Identification of long non-coding RNAs involved in neuronal development and intellectual disability

Recently, exome sequencing led to the identification of causal mutations in 16–31% of patients with intellectual disability (ID), leaving the underlying cause for many patients unidentified. In this context, the noncoding part of the human genome remains largely unexplored. For many long non-coding RNAs (lncRNAs) a crucial role in neurodevelopment and hence the human brain is anticipated. Here we aimed at identifying lncRNAs associated with neuronal development and ID. Therefore, we applied an integrated genomics approach, harnessing several public epigenetic datasets. We found that the presence of neuron-specific H3K4me3 confers the highest specificity for genes involved in neurodevelopment and ID. Based on the presence of this feature and GWAS hits for CNS disorders, we identified 53 candidate lncRNA genes. Extensive expression profiling on human brain samples and other tissues, followed by Gene Set Enrichment Analysis indicates that at least 24 of these lncRNAs are indeed implicated in processes such as synaptic transmission, nervous system development and neurogenesis. The bidirectional or antisense overlapping orientation relative to multiple coding genes involved in neuronal processes supports these results. In conclusion, we identified several lncRNA genes putatively involved in neurodevelopment and CNS disorders, providing a resource for functional studies

The SLS-Berlin: Validation of a German Computer-Based Screening Test to Measure Reading Proficiency in Early and Late Adulthood

Reading proficiency, i.e., successfully integrating early word-based information and utilizing this information in later processes of sentence and text comprehension, and its assessment is subject to extensive research. However, screening tests for German adults across the life span are basically non-existent. Therefore, the present article introduces a standardized computerized sentence-based screening measure for German adult readers to assess reading proficiency including norm data from 2,148 participants covering an age range from 16 to 88 years. The test was developed in accordance with the children’s version of the Salzburger LeseScreening (SLS, Wimmer and Mayringer, 2014). The SLS-Berlin has a high reliability and can easily be implemented in any research setting using German language. We present a detailed description of the test and report the distribution of SLS-Berlin scores for the norm sample as well as for two subsamples of younger (below 60 years) and older adults (60 and older). For all three samples, we conducted regression analyses to investigate the relationship between sentence characteristics and SLS-Berlin scores. In a second validation study, SLS-Berlin scores were compared with two (pseudo)word reading tests, a test measuring attention and processing speed and eye-movements recorded during expository text reading. Our results confirm the SLS-Berlin’s sensitivity to capture early word decoding and later text related comprehension processes. The test distinguished very well between skilled and less skilled readers and also within less skilled readers and is therefore a powerful and efficient screening test for German adults to assess interindividual levels of reading proficiency

Other city symphonies

Catalogue description of the film program curated by Eva Hielscher and Steven Jacobs on 'Other City Symphonies' during the 2015 Pordenone Silent Film Festival, including paragraphs on individual films

Spinal aging

The age distribution of the global population is shifting upwards. As a result, clinicians worldwide are faced with an increasing number of spinal disorders related to the elderly and spinal aging. Spinal pathology in the elderly specifically includes osteoporosis and osteoporotic vertebral compression fractures and degenerative spinal deformity. The impact of spinal disorders on health-related quality of life is more severe than the impact of many common diseases, such as cardiovascular diseases or type 2 diabetes. Spinal disorders affect more than 1.7 billion people worldwide and represent significant economic costs to society by the utilization of vast amounts of healthcare resources and by indirect costs such as loss of productivity. With the aging of our population the burden of spinal disorders on society is estimated to increase even further. Spinal aging encompasses a set of spinal disorders which are complex and heterogeneous with highly individualized surgical planning. As this patient category is associated with multiple medical comorbidities, decreased mobility, poor balance, and a greater propensity to falling, more patient tailored and multidisciplinary treatment strategies will be needed. Due to the confluence of an aging population and an increased capacity and willingness by the spinal community to manage difficult problems in older patients, it is essential that, when designing and implementing therapeutic strategies, clinicians must consider all of these factors. By shared decision making, medical and technical knowledge from surgeons is combined with values and preferences from patients in order to achieve effective and safe treatment modalities and ensure adequate patient support. This thesis addresses both clinical and preclinical aspects of spinal aging. In anticipation of an aging population, the main motivation of this thesis was to emphasize the significant and growing burden of spinal disorders in the elderly; to optimize current conservative and operative treatment for spinal aging; and to argue that allocation of resources to the management of spinal disorders should be a priority for our healthcare economy

CRISPR/Cas9-mediated genome editing in naïve human embryonic stem cells

The combination of genome-edited human embryonic stem cells (hESCs) and subsequent neural differentiation is a powerful tool to study neurodevelopmental disorders. Since the naive state of pluripotency has favourable characteristics for efficient genome-editing, we optimized a workflow for the CRISPR/Cas9 system in these naive stem cells. Editing efficiencies of respectively 1.3-8.4% and 3.819% were generated with the Cas9 nuclease and the D10A Cas9 nickase mutant. Next to this, wildtype and genome-edited naive hESCs were successfully differentiated to neural progenitor cells. As a proofof- principle of our workflow, two monoclonal genome-edited naive hESCs colonies were obtained for TUNA, a long non-coding RNA involved in pluripotency and neural differentiation. In these genome-edited hESCs, an effect was seen on expression of TUNA, although not on neural differentiation potential. In conclusion, we optimized a genome-editing workflow in naive hESCs that can be used to study candidate genes involved in neural differentiation and/or functioning

A Diffusion Model Analysis

Effects of stimulus length on reaction times (RTs) in the lexical decision task are the topic of extensive research. While slower RTs are consistently found for longer pseudo-words, a finding coined the word length effect (WLE), some studies found no effects for words, and yet others reported faster RTs for longer words. Moreover, the WLE depends on the orthographic transparency of a language, with larger effects in more transparent orthographies. Here we investigate processes underlying the WLE in lexical decision in German-English bilinguals using a diffusion model (DM) analysis, which we compared to a linear regression approach. In the DM analysis, RT-accuracy distributions are characterized using parameters that reflect latent sub-processes, in particular evidence accumulation and decision-independent perceptual encoding, instead of typical parameters such as mean RT and accuracy. The regression approach showed a decrease in RTs with length for pseudo-words, but no length effect for words. However, DM analysis revealed that the null effect for words resulted from opposing effects of length on perceptual encoding and rate of evidence accumulation. Perceptual encoding times increased with length for words and pseudo-words, whereas the rate of evidence accumulation increased with length for real words but decreased for pseudo-words. A comparison between DM parameters in German and English suggested that orthographic transparency affects perceptual encoding, whereas effects of length on evidence accumulation are likely to reflect contextual information and the increase in available perceptual evidence with length. These opposing effects may account for the inconsistent findings on WLEs

Gait in patients with symptomatic osteoporotic vertebral compression fractures over 6 months of recovery

BACKGROUND: One factor related to disability in people with spinal deformity is decreased postural control and increased risk of falling. However, little is known about the effect of osteoporotic vertebral compression fractures (OVCFs) and their recovery on gait and stability. Walking characteristics of older adults with and without vertebral fractures have not yet been compared. AIMS: The purpose of the current study was to examine the spatiotemporal gait parameters and their variability in patients with an OVCF and healthy participants during treadmill walking at baseline and after 6 months of recovery. METHODS: Twelve female patients suffering a symptomatic OVCF were compared to 11 matched controls. Gait analysis was performed with a dual-belt instrumented treadmill with a 180° projection screen providing a virtual environment (computer-assisted rehabilitation environment). Results of patients with an OVCF and healthy participants were compared. Furthermore, spatiotemporal gait parameters were assessed over 6 months following the fracture. RESULTS: Patients suffering from an OVCF appeared to walk with significantly shorter, faster and wider strides compared to their healthy counterparts. Although stride time and length improved over time, the majority of the parameters analysed remained unchanged after 6 months of conservative treatment. DISCUSSION: Since patients do not fully recover to their previous level of mobility after 6 months of conservative treatment for OVCF, it appears of high clinical importance to add balance and gait training to the treatment algorithm of OVCFs. CONCLUSIONS: Patients suffering from an OVCF walk with shorter, faster and wider strides compared to their healthy counterparts adopt a less stable body configuration in the anterior direction, potentially increasing their risk of forward falls if perturbed. Although stride time and stride length improve over time even reaching healthy levels again, patients significantly deviate from normal gait patterns (e.g. in stability and step width) after 6 months of conservative treatment