Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of MAP kinase by prostaglandin E2 and forskolin in rat renal mesangial cells.

Activation of the mitogen-activated protein (MAP) kinase pathway is believed to play a critical role in normal and pathophysiological proliferation of mesangial cells. Recent studies have shown that MAP kinase activation by growth factors in other cell types involves activation of the low-molecular-weight G protein Ras and the protooncogene serine kinase c-Raf-1. In this study, the role of this pathway in rat renal mesangial cells was assessed. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), as well as phorbol esters (PMA) rapidly activated MAP kinase three- to fourfold in these cells. PDGF and EGF, but not PMA, were able to activate c-Raf-1 and Ras activity. Stimulation of mesangial cells with the inflammatory mediator prostaglandin E2 (PGE2) or elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) by treatment with forskolin markedly blunted activation of MAP kinase induced by PDGF and EGF, but not by PMA. Consistent with this observation, PGE2 abolished growth factor-induced activation of c-Raf-1. However, Ras activation induced by growth factors was not affected by PGE2 and forskolin. These results suggest that MAP kinase activation can occur by at least two separate pathways in mesangial cells. Tyrosine kinase receptors activate MAP kinase through activation of Ras and Raf. This pathway can be blocked by PGE2 and elevation of cAMP, presumably by interfering with the ability of Ras to activate Raf. In addition, activation of protein kinase C by phorbol esters can activate MAP kinase in a Ras/Raf-independent manner. (ABSTRACT TRUNCATED AT 250 WORDS)
A New d,l-Endopeptidase Gene Product, YojL (Renamed CwlS), Plays a Role in Cell Separation with LytE and LytF in Bacillus subtilis

ABSTRACT A new peptidoglycan hydrolase, Bacillus subtilis YojL (cell wall-lytic enzyme associated with cell separation, renamed CwlS), exhibits high amino acid sequence similarity to LytE (CwlF) and LytF (CwlE), which are associated with cell separation. The N-terminal region of CwlS has four tandem repeat regions (LysM repeats) predicted to be a peptidoglycan-binding module. The C-terminal region exhibits high similarity to the cell wall hydrolase domains of LytE and LytF at their C-terminal ends. The C-terminal region of CwlS produced in Escherichia coli could hydrolyze the linkage of d-γ-glutamyl-meso-diaminopimelic acid in the cell wall of B. subtilis, suggesting that CwlS is a d,l-endopeptidase. β-Galactosidase fusion experiments and Northern hybridization analysis suggested that the cwlS gene is transcribed during the late vegetative and early stationary phases. A cwlS mutant exhibited a cell shape similar to that of the wild type; however, a lytE lytF cwlS triple mutant exhibited aggregated microfiber formation. Moreover, immunofluorescence microscopy showed that FLAG-tagged CwlS was localized at cell separation sites and cell poles during the late vegetative phase. The localization sites are similar to those of LytF and LytE, indicating that CwlS is involved in cell separation with LytF and LytE. These specific localizations may be dependent on the LysM repeats in their N-terminal domains. The roles of CwlS, LytF, and LytE in cell separation are discussed.
Ultrastructural Characterization of Gills in Juveniles of the Argentinian Silverside, Odontesthes bonariensis (Valenciennes, 1835) (Teleostei: Atheriniformes)

An ultrastructural study was performed on the gills of juvenile Argentinian silverside, Odontesthes bonariensis. The gills are composed of two sets of four holobranchs and, in turn, each holobranch consists of a gill arch and two rows of caudolaterally projecting branchial filaments. From the dorsal and ventral surfaces of each filament, branchial lamellae radiate out as foldings of the epithelial layer. Gill rakers are present on each of the gill arches, on the anteromedial side of the arch opposite to the filaments. Gill rakers, gill arches and branchial filaments are covered by a stratified epithelium, whereas branchial lamellae essentially consist of a thin epithelial envelope containing capillaries. In the stratified epithelium, mucous cells, rodlet cells, granular cells, pavement epithelial cells and mitochondria‐rich cells are identified. The thin epithelium that lines the lamellae comprises two cell types, outer and inner epithelial cells, and the capillary walls on the inside of the epithelial envelope are defined by pillar cells. The ultrastructure of all these cell types is described and our findings are discussed in light of the existing data on fish gill morphology. In the gills of juvenile Argentinian silverside is of particular interest the characteristics showed by mitochondria‐rich cells, such as their arrangement in clusters of 2–3 cells and their small and depressed surface in contact with the aquatic milieu, features which strongly resemble those of euryhaline species.
Specificity of stain distribution in electron micrographs of protein molecules contrasted with uranyl acetate

The mechanism of contrast enhancement of protein molecules by negative staining with uranyl acetate has been investigated by analysing electron micrographs of microcrystals of the human immunoglobulin Dob. Digitally filtered micrographs were compared systematically with idealized reference images which were constructed computationally, starting from knowledge of the primary sequence and three‐dimensional crystal structure of this IgG molecule. By separately modelling negative staining as bulk exclusion of heavy metals, and positive staining as the specific decoration of charged amino acid residues, and then combining these simulated images, we were able to assess quantitatively the amount of positive staining present in micrographs of ostensibly ‘negatively stained’ proteins. At a resolution of 2 nm, we find that the experimental images do indeed exhibit predominantly negative staining, the best matches being obtained by simulations which also include a minor contribution (10–40%) of positive staining. We have also compared two independent measures for the significant resolution present in images of periodic biological specimens: (i) the outermost visible orders of optical diffraction patterns, and (ii) the band‐limited resolutions of the idealized simulations when they most closely match the experimental images. These criteria observe close correspondence, thus vindicating the traditional practice of inferring resolution from the optical diffraction spectra of indirectly represented (stained) objects.
Purinergic neuromuscular transmission is absent in the colon of P2Y1 knocked out mice

Key points • Neural‐mediated relaxation occurs in the gastrointestinal tract. To accomplish this function, two neurotransmitters, ATP or a related purine and nitric oxide, are released by inhibitory motorneurons. • The type of purinergic receptor is still under debate but previous data using a classical pharmacological approach (receptor agonists and antagonists) suggested that P2Y1 receptors are responsible for purinergic neurotransmission in the gastrointestinal tract. • In the present study we used a genetically modified mouse in which P2Y1 receptors had been knocked out. • P2Y1‐deficient mice had functional nitrergic neurotransmission but purinergic neurotransmission was absent. • The present work confirms the hypothesis demonstrating that P2Y1 receptors mediate the purinergic component of the smooth muscle relaxation in the gastrointestinal tract.
The kinetics of CD154 (CD40L) expression in peripheral blood mononuclear cells of healthy subjects in liver allograft recipients and X‐linked hyper‐IgM syndrome

The costimulatory pathways play a key role in T cell activation during allograft rejection (AR). Inhibition of the T cell costimulatory molecule CD154 (CD40 ligand) has been effective in producing long‐term allograft survival in rodents and non‐human primates. The role of the CD40‐CD154 pathway in human orthotopic liver transplantation (OLT) has not been examined. Aim: To describe the patterns of CD154, CD69 and CD152 (CTLA4) expression in OLT recipients and to determine their temporal relationship to AR. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 15 OLT allograft recipients just prior to and for seven consecutive days postoperatively. Gene and protein expression of CD154, CD69 and CD154 were examined by reverse transcription‐polymerase chain reaction (RT‐PCR) and flow cytometry (FC), respectively. Results: FC failed to demonstrate an up‐regulation of CD154 and CD152 protein expression during the first postoperative week. Intracellular FC did not increase the sensitivity. There was an increased level of CD3+CD8+ T cells expressing CD69 at the time of rejection compared to that on day 0. RT‐PCR demonstrated a sporadic expression of CD154 and CD69 mRNA, with no correlation to episodes of acute cellular rejection. In vitro stimulation of PBMCs revealed an impaired up‐regulation of CD154 in patients receiving conventional immunosuppression compared to healthy controls. The assays were validated using positive and negative controls, including a family with X‐linked hyper‐IgM syndrome. Conclusion: We found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Immunosuppression resulted in impaired responses to ex vivo stimulation. Lymphocyte costimulatory pathways play a critical role in mediating acute allograft rejection. However, we found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Furthermore, stimulation in vitro resulted in less up‐regulation of CD154 than for healthy controls.
Evidence for the role of PO4 deficiency in antihypertensive action of a high-Ca diet.

Previous studies indicated a salutary effect of a high-Ca diet on high blood pressure (BP). The mechanism, however, is obscure. With balance and clearance techniques, the role of parathyroid hormone (PTH), volume contraction, hypercalcemia, and PO4 deficiency was evaluated in female spontaneous hypertensive rats (SHR). The antihypertensive effects of a high (4.3%) Ca diet in intact animals (groups I and II) could be reproduced in both 9- and 22-wk-old chronic stable parathyroidectomized (PTX) rats (groups III and IV), when compared with a low (0.22%) or normal (1.2%) CA diet. In both short (7 days) and long (12 wk) term exposure to the high-Ca diet, evidence for volume contraction could not be documented despite hypercalcemia sustained through the 12th wk (10.8 vs. 9.7 mg/100 ml, group I control, P less than 0.02). When produced by ip injections, chronic hypercalcemia of similar magnitudes as oral Ca supplements failed to reduce BP in either intact (group VI) or PTX (group IV) rats. Rats in group IV fed the high-Ca diet displayed marked hypophosphatemia (3.2 vs. 6.9 mg/100 ml), hypophosphaturia (0.15 vs. 15 mg/day), hypermagnesiuria (11 vs. 7.7 mg/day), and drastically reduced net intestinal PO4 absorption (13.3 +/- 7.5 vs. 66.8 +/- 7.5 mg/day) compared with rats fed 1.2% Ca diet. To test the PO4-deficiency hypothesis, additional SHR (group V) were fed either 1.2% Ca diet and injected ip with NaCl or fed 4.3% Ca diet, with half of these animals injected with neutral NaPO4 and half with NaCl. (ABSTRACT TRUNCATED AT 250 WORDS)
A unique covalent bond in basement membrane is a primordial innovation for tissue evolution

Significance The evolution of multicellular animals from single-celled ancestors was one of the most significant transitions of life on earth. The emergence of larger, more complex animals able to resist predation and colonize new environments was enabled, in part, by a collagen scaffold, which anchors cells together to form tissues and organs. Here, we show that a unique chemical bond, a link between sulfur and nitrogen atoms called a sulfilimine bond, arose over 500 Mya, binding this scaffold together and enabling tissues to withstand mechanical forces. Peroxidasin forms the bond by generating hypohalous acids as strong oxidants, a form of bleach, which normally function as antimicrobial agents. These understandings may lead to approaches for targeting tumors and treatment of other diseases. Basement membrane, a specialized ECM that underlies polarized epithelium of eumetazoans, provides signaling cues that regulate cell behavior and function in tissue genesis and homeostasis. A collagen IV scaffold, a major component, is essential for tissues and dysfunctional in several diseases. Studies of bovine and Drosophila tissues reveal that the scaffold is stabilized by sulfilimine chemical bonds (S = N) that covalently cross-link methionine and hydroxylysine residues at the interface of adjoining triple helical protomers. Peroxidasin, a heme peroxidase embedded in the basement membrane, produces hypohalous acid intermediates that oxidize methionine, forming the sulfilimine cross-link. We explored whether the sulfilimine cross-link is a fundamental requirement in the genesis and evolution of epithelial tissues by determining its occurrence and evolutionary origin in Eumetazoa and its essentiality in zebrafish development; 31 species, spanning 11 major phyla, were investigated for the occurrence of the sulfilimine cross-link by electrophoresis, MS, and multiple sequence alignment of de novo transcriptome and available genomic data for collagen IV and peroxidasin. The results show that the cross-link is conserved throughout Eumetazoa and arose at the divergence of Porifera and Cnidaria over 500 Mya. Also, peroxidasin, the enzyme that forms the bond, is evolutionarily conserved throughout Metazoa. Morpholino knockdown of peroxidasin in zebrafish revealed that the cross-link is essential for organogenesis. Collectively, our findings establish that the triad—a collagen IV scaffold with sulfilimine cross-links, peroxidasin, and hypohalous acids—is a primordial innovation of the ECM essential for organogenesis and tissue evolution.
Use of Fourier-transform infrared spectroscopy for the diagnosis of failure of transfer of passive immunity and measurement of immunoglobulin concentrations in horses.

BACKGROUND The economic, accurate, and rapid screening of foals for failure of transfer of passive immunity (FPT) is essential to ensure timely intervention. HYPOTHESIS Infrared (IR) spectroscopy of foal sera and pattern recognition may be used to diagnose FPT and quantify serum IgG. SAMPLES Sera from 194 foals (24-72 hours) with serum immunoglobulin G (IgG) concentrations determined previously by radial immunodiffusion assay (RID) were used. METHODS IR spectra were recorded for the serum samples, and the data were randomly divided into training and independent test sets, each containing both FPT-positive (IgG <400 mg/dL) and non-FPT samples. A genetic optimal region selection algorithm and linear discriminant analysis were used to partition the training spectra, and the resulting classifier was then validated by comparing the IR-predicted FPT status for each of the test samples to that provided by the RID IgG assay. A quantitative IR-based assay for IgG was developed using partial least squares (PLS) and validated by testing its ability to predict IgG concentrations. RESULTS Specificity, sensitivity, and accuracy for the combined data were 92.5, 96.8, and 95.9%, respectively. Corresponding positive (88.1%) and negative predictive (98.0%) values determined a success rate of 95-97% as compared to RID-based IgG concentrations. The IR-based quantitative assay yielded correlation coefficients for IR spectroscopy versus RID-based IgG concentrations of 0.90 and 0.86 for the training and test sets, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE The overall performance of the IR-based test was similar to that of the colorimetric assay and was superior and more economic than other available tests.
Zoledronate Is a Potent Inhibitor of Myeloma Cell Growth and Secretion of IL‐6 and MMP‐1 by the Tumoral Environment

Bisphosphonates have recently been introduced in the therapeutic armamentarium for the long‐term treatment of patients with multiple myeloma (MM). These pyrophosphate analogs not only reduce the occurrence of skeletal‐related events but also provide patients with a clinical benefit and improve the survival of some of them. We investigated the effects of two bisphosphonates, pamidronate and zoledronate, on both myeloma cells and bone marrow stromal cells (BMSCs). We show here that both bisphosphonates induce both myeloma cell and BMSC apoptosis. Furthermore, at lower concentrations, they induce a significant inhibition (40% and 60%, respectively) of the constitutive production of interleukin‐6 (IL‐6) by BMSCs. We have recently shown that BMSCs produce MMP‐1, the major metalloproteinase involved in the initiation of bone resorption, production up‐regulated by IL‐1β. Here, we demonstrate that zoledronate significantly inhibits MMP‐1 production by BMSCs stimulated with IL‐1β more efficiently than pamidronate. However, zoledronate and to a lesser extent pamidronate are responsible for an up‐regulation of MMP‐2 secretion by BMSCs. MMP‐2 is involved both in bone resorption and in the metastatic process. In conclusion, the apoptosis of myeloma cells and BMSCs and the inhibition of both IL‐6 and MMP‐1 production induced by bisphosphonates, mainly zoledronate, could have antitumoral effects in patients with MM. However, the up‐regulation of MMP‐2 secretion observed in vitro suggests a putative risk of tumor cell dissemination in vivo when using these new potent bisphosphonates. This potentially deleterious effect could be abolished by combining bisphosphonates with metalloproteinase inhibitors.
Single-chip 16-ch variable attenuator multiplexer (V-AWG) with stacked PD-array using integrated micro-mirrors on PLC

We have developed a variable optical attenuator AWG multiplexer (V-AWG) integrated on a single planar light-wave circuit (PLC) chip. We successfully employed a stacked structure using micro-mirrors formed on the PLC to integrate monitor photodiodes (PDs) and achieved a low transmission loss of 5.5 dB and a high PD responsivity of better than 0.9 A/W
When Google Translate is better than Some Human Colleagues, those People are no longer Colleagues

We analyse posts on social media (Facebook, LinkedIn, and Twitter) as a means to understand how translators feel about machine translation (MT). A quantitative analysis of more than 13,000 tweets shows that negative perceptions outweigh positive ones by a ratio of 3:1 overall, and 5:1 in tweets relating MT to human translation. Our study indicates a disconnect between translation and research communities, and we outline three suggestions to bridge this gap: (i) identifying and reporting patterns rather than isolated errors, (ii) participating in evaluation campaigns, and (iii) engaging in cross-disciplinary discourse. Rather than pointing out each other's deficiencies, we call for computer scientists, translation scholars, and professional translators to advance translation technology by acting in concert.
Regulation of human osteoclast development by dendritic cell‐specific transmembrane protein (DC‐STAMP)

Osteoclasts (OC) are bone‐resorbing, multinucleated cells that are generated via fusion of OC precursors (OCP). The frequency of OCP is elevated in patients with erosive inflammatory arthritis and metabolic bone diseases. Although many cytokines and cell surface receptors are known to participate in osteoclastogenesis, the molecular mechanisms underlying the regulation of this cellular transformation are poorly understood. Herein, we focused our studies on the dendritic cell‐specific transmembrane protein (DC‐STAMP), a seven‐pass transmembrane receptor‐like protein known to be essential for cell‐to‐cell fusion during osteoclastogenesis. We identified an immunoreceptor tyrosine‐based inhibitory motif (ITIM) in the cytoplasmic tail of DC‐STAMP, and developed an anti‐DC‐STAMP monoclonal antibody 1A2 that detected DC‐STAMP expression on human tumor giant cells, blocked OC formation in vitro, and distinguished four patterns of human PBMC with a positive correlation to OC potential. In freshly isolated monocytes, DC‐STAMPhigh cells produced a higher number of OC in culture than DC‐STAMPlow cells and the surface expression of DC‐STAMP gradually declined during osteoclastogenesis. Importantly, we showed that DC‐STAMP is phosphorylated on its tyrosine residues and physically interacts with SHP‐1 and CD16, an SH2‐domain‐containing tyrosine phosphatase and an ITAM‐associated protein, respectively. Taken together, these data show that DC‐STAMP is a potential OCP biomarker in inflammatory arthritis. Moreover, in addition to its effect on cell fusion, DC‐STAMP dynamically regulates cell signaling during osteoclastogenesis. © 2012 American Society for Bone and Mineral Research
Parental and peer attachment and identity development in adolescence.

The main aim of this study was to test the situational hypothesis of parent-peer conflict and the parent-peer linkages hypothesis with regard to parental and peer attachment and identity. The situational hypothesis predicts that parental attachment will be associated with school identity and peer attachment with relational identity. The parent-peer linkages hypothesis suggests that parental attachment influences peer attachment and through peer attachment school and relational identity. Data from a survey of 148 middle adolescents from various ethnic groups were used. The findings offer strong support for the situational hypothesis, and only limited evidence in favor of the parent-peer linkages hypothesis. In addition, systematic links were found between parent and peer trust and commitment, and parent and peer communication and exploration. Adolescents from ethnic minority groups reported higher levels of school commitment and exploration compared with indigenous Dutch adolescents.
Change Processes Towards Lean Production: The Role of the Management Accounting System

Explores the role of the management accounting system in the process of adopting a complex manufacturing strategy, lean production. Finds, in a longitudinal field study, using the clinical methodology, that in order to change the management accounting system to support the adoption of lean production, traditional performance measures have to reach a certain threshold. An important way to create impetus for this change is to raise the level of the unit of analysis in the management accounting system, both horizontally and vertically. Finally, the management accounting system affects the process in three concurrent ways: technically, through its design; formally, through its role in the organization; and cognitively, through the way in which actors think about and use the management accounting system. Proposes that in order for the system to be congruent with lean production principles, all three of these perspectives need to be changed.