Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto-axonal target in late-stage Parkinson's disease

Parkinson's disease (PD) affects a significant proportion of the population over the age of 60 years, and its prevalence is increasing. While symptomatic treatment is available for motor symptoms of PD, non-motor complications such as dementia result in diminished life quality for patients and are far more difficult to treat. In this study, we analyzed PD-associated alterations in the hippocampus of PD patients, since this brain region is strongly affected by PD dementia. We focused on synapses, analyzing the proteome of post-mortal hippocampal tissue from 16 PD cases and 14 control subjects by mass spectrometry. Whole tissue lysates and synaptosomal fractions were analyzed in parallel. Differential analysis combined with bioinformatic network analyses identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Modulation of NPTX1 protein levels in primary hippocampal neuron cultures validated its role in synapse morphology. Our analysis suggests that NPTX1 contributes to synaptic pathology in late-stage PD and represents a putative target for novel therapeutic strategies

Tree recruitment is determined by stand structure and shade tolerance with uncertain role of climate and water relations

Tree regeneration is a key process for long-term forest dynamics, determining changes in species composition and shaping successional trajectories. While tree regeneration is a highly stochastic process, tree regeneration studies often cover narrow environmental gradients only, focusing on specific forest types or species in distinct regions. Thus, the larger-scale effects of temperature, water availability, and stand structure on tree regeneration are poorly understood. We investigated these effects in respect of tree recruitment (in-growth) along wide environmental gradients using forest inventory data from Flanders (Belgium), northwestern Germany, and Switzerland covering more than 40 tree species. We employed generalized linear mixed models to capture the abundance of tree recruitment in response to basal area, stem density, shade casting ability of a forest stand as well as site-specific degree-day sum (temperature), water balance, and plant-available water holding capacity. We grouped tree species to facilitate comparisons between species with different levels of tolerance to shade and drought. Basal area and shade casting ability of the overstory had generally a negative impact on tree recruitment, but the effects differed between levels of shade tolerance of tree recruitment in all study regions. Recruitment rates of very shade-tolerant species were positively affected by shade casting ability. Stem density and summer warmth (degree-day sum) had similar effects on all tree species and successional strategies. Water-related variables revealed a high degree of uncertainty and did not allow for general conclusions. All variables had similar effects independent of the varying diameter thresholds for tree recruitment in the different data sets. Synthesis: Shade tolerance and stand structure are the main drivers of tree recruitment along wide environmental gradients in temperate forests. Higher temperature generally increases tree recruitment rates, but the role of water relations and drought tolerance remains uncertain for tree recruitment on cross-regional scales.ISSN:2045-775

Optimizing the structure of interdisciplinary tumor boards for effective cancer care

Introduction Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.Open-Access-Publikationsfonds 202

DataSheet_1_Optimizing the structure of interdisciplinary tumor boards for effective cancer care.pdf

IntroductionMulti-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements.MethodsIn this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures.ResultsBy changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=DiscussionThere are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.</p