Targeting tyrosine kinases in cancer: the second wave

One of the most exciting developments in cancer research in recent years has been the clinical validation of molecularly targeted drugs that inhibit the action of pathogenic tyrosine kinases. Treatment of appropriately selected patients with these drugs can alter the natural history of their disease and improve survival. The clinical validation of these "first-generation" tyrosine kinase inhibitors has been the prelude to a second wave of advances in molecular targeting that is expected to further change the way we classify and treat cancer. Efforts are now being directed at identifying the tumor subtypes and patients who will benefit the most from these drugs. In addition, new compounds that circumvent acquired resistance to the first-generation tyrosine kinase inhibitors are being tested in patients with refractory disease. Agents directed against new molecular targets are also being explored.     

Mycoplasma mycoides subsp. capri associated with goat respiratory disease and high flock mortality

A high mortality outbreak of respiratory mycoplasmosis occurred in goats in Mexico. The clinicopathologic presentation resembled contagious caprine pleuropneumonia caused by Mycoplasma capricolum subspecies capripneumoniae. By using a battery of polymerase chain reaction assays, the mycoplasma associated with this outbreak was identified as Mycoplasma mycoides subsp. capri.     

Immune responses to a Staphylococcus aureus GapC/B chimera and its potential use as a component of a vaccine for S. aureus mastitis

Bovine mastitis caused by strains of S. aureus is the most economically important disease affecting the dairy industry worldwide. Commercially available vaccines show various degrees of success and work in research laboratories with experimental vaccines suggests that in part, the failure of these vaccines lies in the limited antigenic repertoire contained in the vaccine formulations. Since it seems impractical to produce a vaccine containing antigens from all major S. aureus mastitis isolates, we took the approach of using two surface antigens GapB and GapC that appear to be conserved and constructed a GapC/B chimera as the basis for a vaccine. The humoral and cellular immune responses to GapC/B were compared to the responses to the individual proteins, alone or in combination. The GapC/B protein elicited strong humoral and cellular responses in mice as judged by the levels of total IgG, IgG1, IgG2a, and number of IL-4- and IFN-gamma-secreting cells. These results suggest that this chimeric protein could be an attractive target for further vaccine efficacy studies.     

Effect of changes in ionized calcium concentration in arterial blood and metabolic acidosis on the arterial partial pressure of oxygen in dogs

OBJECTIVE: To evaluate the effects of metabolic acidosis and changes in ionized calcium (Ca2+) concentration on PaO2 in dogs. ANIMALS: 33 anesthetized dogs receiving assisted ventilation. PROCEDURE: Normal acid-base status was maintained in 8 dogs (group I), and metabolic acidosis was induced in 25 dogs. For 60 minutes, normocalcemia was maintained in group I and 10 other dogs (group II), and 10 dogs were allowed to become hypercalcemic (group III); hypocalcemia was then induced in groups I and II. Groups II and IV (5 dogs) were treated identically except that, at 90 minutes, the latter underwent parathyroidectomy. At intervals, variables including PaO2, Ca2+ concentration, arterial blood pH (pHa), and systolic blood pressure were assessed. RESULTS: In group II, PaO2 increased from baseline value (96 +/- 2 mm Hg) within 10 minutes (pHa, 7.33 +/- 0.001); at 60 minutes (pHa, 7.21 +/- 0.02), PaO2 was 108 +/- 2 mm Hg. For the same pHa decrease, the PaO2 increase was less in group III. In group I, hypocalcemia caused PaO2 to progressively increase (from 95 +/- 2 mm Hg to 104 +/- 3 mm Hg), which correlated (r = -0.66) significantly with a decrease in systolic blood pressure (from 156 +/- 9 mm Hg to 118 +/- 10 mm Hg). Parathyroidectomy did not alter PaO2 values. CONCLUSIONS AND CLINICAL RELEVANCE: Induction of hypocalcemia and metabolic acidosis each increased PaO2 in anesthetized dogs, whereas acidosis-induced hypercalcemia attenuated that increase. In anesthetized dogs, development of metabolic acidosis or hypocalcemia is likely to affect ventilatory control.     

Correlation of magnetic resonance images with anatomic features of the equine tarsus

OBJECTIVE: To correlate anatomic features of the equine tarsus identified in plastinated sections with images obtained via magnetic resonance imaging (MRI). ANIMALS: 4 horses. PROCEDURE: MRI (1.5-Tesla magnet) of the tarsus was performed on the pelvic limbs of 4 clinically normal horses following euthanasia. After imaging, tarsocrural joint spaces and vasculature were injected with colored latex. Sagittal and transverse sections of the tarsi were plastinated to facilitate interpretation of MR images. RESULTS: Relevant anatomic structures were identified and labeled on the plastinated tissue slices and corresponding MR images. Results indicated high correlations between MRI findings and those of plastinated sections. CONCLUSIONS AND CLINICAL RELEVANCE: The data obtained provided certain reference standards for normal anatomic structure sizes and positions in the equine tarsus. This information may aid future physiologic or clinical studies of this joint.     

The fracture toughness and properties of thermally modified beech and ash at different moisture contents

The fracture toughness of thermally modified beech (Fagus sylvatica L) and ash (Fraxinus excelsior L) wood under Mode I loading was quantified using Compact Tension (CT) specimens, loaded under steady-state crack propagation conditions. The influence of three heat-treatment levels and three moisture contents, as well as two crack propagation systems (RL and TL) was studied. Complete load–displacement records were analysed, and the initial slope, k _init, critical stress intensity factor, K _Ic, and specific fracture energy, G _f, evaluated. In the case of both species, thermal modification was found to be significantly affect the material behaviour; the more severe the thermal treatment, the lower the values of K _Ic and G _f, with less difference being observed between the most severe treatments. Moisture content was also found to influence fracture toughness, but had a much less significant effect than the heat treatment.     

Homegarden agroforestry systems: an intermediary for biodiversity conservation in Bangladesh

Biodiversity conservation is one of the important ecosystem services that has been negatively impacted by anthropogenic activities. Natural forests (NF) harbor some of the highest species diversity around the world. However, deforestation and degradation have resulted in reduced forest land cover and loss of diversity. Homegarden agroforestry (AF) systems have been proven to be an intermediary for biodiversity conservation. In this study, we evaluate the effectiveness of home garden AF practices to conserve tree species diversity in Bangladesh and compare them with tree species diversity in NF. A total of nine locations were selected for this synthesis from published literature which comprised of five AF sites and four NFs. Shannon?CWeiner Diversity Index (H) was similar for home-garden AF (3.50) and NF (2.99), with no statistical difference between them. Based on non-metric multi-dimensional scaling (NMDS) ordination analysis, the AF and NF plots showed distinct separation. However, Bray?CCurtis dissimilarity index ranged from 0.95 to 0.70 indicating nearly no overlap in species composition to significant overlap between AF and NF. Based on our results, we conclude that AF can serve as an important ecological tool in conserving tree species diversity, particularly on landscapes where NF fragments represent only a small fraction of the total land area. Creating and maintaining AF habitats in such human dominated landscapes should be part of the biodiversity conservation strategy.     

Deep planting with shelters improves performance of different stocktype sizes under arid Mediterranean conditions

New Forests - Increasing plant size has been considered a way to improve survival and growth of planted containerized stock under dry conditions. Additionally, deep planting provides advantages to...