DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Rapid Response of a Marine Mammal Species to Holocene Climate and Habitat Change

Environmental change drives demographic and evolutionary processes that determine diversity within and among species. Tracking these processes during periods of change reveals mechanisms for the establishment of populations and provides predictive data on response to potential future impacts, including those caused by anthropogenic climate change. Here we show how a highly mobile marine species responded to the gain and loss of new breeding habitat. Southern elephant seal, Mirounga leonina, remains were found along the Victoria Land Coast (VLC) in the Ross Sea, Antarctica, 2,500 km from the nearest extant breeding site on Macquarie Island (MQ). This habitat was released after retreat of the grounded ice sheet in the Ross Sea Embayment 7,500–8,000 cal YBP, and is within the range of modern foraging excursions from the MQ colony. Using ancient mtDNA and coalescent models, we tracked the population dynamics of the now extinct VLC colony and the connectivity between this and extant breeding sites. We found a clear expansion signal in the VLC population ~8,000 YBP, followed by directional migration away from VLC and the loss of diversity at ~1,000 YBP, when sea ice is thought to have expanded. Our data suggest that VLC seals came initially from MQ and that some returned there once the VLC habitat was lost, ~7,000 years later. We track the founder-extinction dynamics of a population from inception to extinction in the context of Holocene climate change and present evidence that an unexpectedly diverse, differentiated breeding population was founded from a distant source population soon after habitat became available

Bile acids induce hepatic stellate cell proliferation via activation of the epidermal growth factor receptor.

BACKGROUND & AIMS: Hepatic stellate cell (HSC) proliferation is a key event in the development of liver fibrosis. In many liver diseases, HSCs are exposed to inflammatory cytokines, reactive oxygen species, and bile acids. Although inflammatory cytokines and reactive oxygen species are known to promote proliferation of HSCs, nothing is known about the effects of bile acids on HSC proliferation or apoptosis. The aim of this study was to investigate the effects of bile acids on HSC proliferation. METHODS: HSCs were exposed to bile acids with different hydrophobicity (5-200 micromol/L). HSC proliferation and cell cycle-related events were assessed by bromodeoxyuridine incorporation, cell counting and proliferating cell nuclear antigen and cyclin E expression, apoptosis by caspase-3 activity assay, immunocytochemistry for active caspase-3 and acridine orange staining, and activation of signal transduction pathways by Western blot using phospho-specific antibodies. Uptake of bile acids was investigated using fluorescent bile acids. RESULTS: All bile acids, at concentrations >25 micromol/L, induce a 2.5- to 3-fold increase in HSC proliferation via activation of the epidermal growth factor receptor. Bile acid-induced proliferation is mediated by activation of a protein kinase C/extracellular signal-regulated kinase/p70S6K-dependent pathway. Bile acids did not induce apoptosis in HSCs. HSCs do not take up fluorescent bile acids and do not express the bile acid importer ntcp. CONCLUSIONS: Bile acids at levels reached in cholestatic conditions are an independent profibrogenic factor. Bile acids induce HSC proliferation via the activation of the epidermal growth factor receptor, whereas HSCs are protected against bile acid-induced apoptosis by excluding bile acids

Combining Networks Using Cherry Picking Sequences

Phylogenetic networks are important for the study of evolution. The number of methods to find such networks is increasing, but most such methods can only reconstruct small networks. To find bigger networks, one can attempt to combine small networks. In this paper, we study the Network Hybridization problem, a problem of combining networks into another network with low complexity. We characterize this complexity via a restricted problem, Tree-child Network Hybridization, and we present an FPT algorithm to efficiently solve this restricted problem.Accepted author manuscriptOptimizatio

The effect of residual water on antacid properties of sucralfate gel dried by microwaves

The aim of this work was to study the acid neutralization characteristics of microwave-dried sucralfate gel in relation to the water content and physical structure of the substance. Several dried sucralfate gels were compared with humid sucralfate gel and sucralfate nongel powder in terms of neutralization rate and buffering capacity. Humid sucralfate gel and microwave-dried gel exhibited antacid effectiveness. In particular, the neutralization rate of dried gel powders was inversely related to the water content: as the water content of dried powders decreased, the acid reaction rate linearly increased. The relationship was due to the different morphology of dried sucralfate gels. In fact, the porosity of the dried samples increased with the water reduction. However, the acid neutralization equivalent revealed that the dried sucralfate gel became more resistant to acid attack in the case of water content below 42%. Then, the microwave drying procedure had the opposite effect on the reactivity of the aluminum hydroxide component of dried sucralfate gel powders, since the rate of the reaction increased whereas the buffering capacity decreased as the amount of water was reduced

Transfer of learning in choice reactions: The roles of stimulus type, response mode, and set-level compatibility

The Simon effect refers to the advantage of responding to spatially compatible stimuli. This effect can be eliminated or even reversed to favor spatially incompatible stimuli after participants practice a choice-reaction task with spatially incompatible mappings (e.g., pressing left and right keys to stimuli on the right and left, respectively). This transfer of incompatible spatial associations has been observed under conditions in which responses were made manually (e.g., keypresses, moving a joystick). The present study used vocal responses to reveal the primary determinants of the transfer effect, dissociating the influences of stimulus type, response mode, and their interaction (set-level compatibility). The results suggest that contextual match between the practice and transfer tasks with respect to stimulus type and response mode determined transfer of incompatible associations to the Simon task, and stimulus type determined the efficiency of acquiring new associations. However, there was little evidence that set-level compatibility plays any major role in either acquisition or transfer of spatial associations