Biology subjects

Fischer, M.

Publications and source records attributed to Fischer, M..

81 records · Page 5Linked to original sources

bioRxiv2019

Biodistribution and inflammatory response of intracranial delivery of scintillating nanoparticles

Nanoparticle-based delivery systems have become a popular method for targeting tumors and impermeable tissue with drugs for treatment and imaging markers for biodetection. Nanomaterials are beneficial for medical treatment because they can be modified to have increased stability and carrying capacity, and their size and surface modifications allow them to reach otherwise impenetrable tissue. Localized or systemic injection can be used for delivery of nanoparticles; however, systemic injection without appropriate surface modifications is subjected to uptake by the mononuclear phagocytic system which clears particles from the circulation rapidly limiting their accumulation at target tissue and reducing efficacy. Here we demonstrate the biodistribution of Yttrium oxyorthosilicate nanoparticles doped with Cerium after localized injection to the cerebral cortex as well as the immune response at the site of injection over time.

bioengineering↗

bioRxiv2019

Microbiota differences of the comb jelly Mnemiopsis leidyi in native and invasive sub-populations

The translocation of non-indigenous species around the world, especially in marine systems, is a matter of concern for biodiversity conservation and ecosystem functioning. While specific traits are often recognized to influence establishment success of non-indigenous species, the impact of the associated microbial community for the fitness, performance and invasion success of basal marine metazoans remains vastly unknown. In this study we compared the microbiota community composition of the invasive ctenophore Mnemiopsis leidyi in different native and invasive sub-populations along with characterization of the genetic structure of the host. By 16S rRNA gene amplicon sequencing we showed that the sister group to all metazoans, namely ctenophores, harbored a distinct microbiota on the animal host, which significantly differed across two major tissues, namely epidermis and gastrodermis. Additionally, we identified significant differences between native and invasive sub-populations of M. leidyi, which indicate, that the microbiota community is likely influenced by the genotypic background of the ctenophore. To test the hypothesis that the microbiota is genotypically selected for by the ctenophore host, experiments under controlled environments are required.

microbiology↗

bioRxiv2018

Pain neuroscience education on YouTube: a systematic review

ObjectivesThe Internet in general, and YouTube in particular, is now one of the most popular sources of health-related information. Pain neuroscience education has become a primary tool for managing persistent pain, based in part on the discovery that information about pain can change pain. Our objective was to examine the availability, characteristics, and content of YouTube videos providing pain neuroscience education.\n\nMethodsWe conducted a systematic review of videos on YouTube using the search terms \"pain education\", \"what is pain\", and \"pain brain\" in January 2018. Videos were included if they were in English, were under 10 minutes long, and included information on the neuroscience of pain. Videos were coded for i) descriptive characteristics (e.g., number of views, duration on YouTube), ii) source and style, iii) whether or not they addressed seven pre-determined target concepts of pain neuroscience education (e.g., Pain is not an accurate marker of tissue state), and iv) how engaging they were.\n\nResultsWe found 106 unique videos that met the inclusion criteria. The videos ranged from having four views to over five million views (Mdn = 1163 views), with the three most highly viewed videos accounting for 75% of the total views. Animated videos were much more highly viewed than non-animated videos. Only a small number of videos had been posted by a clearly-identifiable reputable source such as an academic or medical research institution (10%), although a number of videos were posted by healthcare professionals and professional medical societies. For a small number of videos (7%), the source was unclear. We found 17 videos that addressed at least one target concept of pain neuroscience science education, only nine of which were considered to be engaging. The target concept Pain is a brain output was considered to be well addressed by the most videos (N = 11), followed by Pain is a protector (N = 10). We found only one video that adequately addressed all seven target concepts of pain neuroscience education.\n\nDiscussionYouTube contains a variety of videos that practitioners, patients, and families may view to access pain neuroscience education information. A small portion of these videos addressed one or more target concepts of pain neuroscience education in an engaging manner. It is yet to be determined to what extent patients are able to learn information from these videos, to what extent the videos promote behavior change, and thus to what extent the videos may be useful for clinical practice.

scientific communication and education↗

bioRxiv2018

Specific detection of cell-free DNA derived from intestinal epithelial cells using methylation patterns

Epithelial cells of the intestine undergo rapid turnover and are thought to be cleared via stool. Disruption of tissue architecture, as occurs in colorectal cancer (CRC), results in the release of material from dying intestinal epithelial cells to blood. This phenomenon could be utilized for diagnosis and monitoring of intestinal diseases, if circulating cell-free DNA (cfDNA) derived from intestinal cells could be specifically identified. Here we describe two genomic loci that are unmethylated specifically in intestinal epithelial cells, allowing for sensitive and specific detection of DNA derived from such cells. As expected, intestinal DNA is found in stool, but not in plasma, of healthy individuals. Patients with inflammatory bowel disease (IBD) have minimal amounts of intestinal cfDNA in the plasma, whereas patients with advanced CRC show a strong signal. The intestinal markers are not elevated in plasma samples from patients with pancreatic ductal adenocarcinoma (PDAC), and a combination of intestine- and pancreas-specific markers allowed for robust differentiation between plasma cfDNA derived from CRC and PDAC patients. Intestinal DNA markers provide a mutation-independent tool for monitoring intestinal dynamics in health and disease.

developmental biology↗

bioRxiv2018

Molecular mechanisms in fungal fatty acid synthase (FAS) assembly

The fungal fatty acid synthase (fFAS) multienzyme is a barrel-shaped 2.6 MDa complex comprising six times eight catalytic domains. Upon barrel-formation, up to several hundred kDa large polypeptides intertwine to bury about 170,000 [A]2 of protein surface. Functional, regulatory and structural data as well as evolutionary aspects of fFAS have been elucidated during the last decades. Notwithstanding a profound knowledge of this protein family, the biogenesis of the elaborate structure remained elusive. Remarkably, experimental data have recently demonstrated that fFAS self-assembles without the assistance of specific factors. Considering the infinitesimal probability that the barrel-shaped complex forms simply by domains approaching in the correct orientation, we were interested in understanding the sequence of events that have to orchestrate fFAS assembly. Here, we show that fFAS attains its quaternary structure along a pathway of successive domain-domain interactions, which is strongly related to the evolutionary development of this protein family. The knowledge on fFAS assembly may pave the way towards antifungal therapy, and further develops fFAS as biofactory in technological applications.

molecular biology↗

bioRxiv2018

Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of non-invasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in two independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis and overall survival, revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential expression analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume, suggesting this miRNA signature may be applied to monitor disease burden.

cancer biology↗

bioRxiv2017

Strong positive biodiversity-productivity relationships in a subtropical forest experiment

Forest ecosystems contribute substantially to global terrestrial primary productivity and climate regulation, but, in contrast to grasslands, experimental evidence for a positive biodiversity-productivity relationship in highly diverse forests is still lacking1. Here, we provide such evidence from a large forest biodiversity experiment with a novel design2 in subtropical China. Productivity (stand-level tree basal area, aboveground volume and carbon and their annual increment) increased linearly with the logarithm of tree species richness. Additive partitioning3 showed that increasing positive complementarity effects combined with weakening negative selection effects caused a strengthening of the relationship over time. In 2-species mixed stands, complementary effects increased with functional distance and selection effects with vertical crown dissimilarity between species. Understorey shrubs reduced stand-level tree productivity, but this effect of competition was attenuated by shrub species richness, indicating that a diverse understorey may facilitate overall ecosystem functioning. Identical biodiversity-productivity relationships were found in plots of different size, suggesting that extrapolation to larger scales is possible. Our results highlight the potential of multi-species afforestation strategies to simultaneously contribute to mitigation of climate change and biodiversity restoration.

ecology↗

bioRxiv2017

Preliminary results of models to predict areas in the Americas with increased likelihood of Zika virus transmission in 2017.

Numerous Zika virus vaccines are being developed. However, identifying sites to evaluate the efficacy of a Zika virus vaccine is challenging due to the general decrease in Zika virus activity. We compare results from three different modeling approaches to estimate areas that may have increased relative risk of Zika virus transmission during 2017. The analysis focused on eight priority countries (i.e., Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru). The models projected low incidence rates during 2017 for all locations in the priority countries but identified several subnational areas that may have increased relative risk of Zika virus transmission in 2017. Given the projected low incidence of disease, the total number of participants, number of study sites, or duration of study follow-up may need to be increased to meet the efficacy study endpoints.

epidemiology↗

bioRxiv2016

Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes.

The yeast Chd1 protein acts to position nucleosomes across genomes. Here we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state the DNA binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA binding domain with respect to the ATPase domains. The orientation of the DNA-binding domain is mediated by sequences in the N-terminus and mutations to this part of the protein have positive and negative effects on Chd1 activity. These observations indicate that the unfavourable alignment of C-terminal DNA binding region in solution contributes to an auto-inhibited state.

molecular biology↗