Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid

The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an α2β heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes’ departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16 architecture. These observations also yielded new insights into maturation

FSC-Q: a CryoEM map-to-atomic model quality validation based on the local Fourier shell correlation

In recent years, advances in cryoEM have dramatically increased the resolution of reconstructions and, with it, the number of solved atomic models. It is widely accepted that the quality of cryoEM maps varies locally; therefore, the evaluation of the maps-derived structural models must be done locally as well. In this article, a method for the local analysis of the map-to-model fit is presented. The algorithm uses a comparison of two local resolution maps. The first is the local FSC (Fourier shell correlation) between the full map and the model, while the second is calculated between the half maps normally used in typical single particle analysis workflows. We call the quality measure “FSC-Q”, and it is a quantitative estimation of how much of the model is supported by the signal content of the map. Furthermore, we show that FSC-Q may be helpful to detect overfitting. It can be used to complement other methods, such as the Q-score method that estimates the resolvability of atomsWe thank Prof. David Veesler for providing us the half maps of the spike glycoprotein of SARS-CoV-2. The authors would like to acknowledge financial support from: the Comunidad de Madrid through grant CAM (S2017/BMD-3817), the Spanish National Research Council (PIE/COVID-19 number 202020E079), the Spanish Ministry of Economy and Competitiveness through grants SEV 2017-0712, PID2019-104757RB-I00/AEI/10.13039/501100011033, the Instituto de Salud Carlos III through grant PT17/0009/0010 (ISCIII-GEFI/ERDF-). Instruct-ULTRA (Grant 731005), an EU H2020 project to further develop the services of Instruct-ERIC. UE H2020 grant HighResCells (ERC-2018-SyG, Proposal: 810057). This work was supported by the Intramural Research Program of the National Institute for Arthritis, musculoskeletal, and Skin Diseases, NIH. The authors acknowledge the support and the use of resources of Instruct, a Landmark ESFRI projec

Recent advances in electron cryotomography and their application to imaging purified protein complexes, isolated organelles, and small cells

A new 300kV, FEG, helium-cooled, energy-filtered "G2 Polara" electron cryoTEM was recently installed at Caltech. Using this instrument, we have now extensively tested the potential advantages of liquid helium cooling and the inclusion of two orthogonal tilt-series in the context of electron cryotomography. These results and the application of the technology to several specific biological problems are reported

Pain, quality of life, self perception of health and depression in patients with fibromyalgia, submited to hydrocinesiotherapy

OBJECTIVES: The aim of this study was to analyze the effects of treatment by hydrotherapy on quality of life, perception of pain and the severity of depression in a group of patients with fibromyalgia. MATERIALS AND METHODS: We evaluated 64 females divided into two groups: hydrocinesiotherapy (n = 33, 58.2 ± 10.6 years) and control group (n = 31 with 59.6 ± 9.4 years) with clinical diagnosis of fibromyalgia. Individuals were assessed by Visual Analog Scale of Pain (VAS), the Fibromyalgia Impact Questionnaire (FIQ) and the Beck Depression Inventory. Participants underwent a treatment in a hydrotherapy pool heated to 33ºC over a period of 15 weeks, two sessions per week of 45 minutes, a total of 30 sessions. The exercises were underwater: cardiovascular conditioning, strength training, mobility, coordination, balance and still, stretching exercises and muscle relaxation. The ANOVA 2×2 and Kruskall-Wallis was used for statistical analysis RESULTS: There were statistically significant improvements in the perception of pain intensity (Δ% = -28.2%, p < 0, 01), quality of life (Δ% = -32.4%, p < 0, 05) and depression symptoms (Δ% = -35.4%, p < 0, 05) in favor of the Hydrotherapy group compared to the control group. CONCLUSIONS: The study suggests that hydrocinesiotherapy was effective as an alternative therapy for fibromyalgia, however further studies are recommended to test the associations between the variables and intervention programs and using the water activities, and the modifiability of the parameters of physical and mental health when these individuals undergo programs of short, medium and long duration.OBJETIVOS: Analisar os efeitos do tratamento hidrocinesioterapêutico na qualidade de vida, percepção de dor e gravidade de episódios depressivos em um grupo de pacientes com fibromialgia. MATERIAIS E MÉTODOS: Foram avaliados 64 indivíduos do sexo feminino, separados em dois grupos: hidrocinesioterapia (n = 33; 58,2 ± 10,6 anos) e grupo controle (n = 31; 59,6 ± 9,4 anos), com diagnóstico de fibromialgia. Os indivíduos foram avaliados através da Escala Analógica Visual de Dor (EVA), o Fibromyalgia Impact Questionnaire (FIQ), e o Inventário de Beck. Os participantes foram submetidos a um tratamento hidrocinesioterápico numa piscina aquecida a 33ºC com duas sessões de 45 minutos por semana, ao longo 15 semanas, num total de 30 sessões. Os exercícios subaquáticos foram: de condicionamento cardiovascular, de força, de mobilidade, de coordenação, de equilíbrio, de alongamento e de relaxamento muscular. Utilizou-se a ANOVA 2×2 e Kruskal-Wallis para análise estatística. RESULTADOS: Foram observadas melhorias estatisticamente significativas na percepção da intensidade da dor (Δ% = -28,2%, p < 0,01), na qualidade de vida (Δ% = -32,4%, p < 0,05) e nos sintomas de depressão (Δ% = -35,4%, p < 0,05) favoráveis ao grupo hidrocinesioterapia comparado ao grupo controle. CONCLUSÕES: O estudo sugere que a hidrocinesioterapia mostrou-se eficaz como terapia alternativa da fibromialgia. No entanto, recomenda novos estudos que testem as associações existentes entre as variáveis analisadas e os programas de intervenção, utilizando as atividades aquáticas, bem como a modificabilidade dos parâmetros de saúde física e psíquica quando estes indivíduos são submetidos a programas de curta, média e longa duração.Faculdade Católica Rainha do SertãoUniversidade de Coimbra Faculdade de Ciências do Desporto e Educação FísicaCentro Universitário da Fundação Educacional GuaxupéUniversidade Federal do ParanáFederal do Estado do Rio de JaneiroUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Marine harmful algal blooms, human health and wellbeing : challenges and opportunities in the 21st century

Author Posting. © Marine Biological Association of the United Kingdom, 2015. This is the author's version of the work. It is posted here by permission of Marine Biological Association of the United Kingdom for personal use, not for redistribution. The definitive version was published in Journal of the Marine Biological Association of the United Kingdom 96 (2016): 61-91, doi:10.1017/S0025315415001733.Microalgal blooms are a natural part of the seasonal cycle of photosynthetic organisms in marine ecosystems. They are key components of the structure and dynamics of the oceans and thus sustain the benefits that humans obtain from these aquatic environments. However, some microalgal blooms can cause harm to humans and other organisms. These harmful algal blooms (HABs) have direct impacts on human health and negative influences on human wellbeing, mainly through their consequences to coastal ecosystem services (valued fisheries, tourism and recreation) and other marine organisms and environments. HABs are natural phenomena, but these events can be favoured by anthropogenic pressures in coastal areas. Global warming and associated changes in the oceans could affect HAB occurrences and toxicity as well, although forecasting the possible trends is still speculative and requires intensive multidisciplinary research. At the beginning of the 21st century, with expanding human populations, particularly in coastal and developing countries, there is an urgent need to prevent and mitigate HABs’ impacts on human health and wellbeing. The available tools to address this global challenge include maintaining intensive, multidisciplinary and collaborative scientific research, and strengthening the coordination with stakeholders, policymakers and the general public. Here we provide an overview of different aspects to understand the relevance of the HABs phenomena, an important element of the intrinsic links between oceans and human health and wellbeing.The research was funded in part by the UK Medical Research Council (MRC) and UK Natural Environment Research Council (NERC) for the MEDMI Project; the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London and the Met Office; and the European Regional Development Fund Programme and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly (University of Exeter Medical School). EB was supported by the CTM2014-53818-R project, from the Spanish Government (MINECO). KDA was in receipt of funding from the BBSRC-NERC research programme for multidisciplinary studies in sustainable aquaculture: health, disease and the environment. P. Hess was supported by Ifremer (RISALTOX) and the Regional Council of the Pays de la Loire (COSELMAR). Porter Hoagland was supported by the US National Science Foundation under NSF/CNH grant no. 1009106.2016-05-2

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Community recommendations on cryoEM data archiving and validation

In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for the deposition and validation of cryoEM structures, with a focus on single-particle analysis. The meeting was attended by 47 experts in data processing, model building and refinement, validation, and archiving of such structures. This report describes the workshop’s motivation and history, the topics discussed, and the resulting consensus recommendations. Some challenges for future methods-development efforts in this area are also highlighted, as is the implementation to date of some of the recommendations.The workshop was supported by funding to PDBe and EMDB by the Wellcome Trust (grant No. 104948/Z/14/Z awarded to GJK, SV and AP) and by the European Molecular Biology Laboratory. Travel was supported by the PDBe, EMDB, RCSB PDB, PDBj, BMRB and EMDR. RCSB PDB is jointly funded by the National Science Foundation (grant No. DBI1832184); the US Department of Energy (grant No. DESC0019749); and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health (grant No. R01GM133198). PDBj is funded by JST-NBDC and BMRB by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) (grant No. R24GM150793). EMDR was funded by the NIGMS of the NIH (grant No. R01GM079429).Peer reviewe

Acute inflammatory myelopathies

Inflammatory injury to the spinal cord causes a well-recognized clinical syndrome. Patients typically develop bilateral weakness, usually involving the legs, although the arms may also become affected, in association with a pattern of sensory changes that suggests a spinal cord dermatomal level. Bowel and bladder impairment is also common in many patients. Recognition of the clinical pattern of spinal cord injury should lead clinicians to perform imaging studies to evaluate for compressive etiologies. MRI of the spine is particularly useful in helping visualize intraparenchymal lesions and when these lesions enhance following contrast administration a diagnosis of myelitis is made. Cerebrospinal fluid analysis can also confirm a diagnosis of myelitis when a leukocytosis is present. There are many causes of non-compressive spinal cord injury including infectious, parainfectious, toxic, nutritional, vascular, systemic as well as idiopathic inflammatory etiologies. This review focuses on inflammatory spinal cord injury and its relationships with multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis and systemic collagen vascular and paraneoplastic diseases