Radiation-induced Assembly of Rad51 and Rad52 Recombination Complex Requires ATM and c-Abl

Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R

STEM gender stereotypes from early childhood through adolescence at informal science centers.

Stereotypes about science, technology, engineering and mathematics (STEM) are associated with reduced STEM engagement amongst girls and women. The present study examined these stereotypes from early childhood through adolescence within informal science learning sites (ISLS; science museums, zoos, aquariums). Further, the study explored whether interactions with male or female educators influenced STEM stereotypes. Participants (n = 997, female = 572) were ISLS visitors in the UK and USA who either interacted with an educator, or no educator. With age participants were more likely to report that "both boys and girls" are "usually", "should" be, and "can" be good at STEM. Independent of age, male participants reported that their own gender group "should" be good at STEM. Educator interactions did not influence stereotype responses. These results highlight early childhood as a key developmental window in which to challenge ideas about who can and should be proficient in STEM

The Effect of Clothing on the Rate of Decomposition and Diptera Colonization onSus scrofaCarcasses

Twenty Sus scrofa carcasses were used to study the effect the presence of clothing had on decomposition rate and colonization locations of Diptera species; 10 unclothed control carcasses were compared to 10 clothed experimental carcasses over 58 days. Data collection occurred at regular accumulated degree day intervals; the level of decomposition as Total Body Score (TBSsurf), pattern of decomposition, and Diptera present was documented. Results indicated a statistically significant difference in the rate of decomposition, (t427 = 2.59, p = 0.010), with unclothed carcasses decomposing faster than clothed carcasses. However, the overall decomposition rates from each carcass group are too similar to separate when applying a 95% CI, which means that, although statistically significant, from a practical forensic point of view they are not sufficiently dissimilar as to warrant the application of different formulae to estimate the postmortem interval. Further results demonstrated clothing provided blow flies with additional colonization locations

‘BETTER OFF DEAD THAN DISFIGURED’? THE CHALLENGES OF FACIAL INJURY IN THE PRE-MODERN PAST

This paper contrasts modern representations of facial disfigurement, which often focus on the personal story of 'triumph over adversity', with the problems of accessing such first-person accounts in the medieval past. It examines a number of approaches to the history of facial disfigurement in early medieval Europe, and suggests that this history has been neglected because it does not fit comfortably into existing disciplinary categories such as medical history or disability studies

Interest and learning in informal science learning sites: Differences in experiences with different types of educators.

This study explored topic interest, perceived learning and actual recall of exhibit content in 979 children and adolescents and 1,184 adults who visited informal science learning sites and interacted with an adult or youth educator or just the exhibit itself as part of family visits to the sites. Children in early childhood reported greater topic interest and perceived learning, but actually recalled less content, than participants in middle childhood or adolescence. Youth visitors reported greater interest after interacting with a youth educator than just the exhibit, and perceived that they learn more if they interact with an educator (youth or adult). Participants in middle childhood recall more when they encounter a youth educator. Adult visitors reported greater interest after interaction with a youth educator than with the exhibit alone or an adult educator. They also perceived that they learn more if they interact with an educator (youth or adult) than just the exhibit and perceived that they learned more if they interacted with a youth educator than an adult educator. Results highlight the benefits of educators in informal science learning sites and document the importance of attention to developmental needs

Initial Medical Attention on Patients with Early-Stage Non-Small Cell Lung Cancer

Detection of early stage non-small cell lung cancer (NSCLC) is commonly believed to be incidental. Understanding the reasons that caused initial detection of these patients is important for early diagnosis. However, these reasons are not well studied.We retrospectively reviewed medical records of patients diagnosed with stage I or II NSCLC between 2000 and 2009 at UT MD Anderson Cancer Center. Information on suggestive LC-symptoms or other reasons that caused detection were extracted from patients' medical records. We applied univariate and multivariate analyses to evaluate the association of suggestive LC-symptoms with tumor size and patient survival.Of the 1396 early stage LC patients, 733 (52.5%) presented with suggestive LC-symptoms as chief complaint. 347 (24.9%) and 287 (20.6%) were diagnosed because of regular check-ups and evaluations for other diseases, respectively. The proportion of suggestive LC-symptom-caused detection had a linear relationship with the tumor size (correlation 0.96; with p<.0001). After age, gender, race, smoking status, therapy, and stage adjustment, the symptom-caused detection showed no significant difference in overall and LC-specific survival when compared with the other (non-symptom-caused) detection.Symptoms suggestive of LC are the number one reason that led to detection in early NSCLC. They were also associated with tumor size at diagnosis, suggesting early stage LC patients are developing symptoms. Presence of symptoms in early stages did not compromise survival. A symptom-based alerting system or guidelines may be worth of further study to benefit NSCLC high risk individuals

Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques

HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeated intravaginal SIV challenges. Vaccination induced anti-SIV IgG responses and neutralizing antibodies were found in all vaccinated RMs. Three of the eight vaccinated RM remained uninfected (vaccinated and protected, VP) after 13 repeated challenges with the pathogenic SIVmac251-CX-1. The remaining five vaccinated and infected (VI) macaques had significantly reduced plasma viral loads compared with the infected controls (IC). A significant increase in systemic central memory CD4+ T cells and mucosal CD8+ effector memory T-cell responses was detected in vaccinated RMs compared to controls. Variability in lymph node SIV-Gag and Env specific CD4+ and CD8+ T cell cytokine responses were detected in the VI RMs while all three VP RMs had more durable cytokine responses following vaccination and prior to challenge. VI RMs demonstrated predominately SIV-specific monofunctional cytokine responses while the VP RMs generated polyfunctional cytokine responses. This study demonstrates that varicella virus-vectored SIV vaccination with protein boosts induces a 37.5% efficacy rate against pathogenic SIV challenge by generating mucosal memory, virus specific neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses

Large-Scale Variation in Wave Attenuation of Oyster Reef Living Shorelines and the Influence of Inundation Duration

One of the paramount goals of oyster reef living shorelines is to achieve sustained and adaptive coastal protection, which requires meeting ecological (i.e., develop a self-sustaining oyster population) and engineering (i.e., provide coastal defense) targets. In a large-scale comparison along the Atlantic and Gulf coasts of the United States, the efficacy of various designs of oyster reef living shorelines at providing wave attenuation was evaluated accounting for the ecological limitations of oysters with regards to inundation duration. A critical threshold for intertidal oyster reef establishment is 50% inundation duration. Living shorelines that spent less than half of the time (\u3c 50%) inundated were not considered suitable habitat for oysters, however, were effective at wave attenuation (68% reduction in wave height). Reefs that experienced \u3e 50% inundation were considered suitable habitat for oysters, but wave attenuation was similar to controls (no reef; ~5% reduction in wave height). Many of the oyster reef living shoreline approaches therefore failed to optimize the ecological and engineering goals. In both inundation regimes, wave transmission decreased with an increasing freeboard (difference between reef crest elevation and water level), supporting its importance in the wave attenuation capacity of oyster reef living shorelines. However, given that the reef crest elevation (and thus freeboard) should be determined by the inundation duration requirements of oysters, research needs to be re-focused on understanding the implications of other reef parameters (e.g. width) for optimising wave attenuation. A broader understanding of the reef characteristics and seascape contexts that result in effective coastal defense by oyster reefs is needed to inform appropriate design and implementation of oyster-based living shorelines globally

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia