Cell entry of a host targeting protein of oomycetes requires gp96

This work is supported by the [European Community’s] Seventh Framework Programme [FP7/2007–2013] under grant agreement no. [238550] (L.L., J.D.-U., C.J.S., P.v.W.); BBSRC [BBE007120/1, BB/J018333/1 and BB/G012075/1] (F.T., I.d.B., C.J.S., S.W., P.v.W.); Newton Global Partnership Award [BB/N005058/1] (F.T., P.v.W.), the University of Aberdeen (A.D.T., T.R., C.J.S., P.v.W.) and Deutsche Forschungsgemeinschaft [CRC1093] (P.B., T.S.). We would like to acknowledge the Ministry of Higher Education Malaysia for funding INA. We would like to thank Brian Haas for his bioinformatics support. We would like to acknowledge Neil Gow and Johannes van den Boom for critical reading of the manuscript. We would like to acknowledge Svetlana Rezinciuc for technical help with pH-studies.Peer reviewedPublisher PD

Plant Food Delphinidin-3-Glucoside Significantly Inhibits Platelet Activation and Thrombosis: Novel Protective Roles against Cardiovascular Diseases

Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

A comparison of the laryngeal mask airway with facemask and oropharyngeal airway for manual ventilation by critical care nurses in children.

The laryngeal mask airway is included as a first line airway device during adult resuscitation by first responders. However, there is little evidence for its role in paediatric resuscitation. Using anaesthetised children as a model for paediatric cardiopulmonary arrest, we compared the ability of critical care nurses to manually ventilate the anaesthetised child via the laryngeal mask airway compared with the facemask and oropharyngeal airway. The airway devices were inserted in random order and chest expansion was measured using an ultrasound distance transducer. The critical care nurses were able to place the laryngeal mask airway and achieve successful ventilation in 82% of children compared to 70% using the facemask and oropharyngeal airway, although the difference was not statistically significant (p = 0.136). The median time to first successful breath using the laryngeal mask airway was 39 s compared to 25 s using the facemask (p < 0.001). In this group of nurses, we did not show a difference in ventilation via a laryngeal mask airway or facemask, although facemask ventilation was achieved more quickly

A comparison of the laryngeal mask airway with the facemask and oropharyngeal airway for manual ventilation by first responders in children.

In adults, first responders to a cardiopulmonary arrest provide better ventilation using a laryngeal mask airway than a facemask. It is unclear if the same is true in children. We investigated this by comparing the ability of 36 paediatric ward nurses to ventilate the lungs of 99 anaesthetised children (a model for cardiopulmonary arrest) using a laryngeal mask airway and using a facemask with an oropharyngeal airway. Anteroposterior chest wall displacement was measured using an ultrasonic detector. Nurses achieved successful ventilation in 74 (75%) of cases with the laryngeal mask airway and 76 (77%) with facemask and oropharyngeal airway (p = 0.89). Median (IQR [range]) time to first breath was longer for the laryngeal mask airway (48 (39-65 [8-149])) s than the facemask/airway (35 (25-53 [14-120]) s; p < 0.0001). In 10 cases (10%) the lungs were ventilated using the laryngeal mask airway but not using the facemask/oropharyngeal airway. We conclude that ventilation is achieved rapidly using a facemask and oropharyngeal airway, and that the laryngeal mask airway may represent a useful second line option for first responders

A comparison of the laryngeal mask airway with the facemask and oropharyngeal airway for manual ventilation by first responders in children.

In adults, first responders to a cardiopulmonary arrest provide better ventilation using a laryngeal mask airway than a facemask. It is unclear if the same is true in children. We investigated this by comparing the ability of 36 paediatric ward nurses to ventilate the lungs of 99 anaesthetised children (a model for cardiopulmonary arrest) using a laryngeal mask airway and using a facemask with an oropharyngeal airway. Anteroposterior chest wall displacement was measured using an ultrasonic detector. Nurses achieved successful ventilation in 74 (75%) of cases with the laryngeal mask airway and 76 (77%) with facemask and oropharyngeal airway (p = 0.89). Median (IQR [range]) time to first breath was longer for the laryngeal mask airway (48 (39-65 [8-149])) s than the facemask/airway (35 (25-53 [14-120]) s; p < 0.0001). In 10 cases (10%) the lungs were ventilated using the laryngeal mask airway but not using the facemask/oropharyngeal airway. We conclude that ventilation is achieved rapidly using a facemask and oropharyngeal airway, and that the laryngeal mask airway may represent a useful second line option for first responders

The antecedents of simultaneous appointments to CEO and Chair

Duality, Succession, Corporate governance,