First description of frequent occurrence of supernumerary lumbar ribs and transitional vertebrae in children with Williams-Beuren syndrome.

BACKGROUND: Williams-Beuren syndrome is a rare multisystemic genetic disorder with an incidence of 1 in 7,500 live births. Because these children often have scoliosis, they undergo routine radiographic examinations of the spine. During these examinations we have found many children with supernumerary lumbar ribs arising from the first lumbar vertebra, often associated with lumbosacral transitional vertebrae. OBJECTIVE: To describe the incidence of supernumerary ribs and transitional vertebrae in children with Williams-Beuren syndrome and compare it to the incidence in a general population. Our hypothesis is that these findings are common, but they have not been described in the literature concerning Williams-Beuren syndrome. MATERIALS AND METHODS: From January 2015 to October 2021, 308 patients (138 male) with Williams-Beuren syndrome were treated at our hospital. Of these, 106 (47 male) underwent diagnostic imaging, mostly for suspected scoliosis. Panoramic radiographs of the whole spine were performed in 88 patients and radiographs of regions of the spine, chest radiographs, CT, MRI or fluoroscopy in 18 patients. We retrospectively analysed the images concerning the number of ribs and vertebrae. We correlated the frequency of lumbar ribs and transitional vertebrae in comparison to a general population as described in the literature. RESULTS: After exclusions for insufficient imaging, we analysed imaging in 91 patients. Of these, 67 patients (73.6%) had 13 ribs, of which 85% were located on both sides, 9% on the right and 6% on the left side. Of the 67 patients with supernumerary lumbar ribs, 38 (57%) also had transitional vertebrae. CONCLUSION: Supernumerary lumbar ribs arising from the first lumbar vertebra, often accompanied by lumbosacral transitional vertebrae, are common in children with Williams-Beuren syndrome.

An electrochemical in situ study of freezing and thawing of ionic liquids in carbon nanopores.

Room temperature ionic liquids (RTILs) are an emerging class of electrolytes enabling high cell voltages and, in return, high energy density of advanced supercapacitors. Yet, the low temperature behavior, including freezing and thawing, is little understood when ions are confined in the narrow space of nanopores. This study shows that RTILs may show a tremendously different thermal behavior when comparing bulk with nanoconfined properties as a result of the increased surface energy of carbon pore walls. In particular, a continuous increase in viscosity is accompanied by slowed-down charge-discharge kinetics as seen with in situ electrochemical characterization. Freezing reversibly collapses the energy storage ability and thawing fully restores the initial energy density of the material. For the first time, a different thermal behavior in positively and negatively polarized electrodes is demonstrated. This leads to different freezing and melting points in the two electrodes. Compared to bulk, RTILs in the confinement of electrically charged nanopores show a high affinity for supercooling; that is, the electrode may freeze during heating.

Potential screening assays for individual radiation sensitivity and susceptibility and their current validation state.

Purpose: The workshop on 'Individual Radiosensitivity and Radiosusceptibility' organized by MELODI and CONCERT on Malta in 2018, evaluated the current state of assays to identify sensitive and susceptible subgroups. The authors provide an overview on potential screening assays detecting individuals showing moderate to severe early and late radiation reactions or are at increased risk to develop cancer upon radiation exposure.Conclusion: It is necessary to separate clearly between tissue reactions and stochastic effects such as cancer when comparing the existing literature to validate various test systems. Requirements for the assays are set up. The literature is reviewed for assays that are reliable and robust. Sensitivity and specificity of the assays are regarded and scrutinized for modifying factors. Accuracy of an assay system is required to be more than 90% to balance risks of adverse reactions against risk to fail to cure the cancer. No assay/biomarker is in routine use. Assays that have shown predictive potential for radiosensitivity include SNPs, the RILA assay, and the pATM assay. A tree of risk guideline for radiologists is provided to assist medical treatment decisions. Recommendations for effective research include the setup of common retrospective and prospective cohorts/biobanks to validate current and future tests.

Nrf2 Signaling in Sodium Azide-Treated Oligodendrocytes Restores Mitochondrial Functions.

Mitochondrial dysfunctions mark a critical step in many central nervous system (CNS) pathologies, including multiple sclerosis (MS). Such dysfunctions lead to depolarization of mitochondrial membranes and imbalanced redox homeostasis. In this context, reactive oxygen species (ROS) are potentially deleterious but can also act as an important signaling step for cellular maintenance. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the key regulator in the cellular oxidative stress-response, induces a battery of genes involved in repair and regeneration. Here, we investigated the relevance of Nrf2 signaling for the prevention of cellular damage caused by dysfunctional mitochondria. We employed sodium azide (SA) as mitochondrial inhibitor on oligodendroglial OliNeu cells in vitro, and the cuprizone model with wild type and GFAP-Cre+::Keap1loxP/loxP mice to induce mitochondrial defects. The importance of Nrf2 for cellular functions and survival after SA treatment was elucidated by in vitro knockdown experiments with shRNA directed against Nrf2 and its inhibitor Keap1 as well as by methysticin treatment. Metabolic activity, cytotoxicity, and depolarization of the mitochondrial membrane were analyzed after SA treatment. The expression of Nrf2 target genes as well as endoplasmic reticulum stress response genes was additionally measured by real-time PCR (in vitro) and PCR gene arrays (in vivo). Treatment of OliNeu cells with SA resulted in significant depolarization of the mitochondrial membrane, decreased metabolic activity, and increased cytotoxicity. This was partly counteracted in Nrf2-hyperactivated cells and intensified in Nrf2-knockdown cells. Our studies demonstrate a key role of Nrf2 in maintaining cellular functions and survival in the context of mitochondrial dysfunction.

Heritability of susceptibility to ionizing radiation-induced apoptosis of human lymphocyte subpopulations.

PURPOSE: To evaluate the heritability of intrinsic radiosensitivity, the induction of apoptosis in lymphocyte subpopulations was determined on samples from related individuals belonging to large kindred families. METHODS AND MATERIALS: Quiescent lymphocytes from 334 healthy individuals were gamma-irradiated in vitro. Apoptosis was determined 18 h after irradiation by eight-color flow cytometry. Radiosensitivity was quantified from dose-effect curves. Intrafamilial correlations and heritability were computed for 199 father-mother-offspring trios using the programs SOLAR (Sequential Oligogenic Linkage Analysis Routines) and SAGE (Statistical Analysis for Genetic Epidemiology). Segregation analyses were conducted using SAGE. RESULTS: Marked differential susceptibility of naive and memory T lymphocytes was demonstrated. Also, although age and gender were significant covariates, their effects only accounted for a minor part of the inter-individual variation. Parent-offspring and sib-sib correlations were significant for the radiosensitivity of B cells, T4, and T8 and of effector memory T4 and T8 subpopulations. In the T4-effector memory subpopulation, the phenotype showed correlations most consistent with dominant or additive genetic effects, and the results of the segregation analysis were consistent with the contribution of a bi-allelic dominant locus. CONCLUSIONS: Heritability was demonstrated for the susceptibility to ionizing radiation-induced apoptosis of lymphocyte populations, and the segregation of the T4-effector memory radiosensitivity phenotype was consistent with a simple mendelian transmission model involving one major gene.

TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis.

Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10)mRNA level and a higher level of membrane bound TRAIL (mTRAIL) on radiosensitive compared to radioresistant T4EM lymphocytes. Functionally, we show that mTRAIL mediates a pro-apoptotic autocrine signaling after irradiation of T4EM lymphocytes linking mTRAIL expression to T4EM radiosensitivity. Using single marker and multimarker Family-Based Association Testing, we identified 3 SNPs in the TRAIL gene that are significantly associated with T4EM lymphocytes radiosensitivity. Among these 3 SNPs, two are also associated with acute and subacute dermatitis after radiotherapy in breast cancer indicating that T4EM lymphocytes radiosensitivity may be used to predict response to radiotherapy. Altogether, these results show that mTRAIL level regulates the response of T4EM lymphocytes to ionizing radiation and suggest that TRAIL/TNFSF10 genetic variants hold promise as markers of individual radiosensitivity.

Intrinsic susceptibility to radiation-induced apoptosis of human lymphocyte subpopulations.

PURPOSE: With the aim to evaluate intrinsic radiosensitivity, the susceptibility of lymphocyte subpopulations to radiation-induced apoptosis was determined. The investigated parameters included measurement reliability, phenotypic variance, intra- and inter-individual variability, and correlations between radiation-induced and spontaneous apoptosis. METHODS AND MATERIALS: Quiescent lymphocytes of 63 healthy volunteers, sampled up to four times over a 1-year period were gamma-irradiated in vitro. Subsequent apoptosis (annexin V) was measured for T4-, T8-, and B-lymphocyte subpopulations using 6-color flow cytometry. Spontaneous apoptosis was measured and radiosensitivity was quantified from the dose-effect curves. RESULTS: After thawing and short-term culture, both spontaneous apoptosis as well as radiation-induced apoptosis (radiosensitivity) differed among the three lymphocyte subpopulations, with T4 being most resistant, and B most sensitive. Spontaneous and radiation-induced apoptosis were correlated in all cell types, and variance between individuals was considerably higher than variance within individuals for both. A small but highly significant increase of both spontaneous and radiation-induced apoptosis was observed with age for T8, but not for T4 and B. Radiosensitivity of T8 and B proved to be sex-independent, whereas female T4 lymphocytes were less radiosensitive than those from males. T4 and T8 radiosensitivities were loosely correlated, and neither of them was related to B radiosensitivity. CONCLUSION: Tendency to spontaneous and radiation-induced apoptosis of lymphocyte subpopulations differs among individuals. In addition, depending on the cell types, age and sex are factors influencing these parameters.

Narrowly dispersed silica supported osmium nanoparticles prepared by an organometallic approach: H2 and CO adsorption stoichiometry and hydrogenolysis catalytic activity.

Osmium(cyclooctadiene)(cyclooctatetraene) is used as a molecular precursor to prepare small and narrowly distributed silica supported nanoparticles upon a mild treatment under H2 (1.1 ± 0.3 nm, ca. 90 atoms). Static volumetric chemisorption combined with HAADF-STEM shows that Os nanoparticles adsorb 1.7 ± 0.1 H and 1.4 ± 0.1 CO per surface atom. These particles present high activity in the hydrogenolysis of alkanes via a dimetallacyclopentane mechanism.

Allele-specific relative telomere lengths are inherited.

Previous studies have indicated that single relative telomere lengths are defined in the zygote. In order to explore the possibility that single telomere lengths segregate in families, we compared relative telomere lengths obtained from allelic chromosome extremities transmitted from parent to child, representing a total of 31 independent meiotic events. We find a significant positive correlation of 0.65 (P=0.0004) between these telomere lengths, whereas the correlation between the non-transmitted parental homologue and the transmitted homologue in the child is not statistically significant (r=0.16; P=0.195). This study indicates that, even though there is a telomerase-mediated maintenance/elongation of telomeres in germ cells, allele-specific relative telomere lengths are preserved in the next generation.