The terrestrial chapter of the Circumpolar Biodiversity Monitoring Programme (CBMP) has the potential to bring international multi-taxon, long-term monitoring together, but detailed fundamental species information for Arctic arthropods lags far behind that for vertebrates and plants. In this paper, we demonstrate this major challenge to the CBMP by focussing on spiders (Order: Araneae) as an example group. We collate available circumpolar data on the distribution of spiders and highlight the current monitoring opportunities and identify the key knowledge gaps to address before monitoring can become efficient. We found spider data to be more complete than data for other taxa, but still variable in quality and availability between Arctic regions, highlighting the need for greater international cooperation for baseline studies and data sharing. There is also a dearth of long-term datasets for spiders and other arthropod groups from which to assess status and trends of biodiversity. Therefore, baseline studies should be conducted at all monitoring stations and we make recommendations for the development of the CBMP in relation to terrestrial arthropods more generally.
The Lepidoptera of North America Network, or LepNet, is a digitization effort recently launched to mobilize biodiversity data from 3 million specimens of butterflies and moths in United States natural history collections (http://www.lep-net.org/). LepNet was initially conceived as a North American effort but the project seeks collaborations with museums and other organizations worldwide. The overall goal is to transform Lepidoptera specimen data into readily available digital formats to foster global research in taxonomy, ecology and evolutionary biology.
Dystrobrevin-binding protein 1 (Dtnbp1) is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTNBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-null mutant mice exhibit abnormalities in behaviors and impairments in neuronal activities. However, how diminished DTNBP1 expression contributes to clinical relevant features of schizophrenia remains to be illustrated. Here, using a conditional Dtnbp1 knockout mouse line, we identified an in vivo schizophrenia-relevant function of DTNBP1 in pyramidal neurons of the medial prefrontal cortex (mPFC). We demonstrated that DTNBP1 elimination specifically in pyramidal neurons of the mPFC impaired mouse pre-pulse inhibition (PPI) behavior and reduced perisomatic GABAergic synapses. We further revealed that loss of DTNBP1 in pyramidal neurons diminished activity-dependent secretion of brain-derived neurotrophic factor (BDNF). Finally, we showed that chronic BDNF infusion in the mPFC fully rescued both GABAergic synaptic dysfunction and PPI behavioral deficit induced by DTNBP1 elimination from pyramidal neurons. Our findings highlight brain region- and cell type-specific functions of DTNBP1 in the pathogenesis of schizophrenia, and underscore BDNF restoration as a potential therapeutic strategy for schizophrenia.
The inflammatory response, modulated both by tissue resident macrophages and recruited monocytes from peripheral blood, plays a critical role in human diseases such as cancer and neurodegenerative disorders. Here, we sought a model to interrogate human immune behavior in vivo. We determined that primary human monocytes and macrophages survive in zebrafish for up to two weeks. Flow cytometry revealed that human monocytes cultured at the physiological temperature of the zebrafish survive and differentiate comparable to cohorts cultured at human physiological temperature. Moreover, key genes that encode for proteins that play a role in tissue remodeling were also expressed. Human cells migrated within multiple tissues at speeds comparable to zebrafish macrophages. Analysis of gene expression of in vivo educated human macrophages confirmed expression of activated macrophage phenotypes. Here, human cells adopted phenotypes relevant to cancer progression, suggesting that we can define the real time immune modulation of human tumor cells during the establishment of a metastatic lesion in zebrafish.
Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using magnetic-field driven assembly of paramagnetic colloidal particles functionalized with three types of human ECM proteins found in vivo. We investigated if cells cultured in matrices comprised of fibrils of the same size and arranged in similar geometries will show similar behavior for each of the ECM proteins tested. We were able to resolve spatial heterogeneities in microscale mechanical properties near aligned fibers that were not observed in bulk tissue mechanics. We then used this platform to examine factors contributing to cell alignment in response to topographical cues in 3D laminin-rich matrices. Multiple human cell lines extended protrusions preferentially in directions parallel or perpendicular to aligned fibers independently of the ECM coating. Focal adhesion proteins, as measured by paxillin localization, were mainly diffuse in the cytoplasm, with few puncta localized at the protrusions. Integrin β1 and fascin regulated protrusion extension but not protrusion alignment. Myosin II inhibition did not reduce observed protrusion length. Instead, cells with reduced myosin II activity generated protrusions in random orientations when cultured in hydrogels with aligned fibers. Similarly, myosin II dependence was observed in vivo, where cells no longer aligned along the abluminal surfaces of blood vessels upon treatment with blebbistatin. These data suggest that myosin II can regulate sensing of topography in 3D engineered matrices for both normal and transformed cells.
Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, architecture or topography of the extracellular matrix (ECM), and the repertoire of ECM ligands present, all of which provide cues to drive cellular response. Cell-ECM interactions are important regulators of both normal tissue homeostasis and malignancy.Thus, understanding both extracellular cues and the cellular responses they elicit is fundamental to developing therapeutic strategies. Various in vitro platforms for 3D cell culture and tissue engineering have been used to study cellular response to the microenvironment. However, recapitulating the diversity of tissue architectures present in vivo in a controlled manner in threedimensional tissue mimetics is challenging using naturally derived ECM hydrogels. Here, we use a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using selfassembly of magnetic colloidal particles functionalized with human ECM proteins. Human ECM proteins associated with organ-specific pathological states were used. We determined that, while the bulk tissue mechanics of hydrogels containing either aligned fibers or randomly distributed colloidal particles were similar, aligned hydrogels exhibited spatial heterogeneities in microscale mechanical properties near aligned fibers. We then used this platform in combination with 2D substrates of defined elastic modulus to decouple the role of topography from microscale tissue mechanics for normal and tumor cells. We determined that topographical cues dominate cellular response for human and normal cells, which responded independently of microscale mechanics and ECM composition in 3D hydrogels. These data suggest that topography alone can drive fundamental cellular responses such as polarization and migration for both normal and transformed cells.
If the current rate of climate change continues, the composition, distribution, and relative population sizes of species in the higher latitudes of the Northern Hemisphere are likely to change considerably. Understanding the magnitude of this change requires a well-documented baseline against which to compare. Although specimen-less observations can help augment such a baseline for the minority of organisms that can be confidently identified in the field or from photographs, the vast majority of species are small-bodied invertebrates, primarily arthropods, that can only be identified from preserved specimens and (or) their tissues. Museum staff archive specimens and make them and their data available for research. This paper describes a number of challenges to the goal of thorough documentation of high-latitude arthropod biodiversity and their potential solutions. Examples are provided from ongoing and recently completed research that demonstrates the value of museum specimens and the sharing of their data via global portals like GBIF.org.Key words: Arctic, biodiversity, Arthropoda, monitoring, inventory, taxonomic bottleneck.Résumé : Si le taux actuel du changement climatique se maintient, la composition, la répar-tition et les tailles de population relatives d'espèces dans les latitudes plus hautes de l'hémi-sphère nord sont susceptibles de changer considérablement. Pour comprendre l'ampleur de ce changement, il faut une ligne de référence bien documentée contre laquelle on peut comparer. Bien que les observations sans spécimens puissent aider à augmenter une telle ligne de référence pour la minorité d'organismes qui peuvent être identifiés avec assurance sur le terrain ou à partir de photographies, la grande majorité d'espèces est composée d'inverté-brés à petit corps, principalement des arthropodes, qui ne peuvent être identifiés qu'à partir de spécimens préservés et (ou) de leurs tissus. Le personnel de musées archive les spécimens et les rend disponibles ainsi que les données connexes aux fins de recherche. Dans cet article, on décrit un certain nombre de défis à l'encontre du but de la documentation minutieuse de la biodiversité d'arthropodes à hautes latitudes et les solutions potentielles à ces défis. On fournit des exemples de recherche en cours et récemment complétée qui démontr-ent la valeur de spécimens de musée et le partage de données via des portails mondiaux comme le Système mondial d'informations sur la biodiversité (GBIF.org).
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