Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia

Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish diseaseassociated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey(Macaca fascicularis) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral,neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging(MRI), behavioral tasks, flash visual evoked potentials(FVEP),electroretinogram(ERG), optical coherence tomography(OCT), and whole-genome sequencing(WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway.Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion,natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system,especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.

Identification of Genetic Variants Underlying Anxiety and Multiple Sclerosis in Heterogeneous Stock Rats

Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats with sequence data from the progenitors of the population made it possible to identify causal variants and genes for a large number of phenotypes. We identified 355 genomic loci contributing to 122 measures relevant to six models of disease, including fear-related behaviors and experimental autoimmune encephalomyelitis. At 35 of those loci we identified the responsible gene, and in some cases, the responsible variant.

Candidate genes underlying QTL for flowering time and their interactions in a wide spring barley(Hordeum vulgare L.) cross

Response to vernalization and photoperiod are the main determinants controlling the time to flowering in temperate cereals. While the individual genes that determine a plant's response to these environmental signals are well characterized, the combinatorial effect on flowering time of allelic variants for multiple genes remains unresolved. This study investigated the genetic control of flowering-time in a biparental population of spring barley, derived from a wide cross between a late-flowering European and an early-flowering North-American cultivar. While the major flowering time genes are not segregating in the Beka ×Logan cross, large variation in flowering was observed. We identified five QTL, with both parents found to contribute early alleles. The catalog of QTL discovered aligns with several candidate genes affecting flowering time in barley. The combination of particular alleles at HvCEN, HvELF3 and HvFT1 in Logan are responsible for the earliness of this cultivar. Interestingly, earliness for flowering could be further enhanced, with Beka found to contribute three early alleles, including a QTL colocating with a HvFD-like gene, suggesting that there are diverse aspects of the flowering-time pathway that have been manipulated in these two cultivars. Epistatic interactions between flowering-time QTL or candidate genes were observed in field data and confirmed under controlled conditions. The results of this study link photoperiod-dependent flowering-time genes with earliness per se genes into a single model, thus providing a unique framework that can be used by geneticists and breeders to optimize flowering time in barley.

Database Commons:A Catalog of Worldwide Biological Databases

Biological databases serve as a global fundamental infrastructure for the worldwide scientific community,which dramatically aid the transformation of big data into knowledge discovery and drive significant innovations in a wide range of research fields.Given the rapid data production,biological databases continue to increase in size and importance.To build a catalog of worldwide biological databases,we curate a total of 5825 biological databases from 8931 publications,which are geographically distributed in 72 countries/regions and developed by 1975 institutions(as of September 20,2022).We further devise a z-index,a novel index to characterize the scientific impact of a database,and rank all these biological databases as well as their hosting institutions and countries in terms of citation and z-index.Consequently,we present a series of statistics and trends of worldwide biological databases,yielding a global perspective to better understand their status and impact for life and health sciences.An up-to-date catalog of worldwide biological databases,as well as their curated meta-information and derived statistics,is publicly available at Database Commons(https://ngdc.cncb.ac.cn/databasecommons/).

Unique,Persistent,Resolvable:Identifiers as the Foundation of FAIR

The FAIR principles describe characteristics intended to support access to and reuse of digital artifacts in the scientific research ecosystem.Persistent,globally unique identifiers,resolvable on the Web,and associated with a set of additional descriptive metadata,are foundational to FAIR data.Here we describe some basic principles and exemplars for their design,use and orchestration with other system elements to achieve FAIRness for digital research objects.

Reliable protocols for whole-mount fluorescent in situ hybridization （FISH） in the pea aphid Acyrthosiphon pisum： A comprehensive survey and analysis

RNA in situ hybridization （ISH）, including chromogenic ISH （CISH） and fluorescent ISH （FISH）, has become a powerful tool for revealing the spatial distribution ofgene transcripts in model organisms. Previously, we developed a robust protocol for wholemount RNA CISH in the pea aphid Acyrthosiphon pisum, an emerging insect genomicmodel. In order to improve the resolving capacity of gene detection, we comprehensively surveyed current protocols of whole-mount RNA-FISH and developed protocols that allow,using confocal microscopy, clearer visualization of target messenger RNAs （mRNAs） - including those subcellularly localized and those with spatially overlapping expression. Wefind that Fast dye-based substrate fluorescence （SF）, tyramide signal amplification （TSA）, and TSA Plus all enable identifying gene expression thanks to multiplex amplificationof fluorescent signals. By contrast, methods of direct fluorescence （DF） do not allow visualizing signals. Detection of a single gene target was achieved with SF and TSA Plusfor most mRNAs, whereas TSA only allowed visualization of abundant transcripts such as Apvasl andAppiwi2 in the germ cells. For detection of multiple gene targets using doubleFISH, we recommend： （i） TSA/TSA, rather than TSA Plus/TSA Plus for colocalized mRNAs abundantly expressed in germ ceils, as proteinase K treatment can be omitted;and （ii） SF/TSA Plus for other gene targets such as Apenl and Apen2 as inactivation of enzyme conjugates is not required. SF/SF is not ideal for double FISH experiments due tosignal blurring. Based on these new conditions for RNA-FISH, we have obtained a better understanding of germline specification and embryonic segmentation in the pea aphid.We anticipate that the RNA-FISH protocols for the pea aphid may also be used for other aphids and possibly other insect species, thus expanding the range of species from whichuseful insights into development and evolution may be obtained.

Quality Matters:Biocuration Experts on the Impact of Duplication and Other Data Quality Issues in Biological Databases

Introduction Biological databases represent an extraordinary collective volume of work.Diligently built up over decades and comprising many millions of contributions from the biomedical research community,biological databases provide worldwide access to a massive number of records(also known as entries)[1].Starting from individual laboratories,genomes are sequenced.

Making Canonical Workflow Building Blocks Interoperable across Workflow Languages

We introduce the concept of Canonical Workflow Building Blocks(CWBB),a methodology of describing and wrapping computational tools,in order for them to be utilised in a reproducible manner from multiple workflow languages and execution platforms.The concept is implemented and demonstrated with the BioExcel Building Blocks library(BioBB),a collection of tool wrappers in the field of computational biomolecular simulation.Interoperability across different workflow languages is showcased through a protein Molecular Dynamics setup transversal workflow,built using this library and run with 5 different Workflow Manager Systems(WfMS).We argue such practice is a necessary requirement for FAIR Computational Workflows and an element of Canonical Workflow Frameworks for Research(CWFR)in order to improve widespread adoption and reuse of computational methods across workflow language barriers.

FAIR Principles:Interpretations and Implementation Considerations

The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.