Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD

Purpose: 3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD. Methods: We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. Results: We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD. Conclusion: Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes

An integrated optical CO2 sensor. Phase 0: Design and fabrication of critical elements

Significant progress has been made toward all of the goals for the first phase of the project short of actual fabrication of a light path. Two alternative approaches to fabricating gold mirrors using the basic LIGA process were developed, one using electroplated solid gold mirrors and the second using gold plated over a nickel base. A new method of fabrication, the transfer mask process, was developed and demonstrated. Analysis of the projected surface roughness and beam divergence effects was completed. With gold surface with low surface roughness scattering losses are expected to be insignificant. Beam divergence due to diffraction will require a modification of the original design, but should be eliminated by fabricating mirrors 1000 mu m in height by 1000 mu m in width and using a source with an initial beam radius greater than 300 mu m. This may eliminate any need for focusing optics. Since the modified design does not affect the mask layout, ordering of the mask and fabrication of the test structures can begin immediately at the start of Phase 1

Towards quality criteria for regional public health reporting: concept mapping with Dutch experts

Background: In the Netherlands, municipal health assessments are carried out by 28 Regional Health Services, serving 418 municipalities. In the absence of guidelines, regional public health reports were developed in two pilot regions on the basis of the model and experience of national health reporting. Though they were well received and positively evaluated, it was not clear which specific characteristics determined ‘good public health reporting’. Therefore, this study was set up to develop a theoretical framework for the quality of regional public health reporting in The Netherlands. Methods: Using concept mapping as a standardized tool for conceptualization, 35 relevant reporting experts formulated short statements in two different brainstorming sessions, describing specific quality criteria of regional public health reports. After the removal of duplicates, the list was supplemented with international criteria, and the statements were sent to each participant for rating and sorting. The results were processed statistically and represented graphically. The output was discussed and interpreted, leading to the final concept map. Results: The final concept map consisted of 97 criteria, grouped into 13 clusters, and plotted in two dimensions: a ‘product’ dimension, ranging from ‘production’ to ‘content’, and a ‘context’ dimension, ranging from ‘science’ to ‘policy’. The three most important clusters were: (i) ‘solution orientation’, (ii) ‘policy relevance’ and (iii) ‘policy impact’. Conclusion: This study provided a theoretical framework for the quality of regional public health reporting, indicating relevant domains and criteria. Further work should translate domains and criteria into operational indicators for evaluating regional public health reports

Lignin biomarkers as tracers of mercury sources in lakes water column

This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

Short-term and spike-timing-dependent plasticity facilitate the formation of modular neural networks

The brain has the phenomenal ability to reorganise itself by forming new connections among neurons and by pruning others. The so-called neural or brain plasticity facilitates the modification of brain structure and function over different time scales. Plasticity might occur due to external stimuli received from the environment, during recovery from brain injury, or due to modifications within the body and brain itself. In this paper, we study the combined effect of short-term (STP) and spike-timing-dependent plastic- ity (STDP) on the synaptic strength of excitatory coupled Hodgkin-Huxley neurons and show that plasticity can facilitate the formation of modular neural networks with complex topologies that resemble those of networks with preferential attachment properties. In particular, we use an STDP rule that alters the synaptic coupling intensity based on time intervals between spikes of postsynaptic and presynaptic neurons. Previous work has shown that STDP may induce the emergence of directed connections from high to low frequency spiking neurons. On the other hand, STP is attributed to the release of neurotransmitters in the synaptic cleft of neurons that alter its synaptic efficiency. Our results suggest that the combined effect of STP and STDP with long recovery times facilitates the formation of connections among neurons with similar spike frequencies only, a kind of preferential at- tachment. We then pursue this further and show that, when starting with all-to-all neural configurations, depending on the STP recovery time and dis- tribution of neural frequencies, modular neural networks can emerge as a direct result of the combined effect of STP and STDP

Boring bivalve traces in modern reef and deeper-water macroid and rhodolith beds

Macroids and rhodoliths, made by encrusting acervulinid foraminifera and coralline algae, are widely recognized as bioengineers providing relatively stable microhabitats and increasing biodiversity for other species. Macroid and rhodolith beds occur in different depositional settings at various localities and bathymetries worldwide. Six case studies of macroid/rhodolith beds from 0 to 117m water depth in the Pacific Ocean (northern Central Ryukyu Islands, French Polynesia), eastern Australia (Fraser Island, One Tree Reef, Lizard Island), and the Mediterranean Sea (southeastern Spain) show that nodules in the beds are perforated by small-sized boring bivalve traces (Gastrochanolites). On average, boring bivalve shells (gastrochaenids and mytilids) are more slender and smaller than those living inside shallow-water rocky substrates. In the Pacific, Gastrochaena cuneiformis, Gastrochaena sp., Leiosolenus malaccanus, L. mucronatus, L. spp., and Lithophaga/Leiosolenus sp., for the first time identified below 20m water depth, occur as juvenile forms along with rare small-sized adults. In deep-water macroids and rhodoliths the boring bivalves are larger than the shallower counterparts in which growth of juveniles is probably restrained by higher overturn rates of host nodules. In general, most boring bivalves are juveniles that grew faster than the acervulinid foraminiferal and coralline red algal hosts and rarely reached the adult stage. As a consequence of phenotypic plasticity, small-sized adults with slow growth rates coexist with juveniles. Below wave base macroids and rhodoliths had the highest amounts of bioerosion, mainly produced by sponges and polychaete worms. These modern observations provide bases for paleobiological inferences in fossil occurrences.Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) 25247083Erasmus+FAR2012-2017FIR2016FIR2018PRIN "Biotic resilience to global change: biomineralization of planktonic and benthic calcifiers in the past, present and future" 2017RX9XXXYBioMed Central-Prepay Membership at the University of FerraraJunta de Andalucía RNM 190Committee on ResearchMuseum of PaleontologyDepartment of Integrative Biology, UC BerkeleyUC Pacific Rim Projec

Understanding young people's citizenship learning in everyday life: The role of contexts, relationships and dispositions

In this article we present insights from research which has sought to deepen understanding of the ways in which young people (13-21) learn democratic citizenship through their participation in a range of different formal and informal practices and communities. Based on the research, we suggest that such understanding should focus on the interplay between contexts for action, relationships within and across contexts, and the dispositions that young people bring to such contexts and relationships. In the first part of the paper we show how and why we have broadened the narrow parameters of the existing citizenship discourse with its focus on political socialisation to encompass a more wide-ranging conception of citizenship learning which is not just focused on school or the curriculum. In the second part of the paper we describe our research and present two exemplar case studies of young people who formed part of the project. In the third part we present our insights about the nature and character of citizenship learning that we have been able to draw from our research. In the concluding section we highlight those dimensions of citizenship learning that would have remained invisible had we focused exclusively on schools and the curriculum. In this way we demonstrate the potential of the approach to understanding citizenship learning that we have adopted