From the cauldron of conflict: Endogenous gene regulation by piRNA and other modes of adaptation enabled by selfish transposable elements.

Transposable elements (TEs) provide a prime example of genetic conflict because they can proliferate in genomes and populations even if they harm the host. However, numerous studies have shown that TEs, though typically harmful, can also provide fuel for adaptation. This is because they code functional sequences that can be useful for the host in which they reside. In this review, I summarize the "how" and "why" of adaptation enabled by the genetic conflict between TEs and hosts. In addition, focusing on mechanisms of TE control by small piwi-interacting RNAs (piRNAs), I highlight an indirect form of adaptation enabled by conflict. In this case, mechanisms of host defense that regulate TEs have been redeployed for endogenous gene regulation. I propose that the genetic conflict released by meiosis in early eukaryotes may have been important because, among other reasons, it spurred evolutionary innovation on multiple interwoven trajectories - on the part of hosts and also embedded genetic parasites. This form of evolution may function as a complexity generating engine that was a critical player in eukaryotic evolution.

Restoration of peripheral neuropathy in Fabry mice via intrathecal administration of an adeno-associated virus vector encoding mGLA cDNA.

Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a pathological variant of the α-galactosidase A (GLA) gene that results in deficient GLA activity. GLA deficiency leads to the accumulation of globotriaosylceramide (Gb3) and lyso-Gb3 in many tissues. A certain number of FD patients have burning pain or acroparesthesia in the feet and hands since childhood. Enzyme replacement therapy (ERT) is available for FD patients. However, ERT does not dramatically improve these FD-related peripheral neuropathic pain. We generated an adeno-associated virus serotype PHP.eB (AAV-PHP.eB) vector encoding mouse GLA cDNA, which was administered to FD mice intrathecally (it) or intravenously (iv). In the it-administered AAV (it-AAV) FD mice, the GLA enzyme activity in the lumbar dorsal root ganglion (DRG) was significantly greater than that in the untreated (NT) FD mice, and the level of activity was similar to that in wild-type (WT) B6 mice. However, in iv-administered AAV (iv-AAV) FD mice, GLA activity in the DRG did not increase compared to that in NT FD mice. Gb3 storage in the DRG of it-AAV FD mice was reduced compared to that in the DRG of NT FD mice. However, compared with NT FD mice, iv-AAV FD mice did not exhibit a significant reduction in the expression of the Gb3 substrate. Compared with WT mice, FD mice were thermally hyposensitive at 52 °C according to the hot plate test. The it-AAV FD mice showed significant recovery from thermal hyposensitivity. However, the iv-AAV FD mice did not exhibit significant improvement in thermal hyposensitivity. These results suggest that the intrathecal delivery of AAV-PHP.eB-mGLA may be a valuable tool for the treatment of FD-related peripheral neuropathic pain.

Evaluation of the expression of fibrosis-related genes as non-invasive diagnostic biomarkers for cirrhotic HCV-infected patients.

Liver cirrhosis is a condition with high mortality that poses a significant health and economic burden worldwide. The clinical characteristics of liver cirrhosis are complex and varied. Therefore, the evaluation of immune infiltration-involved genes incirrhosis has become mandatory in liver disease research, not only to identify the potential biomarkers but also to provide important insights into the underlying mechanisms of the disease. In this study, we aimed to investigate the expression profile of cytokine genes in peripheral blood mononuclear cells (PBMCs) of HCV patients and identify the gene expression signature associated with advanced cirrhosis. A cross-sectional study of 90 HCV genotype 4 patients, including no fibrosis patients (F0, n = 24), fibrotic patients (F1-F3, n = 36), and cirrhotic patients (F4, n = 30) has been conducted. The expression of cytokine genes was analyzed by quantitative real-time PCR in the subjects' PBMCs, and the serum level of TGFß2 was measured by ELISA. Our findings showed that the expression level of the TGIF1 transcript was lower in cirrhotic and fibrotic patients compared to no fibrosis patients (p = 0.046 and 0.022, respectively). Also, there was an upregulation of the TGFß1 gene in cirrhotic patients relative to fibrotic patients (p = 0.015). Additionally, the cirrhotic patients had higher expression levels of the TGF-ß2 transcript and elevated levels of the TGF-ß2 protein than patients with no cirrhosis or fibrosis. According to the ROC analysis, TGFß1, TGIF1 transcripts, and TGFß2 protein have a good discriminatory performance in distinguishing between cirrhotic, fibrotic, and non-fibrotic patients. Our results suggested that the expression of TGIF1, TGF-ß1, and TGF-ß2 genes in PBMCs may provide a valuable tool for identifying patients with advanced cirrhosis and that TGF-ß and TGIF1 may be potential biomarkers for cirrhosis. These findings may have implications for the diagnosis and treatment of cirrhosis in HCV patients.

Comprehensive evaluation of phosphate deficiency tolerance in common vetch germplasms and the adaption mechanism to phosphate deficiency.

Common vetch (Vicia sativa L.) is widely planted as forage, green manure and food. Phosphate (Pi) deficiency is an important constraint for legume crop production. In this study, P-deficiency tolerance in 40 common vetch collections was evaluated under hydroponic condition. The collections were clustered into three groups based on the tolerance level. Physiological responses to P-deficiency in two tolerant collections (418 and 426) in comparison with one sensitive collection (415) were investigated. Greater growth inhibition was observed in sensitive collection compared with two tolerant collections, although the inorganic phosphorus (P) content in sensitive collection was higher than those in tolerant collections. The internal and external purple acid phosphatase activity in plants showed no significant difference between 418 and 415 under low phosphate condition. Transcriptomic analysis in the tolerant collection 426 in response to Pi starvation showed that many common adaptive strategies were applied and PHOSPHATE STARVATION RESPONSE (PHR)-related Pi signaling and transporter genes were altered. VsPHT1.2 had the highest expression level in root among all VsPHT1s, and it was remarkably upregulated after short time of P-deficiency treatment in tolerant collections compared with sensitive collection. In conclusion, common vetch response to P starvation by altering the expressions of core genes involved in Pi transport and signaling, and the elevated expression of VsPHT1.2 gene might contribute to higher Pi acquisition efficiency in P-deficiency tolerant collections.

PIP family-based association studies uncover ZmPIP1;6 involved in Pb accumulation and water absorption in maize roots.

Excessive lead (Pb) in the soil affects crop growth and development, thus threatening human beings via food chains. Plasma membrane intrinsic proteins (PIPs) facilitate the transport of substrates across cell membranes. Herein, we characterized maize PIPs and identified eight Pb accumulation-associated PIP genes using association studies. Among these, ZmPIP1;6 was simultaneously correlated with root Pb concentrations under various Pb treatment stages. Significant correlations were observed between the ZmPIP1;6 expression abundance and Pb accumulation in maize roots. Ectopic expression in yeast showed that ZmPIP1;6 conferred Pb accumulation in the cells and affected Pb tolerance in yeast. Overexpression in maize demonstrated that ZmPIP1;6 altered the Pb concentration performance and root moisture content under Pb stress. Meanwhile, protein interaction analyses suggested that ZmPIP1; 6 and three PIP2 members formed isoforms and facilitate water uptake in maize roots. However, ZmPIP1; 6 improved Pb absorption in maize roots probably by interacting with CASP-like protein 2C3 and/or another metal transporter. Moreover, the significant variants in the ZmPIP1;6 promoter caused the variations in ZmPIP1;6 expression level and Pb accumulation among various maize germplasms. Our study will contribute to understanding of PIP family-mediated Pb accumulation in crops and bioremediation of Pb-polluted soils.

Identification and Characterization of four Bacillus species from the intestine of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), their antagonistic role on common pathogenic bacteria, and effects on intestinal health.

As an alternative to the criticized antibiotics, probiotics have been adopted for their eco-friendly nature and ability to enhance host growth and immunity. Nevertheless, reports suggest ineffectiveness in commercially available probiotics since most are from non-fish sources; thus, this study was envisaged to isolate and characterize new Bacillus spp. from the gut of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂) as potential probiotics. The isolation and characterization were performed based on their morphological and biochemical properties and 16S rRNA sequencing homology analysis, and a subsequent 4-week in vivo biosafety feeding trial was conducted to ascertain the effects on isolates' non-pathogenicity, growth, and intestinal mucosal microvilli via scanning electron microscopy (SEM) analysis. Four Bacillus spp. strains, namely, B. velezensis strain PGSAK01 (accession number OQ726606), B. stercoris strain PGSAK05 (accession number OQ726607), B. velezensis strain PGSAK17 (accession number OQ726601), and B. subtilis strain PGSAK19 (accession number OQ726605), were identified and characterized in the current study. The strains showed promising probiotic properties such as showing higher adhesion capability, higher thermotolerance, displaying higher survivability to 0.5% bile, lower pH tolerance, γ-haemolytic activity, and multispecies characteristics. Among the 24 antibiotics tested, isolates were susceptible to 21, whereas the PGSAK01 strain showed resistance to furazolidone antibiotics. None of the isolates showed possession of i) virulence factor genes encoding enterotoxigenic (hblA, hblC, hblD, nheA, nheB, and entFM) and emetic (cereulide synthetase gene, ces) genes, and ii) streptomycin resistance gene (vat c), ampicillin-resistant genes (mecA and bla), and vancomycin-resistant gene (van B). Nevertheless, the PGSAK01 and PGSAK17 strains showed possession of tek K, cat, and ant(4')-Ia (adenylyltransferase) (except the PGSAK01) resistant genes. All isolates displayed better antimicrobial effects against pathogenic bacteria Streptococcus agalactiae, S. iniae, Vibrio harveyi, and V. alginolyticus. The vivo biosafety trial involved hybrid grouper fish being grouped into five (average weight 32±0.94 g), namely, the group fed the basal diet void of isolate's supplementation (control), and the remaining four groups fed the basal diet with 1×108 CFU/g diet of individual strain PGSAK01, PGSAK05, PGSAK17, and PGSAK19 supplementation. At the end of the study, a significantly higher WGR, K (except the PGSAK01 group), VSI; lysozyme (except PGSAK01 group), superoxide dismutase, total antioxidant activity, alkaline phosphatase enzyme activities; highly dense intestinal mucosal villi (based on the scanning electron microscopy analysis); and significantly lower malondialdehyde levels were witnessed in the isolated treated groups compared to the control, supporting the results obtained in the auto-aggregation and cell-surface hydrophobicity test. This work's results have provided thought-provoking targets; thus, studies involving extensive genome sequencing and functional annotation analysis will be explored to offer unfathomable insights into their mechanisms of action and potential health benefits, further establishing the four Bacillus strains PGSAK01, PGSAK05, PGSAK17, and PGSAK19 potential role in probiotic fields and functional foods.

Prospective One-Health investigation into low-abundant extended-spectrum ß-lactamase producing Enterobacterales enables detection of potential dissemination events and persistence.

BACKGROUND: Following a one-health approach, we sought to determine reservoirs of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), other than Escherichia coli or Klebsiella pneumoniae complex species (i.e., low-abundant species), and their associated ESBL genes and plasmid-replicon profiles. METHODS: From 06/2017-05/2019, ESBL-PE isolates were recovered from clinical samples routinely collected at the University Hospital Basel (Basel, Switzerland), as well as from wastewater and foodstuffs collected monthly at predefined locations throughout the city of Basel. Whole-genome sequencing was performed for characterization of ESBL-PE isolates. RESULTS: Among 1634 isolates recovered, 114 (7 %) belonged to 17 low-abundant ESBL-PE species. Seven species originated from more than one compartment, mainly from clinical and wastewater samples (6/17). Sixteen different ESBL genes were identified, with blaCTX-M-15 (27 %), blaFONA-6 (23 %) and blaSHV-12 (16 %) being most frequent. The blaCTX-M-1 gene was the only ESBL gene recovered from all three compartments. Putative plasmids constituted 60 % of ESBL gene-containing contigs, while chromosomes comprised 40 %. Foodstuff isolates showed the highest proportion (91 %, 41/45) of ESBL genes located on chromosomes, whereas wastewater isolates had the highest proportion (95 %, 37/39) of putative plasmids. Multi-replicon combinations were identified in 81 % of the isolates. Epidemiological links were found among some clinical and wastewater isolates. CONCLUSIONS: The dominance of blaCTX-M-15 among low-abundant ESBL-PE species supports its species-independent transmission potential beyond the E. coli and K. pneumoniae complex, and blaCTX-M-1 may be transmitted between strains recovered from different environments. The substantial overlap between non-abundant ESBL-PE present in wastewater and clinical samples supports the utility of wastewater surveillance for antibiotic resistance monitoring.

Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with Gilbert and Crigler-Najjar II syndrome.

The spectrum of UDP-glucuronosyltransferase (UGT1A1) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual UGT1A1 variants in GS and CNS-II remains to be clarified. To explore the UGT1A1 variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene UGT1A1 by a polymerase chain reaction and Sanger sequencing. The correlation between different UGT1A1 variants and clinical phenotypes was analyzed. A total of 21 UGT1A1 variants were identified, including nine novel variants, and constituted 42 UGT1A1 genotypes in the GS and CNS-II patients. The most common UGT1A1 variants were A(TA)7TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A(TA)7TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of UGT1A1, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A(TA)7TAA, homozygous p.G71R, compound heterozygous A(TA)7TAA/p.G71R and A(TA)7TAA/p.P364L, and combined heterozygous A(TA)7TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A(TA)7TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A(TA)7TAA/p.G71R, single heterozygous A(TA)7TAA, single heterozygous p.G71R, and homozygous A(TA)7TAA. The spectrum of UGT1A1 genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of UGT1A1.

Phenotypic Spectrum in Weiss-Kruszka Syndrome caused by ZNF462 variants: Three New Patients and Literature Review.

Weiss-Kruszka Syndrome (WSKA) is caused by pathogenic variants in ZNF462 representing a rare autosomal dominant congenital anomaly syndrome. It is characterized by global developmental delay, hypotonia, feeding difficulties, and craniofacial abnormalities, documented in fewer than 30 patients. ZNF462, located on chromosome 9p31.2, is a transcription factor and has an important role during embryonic development and chromatin remodelling. Here, we report three new patients with WSKA, Through whole exome sequencing (WES) analysis, we identified two novel variants in three patients, two of whom are siblings. These variants (c.3078dup, p.Val1027Cysfs5 and c.4792A>T p.Lys1598*) in the ZNF462 gene are likely resulting in haploinsufficiency. Our patients help to further delineate the phenotype, genotype and potential therapeutic management strategies for WSKA. Since we report a second WSKA patient with an autoimmune disease further clinical and functional studies are needed to elucidate the association between this chromatin remodelling disorder and the development of autoimmune problems. In the future, collaborative efforts are encouraged to develop an episignature for WSKA, given the gene's function and associated patient phenotypes. This new technology has the potential to provide valuable insights into the disorder.

Clinical, biochemical and genetic characteristics and long-term follow-up of five patients with malonyl-CoA decarboxylase deficiency.

BACKGROUND: Malonyl-CoA decarboxylase (MLYCD) deficiency, also known as malonic aciduria (MAD), is a rare autosomal recessive inherited metabolic defect. In this study, we aimed to investigate the clinical and molecular features of five patients with MAD in order to increase clinicians' awareness of the disease. METHODS: Sanger sequencing was used to detect and genetically analyze the MLYCD variations in the preexisting patients and their parents. RESULTS: Five patients with MAD (5 months to 9.6 years old; two males and three females) rarely exhibited metabolic decompensation episodes or seizures. All patients exhibited varying degrees of developmental delay and hypotonia. Our study expands the spectrum of variants of the MLYCD gene. MLYCD gene variations were detected in all five patients, and five new variants were identified: c.60delG (p.Arg21Glyfs*52), c.928C > T (p.Arg310*), c.1293G > T (p.Trp431Cys), c.721T > C (p.Ser241Pro), and Exons 4-5 deletion. Additionally, there is no correlation between various genotypes and phenotypes. CONCLUSION: A high-medium-chain triglyceride and low-long-chain triglyceride diet supplemented with L-carnitine was effective in most patients and may improve cardiomyopathy and muscle weakness. Newborn screening may aid in the early diagnosis, treatment, and prognosis of this rare disorder.

Thiamine status and genes encoding intestinal thiamine transporters and transcription factors in obese subjects.

BACKGROUND AND AIMS: The inconsistent data on thiamine status in obese subjects necessitates an examination of genes associated with intestinal absorption of thiamine. We aimed to reveal thiamine status in obese subjects and examine the expression of SLC19A2/3 genes encoding thiamine transporters and Sp1 transcription factor. METHODS AND RESULTS: Thirty-five adult obese subjects and 11 healthy controls were included in this cross-sectional study. Small intestine epithelial cells were used for quantitative RT-PCR analysis of the gene expression. The daily thiamine and energy intake were assessed with a food frequency questionnaire. Thiamine phosphate esters were hydrolyzed to free thiamine, and liquid chromatography with a tandem mass spectrometry-based method was used to measure total thiamine in whole blood. Daily energy intake according to body weight and daily carbohydrate intake were not significantly different between groups after adjustment for sex. Although daily thiamine intake was significantly lower in the obesity group (p = 0.015), obese subjects had significantly higher whole blood thiamine levels than controls (44.96 ± 14.6 ng/mL and 33.05 ± 8.6 ng/mL, p = 0.002). There was a significant positive correlation between whole blood thiamine and BMI (r = 0.342, p = 0.020). SLC19A2 gene expression was lower in those with BMI ≥35 kg/m2 (p = 0.036). A significant positive correlation was found between SLC19A2 expression and whole blood thiamine level (r = 0.310, p = 0.038). CONCLUSION: A possible association between intestinal thiamine intake and total thiamine in whole blood was determined. The transcriptional changes of genes encoding the high-affinity membrane thiamine transporters, especially SLC19A2, probably play a role in this relationship.

Diabetic macular edema: Upcoming therapies.

Diabetic macular edema (DME) is a serious vision-threatening complication that can arise at any stage of diabetic retinopathy. Primary treatment involves anti-vascular endothelial growth factor (VEGF) agents, which are highly effective but associated with challenges, such as the need for frequent injections, relapses, and resistance to therapy. Therefore, there has been a growing interest in developing new treatments that offer similar or superior outcomes in DME. This review article explores emerging treatments, including WNT agonists, gene therapy, protein inhibitors, and, most importantly, the first-ever non-invasive and oral drugs. The evolving therapies in diabetic retinopathy offer hope for continued improvement in vision loss associated with one of the most common chronic conditions worldwide.

The potential of gene delivery for the treatment of traumatic brain injury.

Therapeutics for traumatic brains injuries constitute a global unmet medical need. Despite the advances in neurocritical care, which have dramatically improved the survival rate for the ~ 70 million patients annually, few treatments have been developed to counter the long-term neuroinflammatory processes and accompanying cognitive impairments, frequent among patients. This review looks at gene delivery as a potential therapeutic development avenue for traumatic brain injury. We discuss the capacity of gene delivery to function in traumatic brain injury, by producing beneficial biologics within the brain. Gene delivery modalities, promising vectors and key delivery routes are discussed, along with the pathways that biological cargos could target to improve long-term outcomes for patients. Coupling blood-brain barrier crossing with sustained local production, gene delivery has the potential to convert proteins with useful biological properties, but poor pharmacodynamics, into effective therapeutics. Finally, we review the limitations and health economics of traumatic brain injury, and whether future gene delivery approaches will be viable for patients and health care systems.

Impact of IL-6 and IL-10 genotypes on tacrolimus dose requirements in kidney transplant recipients: Monte Carlo analysis.

Introduction: IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes. Aim: To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C0/D) in various post-transplantation periods. Materials & methods: IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C0, C0/D and intrapatient variability data were collected from 113 patients. Results: Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen. Conclusion: This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.

[Box: see text].

Engineering single-cycle MeV vector for CRISPR-Cas9 gene editing.

CRISPR-Cas9-mediated gene editing has vast applications in basic and clinical research and is a promising tool for several disorders. Our lab previously developed a non-integrating RNA virus, measles virus (MeV), as a single-cycle reprogramming vector by replacing the viral attachment protein with the reprogramming factors for induced pluripotent stem cell generation. Encouraged by the MeV reprogramming vector efficiency, in this study, we develop a single-cycle MeV vector to deliver the gRNA(s) and Cas9 nuclease to human cells for efficient gene editing. We show that the MeV vector achieved on-target gene editing of the reporter (mCherry) and endogenous genes (HBB and FANCD1) in human cells. Additionally, the MeV vector achieved precise knock-in via homology-directed repair using a single-stranded oligonucleotide donor. The MeV vector is a new and flexible platform for gene knock-out and knock-in modifications in human cells, capable of incorporating new technologies as they are developed.

Evaluation of anti-vector immune responses to adenovirus-mediated lung gene therapy and modulation by αCD20.

Although the last decade has seen tremendous progress in drugs that treat cystic fibrosis (CF) due to mutations that lead to protein misfolding, there are approximately 8%-10% of subjects with mutations that result in no significant CFTR protein expression demonstrating the need for gene editing or gene replacement with inhaled mRNA or vector-based approaches. A limitation for vector-based approaches is the formation of neutralizing humoral responses. Given that αCD20 has been used to manage post-transplant lymphoproliferative disease in CF subjects with lung transplants, we studied the ability of αCD20 to module both T and B cell responses in the lung to one of the most immunogenic vectors, E1-deleted adenovirus serotype 5. We found that αCD20 significantly blocked luminal antibody responses and efficiently permitted re-dosing. αCD20 had more limited impact on the T cell compartment, but reduced tissue resident memory T cell responses in bronchoalveolar lavage fluid. Taken together, these pre-clinical studies suggest that αCD20 could be re-purposed for lung gene therapy protocols to permit re-dosing.

Concurrent Cardiac and Renal Anomalies in Waardenburg Syndrome Type 1: A Report of a Rare Case.

Waardenburg syndrome (WS) is an autosomal dominant genetic disorder characterized by the absence of melanocytes, leading to distinctive pigmentary abnormalities and sensorineural hearing loss. This case report describes extremely rare concurrent anomalies in a preterm male infant diagnosed with WS type 1. The newborn, delivered prematurely at 35 weeks due to maternal complications, presented with multiple congenital anomalies and required immediate resuscitation. He exhibited hallmark features of WS, including a white forelock, dystopia canthorum, and bilateral sensorineural hearing loss. Genetic testing confirmed a PAX3 gene mutation. The infant experienced significant respiratory and feeding challenges, necessitating intensive care. Management included mechanical ventilation, surfactant therapy, phototherapy for hyperbilirubinemia, and broad-spectrum antibiotics for suspected sepsis. The cardiac assessment revealed multiple anomalies, such as a patent foramen ovale and left ventricular hypertrophy, while renal ultrasound identified multicystic dysplastic kidney and bilateral hydronephrosis. Multidisciplinary care facilitated the infant's stabilization, transition to oral feeding, and ongoing specialized care. WS type 1 is associated with mutations in the PAX3 gene and presents with diverse clinical manifestations. Although renal and cardiac anomalies are uncommon in WS, their presence in this case underscores the complexity of the syndrome. Early intervention for hearing impairment and genetic counseling are critical for optimal outcomes. This report highlights the importance of a comprehensive and interdisciplinary approach to managing infants with WS, addressing both typical and atypical manifestations. It is worth noting that effective management of WS in neonates requires prompt identification and treatment of associated complications.

Association Between FADS1 Gene Polymorphism (rs174549) and Chronic Periodontitis: A Cross-Sectional Study.

Introduction FADS1 (fatty acid desaturase 1) gene polymorphism results in more susceptibility to certain metabolic diseases and chronic inflammatory diseases like periodontitis. This study aims to analyze the association between FADS1 gene polymorphism and various stages of periodontitis. Materials and methods One hundred subjects included in the study were categorized into two groups: group A (n = 50) had healthy periodontium, and group B (n = 50) had ≥stage II periodontitis. They were graded based on the clinical parameters of probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP). Five milliliters of venous blood were collected, and DNA isolation was done. Genomic DNA was extracted. The DNA was then subjected to amplification with the help of specific primers flanking the Providencia stuartii I (PstI) polymorphic site of the FADS1 gene. A chi-square test aimed to examine the genotype and allele frequency distributions in both groups; p < 0.05 was considered statistically significant. Results The difference in genotype frequency of FADS1 polymorphism was statistically insignificant (p = 0.91). Our study revealed no significant difference (AA vs. AG+GG) between the periodontitis and control groups between homozygous and heterozygous variant genotypes with a p-value of 0.7764. The frequency of AG (28% vs. 30%) and GG (62% vs. 58%) genotypes showed no significant difference between the periodontitis group and healthy control subjects. No significant difference was seen in the G allele (77% vs. 73%) and A allele (23% vs. 27%) between the periodontitis and control groups. Conclusion The study concluded that FADS1 receptor polymorphism is not associated with periodontitis in the study population.

A Comprehensive Review of the Endometrial Receptivity Array in Euploid Embryo Transfer Cycles.

The Endometrial Receptivity Array (ERA) is a revolutionary molecular diagnostic tool that determines the optimal timing for embryo transfer by analyzing the gene expression profile of endometrial tissue. This comprehensive review examines the significance and application of ERA in euploid embryo transfer cycles, where the implantation of embryos with the correct number of chromosomes is critical for achieving successful pregnancy outcomes. This review underscores its role in enhancing implantation rates and reducing pregnancy loss by assessing the evolution, methodology, clinical applications, efficacy, and challenges associated with ERA. Key findings highlight ERA's superior accuracy in identifying the window of implantation compared to traditional methods, resulting in improved clinical outcomes in assisted reproductive technology (ART) cycles. Despite its benefits, the review acknowledges challenges such as cost, accessibility, and the need for standardization. Recommendations for clinical practice emphasize the integration of ERA into routine ART protocols, comprehensive patient counseling, and the importance of multidisciplinary collaboration. The review outlines promising prospects, including technological advancements to make ERA more cost-effective, the development of refined gene expression profiles, and the potential integration with other emerging ART technologies. Further research directions include long-term studies on the outcomes of ERA-guided pregnancies and exploring its application in cases of recurrent implantation failure and unexplained infertility. Overall, ERA represents a significant advancement in reproductive medicine, offering a personalized approach to embryo transfer timing that can significantly improve the success rates of euploid embryo transfers.

QTL detection and candidate gene identification of qCTB1 for cold tolerance in the Yunnan plateau landrace rice.

Cold stress is one of the main abiotic stresses that affects rice growth and production worldwide. Dissection of the genetic basis is important for genetic improvement of cold tolerance in rice. In this study, a new source of cold-tolerant accession from the Yunnan plateau, Lijiangxiaoheigu, was used as the donor parent and crossed with a cold-sensitive cultivar, Deyou17, to develop recombinant inbred lines (RILs) for quantitative trait locus (QTL) analysis for cold tolerance at the early seedling and booting stages in rice. In total, three QTLs for cold tolerance at the early seedling stage on chromosomes 2 and 7, and four QTLs at the booting stage on chromosomes 1, 3, 5, and 7, were identified. Haplotype and linear regression analyses showed that QTL pyramiding based on the additive effect of these favorable loci has good potential for cold tolerance breeding. Effect assessment in the RIL and BC3F3 populations demonstrated that qCTB1 had a stable effect on cold tolerance at the booting stage in the genetic segregation populations. Under different cold stress conditions, qCTB1 was fine-mapped to a 341-kb interval between markers M3 and M4. Through the combination of parental sequence comparison, candidate gene-based association analysis, and tissue and cold-induced expression analyses, eight important candidate genes for qCTB1 were identified. This study will provide genetic resources for molecular breeding and gene cloning to improve cold tolerance in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01488-3.