Biology subjects

Weiss, M.

Publications and source records attributed to Weiss, M..

45 records · Page 3Linked to original sources

bioRxiv2021

The Serine Protease HtrA2 mediates radiation-induced senescence in cancer cells

Radiation therapy can induce cellular senescence in cancer cells leading to short-term tumor growth arrest, yet increased long-term recurrence. To better understand the molecular mechanisms involved, we developed a model of radiation-induced senescence in cultured cancer cells, which exhibited a typical senescent phenotype, including upregulation of p53 and its target p21, followed by sustained reduction in cellular proliferation, changes in cell size and cytoskeleton organization, and senescence-associated beta-galactosidase activity. A functional siRNA screen using a cell death-related library identified the mitochondrial Ser protease HtrA2 as necessary for senescence development. Mass spectrometry-based proteomic profiling of the senescent cells indicated downregulation of proteins involved in cell cycle progression and DNA repair, and upregulation of proteins associated with malignancy, while irradiation with HtrA2 inhibition upregulated cell proliferation components. In search of direct HtrA2 substrates following radiation, we determined that HtrA2 cleaves the intermediate filament protein vimentin, affecting its cytoplasmic organization. Ectopic expression of active cytosolic HtrA2 resulted in similar changes to vimentin filament assembly. Thus HtrA2, contributes to several hallmarks of senescence and is involved in the cytoskeletal reorganization that accompanies radiation-induced senescence. SummaryHere the authors identify the Ser protease HtrA2 as a novel mediator of radiation-induced senescence, necessary for sustained proliferation arrest and reorganization of the vimentin filament network.

cancer biology↗

bioRxiv2020

Magnetoencephalographic Signatures of Conscious Processing Before Birth

The concept of fetal consciousness is a widely discussed topic. In this study, we applied a hierarchical rule learning paradigm to investigate the possibility of fetal conscious processing during the last trimester of pregnancy. We used fetal magnetoencephalography, to assess fetal brain activity in 56 healthy fetuses between gestational week 25 and 40, during an auditory oddball paradigm containing first- and second-order regularities. The comparison of fetal brain responses towards standard and deviant tones revealed that the investigated fetuses show signs of hierarchical rule learning, and thus the formation of a memory trace for the second-order regularity. This ability develops over the course of the last trimester of gestation, in accordance with processes in physiological brain development and was only reliably present in fetuses older than week 35 of gestation. Analysis of fetal autonomic nervous system activity replicates findings in newborns, showing importance of activity state for cognitive processes. On the whole, our results support the assumption that fetuses in the last weeks of gestation are capable of consciously processing stimuli that reach them from outside the womb.

neuroscience↗

bioRxiv2020

Small in-stream barriers contribute little to strong local population genetic structure in five hololimnic macroinvertebrate taxa

Water flow in river networks is frequently regulated by man-made in-stream barriers. These obstacles can hinder dispersal of aquatic organisms and isolate populations leading to the loss of genetic diversity. Although millions of small in-stream barriers exist worldwide, such as weirs below 2 m or tunnels and pipes, their impact on the dispersal of macroinvertebrates with strictly aquatic life cycles is unclear. We therefore assessed the effects of such barriers on the population structure and effective dispersal of five macroinvertebrate species with strictly aquatic life cycles: the amphipod crustacean Gammarus fossarum (clade 11), three snail species of the Ancylus fluviatilis species complex and the flatworm Dugesia gonocephala. We studied populations at nine weirs and eight culverts (3 pipes, 5 tunnels), built 33-109 years ago, in the heavily fragmented catchment of the river Ruhr (Sauerland, Germany). To assess fragmentation and barrier effects, we generated genome-wide SNP data using ddRAD sequencing and evaluated clustering, differentiation between populations up- and downstream of each barrier and effective migration rates among sites and across barriers. Additionally, we applied population genomic simulations to assess expected differentiation patterns under different gene flow scenarios. Our data show that populations of all species are highly isolated at regional and local scales within few kilometres. While the regional population structure likely results from historical processes, the strong local differentiation suggests that contemporary dispersal barriers exist. However, we identified significant barrier effects only for pipes (for A. fluviatilis II and III) and few larger weirs (>1.3 m; for D. gonocephala). Therefore our data suggest that most small in-stream barriers can probably be overcome by all studied taxa frequently enough to prevent fragmentation. Thus, the barriers leading to population isolation after few kilometres still need to be identified. Specifically, it remains to be tested if the strong local differentiation is a result of a cumulative effect of small barriers, or if e.g. larger in-stream barriers, land use, chemical pollution, urbanisation, or a combination of these factors impede gene flow.

ecology↗

bioRxiv2020

Sublethal concentrations of clothianidin affect honey bee colony behavior and interact with landscapes to affect colony growth

Honey bee colonies were exposed to sublethal concentrations (5 and 20 ppb) of clothianidin in sugar syrup, while control colonies were fed syrup with no pesticide. In addition to standard colony assessments of adult bees and brood, hive weight and internal temperature were monitored on a continuous basis at all sites. Experiments were conducted twice in Arizona, in successive years at the same site, and once in Mississippi, to examine the concomitant effects of weather and landscape. Adult bee masses at the Arizona site were significantly affected by clothianidin concentration. Newly-emerged bee dry weights, measured only at the Arizona site, were significantly lower for colonies fed 5 ppb clothianidin compared to the other groups. CO2 concentration, also only measured at the Arizona site, was higher in colonies fed 20 ppb clothianidin. Neither daily hive weight change nor colony thermoregulation were affected by clothianidin exposure. The Mississippi site had higher rainfall, more diverse land use, and a different temperature regime, and bee colonies there did not show any effects of clothianidin. These results suggest that bee colonies in more stressful environments, such as the Sonoran desert of southern Arizona, are affected more by clothianidin exposure than colonies at sites with higher rainfall and more forage. Clothianidin was also found to be, like imidacloprid, highly stable in honey in the hive environment at least over several months. These results also showed that CO2 concentration within the hive is potentially valuable in measuring the effects of stressors on bee health.

ecology↗

bioRxiv2020

Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns

Estimating the extent to which newborn humans process input from their environment, especially regarding the depth of processing, is a challenging question. To approach this problem, we measured brain responses in 20 newborns with magnetoencephalography (MEG) in a "local-global" auditory oddball paradigm in which two-levels of hierarchical regularities are presented. Results suggest that infants in the first weeks of life are able to learn hierarchical rules, yet a certain level of vigilance seems to be necessary. Newborns detected violations of the first-order regularity and displayed a mismatch response between 200-400ms. Violations of the second-order regularity only evoked a late response in newborns in an active state, which was expressed by a high heart rate variability. These findings are in line with those obtained in human adults and older infants suggesting a continuity in the functional architecture from term- birth on, despite the important immaturity of the human brain at this age.

neuroscience↗

bioRxiv2020

Can metabarcoding resolve intraspecific genetic diversity changes to environmental stressors? A test case using river macrozoobenthos

Genetic diversity is the most basal level of biodiversity and determines the evolutionary capacity of species to adapt to changing environments, yet it is typically neglected in routine biomonitoring and stressor impact assessment. For a comprehensive analysis of stressor impacts on genetic diversity, it is necessary to assess genetic variants simultaneously in many individuals and species. Such an assessment is not as straight-forward and usually limited to one or few individual species. However, nowadays species diversity can be assessed by analysing thousands of individuals of a community simultaneously with DNA metabarcoding. Recent bioinformatic advances also allow for the extraction of exact sequence variants (ESVs or haplotypes) in addition to Operational Taxonomic Units (OTUs). By using this new capability, we here evaluated if the analysis of mitochondrial genetic diversity in addition to species diversity can provide insights into responses of stream macrozoobenthic communities to environmental stressors. For this purpose, we analysed macroinvertebrate bulk samples of three German river systems with different stressor levels using DNA metabarcoding. While OTU and haplotype number were negatively correlated with stressor impact, this association was not as clear when looking at haplotype diversity. Here, stressor responses were only found for sensitive EPT (Ephemeroptera, Plecoptera, Trichoptera) taxa, and those exceedingly resistant to organic stress. An increase in haplotype number per OTU and haplotype diversity of sensitive taxa was observed with an increase in ecosystem quality and stability, while the opposite pattern was detected for pollution resistant taxa. However, this pattern was less prominent than expected based on the strong differences in stressor intensity between sites. To compare genetic diversity among river systems, only OTUs could be used, which were present in all systems. As OTU composition differed strongly between the rivers, this led to the exclusion of a high number of OTUs, especially in diverse river systems of good quality, which potentially diminished the genetic diversity patterns. To better understand responses of genetic diversity to environmental stressors for example in river ecosystems, it would be important to increase OTU overlap between sites of comparisons, e.g. by sampling a narrower stressor gradient, and to perform calibrated studies controlling for the number and individual genotypes. However, this pioneer study shows that the extraction of haplotypes from DNA metabarcoding datasets is a promising tool to simultaneously assess mitochondrial genetic diversity changes in response to environmental impacts for a metacommunity.

molecular biology↗

bioRxiv2018

Effects of exposure to sublethal concentrations of methoxyfenozide on honey bee colony activity and thermoregulation

Methoxyfenozide is an insect growth regulator (IGR) commonly used in agricultural to simultaneously control pests and preserve beneficial insect populations; however, its impact on honey bees in not fully understood. We conducted field and laboratory experiments to investigate bee health in response to field-relevant doses of this pesticide. Significant effects were observed in honey bee colony flight activity and thermoregulation after being treated with methoxyfenozide. Data collected indicated that hives fed 500 ppb methoxyfenozide treated pollen patty had: 1) a significantly reduced rate of daily hive weight loss due to forager departure at the start of the colonys daily activity; 2) the end of the colonys daily activity delayed by 17-21 minutes compared to Control; and 3) higher temperature variability during the winter. Colonies in the 125 ppb treatment group had fewer differences with the Control group, but did show a delay in the foraging end time by 30-46 minutes compared to the Control. Bee colony metrics of adult bee mass and brood surface area, and individual bee measurements of head weight, newly-emerged bee weight, and hypopharyngeal gland size were not significantly affected by the methoxyfenozide exposure levels of our experiments. An experiment conducted using the same treatment groups in the spring resulted in fewer differences among groups than did the experiments conducted in the fall. Analyses of methoxyfenozide concentrations in the treatment patty, wax, and bee bread showed that: 1) observed methoxyfenozide concentrations were about 18-60% lower than the calculated concentrations; 2) no residues were observed in wax in any treatment; and 3) methoxyfenozide was detected in stored bee bread in the 500 ppb treatment, at concentrations about 1-2.5% of the observed concentration for that treatment. These results suggest that there may be significant effects on honey bee colony behavior (and possibly health) in the field that are difficult to detect through traditional hive inspections and individual metrics.

zoology↗

bioRxiv2018

Diffusion of exit sites on the endoplasmic reticulum - a random walk on a shivering backbone

Major parts of the endoplasmic reticulum (ER) in eukaryotic cells are organized as a dynamic network of membrane tubules connected by three-way junctions. On this network, self-assembled membrane domains, called ER exit sites (ERES), provide platforms at which nascent cargo proteins are packaged into vesicular carriers for subsequent transport along the secretory pathway. While ERES appear stationary and spatially confined on long time scales, we show here via single-particle tracking that they exhibit a microtubule-dependent anomalous diffusion behavior on short and intermediate time scales. By quantifying key parameters of their random walk, we show that the subdiffusive motion of ERES is distinct from that of ER junctions, i.e. ERES are not tied to junctions but rather are mobile on ER tubules. We complement and corroborate our experimental findings with model simulations that also indicate that ERES are not actively moved by microtubules. Altogether, our study shows that ERES perform a random walk on the shivering ER backbone, indirectly powered by microtubular activity. Similar phenomena can be expected for other domains on subcellular structures, setting a caveat for the interpretation of domain tracking data.

biophysics↗

bioRxiv2017

Assessment of asymmetric cell divisions in the early development of Caenorhabditis elegans

Asymmetric cell divisions are of fundamental importance for developmental processes, e.g. for the generation of founder cells. Prime examples are asymmetric cell divisions in the P lineage during early embryogenesis of the model organism Caenorhabditis elegans. However, due to a lack of quantitative data it has remained unclear how frequent unequal daughter cell sizes emerge in the nematodes early embryogenesis, and whether these originate from sterical or biochemical cues. Using quantitative light-sheet microscopy, we have found that about 40% of all cell divisions in C. elegans until gastrulation generate daughter cells with significantly different volumes. Removing the embryos rigid eggshell revealed asymmetric divisions in somatic cells to be primarily induced by steric effects. Division asymmetries in the germline remained unaltered and were correctly reproduced by a model based on a cell-size independent, eccentric displacement of the metaphase plate. Our data suggest asymmetric cell divisions to be essential for establishing important cell-cell interactions that eventually fuel a successful embryogenesis.\n\nSummary statementAbout 40% of all cell divisions in early C. elegans embryogenesis are found to be asymmetric. A cell-size independent displacement of the mitotic spindle explains division asymmetries in the germline whereas the confining eggshell induces asymmetries of somatic cells.

developmental biology↗