56 research outputs found
Magnetization transfer imaging in ‘premanifest’ Huntington’s disease
To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in ‘premanifest’ carriers of the Huntington’s disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity
Telling the collective story? Moroccan-Dutch young adults’ negotiation of a collective identity through storytelling
Researchers taking a social constructionist perspective on identity agree that identities are constructed and negotiated in interaction. However, empirical studies in this field are often based on interviewer–interviewee interaction or focus on interactions with members of a socially dominant out-group. How identities are negotiated in interaction with in-group members remains understudied. In this article we use a narrative approach to study identity negotiation among Moroccan-Dutch young adults, who constitute both an ethnic and a religious (Muslim) minority in the Netherlands. Our analysis focuses on the topics that appear in focus group participants’ stories and on participants’ responses to each other’s stories. We find that Moroccan-Dutch young adults collectively narrate their experiences in Dutch society in terms of discrimination and injustice. Firmly grounded in media discourse and popular wisdom, a collective narrative of a disadvantaged minority identity emerges. However, we also find that this identity is not uncontested. We use the concept of second stories to explain how participants negotiate their collective identity by alternating stories in which the collective experience of deprivation is reaffirmed with stories in which challenging or new evaluations of the collective experience are offered. In particular, participants narrate their personal experiences to challenge recurring evaluations of discrimination and injustice. A new collective narrative emerges from this work of joint storytelling
Deficient sustained attention to response task and P300 characteristics in early Huntington’s disease
Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington’s disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (p < 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (p < 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group
Transcriptional Control of Steroid Biosynthesis Genes in the Drosophila Prothoracic Gland by Ventral Veins Lacking and Knirps.
Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG) that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl) and the nuclear receptor Knirps (Kni), have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH) signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld), controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development
Transmission of H7N9 influenza virus in mice by different infective routes
BACKGROUND: On 19 February 2013, the first patient infected with a novel influenza A H7N9 virus from an avian source showed symptoms of sickness. More than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland China since then. Laboratory-confirmed, human-to-human H7N9 virus transmission has not been documented between individuals having close contact; however, this transmission route could not be excluded for three families. To control the spread of the avian influenza H7N9 virus, we must better understand its pathogenesis, transmissibility, and transmission routes in mammals. Studies have shown that this particular virus is transmitted by aerosols among ferrets. METHODS: To study potential transmission routes in animals with direct or close contact to other animals, we investigated these factors in a murine model. RESULTS: Viable H7N9 avian influenza virus was detected in the upper and lower respiratory tracts, intestine, and brain of model mice. The virus was transmissible between mice in close contact, with a higher concentration of virus found in pharyngeal and ocular secretions, and feces. All these biological materials were contagious for naïve mice. CONCLUSIONS: Our results suggest that the possible transmission routes for the H7N9 influenza virus were through mucosal secretions and feces. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-422X-11-185) contains supplementary material, which is available to authorized users
Role of zinc transporter ZIP12 in susceptibility‐weighted brain magnetic resonance imaging (MRI) phenotypes and mitochondrial function
Severe early basal ganglia hypometabolism in neurodegeneration with brain iron accumulation
Diversity patterns and activity of uncultured marine heterotrophic flagellates unveiled with pyrosequencing
11 pages, 7 figures, 2 tablesFlagellated heterotrophic microeukaryotes have key roles for the functioning of marine ecosystems as they channel large amounts of organic carbon to the upper trophic levels and control the population sizes of bacteria and archaea. Still, we know very little on the diversity patterns of most groups constituting this evolutionary heterogeneous assemblage. Here, we investigate 11 groups of uncultured flagellates known as MArine STramenopiles (MASTs). MASTs are ecologically very important and branch at the base of stramenopiles. We explored the diversity patterns of MASTs using pyrosequencing (18S rDNA) in coastal European waters. We found that MAST groups range from highly to lowly diversified. Pyrosequencing (hereafter ‘454’) allowed us to approach to the limits of taxonomic diversity for all MAST groups, which varied in one order of magnitude (tens to hundreds) in terms of operational taxonomic units (98% similarity). We did not evidence large differences in activity, as indicated by ratios of DNA:RNA-reads. Most groups were strictly planktonic, although we found some groups that were active in sediments and even in anoxic waters. The proportion of reads per size fraction indicated that most groups were composed of very small cells (~2–5 μm). In addition, phylogenetically different assemblages appeared to be present in different size fractions, depths and geographic zones. Thus, MAST diversity seems to be highly partitioned in spatial scales. Altogether, our results shed light on these ecologically very important but poorly known groups of uncultured marine flagellatesFinancial support for this work has been provided by a Marie Curie Intra-European Fellowship grant (PIEF-GA-2009-235365) to RL and by projects BioMarKs (2008-6530, ERA-net Biodiversa, EU) and FLAME (CGL2010-16304, MICINN, Spain) to RM. Large-scale computing resources were provided by the Canarian Institute of Astrophysics (www.iac.es), through the Barcelona Supercomputer Center
and the Spanish Network of Supercomputing (grants BCV-2010-3-0003 and 2011-2-0003/3-0005 to RL and RM). We thank the BioMarKs consortium for undertaking the sampling and performing the initial laboratory processing of the samples, in particular Sarah Romac. We thank Hiroyuki Ogata and Jean-Michel Claverie for the implementation of bioinformatics tools through a BioMarKs grant and a project from the French National Research Agency (ANR-08-BDVA-003) to Jean-Michel Claverie. Javier del Campo is thanked for providing curated Sanger sequences of Ochrophyta. Berit Kaasa at the University of Oslo is thanked for running the nutrient analyses. We thank the three reviewers and the editor who helped to improve this workPeer reviewe
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