Medulloblastoma growth inhibition by hedgehog pathway blockade

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.     

Coherent spin transfer between molecularly bridged quantum dots

Femtosecond time-resolved Faraday rotation spectroscopy reveals the instantaneous transfer of spin coherence through conjugated molecular bridges spanning quantum dots of different size over a broad range of temperature. The room-temperature spin-transfer efficiency is approximately 20%, showing that conjugated molecules can be used not only as interconnections for the hierarchical assembly of functional networks but also as efficient spin channels. The results suggest that this class of structures may be useful as two-spin quantum devices operating at ambient temperatures and may offer promising opportunities for future versatile molecule-based spintronic technologies.     

Ecology of otters in Northern Scotland IV. A model scheme for otter Lutra lutra L. conservation in a freshwater system in aberdeenshire

Habitats for inclusion within otter havens are illustrated from a case-history study on the middle part of the Aberdeenshire River Dee. The environment is divided into breeding and rearing areas and places for non-breeding otters. One good location for a haven incorporating all three habitats includes 12–13 km of river and two nearly lochs. In this area, part of the river bank is inaccessible, and there are secluded islands and deep woods. Havens should include tiny tributaries leading to shelter where otters are likely to have their young. An otter haven in mid-Deeside planned to incorporate all these habitats may be regarded as a model for conservation that could be followed in other similar environments elsewhere.     

Osteomyelitis secondary to trauma involving the proximal end of the radius in horses: five cases (1987-2001)

OBJECTIVE: To determine clinical, radiographic, and scintigraphic abnormalities in and treatment and outcome of horses with trauma-induced osteomyelitis of the proximal aspect of the radius. DESIGN: Retrospective study. ANIMALS: 5 horses. PROCEDURE: Data collected from the medical records included signalment; history; horse use; degree of lameness; radiographic, ultrasonographic, and scintigraphic findings; treatment; and outcome. RESULTS: Duration of lameness prior to referral ranged from 14 to 60 days. Mean severity of lameness was grade 3 of 5, and all horses had a single limb affected. All horses had signs of pain during elbow joint manipulation and digital palpation over the lateral aspect of the proximal end of the radius. Radiographic lesions consisted of periosteal proliferation, osteolysis, and subchondral bone lysis. Scintigraphy in 3 horses revealed intense pharmaceutical uptake diffusely involving the proximal end of the radius. Two horses had sepsis of the elbow joint. All horses were treated with antimicrobials long-term; 1 horse was also treated by local perfusion of the radial medullary cavity through an indwelling cannulated screw. At follow-up, all horses had returned to their previous function. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that osteomyelitis of the proximal end of the radius can result from a traumatic injury to the antebrachium. Because lesions may be an extension of septic arthritis, a thorough examination of the wound area and elbow joint is recommended. Prolonged systemic antimicrobial treatment can result in a successful outcome.     

A climatic risk analysis of the threat posed by the South American leaf blight (SALB) pathogen <Emphasis Type="Italic">Microcyclus ulei</Emphasis> to major rubber producing countries

In 2010, symptoms of cobweb disease were observed on cultivated Pleurotus eryngii crops in Spain. Based on morphological and genetic analyses, the causal agent of cobweb was identified as Cladobotryum mycophilum. Pathogenicity tests on fruit bodies were performed using conidial suspensions of three C. mycophilum isolates. The causal agent was re-isolated in 80–85 % of the fruit bodies inoculated internally and 15–40 % of those fruit bodies inoculated on the cap surface. The results pointed to a certain resistance of the P. eryngii cap surface to the mycelium of C. mycophilum. Two cropping trials inoculated with C. mycophilum were set up to evaluate the pathogenicity of the causal agent of cobweb in two casings. At the end of the growth cycle, 50–60 % of the inoculated blocks cased with mineral soil, and 20–33 % of the inoculated blocks cased with black peat showed cobweb symptoms. This difference in the appearance of the disease and its aggressiveness may be partly explained by different electrical conductivity values of the casing materials used. In vitro sensitivity of the C. mycophilum isolates and P. eryngii strains against four fungicides (chlorothalonil, prochloraz-Mn, thiabendazole and thiophanate-methyl) was assessed in radial growth experiments on fungicide-amended media. The most effective fungicides for inhibiting the in vitro growth of C. mycophilum were prochloraz-Mn and chlorothalonil, while prochloraz-Mn was also the most selective fungicide between P. eryngii and C. mycophilum, and chlorothalonil was the most toxic fungicide against the P. eryngii mycelium.     

Comparison of biopsy samples obtained using standard endoscopic instruments and the harmonic scalpel during laparoscopic and laparoscopic-assisted surgery in normal dogs

Objectives— To compare tissue specimens of canine abdominal organs collected by standard techniques (ST) and harmonic scalpel (HS) and to determine the effect of each technique on wound healing.
Study Design— Experimental.
Animals— Twelve dogs.
Methods— Paired biopsy samples (ST, HS) were collected from liver, spleen, adrenal gland, pancreas, stomach, jejunum, and bladder using laparoscopic or laparoscopic-assisted methods. Hemorrhage at biopsy sites was assessed (present or absent). Specimens were evaluated for diagnostic quality and histologic changes. Dogs were necropsied at 4 or 14 days postoperatively.
Results— HS incision caused less frequent hemorrhage of all organs except spleen. HS specimens had more coagulation necrosis than ST specimens, but both techniques yielded specimens that were sized similarly and were of diagnostic quality. At necropsy, HS biopsy sites of the stomach, jejunum, bladder, adrenal gland, and pancreas were more hyperemic than ST sites. There were more adhesions at jejunal and pancreatic ST biopsy sites. HS biopsy sites had more coagulation necrosis at days 4 and 14 postoperatively. Differences in fibrin deposition, inflammation, and fibrosis were present at biopsy sites of some organs at days 4 or 14 and in comparisons between days 4 and 14.
Conclusions— Diagnostic quality biopsy specimens were obtained with HS and ST. Although HS-induced gross and histologic changes during the first 2 postoperative weeks, no clinical complications were observed.
Clinical Relevance— Both HS and ST can yield specimens with minimal hemorrhage and HS resulted in no apparent postoperative problems in normal dogs. Although HS caused more inflammation and adhesions at biopsy sites of the pancreas, adrenal gland, and jejunum, no clinical complications occurred.     

Plasma concentrations of natriuretic peptides in normal cats and normotensive and hypertensive cats with chronic kidney disease

ObjectivesTo determine if natriuretic peptide concentrations are increased in cats with systemic hypertension and/or chronic kidney disease (CKD).Animals22 normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15 hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with severe CKD (NT-CKD-severe).MethodsN-terminal pro-B-type (NT-proBNP) and pro-A-type (NT-proANP) natriuretic peptides were measured in plasma samples from all cats using commercially available assays and concentrations in the normal and diseased groups compared using non-parametric statistical tests. Spearman's rank correlation was used to test for an association between natriuretic peptide and creatinine concentrations.ResultsNT-proANP was significantly higher in the NT-CKD-severe than the normal group of cats (P = 0.006) but there were no other differences between groups. NT-proBNP concentrations were significantly higher in the HT-CKD group than both the normal (P < 0.001) and the NT-CKD (P < 0.001) groups. NT-proBNP concentrations were also higher in the NT-CKD-severe (P < 0.001) and the NT-CKD (P = 0.005) groups than the normal group. NT-proANP but not NT-proBNP was significantly and positively associated with plasma creatinine concentration.ConclusionsMeasurement of NT-proBNP shows promise as a diagnostic marker for systemic hypertension in the cat. Its concentration is not significantly increased in cats with mild-moderate normotensive CKD.     

A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1.