Conduction velocity of peristaltic waves in the in vivo ureter: application of a new diameter gauge

Summary The conduction velocity of peristaltic movements of the canine ureter was measured under anaesthesia with a new type of diameter gauge using an image sensor. The peristaltic velocity was 34.1±6.2 mm/sec in 10 experiments. Noradrenaline at a low dosage of 1 g/kg i.v. reduced the resting diameter, increased the conduction velocity to 47–56 mm/sec, and approximately doubled the frequency of contraction. The application of acetylcholine also caused an increase in both frequency and conduction velocity (42–46 mm/sec). A plot of the conduction velocity against the mean period of peristaltic contraction was hyperbolic in shape.     

On the pathway of the rectosphincteric reflex

In several rat models, including those with circular and semicircular rectal aganglionosis, the rectosphincteric reflex was examined. The reflex was confirmed to be essentially an intramural one and its route is considered to run mainly in the longitudinal and partly in the oblique directions.     

On the pathway of the rectosphincteric reflex

Summary In several rat models, including those with circular and semicircular rectal aganglionosis, the rectosphincteric reflex was examined. The reflex was confirmed to be essentially an intramural one and its route is considered to run mainly in the longitudinal and partly in the oblique directions.     

Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II

Proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors are functionally divided into two groups: B-cell growth factor (BCGF), thought to be involved in B-cell proliferation; and B-cell differentiation factor (BCDF), responsible for maturation of activated B cells into immunoglobulin-secreting cells. This classification needs to be re-examined in the light of the recent cloning of complementary DNA encoding IgG1 induction factor (interleukin-4, IL-4) from the 2.19 mouse T-cell line. Recombinant IL-4 has BCGF and BCDF activities and affects B cells, T cells and mast cells (refs 7, 8; our unpublished data). Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells. Although TRF from B151K12 was classified as BCDF, purified TRF has BCGF-II activity. To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine.     

Toll-like receptor 3 promotes cross-priming to virus-infected cells

Cross-presentation of cell-associated antigens plays an important role in regulating CD8+ T cell responses to proteins that are not expressed by antigen-presenting cells (APCs). Dendritic cells are the principal cross-presenting APCs in vivo and much progress has been made in elucidating the pathways that allow dendritic cells to capture and process cellular material. However, little is known about the signals that determine whether such presentation ultimately results in a cytotoxic T cell (CTL) response (cross-priming) or in CD8+ T cell inactivation (cross-tolerance). Here we describe a mechanism that promotes cross-priming during viral infections. We show that murine CD8alpha+ dendritic cells are activated by double-stranded (ds)RNA present in virally infected cells but absent from uninfected cells. Dendritic cell activation requires phagocytosis of infected material, followed by signalling through the dsRNA receptor, toll-like receptor 3 (TLR3). Immunization with virus-infected cells or cells containing synthetic dsRNA leads to a striking increase in CTL cross-priming against cell-associated antigens, which is largely dependent on TLR3 expression by antigen-presenting cells. Thus, TLR3 may have evolved to permit cross-priming of CTLs against viruses that do not directly infect dendritic cells.     

Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity

Helicobacter pylori cagA-positive strains are associated with gastritis, ulcerations and gastric adenocarcinoma. CagA is delivered into gastric epithelial cells and, on tyrosine phosphorylation, specifically binds and activates the SHP2 oncoprotein, thereby inducing the formation of an elongated cell shape known as the 'hummingbird' phenotype. In polarized epithelial cells, CagA also disrupts the tight junction and causes loss of apical-basolateral polarity. We show here that H. pylori CagA specifically interacts with PAR1/MARK kinase, which has an essential role in epithelial cell polarity. Association of CagA inhibits PAR1 kinase activity and prevents atypical protein kinase C (aPKC)-mediated PAR1 phosphorylation, which dissociates PAR1 from the membrane, collectively causing junctional and polarity defects. Because of the multimeric nature of PAR1 (ref. 14), PAR1 also promotes CagA multimerization, which stabilizes the CagA-SHP2 interaction. Furthermore, induction of the hummingbird phenotype by CagA-activated SHP2 requires simultaneous inhibition of PAR1 kinase activity by CagA. Thus, the CagA-PAR1 interaction not only elicits the junctional and polarity defects but also promotes the morphogenetic activity of CagA. Our findings revealed that PAR1 is a key target of H. pylori CagA in the disorganization of gastric epithelial architecture underlying mucosal damage, inflammation and carcinogenesis.     

A 'checkerboard' electronic crystal state in lightly hole-doped Ca2-xNaxCuO2Cl2

The phase diagram of hole-doped copper oxides shows four different electronic phases existing at zero temperature. Familiar among these are the Mott insulator, high-transition-temperature superconductor and metallic phases. A fourth phase, of unknown identity, occurs at light doping along the zero-temperature bound of the 'pseudogap' regime. This regime is rich in peculiar electronic phenomena, prompting numerous proposals that it contains some form of hidden electronic order. Here we present low-temperature electronic structure imaging studies of a lightly hole-doped copper oxide: Ca2-xNaxCuO2Cl2. Tunnelling spectroscopy (at energies |E| > 100 meV) reveals electron extraction probabilities greatly exceeding those for injection, as anticipated for a doped Mott insulator. However, for |E| < 100 meV, the spectrum exhibits a V-shaped energy gap centred on E = 0. States within this gap undergo intense spatial modulations, with the spatial correlations of a four CuO2-unit-cell square 'checkerboard', independent of energy. Intricate atomic-scale electronic structure variations also exist within the checkerboard. These data are consistent with an unanticipated crystalline electronic state, possibly the hidden electronic order, existing in the zero-temperature pseudogap regime of Ca2-xNaxCuO2Cl2.     

High-resolution record of Northern Hemisphere climate extending into the last interglacial period

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.