cell differentiation in which a fraction of fully competent effector T cells transition into long-lived memory T cells. Delineation of CD4 T-cell memory development has proved more difficult as a result of limitations on tracking the smaller populations of CD4 effector T cells generated during a pathogenic challenge, complicating efforts to determine whether CD4 memory T cells are direct descendants of effector T cells or whether they develop by alternative pathways. Here, using two complementary cytokine reporter mouse models to identify interferon (IFN)-gamma-positive effector T cells and track their fate, we show that the lineage relationship between effector and memory CD4 T cells resembles that for CD8 T cells responding to the same pathogen. We find that, in parallel with effector CD8 T cells, IFN-gamma-positive effector CD4 T cells give rise to long-lived memory T cells capable of anamnestic responses to antigenic rechallenge.     

Reciprocal interactions of the intestinal microbiota and immune system

The emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates the mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defence. These same attributes can put the host at risk of immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how the system integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks to treat and prevent disease.     

The principle of rigidification

Communicated by C. Truesdell & H. J. M. Bos     

Transforming growth factor-beta induces development of the T(H)17 lineage

A new lineage of effector CD4+ T cells characterized by production of interleukin (IL)-17, the T-helper-17 (T(H)17) lineage, was recently described based on developmental and functional features distinct from those of classical T(H)1 and T(H)2 lineages. Like T(H)1 and T(H)2, T(H)17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens, such as extracellular bacteria. Aberrant T(H)17 responses have been implicated in a growing list of autoimmune disorders. T(H)17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rbeta1, that pairs with unique, inducible components, IL-23R and IL-12Rbeta2, to confer receptor responsiveness. Here we identify transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to T(H)17 development. TGF-beta acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages.     

Coenzymes Q: Stimulants of the phaǵocytic activity in rats and immune response in mice

Zusammenfassung Mittels der Tusche-Clearance-Methode wird gezeigt, dass Coenzym Q₆ und Q₁₀ die phagozytische Aktivität bei Ratten steigert. Im Vergleich mit Schaferythrozyten wurde bei Mäusen durch Zufuhr von Coenzym Q₁₀ eine Verdoppelung der primären hämolytischen Antikörperbildung festgestellt.

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The authors are deeply indebted to Drs. J. H.Heller, J. H.Green and A. D.Adler for support and helpful discussions in the course of this work. We thank Mrs. G.Katopodis, Mrs. R.Wells, Miss J.Mannion, Mrs. S._Reynolds and Mrs. A._Lee for technical assistance.     

Bonding and reactivity at oxide mineral surfaces from model aqueous complexes

The kinetic stability of oxide surfaces affects a broad range of physical phenomena, including mineral dissolution and sorption reactions, stable-isotope fractionation, and catalyst support degradation. Our knowledge of the rates of these processes derives mostly from the rates of net mass transfer between the bulk solid and fluid phases. But from such data it is difficult to determine rates of elementary steps that are needed to test theoretical models. Here we determine the rates of oxygen exchange between an aqueous fluid and specific sites on the 'Al13' polyoxocation--AlO4Al12(OH)24(H2O)12(7+)--the structure of which closely resembles the surfaces of some Al-(hydr)oxide minerals in soils and catalyst supports. Extrapolation of these data to 298 K (and near pH 5.3) yields half-lives for oxygen on the complex that range from approximately 0.6 milliseconds for bound water to 41 seconds and 13 hours for the two distinct, but structurally similar, bridging hydroxyls. This surprisingly large range of labilities (approximately 10(7)) indicates that reactivity is very sensitive to molecular structure. Moreover, these results indicate that well chosen aqueous complexes provide important information to relate bonding to reactivity at mineral surfaces.     

Genome-wide atlas of gene expression in the adult mouse brain

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.