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The authors discuss the method developed for generating targeting constructs, the first step in generating knockout mice. They report that this method capitalizes homologous recombination between linear DNA fragments and circular plasmids in Escherichia coli, the accessibility of the mouse genome sequence, and the availability of bacterial artificial chromosomes.

Basic dykes crosscutting the crystalline basement in Valsugana (Southern Alps, Italy) have been investigated for the first time in the framework of the known tectonomagmatic cycles. Petrographic observations and bulk rock analyses suggest a serial affinity variable between calc‐alkaline (subordinate) and shoshonitic (prevalent), which are generally ascribed to a convergent plate setting. This is confirmed by Sr‐Nd‐Pb isotopic analyses that display extreme values that are often observed in postcollisional settings. A bulk rock Rb‐Sr pseudoisochron suggests an age of the magmatism around 260 Ma, whereas K‐Ar datings yield ages between 227 and 251 Ma, suggesting that these dykes plausibly represent a transition between the Permian and the Triassic volcanic episodes that are known in neighboring sectors of the Southern Alps. Considering that Permo‐Triassic active subduction beneath the South Alpine is scarcely constrained, we ascribe the metasomatism of the related mantle sources to the Variscan cycle, proposing that magma genesis was delayed with respect to the time of the active subduction(s). According to recent reconstructions, parts of southeastern Europe, including the South Alpine domain, were formed by the breakup of the northern Gondwana margin from the Late Cambrian, in connection with important transtensional movements, leaving rifted continental basins or narrow oceanic seaways. In our view, the subduction processes that induced metasomatism in mantle sources of the South Alpine region occurred in the connection with the subsequent (Carboniferous?) consumption of lithosphere of these basins, a framework that is compatible with pervasive recycling of continental crust components within the mantle wedge. Then, calc‐alkaline/shoshonite magmatism was triggered in the Early Triassic by postcollisional extensional tectonics that followed the Variscan orogenic cycle. The studied basic dykes in the South Alpine reveal Early Triassic age and subduction‐related affinityPrevalent shoshonitic affinity and Sr‐Nd‐Pb isotopic data suggest significant recycling of crustal components in their mantle sourcesMagma genesis plausibly occurred in postcollisional setting, following Variscan subduction(s) and continental collision(s)

•Tonoshiki formation occurs in the Permian Maizuru Terrane, SW Japan.•This breccia-dominated unit reveals two pulses of subaqueous slope failure.•U-Pb detrital zircon age implies that slope failures occurred at the P-T boundary.•These also reveal a switch in provenance during Maizuru back-arc basin closure.•The tectonic model constraints this basin evolution at the East Asian margin.

Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents.Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis.The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06–4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19–8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47–11.80, P.007) were significant risk factors after discharge.Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice.

This study evaluated multiple factors that may contribute to an increased risk of childhood diarrhea in eastern Indonesia. Mothers with at least one child under the age of 5 years (n = 303) were interviewed face-to-face in two sub-districts of a large city in eastern Indonesia. Results showed that children were 4.72 times more likely to develop diarrhea if mothers washed their hands without soap after defecation (95% confidence interval (CI) 1.22–18.3; p = 0.03), 3.83 times more likely if households had no access to improved sources of drinking water (95% CI 1.12–13.1; p = 0.03), and 3.21 times more likely if households had income levels below $152/month (95% CI 1.40–7.35; p < 0.01). Although lower household income did not influence accessibility to improved drinking water sources, lower income households more likely lacked a refrigerator (odds ratio (OR) = 8.96; 95% CI 4.87–16.5; p < 0.01) and were also associated with mothers who had no primary education (OR = 5.44; 95% CI 1.71–17.3; p < 0.01). Mothers without primary education tended to think childhood diarrhea was not life threatening (OR = 10.8; 95% CI 3.45–33.6; p < 0.01), and mothers with such a perception were more likely wash their hands without soap after defecation (OR = 9.31; 95% CI 2.80–31.0; p < 0.01). In order to protect low-income children from diarrhea, it will be necessary to apply multiple health promotion efforts at both individual and community levels. Promoting mothers’ education is a key intervention for improving childhood health.

AbstractPlummer-Vinson syndrome (PVS) is a rare entity characterized by upper esophageal webs and iron deficiency anemia. We report a case of PVS whose esophageal web was rapidly improved by iron therapy. A 77-year-old woman was admitted to our hospital with complaints of dysphagia, vomiting, shortness of breath and weight loss for 1 month. Physical examination revealed conjunctival pallor, koilonychia, angular cheilitis and smooth tongue, and laboratory findings were consistent with microcytic hypochromic anemia with iron deficiency. Gastrointestinal endoscopy and barium-swallow esophagography detected a web that prevented passage of the endoscope into the upper portion of the esophagus. The patient received oral iron therapy daily; the hemoglobin concentration rose to 8.9 g/dl and the complaints of dysphagia were dramatically improved after 2 weeks, with improvement of luminal stenosis confirmed by gastrointestinal endoscopy and barium-swallow esophagography. The PVS described in this report had a distinct clinical course, showing very rapid improvement of dysphagia and esophageal web after 2 weeks of oral iron therapy.© 2014 S. Karger AG, Basel

We analysed major and trace elements and Sr–Nd–Pb isotope ratios of Himeshima, Futagoyama and Aso volcanoes, northern Kyushu, Japan. The purpose of the study was to investigate the petrogenesis of Quaternary arc magmas of the northern Kyushu arc, Japan, through along-strike variations. The northern Kyushu arc is underlain by the Philippine Sea Plate, which is divided by the Kyushu–Palau Ridge into the Palaeogene West Philippine Basin segment (60–40 Ma) and the Miocene Shikoku Basin segment (26–15 Ma). The Sr/Y ratios of the arc lavas decrease from north to south along the volcanic front. Mixing relations in Sr–Nd–Pb isotope space suggest recycling of the subducted slab materials from the Philippine Sea Plate to the arc. The 87Sr/86Sr ratios decrease with increasing Sr/Y and SiO2, which argues against a genetic link of fractional crystallization between adakites and basaltic magmas. The observations further suggest that partial melting of the hot and young Shikoku Basin slab produces the high Sr/Y component visible in the arc magmas in the north, whereas dehydration of the older West Philippine Basin slab produces the low Sr/Y arc magmas in the south.

ABSTRACTThe human pathogens enteropathogenic Escherichia coli(EPEC) and vaccinia virus trigger actin assembly in host cells by activating the host adaptor Nck and the actin nucleation promoter neural Wiskott-Aldrich syndrome protein (N-WASP). EPEC translocates effector molecules into host cells via type III secretion, and the interaction between the translocated intimin receptor (Tir) and the bacterial membrane protein intimin stimulates Nck and N-WASP recruitment, leading to the formation of actin pedestals beneath adherent bacteria. Vaccinia virus also recruits Nck and N-WASP to generate actin tails that promote cell-to-cell spread of the virus. In addition to Nck and N-WASP, WASP-interacting protein (WIP) localizes to vaccinia virus tails, and inhibition of actin tail formation upon ectopic expression of WIP mutants led to the suggestion that WIP is required for this process. Similar studies of WIP mutants, however, did not affect the ability of EPEC to form actin pedestals, arguing against an essential role for WIP in EPEC-induced actin assembly. In this study, we demonstrate that Nck and N-WASP are normally recruited by vaccinia virus and EPEC in the absence of WIP, and neither WIP nor the WIP family members CR16 and WIRE/WICH are essential for pathogen induced actin assembly. In addition, although Nck binds EPEC Tir directly, N-WASP is required for its localization during pedestal formation. Overall, these data highlight similar pathogenic strategies shared by EPEC and vaccinia virus by demonstrating a requirement for both Nck and N-WASP, but not WIP or WIP family members in pathogen-induced actin assembly.

AbstractWe report the case of a 56-year-old woman who had a gastrointestinal stromal tumor (GIST) of the stomach. She was admitted to our hospital for epigastric pain, nausea, and severe acute anemia (hemoglobin level 4.3 g/dl). Esophagogastroduodenoscopy revealed a narrow stalk-like based, hemorrhagic and uneven protruding lesion in the lesser curvature of the gastric upper corpus. Although the tumor was less than 2 cm in diameter and was probably a benign GIST according to histology, laparoscopy-assisted local resection was needed because the patient had continuous severe anemia and epigastric pain. Histological assessment showed that the elongated spindle-like tumor cells originated from the intrinsic muscle layer, and was shown with growth to the mucosal side, cropping out to the surface in most areas of the protruding lesion. Only a small part of the tumor was within nontumoral gastric mucosa. Most of the tumor cells demonstrated immunoreactivity for KIT and CD34 in the cytoplasm but not for aSMA, S100, and desmin. Mitotic activity (0/50 high power field) and the labeling index for MIB-1 (about 1) were low. The GIST of the stomach described in this report was a rare case with a narrow stalk-like based, uneven protruding mass presenting with severe acute anemia despite small size.Copyright © 2010 S. Karger AG, Basel

Capsaicinvanilloid (transient receptor potential vanilloid 1, (TRPV1) receptor has been shown to be expressed in gastrointestinal tract and play a role as a member of sensory ion channel superfamily. The G315C polymorphism affects the TRPV1 gene and alters its protein level. We aimed to investigate the effect of TRPV1 G315C polymorphism on functional dyspepsia (FD) in a Japanese population.

Reaction between 4-(1-phenyl-1-propenyl)morpholine and N-benzylideneanilines provided N-(3-aryl-2-methyl-1-phenylallylidene)anilines in 60–65% yields, which unequivocally established the initial [2+2] cycloaddition reaction between enamines and Schiff bases.