INTRODUCTION: According to the common disease/rare variant hypothesis, it is important to study the role of rare variants in complex diseases. The association of rare variants with psoriasis has been demonstrated, but the association between rare variants and specific clinical subtypes of psoriasis has not been investigated. METHODS: Gene-based and gene-level meta-analyses were performed on data extracted from our previous study data sets (2,483 patients with guttate psoriasis and 8,292 patients with non-guttate psoriasis) for genotyping. Then, haplotype analysis was performed for rare loss-of-function variants located in MED12L, and protein function prediction was performed for MED12L. Gene-based analysis at each stage had a moderate significance threshold (p < 0.05). A χ2 test was then conducted on the three potential genes, and the merged gene-based analysis was used to confirm the results. We also conducted association analysis and meta-analysis for functional variants located on the identified gene. RESULTS: Through these gene-level analyses, we determined that MED12L is a guttate psoriasis susceptibility gene (p = 9.99 × 10-5), and the single-nucleotide polymorphism with the strongest association was rs199780529 (p_combine = 1 × 10-3, p_meta = 2 × 10-3). CONCLUSIONS: In our study, a guttate psoriasis-specific subtype-associated susceptibility gene was confirmed in a Chinese Han population. These findings contribute to a better genetic understanding of different subtypes of psoriasis.
Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in SLC29A3 and CDH23 and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10-6, OR = 0.84; p = 9.47 × 10-5, OR = 1.18; p = 6.90 × 10-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r2 = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.
Cadherin Related Proteins , Nucleoside Transport Proteins , Vitiligo , Humans , China , Genome-Wide Association Study , Genotype , Nucleoside Transport Proteins/genetics , Vitiligo/genetics , East Asian People , Cadherin Related Proteins/genetics
Bilirubin, a key active ingredient of bezoars with extensive clinical applications in China, is produced through a chemical process. However, this method suffers from inefficiency and adverse environmental impacts. To address this challenge, we present a novel and efficient approach for bilirubin production via whole-cell transformation. In this study, we employed Corynebacterium glutamicum ATCC13032 to express a ß-glucuronidase (StGUS), an enzyme from Staphylococcus sp. RLH1 that effectively hydrolyzes conjugated bilirubin to bilirubin. Following the optimization of the biotransformation conditions, a remarkable conversion rate of 79.7% in the generation of bilirubin was obtained at temperate 40 °C, pH 7.0, 1 mM Mg2+ and 6 mM antioxidant NaHSO3 after 12 h. These findings hold significant potential for establishing an industrially viable platform for large-scale bilirubin production.
Bilirubin , Corynebacterium glutamicum , Glucuronidase/genetics , Glucuronidase/metabolism , Corynebacterium glutamicum/metabolism , Staphylococcus , China
Controlled synthesis of lead-halide perovskite crystals is challenging yet attractive because of the pivotal role played by the crystal structure and growth conditions in regulating their properties. This study introduces data-driven strategies for the controlled synthesis of oriented quasi-spherical CsPbBr3, alongside an investigation into the synthesis mechanism. High-throughput rapid characterization of absorption spectra and color under ultraviolet illumination was conducted using 23 possible ligands for the synthesis of CsPbBr3 crystals. The links between the absorption spectra slope (difference in the absorbance at 400â nm and 450â nm divided by a wavelength interval of 50â nm) and crystal size were determined through statistical analysis of more than 100 related publications. Big data analysis and machine learning were employed to investigate a total of 688 absorption spectra and 652 color values, revealing correlations between synthesis parameters and properties. Ex situ characterization confirmed successful synthesis of oriented quasi-spherical CsPbBr3 perovskites using polyvinylpyrrolidone and Acacia. Density functional theory calculations highlighted strong adsorption of Acacia on the (110) facet of CsPbBr3. Optical properties of the oriented quasi-spherical perovskites prepared with these data-driven strategies were significantly improved. This study demonstrates that data-driven controlled synthesis facilitates morphology-controlled perovskites with excellent optical properties.
BACKGROUND: Dementia has become one of the leading causes of death across the world. AIMS: The aim of this study was to investigate the incidence, prevalence, and mortality of dementia in China between 2010 and 2020, and to investigate any geographical, age, and sex differences in the prevalence and incidence of dementia. METHODS: Five databases were searched. The Joanna Briggs Institute (JBI) critical appraisal tool was used to assess the quality of the included studies. A random-effects meta-analysis was performed to estimate the pooled prevalence of dementia. Subgroup analysis was based on the type of dementia. The incidence and mortality of dementia were synthesized qualitatively. RESULTS: A total of 19 studies were included. The meta-analysis showed that the prevalence of dementia was 6% (95%CI 5%, 8%), the prevalence of Alzheimer's disease (AD) was 5% (95%CI 4%, 6%), and the prevalence of vascular dementia (VaD) was 1% (95%CI 0%, 2%). The subgroup analysis showed that the prevalence rates of dementia in rural (6%, 95%CI 4%, 8%) and urban areas were similar (6%, 95%CI 4%, 8%). Deaths due to dementia increased over time. CONCLUSION: The prevalence, incidence, and mortality of dementia increased with age and over time. Applying consistent criteria to the diagnosis of cognitive impairment and dementia is necessary to help with disease monitoring. Promoting dementia knowledge and awareness at the community level is necessary.
Research on perovskites has grown exponentially in the past decade due to the potential of methyl ammonium lead iodide in photovoltaics. Although these devices have achieved remarkable and competitive power conversion efficiency, concerns have been raised regarding the toxicity of lead and its impact on scaling up the technology. Eliminating lead while conserving the performance of photovoltaic devices is a great challenge. To achieve this goal, the research has been expanded to thousands of compounds with similar or loosely related crystal structures and compositions. Some materials are "re-discovered", and some are yet unexplored, but predictions suggest that their potential applications may go beyond photovoltaics, for example, spintronics, photodetection, photocatalysis, and many other areas. This short review aims to present the classification, some current mapping strategies, and advances of lead-free halide double perovskites, their derivatives, lead-free perovskitoid, and low-dimensional related crystals.
Nanoplatelets (NPLs) share excellent luminescent properties with their symmetric quantum dots counterparts and entail special characters benefiting from the shape, like the thickness-dependent bandgap and anisotropic luminescence. However, perovskite NPLs, especially those based on iodide, suffer from poor spectral and phase stability. Here, stable CsPbI3 NPLs obtained by accelerating the crystallization process in ambient-condition synthesis are reported. By this kinetic control, the rectangular NPLs into quasi-square NPLs are tuned, where enlarged width endows the NPLs with a lower surface-area-to-volume ratio (S/V ratio), leading to lower surficial energy and thus improved endurance against NPL fusion (cause for spectral shift or phase transformation). The accelerated crystallization, denoting the fast nucleation and short period of growth in this report, is enabled by preparing a precursor with complete transformation of PbI2 into intermediates (PbI3 -), through an additional iodide supplier (e.g., zinc iodide). The excellent color stability of the materials remains in the light-emitting diodes under various bias stresses.
Conventional spectroscopies are not sufficiently selective to comprehensively understand the behaviour of trapped carriers in perovskite solar cells, particularly under their working conditions. Here we use infrared optical activation spectroscopy (i.e., pump-push-photocurrent), to observe the properties and real-time dynamics of trapped carriers within operando perovskite solar cells. We compare behaviour differences of trapped holes in pristine and surface-passivated FA0.99Cs0.01PbI3 devices using a combination of quasi-steady-state and nanosecond time-resolved pump-push-photocurrent, as well as kinetic and drift-diffusion models. We find a two-step trap-filling process: the rapid filling (~10 ns) of low-density traps in the bulk of perovskite, followed by the slower filling (~100 ns) of high-density traps at the perovskite/hole transport material interface. Surface passivation by n-octylammonium iodide dramatically reduces the number of trap states (~50 times), improving the device performance substantially. Moreover, the activation energy (~280 meV) of the dominant hole traps remains similar with and without surface passivation.
Data-driven predictive methods that can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining an accurate folding landscape using coevolutionary information is fundamental to the success of modern protein structure prediction methods. As the state of the art, AlphaFold2 has dramatically raised the accuracy without performing explicit coevolutionary analysis. Nevertheless, its performance still shows strong dependence on available sequence homologues. Based on the interrogation on the cause of such dependence, we presented EvoGen, a meta generative model, to remedy the underperformance of AlphaFold2 for poor MSA targets. By prompting the model with calibrated or virtually generated homologue sequences, EvoGen helps AlphaFold2 fold accurately in the low-data regime and even achieve encouraging performance with single-sequence predictions. Being able to make accurate predictions with few-shot MSA not only generalizes AlphaFold2 better for orphan sequences but also democratizes its use for high-throughput applications. Besides, EvoGen combined with AlphaFold2 yields a probabilistic structure generation method that could explore alternative conformations of protein sequences, and the task-aware differentiable algorithm for sequence generation will benefit other related tasks including protein design.
Algorithms , Amino Acid Sequence , Protein Conformation
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. A. muciniphila and its outer membrane protein Amuc_1100 ameliorate metabolic disorders, enteritis, depression, and other diseases in mice. The NAFLD mouse model was established by feeding a high-fat diet (HFD) for 10 weeks. To assess the effect of A. muciniphila and Amuc_1100 on NAFLD, we used atorvastatin, a common lipid-lowering drug, as a positive control. A. muciniphila and Amuc_1100 significantly reduced body weight and serum ALT and AST levels, and improved serum lipid levels in NAFLD mice, which had similar effects to Ator. In addition, A. muciniphila and Amuc_1100 decreased the concentration of LPS in the serum and upregulated the mRNA expression of the colonic tight junction proteins. In the liver, A. muciniphila and Amuc_1100 significantly reduced the mRNA expression levels of nodular receptor protein 3 (NLRP3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB), and the protein and mRNA expression levels inflammatory cytokines. At the genus level, Amuc_1100 treatment significantly reduced the abundance of Coriobacteriaceae_UCG-002 produced by the HFD. The abundances of Blautia, norank_f__Ruminococcaceae, Lachnoclostridium, GCA-900066575 and Lachnospiraceae_UCG-006 increased dramatically. Together, A. muciniphila and Amuc_1100 alleviate HFD-induced NAFLD by acting on the gut-liver axis and regulating gut microbes.
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/drug therapy , Diet, High-Fat/adverse effects , Membrane Proteins/metabolism , Verrucomicrobia , Liver/metabolism , Lipids , RNA, Messenger/metabolism , Mice, Inbred C57BL
BACKGROUND: Global Cancer Statistics 2020 reported that breast cancer had exceeded lung cancer as the most frequently diagnosed cancer. Surgery is the primary treatment modality for breast cancer, but postoperative upper limb dysfunction often occurs; functional exercise can alleviate this and restore upper limb function. However, exercise compliance is low in postoperative breast cancer patients; thus, many studies have been conducted in recent years to improve patient compliance with exercise. OBJECTIVE: The aim of this study was to compare the effectiveness of different interventions to improve exercise adherence in postoperative breast cancer patients. METHODS: We searched PubMed, Cochrane Library, Web of Science, EMBASE, Wan Fang, CNKI, VIP, and CBM databases for eligible studies. Exercise adherence rate and quality-of-life difference were assessed as outcomes. Sensitivity analysis and inconsistency detection were performed to evaluate whether the exclusion of high-risk studies affected the validity. Risk of bias was assessed using the risk-of-bias table in RevMan 5.4. Surface under the cumulative ranking was used to estimate the rankings among different interventions. RESULTS: Twenty-five randomized controlled trials involving 9 interventions were included, and the network meta-analysis results showed that patients in the pedometer + counseling group had the best exercise adherence. CONCLUSION: Pedometer + counseling care measures are recommended to improve exercise adherence in postoperative breast cancer patients. IMPLICATIONS FOR PRACTICE: Oncology nurses can improve patients' exercise compliance through counseling and by giving them pedometers to wear.
Acid mine drainage (AMD) serves as an ideal model system for investigating microbial ecology, interaction, and assembly mechanism in natural environments. While previous studies have explored the structure and function of microbial communities in AMD, the succession patterns of microbial association networks and underlying assembly mechanisms during natural attenuation processes remain elusive. Here, we investigated prokaryotic microbial diversity and community assembly along an AMD-impacted river, from the extremely acidic, heavily polluted headwaters to the nearly neutral downstream sites. Microbial diversity was increased along the river, and microbial community composition shifted from acidophile-dominated to freshwater taxa-dominated communities. The complexity and relative modularity of the microbial networks were also increased, indicating greater network stability during succession. Deterministic processes, including abiotic selection of pH and high contents of sulfur and iron, governed community assembly in the headwaters. Although the stochasticity ratio was increased downstream, manganese content, microbial negative cohesion, and relative modularity played important roles in shaping microbial community structure. Overall, this study provides valuable insights into the ecological processes that govern microbial community succession in AMD-impacted riverine ecosystems. These findings have important implications for in-situ remediation of AMD contamination.
Ecosystem , Microbiota , Mining , Microbial Consortia , Fresh Water , Iron
As crucial enzymes in the lipid metabolic network, long-chain acyl-CoA synthases (LACSs) are members of the acyl-activated enzyme superfamily and play a crucial role in epidermal wax synthesis, plant lipid anabolic metabolism, and stress tolerance. In this study, 11 pecan LACS genes were identified and categorized into five groups and located on nine chromosomes. The significant degree of conservation in the AtLACS and CiLACS protein sequences was demonstrated by multiple sequence alignment and conserved motif analysis. Cis-acting element analysis identified numerous stress-responsive and hormone-inducible elements in the promoter regions of CiLACS genes. The expression levels of CiLACS9 and CiLACS9-1 were considerably up-regulated under salt and drought stress, according to the qRT-RCR study. Treatment with ABA also led to increased expression levels of CiLACS1, CiLACS1-1, CiLACS2, and CiLACS9-1. Notably, CiLACS4, CiLACS4-1, CiLACS9, and CiLACS9-1 exhibited peak expression levels at 135 days after anthesis and are likely to have been crucial in the accumulation of seed kernel oil. Moreover, the CiLACS9 gene was shown to be located in the cytoplasm. These findings offer a theoretical framework for clarifying the roles of LACS genes in the processes of pecan kernel oil synthesis and response to abiotic stressors.
Carya , Carya/genetics , Amino Acid Sequence , Lipids , Ligases/metabolism , Phylogeny , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics
BACKGROUND: Phosphonates are the main components in the global phosphorus redox cycle. Little is known about phosphonate metabolism in freshwater ecosystems, although rapid consumption of phosphonates has been observed frequently. Cyanobacteria are often the dominant primary producers in freshwaters; yet, only a few strains of cyanobacteria encode phosphonate-degrading (C-P lyase) gene clusters. The phycosphere is defined as the microenvironment in which extensive phytoplankton and heterotrophic bacteria interactions occur. It has been demonstrated that phytoplankton may recruit phycospheric bacteria based on their own needs. Therefore, the establishment of a phycospheric community rich in phosphonate-degrading-bacteria likely facilitates cyanobacterial proliferation, especially in waters with scarce phosphorus. We characterized the distribution of heterotrophic phosphonate-degrading bacteria in field Microcystis bloom samples and in laboratory cyanobacteria "phycospheres" by qPCR and metagenomic analyses. The role of phosphonate-degrading phycospheric bacteria in cyanobacterial proliferation was determined through coculturing of heterotrophic bacteria with an axenic Microcystis aeruginosa strain and by metatranscriptomic analysis using field Microcystis aggregate samples. RESULTS: Abundant bacteria that carry C-P lyase clusters were identified in plankton samples from freshwater Lakes Dianchi and Taihu during Microcystis bloom periods. Metagenomic analysis of 162 non-axenic laboratory strains of cyanobacteria (consortia cultures containing heterotrophic bacteria) showed that 20% (128/647) of high-quality bins from eighty of these consortia encode intact C-P lyase clusters, with an abundance ranging up to nearly 13%. Phycospheric bacterial phosphonate catabolism genes were expressed continually across bloom seasons, as demonstrated through metatranscriptomic analysis using sixteen field Microcystis aggregate samples. Coculturing experiments revealed that although Microcystis cultures did not catabolize methylphosphonate when axenic, they demonstrated sustained growth when cocultured with phosphonate-utilizing phycospheric bacteria in medium containing methylphosphonate as the sole source of phosphorus. CONCLUSIONS: The recruitment of heterotrophic phosphonate-degrading phycospheric bacteria by cyanobacteria is a hedge against phosphorus scarcity by facilitating phosphonate availability. Cyanobacterial consortia are likely primary contributors to aquatic phosphonate mineralization, thereby facilitating sustained cyanobacterial growth, and even bloom maintenance, in phosphate-deficient waters. Video Abstract.
Cyanobacteria , Microcystis , Organophosphonates , Microcystis/genetics , Microcystis/metabolism , Ecosystem , Organophosphonates/metabolism , Cyanobacteria/genetics , Phytoplankton , Lakes/microbiology , Phosphorus/metabolism
Nitrogen (N) limits plant productivity, and its uptake and assimilation may be regulated by N sources, N assimilating enzymes, and N assimilation genes. Mastering the regulatory mechanisms of N uptake and assimilation is a key way to improve plant nitrogen use efficiency (NUE). However, it is poorly known how these factors interact to influence the growth process of pecans. In this study, the growth, nutrient uptake and N assimilation characteristics of pecan were analyzed by aeroponic cultivation at varying NH4 +/NO3 - ratios (0/0, 0/100,25/75, 50/50, 75/25,100/0 as CK, T1, T2, T3, T4, and T5). The results showed that T4 and T5 treatments optimally promoted the growth, nutrient uptake and N assimilating enzyme activities of pecan, which significantly increased aboveground biomass, average relative growth rate (RGR), root area, root activity, free amino acid (FAA) and total organic carbon (TOC) concentrations, nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (Fd-GOGAT and NADH-GOGAT), and glutamate dehydrogenase (GDH) activities. According to the qRT-PCR results, most of the N assimilation genes were expressed at higher levels in leaves and were mainly significantly up-regulated under T1 and T4 treatments. Correlation analysis showed that a correlation between N assimilating enzymes and N assimilating genes did not necessarily exist. The results of partial least squares path model (PLS-PM) analysis indicated that N assimilation genes could affect the growth of pecan by regulating N assimilation enzymes and nutrients. In summary, we suggested that the NH4 +/NO3 - ratio of 75:25 was more beneficial to improve the growth and NUE of pecan. Meanwhile, we believe that the determination of plant N assimilation capacity should be the result of a comprehensive analysis of N concentration, N assimilation enzymes and related genes.
Background: Increased medication adherence leads to better asthma control and health outcomes. However, many studies have found that patient adherence to maintenance medication is poor. Aim: We undertook a meta-synthesis of qualitative studies, to investigate asthma patient and healthcare professionals' perspectives of medication adherence. Methods: This systematic review was reported by following the PRISMA guidelines. The Joanna Briggs Institute (JBI) meta-aggregative approach was used for the qualitative synthesis. The protocol was registered in PROSPERO (CRD42022346831). Results: In total, 12 articles were included in the review. These articles reported findings from 433 participants in total, which included 315 patients and 118 healthcare professionals. Four synthesised findings with sub-themes were identified from the reviewed studies. These synthesised findings were described as: 1) The role of relationship and communication with/between Healthcare Professionals in medication adherence; 2) Insufficient information from Healthcare Professionals acting as a barrier for adherence; 3) How patient's attitude/beliefs effect their adherence to medication; and 4) Patients' personal behaviour and other relevant barriers. Conclusion: The synthesized findings provide a strong evidence-base of patient and health professionals' perspectives and behaviours toward medication adherence, which helps to identify and address non-adherence. Healthcare providers can use these findings to support patients' adherence to asthma medications. The findings suggest that empowering people to make informed decisions around medication adherence rather than "adherence controlling" by health professionals is very important. Effective dialogue and appropriate education are critical approaches to increase medication adherence.
PROBLEM: There have been some studies on the needs of women experiencing perinatal loss in various socio-cultural contexts, but there is no research that systematically and comprehensively synthesizes these needs. BACKGROUND: Perinatal loss has profound psychosocial effects. The misconceptions and prejudices existing in the public, the lack of satisfactory clinical care, and the available social support may all increase the negative impact. AIM: To synthesize evidence for the needs of women experiencing perinatal loss, attempt to explain the findings, and provide insights into the application of evidence. METHODS: Published papers were searched in seven electronic databases until 26 March 2022. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research was used to assess the methodological quality of the included studies. Through meta-aggregation, the data was extracted, rated, and synthesized, resulting in new categories and findings. The credibility and dependability of the synthesized evidence were evaluated by ConQual. FINDINGS: Thirteen studies that fulfilled the inclusion criteria and quality assessment were included in the meta-synthesis. Five synthesized findings were identified, covering information needs, emotional needs, social needs, clinical care needs, as well as spiritual and religious needs. CONCLUSION: Women's perinatal bereavement needs were individualized and diverse. There is a necessity to understand, identify, and respond to their needs in a sensitive and personalized way. Families, communities, healthcare institutions, and society form a coordinated whole and provide accessible resources to improve recovery from perinatal loss and a satisfactory outcome in the subsequent pregnancy.
Delivery of Health Care , Pregnancy , Female , Humans , Qualitative Research
AIM: The aim of the study is to provide insight and facilitate a deeper understanding of family members who have experienced their older family member's suicide. DESIGN: Interpretative phenomenological analysis (IPA) study. METHODS: Semi-structured individual interviews with five family members of older people who died by suicide recruited from a rural area of Shanxi Province, China. Smith's (2009) six steps of IPA was used for data analysis. RESULTS: Three main themes emerged from the study: (a) Initial psychological reactions; (b) Long-term life effects; (c) Social attitudes. The study shows how the family members of older people who died by suicide have experienced stigmatization and felt largely ignored. A suicide event poses a challenge to the future living quality of the family members. The study also highlights that it is necessary to pay attention to families of older people who died by suicide and providing support is required to improve the quality of life of these family members in rural China. CONCLUSION: The study adds to the understanding of the lived experience of family members of older people who died by suicide in less economically developed rural areas. PATIENT OR PUBLIC CONTRIBUTION: Patients and the public were not involved in the design, conduct or reporting of this study. Participants of this study helped with recruitment via snowball sampling.
Quality of Life , Suicide , Humans , Aged , Suicide/psychology , Emotions , Stereotyping , Family/psychology
Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.
Connexins , Ectodermal Dysplasia , Humans , Connexin 30/genetics , Connexins/genetics , East Asian People , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/diagnosis , Ectodermal Dysplasia/pathology , Phenotype
Bacterial evolution is characterized by strong purifying selection as well as rapid adaptive evolution in changing environments. In this context, the genomic GC content (genomic GC) varies greatly but presents some level of phylogenetic stability, making it challenging to explain based on current hypotheses. To illuminate the evolutionary mechanisms of the genomic GC, we analyzed the base composition and functional inventory of 11,083 representative genomes. A phylogenetically constrained bimodal distribution of the genomic GC, which mainly originated from parallel divergences in the early evolution, was demonstrated. Such variation of the genomic GC can be well explained by DNA replication and repair (DRR), in which multiple pathways correlate with the genomic GC. Furthermore, the biased conservation of various stress-related genes, especially the DRR-related ones, implies distinct adaptive processes in the ancestral lineages of high- or low-GC clades which are likely induced by major environmental changes. Our findings support that the mutational biases resulting from these legacies of ancient adaptation have changed the course of adaptive evolution and generated great variation in the genomic GC. This highlights the importance of indirect effects of natural selection, which indicates a new model for bacterial evolution. IMPORTANCE GC content has been shown to be an important factor in microbial ecology and evolution, and the genomic GC of bacteria can be characterized by great intergenomic heterogeneity, high intragenomic homogeneity, and strong phylogenetic inertia, as well as being associated with the environment. Current hypotheses concerning direct selection or mutational biases cannot well explain these features simultaneously. Our findings of the genomic GC showing that ancient adaptations have transformed the DRR system and that the resulting mutational biases further contributed to a bimodal distribution of it offer a more reasonable scenario for the mechanism. This would imply that, when thinking about the evolution of life, diverse processes of adaptation exist, and combined effects of natural selection should be considered.
Bacteria , Genomics , Phylogeny , Base Composition , Bacteria/genetics , Mutation , Evolution, Molecular
