Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose γ-irradiation

Molecular paradigms underlying the death of hematopoietic stem cells (HSCs) induced by ionizing radiation are poorly defined. We have examined the role of Puma (p53 up-regulated mediator of apoptosis) in apoptosis of HSCs after radiation injury. In the absence of Puma, HSCs were highly resistant to γ-radiation in a cell autonomous manner. As a result, Puma-null mice or the wild-type mice reconstituted with Puma-null bone marrow cells were strikingly able to survive for a long term after high-dose γ-radiation that normally would pose 100% lethality on wild-type animals. Interestingly, there was no increase of malignancy in the exposed animals. Such profound beneficial effects of Puma deficiency were likely associated with better maintained quiescence and more efficient DNA repair in the stem cells. This study demonstrates that Puma is a unique mediator in radiation-induced death of HSCs. Puma may be a potential target for developing an effective treatment aimed to protect HSCs from lethal radiation

A mitochondrial pathway for biosynthesis of lipid mediators

The central role of mitochondria in metabolic pathways and in cell death mechanisms requires sophisticated signaling systems. Essential in this signaling process is an array of lipid mediators derived from polyunsaturated fatty acids. However, the molecular machinery for the production of oxygenated polyunsaturated fatty acids is localized in the cytosol and their biosynthesis has not been identified in mitochondria. Here we report that a range of diversified polyunsaturated molecular species derived from a mitochondria-specific phospholipid, cardiolipin, are oxidized by the intermembrane space hemoprotein, cytochrome c. We show that an assortment of oxygenated cardiolipin species undergoes phospholipase A2-catalyzed hydrolysis thus generating multiple oxygenated fatty acids, including well known lipid mediators. This represents a new biosynthetic pathway for lipid mediators. We demonstrate that this pathway including oxidation of polyunsaturated cardiolipins and accumulation of their hydrolysis products – oxygenated linoleic, arachidonic acids and monolyso-cardiolipins – is activated in vivo after acute tissue injury

Long-Term Seasonal and Interannual Patterns of Marine Mammal Strandings in Subtropical Western South Atlantic

Understanding temporal patterns of marine mammal occurrence is useful for establishing conservation strategies. We used a 38 yr-long dataset spanning 1976 to 2013 to describe temporal patterns and trends in marine mammal strandings along a subtropical stretch of the east coast of South America. This region is influenced by a transitional zone between tropical and temperate waters and is considered an important fishing ground off Brazil. Generalized Additive Models were used to evaluate the temporal stranding patterns of the most frequently stranded species. Forty species were documented in 12,540 stranding events. Franciscana (n = 4,574), South American fur seal, (n = 3,419), South American sea lion (n = 2,049), bottlenose dolphins (n = 293) and subantarctic fur seal (n = 219) were the most frequently stranded marine mammals. The seasonality of strandings of franciscana and bottlenose dolphin coincided with periods of higher fishing effort and strandings of South American and subantarctic fur seals with post-reproductive dispersal. For South American sea lion the seasonality of strandings is associated with both fishing effort and post-reproductive dispersal. Some clear seasonal patterns were associated with occurrence of cold- (e.g. subantarctic fur seal) and warm-water (e.g. rough-toothed dolphin) species in winter and summer, respectively. Inter-annual increases in stranding rate were observed for franciscana and South American fur seal and these are likely related to increased fishing effort and population growth, respectively. For subantarctic fur seal the stranding rate showed a slight decline while for bottlenose dolphin it remained steady. No significant year to year variation in stranding rate was observed for South American sea lion. The slight decrease in frequency of temperate/polar marine mammals and the increased occurrence of subtropical/tropical species since the late 1990s might be associated with environmental changes linked to climate change. This long-term study indicates that temporal stranding patterns of marine mammals might be explained by either fishing-related or environmental factors