Current Issue : October-December Volume : 2025 Issue Number : 4 Articles : 5 Articles
Hemolytic anemias (HAs) encompasses a heterogeneous group of disorders with either congenital or acquired etiologies. We present a complex case of a 27-year-old woman with hemolytic anemia of multifactorial origin, involving both inherited RBC membrane defects and multiple autoimmune comorbidities. Genetic testing identified heterozygous variants in SPTA1 and SBDS, consistent with carrier status for hereditary elliptocytosis and Shwachman–Diamond syndrome. The patient was also diagnosed with Caspr2-positive Isaacs syndrome, systemic lupus erythematosus, seronegative antiphospholipid syndrome, and anti-aquaporin-4 antibody-positive optic neuritis. Despite extensive immunosuppressive and immunotherapic treatment and splenectomy, the clinical course was marked by recurrent hemolytic crises, thrombotic complications, and progressive neurological involvement, ultimately leading to death. Our experience highlights the challenges posed by the diagnosis and management of HAs, underlining the relevance of a multidisciplinary and personalized approach....
Epileptic seizures often track with time of day and/or changes in vigilance state; however, specific molecular and cellular mechanisms driving the ictal and temporal associations are lacking. Astrocytes are a type of glial cell known to modulate neuronal excitability and circadian rhythms. These cells also abundantly express fatty acid–binding protein 7 (Fabp7), a clock-driven molecule necessary for normal sleep regulation, lipid signaling, and gene transcription. To determine whether Fabp7 influences time-of-day-dependent seizure susceptibility, we tested male C57/BL6N wild-type (WT) and Fabp7 knockout (KO) mice using electroshock seizure threshold. Compared with WT mice, Fabp7 KO mice exhibited markedly higher general- and maximal-electroshock seizure thresholds (GESTs and MESTs, respectively) during the dark phase, but not the light phase. We used RNA-seq to determine the role of Fabp7 in activitydependent gene expression in nocturnal seizures and compared genome-wide mRNA expression in cortical/hippocampal tissue collected from WT-MEST and Fabp7 KO-MEST mice with WT-SHAM and Fabp7 KO-SHAM mice during the dark period. Whereas significant differential expression of immediate early genes was observed in WT-MEST compared with WT-SHAM, this effect was blocked in the Fabp7 KO-MEST versus Fabp7 KO-SHAM. Gene ontology and pathway analysis of all groups revealed significant overlap between WT-MEST:WT-SHAM and Fabp7 KO-SHAM:WT-SHAM comparisons, suggesting basal mRNA levels of core molecular and cellular mechanisms in the brain of Fabp7 KO approximate postictal WT brain. Together, these data suggest that Fabp7 regulates time-of-day-dependent neural excitability and that neural activity likely interacts with astrocyte Fabp7-mediated signaling cascades to influence activity-dependent gene expression....
Hyaluronan, a key component of the extracellular matrix, plays a crucial role in joint development and maintenance. In order to determine the role of hyaluronan function in joint development and homeostasis, conditional loss-of-function experiments of Hyaluronan Synthase 2 (Has2) were carried out in mice. Has2 depletion in limb mesenchymal cells led to severely shortened limbs with appendicular joints that are deformed, decreased proteoglycan content as characterized by Safranin-O staining, and severely pitted epiphyseal ends of long bones and deformed joints as viewed by micro-CT reconstructions. The embryonic deletion of Has2 in mesoderm mesenchyme of limbs by Prx1-Cre confirmed its involvement in joint development, while in situ hybridization and hyaluronan staining confirmed Has2 expression and abundant accumulation of hyaluronan in the onset of joint formation, the joint interzone. These findings position Has2 as the main hyaluronan-making enzyme in articular cartilage and highlight its essential function in joint formation and retention of proteoglycans of the extracellular matrix of the cartilage....
Background: Large-scale family pedigrees are commonly used across medical, evolutionary, and forensic genetics. These pedigrees are tools for identifying genetic disorders, tracking evolutionary patterns, and establishing familial relationships via forensic genetic identification. However, there is a lack of software to accurately simulate different pedigree structures along with genomes corresponding to those individuals in a family pedigree. This limits simulation-based evaluations of methods that use pedigrees. Results: We have developed a python command-line-based tool called py_ped_sim that facilitates the simulation of pedigree structures and the genomes of individuals in a pedigree. py_ped_sim represents pedigrees as directed acyclic graphs, enabling conversion between standard pedigree formats and integration with the forward population genetic simulator, SLiM. Notably, py_ped_sim allows the simulation of varying numbers of offspring for a set of parents, with the capacity to shift the distribution of sibship sizes over generations. We additionally add simulations for events of misattributed paternity, which offers a way to simulate half-sibling relationships, and simulations to extend the breadth of a family pedigree. We validated the accuracy of both our genome simulator and pedigree simulator. We show that we can simulate genomes onto family pedigrees with levels of expected kinship. Conclusions: py_ped_sim is a user-friendly and open-source solution for simulating pedigree structures and conducting pedigree genome simulations. It empowers medical, forensic, and evolutionary genetics researchers to gain deeper insights into the dynamics of genetic inheritance and relatedness within families....
As gestational diabetes mellitus (GDM) rises as a major public health concern, various factors have been identified as potential contributors, with air pollution drawing increasing attention. The mechanisms by which air pollutants lead to detrimental impacts are largely attributed to oxidative stress. However, the role of air pollution is still not entirely clarified, suggesting that additional factors, such as genetic variability, particularly of genes involved in redox homeostasis, influence the GDM risk. This study addresses three questions: (1) whether ambient PM2.5, PM10, O3, and NO2 exposures associate with GDM risk; (2) if GSTM1‐/GSTT1‐null genotypes affect the risk of GDM; and (3) whether these genotypes modify pollution–GDM associations. This case–control study comprised 133 women in the case group and 144 in the control group. Exposure to air pollutants was assessed based on the participants’ residential addresses and during different time windows: pre‐pregnancy period, first trimester, and second trimester. GSTM1/GSTT1 genotyping was conducted from blood samples. Higher PM2.5, PM10, and O3 levels increased GDM risk in women. While GSTM1‐/GSTT1‐null genotypes showed no overall link to GDM, non‐smokers with GSTM1‐null had higher GDM risk when exposed to PM2.5 during the first trimester. While further research on gene–environment interactions is needed, our findings highlight that reducing air pollution may lower GDM risk....
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