Formation of body appendages during caudal regeneration in Platynereis dumerilii: adaptation of conserved molecular toolsets

Background: Platynereis and other polychaete annelids with homonomous segmentation are regarded to closely resemble ancestral forms of bilateria. The head region comprises the prostomium, the peristomium, a variable number of cephalized body segments and several appendages, like cirri, antennae and palps. The trunk of such polychaetes shows numerous, nearly identical segments. Each segment bears a parapodium with species-specific morphology on either side. The posterior end of the trunk features a segment proliferation zone and a terminal pygidium with the anus and anal cirri. The removal of a substantial part of the posterior trunk is by no means lethal. Cells at the site of injury dedifferentiate and proliferate forming a blastema to regenerate both the pygidium and the proliferation zone. The pygidium forms new anal cirri, and the proliferation zone generates new segments at a rapid pace. The formation of body appendages like the cirri and the segmental parapodia can thus be studied in the caudal regenerate of Platynereis within only a few days. Results: The development of body appendages in Platynereis is regulated by a network of genes common to polychaetes but also shared by distant taxa. We isolated DNA sequences from P. dumerilii of five genes known to be involved in appendage formation within other groups: Meis/homothorax, Pbx1/extradenticle, Dlx/Distal-less, decapentaplegic and specific protein 1/buttonhead. Analyses of expression patterns during caudal regeneration by in situ hybridization reveal striking similarities related to expression in arthropods and vertebrates. All genes exhibit transient expression during differentiation and growth of segments. As was shown previously in other phyla Pdu-Meis/hth and Pdu-Pbx1/exd are co-expressed, although the expression is not limited to the proximal part of the parapodia. Pdu-Dll is prominent in parapodia but upregulated in the anal cirri. No direct dependence concerning Pdu-Dll and Pdu-sp/btd expression is observed in Platynereis. Pdu-dpp shows an expression pattern not comparable to its expression in other taxa. Conclusions: The expression patterns observed suggest conserved roles of these genes during appendage formation across different clades, but the underlying mechanisms utilizing this toolset might not be identical. Some genes show broad expression along the proximodistal axis indicating a possible role in proximodistal patterning of body appendages. Other genes exhibit expression patterns limited to specific parts and tissues of the growing parapodia, thus presumably being involved in formation of taxon-specific morphological differences

Chemoton 2.0: Autonomous Exploration of Chemical Reaction Networks

Fueled by advances in hardware and algorithm design, large-scale automated explorations of chemical reaction space have become possible. Here, we present our approach to an open-source, extensible framework for explorations of chemical reaction mechanisms based on the first-principles of quantum mechanics. It is intended to facilitate reaction network explorations for diverse chemical problems with a wide range of goals such as mechanism elucidation, reaction path optimization, retrosynthetic path validation, reagent design, and microkinetic modeling. The stringent first-principles basis of all algorithms in our framework is key for the general applicability that avoids any restrictions to specific chemical systems. Such an agile framework requires multiple specialized software components of which we present three modules in this work. The key module, Chemoton, drives the exploration of reaction networks. For the exploration itself, we introduce two new algorithms for elementary-step searches that are based on Newton trajectories. The performance of these algorithms is assessed for a variety of reactions characterized by a broad chemical diversity in terms of bonding patterns and chemical elements. Chemoton successfully recovers the vast majority of these. We provide the resulting data, including large numbers of reactions that were not included in our reference set, to be used as a starting point for further explorations and for future reference.ISSN:1549-9618ISSN:1549-962

qcscine/molassembler: Release 2.0.1

<p>Changes:</p> <ul> <li>Update address in license</li> </ul&gt

qcscine/xtb_wrapper: Release 3.0.0

<p>Changes:</p> <ul> <li>Enable external point charges for QM/MM</li> <li>Update address in license</li> </ul&gt

qcscine/puffin: Release 1.3.0

<p>Changes:</p><ul><li>Store found elementary step even if none of the endpoints corresponds to the initial starting structures</li><li>Add restart information with valid TS for jobs trying to find new elementary steps, where the IRC failed to produce different endpoints </li><li>Consider potential surface structures for label determination of new structures </li><li>Logic to transfer indices information and other complex properties from reactants to products </li><li>Save close lying spin multiplicities and allow to manipulate exact spin propensity check behavior with added settings </li><li>Microkinetic modeling with the program Reaction Mechanism Simulator. </li><li>AMS via SCINE AMS Wrapper </li><li>MRCC (release version March 2022) </li><li>Ensure that only_distance_connectivity is adhered in all reaction jobs </li><li>Update address in license</li></ul&gt

Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss

Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata511 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata511 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype