Confocal imaging with a fluorescent bile acid analogue closely mimicking hepatic taurocholate disposition.

This study aimed to characterize the in vitro hepatic transport mechanisms in primary rat and human hepatocytes of the fluorescent bile acid derivative N-(24-[7-(4-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole)]amino-3α,7α,12α-trihydroxy-27-nor-5β-cholestan-26-oyl)-2'-aminoethanesulfonate (tauro-nor-THCA-24-DBD), previously synthesized to study the activity of the bile salt export pump (BSEP). The fluorescent bile acid derivative exhibited saturable uptake kinetics in suspended rat hepatocytes. Hepatic uptake was inhibited in the presence of substrates/inhibitors of the organic anion transporting polypeptide (Oatp) family and Na(+) -taurocholate cotransporting peptide (Ntcp).

Transport of estradiol-17β-glucuronide, estrone-3-sulfate and taurocholate across the endoplasmic reticulum membrane: evidence for different transport systems.

Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. Consequently, UGT generated glucuronides, like estradiol-17β-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis.

The role of organic anion transporters in diagnosing liver diseases by magnetic resonance imaging.

The expression and transport functions of organic anion transporters are modified in liver diseases, and therefore the vascular clearances of endogenous and exogenous organic anions that are taken up by these transporters have been used to assess liver diseases in patients. More recently, liver imaging with hepatobiliary contrast agents, tracers, and dyes that cross hepatocytes through the organic anion transporting polypeptides (OATPs)-multidrug resistance-associated proteins (MRPs) pathway were developed to detect and characterize focal lesions and to assess the severity of diffuse liver diseases. This review focuses mainly on magnetic resonance imaging and highlights the growing interest in imaging the OATPs-MRP2 pathway to better understand liver diseases.

Measurement of top quark-antiquark pair production in association with a W or Z boson in pp collisions at [Formula: see text][Formula: see text].

A measurement of the cross section for the production of top quark-antiquark pairs ([Formula: see text]) in association with a vector boson V (W or Z) in proton-proton collisions at [Formula: see text][Formula: see text] is presented. The results are based on a dataset corresponding to an integrated luminosity of 19.5 fb[Formula: see text] recorded with the CMS detector at the LHC.

Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV.

Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text].

Search for invisible decays of Higgs bosons in the vector boson fusion and associated ZH production modes.

A search for invisible decays of Higgs bosons is performed using the vector boson fusion and associated ZH production modes. In the ZH mode, the Z boson is required to decay to a pair of charged leptons or a [Formula: see text] quark pair. The searches use the 8 [Formula: see text] pp collision dataset collected by the CMS detector at the LHC, corresponding to an integrated luminosity of up to 19.

Measurement of WZ and ZZ production in pp collisions at [Formula: see text] in final states with b-tagged jets.

Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.

Probing color coherence effects in pp collisions at [Formula: see text].

A study of color coherence effects in pp collisions at a center-of-mass energy of 7[Formula: see text] is presented. The data used in the analysis were collected in 2010 with the CMS detector at the LHC and correspond to an integrated luminosity of 36 pb[Formula: see text]. Events are selected that contain at least three jets and where the two jets with the largest transverse momentum exhibit a back-to-back topology.

Study of the production of charged pions, kaons, and protons in pPb collisions at [Formula: see text]5.02[Formula: see text].

Spectra of identified charged hadrons are measured in pPb collisions with the CMS detector at the LHC at [Formula: see text]. Charged pions, kaons, and protons in the transverse-momentum range [Formula: see text]-1.7[Formula: see text] and laboratory rapidity [Formula: see text] are identified via their energy loss in the silicon tracker.

Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes.

Type VII collagen is the main component of anchoring fibrils, structures that are integral to basement membrane homeostasis in skin. Mutations in the gene encoding type VII collagen COL7A1 cause recessive dystrophic epidermolysis bullosa (RDEB) an inherited skin blistering condition complicated by frequent aggressive cutaneous squamous cell carcinoma (cSCC). OATP1B3, which is encoded by the gene SLCO1B3, is a member of the OATP (organic anion transporting polypeptide) superfamily responsible for transporting a wide range of endogenous and xenobiotic compounds.

Search for top squarks in R-parity-violating supersymmetry using three or more leptons and b-tagged jets.

A search for anomalous production of events with three or more isolated leptons and bottom-quark jets produced in pp collisions at √s=8 TeV is presented. The analysis is based on a data sample corresponding to an integrated luminosity of 19.5 fb(-1) collected by the CMS experiment at the LHC in 2012.

Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters.

The SLC10A transporter gene family consists of seven members and substrates transported by three members (SLC10A1, SLC10A2 and SLC10A6) are Na(+)-dependent. SLC10A1 (sodium taurocholate cotransporting polypeptide [NTCP]) and SLC10A2 (apical sodium-dependent bile salt transporter [ASBT]) transport bile salts and play an important role in maintaining enterohepatic circulation of bile salts. Solutes other than bile salts are also transported by NTCP.

Chronic cholestatic liver diseases: clues from histopathology for pathogenesis.

Chronic cholestatic liver diseases include fibrosing cholangiopathies such as primary biliary cirrhosis or primary sclerosing cholangitis. These and related cholangiopathies clearly display pathologies associated with (auto)immunologic processes. As the cholangiocyte's apical membrane is exposed to the toxic actions of the bile fluid, the interaction of bile with cholangiocytes and the biliary tree in general must be considered to completely understand the pathogenesis of cholangiopathies.

ATP-binding cassette transporters in liver.

The human ATP-binding cassette (ABC) superfamily consists of 48 members with 14 of them identified in normal human liver at the protein level. Most of the ABC members act as ATP dependent efflux transport systems. In the liver, ABC transporters are involved in diverse physiological processes including export of cholesterol, bile salts, and metabolic endproducts.

Inclusive search for supersymmetry using razor variables in pp collisions at √s=7 TeV.

An inclusive search is presented for new heavy particle pairs produced in √s=7 TeV proton-proton collisions at the LHC using 4.7±0.1 fb(-1) of integrated luminosity.

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways.

Characteristics and functional relevance of apolipoprotein-A1 and cholesterol binding in mammary gland tissues and epithelial cells.

Cholesterol in milk is derived from the circulating blood through a complex transport process involving the mammary alveolar epithelium. Details of the mechanisms involved in this transfer are unclear. Apolipoprotein-AI (apoA-I) is an acceptor of cellular cholesterol effluxed by the ATP-binding cassette (ABC) transporter A1 (ABCA1).

Polarized expression of drug transporters in differentiated human hepatoma HepaRG cells.

The HepaRG cell line is a well-differentiated human hepatoma cell line proposed as a surrogate for human hepatocytes, especially for hepatic detoxification studies. Polarized status of drug transporters, i.e.