gebhart/patrepeval huggingface dataset:
An inward rectifier K+ channel at the basolateral membrane of the mouse distal convoluted tubule: similarities with Kir4‐Kir5.1 heteromeric channels (2002)

In this study, K(+) channels present in the basolateral membrane of the distal convoluted tubule (DCT) were investigated using patch-clamp methods. In addition, Kir4.1, Kir4.2 and Kir5.1 inward rectifier channels were investigated using RT-PCR and immunohistochemistry (Kir4.1). DCTs were microdissected from collagenase-treated mouse kidneys. One type of K(+) channel was detected in about 50 % of cell-attached patches from the DCT basolateral membrane; this channel was inwardly rectifying and had an inward conductance (g(in)) of approximately 40 pS at an external [K(+)] of 145 mM. The current-voltage relationship was linear when inside-out patches were exposed to a Mg(2+)-free medium. Mg(2+) at a concentration of 1.2 mM considerably reduced the outward conductance (g(out)), yielding a g(in)/g(out) ratio of approximately 4.7. The polycation spermine (5 x 10(-7) M) reduced the open probability (P(o)) by 50 %. Channel activity was dependent upon the intracellular pH, with acid pH decreasing, and basic pH increasing, P(o). Internal ATP (2 mM) and Ca(2+) (up to 10(-3) M) had no effect. Channel activity declined irreversibly when the inner side of the patch was exposed to Mg(2+). Kir4.1, Kir4.2 and Kir5.1 mRNAs were all detected in the DCT. The Kir4.1 protein co-localised with the Na(+)-Cl(-) cotransporter, which is specific to the DCT, and was located on basolateral membranes. The DCT K(+) channel differs from other functionally identified renal K(+) channels with regard to its inhibition by spermine and insensitivity to internal ATP and Ca(2+). At the current state of knowledge, the channel is similar to Kir4.1-Kir5.1 and Kir4.2-Kir5.1 heteromeric channels, but not to Kir4.1 or Kir4.2 homomeric channels.
Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis (2015)

Umbilical cord mesenchymal stem cells (UC-MSCs) have been suggested as a candidate for various clinical applications, however, major limitations include the lack of organ-specific accumulation and low survival rates of transplanted cells. In the present study, it was hypothesized that the paracrine effects of UC‑MSCs may enhance stem cell-based tissue repair and regeneration by promoting the specific homing of stem/progenitor cells and the overall ability to drive them to the damaged area. UC-MSCs-derived conditioned medium (UC-CM) was analyzed using liquid chip and ELISA techniques. In vitro tube formation assays of human umbilical vein endothelial cells (HUVECs) and UC-MSCs were then performed to assess the angiogenic properties of UC-CM. Subsequently, UC-MSCs, HUVECs and fibroblasts were labeled with PKH26 for an in vivo cell migration assay. The expression levels of C-X-C chemokine receptor 4 (CXCR4), C-C chemokine receptor 2 (CCR2) and c-met were determined in the UC-MSCs, HUVECs and fibroblasts using reverse transcription-quantitative polymerase chain reaction and flow cytometry. UC-CM was incubated with or without antibodies, and the contribution of stromal cell-derived factor 1 (SDF-1), monocyte chemotactic protein 1 (MCP-1) and hepatocyte growth factor (HGF) on the migration of cells was investigated in vitro. The results demonstrated that UC-MSCs secreted different cytokines and chemokines, including increased quantities of SDF-1, MCP-1 and HGF, in addition to the angiogenic factors, vascular cell adhesion protein-1, interleukin-8, insulin-like growth factor-1 and vascular endothelial growth factor. The total lengths of the tubes were significantly increased in the UC-MSCs and HUVECs incubated in UC-CM compared with those incubated in Dulbecco's modified Eagle's medium. In vivo cell migration assays demonstrated that UC-CM was a chemotactic stimulus for the UC-MSCs and HUVECs. In vitro Matrigel migration and scratch healing assays demonstrated that UC-CM increased the migration of CXCR4-positive or/and CCR2-positive cells in a dose-dependent manner. In addition, different molecules were screened under antibody-based blocking migration conditions. The data revealed that the SDF-1/CXCR4 and MCP-1/CCR2 axes were involved in the chemoattractive activity of UC-CM and suggested that the effective paracrine factor of UC-CM is a large complex rather than a single factor. The results of the present study supported the hypothesis that UC-MSCs release soluble factors, which may extend the therapeutic applicability of stem cells.
Intracellular inclusions, pathological markers in diseases caused by expanded polyglutamine tracts? (1999)

The largest group of currently known trinucleotide repeat diseases is caused by (CAG)n repeat expansions. These (CAG)n repeats are translated into polyglutamine tracts from both mutant and wild type alleles. Genetic and transgenic mouse data suggest that the expanded polyglutamines cause disease by conferring a novel deleterious gain of function on the mutant protein. These mutations are associated with the formation of intracellular inclusions. This review will consider findings from necropsy studies of human patients and transgenic mouse models of these diseases, along with in vitro models, in order to try to synthesise the current understanding of these diseases and the evidence for and against inclusion formation as a primary mechanism leading to pathology.
Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease (2005)

Our findings suggest that IL-15 plays a crucial role in the generation of epithelial damage in active CD. Its promotion of IEL survival in CD may predispose to the emergence of T cell clonal proliferations. Blocking IL-15, by suppressing uncontrolled IEL activation and survival, has the potential to provide new therapeutic tools to prevent tissue damage and lymphomagenesis in CD.
Characterization of Therapeutic Antibodies and Related Products (2012)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTCharacterization of Therapeutic Antibodies and Related ProductsAlain Beck*†, Elsa Wagner-Rousset†, Daniel Ayoub†, Alain Van Dorsselaer‡, and Sarah Sanglier-Cianférani‡View Author Information† Centre d'Immunologie Pierre Fabre (CIPF), 5 Av. Napoléon III, BP 60497, 74164 Saint-Julien-en-Genevois, France‡ Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg, IPHC, 25 rue Becquerel 67087, Strasbourg, France and CNRS, UMR7178, 67037 Strasbourg, France*E-mail: [email protected]Cite this: Anal. Chem. 2013, 85, 2, 715–736Publication Date (Web):November 7, 2012Publication History Published online14 December 2012Published inissue 15 January 2013https://pubs.acs.org/doi/10.1021/ac3032355https://doi.org/10.1021/ac3032355review-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views17097Altmetric-Citations495LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biopolymers,Carbohydrates,Immunology,Monomers,Peptides and proteins Get e-Alerts
Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein (2002)

Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.
Comparison of virus production in chicken embryo fibroblasts infected with the WR, IHD-J and MVA strains of vaccinia virus: IHD-J is most efficient in trans-Golgi network wrapping and extracellular enveloped virus release (2003)

Modified vaccinia virus Ankara (MVA) is an attenuated strain derived from vaccinia virus (VV) Ankara that grows efficiently in primary chicken embryo fibroblasts (CEFs) and baby hamster kidney cells only. MVA produces significantly more of the enveloped forms of VV in infected CEFs compared with VV strain Copenhagen. In the present study, production of the different infectious forms of VV was compared in CEFs infected with MVA or with two well-characterized replication-competent VV strains, WR and IHD-J. In a time-course experiment, the infectivity associated with the extracellular enveloped virus (EEV), the cell-associated enveloped virus (CEV) and intracellular mature and enveloped viruses was determined. Further, the production of the different viral forms was quantified by electron microscopy (EM). The data collectively indicate that IHD-J is most efficient in producing all of the trans-Golgi network-wrapped forms and releases the highest titres of EEVs into the extracellular medium, with WR being least efficient. MVA initially replicated with faster kinetics, resulting in more intracellular virus and CEVs between 8 and 24 h post-infection (p.i.). As assessed by EM, the faster growth kinetics of MVA resulted in 3.5-fold more CEVs at the cell surface at 24 h p.i., compared with both WR and IHD-J. Accordingly, we found that despite the presence of two in-frame deletions in the A36R gene of MVA, this virus was able to make actin tails in CEFs.
Once‐weekly administration of a long‐acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non‐human primates (2017)

Once-weekly PF-05231023 lowered triglycerides markedly in the absence of weight loss, with modest changes in markers of bone homeostasis. This is the first report showing increases in BP and pulse rate in humans and rats after pharmacological administration of a long-acting FGF21 molecule.
Targeting ATR and Chk1 kinases for cancer treatment: A new model for new (and old) drugs (2011)

Trying to kill cancer cells by generating DNA damage is by no means a new idea. Radiotherapy and genotoxic drugs are routinely used in cancer therapy. More recent developments also explored the potential of targeting the DNA damage response (DDR) in order to increase the toxicity of radio- and chemo- therapy. Chk1 inhibitors have pioneered studies in this regard. Interestingly, early studies noted that Chk1 inhibitors were particularly toxic for p53-deficient cells. The model proposed for this observation was that this effect was due to the simultaneous abrogation of the G2 (Chk1) and G1 (p53) checkpoints. We here challenge this view, and propose a model where the toxicity of Chk1 inhibitors is rather due to the fact that these compounds generate high loads of replicative stress (RS) during S-phase, which are further boosted by the less restrictive S-phase entry found in p53-deficient cells. This new model implies that the particular toxicity of Chk1 inhibitors might not be restricted to p53-deficient cells, but could be extended to other mutations that promote a promiscuous S-phase entry. In addition, this rationale also implies that the same effect should also be observed for other molecules that target the RS-response (RSR), such as inhibitors of the Chk1-activating kinase ATR.
Flow-conditioned HUVECs support clustered leukocyte adhesion by coexpressing ICAM-1 and E-selectin (2004)

Endothelial sequestration of circulating monocytes is a key event in early atherosclerosis. Hemodynamics is proposed to regulate monocyte-endothelial cell interactions by direct cell activation and establishment of flow environments that are conducive or prohibitive to cell-cell interaction. We investigated fluid shear regulation of monocyte-endothelial cell adhesion in vitro using a disturbed laminar shear system that models in vivo hemodynamics characteristic of lesion-prone vascular regions. Human endothelial cell monolayers were flow conditioned for 6 h before evaluation of monocyte adhesion under static and dynamic flow conditions. Results revealed a distinctive clustered cell pattern of monocyte adhesion that strongly resembles in vivo leukocyte adhesion in early- and late-stage atherosclerosis. Clustered monocyte cell adhesion correlated with endothelial cells coexpressing intercellular adhesion molecule-1 (ICAM-1) and E-selectin as result of a flow-induced, selective upregulation of E-selectin expression in a subset of ICAM-1-expressing cells. Clustered monocyte cell adhesion assayed under static conditions exhibited a spatial variation in size and frequency of occurrence, which demonstrates differential regulation of endothelial cell adhesiveness by the local flow environment. Dynamic adhesion studies conducted with circulating monocytes resulted in clustered cell adhesion only within the disturbed flow region, where the monocyte rate of motion is sufficiently low for cell-cell interaction. These studies provide evidence and reveal mechanisms of local hemodynamic regulation of endothelial adhesiveness and endothelial monocyte interaction that lead to localized monocyte adhesion and potentially contribute to the focal origin of arterial diseases such as atherosclerosis.
Hematologic Remission and Cytogenetic Improvement Induced by Recombinant Human Interferon AlphaAin Chronic Myelogenous Leukemia (1986)

We treated 17 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia (4 of whom had not received therapy and 13 of whom had been treated with hydroxyurea or busulfan for less than six months) with recombinant human interferon alpha A (Roferon-A). The interferon was given as 5 X 10(6) units per square meter of body-surface area per day intramuscularly during induction therapy. Fourteen patients responded to the treatment, of whom 13 had a hematologic remission and 1 had a partial hematologic remission. The median number of white cells in those patients declined from 60.9 X 10(3) to 3.4 X 10(3) per microliter, and the median number of platelets decreased from 476 X 10(3) to 231 X 10(3) per microliter. Among the five responding patients who had splenomegaly before treatment, the spleen size returned to normal in four and decreased by 75 percent in one, although it remained enlarged. Bone marrow cellularity declined from a median of 92.5 percent to a median of 57.5 percent. In six of the patients with hematologic remission, complete suppression of Philadelphia cells was observed on at least one examination. Of the 14 patients who responded, 11 have received the interferon therapy for 9 to 15 months. One patient relapsed during the treatment, and the treatment has been temporarily interrupted in two patients because of toxicity. These data are preliminary and will need further confirmation, but they suggest that recombinant human interferon alpha A is effective in inducing hematologic remission in most patients with benign-phase chronic myelogenous leukemia and in suppressing the Philadelphia chromosome in some of these patients.
THE REACTION OF ANILS WITH 8-QUINOLINOL (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE REACTION OF ANILS WITH 8-QUINOLINOLJ. P. PHILLIPS, R. W. KEOWN, and QUINTUS FERNANDOCite this: J. Org. Chem. 1954, 19, 6, 907–909Publication Date (Print):June 1, 1954Publication History Published online1 May 2002Published inissue 1 June 1954https://pubs.acs.org/doi/10.1021/jo01371a005https://doi.org/10.1021/jo01371a005research-articleACS PublicationsRequest reuse permissionsArticle Views242Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Effect of Gas Properties on Bubble Formation, Growth, and Detachment (2015)

Bubble formation and growth play an important role in various processes and industries, where the dispersion of gas bubbles in a liquid medium occurs frequently. In this paper, the formation, growth, and detachment of gas bubbles produced from a submerged needle in water are numerically and experimentally investigated. The effect of injected gas properties on bubble characteristics, including bubble diameter, contact angle, and the frequency of bubble formation, is evaluated. In particular, the changes in bubble characteristics during the injection process are investigated for three different gases to evaluate the effect of density and surface tension on the bubble detachment criteria. The present numerical results show an acceptable agreement with experiments under different operating conditions. The results show that the increase in surface tension, and the decrease in gas density result in larger bubble sizes before detachment occurs. Moreover, the bubble generation frequency is found to strongly depend on the contact angle and the surface tension.
Synthesis and Hypnotic Activities of 4-Thio Analogues of N3-Substituted Uridines. (2001)

Reaction of tri-O-acetyluridine (1) with benzyl bromide or 2-chloroacetophenone in the presence of K2CO3 gave the N3-substituted analogues 2a,c. Condensation of 1 with (+/-)-1-phenylethanol or 3,5-dimethylbenzyl alcohol using the Mitsunobu reaction also gave 2b,d in good yields. These compounds were allowed to react with Lawesson's reagent and were subsequently treated with ammonia to afford the 4-thiouracil derivatives 5a-d. Compounds 5a-c showed moderate hypnotic activity in mice. However, N3-(3,5-dimethyl)benzyl derivatives 3d, 5d were found to be almost inactive in this assay.
Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice. (1998)

Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine. These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function.
The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans (2009)

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.
Strong sequence conservation among horizontally transmissible, minimally pathogenic feline leukemia viruses (1988)

We report the first complete nucleotide sequence (8,440 base pairs) of a biologically active feline leukemia virus (FeLV), designated FeLV-61E (or F6A), and the molecular cloning, biological activity, and env-long terminal repeat (LTR) sequence of another FeLV isolate, FeLV-3281 (or F3A). F6A corresponds to the non-disease-specific common-form component of the immunodeficiency disease-inducing strain of FeLV, FeLV-FAIDS, and was isolated from tissue DNA of a cat following experimental transmission of naturally occurring feline acquired immunodeficiency syndrome. F3A clones were derived from a subgroup-A-virus-producing feline tumor cell line. Both are unusual relative to other molecularly cloned FeLVs studied to date in their ability to induce viremia in weanling (8-week-old) cats and in their failure to induce acute disease. The F6A provirus is organized into 5'-LTR-gag-pol-env-LTR-3' regions; the gag and pol open reading frames are separated by an amber codon, and env is in a different reading frame. The deduced extracellular glycoproteins of F6A, F3A, and the Glasgow-1 subgroup A isolate of FeLV (M. Stewart, M. Warnock, A. Wheeler, N. Wilkie, J. Mullins, D. Onions, and J. Neil, J. Virol. 58:825-834, 1986) are 98% homologous, despite having been isolated from naturally infected cats 6 to 13 years apart and from widely different geographic locations. As a group, their envelope gene sequences differ markedly from those of the disease-associated subgroup B and acutely pathogenic subgroup C viruses. Thus, F6A and F3A correspond to members of a highly conserved family and represent prototypes of the horizontally transmitted, minimally pathogenic FeLV present in all naturally occurring infections.