The global H5N1 influenza panzootic in mammals.

Influenza A viruses have caused more documented global pandemics in human history than any other pathogen. High pathogenicity avian influenza viruses belonging to the H5N1 subtype are a leading pandemic risk. Two decades after H5N1 'bird flu' became established in poultry in Southeast Asia, its descendants have resurged, setting off a H5N1 panzootic in wild birds that is fuelled by: (1) rapid intercontinental spread, reaching South America and Antarctica for the first time; (2) fast evolution via genomic reassortment; and (3) frequent spillover into terrestrial and marine mammals.

Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve distinct globally dominant subvariants. Here we compared their replication in human cell lines and primary airway cultures and measured host responses to infection.

SARS-CoV-2 variant biology: immune escape, transmission and fitness.

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a major step change in its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates of transmission relative to previous variants and were termed 'variants of concern' (VOCs). Designated Alpha, Beta, Gamma, Delta and Omicron, the VOCs emerged independently from one another, and in turn each rapidly became dominant, regionally or globally, outcompeting previous variants.

SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies.

Monoclonal antibodies (mAbs) offer a treatment option for individuals with severe COVID-19 and are especially important in high-risk individuals where vaccination is not an option. Given the importance of understanding the evolution of resistance to mAbs by SARS-CoV-2, we reviewed the available in vitro neutralization data for mAbs against live variants and viral constructs containing spike mutations of interest. Unfortunately, evasion of mAb-induced protection is being reported with new SARS-CoV-2 variants.

Tracking SARS-CoV-2 mutations and variants through the COG-UK-Mutation Explorer.

COG-UK Mutation Explorer (COG-UK-ME, https://sars2.cvr.gla.

Factors influencing the uptake of evidence in child health policy-making: results of a survey among 23 European countries.

Background: The ability to successfully transfer knowledge across international boundaries to improve health across the European Region is dependent on an in-depth understanding of the many factors involved in policy creation. Across countries we can observe various approaches to evidence usage in the policy-making process. This study, which was a part of the Models of Child Health Appraised (MOCHA) project assessing patterns of children's primary care in Europe, focused on how and what kind of evidence is used in child health policy-making processes in European countries and how it is applied to inform policy and practice.

IRAK4 Deficiency Presenting with Anti-NMDAR Encephalitis and HHV6 Reactivation.

IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of IRAK4 mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation.

HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection.

Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes.

A bimodal switch in global protein translation coupled to eIF4H relocalisation during advancing cell-cell transmission of herpes simplex virus.

We used the bioorthogonal protein precursor, homopropargylglycine (HPG) and chemical ligation to fluorescent capture agents, to define spatiotemporal regulation of global translation during herpes simplex virus (HSV) cell-to-cell spread at single cell resolution. Translational activity was spatially stratified during advancing infection, with distal uninfected cells showing normal levels of translation, surrounding zones at the earliest stages of infection with profound global shutoff. These cells further surround previously infected cells with restored translation close to levels in uninfected cells, reflecting a very early biphasic switch in translational control.

Spatiotemporal dynamics of HSV genome nuclear entry and compaction state transitions using bioorthogonal chemistry and super-resolution microscopy.

We investigated the spatiotemporal dynamics of HSV genome transport during the initiation of infection using viruses containing bioorthogonal traceable precursors incorporated into their genomes (HSVEdC). In vitro assays revealed a structural alteration in the capsid induced upon HSVEdC binding to solid supports that allowed coupling to external capture agents and demonstrated that the vast majority of individual virions contained bioorthogonally-tagged genomes. Using HSVEdC in vivo we reveal novel aspects of the kinetics, localisation, mechanistic entry requirements and morphological transitions of infecting genomes.

Spatial and Temporal Resolution of Global Protein Synthesis during HSV Infection Using Bioorthogonal Precursors and Click Chemistry.

We used pulse-labeling with the methionine analogue homopropargylglycine (HPG) to investigate spatiotemporal aspects of protein synthesis during herpes simplex virus (HSV) infection. In vivo incorporation of HPG enables subsequent selective coupling of fluorochrome-capture reagents to newly synthesised proteins. We demonstrate that HPG labeling had no effect on cell viability, on accumulation of test early or late viral proteins, or on overall virus yields.

Mitochondria mediate septin cage assembly to promote autophagy of Shigella.

Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established.

Structured review of papers reporting specific functions in patients with cancer of the head and neck: 2006 - 2013.

Health-related quality of life (HRQoL) focuses on 4 core domains: physical and psychological function, social interaction, disease, and treatment-related symptoms, and is a key outcome in patients with cancer of the head and neck. We reviewed papers published between 2006 and 2013 that used validated questionnaires to report functional outcome in this group. A total of 572 papers were identified and 118 of them concerned function.

Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by Infected Cells in Advance of Virus Transmission.

Unlabelled: Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself. Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores. We report a hitherto unknown and unexpected outcome of virus-host interaction.

Herpes Simplex Virus 1 (HSV-1) ICP22 protein directly interacts with cyclin-dependent kinase (CDK)9 to inhibit RNA polymerase II transcription elongation.

The Herpes Simplex Virus 1 (HSV-1)-encoded ICP22 protein plays an important role in viral infection and affects expression of host cell genes. ICP22 is known to reduce the global level of serine (Ser)2 phosphorylation of the Tyr1Ser2Pro3Thr4Ser5Pro6Ser7 heptapeptide repeats comprising the carboxy-terminal domain (CTD) of the large subunit of RNA polymerase (pol) II. Accordingly, ICP22 is thought to associate with and inhibit the activity of the positive-transcription elongation factor b (P-TEFb) pol II CTD Ser2 kinase.

Interpreting tuberculin skin tests in a population with a high prevalence of HIV, tuberculosis, and nonspecific tuberculin sensitivity.

Understanding the epidemiology and clinical course of tuberculosis is hampered by the absence of a perfect test for latent tuberculosis infection. The tuberculin skin test (TST) is widely used but suffers poor specificity in those receiving the bacille Calmette-Guérin vaccine and poor sensitivity in individuals with human immunodeficiency virus (HIV) infections. TST responses for a target population in Harare, Zimbabwe (HIV prevalence, 21%), recruited in 2005-2006, were interpreted by using a separate calibration population in Harare, for which interferon-gamma release assays (enzyme-linked immunosorbent spot (ELISpot)) results were also known.

A study of the variation in tuberculosis incidence and possible influential variables in Manchester, Liverpool, Birmingham and Cardiff in 1991-1995.

Setting And Objective: The reversal of the decline in United Kingdom tuberculosis rates has sparked a resurgence of interest in the epidemiology and prevention of tuberculosis in the UK. In this paper we quantify the primary factors explaining the variability in the electoral ward level relative risk of tuberculosis in Manchester, Liverpool, Birmingham and Cardiff.

Design: Ecological analysis of the incidence of tuberculosis in 397 wards using hospital admissions data as a proxy for tuberculosis incidence.

Effects of equine oestrogens on markers of vasoactive function in human coronary artery endothelial cells.

A large proportion of the beneficial effects that oestrogens demonstrate on the vasculature are believed to be mediated via direct effects on the vascular wall. In this study we compared a number of oestrogenic compounds isolated from pregnant mare's urine including 17beta-oestradiol and oestrone, in terms of their abilities to inhibit stimulated endothelin-1 release from normal human coronary artery endothelial cells (CAEC). We also examined their ability to stimulate expression of constitutive endothelial nitric oxide synthase (eNOS) and explored their effects on cellular angiotensin converting enzyme (ACE).

A preliminary report: a new scale to identify the pseudodementia syndrome.

Background: The literature was reviewed to abstract items which were claimed to distinguish organic dementia from pseudodementia. Their discriminating powers were tested in a prospective study. Eighteen of these items were selected to create a questionnaire which should distinguish organic dementia from pseudodementia.

Expression, purification, and partial characterization of HCV RNA polymerase.

The product of the NS5B gene of Hepatitis C Virus (HCV) has been expressed in Escherichia Coli both as a fusion protein with glutathione-S-transferase (GST) of molecular weight 91 KDa and at high level as a single protein of molecular weight 65 KDa. The protein was sequestered within inclusion bodies and a variety of procedures designed to minimize inclusion body formation proved unsuccessful. The method finally adopted involved the purification of inclusion bodies followed by the solubilization, purification, and refolding of the expressed protein.

Arterial wall changes in type 2 diabetic subjects.

Arterial ultrasonic appearances using high resolution ultrasound were studied in 97 subjects with Type 2 diabetes and age- and sex-matched controls. The intima-media thickness of both common carotid arteries was measured 2 cm proximal to the bifurcation and the presence or absence of plaque on both common and femoral bifurcations was recorded. The mean intima-media thickness in subjects with diabetes was 0.

Early days in the St. Mary's Medical School Photographic Department: Part 2.

Following Part 1 (1992; 15: 133-137), this second article covers the 1950s and 1960s. The enormous amount of work done for the Medical School's Centenary Exhibition to which no visitors came is outlined: Sir Alexander Fleming's picture of the 1928 culture plate of Penicillium; development of the cinelaryngeal camera; the introduction of modern techniques of duplication. Some comments on the quality that is lost with the use of modern automated 'foolproof' equipment.

On the origin of Alzheimer's disease: a hypothesis.

There is no unifying hypothesis to account for the anatomical distribution of neuropathology, the involvement of beta-amyloid precursor protein (beta APP) and the role of increasing age in triggering the Alzheimer disease process. We report here that layer II pre-alpha neurones in transentorhinal and entorhinal cortex contain more beta APP immunoreactivity than other cortical neurones in normal individuals. This immunoreactivity increased in the early stages of Alzheimer's disease and was lost as the disease progressed.