Multi-scale structures of the mammalian radial spoke and divergence of axonemal complexes in ependymal cilia.

Radial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. Atomic-resolution structures of metazoan RS and structures of axonemal complexes in ependymal cilia, whose rhythmic beating drives the circulation of cerebrospinal fluid, however, remain obscure. Here, we present near-atomic resolution cryo-EM structures of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic flexibility of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the cryo-ET and sub-tomogram averaging map of mouse ependymal cilia and build the models for RS1-3, IDAs, and N-DRC. Contrary to the conserved RS structure, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of Tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella, further exemplifying the structural diversity of mammalian motile cilia. Our findings shed light on the stepwise mammalian RS assembly mechanism, the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understanding on the etiology of ciliary dyskinesia-related ciliopathies and on the ependymal cilia in the development of hydrocephalus.

Rationalized deep learning super-resolution microscopy for sustained live imaging of rapid subcellular processes.

The goal when imaging bioprocesses with optical microscopy is to acquire the most spatiotemporal information with the least invasiveness. Deep neural networks have substantially improved optical microscopy, including image super-resolution and restoration, but still have substantial potential for artifacts. In this study, we developed rationalized deep learning (rDL) for structured illumination microscopy and lattice light sheet microscopy (LLSM) by incorporating prior knowledge of illumination patterns and, thereby, rationally guiding the network to denoise raw images. Here we demonstrate that rDL structured illumination microscopy eliminates spectral bias-induced resolution degradation and reduces model uncertainty by five-fold, improving the super-resolution information by more than ten-fold over other computational approaches. Moreover, rDL applied to LLSM enables self-supervised training by using the spatial or temporal continuity of noisy data itself, yielding results similar to those of supervised methods. We demonstrate the utility of rDL by imaging the rapid kinetics of motile cilia, nucleolar protein condensation during light-sensitive mitosis and long-term interactions between membranous and membrane-less organelles.

Improving biomedical named entity recognition by dynamic caching inter-sentence information.

MOTIVATION: Biomedical Named Entity Recognition (BioNER) aims to identify biomedical domain-specific entities (e.g. gene, chemical and disease) from unstructured texts. Despite deep learning-based methods for BioNER achieving satisfactory results, there is still much room for improvement. Firstly, most existing methods use independent sentences as training units and ignore inter-sentence context, which usually leads to the labeling inconsistency problem. Secondly, previous document-level BioNER works have approved that the inter-sentence information is essential, but what information should be regarded as context remains ambiguous. Moreover, there are still few pre-training-based BioNER models that have introduced inter-sentence information. Hence, we propose a cache-based inter-sentence model called BioNER-Cache to alleviate the aforementioned problems. RESULTS: We propose a simple but effective dynamic caching module to capture inter-sentence information for BioNER. Specifically, the cache stores recent hidden representations constrained by predefined caching rules. And the model uses a query-and-read mechanism to retrieve similar historical records from the cache as the local context. Then, an attention-based gated network is adopted to generate context-related features with BioBERT. To dynamically update the cache, we design a scoring function and implement a multi-task approach to jointly train our model. We build a comprehensive benchmark on four biomedical datasets to evaluate the model performance fairly. Finally, extensive experiments clearly validate the superiority of our proposed BioNER-Cache compared with various state-of-the-art intra-sentence and inter-sentence baselines. AVAILABILITYAND IMPLEMENTATION: Code will be available at https://github.com/zgzjdx/BioNER-Cache. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Parental centrioles are dispensable for deuterosome formation and function during basal body amplification.

Mammalian epithelial cells use a pair of parental centrioles and numerous deuterosomes as platforms for efficient basal body production during multiciliogenesis. How deuterosomes form and function, however, remain controversial. They are proposed to arise either spontaneously for massive de novo centriole biogenesis or in a daughter centriole-dependent manner as shuttles to carry away procentrioles assembled at the centriole. Here, we show that both parental centrioles are dispensable for deuterosome formation. In both mouse tracheal epithelial and ependymal cells (mTECs and mEPCs), discrete deuterosomes in the cytoplasm are initially procentriole-free. They emerge at widely dispersed positions in the cytoplasm and then enlarge, concomitant with their increased ability to form procentrioles. More importantly, deuterosomes still form efficiently in mEPCs whose daughter centriole or even both parental centrioles are eliminated through shRNA-mediated depletion or drug inhibition of Plk4, a kinase essential to centriole biogenesis in both cycling cells and multiciliated cells. Therefore, deuterosomes can be assembled autonomously to mediate de novo centriole amplification in multiciliated cells.

Two new brackish-water species of Macrostomum (Platyhelminthes, Macrostomida) from mangrove wetland in southern China.

In this paper, two new brackish-water species of Macrostomum (M. shenzhenensis n. sp. and M qiaochengensis n. sp.) collected from the artificial lake in Overseas Chinese Town mangrove wetland, are described based on the morphology of the penis stylet and on a molecular phylogenetic analysis. M. shenzhenensis n. sp. has an elongate, narrow stylet with torus-shaped distal wall thickening, while M. qiaochengensis n. sp. has a hook-like stylet with a pointed end. Both the 18S and 28S rDNA phylogenetic analyses of M shenzhenensis n. sp. and M qiaochengensis n. sp. support the establishments of these two new species. Finally, categorization of these two new species based on the morphology of sperm and penis stylet, as well as other morphological features of the reproductive system is briefly discussed.

Two new species of brackish-water Macrostomum (Platyhelminthes, Macrostomida) from southern China.

Two new species of brackish-water Macrostomum (M. zhujiangensis n. sp. and M. baoanensis n. sp.) were described based on samples collected from the littoral zone of the Zhujiang Estuary. These are the first records of brackish-water Macrostomum from southern China. Macrostomum zhujiangensis n. sp. and M. baoanensis n. sp. differ from other similar species in the length and morphology of the penis stylet.  The penis stylet of M. zhujiangensis n. sp. is C-shaped and its distal opening has a beveled edge. The penis stylet of M. baoanensis n. sp. is J-shaped and the distal region is thicker than other parts of the penis stylet. Molecular phylogenetic analysis supports the establishment of the new species.