Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiomyocytes develop from anterior primitive streak cells induced by β‐catenin activation and the blockage of BMP signaling in hESCs

Cardiomyocytes arise from cells that migrate to the mid‐to‐anterior region of the primitive streak (PS) during embryogenesis. We previously showed that canonical Wnt/β‐catenin pathway signaling leads to the development of nascent PS populations from human embryonic stem cells (hESCs) and that synergistic activation of the Wnt/β‐catenin pathway and inhibition of bone morphogenetic protein (BMP) signaling by Noggin induced the formation of anterior PS cells. We herein demonstrate that anterior PS cells induced by the activation of β‐catenin with Noggin differentiate into functional cardiomyocytes when cultured in suspension with BMP4 and fibroblast growth factor 2 (FGF2). All aggregates generated from the anterior PS cells developed into contracting cells demonstrating their cardiac potential. More than 30% of the cells in each aggregate were α‐actinin‐positive cardiomyocytes. In addition, these cardiomyocytes could be easily purified up to 80% by simple size fractionation. In contrast, the posterior PS cells induced by β‐catenin activation without Noggin showed poor cardiac potential. These results show that the commitment to a cardiac lineage in vitro occurs through similar cellular and molecular signaling pathways involved in cardiac development in vivo, thus providing a valuable culture model for studying early cardiac developmental events in hESCs.
Hemodialysis Arteriovenous Fistulas: A Nineteenth Century View of a Twenty First Century Problem

This is a literature review which approaches the problem of successful use of arteriovenous fistulas for dialysis within the construct of Virchow's triad. By organizing the literature with regard to Virchow's concepts of blood flow, vascular injury, and thrombophilia an improved understanding arteriovenous fistula placement, maintenance and repair can be obtained. This process is designed to increase understanding and options for treatment by looking at this problem and using scientific knowledge gained in cardiology, oncology and vascular surgery medicine. Future approaches to fistulas will hopefully be a multifaceted and based in cellular pathophysiology as well as surgical and radiologic interventions and repairs.
Parenteral Iron Therapy in Treatment of Anemia in End-Stage Renal Disease Patients: A Comparative Study between Iron Saccharate and Gluconate

Background: Anemia in hemodialysis patients is a complex syndrome. The impetus of this study was to assess the safety and efficacy of iron saccharate complex (ISC) and sodium ferric gluconate complex (SFGC) in treating anemia in hemodialysis patients. Methods: Forty-eight adult anemic patients of both genders (33 males and 15 females) who had an adequate level of both hemodialysis and nutrition status and received neither EPO nor parenteral iron therapy during the preceding 6 months were randomized to 2 groups. The first group comprised 22 patients who were treated with parenteral ISC, 100 mg twice weekly for 2 months and once weekly thereafter. The second group included 26 patients who received SFGC, 62.5 mg twice weekly for 2 months and once weekly thereafter. The patients were followed up for 6 months. Results: This head-to-head study showed that iron stores were adequately repleted by the use of both drugs. Repletion of iron stores was associated with a significant rise in both hemoglobin and hematocrit in both groups at the end of the follow-up period in comparison to their initial values at the start of the study (p < 0.001). Both parenteral iron therapy preparations were tolerated without a statistical difference between both groups. Conclusion: This head-to-head study confirmed that both parenteral iron preparations are effective for adequate repletion of iron stores and constituted a step forward in the management of anemic hemodialysis patients without noticeable adverse effects related to the administration of both iron preparations.
Subunit composition of mammalian transient receptor potential channels in living cells

Hormones, neurotransmitters, and growth factors give rise to calcium entry via receptor-activated cation channels that are activated downstream of phospholipase C activity. Members of the transient receptor potential channel (TRPC) family have been characterized as molecular substrates mediating receptor-activated cation influx. TRPC channels are assumed to be composed of multiple TRPC proteins. However, the cellular principles governing the assembly of TRPC proteins into homo- or heteromeric ion channels still remain elusive. By pursuing four independent experimental approaches—i.e., subcellular cotrafficking of TRPC subunits, differential functional suppression by dominant-negative subunits, fluorescence resonance energy transfer between labeled TRPC subunits, and coimmunoprecipitation—we investigate the combinatorial rules of TRPC assembly. Our data show that (i) TRPC2 does not interact with any known TRPC protein and (ii) TRPC1 has the ability to form channel complexes together with TRPC4 and TRPC5. (iii) All other TRPCs exclusively assemble into homo- or heterotetramers within the confines of TRPC subfamilies—e.g., TRPC4/5 or TRPC3/6/7. The principles of TRPC channel formation offer the conceptual framework to assess the physiological role of distinct TRPC proteins in living cells.
Effect of valproate on the plasma concentrations of aripiprazole in bipolar patients

Abstract Objective. There is very limited documentation available on the effects of valproate co-medication on the pharmacokinetics of aripiprazole in a naturalistic setting. The aim of the present study was to investigate the effect of co-medication with valproate on serum concentrations of aripiprazole in bipolar disorder patients in a clinical setting. Method. Plasma samples of bipolar disorder patients (n = 69) on a stable dose of aripiprazole 20 mg/day were analyzed by a liquid chromatography-mass spectrometry method in a routine therapeutic drug monitoring setting. Therapeutic drug monitoring was done for the entire study group before and after valproate co-administration. Results. We observed a statistically significant difference between the aripiprazole monotherapy and aripiprazole-valproate combination with respect to total aripiprazole plasma levels (p < 0.01). However, no statistically significant differences were noted in aripiprazole levels between the first week and the second week of valproate co-administration. Conclusion. In conclusion, concurrent treatment with valproate resulted in changes in the total aripiprazole plasma levels by 23%. But a lower total aripiprazole concentration during co-medication with valproate, caused by protein binding displacement, is reported being clinically insignificant in previous studies. The results from these studies are important in order to clarify clinical safety and efficacy.
Prp43 Is an Essential RNA-dependent ATPase Required for Release of Lariat-Intron from the Spliceosome*

The essential Saccharomyces cerevisiae PRP43 gene encodes a 767-amino acid protein of the DEXH-box family. Prp43 has been implicated in spliceosome disassembly (Arenas, J. E., and Abelson, J. N. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 11798–11802). Here we show that purified recombinant Prp43 is an RNA-dependent ATPase. Alanine mutations at conserved residues within motifs I (119GSGKT123), II (215DEAH218) and VI (423QRAGRAGR430) that diminished ATPase activity in vitro were lethal in vivo, indicating that ATP hydrolysis is necessary for the biological function of Prp43. Overexpression of lethal, ATPase-defective mutants in a wild-type strain resulted in dominant-negative growth inhibition. The ATPase-defective mutant T123A interfered in trans with thein vitro splicing function of wild-type Prp43. T123A did not affect the chemical steps of splicing or the release of mature mRNA from the spliceosome, but it blocked the release of the excised lariat-intron from the spliceosome. We show that the lariat-intron is not accessible to debranching by purified Dbr1 when it is held in the T123A-arrested splicing complex. Our results define a new ATP-dependent step of splicing that is catalyzed by Prp43.
Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review.

AIM To summarize the evidence available for the clinical effectiveness of insulin sensitizers in the treatment of nonalcoholic fatty liver disease (NAFLD) systematically. METHODS Relevant articles were located using computer-assisted searches of Medline (1966-March 2006), EMBASE (1988-March 2006), CINAHL (1982-March 2003), Educational Resource Information Center (1966-March 2006), Library, Information Science and Technology Abstracts (1967-March 2006), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (1994-2006), dissertations in ProQuest and FirstSearch databases. Manual searches were made in the abstracts from meetings of the American Gastroenterological Association (1999-2006), and the American Association for the Study of Liver Diseases (2003-2005). Studies were retrieved using the following selection criteria: (1) clinical trials using insulin sensitizers in subjects with NAFLD, (2) adult patients, (3) published as full manuscripts or abstracts, and (4) English, Spanish, German, and French languages only. Data were abstracted independently by two reviewers following standardized procedures. A face-to-face comparison of data was conducted to ensure the completeness and reliability of the abstraction process. RESULTS Nine studies were included, six using metformin and three using thiazolidinediones. Only two studies were placebo-controlled trials. The median sample size for all studies was 18 subjects. In the placebo-controlled trials, metformin improved insulin resistance markers and liver function tests, but not histological scores. In the single-arm trials, metformin and thiazolidinediones improved insulin resistance markers and liver function tests, and beneficial histological changes were reported. There is limited high-quality information available from which to draw categorical conclusions about the clinical use of insulin sensitizers in NAFLD. CONCLUSION Current information indicates that the use of insulin sensitizers in NAFLD improves insulin resistance and liver function. Histological changes must be corroborated in randomized controlled trials.
Ventral nucleus of the lateral lemniscus in guinea pigs: Cytoarchitecture and inputs from the cochlear nucleus

Cytoarchitectonic criteria were used to distinguish three subdivisions of the ventral nucleus of the lateral lemniscus in guinea pigs. Axonal tracing techniques were used to examine the projections from the cochlear nucleus to each subdivision. Based on the cell types they contain and their patterns of input, we distinguished ventral, dorsal, and anterior subdivisions of the ventral nucleus of the lateral lemniscus. All three subdivisions receive bilateral inputs from the cochlear nucleus, with contralateral inputs greatly outnumbering ipsilateral inputs. However, the relative density of the inputs varies: the ventral subdivision receives the densest projection, whereas the anterior subdivision receives the sparsest projection. Further differences are apparent in the morphology of the afferent axons. Following an injection of Phaseolus vulgaris‐leucoagglutinin into the ventral cochlear nucleus, most of the axons on the contralateral side and all of the axons on the ipsilateral side are thin. Thick axons are present only in the ventral subdivision contralateral to the injection site. The evidence from both anterograde and retrograde tracing studies suggests that the thick axons originate from octopus cells, whereas the thin axons arise from multipolar cells and spherical bushy cells. The differences in constituent cell types and in patterns of inputs suggest that each of the three subdivisions of the ventral nucleus of the lateral lemniscus makes a distinct contribution to the analysis of acoustic signals. J. Comp. Neurol. 379:363–385, 1997. © 1997 Wiley‐Liss, Inc.
Inactivation of the protein phosphatase 2A regulatory subunit A results in morphological and transcriptional defects in Saccharomyces cerevisiae

We have determined that TPD3, a gene previously identified in a screen for mutants defective in tRNA biosynthesis, most likely encodes the A regulatory subunit of the major protein phosphatase 2A species in the yeast Saccharomyces cerevisiae. The predicted amino acid sequence of the product of TPD3 is highly homologous to the sequence of the mammalian A subunit of protein phosphatase 2A. In addition, antibodies raised against Tpd3p specifically precipitate a significant fraction of the protein phosphatase 2A activity in the cell, and extracts of tpd3 strains yield a different chromatographic profile of protein phosphatase 2A than do extracts of isogenic TPD3 strains. tpd3 deletion strains generally grow poorly and have at least two distinct phenotypes. At reduced temperatures, tpd3 strains appear to be defective in cytokinesis, since most cells become multibudded and multinucleate following a shift to 13 degrees C. This is similar to the phenotype obtained by overexpression of the protein phosphatase 2A catalytic subunit or by loss of CDC55, a gene that encodes a protein with homology to a second regulatory subunit of protein phosphatase 2A. At elevated temperatures, tpd3 strains are defective in transcription by RNA polymerase III. Consistent with this in vivo phenotype, extracts of tpd3 strains fail to support in vitro transcription of tRNA genes, a defect that can be reversed by addition of either purified RNA polymerase III or TFIIIB. These results reinforce the notion that protein phosphatase 2A affects a variety of biological processes in the cell and provide an initial identification of critical substrates for this phosphatase.
[Papillary renal cell carcinoma: clinico-pathologic studies of 33 cases].

OBJECTIVE To investigate the morphologic features, differential diagnosis, prognosis and histogenesis of papillary renal cell carcinoma (PRCC). METHODS Tumors composed of at least 50% papillae and > 1 cm in diameter were included in this study. Light microscopic observation, immunohistochemical assay of EMA, CK7, CD10, Vim, 34 beta E12 by tissue chip were performed. RESULTS Among 516 cases of renal epithelial tumors 33 cases of PRCC were detected. Grossly, hemorrhage, necrosis and multifocality were commonly seen. Besides typical papillae, inconspicuous papillary patterns, such as trabecular, tubular, micronodular and pseudostratified patterns could be seen. Foam cells and psammoma bodies in stroma, and hemosiderin in tumor cells were characteristic. Tumors were of two major types: basophilic type (n = 10), with small cuboid cell and pale cytoplasm (n = 10), 9 of them were low in Fuhrman grading; eosinophilic type (n = 22) with large columnar cells, rich in eosinophilic cytoplasm, 19 of them were high in Fuhrman grading. The remaining case was of clear cell type. The basophilic tumors were all positive for distal tubule marker EMA/CK7, none for proximal tubule marker CD10, 7 tumors positive for Vim. Eosinophilic tumors were positive for EMA/CK7 (9/22), CD10 (10/22) and Vim (6/22). All the tumors studied were negative for 34 beta E12. Follow-up data were available for 24 cases (mean 37 months) with 3-year survival rate of 64.3%, 5-year survival rate of 50%. CONCLUSION PRCC was a distinct malignant entity with unique pathological features. The prognosis of PRCC was worse than that of chromophobe renal cell carcinoma.
Characterization and Modeling of Broad Spectrum InAs–GaAs Quantum-Dot Superluminescent Diodes Emitting at 1.2–1.3 $\mu$m

High-power broadband superluminescent diodes (SLDs) emitting in the 1.2-1.3-mum region are demonstrated using InAs-GaAs quantum dots (QDs). The highest output powers of ~30-50 mW are achieved using 18 QD layers with p-doped GaAs spacers. At these high powers the device operates in a regime of broad bandwidth (~100 nm) with a spectral dip of ~5 dB between two separate peaks originated by the QD ground and excited states. Spectral calculations performed with a traveling-wave rate equation model show excellent agreement with the experimental data and provide design rules for optimizing the output spectrum. SLD characteristics are presented for two different device structures consisting of tilted and bent waveguides. The latter allows the achievement of higher output powers at lower currents. The coherence properties and the temperature characteristics are also discussed in detail.
Microbial biomass in faeces of dairy cows affected by a nitrogen deficient diet

Since more than half of the faecal nitrogen (N) originates from microbial N, the objective of the study was to develop a method for quantitatively detecting microbial biomass and portion of living microorganisms in dairy cattle faeces, including bacteria, fungi and archaea. Three techniques were tested: (1) the chloroform fumigation extraction (CFE) method, (2) detection of the fungal cell-membrane component ergosterol and (3) analysis of the cell wall components fungal glucosamine and bacterial muramic acid. In a second step, an N deficient (ND) and an N balanced (NB) diets were compared with respect to the impacts on faecal C and N fractions, microbial indices and digestibility. The mean values of microbial biomass C and N concentrations averaged around 37 and 4.9 mg g−1 DM, respectively. Ergosterol, together with fungal glucosamine and bacterial muramic acid, revealed a 25% fungal C in relation to the total microbial C content in dairy cattle faeces. Changes in ruminal N supply showed significant effects on faecal composition. Faecal concentrations of NDF, hemicelluloses and undigested dietary N and the total C/N ratio were significantly higher in ND treatment compared to the NB treatment. N deficiency was reflected also by a higher microbial biomass C/N ratio. It was concluded that the assessment of microbial indices provides valuable information with respect to diet effects on faecal composition and the successive decomposition. Further studies should be conducted to explore the potentials for minimising nutrient losses from faeces.
Sequence variations in alleles of the avirulence gene avrPphE.R2 from Pseudomonas syringae pv. phaseolicola lead to loss of recognition of the AvrPphE protein within bean cells and a gain in cultivar‐specific virulence

The bean halo blight pathogen, Pseudomonas syringae pv. phaseolicola (Psph), is differentiated into nine races based on the presence or absence of five avirulence (avr ) genes in the bacterium, which interact with corresponding resistance genes, R1–R5, in Phaseolus vulgaris. The resistance gene R2 is matched by avrPphE, which is located adjacent to the cluster of hrp genes that are required for pathogenicity of Psph. Although only races 2, 4, 5 and 7 are avirulent on cultivars with R2 (inducing the hypersensitive response; HR), homologues of avrPphE are present in all races of Psph. DNA sequencing of avrPphE alleles from races of Psph has demonstrated two routes to virulence: via single basepair changes conferring amino acid substitutions in races 1, 3, 6 and 9 and an insertion of 104 bp in the allele in race 8. We have demonstrated that these base changes are responsible for the difference between virulence and avirulence by generating transconjugants of a virulent race harbouring plasmids expressing the various alleles of avrPphE. Agrobacterium tumefaciens‐directed expression of avrPphE from race 4 in bean leaves induced the HR in a resistance gene‐specific manner, suggesting that the AvrPphE protein is alone required for HR induction and is recognized within the plant cell. The allele from race 6, which is inactive if expressed in Psph, elicited a weak HR if expressed in planta, whereas the allele from race 1 did not. Our results suggest that the affinity of interaction between AvrPphE homologues and an unknown plant receptor mediates the severity of the plant's response. Mutation of avrPphE alleles did not affect the ability to colonize bean from a low level of inoculum. The avirulence gene avrPphB, which matches the R3 resistance gene, also caused a gene‐specific HR following expression in the plant after delivery by A. tumefaciens.
Functional expression of Kir 6.1/SUR1‐KATP channels in frog retinal Müller glial cells

The retinae and brains of larval and adult amphibians survive long‐lasting anoxia; this finding suggests the presence of functional KATP channels. We have previously shown with immunocytochemistry studies that retinal glial (Müller) cells in adult frogs express the KATP channel and receptor proteins, Kir6.1 and SUR1, while retinal neurons display Kir6.2 and SUR2A/B (Skatchkov et al., 2001a : NeuroReport 12:1437–1441; Eaton et al., in press : NeuroReport). Using both immunocytochemistry and electrophysiology, we demonstrate the expression of Kir6.1/SUR1 (KATP) channels in adult frog and tadpole Müller cells. Using conditions favoring the activation of KATP channels (i.e., ATP‐ and spermine‐free cytoplasm‐dialyzing solution containing gluconate) in Müller cells isolated from both adult frogs and tadpoles, we demonstrate the following. First, using the patch‐clamp technique in whole‐cell recordings, tolbutamide, a blocker of KATP channels, blocks nearly 100% of the transient and about 30% of the steady‐state inward currents and depolarizes the cell membrane by 5–12 mV. Second, inside‐out membrane patches display a single‐channel inward current induced by gluconate (40 mM) and blocked by ATP (200 μM) at the cytoplasmic side. The channels apparently show two sublevels (each of ∼27–32 pS) with a total of 85‐pS maximal conductance at −80 mV; the open probability follows a two‐exponential mechanism. Thus, functional KATP channels, composed of Kir6.1/SUR1, are present in frog Müller cells and contribute a significant part to the whole‐cell K+ inward currents in the absence of ATP. Other inwardly rectifying channels, such as Kir4.1 or Kir2.1, may mediate the remaining currents. KATP channels may help maintain glial cell functions during ATP deficiency. GLIA 38:256–267, 2002. © 2002 Wiley‐Liss, Inc.
Bone morphogenetic protein type I receptor inhibition induces cleft palate associated with micrognathia and cleft lower lip in mice.

BACKGROUND Gain-of- and loss-of-function studies have demonstrated that changes in bone morphogenetic protein (BMP) signaling during embryo development cause craniofacial malformations, including cleft palate. It remains uncertain whether BMP signaling could be targeted pharmacologically to affect craniofacial morphogenesis. METHODS Pregnant C57Bl/6J mice were treated with the BMP type I receptor inhibitor LDN-193189 at the dose of 3, 6, or 9 mg/kg twice a day by intraperitoneal injection from embryonic day 10.5 (E10.5) to E15.5. At E16.5, embryos were investigated by facial measurement analysis and histology to determine the optimal concentration for malformation. Subsequent embryonic phenotypes were analyzed in detail by histology, whole-mount skeletal staining, micro-computed tomography, and palatal organic culture. We further used immunohistochemistry to analyze protein expression of the BMP-mediated canonical and noncanonical signaling components. RESULTS The optimal concentration of LDN-193189 was determined to be 6 mg/kg. In utero, LDN-193189 exposures induced partial clefting of the anterior palate or complete cleft palate, which was attributed to a reduced cell proliferation rate in the secondary palate, and delayed palatal elevation caused by micrognathia. Analysis of signal transduction in palatal shelves at E12.5 and E13.5 identified a significant reduction of BMP/Smad signaling (p-Smad1/5/8) and unchanged BMP noncanonical signaling (p-p38, p-Erk1/2) after treatment with LDN-193189. CONCLUSION The results of this study indicate that LDN-193189 can be used to manipulate BMP signaling by selectively targeting the BMP/Smad signaling pathway to affect palatal morphogenesis and produce phenotypes mimicking those caused by genetic mutations. This work established a novel mouse model for teratogen-induced cleft palate. Birth Defects Research (Part A) 106:612-623, 2016. © 2016 Wiley Periodicals, Inc.