Measured proton electromagnetic structure deviates from theoretical predictions.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities1 that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities2 map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades2. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.

Unique Access to u-Channel Physics: Exclusive Backward-Angle Omega Meson Electroproduction.

Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e^{'}pω, at central Q^{2} values of 1.60, 2.45 GeV^{2}, at W=2.21 GeV. The results of our pioneering -u≈-u_{min} study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q^{2}=2.45 GeV^{2}, the observed dominance of σ_{T} over σ_{L}, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.

NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1(S340A/S340A)mice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.

Combined effects of malathion and nitrate on early growth, abnormalities, and mortality of wood frog (Rana sylvatica) tadpoles.

Use of pesticides and other agro-chemicals adversely influence amphibians either directly by killing them or by inducing sublethal, chronic effects. Many studies have investigated the effect of mixtures of pesticides or fertilizers. We studied the combined effects of nitrate and malathion ([(dimethoxy phosphino thioyl] butanediotae) on the early growth, expression of abnormalities, and mortality of Wood Frog (Rana sylvatica) tadpoles in a laboratory experiment. Tadpoles were treated with factorial combinations of 0, 8, and 16 mg NO(3)-N l(-1) and 0, 250, 500, and 1,000 µg malathion l(-1) for a period of 14 days. Feeding behaviour, total length, mean tadpole mass, frequencies of abnormalities, and survivorship in each treatment were recorded. Malathion showed a significant negative influence on all parameters and strongly influenced the frequencies of morphological anomalies. In contrast, nitrate alone did not produce any significant effects on behavior, total length, tadpole mass, or the frequency of abnormalities during the experiment. Malathion and nitrate had an interactive effect on tadpole length and mass, but did not affect any other parameters. Our results suggest that exposure to malathion, even at relatively low concentrations can have serious negative consequences for Wood Frog tadpoles. In addition, our results also indicate that there was little synergistic interaction between malathion and nitrate exposure under laboratory conditions.

Body mass and temperature influence rates of mitochondrial DNA evolution in North American cyprinid fish.

The mass-specific metabolic rate hypothesis of Gillooly and others predicts that DNA mutation and substitution rates are a function of body mass and temperature. We tested this hypothesis with sequence divergences estimated from mtDNA cytochrome b sequences of 54 taxa of cyprinid fish. Branch lengths estimated from a likelihood tree were compared with metabolic rates calculated from body mass and environmental temperatures experienced by those taxa. The problem of unknown age estimates of lineage splitting was avoided by comparing estimated amounts of metabolic activity along phyletic lines leading to pairs of modern taxa from their most recent common ancestor with sequence divergences along those same pairs of phyletic lines. There were significantly more pairs for which the phyletic line with greater genetic change also had the higher metabolic activity, when compared to the prediction of a hypothesis that body mass and temperature are not related to substitution rate.

Determination of the pion charge form factor at Q2=1.60 and 2.45 (GeV/c)2.

The 1H(e,e'pi+)n cross section was measured at four-momentum transfers of Q2=1.60 and 2.45 GeV2 at an invariant mass of the photon nucleon system of W=2.22 GeV. The charged pion form factor (F(pi)) was extracted from the data by comparing the separated longitudinal pion electroproduction cross section to a Regge model prediction in which F(pi) is a free parameter. The results indicate that the pion form factor deviates from the charge-radius constrained monopole form at these values of Q2 by one sigma, but is still far from its perturbative quantum chromodynamics prediction.

Yellow leaf of sugarcane is caused by at least three different genotypes of sugarcane yellow leaf virus, one of which predominates on the Island of Réunion.

The genetic diversity of sugarcane yellow leaf virus (SCYLV) was analyzed with 43 virus isolates from Réunion Island and 17 isolates from world-wide locations. We attempted to amplify by reverse-transcription polymerase chain reaction (RT-PCR), clone, and sequence four different fragments covering 72% of the genome of these virus isolates. The number of amplified isolates and useful sequence information varied according to each fragment, whereas an amplicon was obtained with diagnostic primers for 59 out of 60 isolates (98%). Phylogenetic analyses of the sequences determined here and additional sequences of 11 other SCYLV isolates available from GenBank showed that SCYLV isolates were distributed in different phylogenetic groups or belonged to single genotypes. The majority of isolates from Réunion Island were grouped in phylogenetic clusters that did not contain any isolates from other origins. The complete six ORFs (5612 bp) of five SCYLV isolates (two from Réunion Island, one from Brazil, one from China, and one from Peru) were amplified, cloned, and sequenced. The existence of at least three distinct genotypes of SCYLV was shown by phylogenetic analysis of the sequences of these isolates and additional published sequences of three SCYLV isolates (GenBank accessions). The biological significance of these genotypes and of the origin of the distinct lineage of SCYLV in Réunion Island remains to be determined.

Effects of nitrate on the tadpoles of two Ranids (Rana catesbeiana and R. clamitans).

Nitrate is a potential stressor of amphibian larvae. Previous research has shown variation in the effects of nitrate among species and even populations of amphibians. However, relatively few species and populations of amphibians have been examined for nitrate tolerance, especially from populations in the agricultural regions of the United States. Using a 15-day laboratory experiment, we investigated the effects of nitrate on the larvae of two species of anurans (Rana catesbeiana and R. clamitans) that are common throughout the agricultural Midwest. Survival of R. catesbeiana and R. clamitans tadpoles was negatively affected by higher concentrations of nitrate (20 mg L(-1)), with R. clamitans being more affected than R. catesbeiana. The final mass of R. catesbeiana tadpoles was affected by nitrate concentration, with tadpoles exposed to intermediate concentrations of nitrate (5 mg L(-1)) being the heaviest. The final mass of R. clamitans tadpoles was not affected by nitrate concentration. These experiments suggest that these two species differ in their responses to the toxic effects of nitrate and, along with previous results on Ranids, suggest there is a great deal of variation in nitrate tolerance in this family.

Etanercept treatment of renal amyloidosis complicating rheumatoid arthritis.

Rheumatoid arthritis and juvenile arthritis represent the commonest diseases complicated by AA amyloidosis in developed countries. Up to 5% of patients with rheumatoid arthritis will develop AA amyloidosis, with renal failure being the commonest cause of mortality. To date, treatment of this condition has focused on suppressing the underlying inflammatory condition with drugs such as cyclophosphamide and chlorambucil, but both these drugs are associated with myelotoxicity, leukaemia and sterility. Tumour necrosis factor-alpha (TNF-alpha) is thought to be involved in amyloid deposition. The efficacy of anti-TNF-alpha therapy (etanercept) in the treatment of renal amyloidosis complicating rheumatoid arthritis is demonstrated here and the current scientific data on this subject are presented.

A variable region of the sugarcane bacilliform virus (SCBV) genome can be used to generate promoters for transgene expression in sugarcane.

Four promoters derived from sugarcane bacilliform virus (SCBV) were compared and characterised. Three were obtained by PCR amplification of purified virion DNA extracted from three sugarcane cultivars. The fourth promoter was obtained by subcloning from an almost genome-length clone of SCBV. All promoters were able to drive stable expression of beta-glucuronidase in sugarcane. The PCR-derived promoter sequences shared more DNA homology with banana streak virus than to the subcloned SCBV. The subcloned promoter was the strongest expressing and was able to drive reporter gene expression in vitro and in the leaves, meristems and roots of glasshouse-grown sugarcane. Expression levels were at least equal to or higher than those measured for the maize polyubiquitin promoter.

Homologues of the maize rust resistance gene Rp1-D are genetically associated with a major rust resistance QTL in sorghum.

As part of a comparative mapping study between sugarcane and sorghum, a sugarcane cDNA clone with homology to the maize Rp1-D rust resistance gene was mapped in sorghum. The cDNA probe hybridised to multiple loci, including one on sorghum linkage group (LG) E in a region where a major rust resistance QTL had been previously mapped. Partial sorghum Rp1-D homologues were isolated from genomic DNA of rust-resistant and -susceptible progeny selected from a sorghum mapping population. Sequencing of the Rp1-D homologues revealed five discrete sequence classes: three from resistant progeny and two from susceptible progeny. PCR primers specific to each sequence class were used to amplify products from the progeny and confirmed that the five sequence classes mapped to the same locus on LG E. Cluster analysis of these sorghum sequences and available sugarcane, maize and sorghum Rp1-D homologue sequences showed that the maize Rp1-D sequence and the partial sugarcane Rp1-D homologue were clustered with one of the sorghum resistant progeny sequence classes, while previously published sorghum Rp1-D homologue sequences clustered with the susceptible progeny sequence classes. Full-length sequence information was obtained for one member of a resistant progeny sequence class ( Rp1-SO) and compared with the maize Rp1-D sequence and a previously identified sorghum Rp1 homologue ( Rph1-2). There was considerable similarity between the two sorghum sequences and less similarity between the sorghum and maize sequences. These results suggest a conservation of function and gene sequence homology at the Rp1 loci of maize and sorghum and provide a basis for convenient PCR-based screening tools for putative rust resistance alleles in sorghum.

Molecular analysis of Fiji disease virus genome segments 5, 6, 8 and 10.

The complete sequences of Fiji disease virus (FDV) genome segments 5 (S5), S6, S8 and S10 were obtained and comprised 3150 nt, 2831 nt, 1959 nt and 1819 nt, respectively. Each segment contained a single ORF which encoded putative proteins of 115 kDa, 97 kDa, 69 kDa and 63.0 kDa, respectively. The putative amino acid sequences encoded by S5 and S6 contained putative leucine zipper motifs while FDV S5 and S8 each contained an ATP-GTP-binding motif. At the amino acid level, FDV S5, S6, S8 and S10 showed most similarity to the corresponding segments of Rice black-streaked dwarf virus. Based on sequence similarities, it is predicted that FDV S8 encodes a minor core protein, while FDV S10 encodes an outer capsid protein. The evolutionary relationships of FDV to other reoviruses are discussed.

Sugarcane bacilliform virus encapsidates genome concatamers and does not appear to integrate into the Saccharum officinarum genome.

Sugarcane bacilliform virus (SCBV) DNA molecules larger than the complete genome length of 7.6 kbp were detected in infected plants and in virions. We have confirmed that these high molecular weight nucleic acids were open circular DNA and viral in origin. Due to their open circular conformation, accurate size determination of the DNA molecules was not possible using conventional electrophoresis. Using field inversion gel electrophoresis (FIGE), however, the DNA appeared to increase in genome size increments, with sizes ranging from 1 to 4 genomes (31 kbp) detected. The DNA was packaged into virions, which may explain the observation of purified virions with lengths corresponding to one, two or three times the modal length of 130 nm. The DNA products were possibly concatamers formed during replication as a result of a terminal overlap on the sense strand, and were shown to be overlapped individual genome-length molecules and not covalently-bonded continuous DNA strands. Southern analysis indicated that SCBV sequences are not integrated into the sugarcane genome and that the high molecular weight DNA observed in the sugarcane accessions analysed represents SCBV concatamers.

Sequence analysis of an Australian isolate of sugarcane bacilliform badnavirus.

The genome of an Australian isolate of Sugarcane bacilliform virus (SCBV-IM) was cloned, sequenced and analysed. The genome consisted of 7687 nucleotides and contained three open reading frames which were similar in size and organisation to those of other badnaviruses. SCBV-IM was found to be most similar to the SCBV-Morocco isolate with amino acid sequence similarity of 91.4 %, 83.8 % and 85.3 % in the ORF I, II and III coding regions, respectively. Phylogenetic analysis of the SCBV-IM ORF III deduced amino acid sequence showed that SCBV isolates were more closely related to each other than to other badnaviruses. Amplification of SCBV sequences from three different sugarcane varieties revealed considerable variability in the viral populations, both within single infected plants as well as between infected plants, suggesting that the SCBV isolates sequenced to date may not be representative of the range of virus variability.

Homologous recombination near and far from DNA breaks: alternative roles and contrasting views.

Double-strand breaks and other lesions in DNA can stimulate homologous genetic recombination in two quite different ways: by promoting recombination near the break (roughly within a kb) or far from the break. Recent emphasis on the repair aspect of recombination has focused attention on DNA interactions and recombination near breaks. Here I review evidence for recombination far from DNA breaks in bacteria and fungi and discuss mechanisms by which this can occur. These mechanisms include entry of a traveling entity ("recombination machine") at a break, formation of long heteroduplex DNA, priming of DNA replication by a broken end, and induction of recombination potential in trans. Special emphasis is placed on contrasting views of how the RecBCD enzyme of Escherichia coli promotes recombination far (tens of kb) from a double-strand break. The occurrence of recombination far from DNA breaks and of correlated recombination events far apart suggests that "action at a distance" during recombination is a widespread feature among diverse organisms.

Electrostatics studies and molecular dynamics simulations of a homology model of the Shaker K+ channel pore.

A homology model of the pore domain of the Shaker K+ channel has been constructed using a bacterial K+ channel, KcsA, as a template structure. The model is in agreement with mutagenesis and sequence variability data. A number of structural features are conserved between the two channels, including a ring of tryptophan sidechains on the outer surface of the pore domain at the extracellular end of the helix bundle, and rings of acidic sidechains close to the extracellular mouth of the channel. One of these rings, that formed by four Asp447 sidechains at the mouth of the Shaker pore, is shown by pK(A) calculations to be incompletely ionized at neutral pH. The potential energy profile for a K+ ion moved along the central axis of the Shaker pore domain model selectivity filter reveals a shallow well, the depth of which is modulated by the ionization state of the Asp447 ring. This is more consistent with the high cation flux exhibited by the channel in its conductance value of 19 pS.

Comparing outcomes of routine care for depression: the dilemma of case-mix adjustment.

The purpose of this study was to formulate and test two case-mix models for depression treatment that permit comparisons of patient outcomes across diverse clinical settings. It assessed demographics; eight, diagnostic-specific, case-mix variables; and clinical status at baseline and follow-up for 187 patients. Regressions were performed to test two models for four dependent variables including depression severity and diagnosis. Individual treatment settings were then ranked based on a comparison of actual versus predicted outcomes using regression coefficients and predictor variables. A model inclusive of baseline physical health status and depression severity predicted depression severity, mental health, and physical health functioning at follow-up. A simpler model performed well in predicting depression remission. This study identifies variables to be included in case-mix adjustment models and demonstrates statistical methods to control for differences across settings when comparing depression outcomes.

Meiotic recombination and chromosome segregation in Schizosaccharomyces pombe.

In most organisms homologous recombination is vital for the proper segregation of chromosomes during meiosis, the formation of haploid sex cells from diploid precursors. This review compares meiotic recombination and chromosome segregation in the fission yeast Schizosaccharomyces pombe and the distantly related budding yeast Saccharomyces cerevisiae, two especially tractable microorganisms. Certain features, such as the occurrence of DNA breaks associated with recombination, appear similar, suggesting that these features may be common in eukaryotes. Other features, such as the role of these breaks and the ability of chromosomes to segregate faithfully in the absence of recombination, appear different, suggesting multiple solutions to the problems faced in meiosis.