Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution

BACKGROUND: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. RESULTS: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. CONCLUSIONS: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates

Experiences of a Novel Structured Foot Examination Form for Patients With Diabetes From the Perspective of Health Care Professionals : Qualitative Study

Background: Diabetes is a growing threat to public health, and secondary diseases like foot complications are common. Foot ulcers affect the individual’s quality of life and are a great cost to society. Regular foot examinations prevent foot ulcers and are a recommended approach both in Sweden and worldwide. Despite existing guidelines, there are differences in the execution of the foot examination, which results in care inequality. A structured foot examination form based on current guidelines was developed in this study as the first step toward digitalized support in the daily routine, and was validated by diabetes health care professionals. Objective: The study aimed to validate a structured foot examination form by assessing health care professionals’ experiences of working with it “foot side” when examining patients with diabetes. Methods: Semistructured interviews were held in a focus group and individually with 8 informants from different diabetes professions, who were interviewed regarding their experiences of working with the form in clinical practice. The users’ data were analyzed inductively using qualitative content analysis. The study is part of a larger project entitled “Optimised care of persons with diabetes and foot complications,” with Västra Götaland Region as the responsible health care authority, where the results will be further developed. Results: Experiences of working with the form were that it simplified the foot examination by giving it an overview and a clear structure. Using the form made differences in work routines between individuals apparent. It was believed that implementing the form routinely would contribute to a more uniform execution. When patients had foot ulcers, the risk categories (established in guidelines) were perceived as contradictory. For example, there was uncertainty about the definition of chronic ulcers and callosities. The expectations were that the future digital format would simplify documentation and elucidate the foot examination, as well as contribute to the accessibility of updated and relevant data for all individuals concerned. Conclusions: The foot examination form works well as a support tool during preventive foot examination, creates a basis for decision-making, and could contribute to a uniform and safer foot examination with more care equality in agreement with current guidelines.CC BY 4.0</p

Proteome- and Transcriptome-Driven Reconstruction of the Human Myocyte Metabolic Network and Its Use for Identification of Markers for Diabetes

Skeletal myocytes are metabolically active and susceptible to insulin resistance and are thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes, and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network context for the integration of high-throughput data. We generated myocyte-specific RNA-sequencing data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the downregulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D

Cold tolerance dataset

This excel-file contains two sheets. The first has data on cold shock tolerance and the second has data on supercooling point of Pieris napi pupae undergoing diapause or direct development. Column headers contain descriptions of coding system. See main article for more information

Data from: Metabolome dynamics of diapause in the butterfly Pieris napi: distinguishing maintenance, termination and post-diapause phases

Diapause is a deep resting stage facilitating temporal avoidance of unfavourable environmental conditions that is used by many insects to adapt their life cycle to seasonal variation. Although considerable work has been invested in trying to understand each of the major diapause stages (induction, maintenance and termination), we know very little about the transitions between stages, especially diapause termination. Understanding diapause termination is critical for modelling and predicting spring emergence and winter physiology of insects, including many pest insects. In order to gain these insights we investigated metabolome dynamics across diapause development in pupae of the butterfly Pieris napi, which exhibits adaptive latitudinal variation in the length of endogenous diapause that is uniquely well characterized. By employing a time-series experiment we show that the whole-body metabolome is highly dynamic throughout diapause and differs between pupae kept at a diapause-terminating (low), or at a diapause-maintaining (high) temperature. We show major physiological transitions through diapause, separated temperature-dependent from temperature-independent processes and identified significant patterns of metabolite accumulation and degradation. Together the data show that while the general diapause phenotype (suppressed metabolism, increased cold tolerance) is established in a temperature-independent fashion, diapause termination is temperature-dependent and requires a cold signal. This revealed several metabolites that are only accumulated in diapause terminating conditions and degraded in a temperature-unrelated fashion during diapause termination. In conclusion, our findings indicate that some metabolites, in addition to functioning as e.g. cryoprotectants, are candidates for having regulatory roles as metabolic clocks or time-keepers during diapause