Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria

High-pitch sounds small for domestic dogs: abstract crossmodal correspondences between auditory pitch and visual size

Humans possess intuitive associations linking certain non-redundant features of stimuli - e.g. high-pitched sounds with small object size (or similarly, low-pitched sounds with large object size). This phenomenon, known as crossmodal correspondence, has been identified in humans across multiple different senses. There is some evidence that non-human animals also form crossmodal correspondences, but the known examples are mostly limited to the associations between the pitch of vocalizations and the size of callers. To investigate whether domestic dogs, like humans, show abstract pitch-size association, we first trained dogs to approach and touch an object after hearing a sound emanating from it. Subsequently, we repeated the task but presented dogs with two objects differing in size, only one of which was playing a sound. The sound was either high or low pitched, thereby creating trials that were either congruent (high pitch from small object; low pitch from large objects) or incongruent (the reverse). We found that dogs reacted faster on congruent versus incongruent trials. Moreover, their accuracy was at chance on incongruent trials, but significantly above chance for congruent trials. Our results suggest that non-human animals show abstract pitch sound correspondences, indicating these correspondences may not be uniquely human but rather a sensory processing feature shared by other species

Prospective assessment of white matter integrity in adult stem cell transplant recipients

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05). There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT

Observation of the DsJ(2317) and DsJ(2457) in B decays

We report the first observation of the B --> Dbar DsJ(2317) and B --> Dbar DsJ(2457) decays based on 123.8 10^6 BBar events collected with the Belle detector at KEKB. We observe the DsJ(2317) decay to Ds pi0 and DsJ(2457) decay to the Ds* pi0 and Ds gamma final states. We also set 90% CL upper limits for the decays DsJ(2317) --> Ds* gamma, DsJ(2457) --> Ds* gamma, DsJ(2457) --> Ds pi0 and DsJ(2457) --> Ds pi+ pi-.Comment: 6 pages, 3 figures. A few minor corrections. Replaced by version accepted to publication in Phys. Rev. Let

Observation of Large CP Violation and Evidence for Direct CP Violation in B0-->pi+pi- Decays

We report the first observation of CP-violating asymmetries in B0 --> pi+pi- decays based on a 140 fb-1 data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. We reconstruct one neutral B meson as a B0 --> pi+pi- CP eigenstate and identify the flavor of the accompanying B meson from its decay products. We apply an unbinned maximum likelihood fit to the distribution of the time intervals between the two B meson decay points. The fit yields the CP-violating asymmetry amplitudes Apipi = +0.58+/-0.15(stat)+/-0.07(syst) and Spipi = -1.00+/-0.21(stat)+/-0.07(syst). We rule out the CP-conserving case, Apipi=Spipi=0, at a level of 5.2 standard deviations. We also find evidence for direct CP violation with a significance at or greater than 3.2 standard deviations for any Spipi value.Comment: 9 pages, 3 figure

Persistence of maternal antibodies to influenza A virus among captive mallards (\u3ci\u3eAnas platyrhynchos\u3c/i\u3e)

Wild waterfowl are maintenance hosts of most influenza A virus (IAV) subtypes and are often the subjects of IAV surveillance and transmission models. While maternal antibodies have been detected in yolks and in nestlings for a variety of wild bird species and pathogens, the persistence of maternal antibodies to IAVs in mallard ducklings (Anas platyrhynchos) has not been previously investigated. Nonetheless, this information is important for a full understanding of IAV transmission dynamics because ducklings protected by maternal antibodies may not be susceptible to infection. In this study, we examined the transfer of IAV-specific maternal antibodies to ducklings. Blood samples were collected approximately every five days from ducklings hatched from hens previously infected with an H6 strain of IAV. Serum samples were tested for antibodies to IAV by an enzyme-linked immunosorbent assay. The median persistence of maternal antibodies in ducklings was 12.5 days (range: 4-33 days) post-hatch. The majority of ducklings (71%) had detectable maternal antibodies from 4 to 17 days post-hatch, while a small subset of individuals (29%) had detectable maternal antibodies for up to 21-33 days post-hatch. Antibody concentrations in hens near the time of egg laying were correlated with maternal antibody concentrations in the initial blood sample collected from ducklings (0-4 days post-hatch). Knowledge of the duration of maternal antibodies in ducklings will aid in the interpretation of IAV serological surveillance results and in the modeling of IAV transmission dynamics in waterfowl

Observation of Large CP Violation in the Neutral B Meson System

We present a measurement of the Standard Model CP violation parameter sin 2phi_1 based on a 29.1 fb^{-1} data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. One neutral B meson is fully reconstructed as a J/psi Ks, psi(2S) Ks, chi_c1 Ks, eta_c Ks, J/psi K_L or J/psi K^{*0} decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin 2phi_1 = 0.99 +- 0.14(stat) +- 0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.Comment: 4 figures, to appear in Phys. Rev. Letter

An Upper Bound on the Decay tau -> mu gamma from Belle

We have performed a search for the lepton-flavor-violating decay tau -> mu gamma using a data sample of 86.3fb^{-1} accumulated by the Belle detector at KEK. No evidence for a signal is seen, and we set an upper limit for the branching fraction of B(tau -> mu gamma) < 3.1 x 10^{-7} at the 90% confidence level.Comment: 6 pages, 4 figuresm, submitted to Phys. Rev. Let

Search for the Lepton-Flavor-Violating Decay τ−→μ−η\tau^- \to \mu^- \eta at Belle

We have searched for the Lepton Flavor Violating decay $\tau^- \to \mu^- \eta$ using a data sample of 84.3 fb$^{-1}$ accumulated with the Belle detector at KEK. The $\eta$-meson was detected through the decay modes: $\eta \to \gamma\gamma$ and $\pi^+\pi^-\pi^0$. No signal candidates are found, and we obtain an upper limit for the branching fraction ${\cal B}(\tau^- \to \mu^- \eta)<3.4\times 10^{-7}$ at the 90% confidence level.Comment: Submitted to Phys.Rev.Let