Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between Arabidopsis thaliana accessions

Accumulation of genetic incompatibilities within species can lead to reproductive isolation and, potentially, speciation. In this study, we show that allelic variation at SRF3 (Strubbelig Receptor Family 3), encoding a receptor-like kinase, conditions the occurrence of incompatibility between Arabidopsis thaliana accessions. The geographical distribution of SRF3 alleles reveals that allelic forms causing epistatic incompatibility with a Landsberg erecta allele at the RPP1 resistance locus are present in A. thaliana accessions in central Asia. Incompatible SRF3 alleles condition for an enhanced early immune response to pathogens as compared to the resistance-dampening effect of compatible SRF3 forms in isogenic backgrounds. Variation in disease susceptibility suggests a basis for the molecular patterns of a recent selective sweep detected at the SRF3 locus in central Asian populations.     

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.     

Bias‐corrected bootstrap prediction intervals for autoregressive model: new alternatives with applications to tourism forecasting

This paper proposes the use of the bias‐corrected bootstrap for interval forecasting of an autoregressive time series with an arbitrary number of deterministic components. We use the bias‐corrected bootstrap based on two alternative bias‐correction methods: the bootstrap and an analytic formula based on asymptotic expansion. We also propose a new stationarity‐correction method, based on stable spectral factorization, as an alternative to Kilian's method exclusively used in past studies. A Monte Carlo experiment is conducted to compare small‐sample properties of prediction intervals. The results show that the bias‐corrected bootstrap prediction intervals proposed in this paper exhibit desirable small‐sample properties. It is also found that the bootstrap bias‐corrected prediction intervals based on stable spectral factorization are tighter and more stable than those based on Kilian's stationarity‐correction. The proposed methods are applied to interval forecasting for the number of tourist arrivals in Hong Kong. Copyright © 2010 John Wiley & Sons, Ltd.     

Triosephosphate isomerase: a highly evolved biocatalyst

Triosephosphate isomerase (TIM) is a perfectly evolved enzyme which very fast interconverts dihydroxyacetone phosphate and d-glyceraldehyde-3-phosphate. Its catalytic site is at the dimer interface, but the four catalytic residues, Asn11, Lys13, His95 and Glu167, are from the same subunit. Glu167 is the catalytic base. An important feature of the TIM active site is the concerted closure of loop-6 and loop-7 on ligand binding, shielding the catalytic site from bulk solvent. The buried active site stabilises the enediolate intermediate. The catalytic residue Glu167 is at the beginning of loop-6. On closure of loop-6, the Glu167 carboxylate moiety moves approximately 2 Å to the substrate. The dynamic properties of the Glu167 side chain in the enzyme substrate complex are a key feature of the proton shuttling mechanism. Two proton shuttling mechanisms, the classical and the criss-cross mechanism, are responsible for the interconversion of the substrates of this enolising enzyme.     

Instruments of Music,Instruments of Science: Hermann von Helmholtz's Musical Practices,his Classicism,and his Beethoven Sonata

The young Hermann Helmholtz, in an 1838 letter home, declared that he always appreciated music much more when he played it for himself. Though a frequent concert-goer, and celebrated for his highly influential 1863 work on the physiological basis of music theory, Die Lehre von den Tonempfindungen, it is likely that Helmholtz's enduring engagement with music began with his initial, personal experience of playing music for himself. I develop this idea, shifting the discussion of Helmholtz's work on sound sensation back to its origins, and examine the role of his material interaction with musical instruments and music itself. In his sound sensation studies, Helmholtz understood sound as an external, physical object. But Helmholtz also conceived of sound in musical terms. Further, Helmholtz's particular musical tastes as well as his deeply personal interaction with musical instruments allowed him to reconcile his conception of sound as physical object with his conception of sound as music. Helmholtz's physiological theory of sound sensation was both the product of and constitutive of how he heard and created sound. I argue that Helmholtz himself was the embodied reconciliation of his physiological theory of sound sensation and his belief that musical aesthetics were historically and culturally contingent.     

Book Review: Current Perspectives in the History of Science in East Asia,edited by Y. S. Kim and F. Bray

In 1670, the Bolognese mathematician Pietro Mengoli published his Speculationi di musica, a highly original work attempting to found the mathematical study of music on the anatomy of the ear. His anatomy was idiosyncratic and his mathematics extraordinarily complex, and he proposed a unique double mechanism of hearing. He analysed in detail the supposed behaviour of the subtle part of the air inside the ear, and the patterns of strokes made on the eardrum by simultaneous sounds. Most strikingly, he divided the musical octave into a continuous set of regions which he colour-coded to show their effects on a listener. His work did not find its way into the mainstream of seventeenth-century mathematical studies of music, but when examined in its context it has the potential to shed light on that discipline, as well as being of considerable interest in its own right. Here, I focus on the anatomical and mathematical basis of Mengoli's work.     

Chemistry and meteorology, 1700–1825

In 1639–1640 Benedetto Castelli (1577–1643) wrote a treatise on the loadstone which is quite unlike any of its contemporaries. In it are the origins of the notion of elementary magnets sharing a common alignment, the idea that all materials are magnetic in different ways, and the first intimation of the conception of magnetic domains. Castelli did not publish his treatise. Nevertheless his work was noted during his life-time, and may have exerted an influence on the development of magnetic theory in the 17th century. The treatise was published in 1883. Since then, however, it has either been neglected or not appreciated. It deserves being rescued from the neglect of more than three centuries.