Design of protein-binding proteins from the target structure alone.

The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge1-5. Here we describe a general solution to this problem that starts with a broad exploration of the vast space of possible binding modes to a selected region of a protein surface, and then intensifies the search in the vicinity of the most promising binding modes. We demonstrate the broad applicability of this approach through the de novo design of binding proteins to 12 diverse protein targets with different shapes and surface properties. Biophysical characterization shows that the binders, which are all smaller than 65 amino acids, are hyperstable and, following experimental optimization, bind their targets with nanomolar to picomolar affinities. We succeeded in solving crystal structures of five of the binder-target complexes, and all five closely match the corresponding computational design models. Experimental data on nearly half a million computational designs and hundreds of thousands of point mutants provide detailed feedback on the strengths and limitations of the method and of our current understanding of protein-protein interactions, and should guide improvements of both. Our approach enables the targeted design of binders to sites of interest on a wide variety of proteins for therapeutic and diagnostic applications.

Perfil do atendimento de pacientes com acidente vascular cerebral em um hospital filantrópico do sul de Santa Catarina e estudo de viabilidade para implantação da Unidade de AVC / Profile of the care of patients with vascular cerebral accident in a phantantrophic hospital of the south of Santa Catarina and feasibility study for implementation of the Stroke Unit

O objetivo do estudo foi conhecer o perfil de atendimento dos pacientes com Acidente Vascular Cerebral (AVC) em um hospital da região Sul de Santa Catarina, no ano de 2016, e avaliar a viabilidade de implantação de uma Unidade de AVC. Trata-se de um estudo epidemiológico observacional e descritivo, realizado por coleta de dados em prontuários eletrônicos de pacientes com AVC e pela aplicação do Formulário de Vistoria para Gestores constante na Portaria nº. 665/2012 do Ministerio da Saúde, que trata da habilitação dos Centros de AVC. Dos 208 casos, 81,3% tiveram AVC isquêmico, os principais fatores de risco foram Hipertensão Arterial (78,4%) e Diabete Melito (36,1%). O intervalo de tempo entre início dos sintomas e o primeiro atendimento variou de 1,5 a 5,5 horas, entre o atendimento inicial e a Tomografia Computadorizada (TC) 1,3h e entre TC e trombolítico foi de 1,12h. Das intervenções apenas 9,2% usaram trombolítico, a principal complicação foi infecção (21,6%) e o tempo de internação foi de 5 dias. Quanto às Unidade de AVC, a Instituição preenche requisitos para Unidades Tipo I. A partir dos resultados conclui-se que houve dificuldade em determinar o tempo de início dos sintomas e, com isso, a indicação da terapia trombolítica. O tempo de internação foi semelhante a de um Hospital com Centro de AVC implantado. Há condições de receber uma Unidade de AVC do tipo I com porte para se adequar a unidades mais complexas, no hospital em estudo.

The aim of this study was to know the profile of stroke patients seen at a hospital in the southern region of Santa Catarina, in 2016, and to evaluate the feasibility of a Stroke Unit. This is an observational and descriptive epidemiological study, carried out by data collection in electronic medical records of stroke patients and by the application of the Inspection Form for Managers contained in Ordinance no. 665/2012 of the Brazilian Ministry of Health, that deals with the habilitation of Stroke Centers. Of the 208 cases, 81.3% had ischemic stroke and the main risk factors were Hypertension (78.4%) and Diabetes Melitos (36.1%). The period between the onset of symptoms and first health care ranged from 1.5 to 5.5 hours; between initial health care and CT scan, 1.3 hours; and between CT and thrombolytic therapy was 1.12 hours. Only 9.2% of the interventions used thrombolytic therapy, the main complication was infection (21.6%) and the hospitalization period was 5 days. The institution fulfills the requirements for Type I Stroke Units. It was difficult to determine the time of onset of symptoms and, therefore, the indication of thrombolytic therapy. The period of hospital stay was similar to that of a Hospital with a Stroke Center implanted. There are conditions in the hospital under study to receive a Type I or more complex Stroke Unit.

Gold nanoparticles prevent cognitive deficits, oxidative stress and inflammation in a rat model of sporadic dementia of Alzheimer's type.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia in the aged brain. Even though its etiology is unknown, factors such as neuroinflammation, mitochondrial dysfunction, formation of reactive oxygen species (ROS), and impaired insulin signaling may play a role. We used a sporadic AD model in rats generated by intracerebroventricular-streptozotocin (i.c.v.-STZ) injection to test the therapeutic effect of gold nanoparticles (GNPs). We tested the null hypothesis that there would be no difference between the STZ+GNPs group and the STZ group in the analyzed markers. We observed that STZ-induced impairment in mitochondrial ATP production, neuroinflammation, and oxidative stress were all prevented by GNP treatment. Moreover, while STZ induced deficits in both spatial and recognition memory, GNPs prevented this effect. These results suggest that GNPs may be considered as a potential treatment for dementias.