Aberrant DJ-1 expression underlies L-type calcium channel hypoactivity in dendrites in tuberous sclerosis complex and Alzheimer's disease.

L-type voltage-gated calcium (Ca2+) channels (L-VGCC) dysfunction is implicated in several neurological and psychiatric diseases. While a popular therapeutic target, it is unknown whether molecular mechanisms leading to disrupted L-VGCC across neurodegenerative disorders are conserved. Importantly, L-VGCC integrate synaptic signals to facilitate a plethora of cellular mechanisms; however, mechanisms that regulate L-VGCC channel density and subcellular compartmentalization are understudied. Herein, we report that in disease models with overactive mammalian target of rapamycin complex 1 (mTORC1) signaling (or mTORopathies), deficits in dendritic L-VGCC activity are associated with increased expression of the RNA-binding protein (RBP) Parkinsonism-associated deglycase (DJ-1). DJ-1 binds the mRNA coding for the alpha and auxiliary Ca2+ channel subunits CaV1.2 and α2δ2, and represses their mRNA translation, only in the disease states, specifically preclinical models of tuberous sclerosis complex (TSC) and Alzheimer's disease (AD). In agreement, DJ-1-mediated repression of CaV1.2/α2δ2 protein synthesis in dendrites is exaggerated in mouse models of AD and TSC, resulting in deficits in dendritic L-VGCC calcium activity. Finding of DJ-1-regulated L-VGCC activity in dendrites in TSC and AD provides a unique signaling pathway that can be targeted in clinical mTORopathies.

Depositing ALD-oxides on MLD-metalcones: enhancing initial growth through O2 plasma densification.

Flexible devices are experiencing a steady increase in popularity, which brings the need of suitable protective/functional coatings for these applications. On the one hand, Atomic Layer Deposition (ALD) produces thin films with great purity, few pinholes and good conformality, but flexibility is rather limited. On the other hand, Molecular Layer Deposition (MLD) can produce partially/fully organic coatings with good flexibility, but stability concerns limit their applications. Therefore, combining ALD and MLD to obtain materials with good flexibility and improved characteristics holds great potential. In this article, we utilised O2 plasma treatments on various metalcone films to improve the compatibility of sequential ALD/MLD depositions. During plasma modification, in situ spectroscopic ellipsometry measurements (in situ SE) suggested that mainly the near-surface region of the metalcone layer was affected by the plasma treatment, locally converting the metalcone into a metal-oxide structure. This structure shielded the underlying metalcone layer from the plasma, thus resulting in a saturative-type behaviour even during extended plasma exposures. X-Ray reflectivity measurements (XRR) could only be fitted with bilayer models, while Fourier-Transform InfraRed spectroscopy (FTIR) showed an absorption decrease in the C-O band and an increase in the CO region. Additionally, film air stability seemed improved by this treatment. ALD-oxides were grown on these plasma-treated metalcones (PT-metalcones), and results were compared to pristine ones. While ALD growth on pristine metalcones always suffered from a delay, after which linear growth was achieved, oxides on PT-metalcones exhibited linear growth immediately, from cycle one. We therefore conclude that, upon O2 plasma exposure, metalcones are densified into a metalcone/oxide bilayer, where the oxide shields the underlying film from further oxidation. And, if an ALD oxide coating is to be deposited on top of these structures, this plasma treatment will make the structure more suitable for post-processing. In applications that require the combination of ALD/MLD multistacks, the use of an intermittent plasma treatment can prove useful.

UV photonic integrated circuits for far-field structured illumination autofluorescence microscopy.

Ultra-violet (UV) light has still a limited scope in optical microscopy despite its potential advantages over visible light in terms of optical resolution and of interaction with a wide variety of biological molecules. The main challenge is to control in a robust, compact and cost-effective way UV light beams at the level of a single optical spatial mode and concomitantly to minimize the light propagation loss. To tackle this challenge, we present here photonic integrated circuits made of aluminum oxide thin layers that are compatible with both UV light and high-volume manufacturing. These photonic circuits designed at a wavelength of 360 nm enable super-resolved structured illumination microscopy with conventional wide-field microscopes and without modifying the usual protocol for handling the object to be imaged. As a biological application, we show that our UV photonic chips enable to image the autofluorescence of yeast cells and reveal features unresolved with standard wide-field microscopy.

Converting molecular layer deposited alucone films into Al2O3/alucone hybrid multilayers by plasma densification.

Alucones are one of the best-known films in the Molecular Layer Deposition (MLD) field. In this work, we prove that alucone/Al2O3 nanolaminate synthesis can be successfully performed by alternating alucone MLD growth with static O2 plasma exposures. Upon plasma treatment, only the top part of the alucone is densified into Al2O3, while the rest of the film remains relatively unaltered. X-ray reflectivity (XRR) and X-ray photoelectron spectroscopy (XPS) depth profiling show that the process yields a bilayer structure, which remains stable in air. Fourier-transform infrared spectroscopy (FTIR) measurements show that Al2O3 features are generated after plasma treatment, while the original alucone features remain, confirming that plasma treatment results in a bilayer structure. Also, an intermediate carboxylate is created in the interface. Calculations of Al atom density during plasma exposure point towards a partial loss of Al atoms during plasma treatment, in addition to the removal of the glycerol backbone. The effect of different process parameters has been studied. Densification at the highest temperature possible (200 °C) has the best alucone preservation without hindering its thermal stability. In addition, operating at the lowest plasma power is found the most beneficial for the film, but there is a threshold that must be surpassed to achieve successful densification. About 70% of the original alucone film thickness can be expected to remain after densification, but thicker films may result in more diffuse interfaces. Additionally, this process has also been successfully performed in multilayers, showing real potential for encapsulation applications.

Mitigation of photon background in nanoplasmonic all-on-chip Raman sensors.

In the quest for a more compact and cheaper Raman sensor, photonic integration and plasmonic enhancement are central. Nanoplasmonic slot waveguides exhibit the benefits of SERS substrates while being compatible with photonic integration and mass-scale (CMOS) fabrication. A difficulty in pursuing further integration of the Raman sensor with lasers, spectral filters, spectrometers and interconnecting waveguides lies in the presence of a photon background generated by the excitation laser field in any dielectric waveguide constituting those elements. Here, we show this problem can be mitigated by using a multi-mode interferometer and a nanoplasmonic slot waveguide operated in back-reflection to greatly suppress the excitation field behind the sensor while inducing very little photon background.

Connecting biology, optics and nanomechanical properties in micro-wasps.

Coloration in insects provides a fruitful opportunity for interdisciplinary research involving both physics and biology, and for a better understanding of the design principles of biological structures. In this research we used nanometric and micrometric analyses to investigate the morphological and mechanical properties of the black-orange-black (BOB) color pattern in scelionid wasps, which has never been studied. The primary objective of the present investigation was to explore the structural and mechanical differences in the mesoscutum of four species: Baryconus with an orange mesosoma (i.e. BOB pattern), all black Baryconus, Scelio with an orange mesosoma (i.e. BOB pattern), and all black Scelio. The most outstanding findings include the absence of multilayer structures that generate structural color, a pigment concentrated in the upper surface of the epicuticle, and surprising differences between the four species. Three of the four species showed an accordion-like structure in the furrow (notaulus), whereas the adjacent mesoscutum was different in each species. Moreover, the normalized color component spectra for blue, green and red colors of the black mesoscutum of each genus showed the same spectral dependence while the orange color manifested small changes in the dominant wavelength, resulting in slightly different orange tones.

Current's Fluctuations through Molecular Wires Composed of Thiophene Rings.

We study theoretically the electronic transport and quantum fluctuations in single-molecule systems using thiophene rings as integrated elementary functions, as well as the dependence of these properties with the increase of the coupled rings, i.e., as a quantum wire. In order to analyze the current flow through these molecular systems, the thiophene rings are considered to be connected to metal contacts, which, in general terms, will be related to the application of voltages (bias voltages or gate voltages) to generate non-equilibrium behavior between the contacts. Due to the nonlinear behavior that is generated when said voltages are applied, it is possible to observe quantum fluctuations in the transport properties of these molecular wires. For the calculation of the transport properties, we applied a tight-binding approach using the Landauer-Büttiker formalism and the Fischer-Lee relationship, by means of a semi-analytic Green's function method within a real-space renormalization (decimation procedure). Our results showed an excellent agreement with results using a tight-binding model with a minimal number of parameters reported so far for these molecular systems.

Aortic root enlargement in octogenarian patients results in less patient prosthesis mismatch.

BACKGROUND: Aortic root enlargement has not been well studied as a modality to prevent patient prosthesis mismatch in octogenarian patients with a small aortic root. METHODS: We reviewed the records of 117 octogenarian patients who received surgical aortic valve replacement (AVR) between 1993 and 2010. From this group, 87 patients received a 19-mm AVR (small aortic valve, SAV group) and 30 received an aortic root enlargement and a 21-mm AVR (aortic root enlargement, ARE group). RESULTS: The median age of the patients was 84 years (range, 80 to 93) and there were 111 women (95%). Aortic cross-clamp time was 50 minutes (26 to 116) in the SAV group and 67 (26 to 136) in the ARE group (p=0.02). There were no differences in the operative morbidity or morality rates between the groups. Postoperative aortic valve area index was 0.77 cm2/m2 (0.25 to 1.47) in the SAV group and 1.06 (0.51 to 1.94) in the ARE group (p<0.001). Severe patient prosthesis mismatch occurred in 23 patients (32%) in the SAV group in comparison with 3 (12%) in the ARE group (p=0.04). There were no differences in the mid-term outcomes of New York Heart Association functional class (p=0.230) or survival between patients with or without mismatch (p=0.84). CONCLUSIONS: Aortic root enlargement in octogenarian patients allows for insertion of larger aortic valve prostheses without any apparent increase in operative morbidity or mortality. The larger prostheses demonstrate better hemodynamic performance and less patient prosthesis mismatch, but no apparent functional or survival advantage.

Estimulación en el tracto de salida de ventrículo derecho en pacientes con persistencia de vena cava superior izquierda / Outflow tract right ventricular pacing in patients with a persistent left superior vena cava

No disponible

Eficacia de la terapia de resincronización en sujetos con insuficiencia cardiaca grados III-IV de la NYHA refractarios a tratamiento farmacológico / Effectiveness of resynchronization therapy in pharmacological treatment-resistant patients with NYHA class III-IV heart failure

Objetivos: Determinar, a partir de una revisión sistemática de ámbito internacional basada en ensayos clínicos con asignación aleatoria, si la terapia de resincronización cardiaca, tanto con estimulación aislada como estimulación asociada a desfibrilación, tiene algún efecto sobre la mortalidad en los pacientes en insuficiencia cardiaca grados III-IV refractaria al tratamiento farmacológico pleno, con una fracción de eyección baja(< 35%) y con un QRS ancho (> 120 ms).Método: Revisión sistemática que evalúa terapia de resincronización cardiaca en pacientes descritos anteriormente. Para ello se han evaluado todos los ensayos clínicos controlados con asignación aleatoria que comparaban resincronización cardiaca frente a terapia convencional. Resultados: Se identificaron 2.417 referencias. Se seleccionaron 2.139 resúmenes de los que 896 eran potencialmente relevantes. Cumplieron criterios generales de inclusión62 estudios. Finalmente 10 cumplían estrictamente los criterios de selección. Conclusiones: En nuestro estudio, cuando comparamos resincronización frente a tratamiento farmacológico aislado, constatamos que la mortalidad total presenta una reducción relativa de riesgo del 29% (RR 0,71 con IC al 95% 0,59 a 0,85). Cuando analizamos la mortalidad por insuficiencia cardiaca en el subanálisis de resincronización frente a tratamiento farmacológico aislado como grupo control, encontramos una reducción significativa (37 eventos en el grupo de resincronización frente a los 66 del grupo de tratamiento farmacológico). Destacamos que esta diferencia para la mortalidad específica debe interpretare como clínicamente relevante (RR 0,55 con IC al 95% 0,38 a 0,81).Conclusión: En pacientes con insuficiencia cardiaca avanzada, la resincronización cardiaca, respecto al tratamiento farmacológico convencional, mejora significativamente la mortalidad total y específica (AU)

Objectives: To assess whether cardiac resynchronization therapy with single stimulation or associated with defibrillation has any effect on pharmacological treatment-resistant subjects with class III-IV heart failure, low ejection fraction(< 35%) and wide QRS (> 120 msec), using an systematic international review based on randomised clinical trials. Method: Systematic search and review of relevant literature on cardiac resynchronization in subjects with the abovementioned characteristics. Randomized controlled clinical trials assessing the effectiveness of cardiac resynchronization therapy versus conventional therapy were reviewed. Results: Among 2417 references identified 2139 abstracts were selected; 896 being considered potentially relevant; 62studies fulfilled our inclusion criteria; and 10 of them were included in the study. Conclusions: Global mortality showed a relative reduction of risk of 29% (RR 0.71; 95% CI 0.59 to 0.85) when comparing resynchronization with only pharmacological treatment. On analysing mortality due to heart failure within the subanalysis of resynchronization versus only pharmacological treatment as control group, a significant reduction was found (37 mortality events in resynchronization group versus 66 in control group). This difference in specific mortality should be interpreted as clinically relevant (RR 0.55; 95% CI 0.38 to 0.81). In patients with advanced heart failure a significant improvement is observed in total, and specific mortality on comparing cardiac resynchronization with conventional pharmacological treatment (AU)