Search Results (172)

Sex determination is a fundamental biological process governing animal reproduction. Although substantial progress has been made in elucidating its genetic basis, the genetic architecture underlying complex sex determination systems remains poorly understood. In this study, we identify sex-associated insertion–deletion (indel) variants, screen candidate genes, and compare sex-associated variation across populations with different genetic backgrounds in the Fujian oyster (Magallana angulata). Based on whole-genome resequencing data of a culture strain (designated FL), a total of 299,774 high-quality indels were identified. By integrating genome-wide association analysis (GWAS), fixation index (F_ST) analysis, and sex-biased genotype frequency comparisons, 77 overlapping sex-associated indels were identified, predominantly clustered within a 1.8 Mb (8.3–10.1 Mb) region on chromosome 9. Principal component analysis (PCA) based on the sex-associated markers and their subsets consistently separated male and female individuals in the FL strain. For two representative sex-associated indels, PCR-based genotyping methods were developed and validated. Functional annotation identified putative candidate genes for sex determination, including PKD1L1, 5-HTRL, SCP, and CCKRa. Comparative analysis of variants within PKD1L1 across wild, farmed, and selectively bred populations revealed a progressive enrichment of male-linked alleles in domesticated and selectively bred groups, particularly in male individuals. This study provides direct evidence that sex in the Fujian oyster is genetically determined and reveals that domestication and artificial selection may drive the emergence of major sex-determining loci, offering important insights into the genetic basis of sex determination in the Fujian oyster, and establishing a theoretical and practical foundation for molecular marker-assisted breeding of monosex lines for this species. Full article

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Background: The Mayo imaging classification (MIC) for polycystic kidney disease (PKD) is a crucial basis for clinical treatment decisions; however, the volumetric assessment for its evaluation remains tedious and inaccurate. While the ellipsoid method for measuring the total kidney volume (TKV) in patients with PKD provides a practical TKV estimation using computed tomography (CT), its inconsistency and inaccuracy are limitations, highlighting the need for improved, accessible techniques in real-world clinics. Methods: We compared manual ellipsoid and artificial intelligence (AI)-based kidney volumetry methods using a convolutional neural network-based segmentation model (3D Dynamic U-Net) for measuring the TKV by assessing 32 patients with PKD in a single tertiary hospital. Results: The median age and average TKV were 56 years and 1200.24 mL, respectively. Most of the patients were allocated to Mayo Clinic classifications 1B and 1C using the ellipsoid method, similar to the AI volumetry classification. AI volumetry outperformed the ellipsoid method with highly correlated scores (AI vs. nephrology professor ICC: r = 0.991, 95% confidence interval (CI) = 0.9780–0.9948, p < 0.01; AI vs. trained clinician ICC: r = 0.983, 95% CI = 0.9608–0.9907, p < 0.01). The Bland–Altman plot also showed that the mean differences between professor and AI volumetry were statistically insignificant (mean difference 159.5 mL, 95% CI = 11.8368–330.7817, p = 0.07). Conclusions: AI-based kidney volumetry demonstrates strong agreement with expert manual measurements and offers a reliable, labor-efficient alternative for TKV assessment in clinical practice. It is helpful and essential for managing PKD and optimizing therapeutic outcomes. Full article

As an important oil and vegetable crop, rapeseed is widely planted and has important economic value worldwide. Rapeseed is often threatened by various pests during its growth. In order to effectively deal with rapeseed pests, this paper proposes a lightweight method based on collaborative compression learning. This method uses YOLOv8s as the basic model, combines model structure analysis and pruning sensitivity evaluation, and implements structured pruning to compress the model size. The Logit distillation method is integrated with the improved generative distillation method MGD, and the LMGD distillation strategy is proposed to enhance the student model’s ability to fit the teacher model’s feature expression. In order to verify the effectiveness of the proposed method, we built a rapeseed pest dataset (ACEFP) and conducted experiments. The improved model achieved 96.7% mAP@0.5, 93.2% accuracy, and 92.7% recall, while the parameter size was compressed from 11.2 MB to 4.4 MB, and the FLOPs were reduced from 28.3 G to 10.01 G, which were reduced by about 60.7% and 64.6%, respectively, and the accuracy was only reduced by 0.1%. The model achieved a measured frame rate of 11.76 FPS on the Jetson Nano edge device, demonstrating excellent real-time inference performance. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic ciliopathy resulting from loss-of-function mutations in the PKD1 and PKD2 genes, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 and PC2 regulate mechanosensation, calcium signaling, and key pathways controlling tubular epithelial structure and function. Loss of PC1/PC2 disrupts calcium homeostasis, elevates cAMP, and activates proliferative cascades such as PKA–B-Raf–MEK–ERK, mTOR, and Wnt, driving cystogenesis via epithelial proliferation, impaired apoptosis, fluid secretion, and fibrosis. Recent evidence also implicates novel signaling axes in ADPKD progression including, the Hippo pathway, where dysregulated YAP/TAZ activity enhances c-Myc-mediated proliferation; the stimulator of interferon genes (STING) pathway, which is activated by mitochondrial DNA release and linked to NF-κB-driven inflammation and fibrosis; and the TWEAK/Fn14 pathway, which mediates pro-inflammatory and pro-apoptotic responses via ERK and NF-κB activation in tubular cells. Mitochondrial dysfunction, oxidative stress, and maladaptive extracellular matrix remodeling further exacerbate disease progression. A refined understanding of ADPKD’s complex signaling networks provides a foundation for precision medicine and next-generation therapeutics. This review gathers recent molecular insights and highlights both established and emerging targets to guide targeted treatment strategies in ADPKD. Full article

Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD), the most common renal genetic disease, leading to the dysregulation of renal tubules and the development of cystic growth that compromises kidney function. Despite significant advances in recent decades, there remains a considerable unmet clinical need, as current therapeutics are not effective at slowing or halting disease progression. Although preclinical animal models have been used extensively, the translatability of such findings is uncertain and human-relevant disease models are urgently needed. The advent of pluripotent stem cells (PSCs) and their ability to more accurately recapitulate organ architecture and function has allowed for the study of renal disease in a more physiological and human-relevant setting. To date, many research groups have studied ADPKD using PSC-derived kidney organoids, identifying many dysregulated pathways and screening drug candidates that may yield effective therapies in the clinic. In this review article, we discuss in detail the development of PSC-derived kidney organoids as ADPKD models and how they have advanced our understanding of the disease’s pathogenesis, as well as their limitations and potential strategies to address them. Full article

The leading causes of pediatric arterial ischemic stroke (PAIS) are arteriopathies, which refer to pathologies of the arterial walls in the brain. Since traditional risk factors for cardiovascular diseases in children play a smaller role than in adults, it can be supposed that genetic factors may be of particular importance in this age group. Therefore, this study aimed to identify mutations affecting the formation of vascular wall pathologies, which can subsequently lead to ischemic stroke. The study used a database of 92 Caucasian children diagnosed with ischemic stroke. From this group, 25 children with arteriopathies were selected. The study had an exploratory and descriptive design, with the aim of characterizing rare genetic variants in a selected cohort, without attempting formal statistical association testing. The sequencing was performed using the Illumina NextSeq 550 platform. A panel of 161 genes known to be associated with stroke or arteriopathies was selected for further analysis. We identified 10 pathogenic or likely pathogenic mutations in 15 patients. Among these, three are likely monogenic causes of stroke (ELN, SCN5A, and VHL genes), two are considered risk factors (FV and ADAMTS13), two have conflicting interpretations (ACAD9 and ENG), and three are most likely benign (CBS, PMM2, and PKD1). The frequency of genetic variants underlying ischemic stroke or acting as risk factors for the disease in the studied group is significantly higher than the estimated frequency of monogenic forms of stroke in young adults and higher than in the general population. NGS testing is worth considering, especially in patients who exhibit certain symptoms that may suggest the presence of mutations. Full article

Regional anesthesia techniques targeting articular nerve branches offer promising avenues for managing articular pain. This study developed and compared the success rates of an ultrasound-guided versus a blind pericapsular knee desensitization (PKD) technique in canine cadavers. In Phase I, gross dissection and ultrasound evaluations were performed in eight limbs to characterize the anatomy of the medial (MAN), lateral (LAN), and posterior (PAN) articular branches of the saphenous, common fibular, and tibial nerves, respectively, and to identify suitable anatomical and ultrasonographic landmarks. In Phase II, ultrasound-guided and blind PKD injections of a dye solution were randomly performed in 10 cadavers (20 limbs), followed by dissection and histological assessment of staining accuracy. The ultrasound-guided technique achieved a significantly higher overall success rate (96.7%) than the blind technique (73.3%; p = 0.02). The MAN was successfully stained in 100% of ultrasound-guided and 50% of blind injections (p = 0.03), while the LAN and PAN were stained with high but comparable success. Parent nerve involvement was minimal for MAN and PAN but frequent for the common fibular nerve following LAN injections. Histological confirmation supported the anatomical findings, although PAN identification remained inconsistent. These results support the feasibility and increased precision of ultrasound-guided PKD, providing a foundation for further clinical evaluation. Full article

Background/Objectives: Horseshoe kidney is a congenital anomaly characterized by the fusion of the kidneys at the lower pole. Polycystic kidney disease with horseshoe kidney is called polycystic horseshoe kidney. Genetic testing is essential for the diagnosis of polycystic horseshoe kidney disease because it can result from a number of genetic disorders. Fewer than 20 cases of polycystic horseshoe kidney have been reported to date. However, polycystic horseshoe kidney disease was mostly diagnosed via autopsy or radiologic imaging techniques including computed tomography, magnetic resonance imaging, and angiography. Because polycystic kidney disease has various causes, genetic testing is essential for the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) in patients with polycystic horseshoe kidney disease. At present, the diagnosis of ADPKD is made using genetic approaches, including next-generation sequencing. We reported a potentially pathogenic polycystin 1 (PKD1) gene in a patient with ADPKD and horseshoe kidney. Methods: We performed the sequencing of the PKD1 gene and radiological examinations (computed abdominal tomography). Results: Computed abdominal tomography revealed enlarged kidneys with multiple cysts fused at the lower poles, indicating polycystic HSK. The sequencing of the PKD1 gene revealed a heterozygous pathogenic variant c.165_171del (p.Leu56ArgfsTer15), which genetically confirmed the diagnosis of ADPKD. The patient was treated with an angiotensin II receptor blocker. Conclusions: In this case report, we suggest that genetic testing becomes the key approach to the diagnosis of ADPKD with horseshoe kidney. Additionally, this approach offers the benefit of avoiding the possibility of the condition being mistakenly diagnosed or diagnosed late due to its uncommon occurrence and nonspecific symptoms. Full article

Polycystic kidney disease (PKD), a ciliopathy caused primarily by mutations in the Pkd1 and Pkd2 genes, disrupts renal structure and function, leading to progressive renal failure. The primary cilium, a sensory organelle essential for cellular signaling, plays a pivotal role in maintaining renal function. Among its signaling components, G-protein-coupled receptors (GPCRs) within the cilium have gained significant attention for their localized functions and their contribution to PKD pathogenesis. Dysfunction of ciliary GPCR signaling alters key downstream pathways, including mammalian target of rapamycin (mTOR), cyclic adenosine monophosphate (cAMP), and calcium homeostasis, exacerbating cyst formation and disease progression. Additionally, interactions between ciliary GPCRs and PKD-associated proteins, such as Polycystin-1 (PC1) and Polycystin-2 (PC2), underline the complexity of PKD mechanisms. Recent advances highlight GPCRs as promising therapeutic targets for ciliopathies, including PKD. Emerging GPCR modulators and drugs in clinical trials show the potential to restore ciliary signaling and attenuate disease progression. This paper explores the physiological functions of ciliary GPCRs, their mechanistic links to PKD, and the therapeutic implications of targeting these receptors, offering insights into future research directions and therapeutic strategies for PKD. Full article

Background and Clinical Significance: Polycystic kidney disease (PKD) is the most common inherited kidney condition, affecting approximately 500,000 individuals in the US. It causes fluid-filled cysts to develop throughout the kidneys, leading to decreased kidney function. Autosomal dominant polycystic kidney disease (ADPKD) is the more prevalent form, subdivided into the PKD1 and PKD2 variants. PKD1 variants typically result in more severe symptoms and an earlier need for dialysis compared to PKD2. A prenatal diagnosis of ADPKD is rare due to its late-onset manifestations, but early detection can be crucial for management and family counseling. Case Presentation: A 24-year-old woman, during her first pregnancy, presented for her first prenatal ultrasound at 22 + 2 weeks gestation. The ultrasound revealed an increased echogenicity of the renal parenchyma in the left kidney, with pelvic dystopia, while the right kidney appeared normal. Follow-up scans showed significant progression, with both kidneys exhibiting thinning parenchyma and cyst formation. The baby was delivered via an elective cesarean section at 38 weeks, and a postnatal ultrasound confirmed ADPKD. Genetic testing identified a heterozygous variant of the PKD1 gene, NM_001009944.3 (PKD1):c.9157G>A p.(Ala3053Thr), classified as likely pathogenic. The baby displayed electrolyte abnormalities but improved after a week of hospitalization. Conclusions: This case highlights an unusual early presentation of ADPKD in a fetus with no family history of the disease. A prenatal diagnosis through ultrasounds and genetic testing can aid in early detection and management, providing valuable information for family counseling. Regular monitoring and genetic identification are essential for managing ADPKD and improving patient outcomes. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inheritable disease of cystic degeneration in the kidney. ADPKD is a significant cause of end-stage renal disease (ESRD). Autosomal Dominant Polycystic Liver Disease (ADPLD) results in substantial PLD with minimal PKD. Currently, there are eight genes which have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). The severity of ADPKD can show an extremely broad range, but the evolution to ESRD is doubtless unavoidable. In some patients, carcinogenesis develops with inflammation as a potential promoting factor. In this chapter, we illustrate the severity of ADPKD and the fate to develop renal cell carcinoma (RCC). Full article

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, affecting approximately 1 in 1000 individuals. This genetically heterogeneous condition is primarily caused by monoallelic pathogenic or likely pathogenic variants in the PKD1 and PKD2 genes, accounting for 78% and 15% of typical cases, respectively. Recently, the application of NGS methods has led to the identification of additional genes associated with ADPKD, which have been incorporated into routine diagnostic testing for detecting phenocopies of the disease. Methods: In this study, targeted NGS (tNGS) analysis of the main cystogenes associated with classic and atypical ADPKD was performed in a cohort of 218 patients clinically diagnosed with cystic nephropathies. Results: Genetic testing identified variants in 175 out of 218 cases (80.3%). Among these, 133 probands (76%) harbored likely pathogenic or pathogenic variants in one or more genes of the panel, while 42 individuals (24%) had a variant of unknown significance (VUS). Specifically, one or more class 4/5 variants in PKD1, PKD2, or both were identified in 111 (83.5%) probands. Remarkably, a pathogenic variant in the IFT140 gene was identified in 14 index cases (8% of positive individuals, 6.4% of the global cohort): 10 distinct loss-of-function (LoF) variants were identified (including four frameshift variants, four nonsense variants, and two splice site defects); one individual carried a second IFT140 missense variant classified as VUS. Furthermore, five affected family members were found to carry a P/LP LoF variant in IFT140. Conclusions: Our data support that IFT140 heterozygous IFT140 LoF variants result in an atypical, mild form of ADPKD, consisting of bilateral kidney cysts and renal functional decline at older ages. Furthermore, we describe the second pediatric patient with a mild form of ADPKD due to an IFT140 variant and discuss hyperuricemia as a previously unappreciated feature of this condition. Full article

Background: Polycystin 1 (PC1) and polycystin 2 (PC2) proteins are members of the transient receptor potential (TRP) channels family and are encoded from PKD1 and PKD2 genes, respectively. Until recently, the role of PKD1 and PKD2 has been associated with the pathogenesis of the kidney since mutations in these genes cause autosomal dominant polycystic kidney disease (ADPKD). Recent data implicates polycystins in the pathogenesis of solid tumors. In this aspect, the expression of PKD1 and PKD2 in human astrocytomas is largely unknown. The aim of the present research study was to investigate the expression of PKD1 and PKD2 in astrocytic tumors and correlate it with clinicopathological characteristics such as the grade of malignancy, age, and gender of the patients. Methods: A total of 70 cases—corresponding to 8 grade II (diffuse fibrillary astrocytomas), 12 grade III (anaplastic astrocytomas), and 50 grade IV (glioblastomas multiforme)—were examined. The mRNA expression levels of PKD1 and PKD2 were determined through molecular qRT-PCR analysis using the relative quantification ΔΔCt method and the expression of PC1 and PC2 was detected through immunohistochemistry using the semi-quantitative H-score system. Results: Increased levels of PKD1 and PKD2 in astrocytomas were found compared with that of a normal brain (p < 0.05). Glioblastomas demonstrated the greatest increase in PKD1 and PKD2 expression compared to other grades of malignancy (p < 0.05). The same pattern of expression showed PC1 and PC2 proteins. A significant correlation between PKD1 and PKD2 as well as PC1 and PC2 expressions was found (p < 0.05). Although no association was detected between PC1 or PC2 and Ki67 expression (p > 0.05), a significant correlation between PC1 and p53 immunoexpressions, in grade III and between PC2 and p53 immunoexpressions, in grade II astrocytomas (p < 0.01) has emerged. PC1 expression was correlated with age of the patients (p < 0.05). PKD1 and PKD2 expression were negatively correlated with the prognosis of glioma patients. Conclusions: The results of this study indicate the potential involvement of polycystins in the pathogenesis of astrocytomas. However, further research is required to fully understand the mechanisms that these molecules are implicated. Full article

The role of calcium, an essential secondary messenger, in cell division remains an outstanding question in cell biology despite several significant findings over the past few decades. Among them is the landmark discovery of intracellular calcium waves during cytokinesis, the last stage of cell division, in fish cells. Nevertheless, subsequent studies have been largely unable to determine the underlying molecular mechanism of these cytokinetic transients. At the center of this stalemate stands two challenging questions, how these calcium transients rise and what they do during cytokinesis. Yeast, despite its proven prowess as a model organism to study cell cycle, has not drawn much interest in addressing these questions. However, the recent discovery of cytokinetic calcium spikes in the fission yeast Schizosaccharomyces pombe has provided novel insights into how calcium regulates cytokinesis. In this review, I will primarily focus on our current understanding of the molecular mechanism of cytokinetic calcium transients in yeast cells. First, I will briefly recount the discovery of cytokinetic calcium transients in animal cells. This will be followed by an introduction to the intracellular calcium homeostasis. Next, I will discuss yeast cytokinetic calcium spikes, the ion channel Pkd2 that promotes these spikes, and the potential molecular targets of these spikes. I will also compare the calcium regulation of cytokinesis between yeast and animal cells. I will conclude by presenting a few critical questions in our continued quest to understand how calcium regulates cytokinesis. Full article