Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias.

We assessed the presence, frequency and pattern of MRI abnormalities in non-dystrophic myotonia patients. We reviewed T1-weighted and STIR (short-tau-inversion-recovery) 3T MRI sequences of lower limb muscles at thigh and calf level in 21 patients with genetically confirmed non-dystrophic myotonia: 11 with CLCN1 mutations and 10 with SCN4A mutations, and 19 healthy volunteers. The MRI examinations of all patients showed hyperintensity within muscles on either T1-weighted or STIR images. Mild extensive or marked T1-weighted changes were noted in 10/21 patients and no volunteers. Muscles in the thigh were equally likely to be affected but in the calf there was sparing of tibialis posterior. Oedema was common in calf musculature especially in the medial gastrocnemius with STIR hyperintensity observed in 18/21 patients. In 10/11 CLCN1 patients this included a previously unreported "central stripe", also present in 3/10 SCN4A patients but no volunteers. Degree of fatty infiltration correlated with age (rho=0.46, p<0.05). Muscle MRI is frequently abnormal in non-dystrophic myotonia providing evidence of fatty infiltration and/or oedema. The pattern is distinct from other myotonic disorders; in particular the "central stripe" has not been reported in other conditions. Correlations with clinical parameters suggest a potential role for MRI as a biomarker

ApoE influences regional white-matter axonal density loss in Alzheimer's disease

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration

Metal-macrofauna interactions determine microbial community structure and function in copper contaminated sediments

Peer reviewedPublisher PD

Influence of soil minerals on chromium(VI) reduction by sulfide under anoxic conditions

The effects of soil minerals on chromate (Cr(VI)O(4)(2-), noted as Cr(VI)) reduction by sulfide were investigated in the pH range of 7.67 to 9.07 under the anoxic condition. The examined minerals included montmorillonite (Swy-2), illite (IMt-2), kaolinite (KGa-2), aluminum oxide (γ-Al(2)O(3)), titanium oxide (TiO(2), P-25, primarily anatase), and silica (SiO(2)). Based on their effects on Cr(VI) reduction, these minerals were categorized into three groups: (i) minerals catalyzing Cr(VI) reduction – illite; (ii) minerals with no effect – Al(2)O(3); and (iii) minerals inhibiting Cr(VI) reduction- kaolinite, montmorillonite, SiO(2 )and TiO(2 ). The catalysis of illite was attributed primarily to the low concentration of iron solubilized from the mineral, which could accelerate Cr(VI) reduction by shuttling electrons from sulfide to Cr(VI). Additionally, elemental sulfur produced as the primary product of sulfide oxidation could further catalyze Cr(VI) reduction in the heterogeneous system. Previous studies have shown that adsorption of sulfide onto elemental sulfur nanoparticles could greatly increase sulfide reactivity towards Cr(VI) reduction. Consequently, the observed rate constant, k(obs), increased with increasing amounts of both iron solubilized from illite and elemental sulfur produced during the reaction. The catalysis of iron, however, was found to be blocked by phenanthroline, a strong complexing agent for ferrous iron. In this case, the overall reaction rate at the initial stage of reaction was pseudo first order with respect to Cr(VI), i.e., the reaction kinetics was similar to that in the homogeneous system, because elemental sulfur exerted no effect at the initial stage prior to accumulation of elemental sulfur nanoparticles. In the suspension of kaolinite, which belonged to group (iii), an inhibitive effect to Cr(VI) reduction was observed and subsequently examined in more details. The inhibition was due to the sorption of elemental sulfur onto kaolinite, which reduced or completely eliminated the catalytic effect of elemental sulfur, depending on kaolinite concentration. This was consistent with the observation that the catalysis of externally added elemental sulfur (50 μM) on Cr(VI) reduction would disappear with a kaolinite concentration of more than 5.0 g/L. In kaolinite suspension, the overall reaction rate law was: -d[Cr(VI)]/dt = k(obs)[H(+)](2)[Cr(VI)][HS(-)](0.70

Evolution in intergenerational exchanges between elderly people and their grandchildren in Taiwan; data from a multiple round cross-sectional study from 1993 to 2007

<p>Abstract</p> <p>Background</p> <p>This study aimed to evaluate social evolution in Taiwan in recent decades using the changing pattern of care provided by grandparents for their grandchildren as an indicator.</p> <p>Methods</p> <p>Data from the second, fourth and sixth wave surveys of the <it>Study of Health and Living Status of the Middle-Aged and Elderly in Taiwan </it>were used for the analysis. This survey collected individual characteristics, including age, gender, education, ethnicity, dwelling place, living with partners, co-resident with children, employment status, self-reported health status and their provision of care for their grandchildren. Information about the attitudes toward National Health Insurance (NHI) was further collected in a questionnaire of 1999 following the implementation of NHI in 1995. By elders, we mean persons 60 or more years old. By grandchildren, we mean persons under 16 years of age. First, changes in individual characteristics were compared during these study periods (chi-square test). Then the logistic regression was performed to determine how significantly elders' grandchild-care behavior was associated with their individual characteristics.</p> <p>Results</p> <p>The percentage of elders providing grandchild care increased from 7.7% in 1993 to 13.6% in 1999, and then to 19.4% in 2007. By analysis, significant association was found between behavior in taking care of grandchildren and individuals of lower age, grandmothers, those living with partners or co-residing with children, those unemployed and those with better self-reported health status. And the effect of year was confirmed in the multivariable analysis.</p> <p>Conclusions</p> <p>This study pointed out the changing pattern of elders' behavior in taking care of their grandchildren as the main indicator and their related individual characteristics. We argue the need for improving social security policies in an ageing society. We suggest that the interaction between population policies and those of social welfare, including policies for health care and childcare, should be carefully evaluated.</p

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Large-Scale Selective Sweep among Segregation Distorter Chromosomes in African Populations of Drosophila melanogaster

Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD+ males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1–5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (∼2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Evaluation of 3D T1-weighted imaging at 3T across scanner vendors and models

Volumetric analyses of 3D T1-weighted images has become an integral part of the clinical work-up and research studies. Variation between scanners, in both vendors and models, is a major confound in combining imaging-derived biomarkers across sites. In this work, we analyse test-retest data from di×erent days on six 3 T scanners from three vendors to quantify this inter-scanner variability compared to intra-scanner variability. Contrast-to-noise ratios as well as volumetric analyses are performed showing between-scanner variation in total brain volumes – indicating di×erent scanner calibrations – but also tissue-speciÒc di×erences – possibly arising from di×erent e×ective contrasts