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Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case–control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case–control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene.
Why are you looking like that? How the context influences evaluation and processing of human faces
(2013)
Perception and evaluation of facial expressions are known to be heavily modulated by emotional features of contextual information. Such contextual effects, however, might also be driven by non-emotional aspects of contextual information, an interaction of emotional and non-emotional factors, and by the observers’ inherent traits. Therefore, we sought to assess whether contextual information about self-reference in addition to information about valence influences the evaluation and neural processing of neutral faces. Furthermore, we investigated whether social anxiety moderates these effects. In the present functional magnetic resonance imaging (fMRI) study, participants viewed neutral facial expressions preceded by a contextual sentence conveying either positive or negative evaluations about the participant or about somebody else. Contextual influences were reflected in rating and fMRI measures, with strong effects of self-reference on brain activity in the medial prefrontal cortex and right fusiform gyrus. Additionally, social anxiety strongly affected the response to faces conveying negative, self-related evaluations as revealed by the participants’ rating patterns and brain activity in cortical midline structures and regions of interest in the left and right middle frontal gyrus. These results suggest that face perception and processing are highly individual processes influenced by emotional and non-emotional aspects of contextual information and further modulated by individual personality traits.
Purpose
This study investigates the redislocation rate and functional outcome at a minimum follow-up of five years after medial patellofemoral ligament (MPFL) reconstruction with soft tissue patellar fixation for patella instability.
Methods
Patients were retrospectively identified and knees were evaluated for trochlea dysplasia according to Dejour, for presence of patella alta and for presence of cartilage lesion at surgery. At a minimum follow-up of five years, information about an incident of redislocation was obtained. Kujala, Lysholm, and Tegner questionnaires as well as range of motion were used to measure functional outcome.
Results
Eighty-nine knees were included. Follow-up rate for redislocation was 79.8% and for functional outcome 58.4%. After a mean follow-up of 5.8 years, the redislocation rate was 5.6%. There was significant improvement of the Kujala score (68.8 to 88.2, p = 0.000) and of the Lysholm score (71.3 to 88.4, p = 0.000). Range of motion at follow-up was 149.0° (115–165). 77.5% of the knees had patella alta and 52.9% trochlear dysplasia types B, C, or D. Patellar cartilage legions were present in 54.2%. Redislocations occurred in knees with trochlear dysplasia type C in combination with patella alta.
Conclusion
MPFL reconstruction with soft tissue patellar fixation leads to significant improvement of knee function and low midterm redislocation rate. Patients with high-grade trochlear dysplasia should be considered for additional osseous correction.
Fabry disease is an X-linked inherited, progressive disorder of lipid metabolism resulting from the deficient activity of the enzyme α-galactosidase. Enzyme replacement therapy (ERT) with recombinant agalsidase, with intravenous infusions of either agalsidase beta or agalsidase alfa, is available and clinical experience now exceeds 15 years. There are very few randomised, placebo-controlled clinical trials evaluating the outcomes of ERT. Data are often derived from observational, registry-based studies and case reports. Pooled analysis of data from different sources may be limited by the heterogeneity of the patient populations, outcomes and treatment. Therefore, comprehensive systematic literature reviews of unpooled data are needed to determine the effects of ERT on disease outcomes. A systematic literature search was conducted in the Embase and PubMed (MEDLINE) databases to retrieve original articles that evaluated outcomes of ERT in patients with Fabry disease; the outcome data were analysed unpooled. The literature analysis included the full range of published literature including observational studies and case series/case reports. Considerable heterogeneity was found among the studies, with differences in sample size, statistical methods, ERT regimens and patient demographic and clinical characteristics. We have demonstrated the value of performing an unpooled systematic literature review of all published evidence of ERT outcomes in Fabry disease, highlighting that in a rare genetic disorder like Fabry disease, which is phenotypically diverse, different patient populations can require different disease management and therapeutic goals depending on age, genotype, and disease severity/level of organ involvement. In addition, these findings are valuable to guide the design and reporting of new clinical studies.
Wetlands in West Africa are among the most vulnerable ecosystems to climate change. West African wetlands are often freshwater transfer mechanisms from wetter climate regions to dryer areas, providing an array of ecosystem services and functions. Often wetland-specific data in Africa is only available on a per country basis or as point data. Since wetlands are challenging to map, their accuracies are not well considered in global land cover products. In this paper we describe a methodology to map wetlands using well-corrected 250-meter MODIS time-series data for the year 2002 and over a 360,000 km2 large study area in western Burkina Faso and southern Mali (West Africa). A MODIS-based spectral index table is used to map basic wetland morphology classes. The index uses the wet season near infrared (NIR) metrics as a surrogate for flooding, as a function of the dry season chlorophyll activity metrics (as NDVI). Topographic features such as sinks and streamline areas were used to mask areas where wetlands can potentially occur, and minimize spectral confusion. 30-m Landsat trajectories from the same year, over two reference sites, were used for accuracy assessment, which considered the area-proportion of each class mapped in Landsat for every MODIS cell. We were able to map a total of five wetland categories. Aerial extend of all mapped wetlands (class “Wetland”) is 9,350 km2, corresponding to 4.3% of the total study area size. The classes “No wetland”/“Wetland” could be separated with very high certainty; the overall agreement (KHAT) was 84.2% (0.67) and 97.9% (0.59) for the two reference sites, respectively. The methodology described herein can be employed to render wide area base line information on wetland distributions in semi-arid West Africa, as a data-scarce region. The results can provide (spatially) interoperable information feeds for inter-zonal as well as local scale water assessments.
This paper retraces the specific conception of the ‘present’ as manifested in Satyrischer Pilgram, Grimmelshausen’s first published work. In the face of progressively vanishing consciousness of the past terrors of the Thirty Years’ War, the Pilgram devises a program for bringing the experience of a whole generation to the present, thereby saving it for the future. Instead of delivering a general reflection on the nature of war, it suggests to narrate individually experienced “particularities.” It is crucial that all of these experiences are negative, not meant to prompt imitation, but instead rather to build and keep up a stronghold against attitudes and actions of the past.
Background
Herpesviruses can infect a wide range of animal species. Herpes simplex virus 1 (HSV-1) is one of the eight herpesviruses that can infect humans and is prevalent worldwide. Herpesviruses have evolved multiple ways to adapt the infected cells to their needs, but knowledge about these transcriptional and post-transcriptional modifications is sparse.
Results
Here, we show that HSV-1 induces the expression of about 1000 antisense transcripts from the human host cell genome. A subset of these is also activated by the closely related varicella zoster virus. Antisense transcripts originate either at gene promoters or within the gene body, and they show different susceptibility to the inhibition of early and immediate early viral gene expression. Overexpression of the major viral transcription factor ICP4 is sufficient to turn on a subset of antisense transcripts. Histone marks around transcription start sites of HSV-1-induced and constitutively transcribed antisense transcripts are highly similar, indicating that the genetic loci are already poised to transcribe these novel RNAs. Furthermore, an antisense transcript overlapping with the BBC3 gene (also known as PUMA) transcriptionally silences this potent inducer of apoptosis in cis.
Conclusions
We show for the first time that a virus induces widespread antisense transcription of the host cell genome. We provide evidence that HSV-1 uses this to downregulate a strong inducer of apoptosis. Our findings open new perspectives on global and specific alterations of host cell transcription by viruses.
Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA and ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes. This results in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated. In contrast to previous reports, we show that HSV-1 does not inhibit co-transcriptional splicing. Our approach thus substantially advances our understanding of HSV-1 biology and establishes HSV-1 as a model system for studying transcription termination.