Limb development genes underlie variation in human fingerprint patterns

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized “pattern-block” correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning

Effects of Different Substrates on Lignocellulosic Enzyme Expression, Enzyme Activity, Substrate Utilization and Biological Efficiency of Pleurotus Eryngii

Background/Aims: Pleurotus eryngii is one of the most valued and delicious mushrooms which are commercially cultivated on various agro-wastes. How different substrates affect lignocellulosic biomass degradation, lignocellulosic enzyme production and biological efficiency in Pleurotus eryngii was unclear. Methods and Results: In this report, Pleurotus eryngii was cultivated in substrates including ramie stalks, kenaf stalks, cottonseed hulls and bulrush stalks. The results showed that ramie stalks and kenaf stalks were found to best suitable to cultivate Pleurotus eryngii with the biological efficiency achieved at 55% and 57%, respectively. In order to establish correlations between different substrates and lignocellulosic enzymes expression, the extracellular proteins from four substrates were profiled with high throughput TMT-based quantitative proteomic approach. 241 non-redundant proteins were identified and 74 high confidence lignocellulosic enzymes were quantified. Most of the cellulases, hemicellulases and lignin depolymerization enzymes were highly up-regulated when ramie stalks and kenaf stalks were used as carbon sources. The enzyme activities results suggested cellulases, hemicellulases and lignin depolymerization enzymes were significantly induced by ramie stalks and kenaf stalks. Conclusion: The lignocelluloses degradation, most of the lignocellulosic enzymes expressions and activities of Pleurotus eryngii had positive correlation with the biological efficiency, which depend on the nature of lignocellulosic substrates. In addition, the lignocellulosic enzymes expression profiles during Pleurotus eryngii growth in different substrates were obtained. The present study suggested that most of the lignocellulosic enzymes expressions and activities can be used as tools for selecting better performing substrates for commercial mushroom cultivation

Rational design, synthesis and prospect of biodegradable magnesium alloy vascular stents

Biodegradable magnesium (Mg) alloys are expected to be promising materials for cardiovascular stents (CVS), which can avoid the long-term clinical problems of current CVS, such as in-stent restenosis, late stent thrombosis, etc. Mg alloy stents exhibit superior biocompatibility and tunable biodegradability, compared with conventional permanent metallic stents. However, the poor formability and non-uniform corrosion of Mg alloy stents hinder their clinical application of CVS. This review focuses on the development of Mg alloys for CVS in recent years. According to the results of bibliometric analysis, we analyzed different biodegradable Mg alloy systems. Moreover, the structural design strategies for Mg alloy stents that can reduce the stress concentration, as well as the surface modification methods to control the corrosion behavior and biological performance of Mg alloy stents are also highlighted. At last, this review systematically discussed the potential directions and challenges of biodegradable magnesium stents (BMgS) in cardiovascular fields

De novo variants in the PABP domain of PABPC1 lead to developmental delay

Purpose: The study aimed to investigate the role of PABPC1 in developmental delay (DD). Methods: Children were examined by geneticists and pediatricians. Variants were identified using exome sequencing and standard downstream bioinformatics pipelines. We performed in silico molecular modeling and coimmunoprecipitation to test if the variants affect the interaction between PABPC1 and PAIP2. We performed in utero electroporation of mouse embryo brains to enlighten the function of PABPC1. Results: We describe 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1. Further symptoms were seizures and behavioral disorders. Molecular modeling predicted that the variants are pathogenic and would lead to decreased binding affinity to messenger RNA metabolism-related proteins, such as PAIP2. Coimmunoprecipitation confirmed this because it showed a significant weakening of the interaction between mutant PABPC1 and PAIP2. Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not. Conclusion: Pathogenic variants in the PABP domain lead to DD, possibly because of interference with the translation initiation and subsequently an impaired neurogenesis in cortical development

De novo variants in the PABP domain of PABPC1 lead to developmental delay

Purpose: The study aimed to investigate the role of PABPC1 in developmental delay (DD). Methods: Children were examined by geneticists and pediatricians. Variants were identified using exome sequencing and standard downstream bioinformatics pipelines. We performed in silico molecular modeling and coimmunoprecipitation to test if the variants affect the interaction between PABPC1 and PAIP2. We performed in utero electroporation of mouse embryo brains to enlighten the function of PABPC1. Results: We describe 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1. Further symptoms were seizures and behavioral disorders. Molecular modeling predicted that the variants are pathogenic and would lead to decreased binding affinity to messenger RNA metabolism-related proteins, such as PAIP2. Coimmunoprecipitation confirmed this because it showed a significant weakening of the interaction between mutant PABPC1 and PAIP2. Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not. Conclusion: Pathogenic variants in the PABP domain lead to DD, possibly because of interference with the translation initiation and subsequently an impaired neurogenesis in cortical development

De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders

Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in UBAP2L, which encodes an essential regulator of SG assembly. Ubap2l haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development. On the basis of data from 40,853 individuals with NDDs, we report a nominally significant excess of de novo variants within 29 genes that are not implicated in NDDs, including 3 essential genes (G3BP1, G3BP2, and UBAP2L) in the core SG interaction network. We validated that NDD-related de novo variants in newly implicated and known NDD genes, such as CAPRIN1, disrupt the interaction of the core SG network and interfere with SG formation. Together, our findings suggest the common SG pathology in NDDs

De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders

Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in UBAP2L, which encodes an essential regulator of SG assembly. Ubap2l haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development. On the basis of data from 40,853 individuals with NDDs, we report a nominally significant excess of de novo variants within 29 genes that are not implicated in NDDs, including 3 essential genes (G3BP1, G3BP2, and UBAP2L) in the core SG interaction network. We validated that NDD-related de novo variants in newly implicated and known NDD genes, such as CAPRIN1, disrupt the interaction of the core SG network and interfere with SG formation. Together, our findings suggest the common SG pathology in NDDs