Correction to “Association of abnormal glucose tolerance with liver‐related disease and cardiovascular diseases in patients with chronic hepatitis C”
Hepatology Research, Volume 54, Issue 4, Page 409-409, April 2024.
Effects of reference population size and structure on genomic prediction of maternal traits in two pig lines using whole‐genome sequence‐, high‐density‐ and combined annotation‐dependent depletion genotypes
Abstract
The aim of this study was to investigate the reference population size required to obtain substantial prediction accuracy within- and across-lines and the effect of using a multi-line reference population for genomic predictions of maternal traits in pigs. The data consisted of two nucleus pig populations, one pure-bred Landrace (L) and one Synthetic (S) Yorkshire/Large White line. All animals were genotyped with up to 30 K animals in each line, and all had records on maternal traits. Prediction accuracy was tested with three different marker data sets: High-density SNP (HD), whole genome sequence (WGS), and markers derived from WGS based on pig combined annotation dependent depletion-score (pCADD). Also, two different genomic prediction methods (GBLUP and Bayes GC) were compared for four maternal traits; total number piglets born (TNB), total number of stillborn piglets (STB), Shoulder Lesion Score and Body Condition Score. The main results from this study showed that a reference population of 3 K–6 K animals for within-line prediction generally was sufficient to achieve high prediction accuracy. However, when the number of animals in the reference population was increased to 30 K, the prediction accuracy significantly increased for the traits TNB and STB. For multi-line prediction accuracy, the accuracy was most dependent on the number of within-line animals in the reference data. The S-line provided a generally higher prediction accuracy compared to the L-line. Using pCADD scores to reduce the number of markers from WGS data in combination with the GBLUP method generally reduced prediction accuracies relative to GBLUP using HD genotypes. The BayesGC method benefited from a large reference population and was less dependent on the different genotype marker datasets to achieve a high prediction accuracy.
The effects of advanced glycation end‐products on skin and potential anti‐glycation strategies
Abstract
The advanced glycation end-products (AGEs) are produced through non-enzymatic glycation between reducing sugars and free amino groups, such as proteins, lipids or nucleic acids. AGEs can enter the body through daily dietary intake and can also be generated internally via normal metabolism and external stimuli. AGEs bind to cell surface receptors for AGEs, triggering oxidative stress and inflammation responses that lead to skin ageing and various diseases. Evidence shows that AGEs contribute to skin dysfunction and ageing. This review introduces the basic information, the sources, the metabolism and absorption of AGEs. We also summarise the detrimental mechanisms of AGEs to skin ageing and other chronic diseases. For the potential strategies for counteracting AGEs to skin and other organs, we summarised the pathways that could be utilised to resist glycation. Chemical and natural-derived anti-glycation approaches are overviewed. This work offers an understanding of AGEs to skin ageing and other chronic diseases and may provide perspectives for the development of anti-glycation strategies.
Issue Information
Experimental Dermatology, Volume 33, Issue 4, April 2024.
The scorpion toxin BeKm‐1 blocks hERG cardiac potassium channels using an indispensable arginine residue
Using computational methods, we constructed a model of the cardiac ion channel hERG in complex with BeKm-1, a scorpion toxin. We identified the crucial role of the toxin residue Arg20 and validated it by in silico and in vitro mutagenesis. The BeKm-1R20K mutant showed dramatically reduced activity, suggesting the significance of Arg20 for channel binding. Our model aids future drug design attempts.
BeKm-1 is a peptide toxin from scorpion venom that blocks the pore of the potassium channel hERG (Kv11.1) in the human heart. Although individual protein structures have been resolved, the structure of the complex between hERG and BeKm-1 is unknown. Here, we used molecular dynamics and ensemble docking, guided by previous double-mutant cycle analysis data, to obtain an in silico model of the hERG–BeKm-1 complex. Adding to the previous mutagenesis study of BeKm-1, our model uncovers the key role of residue Arg20, which forms three interactions (a salt bridge and hydrogen bonds) with the channel vestibule simultaneously. Replacement of this residue even by lysine weakens the interactions significantly. In accordance, the recombinantly produced BeKm-1R20K mutant exhibited dramatically decreased activity on hERG. Our model may be useful for future drug design attempts.
Caspase‐3 targets pro‐interleukin‐1β (IL‐1β) to restrict inflammation
The present study suggests pro-IL-1β as a novel substrate of caspase-3. The activation of apoptotic signaling induces caspase-3 to cleave pro-IL-1β at the Asp26 site, and the generation of the Asp26 site restricts the inflammasome-mediated cleavage at the Asp117 site. Thus, caspase-3 prevents the release of mature IL-1β into the extracellular environment.
The interleukin (IL)-1 family of cytokines plays a pivotal role in immune responses. Among the members of IL-1 family, IL-1β is synthesized as an inactive precursor (pro-IL-1β) and becomes active upon cleavage, which is typically facilitated by inflammasomes through caspase-1. In our research, we explored the potential role of caspase-3 in the cleavage of pro-IL-1β and found that caspase-3 cleaves pro-IL-1β, specifically at Asp26. Moreover, we found that in the absence of caspase-3 cleavage, the release of active IL-1β via the inflammasome is increased. Our study introduces pro-IL-1β as a new substrate for caspase-3 and suggests that caspase-3-mediated cleavage has the potential to suppress IL-1β-mediated inflammatory responses.
Cryo‐EM structure of the Slo1 potassium channel with the auxiliary γ1 subunit suggests a mechanism for depolarization‐independent activation
γ subunits allow Slo potassium channels to open without an action potential. By cryo-EM structure determination, we show how γ1 binds the voltage-sensor domain (VSD) of Slo1. The kinked transmembrane helix and an extracellular hook of γ1 stabilize the VSD in its active conformation, while an intracellular polybasic stretch locally decreases the resting potential.
Mammalian Ca2+-dependent Slo K+ channels can stably associate with auxiliary γ subunits which fundamentally alter their behavior. By a so far unknown mechanism, the four γ subunits reduce the need for voltage-dependent activation and, thereby, allow Slo to open independently of an action potential. Here, using cryo-EM, we reveal how the transmembrane helix of γ1/LRRC26 binds and presumably stabilizes the activated voltage-sensor domain of Slo1. The activation is further enhanced by an intracellular polybasic stretch which locally changes the charge gradient across the membrane. Our data provide a possible explanation for Slo1 regulation by the four γ subunits and also their different activation efficiencies. This suggests a novel activation mechanism of voltage-gated ion channels by auxiliary subunits.
Gulp1 regulates chondrocyte growth arrest and differentiation via the TGF‐β/SMAD2/3 pathway
We report a novel function of Gulp1 in chondrocyte differentiation. Gulp1 knockdown in chondrogenic ATDC5 cells reduces the expression of chondrogenic marker genes, impairs cell growth arrest, and decreases p21 levels during differentiation. This knockdown also desrupts the TGF-β/SMAD2/3 pathway activation linked to p21 expression, highlighting Gulp1's involvment in regulating chondrocyte differentiation and growth arrest via the TGF-β/SMAD2/3 pathway.
Chondrocyte differentiation is crucial for cartilage formation. However, the complex processes and mechanisms coordinating chondrocyte proliferation and differentiation remain incompletely understood. Here, we report a novel function of the adaptor protein Gulp1 in chondrocyte differentiation. Gulp1 expression is upregulated during chondrogenic differentiation. Gulp1 knockdown in chondrogenic ATDC5 cells reduces the expression of chondrogenic and hypertrophic marker genes during differentiation. Furthermore, Gulp1 knockdown impairs cell growth arrest during chondrocyte differentiation and reduces the expression of the cyclin-dependent kinase inhibitor p21. The activation of the TGF-β/SMAD2/3 pathway, which is associated with p21 expression in chondrocytes, is impaired in Gulp1 knockdown cells. Collectively, these results demonstrate that Gulp1 contributes to cell growth arrest and chondrocyte differentiation by modulating the TGF-β/SMAD2/3 pathway.
Mulch alleviates the continuous crop barriers of Codonopsis pilosula (Franch.) Nannf. by regulating the soil bacterial community
This manuscript provides information using developed field experiments to systematically investigate the mechanisms of environment–microbe–plant occurrence of continuous cropping disorder of C. pilosula through 16S high-throughput sequencing in conjunction with actual production, and we explored the effect of the mulched film on the repair of C. pilosula continuous cropping obstacles and provided a theoretical basis for reducing C. pilosula continuous cropping obstacles. The findings of the study revealed a decline in organic matter and inorganic nitrogen content, as well as a decrease in soil microorganism abundance, following continuous cropping of C. pilosula. After mulching, the abundance of beneficial bacteria AKAU4049, Betaproteobacteriales and Gaiellales in the soil increased, and the content of organic matter and inorganic nitrogen was elevated, which improved the soil environment and promoted the growth of C. pilosula under continuous cropping conditions.
Abstract
Codonopsis pilosula (Franch.) Nannf. is an essential traditional medicinal herb in China. Soil sickness caused by continuous cropping is the main reason for the yield reduction of C. pilosula. However, because of the lack of systematic research on the mechanism of continuous cropping obstacles in C. pilosula, there is a lack of effective measures to reduce or even restrain the disorder of continuous cropping obstacles in C. pilosula. The root system, inter-root soil microorganisms and non-inter-root soil of C. pilosula under a continuous cropping system (e.g. crop rotation, two consecutive crops and three consecutive crops) as well as under different mulching methods (the mulched film and the uncovered) were used as experimental materials for the study. The plant growth of C. pilosula was significantly inhibited when continuous cropping reached 2 years. At the same time, the mulched film significantly (p < .05) promoted the development of C. pilosula under continuous cropping and considerably mitigated the plant death rate of C. pilosula in all fields. The content of soil nutrients, such as organic matter and inorganic nitrogen, decreased with increasing years of continuous cropping. In contrast, the mulched film improved this soil nutrient in continuous cropping. There was a tendency for the number of endemic operational taxonomic units (OTUs) to decrease in continuous cropping. Additionally, the mulched film altered the distribution of shared and endemic OTUs in the samples and had a recruiting effect on inter-root microorganisms in continuous cropping. Betaproteobacteriales flora abundance decreased with increasing years of continuous cropping, which showed a strong positive correlation with the immune system and environmental adaptation function. The mulched film increased the abundance of beneficial microorganisms, such as AKAU4049, Betaproteobacteriales and Gaiellales, to adapt and improve the continuous crop disorder of C. pilosula. In conclusion, mulching can enhance the soil environment and facilitate the growth and development of C. pilosula during continuous cultivation.
Prevalence of sex‐chromosome aneuploidy estimated using SNP genotype intensity information in a large population of juvenile dairy and beef cattle
Abstract
Aneuploidy is a genetic condition characterized by the loss or gain of one or more chromosomes. Aneuploidy affecting the sex chromosomes can lead to infertility in otherwise externally phenotypically normal cattle. Early identification of cattle with sex chromosomal aneuploidy is important to minimize the costs associated with rearing infertile cattle and futile breeding attempts. As most livestock breeding programs routinely genotype their breeding populations using single nucleotide polymorphism (SNP) arrays, this study aimed to assess the feasibility of integrating an aneuploidy screening tool into the existing pipelines that handle dense SNP genotype data. A further objective was to estimate the prevalence of sex chromosome aneuploidy in a population of 146,431 juvenile cattle using available genotype intensity data. Three genotype intensity statistics were used: the LogR Ratio (LRR), R-value (the sum of X and Y SNP probe intensities), and B-allele frequency (BAF) measurements. Within the female-verified population of 124,958 individuals, the estimated prevalence rate was 0.0048% for XO, 0.0350% for XXX, and 0.0004% for XXY. The prevalence of XXY in the male-verified population was 0.0870% (i.e., 18 out of 20,670 males). Cytogenetic testing was used to verify 2 of the XXX females who were still alive. The proposed approach can be readily integrated into existing genomic pipelines, serving as an efficient, large-scale screening tool for aneuploidy. Its implementation could enable the early identification of infertile animals with sex-chromosome aneuploidy.