Autism-like behavioral phenotypes in BTBR T+tf/J mice

Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo . The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo , supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms.     

Spatial heterogeneity and plant species richness at different spatial scales under rabbit grazing

Herbivores influence spatial heterogeneity in soil resources and vegetation in ecosystems. Despite increasing recognition that spatial heterogeneity can drive species richness at different spatial scales, few studies have quantified the effect of grazing on spatial heterogeneity and species richness simultaneously. Here we document both these variables in a rabbit-grazed grassland. We measured mean values and spatial patterns of grazing intensity, rabbit droppings, plant height, plant biomass, soil water content, ammonia and nitrate in sites grazed by rabbits and in matched, ungrazed exclosures in a grassland in southern England. Plant species richness was recorded at spatial scales ranging between 0.0001 and 150 m(2). Grazing reduced plant height and plant biomass but increased levels of ammonia and nitrate in the soil. Spatial statistics revealed that rabbit-grazed sites consisted of a mixture of heavily grazed patches with low vegetation and nutrient-rich soils (lawns) surrounded by patches of high vegetation with nutrient-poor soils (tussocks). The mean patch size (range) in the grazed controls was 2.1 +/- 0.3 m for vegetation height, 3.8 +/- 1.8 m for soil water content and 2.8 +/- 0.9 m for ammonia. This is in line with the patch sizes of grazing (2.4 +/- 0.5 m) and dropping deposition (3.7 +/- 0.6 m) by rabbits. In contrast, patchiness in the ungrazed exclosures had a larger patch size and was not present for all variables. Rabbit grazing increased plant species richness at all spatial scales. Species richness was negatively correlated with plant height, but positively correlated to the coefficient of variation of plant height at all plot sizes. Species richness in large plots (<25 m(2)) was also correlated to patch size. This study indicates that the abundance of strong competitors and the nutrient availability in the soil, as well as the heterogeneity and spatial pattern of these factors may influence species richness, but the importance of these factors can differ across spatial scales.     

The effects of herbivory and competition on the invasive alien plant Senecio inaequidens (Asteraceae)

Abstract. Senecio inaequidens DC. (Asteraceae) is an invasive alien plant introduced to Europe from South Africa in around 1896. It contains pyrrolizidine alkaloids that are toxic to livestock and humans. S. inaequidens would therefore be an economic and ecological problem if it became established and abundant in natural or farmed grassland ecosystems. We conducted field experiments using a split‐plot design to determine the effects of rabbit grazing, interspecific plant competition, mollusc and insect herbivory on growth, survival and reproduction of S. inaequidens. Plants were grown from seeds of three different ecotypes under standardized greenhouse conditions and transplanted into field plots. Rabbits (Oryctolagus cuniculus L.) were excluded from experimental plots using rabbit fences. Competition was manipulated by either creating subplots with bare ground or leaving the vegetation cover intact. Data were recorded between June and August 2002. Ecotypes differed significantly in morphological parameters, and in their responses to invertebrate herbivory. Interspecific plant competition and rabbit grazing significantly reduced growth and reproduction of S. inaequidens. Regrowth shoots of S. inaequidens produced after rabbit grazing were not subsequently eaten by rabbits. Unpalatability of regrowth shoots may be attributable to changes in pyrrolizidine alkaloid composition with plant age. Mollusc herbivory significantly reduced the number of capitulae produced. We found adults of Longitarsus jacobaeae Waterhouse (Coleoptera: Chrysomelidae), a specialist herbivore of European Senecio jacobaea L. (Asteraceae), feeding on 79% of S. inaequidens plants. 320 larvae of Tyria jacobaeae L. (Lepidoptera: Arctiidae) did not feed on S. inaequidens under free‐choice field conditions. We conclude that S. inaequidens is able to survive and reproduce in disturbed grassland ecosystems. L. jacobaeae might be a suitable agent for biological control of S. inaequidens in European introduced populations in the future.     

Splinting or surgery for carpal tunnel syndrome? Design of a randomized controlled trial [ISRCTN18853827]

Background  

Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome.     

Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures

Gangliosides are a family of glycosphingolipids that contain sialic acid. Although they are abundant on neuronal cell membranes, their precise functions and importance in the central nervous system (CNS) remain largely undefined. We have disrupted the gene encoding GD3 synthase (GD3S), a sialyltransferase expressed in the CNS that is responsible for the synthesis of b-series gangliosides. GD3S-/- mice, even with an absence of b-series gangliosides, appear to undergo normal development and have a normal life span. To further restrict the expression of gangliosides, the GD3S mutant mice were crossbred with mice carrying a disrupted GalNAcT gene encoding beta1,4-N-acetylgalactosaminyltransferase. These double mutant mice expressed GM3 as their major ganglioside. In contrast to the single mutant mice, the double mutants displayed a sudden death phenotype and were extremely susceptible to induction of lethal seizures by sound stimulus. These results demonstrate unequivocally that gangliosides play an essential role in the proper functioning of the CNS.     

The genus Pyrus L. (Rosaceae) in south-west Europe and North Afkica

A multivariate morphometric study of the genus Pyrus in south-west Europe and North Africa shows that five species may be recognized in the area: P. bourgaeana Decne., P. communis L., P. cordata Dew., P. spinosa Forssk, and P. nivalis Jacq. Some valuable characters for identification of these species are proposed. In particular the width of fruit peduncle, petal size, leaf width and petiole length served to discriminate the taxa. Several names such as P. gharbiona Trab., P. cossonii Rehder (|M= P. longipes Balansa ex Coss. & Durieu) and P. boisseriana Buhse, are regarded as synonyms of P. cordata , while P. marnormis Trab. of P. bourgaeana. Consequently a check-list and a key to these species are provided.     

Structural and conformational modifications of α-MSH/ACTH4–10 provide melanotropin analogues with highly potent behavioral activities

Previous studies have identified the (4–10) heptapeptide sequence as the central core of α-MSH/ACTH peptides required for mediation of important biological activities. In the present study, the structure-activity relationships of Nle⁴-substituted and -bridged cyclic α-MSH analogues, which were previously shown to exhibit a wide range of melanotropic potencies from weak agonism to super potency, were examined for grooming behavioral activity in the rat following intracerebroventricular injections. The results showed that stepwise C-terminal elongation of the linear Nle⁴-substituted Ac-α-MSH_4–10-NH₂ increased grooming potencies of the peptides in a manner similar to their actions on melanocytes. The most interesting finding was the observation that cyclization of the inactive linear “central (4–10) core” of α-MSH (Ac-α-MSH_4–10) to form Ac-[ ]-α-MSH_4–10-NH₂ resulted in a super potent agonist in the grooming assay. However, while cyclization of the (4–10) heptapeptide produced potent agonists on grooming behavior, the structure-activity relationships were different than the frog skin bioassay. These findings support the hypothesis that appropriate structural and confirmational modifications of α-MSH-related peptides can produce profound effects on the bioactivities of the peptides, and suggest that different structural-conformational requirements exist for α-MSH interactions with its various receptors.     

Management of the medial canthal tendon in nasoethmoid orbital fractures: the importance of the central fragment in classification and treatment

The medial canthal tendon and the fragment of bone on which it inserts ("central" fragment) are the critical factors in the diagnosis and treatment of nasoethmoid orbital fractures. The status of the tendon, the tendon-bearing bone segment, and the fracture pattern define a clinically useful classification system. Three patterns of fracture are appreciated: type I--single-segment central fragment; type II--comminuted central fragment with fractures remaining external to the medial canthal tendon insertion; and type III--comminuted central fragment with fractures extending into bone bearing the canthal insertion. Injuries are further classified as unilateral and bilateral and by their extension into other anatomic areas. The fracture pattern determines exposure and fixation. Inferior approaches alone are advised for unilateral single-segment injuries that are nondisplaced superiorly. Superior and inferior approaches are required for displaced unilateral single-segment injuries, for bilateral single-segment injuries, and for all comminuted fractures. Complete interfragment wiring of all segments is stabilized by junctional rigid fixation. All comminuted fractures require transnasal wiring of the bones of the medial orbital rim (medial canthal tendon-bearing or "central" bone fragment). If the fracture does not extend through the canthal insertion, the canthus should not be detached to accomplish the reduction.     

Cultured endothelial cells produce heparinlike inhibitor of smooth muscle cell growth

Using cultured cells from bovine and rat aortas, we have examined the possibility that endothelial cells might regulate the growth of vascular smooth muscle cells. Conditioned medium from confluent bovine aortic endothelial cells inhibited the proliferation of growth-arrested smooth muscle cells. Conditioned medium from exponential endothelial cells, and from exponential or confluent smooth muscle cells and fibroblasts, did not inhibit smooth muscle cell growth. Conditioned medium from confluent endothelial cells did not inhibit the growth of endothelial cells or fibroblasts. In addition to the apparent specificity of both the producer and target cell, the inhibitory activity was heat stable and not affected by proteases. It was sensitive flavobacterium heparinase but not to hyaluronidase or chondroitin sulfate ABC lyase. It thus appears to be a heparinlike substance. Two other lines of evidence support this conclusion. First, a crude isolate of glycosaminoglycans (TCA-soluble, ethanol-precipitable material) from endothelial cell-conditioned medium reconstituted in 20 percent serum inhibited smooth muscle cell growth; glycosaminoglycans isolated from unconditioned medium (i.e., 0.4 percent serum) had no effect on smooth muscle cell growth. No inhibition was seen if the glycosaminoglycan preparation was treated with heparinase. Second, exogenous heparin, heparin sulfate, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate ABC, and hyaluronic acid were added to 20 percent serum and tested for their ability to inhibit smooth muscle cell growth. Heparin inhibited growth at concentrations as low as 10 ng/ml. Other glycosaminoglycans had no effect at doses up to 10 μg/ml. Anticoagulant and non- anticoagulant heparin were equally effective at inhibiting smooth muscle cell growth, as they were in vivo following endothelial injury (Clowes and Karnovsk. Nature (Lond.). 265:625-626, 1977; Guyton et al. Circ. Res. 46:625-634, 1980), and in vitro following exposure of smooth muscle cells to platelet extract (Hoover et al. Circ. Res. 47:578-583, 1980). We suggest that vascular endothelial cells may secrete a heparinlike substance in vivo which may regulate the growth of underlying smooth muscle cells.