Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice

The cytokine transforming growth factor-beta (TGF-beta) is an important negative regulator of adaptive immunity. TGF-beta is secreted by cells as an inactive precursor that must be activated to exert biological effects, but the mechanisms that regulate TGF-beta activation and function in the immune system are poorly understood. Here we show that conditional loss of the TGF-beta-activating integrin alpha(v)beta8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha(v)beta8 on dendritic cells, as mice lacking alpha(v)beta8 principally on dendritic cells develop identical immunological abnormalities as mice lacking alpha(v)beta8 on all leukocytes, whereas mice lacking alpha(v)beta8 on T cells alone are phenotypically normal. We further show that dendritic cells lacking alpha(v)beta8 fail to induce regulatory T cells (T(R) cells) in vitro, an effect that depends on TGF-beta activity. Furthermore, mice lacking alpha(v)beta8 on dendritic cells have reduced proportions of T(R) cells in colonic tissue. These results suggest that alpha(v)beta8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha(v)beta8 on dendritic cells to induce and/or maintain tissue T(R) cells.     

Quantum oscillations and the Fermi surface in an underdoped high-Tc superconductor

Despite twenty years of research, the phase diagram of high-transition-temperature superconductors remains enigmatic. A central issue is the origin of the differences in the physical properties of these copper oxides doped to opposite sides of the superconducting region. In the overdoped regime, the material behaves as a reasonably conventional metal, with a large Fermi surface. The underdoped regime, however, is highly anomalous and appears to have no coherent Fermi surface, but only disconnected 'Fermi arcs'. The fundamental question, then, is whether underdoped copper oxides have a Fermi surface, and if so, whether it is topologically different from that seen in the overdoped regime. Here we report the observation of quantum oscillations in the electrical resistance of the oxygen-ordered copper oxide YBa2Cu3O6.5, establishing the existence of a well-defined Fermi surface in the ground state of underdoped copper oxides, once superconductivity is suppressed by a magnetic field. The low oscillation frequency reveals a Fermi surface made of small pockets, in contrast to the large cylinder characteristic of the overdoped regime. Two possible interpretations are discussed: either a small pocket is part of the band structure specific to YBa2Cu3O6.5 or small pockets arise from a topological change at a critical point in the phase diagram. Our understanding of high-transition-temperature (high-T(c)) superconductors will depend critically on which of these two interpretations proves to be correct.     

B7-H6/NKp30 interaction: a mechanism of alerting NK cells against tumors

Natural killer (NK) cells are lymphocytes of the innate immune system that sense target cells through a panel of activating and inhibitory receptors. Together with NKG2D, the natural cytotoxicity receptors (NCRs) are major activating receptors involved in tumor cell detection. Although numerous NKG2D ligands have been identified, characterization of the molecules interacting with the NCRs is still incomplete. The identification of B7-H6 as a counter structure of the NCR NKp30 shed light on the molecular basis of NK cell immunosurveillance. We review here the current knowledge on NKp30 and B7-H6, and we discuss their potential role in anti-tumor immunity.     

Nest-site selection by Sage Thrashers in southeastern Idaho

Nest sites selected by Sage Thrashers ( Oreoscoptes montanus ) in southeastern Idaho were characterized and compared with available habitat. Microhabitats within 5 m of nests had taller and more aggregated shrubs and less bare ground than the study area in general. Big sagebrush ( Artemisia tridentata wyomingensis ) plants used for nesting were taller than average ,available shrubs, had greater foliage density, were more often living, and more frequently had branches and foliage within 30 cm of the ground. Nest placement was specific with respect to relative nest height and distance from the top and perimeter of the support shrub. Sage Thrashers disproportionately used easterly exposures and underused westerly exposures for their nests.     

BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing

Adult bones have a notable regenerative capacity. Over 40 years ago, an intrinsic activity capable of initiating this reparative response was found to reside within bone itself, and the term bone morphogenetic protein (BMP) was coined to describe the molecules responsible for it. A family of BMP proteins was subsequently identified, but no individual BMP has been shown to be the initiator of the endogenous bone repair response. Here we demonstrate that BMP2 is a necessary component of the signaling cascade that governs fracture repair. Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time. In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked. Although other osteogenic stimuli are still present in the limb skeleton of BMP2-deficient mice, they cannot compensate for the absence of BMP2. Collectively, our results identify BMP2 as an endogenous mediator necessary for fracture repair.     

Bibliography and subject index of the prairie skink, Eumeces septentrionalis (Baird) (Sauria: Scincindae)

The prairie skink, Eumeces septentrionalis , is a small, semifossorial lizard inhabiting the tall-grass prairies and savannas of the central lowland province region of North America. This study provides an extensive bibliography and subject index as a tool for current and future workers studying E. septentrionalis and related species.     

Observations on Double-crested Cormorants ( Phalacrocorax auritus ) at sportfishing waters in southwestern Utah

Counts of Double-crested Cormorants ( Phalacrocorax auritus ) were made at 13 reservoirs and lakes in southwestern Utah during 1989-91 to determine current abundance of that species. Food habits of cormorants were studied at three of the reservoirs in 1989. Data were also collected on trout abundance during standardized gill-netting to make comparisons between cormorant numbers and trout abundance. Cormorants were observed at all waters studied except one and were generally most numerous during the spring as they migrated through the area. Estimated cormorant abundance ranged from 0 to 34 bird-days per ha and was highest at the larger, lower-elevation reservoirs. Cormorants were summer residents at several of the larger reservoirs and nested successfully at Piute Reservoir. Trout accounted for 24-81% of the diet of cormorants, with Utah chubs constituting most of the remainder of the diet. Estimates of the annual consumption of fish by cormorants ranged from 0 to 15.8 kg per ha. The index of trout abundance was inversely related to cormorant abundance ( P < .01) at the waters studied. Cormorants apparently have increased in numbers and extended their range in southwestern Utah during the past decade. This change may be the result of factors that have led to similar changes throughout North America as well as some factors unique to Utah. Methods to mitigate the impact of predation by piscivorous birds of sportfisheries are discussed. The Utah Division of Wildlife Resources has initiated a new management plan at Minersville Reservoir that incorporates piscivorous birds into sportfish management at that reservoir.     

Distribution and abundance of native Bonneville cutthroat trout ( Oncorhynchus clarki utah ) in southwestern Utah

The Bonneville cutthroat trout ( Oncorhynchus clarki utah ; BCT) was once abundant throughout the Bonneville Basin. In southwestern Utah, however, only 3 local populations of the subspecies were known to exist in 1977, when conservation efforts to protect and replicate them began. By 1995 remnant populations were known in 6 streams, and replicate populations had been established in an additional 16. Populations of BCT in southwestern Utah streams were survey by electrofishing in 1994 and 1995 to describe the subspecies' status. Estimated densities of age-1 and older BCT ranged from 118 to 546 fish per km. Biomass estimates ranged from 8 to 64 kg per ha. Several age groups of BCT were collected at most locations. Six populations were classified as self-sustaining, 9 as expanding through natural recruitment, 6 as new, and 1 as hybridized. Overall status of BCT in southwestern Utah has improved since 1977, but conservation measures must continue to maintain a positive trend.     

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ^?/? mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV.