Antibodies to Seasonal Coronaviruses Rarely Cross-React with SARS-CoV-2: Findings from an African Birth Cohort

Antibodies to seasonal human-coronaviruses (sHCoV) may cross-protect against SARS-CoV-2. We investigated antibody responses in biobanked serum obtained before the pandemic from infants with polymerase chain reaction-confirmed sHCoV. Among 141 samples with antibodies to sHCoV, 4 (2.8%) were positive for SARS-CoV-2-S1 and 8 (5.7%) for SARS-CoV-2-S2. Antibodies to sHCoV rarely cross-react with SARS-CoV-2 antigens and are unlikely to account for mild pediatric illness

Assessment of Streptococcus pneumoniae pilus islet-1 prevalence in carried and transmitted isolates from mother–infant pairs on the Thailand–Burma border

AbstractStreptococcus pneumoniae pilus islet-1 (PI–1)-encoded pilus enhances in vitro adhesion to the respiratory epithelium and may contribute to pneumococcal nasopharyngeal colonization and transmission. The pilus subunits are regarded as potential protein vaccine candidates. In this study, we sought to determine PI–1 prevalence in carried pneumococcal isolates and explore its relationship with transmissibility or carriage duration. We studied 896 pneumococcal isolates collected during a longitudinal carriage study that included monthly nasopharyngeal swabbing of 234 infants and their mothers between the ages of 1 and 24 months. These were cultured according to the WHO pneumococcal carriage detection protocol. PI-1 PCR and genotyping by multilocus sequence typing were performed on isolates chosen according to specific carriage and transmission definitions. Overall, 35.2% of the isolates were PI-1-positive, but PI-1 presence was restricted to ten of the 34 serotypes studied and was most frequently associated with serotypes 19F and 23F; 47.5% of transmitted and 43.3% of non-transmitted isolates were PI-1-positive (OR 1.2; 95% CI 0.8-1.7; p 0.4). The duration of first-ever infant pneumococcal carriage was significantly longer with PI-1-positive organisms, but this difference was not significant at the individual serotype level. In conclusion, PI-1 is commonly found in pneumococcal carriage isolates, but does not appear to be associated with pneumococcal transmissibility or carriage duration

Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides

This article is under embargo for 12 months from the date of publication [Publication date: 7 Jan 2015] in accordance with publisher copyright policy.Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)- region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP. Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by 2-dimensional gel electrophoresis and combined de novo database mass spectrometric sequencing. SmD autoantibody proteomes from all six patients with SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69 H-chains and IGKV3-20 and IGKV2-28 L-chains, with shared and individual V-region amino acid replacement mutations. Clonotypic sharing and restricted V-region diversity of systemic autoimmunity can now be extended from the Ro/La cluster to Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in unrelated patients with SLE

Effect of pioglitazone treatment on behavioral symptoms in autistic children

INTRODUCTION: Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARγ), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. CASE DESCRIPTION: The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. DISCUSSION AND EVALUATION: In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients. CONCLUSION: Pioglitazone should be considered for further testing of therapeutic potential in autistic patients

Topos theory and `neo-realist' quantum theory

Topos theory, a branch of category theory, has been proposed as mathematical basis for the formulation of physical theories. In this article, we give a brief introduction to this approach, emphasising the logical aspects. Each topos serves as a `mathematical universe' with an internal logic, which is used to assign truth-values to all propositions about a physical system. We show in detail how this works for (algebraic) quantum theory.Comment: 22 pages, no figures; contribution for Proceedings of workshop "Recent Developments in Quantum Field Theory", MPI MIS Leipzig, July 200

Partner symmetries of the complex Monge-Ampere equation yield hyper-Kahler metrics without continuous symmetries

We extend the Mason-Newman Lax pair for the elliptic complex Monge-Amp\`ere equation so that this equation itself emerges as an algebraic consequence. We regard the function in the extended Lax equations as a complex potential. We identify the real and imaginary parts of the potential, which we call partner symmetries, with the translational and dilatational symmetry characteristics respectively. Then we choose the dilatational symmetry characteristic as the new unknown replacing the K\"ahler potential which directly leads to a Legendre transformation and to a set of linear equations satisfied by a single real potential. This enables us to construct non-invariant solutions of the Legendre transform of the complex Monge-Amp\`ere equation and obtain hyper-K\"ahler metrics with anti-self-dual Riemann curvature 2-form that admit no Killing vectors.Comment: submitted to J. Phys.

Topos Theory and Consistent Histories: The Internal Logic of the Set of all Consistent Sets

A major problem in the consistent-histories approach to quantum theory is contending with the potentially large number of consistent sets of history propositions. One possibility is to find a scheme in which a unique set is selected in some way. However, in this paper we consider the alternative approach in which all consistent sets are kept, leading to a type of `many world-views' picture of the quantum theory. It is shown that a natural way of handling this situation is to employ the theory of varying sets (presheafs) on the space \B of all Boolean subalgebras of the orthoalgebra \UP of history propositions. This approach automatically includes the feature whereby probabilistic predictions are meaningful only in the context of a consistent set of history propositions. More strikingly, it leads to a picture in which the `truth values', or `semantic values' of such contextual predictions are not just two-valued (\ie true and false) but instead lie in a larger logical algebra---a Heyting algebra---whose structure is determined by the space \B of Boolean subalgebras of \UP.Comment: 28 pages, LaTe

Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture

Neuronal Birthdate Reveals Topography in a Vestibular Brainstem Circuit for Gaze Stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture

Bohrification of operator algebras and quantum logic

Following Birkhoff and von Neumann, quantum logic has traditionally been based on the lattice of closed linear subspaces of some Hilbert space, or, more generally, on the lattice of projections in a von Neumann algebra A. Unfortunately, the logical interpretation of these lattices is impaired by their nondistributivity and by various other problems. We show that a possible resolution of these difficulties, suggested by the ideas of Bohr, emerges if instead of single projections one considers elementary propositions to be families of projections indexed by a partially ordered set C(A) of appropriate commutative subalgebras of A. In fact, to achieve both maximal generality and ease of use within topos theory, we assume that A is a so-called Rickart C*-algebra and that C(A) consists of all unital commutative Rickart C*-subalgebras of A. Such families of projections form a Heyting algebra in a natural way, so that the associated propositional logic is intuitionistic: distributivity is recovered at the expense of the law of the excluded middle. Subsequently, generalizing an earlier computation for n-by-n matrices, we prove that the Heyting algebra thus associated to A arises as a basis for the internal Gelfand spectrum (in the sense of Banaschewski-Mulvey) of the "Bohrification" of A, which is a commutative Rickart C*-algebra in the topos of functors from C(A) to the category of sets. We explain the relationship of this construction to partial Boolean algebras and Bruns-Lakser completions. Finally, we establish a connection between probability measure on the lattice of projections on a Hilbert space H and probability valuations on the internal Gelfand spectrum of A for A = B(H).Comment: 31 page