Preoperative evaluation of pleural adhesions with dynamic chest radiography: a retrospective study of 146 patients with lung cancer.

AIM: To assess the utility of dynamic chest radiography (DCR) during the preoperative evaluation of pleural adhesions. MATERIALS AND METHODS: Sequential chest radiographs of 146 patients with lung cancer were acquired during forced respiration using a DCR system. The presence of pleural adhesions and their grades were determined by retrospective surgery video assessment (absent: 121, present: 25). The maximum inspiration to expiration lung area ratio was used as an index for air intake volume. A ratio of ≥0.65 was regarded as insufficient respiration. Two radiologists assessed the images for pleural adhesions based on motion findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared for each adhesion grade and patient group (patients with sufficient/insufficient respiration). Pearson's chi-squared test compared the group. Statistical significance was set at p<0.05. RESULTS: DCR correctly identified 22/25 patients with pleural adhesions, with 20 false-positive results (sensitivity, 88%; specificity, 83.5%; PPV, 52.4%; NPV, 97.12%). Although the diagnostic performances for the various adhesion grades were similar, specificity in patients with sufficient respiration increased to 93.9% (31/33), identifying all cases except for those with loose adhesions. CONCLUSIONS: DCR images revealed restricted and/or distorted motions in lung structures and structural tension in patients with pleural adhesions. DCR could be a useful technique for routine preoperative evaluation of pleural adhesions. Further development of computerised methods can assist in the quantitative assessment of abnormal motion findings.

Control of parental investment changes plastically over time with residual reproductive value.

Evolutionary conflict between parents and offspring over parental resource investment is a significant selective force on the traits of both parents and offspring. Empirical studies have shown that for some species, the amount of parental investment is controlled by the parents, whereas in other species, it is controlled by the offspring. The main difference between these two strategies is the residual reproductive value of the parents or opportunities for future reproduction. Therefore, this could explain the patterns of control of parental investment at the species level. However, the residual reproductive value of the parents will change during their lifetime; therefore, parental influence on the amount of investment can be expected to change plastically. Here, we investigated control of parental investment when parents were young and had a high residual reproductive value, compared to when they were old and had a low residual reproductive value using a cross-fostering experiment in the burying beetle Nicrophorus quadripunctatus. We found that parents exert greater control over parental investment when they are young, but parental control is weakened as the parents age. Our results demonstrate that control of parental investment is not fixed, but changes plastically during the parent's lifetime.

Contemporary evolution of host plant range expansion in an introduced herbivorous beetle Ophraella communa.

Host range expansion of herbivorous insects is a key event in ecological speciation and insect pest management. However, the mechanistic processes are relatively unknown because it is difficult to observe the ongoing host range expansion in natural population. In this study, we focused on the ongoing host range expansion in introduced populations of the ragweed leaf beetle, Ophraella communa, to estimate the evolutionary process of host plant range expansion of a herbivorous insect. In the native range of North America, O. communa does not utilize Ambrosia trifida, as a host plant, but this plant is extensively utilized in the beetle's introduced range. Larval performance and adult preference experiments demonstrated that native O. communa beetles show better survival on host plant individuals from introduced plant populations than those from native plant populations and they also oviposit on the introduced plant, but not on the native plant. Introduced O. communa beetles showed significantly higher performance on and preference for both introduced and native A. trifida plants, when compared with native O. communa. These results indicate the contemporary evolution of host plant range expansion of introduced O. communa and suggest that the evolutionary change of both the host plant and the herbivorous insect involved in the host range expansion.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Spin and orbital contributions to magnetically ordered moments in 5d layered perovskite Sr2IrO4.

The ratio of orbital (L) and spin (S) contributions to the magnetically ordered moments of a 5d transition metal oxide, Sr2IrO4 was evaluated by nonresonant magnetic x-ray diffraction. We applied an improved experimental setting that minimized the experimental error, in which we varied only the linear polarization of incident x ray at a fixed scattering angle. Strong polarization dependence of the intensity of magnetic diffraction was observed, from which we conclude that the ordered moments contain substantial contribution from the orbital degree of freedom with the ratio of /∼5.0, evidencing the pronounced effect of spin-orbit coupling. The obtained ratio is close to, but slightly larger than the expected value for the ideal J(eff) = 1/2 moment of a spin-orbital Mott insulator, ||/|| = 4, which cannot be accounted for by the redistribution of orbital components within the t(2g) bands associated with the elongation of the IrO6 octahedra.

Asynchronous hatching in the burying beetle, Nicrophorus quadripunctatus, maxmizes parental fitness.

Life history theory predicts that natural selection favours parents who balance investment across offspring to maximize fitness. Theoretical studies have shown that the optimal level of parental investment from the offspring's perspective exceeds that of its parents, and the disparity between the two generates evolutionary conflict for the allocation of parental investment. In various species, the offspring hatch asynchronously. The age hierarchy of the offspring usually establishes competitive asymmetries within the brood and determines the allocation of parental investment among offspring. However, it is not clear whether the allocation of parental investment determined by hatching pattern is optimal for parent or offspring. Here, we manipulated the hatching pattern of the burying beetle Nicrophorus quadripunctatus to demonstrate the influence of hatching pattern on the allocation of parental investment. We found that the total weight of a brood was largest in the group that mimicked the natural hatching pattern, with the offspring skewed towards early hatchers. This increases parental fitness. However, hatching patterns with more later hatchers had heavier individual offspring weights, which increases offspring fitness, but this hatching pattern is not observed in the wild. Thus, our study suggests that the natural hatching pattern optimizes parental fitness, rather than offspring fitness.

Electronic phase transition and an anomalous ordered phase in Ba2Ti13O22 with 3d1 ions on a triangle-based lattice.

We found that Ba(2)Ti(13)O(22) with Ti(3+) (3d(1)) ions on a triangle-based lattice exhibits a phase transition at T(c)~200 K, below which the increase of electrical resistivity and decrease of magnetic susceptibility were observed. Transmission electron microscopy and optical reflectivity measurements indicate that the low-temperature phase of the present compound shares characteristics in common with a charge-density-wave state with remnant carriers, although a commensurate wave vector of the modulation and a linear temperature dependence of the magnetic susceptibility below T(c) suggest an exotic ordered state.

A-type antiferro-orbital ordering with I4(1)/a symmetry and geometrical frustration in the spinel vanadate MgV2O4.

We conduct a detailed structural analysis of the S=1 pyrochlore antiferromagnet MgV2O4, which exhibits an antiferromagnetic ordering marginally at TN=40 K, triggered by a structural transition from cubic to tetragonal symmetry at TS=62 K, using high resolution synchrotron x-ray diffraction and convergent beam electron diffraction. We reveal that the tetragonal phase below TS has the symmetry of I4(1)/a and that the distortion pattern of VO6 octahedra is consistent with A-type antiferro-orbital ordering with alternating stacking of layers with yz/xy orbital chains and zx/xy orbital chains along the tetragonal c axis. This implies that an anisotropic coupling of V moments produced by the orbital ordering below TS primarily brings about the antiferromagnetic ordering.

Inflammatory mechanisms of ventilator-induced lung injury: a time to stop and think?

Ventilator-induced lung injury (VILI) is the phenomenon by which mechanical ventilation exacerbates lung injury in critically ill patients. It is particularly relevant for those suffering from acute respiratory distress syndrome, in which the iatrogenic injury caused by VILI contributes to their high mortality. The innate immune system is widely accepted to play an important role during VILI. However, it is our belief that the identification of inflammatory mediators that are crucial during VILI, and thus may make useful therapeutic targets, has become obscured by the wide variety of pre-clinical animal models of VILI reported in the literature. We aim here to summarise some of our work addressing this issue over the last 10 years, and thus, we hope, make interpretation of a convoluted field a little clearer.

Mutation analysis of BRAF and KIT in circulating melanoma cells at the single cell level.

BACKGROUND: The availability of molecular-targeted therapies for the treatment of melanoma has emphasised the need to identify mutations in target genes such as BRAF and KIT. Circulating tumour cells (CTC) are present in the peripheral blood of a significant proportion of cancer patients. METHODS: High molecular weight melanoma-associated antigen (HMW-MAA) was used to isolate melanoma cells from peripheral blood as it is selectively expressed at high levels on melanomas. The HMW-MAA-positive cells were isolated using immunomagnetic beads. After removing CD45(+) cells, CTC were identified by staining with MART-1- and gp100-specific antibodies (HMW-MAA(+), CD45(-), MART-1/gp100(+)). Single, isolated CTC were then subjected to BRAF and KIT mutational analysis. RESULTS: CTC (HMW-MAA(+), CD45(-), MART-1/gp100(+)) were isolated from the blood of 11 patients and BRAF and KIT were sequenced in nine and four patients, respectively. The BRAF sequences identified in the CTC were inconsistent with those identified in autologous melanoma tumours in three patients and the KIT sequences were inconsistent in three patients. In addition, polyclonal BRAF mutations were identified in one patient and concomitant mutations in BRAF and KIT were identified in another patient. CONCLUSION: Melanoma cells show clonal heterogeneity. Therefore, CTC genotyping may be crucial for successful molecular-targeted therapy.

Two-dimensional Heisenberg behavior of J(eff)=1/2 isospins in the paramagnetic state of the spin-orbital Mott insulator Sr2IrO4.

The dynamical correlations of J(eff)=1/2 isospins in the paramagnetic state of spin-orbital Mott insulator Sr2IrO4 were revealed by resonant magnetic x-ray diffuse scattering. We found a two-dimensional antiferromagnetic fluctuation with a large in-plane correlation length exceeding 100 lattice spacings at even 20 K above the magnetic ordering temperature. In marked contrast to the naive expectation of the strong magnetic anisotropy associated with an enhanced spin-orbit coupling, we discovered an isotropic isospin correlation that is well described by the two-dimensional S=1/2 quantum Heisenberg model. The estimated antiferromagnetic coupling constant as large as J∼0.1 eV that is comparable to the small Mott gap (<0.5 eV) points out the weak and marginal Mott character of this spin-orbital entangled system.

Tetrahedral magnetic order and the metal-insulator transition in the pyrochlore lattice of Cd2Os2O7.

Cd2Os2O7 shows a peculiar metal-insulator transition at 227 K with magnetic ordering in a frustrated pyrochlore lattice, but its magnetic structure in the ordered state and the transition origin are yet uncovered. We observed a commensurate magnetic peak by resonant x-ray scattering in a high-quality single crystal. X-ray diffraction and Raman scattering experiments confirmed that the transition is not accompanied with any spatial symmetry breaking. We propose a noncollinear all-in-all-out spin arrangement on the tetrahedral network made of Os atoms. Based on this we suggest that the transition is not caused by the Slater mechanism as believed earlier but by an alternative mechanism related to the formation of the specific tetrahedral magnetic order on the pyrochlore lattice in the presence of strong spin-orbit interactions.

Hyperacute graft-versus-host disease: histological assessment of skin biopsy specimens from 19 cases.

BACKGROUND: Hyperacute graft-versus-host disease (GVHD) is defined as GVHD occurring within 14 days after haematopoietic stem-cell transplantation (HSCT). AIM: To evaluate the usefulness of skin biopsy in assessing hyperacute GVHD. METHODS: We examined 19 cases of hyperacute GVHD from a total of 134 consecutive HSCT cases at Shinshu University Hospital between 1999 and 2008. RESULTS: Exanthemas were seen in all patients, which were mainly disseminated maculopapular erythemas, commonly present in acute GVHD as well. Most patients presented with a high fever, and a few had mild hepatic dysfunction and/or diarrhoea. The clinical grade of GVHD was 1-2 in all patients; there were no cases of clinical grades 3-4. The histological findings of skin biopsy were divided into three groups: (i) eight had grade 2 changes, characterized by diffuse vacuolization of basal cells, with dyskeratotic bodies; (ii) five had grade 1 changes, characterized by vacuolization of epidermal basal cells (all these cases were diagnosed as acute GVHD with grade 2 histological changes at subsequent biopsy); (iii) and six had no significant changes (these cases were also diagnosed as acute GVHD with grade 2 (four cases) or grade 1 (one case) histological changes on the second biopsy). Many of the patients developed acute and later chronic GVHD. CONCLUSION: Skin biopsy should be considered when eruption develops after HSCT even before engraftment, especially when other organ involvement is minimal. If the first skin biopsy is inconclusive, follow-up biopsy within a short time is helpful in the diagnosis of hyperacute GVHD.

Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression.

BACKGROUND: Oncogenic BRAF mutation had been considered to be a founder event in the formation of melanocytic tumours; however, we recently argued against this notion by showing marked polyclonality of BRAF mutations in acquired melanocytic nevi (Lin et al, J Natl Cancer Inst., 2009; 101:1423-7). Here, we tested whether similar heterogeneity of BRAF mutations exists in primary melanomas. METHODS: We isolated and sequenced single melanoma cells from five primary melanoma tissues using antibodies against human high-molecular-weight melanoma-associated antigen. We also examined 10 primary melanomas by the sensitive Mutector assay detecting the BRAF(V600E) mutation, as well as by cloning and sequencing of separated alleles. Furthermore, we estimated the frequency of BRAF mutant alleles in paired samples of primary tumour and recurrence or metastasis in three patients. RESULTS: Single-cell mutation analyses revealed that four of five primary melanomas contained both BRAF-wild-type and BRAF-mutant tumour cells. Tumour heterogeneity in terms of BRAF mutations was also shown in 8 of 10 primary melanomas. Selection of BRAF mutant alleles during progression was demonstrated in all the three patients. CONCLUSION: Acquisition of a BRAF mutation is not a founder event, but may be one of the multiple clonal events in melanoma development, which is selected for during the progression.

A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2.

Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions.

Requirement of phospholipase C-gamma 2 activation in surface immunoglobulin M-induced B cell apoptosis.

Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of sIgM on PLC-gamma 2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-gamma 2- or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-gamma 2 were essential for both its activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC-gamma 2 is mediated by Syk, these results indicate that activation of PLC-gamma 2 through Syk is required for sIgM-induced apoptosis.

Physical and functional association of the cbl protooncogen product with an src-family protein tyrosine kinase, p53/56lyn, in the B cell antigen receptor-mediated signaling.

To identify novel signal transducers involved in signaling mediated by the Src-family protein tyrosine kinases (PTKs), we used a yeast two-hybrid system with a probe corresponding to the regulatory region of p56lyn, a member of Src-family PTKs. One of the isolated clones contained the COOH-terminal 470 amino acid residues of p120c-cbl, the product of the cellular homologue of the v-cbl retroviral oncogene. p120c-cbl is a cytoplasmic protein with nuclear protein-like motifs. Here we show in vivo association of p120c-cbl with p53/56lyn. After stimulation of the B cell antigen receptor (BCR), p120c-cbl was rapidly tyrosine phosphorylated. Studies with lyn- or syk-negative chicken B cells demonstrated that p53/56lyn, but not p72syk, was crucial for tyrosine phosphorylation of p120c-cbl upon stimulation of the BCR. We also show the importance of p59fyn in tyrosine phosphorylation of p120c-cbl in the T-cell receptor-mediated signaling using fyn-overexpressing T cell hybridomas and splenic T cells from fyn-deficient mice. These results suggest that p120c-cbl is an important substrate of Src-family PTKs in the intracellular signaling mediated by the antigen receptors

Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling.

Signaling through the B cell antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Src-protein-tyrosine kinase [PTK]; Lyn, Fyn, Blk, or Lck) and Syk kinase. We have investigated the interaction between the Src-PTK and the Syk kinase in the BCR signaling. In contrast to wild-type B cells, BCR-mediated tyrosine phosphorylation of Syk and activation of its in vitro kinase activity were profoundly reduced in lyn-negative cells. The requirement of the Src-PTK to induce tyrosine phosphorylation and activation of Syk was also demonstrated by cotransfection of syk and src-PTK cDNAs into COS cells. These results suggest that the Src-PTK associated with BCR phosphorylates the tyrosine residue(s) of Syk upon receptor stimulation, enhancing the activity of Syk.

Formation of a three-dimensional network of V trimers in A2V13O22 (A=Ba, Sr).

We found that in A2V13O22 (A=Ba, Sr), which contains a trilayer slab of VO in the sodium-chloride structure with periodically missing ions, the trimerization of V ions occurs at 290 K (A=Ba) and 380 K (A=Sr). V trimers form a three-dimensional network, but some V ions remain untrimerized in these compounds. The suppression of magnetic susceptibility with trimerization and the existence of a Curie tail at low temperatures, together with the result of NMR measurement, indicate that the V trimers are spin singlet, whereas the untrimerized V ions have a magnetic moment; i.e., there is a spontaneous separation between nonmagnetic and magnetic ions in the crystal.