Thermodynamics of Lithium Intercalation into Graphites and Disordered Carbons

The temperature dependence of the open-circuit potential of lithium half-cells was measured for electrodes of carbon materials having different amounts of structural disorder. The entropy of lithium intercalation, DeltaS, and enthalpy of intercalation, DeltaH, were determined over a broad range of lithium concentrations. For the disordered carbons, DeltaS is small. For graphite, an initially large DeltaS decreases with lithium concentration, becomes negative, and then shows two plateaus associated with the formation of intercalation compounds. For all carbons DeltaH is negative, and decreases in magnitude with increased lithium concentration. For lithium concentrations less than x = 0.5 in LixC6, for the disordered carbons the magnitude of DeltaH is significantly more negative than for graphite (i.e., intercalation is more exothermic). The measurements of DeltaH provide an energy spectrum of chemical environments for lithium. This spectrum can be used to understand some of the concentration dependence of configurational entropy, but the negative values of DeltaS require another contribution to entropy, perhaps vibrational in origin

Short range correlations and the isospin dependence of nuclear correlation functions

Pair densities and associated correlation functions provide a critical tool for introducing many-body correlations into a wide-range of effective theories. Ab initio calculations show that two-nucleon pair-densities exhibit strong spin and isospin dependence. However, such calculations are not available for all nuclei of current interest. We therefore provide a simple model, which involves combining the short and long separation distance behavior using a single blending function, to accurately describe the two-nucleon correlations inherent in existing ab initio calculations. We show that the salient features of the correlation function arise from the features of the two-body short-range nuclear interaction, and that the suppression of the pp and nn pair-densities caused by the Pauli principle is important. Our procedure for obtaining pair-density functions and correlation functions can be applied to heavy nuclei which lack ab initio calculations.Comment: 5 pages, 4 figure

OPA1 functions in mitochondria and dysfunctions in optic nerve

OPA1 is the major gene responsible for Dominant Optic Atrophy (DOA), a blinding disease that affects specifically the retinal ganglion cells (RGCs), which function consists in connecting the neuro-retina to the brain. OPA1 encodes an intra-mitochondrial dynamin, involved in inner membrane structures and ubiquitously expressed, raising the critical question of the origin of the disease pathophysiology. Here, we review the fundamental knowledge on OPA1 functions and regulations, highlighting their involvements in mitochondrial respiration, membrane dynamic and apoptosis. In light of these functions, we then describe the remarkable RGC mitochondrial network physiology and analyse data collected from animal models expressing OPA1 mutations. If, to date RGC mitochondria does not present any peculiarity at the molecular level, they represent possible targets of numerous assaults, like light, pressure, oxidative stress and energetic impairment, which jeopardize their function and survival, as observed in OPA1 mouse models. Although fascinating fields of investigation are still to be addressed on OPA1 functions and on DOA pathophysiology, we have reached a conspicuous state of knowledge with pertinent cell and animal models, from which therapeutic trials can be initiated and deeply evaluated

OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database

BACKGROUND: The dysfunction of OPA1, a dynamin GTPase involved in mitochondrial fusion, is responsible for a large spectrum of neurological disorders, each of which includes optic neuropathy. The database dedicated to OPA1 ( https://www.lovd.nl/OPA1 ), created in 2005, has now evolved towards a centralized and more reliable database using the Global Variome shared Leiden Open-source Variation Database (LOVD) installation. RESULTS: The updated OPA1 database, which registers all the patients from our center as well as those reported in the literature, now covers a total of 831 patients: 697 with isolated dominant optic atrophy (DOA), 47 with DOA "plus", and 83 with asymptomatic or unclassified DOA. It comprises 516 unique OPA1 variants, of which more than 80% (414) are considered pathogenic. Full clinical data for 118 patients are documented using the Human Phenotype Ontology, a standard vocabulary for referencing phenotypic abnormalities. Contributors may now make online submissions of phenotypes related to OPA1 mutations, giving clinical and molecular descriptions together with detailed ophthalmological and neurological data, according to an international thesaurus. CONCLUSIONS: The evolution of the OPA1 database towards the LOVD, using unified nomenclature, should ensure its interoperability with other databases and prove useful for molecular diagnoses based on gene-panel sequencing, large-scale mutation statistics, and genotype-phenotype correlations

Metabo-lipidomics of Fibroblasts and Mitochondrial-Endoplasmic Reticulum Extracts from ALS Patients Shows Alterations in Purine, Pyrimidine, Energetic, and Phospholipid Metabolisms

Amyotrophic lateral sclerosis (ALS) is characterized by a wide metabolic remodeling, as shown by recent metabolomics and lipidomics studies performed in samples from patient cohorts and experimental animal models. Here, we explored the metabolome and lipidome of fibroblasts from sporadic ALS patients (n = 13) comparatively to age- and sex-matched controls (n = 11), and the subcellular fraction containing the mitochondria and endoplasmic reticulum (mito-ER), given that mitochondrial dysfunctions and ER stress are important features of ALS patho-mechanisms. We also assessed the mitochondrial oxidative respiration and the mitochondrial genomic (mtDNA) sequence, although without yielding significant differences. Compared to controls, ALS fibroblasts did not exhibit a mitochondrial respiration defect nor an increased proportion of mitochondrial DNA mutations. In addition, non-targeted metabolomics and lipidomics analyses identified 124 and 127 metabolites, and 328 and 220 lipids in whole cells and the mito-ER fractions, respectively, along with partial least-squares-discriminant analysis (PLS-DA) models being systematically highly predictive of the disease. The most discriminant metabolomic features were the alteration of purine, pyrimidine, and energetic metabolisms, suggestive of oxidative stress and of pro-inflammatory status. The most important lipidomic feature in the mito-ER fraction was the disturbance of phosphatidylcholine PC (36:4p) levels, which we had previously reported in the cerebrospinal fluid of ALS patients and in the brain from an ALS mouse model. Thus, our results reveal that fibroblasts from sporadic ALS patients share common metabolic remodeling, consistent with other metabolic studies performed in ALS, opening perspectives for further exploration in this cellular model in ALS

Entry, Descent, and Landing with Propulsive Deceleration: Supersonic Retropropulsion Wind Tunnel Testing and Shock Phenomena

The future exploration of the Solar System will require innovations in transportation and the use of entry, descent, and landing (EDL) systems at many planetary landing sites. The cost of space missions has always been prohibitive, and using the natural planetary and planet's moon atmospheres for entry, and descent can reduce the cost, mass, and complexity of these missions. This paper will describe some of the EDL ideas for planetary entry and survey the overall technologies for EDL that may be attractive for future Solar System missions. Future EDL systems may include an inflatable decelerator for the initial atmospheric entry and an additional supersonic retropropulsion (SRP) rocket system for the final soft landing. A three engine retropropulsion configuration with a 2.5 in. diameter sphere-cone aeroshell model was tested in the NASA Glenn Research Center's 1- by 1-ft (11) Supersonic Wind Tunnel (SWT). The testing was conducted to identify potential blockage issues in the tunnel, and visualize the rocket flow and shock interactions during supersonic and hypersonic entry conditions. Earlier experimental testing of a 70deg Viking-like (sphere-cone) aeroshell was conducted as a baseline for testing of a SRP system. This baseline testing defined the flow field around the aeroshell and from this comparative baseline data, retropropulsion options will be assessed. Images and analyses from the SWT testing with 300- and 500-psia rocket engine chamber pressures are presented here. In addition, special topics of electromagnetic interference with retropropulsion induced shock waves and retropropulsion for Earth launched booster recovery are also addressed

Tailoring communication in consultations with women from high risk breast cancer families

This multicentre study examined the influence of patient demographic, disease status and psychological variables on clinical geneticists/genetic counsellors (consultants) behaviours in initial consultations with women from high-risk breast cancer families. One hundred and fifty-eight women completed a pre-clinic self-report questionnaire. The consultations were audiotaped, transcribed verbatim and coded. Consultants did not vary their behaviour according to women's expectations. However, significantly more aspects of genetic testing were discussed with women who were affected with breast cancer (P<0.001), screening and management with unaffected women (P=0.01) and breast cancer prevention with younger women (P=0.01). Prophylactic mastectomy was discussed more frequently with women with medical and allied health training (P=0.02), and prophylactic oophorectomy with women affected with breast cancer (P=0.03), those in non-professional occupations (P=0.04) and with a family history of breast and ovarian cancer (P<0.001). Consultants used significantly more behaviours to facilitate understanding with women who were in non-professional occupations (P=0.04); facilitated active patient involvement more with women affected with breast cancer (P<0.001) and used more supportive and counselling behaviours with affected women (P=0.02). This study showed that patient demographics were more likely to predict consultants' communication behaviours than the woman's psychological status. Methods to facilitate assessment of psychological morbidity are needed to allow more tailored communication

The human OPA1delTTAG mutation induces premature age-related systemic neurodegeneration in mouse

Dominant optic atrophy is a rare inherited optic nerve degeneration caused by mutations in the mitochondrial fusion gene OPA1. Recently, the clinical spectrum of dominant optic atrophy has been extended to frequent syndromic forms, exhibiting various degrees of neurological and muscle impairments frequently found in mitochondrial diseases. Although characterized by a specific loss of retinal ganglion cells, the pathophysiology of dominant optic atrophy is still poorly understood. We generated an Opa1 mouse model carrying the recurrent Opa1(delTTAG) mutation, which is found in 30% of all patients with dominant optic atrophy. We show that this mouse displays a multi-systemic poly-degenerative phenotype, with a presentation associating signs of visual failure, deafness, encephalomyopathy, peripheral neuropathy, ataxia and cardiomyopathy. Moreover, we found premature age-related axonal and myelin degenerations, increased autophagy and mitophagy and mitochondrial supercomplex instability preceding degeneration and cell death. Thus, these results support the concept that Opa1 protects against neuronal degeneration and opens new perspectives for the exploration and the treatment of mitochondrial diseases

Communication and information-giving in high-risk breast cancer consultations: influence on patient outcomes

This longitudinal study aimed to document (i) the information-giving and patient-communication styles of clinical geneticists and genetic counsellors (consultants) in familial breast cancer clinics and (ii) assess the effect of these styles on women`s knowledge, whether their expectations were met, satisfaction, risk perception and psychological status. A total of 158 women from high-risk breast cancer families completed self-report questionnaires at 2 weeks preconsultation and 4 weeks postconsultation. The consultations were audiotaped, transcribed and coded. Multivariate logistic regressions showed that discussing prophylactic mastectomy (P = 0.00) and oophorectomy (P = 0.01) led to women having significantly more expectations met; discussing genetic testing significantly decreased anxiety (P = 0.03) and facilitating understanding significantly decreased depression (P = 0,05). Receiving a summary letter of the consultation significantly lowered anxiety (P = 0.01) and significantly increased the accuracy of perceived risk (P = 0.02). Women whose consultant used more supportive communications experienced significantly more anxiety about breast cancer at the 4 weeks follow-up (P=0.00), These women were not significantly more anxious before genetic counselling. In conclusion, this study found that consultants vary in the amount of information they give and the way they communicate; and this variation can result in better or worse psychosocial outcomes. Greater use of supportive and counselling communications appeared to increase anxiety about breast cancer. Identifying methods to assist consultants to address emotional issues effectively may be helpful