Structural insights into collagen binding by platelet receptor glycoprotein VI.

Glycoprotein VI (GPVI) mediates collagen-induced platelet activation after vascular damage and is an important contributor to the onset of thrombosis, heart attack, and stroke. Animal models of thrombosis have identified GPVI as a promising target for antithrombotic therapy. Although for many years the crystal structure of GPVI has been known, the essential details of its interaction with collagen have remained elusive.

Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity.

Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spillover. All three viruses attach to 9--acetylated sialoglycans via spike protein S with hemagglutinin-esterase (HE) acting as a receptor-destroying enzyme.

Repatriation for diseases or non-battle injuries (DNBI): long-term impact on quality of life.

Introduction: Throughout history, diseases and non-battle injuries (DNBI) have threatened deployed forces more than battlefield injuries. During the Dutch involvement in Afghanistan, the amount of DNBI that needed medical evacuation out of theatre (60%) exceeded the number of battle injuries (40%). The aim of this study is to explore the long-term quality of life (QoL) of Dutch service members that acquired a DNBI, warranting repatriation during their deployment to Afghanistan between 2003 and 2014.

Human coronaviruses OC43 and HKU1 bind to 9--acetylated sialic acids via a conserved receptor-binding site in spike protein domain A.

Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species , and more closely related to bovine coronavirus (BCoV)-its presumptive ancestor-and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9--acetylated sialic acid (9--Ac-Sia).

Structure and flexibility of the extracellular region of the PirB receptor.

Murine paired immunoglobulin receptor B (PirB) and its human ortholog leukocyte immunoglobulin-like receptor B2 (LILRB2) are widely expressed inhibitory receptors that interact with a diverse set of extracellular ligands and exert functions ranging from down-regulation of immune responses to inhibition of neuronal growth. However, structural information that could shed light on how PirB interacts with its ligands is lacking. Here, we report crystal structures of the PirB ectodomain; the first full ectodomain structure for a LILR family member, at 3.

Molecular basis determining species specificity for TLR2 inhibition by staphylococcal superantigen-like protein 3 (SSL3).

Staphylococcus aureus is a versatile opportunistic pathogen, causing disease in human and animal species. Its pathogenicity is linked to the ability of S. aureus to secrete immunomodulatory molecules.

Reliability of wireless monitoring using a wearable patch sensor in high-risk surgical patients at a step-down unit in the Netherlands: a clinical validation study.

Background And Objectives: Intermittent vital signs measurements are the current standard on hospital wards, typically recorded once every 8 hours. Early signs of deterioration may therefore be missed. Recent innovations have resulted in 'wearable' sensors, which may capture patient deterioration at an earlier stage.

Evaluating the Military Medical Evacuation Chain: Need for Expeditious Evacuation Out of Theater?

Background: An important factor within the military medical logistical chain is the capability of expeditious evacuation from point of injury, through a Medical Treatment Facility, to the country of residence where highest level of care can be provided. Although many factors can relate to patient outcome, the evaluation of the medical evacuation chain related to long-term patient outcome can be important for investigating possibilities for performance improvement in this domain. This article aims to provide a means to evaluate the quality of care of the medical evacuation chain.

Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity.

Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE.

Review of military and civilian trauma registries: Does consensus matter?

Background: Structural collection of data from combat injuries is important to improve provided care and the outcome of (combat) casualties. Trauma registries are used in civilian and military health care systems for systematic administration of injury data. However, these registries often use different methods of data management, compromising international comparison of trauma systems.

Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia.

The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP9) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in GP1BA have been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in GP1BB By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in GP1BB and macrothrombocytopenia.

Amputation: Not a failure for severe lower extremity combat injury.

Introduction: The use of improvised explosive devices is a frequent method of insurgents to inflict harm on deployed military personnel. Consequently, lower extremity injuries make up the majority of combat related trauma. The wounding pattern of an explosion is not often encountered in a civilian population and can lead to substantial disability.

Experience of collaboration between a Dutch surgical team in a Ghanaian Orthopaedic Teaching Hospital.

Background: Surgery is an indivisible, indispensable part of healthcare. In Africa, surgery may be thought of as the neglected stepchild of global public health. We describe our experience over a 3-year period of intensive collaboration between specialized teams from a Dutch hospital and local teams of an orthopaedic hospital in Effiduase-Koforidua, Ghana.

Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation.

Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding "lectin" domain appended to a receptor-destroying sialate-O-acetylesterase ("esterase"). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II).

Cryoelectron Tomography of the NAIP5/NLRC4 Inflammasome: Implications for NLR Activation.

Inflammasomes are high molecular weight protein complexes that play a crucial role in innate immunity by activating caspase-1. Inflammasome formation is initiated when molecules originating from invading microorganisms activate nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) and induce NLR multimerization. Little is known about the conformational changes involved in NLR activation and the structural organization of NLR multimers.

Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3).

Toll-like receptors (TLRs) are crucial in innate recognition of invading micro-organisms and their subsequent clearance. Bacteria are not passive bystanders and have evolved complex evasion mechanisms. Staphylococcus aureus secretes a potent TLR2 antagonist, staphylococcal superantigen-like protein 3 (SSL3), which prevents receptor stimulation by pathogen-associated lipopeptides.

Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins.

Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias).

Cross-sectional analysis of Dutch repatriated service members from southern Afghanistan (2003-2014).

Background: A systematic analysis of the complete medical support organization of the Dutch Armed Forces regarding repatriated service members from Afghanistan has not been performed so far.

Methods: All information were collated in a specifically designed electronic database and gathered from the archive of the Central Military Hospital for all Dutch service members receiving treatment for wounds or diseases sustained in the Afghan theater from July 2003 till January 2014.

Results: Traumatic injuries were the main cause (63%, 141/223) of repatriation, and improvised explosive devices the major (67%, 60/89) mechanism of injury in the battle casualty group.

Long-term impact of battle injuries; five-year follow-up of injured Dutch servicemen in Afghanistan 2006-2010.

Objectives: Units deployed to armed conflicts are at high risk for exposure to combat events. Many battle casualties (BCs) have been reported in the recent deployment to Afghanistan. The long-term impact of these combat injuries, at their five-year end point, is currently unknown.

Impact of explosive devices in modern armed conflicts: in-depth analysis of Dutch battle casualties in southern Afghanistan.

Background: The patterns and mechanisms of injuries of all Dutch battle casualties (BCs) were analyzed to improve the care for injured service members. We performed an in-depth analysis of all Dutch BCs during the participation of The Netherlands as lead nation in the International Security Assistance Force mission in southern Afghanistan.

Methods: Participants were selected from the trauma registry at the Dutch Role 2 Medical Treatment Facility if they met the criteria for Dutch BC between August 2006 and August 2010.

When less becomes more: optimization of protein expression in HEK293-EBNA1 cells using plasmid titration - a case study for NLRs.

Transient transfection of the human HEK293-EBNA1 cell line using polyethyleneimine is widely adopted for recombinant protein production. Whereas high expression of many targets is achieved, purification yields of some highly expressed proteins remain low due to aggregation. We hypothesized that for these proteins the expression rates achieved at standard transfection conditions are too high, causing an overload of the protein folding machinery.

TLR accessory molecule RP105 (CD180) is involved in post-interventional vascular remodeling and soluble RP105 modulates neointima formation.

Background: RP105 (CD180) is TLR4 homologue lacking the intracellular TLR4 signaling domain and acts a TLR accessory molecule and physiological inhibitor of TLR4-signaling. The role of RP105 in vascular remodeling, in particular post-interventional remodeling is unknown.

Methods And Results: TLR4 and RP105 are expressed on vascular smooth muscle cells (VSMC) as well as in the media of murine femoral artery segments as detected by qPCR and immunohistochemistry.

Formation and structure of a NAIP5-NLRC4 inflammasome induced by direct interactions with conserved N- and C-terminal regions of flagellin.

The NOD-like receptors NAIP5 and NLRC4 play an essential role in the innate immune response to the bacterial tail protein flagellin. Upon flagellin detection, NAIP5 and NLRC4 form a hetero-oligomeric inflammasome that induces caspase-1-dependent cell death. So far, both the mechanism of formation of the NAIP5-NLRC4 inflammasome and its structure are poorly understood.

[Dutch military casualties of the war in Afghanistan--quality of life and level of participation after rehabilitation].

Objective: To describe the distribution of injuries and the quality of life and functioning at activity and participation level of rehabilitated Dutch military personnel who were wounded during the mission to Afghanistan.

Design: Retrospective, descriptive.

Method: The study population consisted of military war casualties who followed multidisciplinary rehabilitation treatment for injuries sustained in combat in Afghanistan.

Evasion of Toll-like receptor 2 activation by staphylococcal superantigen-like protein 3.

Toll-like receptors (TLRs) are crucial for our host defense against microbial infections. TLR2 is especially important to fight bacterial infections, as it specifically recognizes bacterial lipoproteins of both Gram-positive and Gram-negative origin. Present on a variety of immune cells, TLR2 is critical for host protection against several bacterial infections, including those caused by Staphylococcus aureus.