Recent experiments on a small-angle/wide-angle X-ray scattering beam line at the ESRF

Recent results using a new combined small-angle/wide-angle X-ray scattering (SAXS/WAXS) beam line at the European Synchrotron Radiation Source (ESRF) will be presented. This beam line is specifically designed to be able to handle complicated sample environments required to perform time-resolved experiments mimicking processing conditions used in material science. Besides the attention that has been given to the interfacing of these sample environments to the beam line data acquisition system also the developments in detector technology will be discussed. The influence that a high count rate and low noise WAXS detector can have on the accuracy of experimental results in polymer crystallisation will be shown. It is shown that it is feasible to detect crystalline volume fractions as low as 10(-3)-10(-4) in polymeric systems

Controls on runoff generation and scale-dependence in a distributed hydrologic model

International audienceHydrologic response in natural catchments is controlled by a set of complex interactions between storm properties, basin characteristics and antecedent wetness conditions. This study investigates the transient runoff response to spatially-uniform storms of varying properties using a distributed model of the coupled surface-subsurface system, which treats heterogeneities in topography, soils and vegetation. We demonstrate the control that the partitioning into multiple runoff mechanisms (infiltration-excess, saturation-excess, perched return flow and groundwater exfiltration) has on nonlinearities in the rainfall-runoff transformation and its scale-dependence. Antecedent wetness imposed through a distributed water table position is varied to illustrate its effect on runoff generation. Results indicate that transitions observed in basin flood response (magnitude, timing and volume) can be explained by shifts in the surface-subsurface partitioning. An analysis of the spatial organization of runoff production also shows that multiple mechanisms have specific catchment niches and can occur simultaneously in the basin. In addition, catchment scale plays an important role in the distribution of runoff production as basin characteristics (soils, vegetation, topography and initial wetness) are varied with basin area. For example, we illustrate how storm characteristics and antecedent wetness play a dramatic role in the scaling properties of the catchment runoff ratio

Budd-Chiari syndrome recurring in a transplanted liver

A patient with Budd-Chiari syndrome who underwent orthotopic liver transplantation and developed recurrent disease is described. The immediate postoperative period was complicated by multiple thrombotic episodes, followed by a period of apparent remission associated with the initiation of coumadin and persantine therapy. After discontinuation of such antithrombotic therapy in order to biopsy the liver, the patient experienced another series of clinically overt vascular thromboses and ultimately died of sepsis 15 mo posttransplantation after a prolonged and complicated terminal hospital course. At autopsy, recurrent Budd-Chiari syndrome as well as thromboses in numerous other organs was demonstrated. © 1983

A combined SAXS/WAXS investigation of the phase behaviour of di-polyenoic membrane lipids

AbstractReal-time measurements of the SAXS/WAXS diffraction patterns of aqueous dispersions (1:1 wt/wt) of the di-polyenoic lipids di-18:2 PC, di-18:3 PC, di-18:2 PE and di-18:3 PE were made over the temperature range 10° to about −80°C. The results of these measurements were compared to similar measurements performed on the corresponding di-18:0 and di-18:1 derivatives. SAXS measurements of the temperature dependence of lamellar repeat distances show that the di-polyenoic lipids undergo broad second-order transitions between their gel and liquid-crystal lamellar phases spanning 30–40°C. The di-18:1 and di-18:0 derivatives, in contrast, undergo abrupt first-order transitions. The gel phases of the di-18:0 derivatives are characterised by two-component WAXS patterns with a sharp component close to 0.42 nm and a broader component at narrower spacings. On cooling, these lipids appear to undergo an initial transition to an Lβ, phase followed by a conversion to an Lc phase. The gel phases of the di-18:1 derivatives also show two-component patterns but with the sharp component centred closer to 0.44 nm. The di-polyenoic lipids, in contrast, are characterised by a single broad peak centred at a spacing of about 0.42 nm, close to that of conventional Lβ, phases. The changes in lamellar repeat distance accompanying the transitions in the di-monoenoic and di-polyenoic lipids, all of which occur in the frozen state, are very similar, indicating that the acyl chains of the polyenoic lipids are close to their maximum extension in the gel state. The WAXS patterns of the polyenoic lipids suggest that the saturated upper parts of the acyl chains are packed on a regular hexagonal lattice while their polyunsaturated termini remain relatively disordered

RARS2 mutations in a sibship with infantile spasms

Pontocerebellar hypoplasia is a group of heterogeneous neurodevelopmental disorders characterized by reduced volume of the brainstem and cerebellum. We report two male siblings who presented with early infantile clonic seizures, and then developed infantile spasms associated with prominent isolated cerebellar hypoplasia/atrophy on magnetic resonance imaging (MRI). Using whole exome sequencing techniques, both were found to be compound heterozygotes for one previously reported and one novel mutation in the gene encoding mitochondrial arginyl-tRNA synthetase 2 (RARS2). Mutations in this gene have been classically described in pontocerebellar hypoplasia type six (PCH6), a phenotype characterized by early (often intractable) seizures, profound developmental delay, and progressive pontocerebellar atrophy. The electroclinical spectrum of PCH6 is broad and includes a number of seizure types: myoclonic, generalized tonic-clonic, and focal clonic seizures. Our report expands the characterization of the PCH6 disease spectrum and presents infantile spasms as an associated electroclinical phenotype

Energy-Dissipation, Runoff Production, and the 3-Dimensional Structure of River Basins

Three principles of optimal energy expenditure are used to derive the most important structural characteristics observed in drainage networks: (1) the principle of minimum energy expenditure in any link of the network, (2) the principle of equal energy expenditure per unit area of channel anywhere in the network, and (3) the principle of minimum total energy expenditure in the network as a whole. Their joint application results in a unified picture of the most important empirical facts which have been observed in the dynamics of the network and its three-dimensional structure. They also link the process of runoff production in the basin with the characteristics of the network

The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders

Summary Alzheimer's disease is a genetically complex disorder; rare variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been shown to as much as triple an individual's risk of developing Alzheimer's disease. TREM2 is a transmembrane receptor expressed in cells of the myeloid lineage, and its association with Alzheimer's disease supports the involvement of immune and inflammatory pathways in the cause of the disease, rather than as a consequence of the disease. TREM2 variants associated with Alzheimer's disease induce partial loss of function of the TREM2 protein and alter the behaviour of microglial cells, including their response to amyloid plaques. TREM2 variants have also been shown to cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy and frontotemporal dementia. Although the low frequency of TREM2 variants makes it difficult to establish robust genotype–phenotype correlations, such studies are essential to enable a comprehensive understanding of the role of TREM2 in different neurological diseases, with the ultimate goal of developing novel therapeutic approaches

Polygenic risk scores for Alzheimer's disease are related to dementia risk in APOE ɛ4 negatives

Introduction: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking. / Methods: A population‐based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD‐PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used. / Results: AD‐PRSs (including 39 or 57 SNPs) were associated with dementia (57‐SNPs AD‐PRS: hazard ratio 1.09, confidence interval 1.01–1.19, P = .03), particularly in APOE ɛ4 non‐carriers (57‐SNPs AD‐PRS: 1.15, 1.05–1.27, P = 4 × 10–3, 39‐SNPs AD‐PRS: 1.22, 1.10–1.35, P = 2 × 10–4). No association was found with the other AD‐PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35–1.92, P = 1 × 10–7). In those aged ≥95 years, the results were similar for the AD‐PRSs, while APOE ɛ4 only predicted dementia in the low‐risk tertile of AD‐PRSs. / Discussion: These results provide information to identify individuals at increased risk of dementia

A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation.

SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations

Different susceptibility of osteosarcoma cell lines and primary cells to treatment with oncolytic adenovirus and doxorubicin or cisplatin

Despite improvements in treatment regimens for osteosarcoma (OS) patients, survival rate has not increased over the last two decades. New treatment modalities are therefore warranted. Preclinical results with conditionally replicative adenoviruses (CRAds) to treat OS are promising. One type of CRAd that was effective against OS cells is Ad5-Δ24RGD. In other types of cancer, CRAds have been shown to interact synergistically with chemotherapeutic agents. Chemotherapy for OS often includes doxorubicin and cisplatin. Therefore, we explored combination treatment of OS cell lines and primary OS cell cultures with Ad5-Δ24RGD and doxorubicin or cisplatin. On OS cell lines, combination treatment was additive to synergistic. Surprisingly, however, on seven of eight primary OS samples no such combination effects were observed. In contrast, in many cases chemotherapy even inhibited CRAd-mediated cell killing. The inhibitory effect of doxorubicin on Ad5-Δ24RGD in primary OS cells appeared to correlate with slow cell growth rate; reduced viral replication and absence of chemotherapy-induced G2 cell cycle arrest. Our results point to the possibility that, at least for OS, virotherapy and chemotherapy should best not be performed simultaneously. In general, our work underscores the importance of testing new genetic anticancer agents and treatment regimens on primary cancer specimens