Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined.Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation.In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research

Clear cell renal cell carcinoma and papillary renal cell carcinoma: differentiation of distinct histological types with multiphase CT

PURPOSEConventional clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) have different behavioral characteristics and clinical management strategies (nephrectomy vs. nephron-sparing surgery). Our aim was to retrospectively evaluate the contrast enhancement pattern of ccRCC and pRCC and evaluate its possible diagnostic role for preoperative differentiation using a standardized protocol.MATERIALS AND METHODSQuadriphasic multidetector computed tomography (CT) images (unenhanced, corticomedullary, nephrographic, and excretory phases) of 19 patients with 20 ccRCC and 14 patients with 15 pRCC lesions (mean ages, 62.3±14.1 and 61.4±13.7 years, respectively) were reviewed retrospectively. The attenuation characteristics were compared with the attenuation of the normal renal cortex using either multiple 10 mm2 regions of interest or whole tumor attenuation measurements. The degree of contrast enhancement was also compared.RESULTSUnivariate analysis revealed that ccRCC lesions showed higher mean attenuation values on the corticomedullary and nephrographic phases compared with pRCC masses (P < 0.05) using both measurement techniques.CONCLUSIONThe findings underscore the importance of multiphase CT in the differentiation of these two subtypes of RCC using standard assessment techniques. The measurement of the degree of enhancement on contrast-enhanced multidetector CT may be a simple and useful method to radiologically differentiate between the two histological types of RCC

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Identification of a Lacosamide Binding Protein Using an Affinity Bait and Chemical Reporter Strategy: 14-3-3 ζ

We have advanced a useful strategy to elucidate binding partners of ligands (drugs) with modest binding affinity. Key to this strategy is attaching to the ligand an affinity bait (AB) and a chemical reporter (CR) group, where the AB irreversibly attaches the ligand to the receptor upon binding and the CR group is employed for receptor detection and isolation. We have tested this AB&CR strategy using lacosamide ((R)-1), a low-molecular-weight antiepileptic drug. We demonstrate that using a (R)-lacosamide AB&CR agent ((R)-2) 14-3-3 ζ in rodent brain soluble lysates is preferentially adducted, adduction is stereospecific with respect to the AB&CR agent, and adduction depends upon the presence of endogenous levels of the small molecule metabolite xanthine. Substitution of lacosamide AB agent ((R)- 5) for (R)-2 led to the identification of the 14-3-3 ζ adduction site (K120) by mass spectrometry. Competition experiments using increasing amounts of (R)-1 in the presence of (R)-2 demonstrated that (R)-1 binds at or near the (R)-2 modification site on 14-3-3 ζ. Structure-activity studies of xanthine derivatives provided information concerning the likely binding interaction between this metabolite and recombinant 14-3-3 ζ. Documentation of the 14-3-3 ζ-xanthine interaction was obtained with isothermal calorimetry using xanthine and the xanthine analogue 1,7-dimethylxanthine

The effect of holes in the dispersion relation of propagative surface plasmon modes of nanoperforated semitransparent metallic films

© 2014 AIP Publishing LLC. We have analysed the effect that holes have on the properties of propagative surface plasmon modes in semitransparent nanoperforated Au films. The modes have been excited in Kretschmann configuration. Contrary to continuous films, where only one mode is excited, two modes are observed in Au nanohole array. The origin of this different behavior is discussed using effective optical properties for the nanoperforated films. The presence of the holes affects the effective optical constants of the membranes in two ways: it changes the contribution of the free electrons, and it gives rise to a localized transition due to a hole induced plasmon resonance. This localized transition interacts with the propagative surface plasmon modes, originating the two detected modes.Funding from Spanish Ministry of Economy and Competitiveness through grants “FUNCOAT” CONSOLIDER CSD2008–00023, MAPS MAT2011–29194-C02–01, and from Comunidad de Madrid through grant “MICROSERES-CM” S2009/TIC-1476 is acknowledged.Peer Reviewe

Photocatalysis on silver-layer silicate/titanium dioxide composite thin films at solid/vapour interface

Silver-montmorillonite/TiO2 composites were prepared using various mixing ratios. The optical properties of the catalyst composites were evaluated DR-UV-vis spectrophotometry. Their photocatalytic efficiencies were tested in the degradation of ethanol vapour at a relative humidity of similar to 70% in a closed circulating reactor. Light sources used were 15 W lamps, one rich in UV (lambda >= 254 nm) and one emitting visible light (lambda >= 435 nm). The course of photodegradation of ethanol vapour was monitored by gas chromatography. By incorporating silver ions into clay minerals/TiO2 mixtures with different ratio, we obtained composites capable of degrading ethanol in the visible wavelength range about twice as fast as the reference photocatalyst, type P25. The synergistic effect is interpreted as the result of the excellent adsorption capabilities of layer silicates combined with the advantageous effect of silver nanoparticles and silver oxides on light absorption in the visible range