A structural modeling approach for the understanding of initiation and elongation of ALS-linked superoxide dismutase fibrils

Familial amyotrophic lateral sclerosis caused by mutations in copper-zinc superoxide dismutase (SOD1) is characterized by the presence of SOD1-rich inclusions in spinal cords. It has been shown that a reduced intra-subunit disulfide bridge apo-SOD1 can rapidly initiate fibrillation forming an inter-subunits disulfide under mild, physiologically accessible conditions. Once initiated, elongation can proceed via recruitment of either apo or partially metallated disulfide-intact SOD1 and the presence of copper, but not zinc, ions inhibit fibrillation. We propose a structural model, refined through molecular dynamics simulations, that, taking into account these experimental findings, provides a molecular explanation for the initiation and the elongation of SOD1 fibrils in physiological conditions. The model indicates the occurrence of a new dimeric unit, prone to interact one with the other due to the presence of a wide hydrophobic surface and specific electrostatic interactions. The model has dimensions consistent with the SOD1 fibril size observed through electron microscopy and provides a structural basis for the understanding of SOD1 fibrillation

UWB FastlyTunable 0.550 GHz RF Transmitter based on Integrated Photonics

Currently, due to the 6G revolution, applications ranging from communication to sensing are experiencing an increasing and urgent need of software-defined ultra-wideband (UWB) and tunable radio frequency (RF) apparatuses with low size, weight, and power consumption (SWaP). Unfortunately, the coexistence of ultra-wideband and software-defined operation, tunability and low SWaP represents a big issue in the current RF technologies. Recently, photonic techniques have been demonstrated to support achieving the desired features when applied in RF UWB transmitters, introducing extremely wide operation and instantaneous bandwidth, tunable filtering, tunable photonics-based microwave mixing with very high port-to-port isolation, and intrinsic immunity to electromagnetic interferences. Moreover, the recent advances in photonics integration also allow to obtain very compact devices. In this article, to the best of our knowledge, the first example of a complete tunable software-defined RF transmitter with low footprint (i.e. on photonic chip) is presented exceeding the state-of-the-art for the extremely large tunability range of 0.5-50 GHz without any parallelization of narrower-band components and with fast tuning (< 200 s). This first implementation represents a breakthrough in microwave photonics

Cellular senescence in vascular wall mesenchymal stromal cells, a possible contribution to the development of aortic aneurysm

Cellular senescence is a hallmark of ageing and it plays a key role in the development of age-related diseases. Abdominal aortic aneurysm (AAA) is an age related degenerative vascular disorder, characterized by a progressive dilatation of the vascular wall and high risk of rupture over time. Nowadays, no pharmacological therapies are available and the understanding of the molecular mechanisms that lead to AAA onset and development are poorly defined. In this study we investigated the cellular features of senescence in vascular mesenchymal stromal cells, isolated from pathological (AAA – MSCs) and healthy (h – MSCs) segments of human abdominal aorta and their implication in impairing the vascular repair ability of MSCs. Cell proliferation, ROS production, cell surface area, the expression of cyclin dependent kinase inhibitors p21CIP1 and p16INK4a, the activation of the DNA damage response and a dysregulated autophagy showed a senescent state in AAA - MSCs compared to h-MSCs. Moreover, a reduced ability to differentiate toward endothelial cells was observed in AAA – MSCs. All these data suggest that the accumulation of senescent vascular MSCs over time impairs their remodeling ability during ageing. This condition could support the onset and development of AAA

Photonics-based tunable 1-50 GHz RF transmitter on silicon chip

The paper presents an innovative tunable software-defined RF transmitter based on integrated photonics, able to work in 1-50GHz with very fast tuning. The system has been characterized and verified in a communication scenario

Design of an Efficient Pumping Scheme for Mid-IR Dy3+:Ga5Ge20Sb10S65PCF Fiber Laser

This letter illustrates the design of a novel medium infrared (Mid-IR) laser based on a photonic crystal fiber made of dysprosium-doped chalcogenide glass, Dy3+:Ga5Ge20Sb10S65. In order to perform a realistic investigation, the simulation is performed by taking into account the spectroscopic parameters measured on the rare earth-doped glass sample. The simulated results show that an optical beam emission close to 4400-nm wavelength can be obtained by employing two pump beams at 2850 nm (pump #1) and 4092 nm (pump #2) wavelengths. As example, for the pump powers of 50 mW (pump #1) and 1 W (pump #2), the input mirror reflectivity of 99%, the output mirror reflectivity of 30%, and the optical cavity length of 50 cm, a signal power close to 350 mW at the wavelength of 4384 nm can be generated. This result indicates that the designed source configuration is feasible for high beam quality Mid-IR light generation and it is efficient enough to find applications in optical free propagation links, optical remote sensing, and medicine

Esculetin provides neuroprotection against mutant huntingtin-induced toxicity in huntington’s disease models

Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic Drosophila melanogaster model of HD, both of which express mHTT fragments. ESC partially inhibited the progression of mHTT aggregation and reduced neuronal death through its ability to counteract the oxidative stress and mitochondria impairment elicited by mHTT in the PC12 model. The ability of ESC to counteract neuronal death was also confirmed in the transgenic Drosophila model. Although ESC did not modify the lifespan of the transgenic Drosophila, it still seemed to have a positive impact on the HD phenotype of this model. Based on our findings, ESC may be further studied as a potential neuroprotective agent in a rodent transgenic model of HD

Cisticercose Bovina no Estado do Espírito Santo no Período de 2009 a 2012: Análise de Registros de Matadouros Frigoríficos

A cisticercose bovina é uma das zoonoses mais encontradas na inspeção post mortem dos bovinos abatidos no Brasil, transmitida ao homem pela ingestão de carne crua ou mal cozida contendo cistos viáveis. O objetivo do presente trabalho foi realizar análise de registros de cisticercose bovina nos matadouros frigoríficos do Estado do Espírito Santo no período de 2009 a 2012. Os dados referentes às condenações de carcaça e órgãos foram obtidos a partir dos registros do órgão de serviço de inspeção federal (SIF) e estadual (SIE) do estado do ES. Foram abatidos um total de 1.340.751 bovinos no período estudado e uma prevalência média de 0,84%. Nos dados registrados no SIF a prevalência média foi de 0,87% e as regiões anatômicas acometidas foram coração, língua, cabeça e fígado, respectivamente. Nos dados do SIE, a prevalência foi de 0,83% e os órgãos mais acometidos foram coração, cabeça, fígado e língua, respectivamente. Em todos os anos o número total de cistos vivos foi maior do que o número de cistos calcificados. As perdas por cisticercose no período foram de R$ 9.092.834,97, para 1.518.256,8 Kg de carne condenada. Os casos de cisticercose aumentaram entre os anos de 2010, 2011 e 2012 (p<0,001), mostrando uma tendência crescente da enfermidade e houve diferença significativa entre as estações do ano (p=0,01), com a estação chuvosa apresentando um número maior de casos de cisticercose. Um questionário sobre diagnóstico para cisticercose foi oferecido aos executores de inspeção, em um dos matadouros no sul do estado, e constatou incapacidade de diferenciar cisticercose da hidatidose

Design of a Multi-Wavelength Fiber Laser Based on Tm:Er:Yb:Ho Co-Doped Germanate Glass

In this article, for the first time, an efficient multi-wavelength fiber laser based on a Tm:Er:Yb:Ho co-doped germanate glass, optically pumped at 980 nm wavelength and simultaneously emitting at 1550 nm, 1800 nm and 2050 nm wavelengths, is designed and optimized. An exhaustive model, taking into account the energy transfer phenomena between different rare earths, is developed. The device behavior is investigated by means of several parametric sweeps with respect to the input pump power, the fiber length, the dopant concentrations and the output mirrors reflectivities. Four optimal concentrations have been found by means of a home-made computer code based on particle swarm optimization (PSO) approach, allowing a global solution search. These concentrations allow levels of output powers very close to each other, equal to 20 mW $pm$ 0.1$$ at 1550 nm, 1800 nm and 2050 nm, respectively. These results predict the possibility of tailoring the dopant concentrations in order to construct broadband optical sources with similar emission powers at multiple wavelengths and broadband amplifiers