Biology subjects

Seemann, J.

Publications and source records attributed to Seemann, J..

3 recordsLinked to original sources

bioRxiv2020

TPX2 activation by GM130 controls astral microtubule formation and spindle orientation

Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The correct orientation of the mitotic spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates the astral microtubule network. TPX2 in the spindle pole area is activated by GM130 on mitotic Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin binding. During mitosis, phosphorylation of importin at Serine 62 by Cdk1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin S62A impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130-importin -TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin is regulated by Cdk1 phosphorylation.

cell biology↗

bioRxiv2019

Towards ecologically valid biomarkers: real-life gait assessment in cerebellar ataxia

BACKGROUNDWith disease-modifying drugs on the horizon for degenerative ataxias, motor biomarkers are highly warranted. While ataxic gait and its treatment-induced improvements can be captured in laboratory-based assessments, quantitative markers of ataxic gait in real life will help to determine ecologically meaningful improvements.\n\nOBJECTIVESTo unravel and validate markers of ataxic gait in real life by using wearable sensors.\n\nMETHODSWe assessed gait characteristics of 43 patients with degenerative cerebellar disease (SARA:9.4{+/-}3.9) compared to 35 controls by 3 body-worn inertial sensors in three conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n=21). Movement analysis focussed on measures of movement smoothness and spatio-temporal step variability.\n\nRESULTSA set of gait variability measures was identified which allowed to consistently identify ataxic gait changes in all three conditions. Lateral step deviation and a compound measure of step length categorized patients against controls in real life with a discrimination accuracy of 0.86. Both were highly correlated with clinical ataxia severity (effect size {rho}=0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the SARAp&g subscore, with highest effect sizes for real-life walking (d=0.67).\n\nCONCLUSIONSWe identified measures of ataxic gait that allowed not only to capture the gait variability inherent in ataxic gait in real life, but also demonstrate high sensitivity to small differences in disease severity - with highest effect sizes in real-life walking. They thus represent promising candidates for quantitative motor markers for natural history and treatment trials in ecologically valid contexts.

bioengineering↗

bioRxiv2019

Environmental DNA survey captures patterns of fish and invertebrate diversity across a tropical seascape

Accurate, rapid, and comprehensive biodiversity assessments are critical for investigating ecological processes and supporting conservation efforts. Environmental DNA (eDNA) surveys show promise as a way to effectively characterize fine-scale patterns of community composition, but most studies to date have evaluated its effectiveness in single habitats and for conspicuous taxonomic groups in temperate ecosystems. We tested whether a single PCR survey of eDNA in seawater using a broad metazoan primer could identify differences in community composition between five adjacent habitats at 19 sites across a tropical Caribbean bay in Panama. We paired this effort with visual fish surveys to compare methods for a conspicuous taxonomic group. eDNA revealed a tremendous diversity of animals (8,586 operational taxonomic units), including many small taxa that would be undetected in traditional in situ surveys. Fish comprised only 0.07% of the taxa detected by a broad COI primer, yet included 43 species not observed in the visual survey. eDNA revealed significant differences in fish and invertebrate community composition across adjacent habitats and areas of the bay driven in part by taxa known to be habitat-specialists or tolerant to wave action. Our results demonstrate the ability of broad eDNA surveys to identify biodiversity patterns in the ocean.

ecology↗