Neuroplasticity and brain repair after stroke.

Purpose of reviewThis review considers recent insights into the neurobiology of repair after stroke in animals and humans, the range of emerging therapies to promote repair and recovery after the acute phase of stroke, and issues related to optimizing trials of such therapies.Recent findingsAnimal studies continue to shed light on the molecular, vascular, glial, neuronal, behavioral, and environmental events that are important to the spontaneous behavioral recovery that is observed during the weeks after a stroke. Animal and human studies are examining a wide range of potential interventions that may favorably modify outcome, including small molecules, growth factors, cell-based approaches, electromagnetic stimulation, a range of devices and robots, and intense physiotherapy methods, including constraint-induced movement therapy. Optimal prescription of these restorative therapies in human patients with stroke requires further study, including defining potential roles for functional neuroimaging.SummaryA wide range of therapies shows promise for improving poststroke brain repair. Insights into the neurobiology of brain repair after stroke in animals and in humans continue to accrue. This information might prove useful in designing and implementing clinical trials that aim to measure the clinical effects of restorative therapies after stroke

Individual and Population Level Resource Selection Patterns of Mountain Lions Preying on Mule Deer along an Urban-Wildland Gradient

Understanding population and individual-level behavioral responses of large carnivores to human disturbance is important for conserving top predators in fragmented landscapes. However, previous research has not investigated resource selection at predation sites of mountain lions in highly urbanized areas. We quantified selection of natural and anthropogenic landscape features by mountain lions at sites where they consumed their primary prey, mule deer (Odocoileus hemionus), in and adjacent to urban, suburban, and rural areas in greater Los Angeles. We documented intersexual and individual-level variation in the environmental conditions present at mule deer feeding sites relative to their availability across home ranges. Males selected riparian woodlands and areas closer to water more than females, whereas females selected developed areas marginally more than males. Females fed on mule deer closer to developed areas and farther from riparian woodlands than expected based on the availability of these features across their home ranges.We suggest that mortality risk for females and their offspring associated with encounters with males may have influenced the different resource selection patterns between sexes. Males appeared to select mule deer feeding sites mainly in response to natural landscape features, while females may have made kills closer to developed areas in part because these are alternative sites where deer are abundant. Individual mountain lions of both sexes selected developed areas more strongly within home ranges where development occurred less frequently. Thus, areas near development may represent a trade-off for mountain lions such that they may benefit from foraging near development because of abundant prey, but as the landscape becomes highly urbanized these benefits may be outweighed by human disturbance

The ecology of human-caused mortality for a protected large carnivore

Mitigating human-caused mortality for large carnivores is a pressing global challenge for wildlife conservation. However, mortality is almost exclusively studied at local (within-population) scales creating a mismatch between our understanding of risk and the spatial extent most relevant to conservation and management of wide-ranging species. Here, we quantified mortality for 590 radio-collared mountain lions statewide across their distribution in California to identify drivers of human-caused mortality and investigate whether human-caused mortality is additive or compensatory. Human-caused mortality, primarily from conflict management and vehicles, exceeded natural mortality despite mountain lions being protected from hunting. Our data indicate that human-caused mortality is additive to natural mortality as population-level survival decreased as a function of increasing human-caused mortality and natural mortality did not decrease with increased human-caused mortality. Mortality risk increased for mountain lions closer to rural development and decreased in areas with higher proportions of citizens voting to support environmental initiatives. Thus, the presence of human infrastructure and variation in the mindset of humans sharing landscapes with mountain lions appear to be primary drivers of risk. We show that human-caused mortality can reduce population-level survival of large carnivores across large spatial scales, even when they are protected from hunting

Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for use in the treatment of African animal trypanosomiasis

African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites Trypanosoma congolense and Trypanosoma vivax, is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12

Airships: A New Horizon for Science

The "Airships: A New Horizon for Science" study at the Keck Institute for Space Studies investigated the potential of a variety of airships currently operable or under development to serve as observatories and science instrumentation platforms for a range of space, atmospheric, and Earth science. The participants represent a diverse cross-section of the aerospace sector, NASA, and academia. Over the last two decades, there has been wide interest in developing a high altitude, stratospheric lighter-than-air (LTA) airship that could maneuver and remain in a desired geographic position (i.e., "station-keeping") for weeks, months or even years. Our study found considerable scientific value in both low altitude (< 40 kft) and high altitude (> 60 kft) airships across a wide spectrum of space, atmospheric, and Earth science programs. Over the course of the study period, we identified stratospheric tethered aerostats as a viable alternative to airships where station-keeping was valued over maneuverability. By opening up the sky and Earth's stratospheric horizon in affordable ways with long-term flexibility, airships allow us to push technology and science forward in a project-rich environment that complements existing space observatories as well as aircraft and high-altitude balloon missions.Comment: This low resolution version of the report is 8.6 MB. For the high resolution version see: http://kiss.caltech.edu/study/airship

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development