Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect

Controlled interfacial assembly of 2D curved colloidal crystals and jammed shells

Assembly of colloidal particles on fluid interfaces is a promising technique for synthesizing two-dimensional micro-crystalline materials useful in fields as diverse as biomedicine1, materials science2, mineral flotation3 and food processing4. Current approaches rely on bulk emulsification methods, require further chemical and thermal treatments, and are restrictive with respect to the materials employed5-9. The development of methods that exploit the great potential of interfacial assembly for producing tailored materials have been hampered by the lack of understanding of the assembly process. Here we report a microfluidic method that allows direct visualization and understanding of the dynamics of colloidal crystal growth on curved interfaces. The crystals are periodically ejected to form stable jammed shells, which we refer to as colloidal armour. We propose that the energetic barriers to interfacial crystal growth and organization can be overcome by targeted delivery of colloidal particles through hydrodynamic flows. Our method allows an unprecedented degree of control over armour composition, size and stability.Comment: 18 pages, 5 figure

Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease

Force spectroscopy in studying infection

Biophysical force spectroscopy tools - for example optical tweezers, magnetic tweezers, atomic force microscopy, - have been used to study elastic, mechanical, conformational and dynamic properties of single biological specimens from single proteins to whole cells to reveal information not accessible by ensemble average methods such as X-ray crystallography, mass spectroscopy, gel electrophoresis and so on. Here we review the application of these tools on a range of infection-related questions from antibody-inhibited protein processivity to virus-cell adhesion. In each case we focus on how the instrumental design tailored to the biological system in question translates into the functionality suitable for that particular study. The unique insights that force spectroscopy has gained to complement knowledge learned through population averaging techniques in interrogating biomolecular details prove to be instrumental in therapeutic innovations such as those in structure-based drug design

Decomposition cross-correlation for analysis of collagen matrix deformation by single smooth muscle cells

Microvascular remodeling is known to depend on cellular interactions with matrix tissue. However, it is difficult to study the role of specific cells or matrix elements in an in vivo setting. The aim of this study is to develop an automated technique that can be employed to obtain and analyze local collagen matrix remodeling by single smooth muscle cells. We combined a motorized microscopic setup and time-lapse video microscopy with a new cross-correlation based image analysis algorithm to enable automated recording of cell-induced matrix reorganization. This method rendered 60–90 single cell studies per experiment, for which collagen deformation over time could be automatically derived. Thus, the current setup offers a tool to systematically study different components active in matrix remodeling

Neonatal Administration of Thimerosal Causes Persistent Changes in Mu Opioid Receptors in the Rat Brain

Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of μ-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development

Pooled extracellular receptor-ligand interaction screening using CRISPR activation.

Extracellular interactions between cell surface receptors are necessary for signaling and adhesion but identifying them remains technically challenging. We describe a cell-based genome-wide approach employing CRISPR activation to identify receptors for a defined ligand. We show receptors for high-affinity antibodies and low-affinity ligands can be unambiguously identified when used in pools or as individual binding probes. We apply this technique to identify ligands for the adhesion G-protein-coupled receptors and show that the Nogo myelin-associated inhibitory proteins are ligands for ADGRB1. This method will enable extracellular receptor-ligand identification on a genome-wide scale

Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment

There is an increasing global interest to support research areas that can assist in understanding disease and improving patient care. The National Cancer Institute (NIH) has identified precision medicine-based approaches as key research strategies to expedite advances in cancer research. The Cancer Moonshot program ( https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative ) is the largest cancer program of all time, and has been launched to accelerate cancer research that aims to increase the availability of therapies to more patients and, ultimately, to eradicate cancer. Mass spectrometry-based proteomics has been extensively used to study the molecular mechanisms of cancer, to define molecular subtypes of tumors, to map cancer-associated protein interaction networks and post-translational modifications, and to aid in the development of new therapeutics and new diagnostic and prognostic tests. To establish the basis for our melanoma studies, we have established the Southern Sweden Malignant Melanoma Biobank. Tissues collected over many years have been accurately characterized with respect to the tumor and patient information. The extreme variability displayed in the protein profiles and the detection of missense mutations has confirmed the complexity and heterogeneity of the disease. It is envisaged that the combined analysis of clinical, histological, and proteomic data will provide patients with a more personalized medical treatment. With respect to disease presentation, targeted treatment and medical mass spectrometry analysis and imaging, this overview report will outline and summarize the current achievements and status within malignant melanoma. We present data generated by our cancer research center in Lund, Sweden, where we have built extensive capabilities in biobanking, proteogenomics, and patient treatments over an extensive time period