Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.     

Does rejection hurt? An FMRI study of social exclusion

A neuroimaging study examined the neural correlates of social exclusion and tested the hypothesis that the brain bases of social pain are similar to those of physical pain. Participants were scanned while playing a virtual ball-tossing game in which they were ultimately excluded. Paralleling results from physical pain studies, the anterior cingulate cortex (ACC) was more active during exclusion than during inclusion and correlated positively with self-reported distress. Right ventral prefrontal cortex (RVPFC) was active during exclusion and correlated negatively with self-reported distress. ACC changes mediated the RVPFC-distress correlation, suggesting that RVPFC regulates the distress of social exclusion by disrupting ACC activity.     

Reversible concerted ligand substitution at alternating metal sites in an extended solid

We report a synthetic material, [Co2(bipy)3(SO4)2(H2O)2](bipy) (CH3OH), (1, where bipy = 4,4'-bipyridyl) that contains discrete reactive and inert structural motifs that undergo a reversible substitution reaction involving the concerted and spatially controlled introduction of bipyridine and methanol molecules at the reactive sites. This reaction defines the pore geometry of the resulting open-framework structure and controls the manner in which this structure sorbs small molecules. The molecules involved in the reaction are positioned by an array of well-defined interactions during their path to binding to the metal centers.     

Turbidity‐induced changes in emergent effects of multiple predators with different foraging strategies

Abstract – In natural systems, prey frequently interact with multiple predators and the outcome often cannot be predicted by summing the effects of individual predator species. Multiple predator interactions can create emergent effects for prey, but how those change across environmental gradients is poorly understood. Turbidity is an environmental factor in aquatic systems that may influence multiple predator effects on prey. Interactions between a cruising predator (largemouth bass Micropterus salmoides) and an ambush predator (muskellunge Esox masquinongy) and their combination foraging on a shared prey (bluegill Lepomis macrochirus) were examined across a turbidity gradient. Turbidity modified multiple predator effects on prey. In clear water, combined predators consumed in total more prey than expected from individual predator treatments, suggesting risk enhancement for prey. In moderately turbid water, the predators consumed fewer prey together than expected, suggesting a risk reduction for prey. At high turbidity, there were no apparent emergent effects; however, the cruising predator consumed more prey than the ambush predator, suggesting an advantage for this predator. Understanding multiple predator traits across a gradient of turbidity increases our understanding of how complex natural systems function.     

Host status of cover crops for root-lesion nematodes (Pratylenchus spp.) associated with apple orchards in South Africa

Journal of Plant Diseases and Protection - The host response of 17 cover crop cultivars to infection by single-species populations of Pratylenchus hippeastri, Pratylenchus vulnus and Pratylenchus...     

Association between porpoise presence and fish choruses: implications for feeding strategies and ecosystem-based conservation of the East Asian finless porpoise

The associations between feeding activities and environmental variables inform animal feeding tactics that maximize energetic gains by minimizing energy costs while maximizing feeding success. Relevant studies in aquatic animals, particularly marine mammals, are scarce due to difficulties in the observation of feeding behaviors in aquatic environments. This data scarcity concurrently hinders ecosystem-based fishery management in the context of small toothed-cetacean conservation. In the present study, a passive acoustic monitoring station was deployed in an East Asian finless porpoise habitat in Laizhou Bay to investigate potential relationships between East Asian finless porpoises and their prey. The data revealed that porpoises were acoustically present nearly every day during the survey period. Porpoise detection rates differed between spring and autumn in concert with activities of fish choruses. During spring, fish choruses were present throughout the afternoon, and this was the time when porpoise vocalizations were the most frequently detected. During autumn, when fish choruses were absent, porpoise detection rates decreased, and diurnal patterns were not detected. The close association between fish choruses and finless porpoise activities implies an “eavesdropping” feeding strategy to maximize energetic gains, similar to other toothed cetaceans that are known to engage similar feeding strategies. Underwater noise pollution, particularly those masking fish choruses, could interrupt finless porpoises’ feeding success. Fisheries competing soniferous fishes with finless porpoise could impact finless porpoise viability through ecosystem disruption, in addition to fishing gear entanglement.     

Evaluation of mechlorethamine,vinblastine, procarbazine,and prednisone for the treatment of resistant multicentric canine lymphoma

Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance. The objective of this study was to report the clinical outcomes and toxicity of 36 dogs with relapsed or refractory multicentric lymphoma treated with a modified MOPP protocol whereby vincristine was replaced with vinblastine (MVPP). The overall response rate to MVPP was 25% with a median progression free survival of 15 days and a median overall survival of 45 days. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses.