Quantitative proteomic analysis of Parkin substrates in Drosophila neurons.

Parkin (PARK2) is an E3 ubiquitin ligase that is commonly mutated in Familial Parkinson's Disease (PD). In cell culture models, Parkin is recruited to acutely depolarised mitochondria by PINK1. PINK1 activates Parkin activity leading to ubiquitination of multiple proteins, which in turn promotes clearance of mitochondria by mitophagy. Many substrates have been identified using cell culture models in combination with depolarising drugs or proteasome inhibitors, but not in more physiological settings.Here we utilized the recently introduced BioUb strategy to isolate ubiquitinated proteins in flies. Following Parkin Wild-Type (WT) and Parkin Ligase dead (LD) expression we analysed by mass spectrometry and stringent bioinformatics analysis those proteins differentially ubiquitinated to provide the first survey of steady state Parkin substrates using an in vivo model. We further used an in vivo ubiquitination assay to validate one of those substrates in SH-SY5Y cells.We identified 35 proteins that are more prominently ubiquitinated following Parkin over-expression. These include several mitochondrial proteins and a number of endosomal trafficking regulators such as v-ATPase sub-units, Syx5/STX5, ALiX/PDCD6IP and Vps4. We also identified the retromer component, Vps35, another PD-associated gene that has recently been shown to interact genetically with parkin. Importantly, we validated Parkin-dependent ubiquitination of VPS35 in human neuroblastoma cells.Collectively our results provide new leads to the possible physiological functions of Parkin activity that are not overtly biased by acute mitochondrial depolarisation

Effects of surgical side and site on mood and behavior outcome in children with pharmacoresistant epilepsy

Children with epilepsy have a high rate of mood and behavior problems; yet few studies consider the emotional and behavioral impact of surgery. No study to date has been sufficiently powered to investigate effects of both side (left/right) and site (temporal/frontal) of surgery. One hundred patients (aged 6-16) and their families completed measures of depression, anxiety, and behavioral function as part of neuropsychological evaluations before and after surgery for pharmacoresistant epilepsy. Among children who had left-sided surgeries (frontal = 16; temporal = 38), there were significant interactions between time (pre to post-operative neuropsychological assessment) and resection site (frontal/temporal) on anhedonia, social anxiety, and withdrawn/depressed scales. Patients with frontal lobe epilepsy (FLE) endorsed greater pre-surgical anhedonia and social anxiety than patients with temporal lobe epilepsy (TLE) with scores normalizing following surgery. While scores on the withdrawn/depressed scale were similar between groups before surgery, the FLE group showed greater symptom improvement after surgery. In children who underwent right-sided surgeries (FLE = 20; TLE = 26), main effects of time (patients in both groups improved) and resection site (caregivers of FLE patients endorsed greater symptoms than those with TLE) were observed primarily on behavior scales. Individual data revealed that a greater proportion of children with left FLE demonstrated clinically significant improvements in anhedonia, social anxiety, and aggressive behavior than children with TLE. This is the first study to demonstrate differential effects of both side and site of surgery in children with epilepsy at group and individual levels. Results suggest that children with FLE have greater emotional and behavioral dysfunction before surgery, but show marked improvement after surgery. Overall, most children had good emotional and behavioral outcomes, with most scores remaining stable or improving. © 2014 Andresen, Ramirez, Kim, Dorfman, Haut, Klaas, Jehi, Shea, Bingaman and Busch

From Macroscopic to Microscopic: Experimental and Computational Methods to Investigate Bio-tribology

Tribology is an important factor (among other factors) during biological interactions of devices and tissues. The paper discusses how new computational and experimental methods can be used to understand and improve the design and development of medical devices at macro and micro scales to sustain life beyond 50 years. We have used pre-clinical experiments and computational methods to understand interactions between orthopaedic implants at the macro scale. The computational model has been validated with experiments. Now this computational model can predict damage in implants for different patients. One such application was successfully tried and tested in collaboration with University National Autonomous Mexico. This methodology can be used in future to design patient specific, affordable (using 3D printing) and robust implants which will be useful for developing countries like Vietnam, India and Mexico. Improvement of catheter designs is important to reduce damage to the internal tissues while being used for cardiovascular problems. We are developing new experimental techniques (in micro scale) that can be used to understand the interaction of cells with the catheter material. These will help reduce the hospital costs incurred during longer stay of the patients admitted for cardiovascular related problems

Falência Vacinal na Doença Invasiva Pneumocócica DIP). Reportar e Investigar. Que Devemos Fazer a Seguir?

Introdução: A vacina conjugada pneumococica 13-valente (VCP13V) foi comercializada em Portugal em 2010 e introduzida no PNV em Junho de 2015. As falências vacinais não põem em causa a eficácia global da vacina, mas devem ser reportadas e investigadas. Objetivos: Avaliar atitudes clínicas face a falências vacinais da VCP13V. Métodos: Estudo retrospetivo, observacional e descritivo, de 2016 a 2018, de doentes com falência vacinal internados num hospital terciário. Identificaram-se serotipos e estado vacinal de acordo com o grupo etário e procedimentos realizados. Resultados: Total de 8 casos, com mediana de 24 meses (máx 5A; mín 12M) sendo 7/8 crianças com menos de 5 anos de idade. Os serotipos implicados foram: 3 (7) e 19A (1). Em 4/8 casos ocorreu co-infecção viral. Os diagnósticos foram pneumonia (7) e meningite (1). Ocorreram complicações em 7/8 doentes: empiema (4), derrame pleural (2), pneumotórax (2), fístula pleural (1) e cerebrite (1). Necessitaram de cuidados intensivos 7/8, drenagem torácica 6/8e ventilação mecânica 4/8 crianças. A duração do internamento foi 22 dias. Foram notificadas no Sistema Nacional de Vigilância Epidemiológica (SINAVE) 5/8 casos e reportados à Autoridade Nacional do Medicamento e Produtos de Saúde, no portal de RAM (Reação Adversa Medicamentosa) do Infarmed e fabricante 4/8 casos. O seguimento hospitalar foi realizado (média 13 meses) para exclusão de deficit de imunidade em 7/8 doentes, identificando-se diminuição de anticorpos vacinais em dois e diminuição das células B de memória em um caso. Conclusão: A investigação e a notificação das falências vacinais DIP não é realizada de forma sistemática e devidamente notificada, pelo que importa sensibilizar para os procedimentos face a este evento.info:eu-repo/semantics/publishedVersio

Low-temperature muon spin rotation studies of the monopole charges and currents in Y doped Ho2Ti2O7

In the ground state of Ho2Ti2O7 spin ice, the disorder of the magnetic moments follows the same rules as the proton disorder in water ice. Excitations take the form of magnetic monopoles that interact via a magnetic Coulomb interaction. Muon spin rotation has been used to probe the low-temperature magnetic behaviour in single crystal Ho2−xYxTi2O7 (x = 0, 0.1, 1, 1.6 and 2). At very low temperatures, a linear field dependence for the relaxation rate of the muon precession λ(B), that in some previous experiments on Dy2Ti2O7 spin ice has been associated with monopole currents, is observed in samples with x = 0, and 0.1. A signal from the magnetic fields penetrating into the silver sample plate due to the magnetization of the crystals is observed for all the samples containing Ho allowing us to study the unusual magnetic dynamics of Y doped spin ice

Catastrophizing mediates the relationship between the personal belief in a just world and pain outcomes among chronic pain support group attendees

Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to one’s own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made

Evolution of aerial spider webs coincided with repeated structural optimization of silk anchorages

Physical structures built by animals challenge our understanding of biological processes and inspire the development of smart materials and green architecture. It is thus indispensable to understand the drivers, constraints, and dynamics that lead to the emergence and modification of building behavior. Here, we demonstrate that spider web diversification repeatedly followed strikingly similar evolutionary trajectories, guided by physical constraints. We found that the evolution of suspended webs that intercept flying prey coincided with small changes in silk anchoring behavior with considerable effects on the robustness of web attachment. The use of nanofiber based capture threads (cribellate silk) conflicts with the behavioral enhancement of web attachment, and the repeated loss of this trait was frequently followed by physical improvements of web anchor structure. These findings suggest that the evolution of building behavior may be constrained by major physical traits limiting its role in rapid adaptation to a changing environment

Dominance of Vaccine Serotypes in Pediatric Invasive Pneumococcal Infections in Portugal (2012-2015)

We evaluated the impact of continued 13-valent pneumococcal conjugate vaccine (PCV13) use in the private market (uptake of 61%) in pediatric invasive pneumococcal disease (pIPD) in Portugal (2012-2015). The most frequently detected serotypes were: 3 (n = 32, 13.8%), 14 (n = 23, 9.9%), 1 (n = 23, 9.9%), 7F (n = 15, 6.4%), 19A (n = 13, 5.6%), 6B and 15B/C (both n = 12, 5.2%), and 24F, 10A and 12B (all with n = 10, 4.3%). Taken together, non-PCV13 serotypes were responsible for 42.2% of pIPD with a known serotype. The use of PCR to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 18.1% (n = 47) of all pIPD. Serotype 3 was mostly detected by PCR (n = 21/32, 65.6%) and resulted from a relevant number of vaccine failures. The incidence of pIPD varied in the different age groups but without a clear trend. There were no obvious declines of the incidence of pIPD due to serotypes included in any of the PCVs, and PCV13 serotypes still accounted for the majority of pIPD (57.8%). Our study indicates that a higher vaccination uptake may be necessary to realize the full benefits of PCVs, even after 15 years of moderate use, and highlights the importance of using molecular methods in pIPD surveillance, since these can lead to substantially increased case ascertainment and identification of particular serotypes as causes of pIPD.info:eu-repo/semantics/publishedVersio