Insights into neutralization of animal viruses gained from study of influenza virus

It has long been known that the binding of antibodies to viruses can result in a loss of infectivity, or neutralization, but little is understood of the mechanism or mechanisms of this process. This is probably because neutralization is a multifactorial phenomenon depending upon the nature of the virus itself, the particular antigenic site involved, the isotype of immunoglobulin and the ratio of virus to immunoglobulin (see below). Thus not only is it likely that neutralization of one virus will differ from another but that changing the circumstances of neutralization can change the mechanism itself. To give coherence to the topic we are concentrating this review on one virus, influenza type A which is itself well studied and reasonably well understood [1–3]. Reviews of the older literature can be found in references 4 to 7

The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Potentially Diagnostic Electron Paramagnetic Resonance Spectra Elucidate the Underlying Mechanism of Mitochondrial Dysfunction in the Deoxyguanosine Kinase Deficient Rat Model of a Genetic Mitochondrial DNA Depletion Syndrome

A novel rat model for a well-characterized human mitochondrial disease, mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase (DGUOK) deficiency, is described. The rat model recapitulates the pathologic and biochemical signatures of the human disease. The application of electron paramagnetic (spin) resonance (EPR) spectroscopy to the identification and characterization of respiratory chain abnormalities in the mitochondria from freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR is shown to be a sensitive technique for detecting mitochondrial functional abnormalities in situ and, here, is particularly useful in characterizing the redox state changes and oxidative stress that can result from depressed expression and/or diminished specific activity of the distinct respiratory chain complexes. As EPR requires no sample preparation or non-physiological reagents, it provides information on the status of the mitochondrion as it was in the functioning state. On its own, this information is of use in identifying respiratory chain dysfunction; in conjunction with other techniques, the information from EPR shows how the respiratory chain is affected at the molecular level by the dysfunction. It is proposed that EPR has a role in mechanistic pathophysiological studies of mitochondrial disease and could be used to study the impact of new treatment modalities or as an additional diagnostic tool

Exploring efficacy in personal constraint negotiation: an ethnography of mountaineering tourists

Limited work has explored the relationship between efficacy and personal constraint negotiation for adventure tourists, yet efficacy is pivotal to successful activity participation as it influences people’s perceived ability to cope with constraints, and their decision to use negotiation strategies. This paper explores these themes with participants of a commercially organised mountaineering expedition. Phenomenology-based ethnography was adopted to appreciate the social and cultural mountaineering setting from an emic perspective. Ethnography is already being used to understand adventure participation, yet there is considerable scope to employ it further through researchers immersing themselves into the experience. The findings capture the interaction between the ethnographer and the group members, and provide an embodied account using their lived experiences. Findings reveal that personal mountaineering skills, personal fitness, altitude sickness and fatigue were the four key types of personal constraint. Self-efficacy, negotiation-efficacy and other factors, such as hardiness and motivation, influenced the effectiveness of negotiation strategies. Training, rest days, personal health, and positive self-talk were negotiation strategies. A conceptual model illustrates these results and demonstrates the interplay between efficacy and the personal constraint negotiation journey for led mountaineers

Peripheral blood lymphocyte proliferative responses in cattle infected with or vaccinated against Anaplasma marginale

An assay was developed for measurement of the peripheral blood lymphocyte proliferative response (PBLPR) in cattle infected with or immunised against Anaplasma marginale. PBLPR was not evident in all cattle that had recovered from A. marginale infection. However, A. marginale-sensitised lymphocytes were detected in the spleens of all immune cattle tested in the absence of detectable PBLPR. During the course of initial infection, cattle exhibited detectable PBLPR for a period corresponding with and up to 2 weeks after patent parasitaemia, followed by a second, usually larger peak in PBLPR corresponding to the time of sub-clinical relapse of cattle. Analysis of the PBLPR of A. marginale chronically infected cattle demonstrated highly variable PBLPR between individuals and over time. A positive PBLPR was induced in cattle by vaccination using a crude A. marginale antigen preparation. The PBLPR of vaccinated cattle subsequently infected with A. marginale was markedly different from that of naive cattle, with reduced PBLPR being associated with the onset of parasitaemia. The antigen used in the PBLPR assay was inactivated by proteolysis. Proteolysis also abolished immunity that had been induced in cattle vaccinated using the antigen preparation. A. marginale-sensitised PBL did not proliferate in response to antigen from the heterologous species A. centrale. A. centrale-sensitised PBL, however, responded to A. marginale antigen. Interferon-γ (IFN-γ) was detected in PBLPR-assay supernatants and was associated with a strong PBLPR

1-Chloro­acetyl-3,3-dimethyl-2,6-di­phenyl­piperidin-4-one

In the mol­ecule of the title compound, C21H22ClNO2, the piperidine ring adopts a distorted boat conformation. The two phenyl rings are nearly orthogonal to each other with a dihedral angle of 87.1 (1)°. In the crystal structure, the mol­ecules are linked into a three-dimensional network by C—H⋯O and C—H⋯π inter­actions

Dispersion of low frequency plasma waves upstream of the quasi-perpendicular terrestrial bow shock

Low frequency waves in the foot of a supercritical quasi-perpendicular shock front have been observed since the very early in situ observations of the terrestrial bow shock (Guha et al., 1972). The great attention that has been devoted to these type of waves since the first observations is explained by the key role attributed to them in the processes of energy redistribution in the shock front by various theoretical models. In some models, these waves play the role of the intermediator between the ions and electrons. It is assumed that they are generated by plasma instability that exist due to the counter-streaming flows of incident and reflected ions. In the second type of models, these waves result from the evolution of the shock front itself in the quasi-periodic process of steepening and overturning of the magnetic ramp. However, the range of the observed frequencies in the spacecraft frame are not enough to distinguish the origin of the observed waves. It also requires the determination of the wave vectors and the plasma frame frequencies. Multipoint measurements within the wave coherence length are needed for an ambiguous determination of the wave vectors. In the main multi-point missions such as ISEE, AMPTE, Cluster and THEMIS, the spacecraft separation is too large for such a wave vector determination and therefore only very few case studies are published (mainly for AMPTE UKS AMPTE IRM pair). Here we present the observations of upstream low frequency waves by the Cluster spacecraft which took place on 19 February 2002. The spacecraft separation during the crossing of the bow shock was small enough to determine the wave vectors and allowed the identification of the plasma wave dispersion relation for the observed waves. Presented results are compared with whistler wave dispersion and it is shown that contrary to previous studies based on the AMPTE data, the phase velocity in the shock frame is directed downstream. The consequences of this finding for both types of models that were developed to explain the generation of these waves are discussed