Stress-Mediated Increases in Systemic and Local Epinephrine Impair Skin Wound Healing: Potential New Indication for Beta Blockers

Rivkah Isseroff and colleagues describe how stress-induced elevation of epinephrine levels can impair the healing of burns in mice and suggest that β2 adrenergic receptor antagonists may have a role in improving skin wound repair

A New Method to Address Unmet Needs for Extracting Individual Cell Migration Features from a Large Number of Cells Embedded in 3D Volumes

Background: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D), which is related to the spread of cancer and metastases. Methodology/Principal Findings: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift) trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6%). We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA) were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. Conclusions/Significance: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment. © 2011 Adanja et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig

Abstract Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties

Survival and Mortality of Pumas (Puma concolor) in a Fragmented, Urbanizing Landscape

Wide-ranging large carnivores pose myriad challenges for conservation, especially in highly fragmented landscapes. Over a 13-year period, we combined monitoring of radio collared pumas (Puma concolor) with complementary multi-generational genetic analyses to inform puma conservation in southern California, USA. Our goals were to generate survivorship estimates, determine causes of mortality, identify barriers to movement, and determine the genetic and demographic challenges to puma persistence among >20,000,000 people and extensive urban, suburban, and exurban development. Despite protection from hunting, annual survival for radio collared pumas was surprisingly low (55.8%), and humans caused the majority of puma deaths. The most common sources of mortality were vehicle collisions (28% of deaths), and mortalities resulting from depredation permits issued after pumas killed domestic animals (17% of deaths). Other human-caused mortalities included illegal shootings, public safety removals, and human-caused wildfire. An interstate highway (I-15) bisecting this study area, and associated development, have created a nearly impermeable barrier to puma movements, resulting in severe genetic restriction and demographic isolation of the small puma population (n ~ 17-27 adults) in the Santa Ana Mountains west of I-15. Highways that bisect habitat or divide remaining "conserved" habitat, and associated ongoing development, threaten to further subdivide this already fragmented puma population and increase threats to survival. This study highlights the importance of combining demographic and genetic analyses, and illustrates that in the absence of effective measures to reduce mortality and enhance safe movement across highways, translocation of pumas, such as was done with the endangered Florida panther (P. c. coryi), may ultimately be necessary to prevent further genetic decline and ensure persistence of the Santa Ana Mountains population