A critical role for the chromatin remodeller CHD7 in anterior mesoderm during cardiovascular development

CHARGE syndrome is caused by spontaneous loss-of-function mutations to the ATP-dependant chromatin remodeller chromodomain-helicase-DNA-binding protein 7 (CHD7). It is characterised by a distinct pattern of congenital anomalies, including cardiovascular malformations. Disruption to the neural crest lineage has previously been emphasised in the aetiology of this developmental disorder. We present evidence for an additional requirement for CHD7 activity in the Mesp1-expressing anterior mesoderm during heart development. Conditional ablation of Chd7 in this lineage results in major structural cardiovascular defects akin to those seen in CHARGE patients, as well as a striking loss of cardiac innervation and embryonic lethality. Genome-wide transcriptional analysis identified aberrant expression of key components of the Class 3 Semaphorin and Slit-Robo signalling pathways in Chd7(fl/fl);Mesp1-Cre mutant hearts. CHD7 localises at the Sema3c promoter in vivo, with alteration of the local chromatin structure seen following Chd7 ablation, suggestive of direct transcriptional regulation. Furthermore, we uncover a novel role for CHD7 activity upstream of critical calcium handling genes, and demonstrate an associated functional defect in the ability of cardiomyocytes to undergo excitation-contraction coupling. This work therefore reveals the importance of CHD7 in the cardiogenic mesoderm for multiple processes during cardiovascular development

Speciation by host switch in brood parasitic indigobirds

A growing body of empirical and theoretical work supports the plausibility of sympatric speciation(1-3), but there remain few examples in which all the essential components of the process are well understood. The African indigobirds Vidua spp. are host-specific brood parasites. Indigobird nestlings are reared along with host young, and mimic the mouth markings of their respective hosts(4-6). As adults, male indigobirds mimic host song(4-7), whereas females use these songs to choose both their mates and the nests they parasitize(8). These behavioural mechanisms promote the cohesion of indigobird populations associated with a given host species, and provide a mechanism for reproductive isolation after a new host is colonized. Here we show that all indigobird species are similar genetically, but are significantly differentiated in both mitochondrial haplotype and nuclear allele frequencies. These data support a model of recent sympatric speciation. In contrast to the cuckoo Cuculus canorus, in which only female lineages are faithful to specific hosts(9,10), host switches have led to speciation in indigobirds because both males and females imprint on their hosts(8,11).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62510/1/nature01863.pd

Is translation semantically mediated? Evidence from Welsh-English bilingual aphasia

The involvement of the semantic system in picture naming is undisputed. However, it has been proposed that translation could take place via direct lexical links between L1 and L2 word forms in addition to or instead of via semantics(i.e., with translation going from a spoken word in L1 accessing its meaning and this meaning then leading to the retrieval of the translation equivalent in L2). There is conflicting evidence in the psycholinguistic literature as to the extent of semantic mediation in translation vs. picture naming tasks (Potter et al, 1984; Kroll and Stewart, 1994). More recently, Hernandez et al (2010) investigated this question in a case study of JFF, a proficient bilingual Spanish-Catalan speaker with Alzheimer’s disease and naming difficulties due to a semantic deficit. As JFF’s semantic deficit did not only affect picture naming but also translation tasks, the authors concluded against the existence of functional direct lexical links to support translation. The goal of our study was to explore this issue further in a larger sample of proficient bilingual patients with aphasia and word finding difficulties in both languages. More specifically, we compare the rate of semantic errors produced in naming vs. translation tasks

Impairment in Activities of Daily Living and unmet need for care among older adults: A population-based study from Burkina Faso

OBJECTIVES: The importance of impairment in performing Activities of Daily Living (ADL) is likely to increase in sub-Saharan Africa since few care options for affected people exist. This study investigated the prevalence of ADL impairment, the extent to which care-need was met and described characteristics of people with ADL impairment and unmet need in Burkina Faso. METHODS: This study used data from the CRSN Heidelberg Aging Study, a population-based study among 3,026 adults aged over 40 years conducted in rural Burkina Faso. Information on six basic ADL items was sought, with a follow-up question asking whether care-needs were not met, partially met or met. Bivariable correlations and multivariable logistic regression were used to determine sociodemographic and health characteristics associated with ADL impairment and unmet need. RESULTS: ADL impairment of any kind was reported by 1,202 (39.7%) respondents and was associated with older age (Adjusted Odds Ratio: 1.05 [95% CI: 1.04-1.06]), being a woman (1.33 [1.06-1.60]) and reporting depressive symptoms (1.90 [1.65-2.18]). Among those with ADL impairment, 67.8% had at least one unmet need. Severe ADL impairment was found in 202 (6.7%) respondents, who reported lower prevalence of unmet need (43.1%). Severe ADL impairment was associated with depressive symptoms (2.55 [2.11-3.07]) to a stronger degree than any ADL impairment. DISCUSSION: Prevalence of ADL impairment and unmet need was high in this setting. Variation in impairment across the population highlighted key groups for future interventions. Unmet need for care was highest in middle-aged adults, indicating a gap in care provision

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

How Much Does Effortful Thinking Underlie Observers’ Reactions to Victimization?

From blaming to helping innocent victims, just-world research has revealed that observers react to victimization in a variety of ways. Recent research suggests that such responses to victimization require effortful thought, whereas other research has shown that people can react to these situations intuitively. Along with manipulating just-world threat, across seven experiments, we manipulated or measured participants’ level of mental processing before assessing judgments of victim derogation, blame, willingness to help, and ultimate justice reasoning. The effect of just-world threat on these responses held constant over a range of manipulations/measures, suggesting that the processes involved in maintaining a belief in a just world are not restricted to the rational, deliberative level of mental processing but also occur intuitively

Cacao seeds are a "Super Fruit": A comparative analysis of various fruit powders and products

<p>Abstract</p> <p>Background</p> <p>Numerous popular media sources have developed lists of "Super Foods" and, more recently, "Super Fruits". Such distinctions often are based on the antioxidant capacity and content of naturally occurring compounds such as polyphenols within those whole fruits or juices of the fruit which may be linked to potential health benefits. Cocoa powder and chocolate are made from an extract of the seeds of the fruit of <it>the Theobroma cacao </it>tree. In this study, we compared cocoa powder and cocoa products to powders and juices derived from fruits commonly considered "Super Fruits".</p> <p>Results</p> <p>Various fruit powders and retail fruit products were obtained and analyzed for antioxidant capacity (ORAC (μM TE/g)), total polyphenol content (TP (mg/g)), and total flavanol content (TF (mg/g)). Among the various powders that were tested, cocoa powder was the most concentrated source of ORAC and TF. Similarly, dark chocolate was a significantly more concentrated source of ORAC and TF than the fruit juices.</p> <p>Conclusions</p> <p>Cocoa powder and dark chocolate had equivalent or significantly greater ORAC, TP, and TF values compared to the other fruit powders and juices tested, respectively. Cacao seeds thus provide nutritive value beyond that derived from their macronutrient composition and appear to meet the popular media's definition of a "Super Fruit".</p