Long-term culture of cholangiocytes from liver fibro-granulomatous lesions

BACKGROUND: Extensive bile duct proliferation is a key feature of the tissue reaction to clinical and experimental forms of liver injury. Experimental infection of mice by Schistosoma mansoni is a well-studied model of liver fibrosis with bile duct hyperplasia. However, the regulatory mechanisms of bile duct changes are not well understood. In this study we report the reproducible isolation of long-term cultures of cholangiocytes from mice livers with schistosomal fibrosis. METHODS: We have isolated a cholangiocyte cell line from Schistosoma-induced liver granulomas using a combination of methods including selective adhesion and isopyknic centrifugation in Percoll. RESULTS: The cell line was characterized by morphological criteria in optical and transmission electron microscopy, ability to form well differentiated ductular structures in collagen gels and by a positive staining for cytokeratin 18 and cytokeratin 19. To our knowledge, this is the first murine cholangiocyte cell line isolated from schistosomal fibrosis reported in the literature. CONCLUSION: After 9 months and 16 passages this diploid cell line maintained differentiated characteristics and a high proliferative capacity. We believe the method described here may be a valuable tool to study bile duct changes during hepatic injury

Isolation and primary cultures of human intrahepatic bile ductular epithelium

A technique for the isolation of human intrahepatic bile ductular epithelium, and the establishment of primary cultures using a serum- and growth-factor-supplemented medium combined with a connective tissue substrata is described. Initial cell isolates and monolayer cultures display phenotypic characteristics of biliary epithelial cells (low molecular weight prekeratin positive; albumin, alphafetoprotein, and Factor VIII-related antigen negative). Ultrastructural features of the cultured cells show cell polarization with surface microvilli, numerous interepithelial junctional complexes and cytoplasmic intermediate prekeratin filaments. © 1988 Tissue Culture Association, Inc

Positive selection in Europeans and East-Asians at the ABCA12 gene

Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago

Ultrafast Suppression of the Ferroelectric Instability in KTaO3_3

We use an x-ray free-electron laser to study the ultrafast lattice dynamics following above band-gap photoexcitation of the incipient ferroelectric potassium-tantalate, \kto. % We use ultrafast near-UV (central wavelength 266\,nm and 50 fs pulse duration) laser light to photoexcite charge carriers across the gap and probe the ultrafast lattice dynamics by recording the x-ray diffuse intensity throughout multiple Brillouin zones using pulses from the Linac Coherent Light Source (LCLS) (central wavelength 1.3\,\AA\, and $< 10$~fs pulse duration). We observe changes in the diffuse intensity that we conclude are associated with a hardening of the soft transverse optical and transverse acoustic phonon branches along $\Gamma$ to $X$ and $\Gamma$ to $M$. Using ground- and excited-state interatomic force constants from density functional theory (DFT) and assuming the phonon populations can be described by a time-dependent temperature, we fit the quasi-equilibrium thermal diffuse intensity to the experimental time-dependent intensity. We obtain the instantaneous lattice temperature and density of photoexcited charge carriers as a function of time delay. The DFT calculations demonstrate that photoexcitation transfers charge from oxygen $2p$ derived $\pi$-bonding orbitals to Ta $5d$ derived antibonding orbitals, further suppressing the ferroelectric instability and increasing the stability of the cubic, paraelectric structure.Comment: 8 pages, 4 figure

The antecedents of biliary cancer: a primary care case–control study in the United Kingdom

In a case–control study using a large UK primary care database, we found that non-steroidal anti-inflammatory drugs had no protective effect against biliary carcinomas (cholangiocarcinoma and gall bladder cancer). Increased risks were observed for cigarette smoking, diabetes, gallstone disease and obesity

A web-based Alcohol Clinical Training (ACT) curriculum: Is in-person faculty development necessary to affect teaching?

<p>Abstract</p> <p>Background</p> <p>Physicians receive little education about unhealthy alcohol use and as a result patients often do not receive efficacious interventions. The objective of this study is to evaluate whether a free web-based alcohol curriculum would be used by physician educators and whether in-person faculty development would increase its use, confidence in teaching and teaching itself.</p> <p>Methods</p> <p>Subjects were physician educators who applied to attend a workshop on the use of a web-based curriculum about alcohol screening and brief intervention and cross-cultural efficacy. All physicians were provided the curriculum web address. Intervention subjects attended a 3-hour workshop including demonstration of the website, modeling of teaching, and development of a plan for using the curriculum. All subjects completed a survey prior to and 3 months after the workshop.</p> <p>Results</p> <p>Of 20 intervention and 13 control subjects, 19 (95%) and 10 (77%), respectively, completed follow-up. Compared to controls, intervention subjects had greater increases in confidence in teaching alcohol screening, and in the frequency of two teaching practices – teaching about screening and eliciting patient health beliefs. Teaching confidence and teaching practices improved significantly in 9 of 10 comparisons for intervention, and in 0 comparisons for control subjects. At follow-up 79% of intervention but only 50% of control subjects reported using any part of the curriculum (p = 0.20).</p> <p>Conclusion</p> <p>In-person training for physician educators on the use of a web-based alcohol curriculum can increase teaching confidence and practices. Although the web is frequently used for disemination, in-person training may be preferable to effect widespread teaching of clinical skills like alcohol screening and brief intervention.</p

Photocurrent-driven transient symmetry breaking in the Weyl semimetal TaAs

Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry change a critical step in developing future technologies that rely on such control. Topological materials, like the newly discovered topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second-harmonic generation spectroscopy as a sensitive probe of symmetry change, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast time scales

Nonlinearity and Topology

The interplay of nonlinearity and topology results in many novel and emergent properties across a number of physical systems such as chiral magnets, nematic liquid crystals, Bose-Einstein condensates, photonics, high energy physics, etc. It also results in a wide variety of topological defects such as solitons, vortices, skyrmions, merons, hopfions, monopoles to name just a few. Interaction among and collision of these nontrivial defects itself is a topic of great interest. Curvature and underlying geometry also affect the shape, interaction and behavior of these defects. Such properties can be studied using techniques such as, e.g. the Bogomolnyi decomposition. Some applications of this interplay, e.g. in nonreciprocal photonics as well as topological materials such as Dirac and Weyl semimetals, are also elucidated