In recent years, the incidence of autism spectrum disorder (ASD) has increased, but the etiology and pathogenesis remain unclear. In this narrative review, we review and systematically summarize the methods used to construct animal models to study ASD and the related behavioral studies based on recent literature. Utilization of various ASD animal models can complement research on the etiology, pathogenesis, and core behaviors of ASD, providing information and a foundation for further basic research and clinical treatment of ASD.

[This corrects the article DOI: 10.3389/fonc.2023.1180099.].

Petioles of non-heading Chinese cabbage are not only an important edible part but also a conduit for nutrient transport, holding significant agricultural and research value. In this study, we conducted a comprehensive genetic analysis of petiole-related traits using a segregating population. Modern quantitative genetic approaches were applied to investigate the genetic regulation of petiole thickness. The results indicated that petiole thickness is a quantitative trait, and the identified genetic model was consistent with two pairs of additive-dominant main genes and additive-dominant polygenes (2MG-AD). BSA-seq analysis identified a major effect of QTL controlling petiole thickness on chromosome A09: 42.08-45.09 Mb, spanning 3.01 Mb, designated as QTL-BrLH9. Utilizing InDel markers, the interval was narrowed down to 51 kb, encompassing 14 genes with annotations for 10 of them. Within the interval, four mutated genes were detected. Combined with gene annotation, protein sequence analysis, and homology alignment, it was found that BraA09g063520.3C\'s homologous gene SMXL6 in Arabidopsis (Arabidopsis thaliana (L.) Heynh) is an inhibitor of the coding and synthesis of the strigolactone pathway. Strigolactone (SLs) plays an important role in plant growth and development. The cloning results showed that multiple frameshift mutations and non-synonymous mutations occurred on the exon. The qPCR results showed that the expression of the gene was significantly different between the two parents at the adult stage, so it was speculated that it would lead to changes in petiole thickness. BraA09g063520.3C was predicted as the final candidate gene.

Many genetic models (including models for epistatic effects as well as genetic-by-environment) involve covariance structures that are Hadamard products of lower rank matrices. Implementing these models requires factorizing large Hadamard product matrices. The available algorithms for factorization do not scale well for big data, making the use of some of these models not feasible with large sample sizes. Here, based on properties of Hadamard products and (related) Kronecker products, we propose an algorithm that produces an approximate decomposition that is orders of magnitude faster than the standard eigenvalue decomposition. In this article, we describe the algorithm, show how it can be used to factorize large Hadamard product matrices, present benchmarks, and illustrate the use of the method by presenting an analysis of data from the northern testing locations of the G × E project from the Genomes to Fields Initiative (n ∼ 60,000). We implemented the proposed algorithm in the open-source \"tensorEVD\" R package.

Diabetes is an endocrine illness involving numerous physiological systems. To understand the intricated pathophysiology and disease progression in diabetes, small animals are still the most relevant model systems, despite the availability and progression in numerous invitro and insilico research methods in recent years. In general, experimental diabetes is instigated mainly due to the effectiveness of animal models in illuminating disease etiology. Most diabetes trials are conducted on rodents, while some research is conducted on larger animals. This review will discuss the methodology and mechanisms in detail for preparing diabetic animal models, considering the following important points. The exact pathophysiology of the disease may or may not be replicated in animal models, the correct induction doses must be given and the combination of different approaches for the models is recommended to get desired results.•Animal models are essential to understand diabetes etiology and pathophysiology.•Diabetic models can be developed in both rodents and non-rodents.•Chemically induced and genetic models of diabetes are widely used to study diabetes and diabetic complications.

UNASSIGNED: Previous genetic-epidemiological studies considered TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) gene polymorphisms as the risk factors specific to glioma. However, the data samples of previous genetic-epidemiological studies are modest to determine whether they have definite association with glioma.
UNASSIGNED: The study paid attention to systematically searching databases of PubMed, Embase, Web of Science (WoS), Scopus, Cochrane Library and Google Scholars. Meta-analysis under 5 genetic models, namely recessive model (RM), over-dominant model (O-DM), allele model (AM), co-dominant model (C-DM) and dominant model (DM) was conducted for generating odds ratios (ORs) and 95% confidence intervals (CIs). That was accompanied by subgroup analyses according to various racial groups. The software STATA 17.0 MP was implemented in the study.
UNASSIGNED: 21 articles were collected. According to data analysis results, in four genetic models (AM, RM, DM and C-DM) TERT gene rs2736100 polymorphism, CCDC26 gene rs4295627 polymorphism, CDKN2A/B gene rs4977756 polymorphism and RTEL1 gene rs6010620 polymorphisms increased the risk of glioma in Caucasians to different degrees. In Asian populations, the CCDC26 gene rs4295627 polymorphism and CDKN2A/B gene rs4977756 polymorphism did not exhibit a relevance to the risk of glioma. It is suggested to cautiously explain these results as the sample size is small.
UNASSIGNED: The current meta-analysis suggested that the SNP of TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) genes in glioma might increase risk of glioma, but there are ethnic differences. Further studies evaluating these polymorphisms and glioma risk are warranted.

UNASSIGNED: Acute myocardial infarction (AMI) is the major cause of cardiovascular mortality worldwide. Most ischemic episodes are triggered by an increase in heart rate, which induces an imbalance between myocardial oxygen delivery and consumption. Developing drugs that selectively reduce heart rate by inhibiting ion channels involved in heart rate control could provide more clinical benefits. The Cav1.3-mediated L-type Ca2+ current (ICav1.3) play important roles in the generation of heart rate. Therefore, they can constitute relevant targets for selective control of heart rate and cardioprotection during AMI.
UNASSIGNED: We aimed to investigate the relationship between heart rate and infarct size using mouse strains knockout for Cav1.3 (Cav1.3-/-) L-type calcium channel and of the cardiac G protein gated potassium channel (Girk4-/-) in association with the funny (f)-channel inhibitor ivabradine.
UNASSIGNED: Wild-type (WT), Cav1.3+/-, Cav1.3-/- and Girk4-/- mice were used as models of respectively normal heart rate, moderate heart rate reduction, bradycardia, and mild tachycardia, respectively. Mice underwent a surgical protocol of myocardial IR (40 min ischemia and 60 min reperfusion). Heart rate was recorded by one-lead surface ECG recording, and infarct size measured by triphenyl tetrazolium chloride staining. In addition, Cav1.3-/- and WT hearts perfused on a Langendorff system were subjected to the same ischemia-reperfusion protocol ex vivo, without or with atrial pacing, and the coronary flow was recorded.
UNASSIGNED: Cav1.3-/- mice presented reduced infarct size (-29%), while Girk4-/- displayed increased infarct size (+30%) compared to WT mice. Consistently, heart rate reduction in Cav1.3+/- or by the f-channel blocker ivabradine was associated with significant decrease in infarct size (-27% and -32%, respectively) in comparison to WT mice.
UNASSIGNED: Our results show that decreasing heart rate allows to protect the myocardium against IR injury in vivo and reveal a close relationship between basal heart rate and IR injury. In addition, this study suggests that targeting Cav1.3 channels could constitute a relevant target for reducing infarct size, since maximal heart rate dependent cardioprotective effect is already observed in Cav1.3+/- mice.

Lettuce (Lactuca sativa L.) production is greatly threatened by Verticillium wilt, which is caused by three pathogenic races (races 1, 2, and 3) of the soilborne fungus Verticillium dahliae. Race 1 is predominant, and resistant varieties that provide full protection against it are commercially available. However, heavily relying on race 1-resistant cultivars could shift the population towards resistance-breaking isolates and impact the durability of plant resistance. This study determined the inheritance of partial resistance to isolate VdLs17 of V. dahliae within Lactuca spp. using 258 F2:3 progeny generated from a cross between two partially resistant accessions, 11G99 (L. serriola) and PI 171674 (L. sativa). Eight experiments were performed under greenhouse and growth room conditions across 3 years using a randomized complete block design, and segregation analysis was conducted to determine the inheritance pattern. The results indicate that partial resistance to isolate VdLs17 of V. dahliae is conditioned by a two-major-gene genetic model with additive-dominance-epistatic effects. Transgressive segregants were infrequent but observed in both directions, indicating that favorable and adverse alleles are dispersed in both parents. Combining favorable alleles of these two partially resistant parents appears to be challenging because of epistatic effects and a significant role of environment in disease severity. The probability of capturing favorable additive genes could be maximized by generating and evaluating a large population and making selections at late generations. This study provides valuable insights into the inheritance pattern of partial resistance to isolate VdLs17 of V. dahliae that will be helpful in designing efficient breeding strategies in lettuce.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Parkinson\'s disease (PD) relates to defective mitochondrial quality control in the dopaminergic motor network. Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset, pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra (SNpc). In a reciprocal manner, LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation. Pharmacological intervention in these disease-modifying pathways may facilitate the development of novel PD therapeutics, despite the current lack of an established drug evaluation model. As such, we reviewed the feasibility of employing the versatile global Pink1 knockout (KO) rat model as a self-sufficient, spontaneous PD model for investigating both disease etiology and drug pharmacology. These rats retain clinical features encompassing basal mitophagic flux changes with PD progression. We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.
帕金森病（PD）是一种常见的神经退行性疾病，与多巴胺能神经元中线粒体功能调控紊乱有关。遗传学研究表示PINK1 和Parkin的基因突变与帕金森病有关，而这两种蛋白被认为是通过线粒体自噬和炎症调控来保护中脑黑质区域的神经元退变死亡。同样，LRRK2通过调节线粒体功能障碍，氧化应激及泛素蛋白酶体系，参与到PINK1/Parkin介导的线粒体自噬调控网络中。因此，针对病变中信号调控通路靶点开发药物，可更有效的针对帕金森病的异质性实现组合疗法。虽然目前并没有完美的帕金森研究模型，但使用相关基因敲除动物模型对研究该疾病具体作用机制和治疗手段具有重要意义。该文总结了目前有关的Pink1基因敲除（KO）模型研究现状，讨论了Pink1敲除小鼠和大鼠模型与PD患者临床差异。该文指出，Pink1基因敲除大鼠作为一种自发的PD模型，不仅表现出帕金森病的临床多样性特征，其线粒体自噬水平和炎症反应也会随着帕金森病情发展发生变化，为进一步研究PD发病机理和开发治疗药物提供模型参考。.

BACKGROUND: Angina pectoris (AP) occurs when oxygen and other nutrients are insufficient to meet the metabolic needs of the heart muscle. Stable angina is the most common, while the unstable angina is less frequent. Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine plays a vital function in the immune response regulation. TNF gene cluster contains many polymorphisms; the most commonly investigated polymorphism is the rs1800629 SNP. This SNP, located at - 308 position with regard to the TNF promoter region, replaces guanine (G) with adenine (A), with the allelic types - 308 G/A, and has been linked to a variety of inflammatory condition and autoimmune diseases. The - 308 G/A SNP was investigated in AP and interconnected to the TNF level to figure out the responsibilities of TNF-alpha gene polymorphism in the pathogenesis of AP.
METHODS: The current work design as a case-control study that involves 300 participant divided to 200 patients evaluated as (stable angina n = 100 and unstable angina n = 100) compared with 100 apparently healthy control subjects. The serum level of TNF-alpha was assessed via enzyme-linked immunosorbent assay (ELISA)/sandwich method. The genotype and allele frequency distribution of TNF-alpha rs1800629 gene polymorphism were investigated by TaqMan probe of allelic discrimination method.
RESULTS: The levels of TNF-alpha were significantly higher in patients with stable and unstable angina pectoris in comparison with controls. The deviation from Hardy-Weinberg equilibrium (HWE) of TNF-alpha genotypes was obvious in control and unstable angina pectoris groups. Moreover, the significant differences between patients with AP and controls under the five genetic models consider the association between TNF-alpha (rs1800629) - 308 G/A and AP with OR > 1. However, data analysis of allelic and genotypic of (rs1800629) - 308 G/A revealed higher significantly differences of GG homozygous and GA heterozygous proportions between stable angina patients and control. The A allele was more represented as etiological allele, and G allele was represented as protective allele. The serum levels of TNF-alpha were significantly higher in subjects with genetically mutated AA genotypes than in subjects with wild GG genotypes in the study groups. ROC curve analysis found the best cutoff value of TNF-alpha level was 77.25 pg/ml.
CONCLUSIONS: As the results, our data observed a linked of TNF-alpha (rs1800629) - 308 G/A genetic variant with angina pectoris patients, and the A allele has been linked to the production or expression of TNF-alpha serum level and represented an etiological factor of angina pectoris.