Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in ataxin-3 (SCA3, MJD1) protein. In biochemical experiments we demonstrate that mutant SCA3exp specifically associated with the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1), an intracellular calcium (Ca2+) release channel. In electrophysiological and Ca2+ imaging experiments we show that InsP3R1 are sensitized to activation by InsP3 in the presence of mutant SCA3exp. We found that feeding SCA3-YAC-84Q transgenic mice with dantrolene, a clinically relevant stabilizer of intracellular Ca2+ signaling, improved their motor performance and prevented neuronal cells loss in pontine nuclei and substantia nigra regions. Our results indicate that deranged Ca2+ signaling may play an important role in SCA3 pathology and that Ca2+ signaling stabilizers such as dantrolene may be considered as potential therapeutic drugs for treatment of SCA3 patients

Controlling competing interactions at oxide interfaces: Enhanced anisotropy in La0.7Sr0.3MnO3 films via interface engineering

We investigated thin La0.7Sr0.3MnO3-SrTiO3 heterostructures, where the band alignment is engineered by a variation of La/Sr stoichiometry only at the interface. In thin films, the engineered interface leads to an enhancement of the reversed spin configuration that mimics bulk behavior. Microscopically, this enhancement is closely connected with an increased magnetic anisotropy as well as intercoupling between an e(g) orbital reconstruction and a corresponding anisotropic lattice fluctuation. Furthermore, a reentrant-type behavior, triggered by this intercoupling, is observed in the remanent spin state. This microscopic perspective leads to insights on developing new strategies for maintaining bulk-like properties even in very thin La0.7Sr0.3MnO3 heterostructures.open11910Ysciescopu

Bounds on SCFTs from Conformal Perturbation Theory

The operator product expansion (OPE) in 4d (super)conformal field theory is of broad interest, for both formal and phenomenological applications. In this paper, we use conformal perturbation theory to study the OPE of nearly-free fields coupled to SCFTs. Under fairly general assumptions, we show that the OPE of a chiral operator of dimension $\Delta = 1+\epsilon$ with its complex conjugate always contains an operator of dimension less than $2 \Delta$. Our bounds apply to Banks-Zaks fixed points and their generalizations, as we illustrate using several examples.Comment: 36 pages; v2: typos fixed, minor change

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy:a systematic review and meta-analysis

Aim: To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method: MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. Results: Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. Interpretation: Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome

Bounds on 4D Conformal and Superconformal Field Theories

We derive general bounds on operator dimensions, central charges, and OPE coefficients in 4D conformal and N=1 superconformal field theories. In any CFT containing a scalar primary phi of dimension d we show that crossing symmetry of implies a completely general lower bound on the central charge c >= f_c(d). Similarly, in CFTs containing a complex scalar charged under global symmetries, we bound a combination of symmetry current two-point function coefficients tau^{IJ} and flavor charges. We extend these bounds to N=1 superconformal theories by deriving the superconformal block expansions for four-point functions of a chiral superfield Phi and its conjugate. In this case we derive bounds on the OPE coefficients of scalar operators appearing in the Phi x Phi* OPE, and show that there is an upper bound on the dimension of Phi* Phi when dim(Phi) is close to 1. We also present even more stringent bounds on c and tau^{IJ}. In supersymmetric gauge theories believed to flow to superconformal fixed points one can use anomaly matching to explicitly check whether these bounds are satisfied.Comment: 47 pages, 9 figures; V2: small corrections and clarification

Lignin biomarkers as tracers of mercury sources in lakes water column

This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

Cervical adenocarcinoma presenting as a cardiac tamponade in a 57-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pericardial effusion as a complication of malignant gynecological disorders is rare. Few cases of endometrial cancer, squamous cell carcinoma of the cervix, ovarian cancer and uterine carcinosarcoma have been previously reported. We report the first case of cardiac tamponade secondary to a cervical adenocarcinoma.</p> <p>Case presentation</p> <p>A 54-year-old Caucasian woman, without any relevant medical history and no gynecological aftercare, was admitted to our hospital emergency room with severe dyspnea. Echocardiography revealed severe pericardial effusion with a swinging heart. An emergency pericardial drainage was performed through a pericardial window, which permitted the draining of 700 mL of bloody fluid and a pericardial biopsy. Cytological examination of the fluid revealed atypical cells, and the biopsy specimen showed tumor emboli suggestive of adenocarcinoma. Magnetic resonance imaging showed a 35 mm cervical lesion indicative of an endocervical tumor. Exploratory laparoscopy revealed diffuse peritoneal lesions and histological examination of cervical curettage showed a poorly differentiated micropapillary adenocarcinoma of the cervix.</p> <p>Conclusion</p> <p>Carcinomatous pericarditis as the first symptom of a malignant gynecological adenocarcinoma has not, to the best of our knowledge, been documented before. This case highlights the extreme severity of pericardial effusion secondary to cervical adenocarcinoma, a sign of advanced disease. Gynecological malignancies have to be considered in cases of neoplastic pericardial effusion.</p

Sociological and Communication-Theoretical Perspectives on the Commercialization of the Sciences

Both self-organization and organization are important for the further development of the sciences: the two dynamics condition and enable each other. Commercial and public considerations can interact and "interpenetrate" in historical organization; different codes of communication are then "recombined." However, self-organization in the symbolically generalized codes of communication can be expected to operate at the global level. The Triple Helix model allows for both a neo-institutional appreciation in terms of historical networks of university-industry-government relations and a neo-evolutionary interpretation in terms of three functions: (i) novelty production, (i) wealth generation, and (iii) political control. Using this model, one can appreciate both subdynamics. The mutual information in three dimensions enables us to measure the trade-off between organization and self-organization as a possible synergy. The question of optimization between commercial and public interests in the different sciences can thus be made empirical.Comment: Science & Education (forthcoming

How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics