gebhart/patrepeval huggingface dataset:
MicroRNA expression profiling in patients with lamin A/C‐associated muscular dystrophy (2011)

Mutations in the lamin A/C gene (LMNA) cause several disorders referred to as laminopathies, which include premature aging syndromes, lipodystrophy, and striated muscle disorders. There is evidence that lamin A/C plays a role in gene expression. MicroRNAs (miRNAs) are short noncoding RNAs regulating mRNAs involved in various biological processes, including the pathophysiology of striated muscles. Here, we profiled the expression of the miRNA transcriptome in skeletal muscle from patients with LMNA-related muscular dystrophy. Results show that control and patient groups can be distinguished based on their miRNA expression profile. Sixteen miRNAs are significantly dysregulated in patients compared with controls. Pathway enrichment analysis in the predicted targets of these miRNAs revealed pathways involved in muscle repair, such as MAPK, transforming growth factor-β, and Wnt signaling. Interestingly, 9 of these miRNAs (hsa-miR-100, -127-3p, -148a, -136*, -192, -335, -376c, -489, and -502-3p) are highly expressed in fetal muscle, suggesting that the fetal miRNA gene program mediates a regenerative process. Overexpression of these miRNAs in C2C12 mouse myoblasts revealed that 3 of them (miR-100, -192, and -335) participate in muscle proliferation and differentiation. We identified target genes that likely mediate this effect, which include the calcineurin gene PPP3CA. Our findings are the first to demonstrate that miRNA expression is affected in laminopathies.
Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance (2003)

Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL-6 and a tendency toward a decrease in circulating TNF-alpha, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.
Functional analysis of amino acid sequences in connexin43 involved in intercellular communication through gap junctions (1995)

Gap junctions allow direct communication between cells without recourse to the extracellular space and have been widely implicated as important mediators of cell-cell signalling. They are constructed from the connexin proteins, which form a large family, and individual connexins show complex spatial and temporal variations in their expression patterns. Understanding how this variation contributes to the control of intercellular signalling, both in the adult and during embryonic development, is an important problem that would be aided by reagents that interfere with gap junctional communication through specific connexins. We have begun to address this issue by raising antibodies to peptides derived from connexin43 and connexin32. Connexin43 peptides were located in the amino terminus, cytoplasmic loop and carboxytail. Connexin32 peptides came from the cytoplasmic loop and the first extracellular loop. Immunoblotting and immunostaining properties of purified IgGs were characterized on mouse heart, liver and the 8- to 16-cell mouse embryo. Effects on transfer through gap junctions were assessed in the fully compacted 8-cell mouse embryo by co-injection with Lucifer Yellow or Cascade Blue. Embryos were maintained in culture to assess the developmental consequences of injection. Peptide competition was used to confirm the specificity of immunostaining and inhibition of dye transfer. All connexin specific antibodies recognized their parent connexin on immunoblots and showed no 43/32 cross-reactivity. The connexin32 extracellular loop antibody recognized both connexin 32 and 43 on immunoblots, as predicted by the amino acid sequence homology in this region, but did not immunostain intact gap junctions. Connexin specific antibodies that immuno-stained showed the predicted connexin specificity. Antibodies to either connexin43 amino acids (AA) 1-16 (amino terminus) or AA 101-112 (cytoplasmic loop) neither immunostained nor prevented functional communication through 8-cell embryo gap junctions. Antibodies to AA 123-136 and AA 131-142 in the cytoplasmic loop immunostained heart and 8-cell embryo gap junctions and blocked transfer through them with high efficiency. Fab' fragments were equally effective. Peptide competition showed that both antibodies contained epitopes within AA 131-136 of connexin43. Antibodies against AA 313-324 in the carboxytail immunostained heart and the 8-cell embryo and, as IgGs, prevented dye transfer. Fab' fragments were ineffective. All connexin43 antibodies that blocked gap junctional communication between cells of the 8-cell mouse embryo induced non-communicating cells subsequently to withdraw from compaction.(ABSTRACT TRUNCATED AT 400 WORDS)
Ruthenium-Catalyzed Olefin Metathesis:  A Quantum Molecular Dynamics Study (1998)

Chemical reactions are usually performed in solvents. The course of the reaction varies with solvent, temperature, etc. Solvent molecules are usually not taken into account in quantum simulations due to the rising computational effort. However, their ability to transfer heat (kinetic energy) to and from the reacting species can be incorporated in the simulations. We demonstrate that different chemistry follows by varying absolute simulation temperature and the range for temperature fluctuations in Car−Parrinello dynamics simulations applied to ruthenium catalyzed metathesis reactions. The bisphosphine Cl2(PH3)2RuCH2 complex and its monophosphine equivalent were taken as model compounds for the Grubbs catalyst. Depending on temperature conditions set in the molecular dynamics simulations, the interaction of these ruthenium−phosphine catalysts with ethylene revealed insertion, the formation of a metallacyclobutane, or a pure metathesis reaction. It was found that selective bond vibrational activation is required to induce metathesis activity. A comparison with recent experimental results from Grubbs et al. (J. Am. Chem. Soc. 1997, 119, 3887) shows that the results of our simulations reveal and lend support to the mechanism proposed by Grubbs. These include, in the order of appearance in the reaction scheme, the relative easiness of Cl−Ru−Cl cis−trans configurational exchange, carbene rotation and the loss of one phosphine, formation of a metallacyclobutane intermediate, and finally completion of the metathesis reaction. The presence of a small fraction of the monophosphine complex (the reaction proposed in Scheme 1, which was adopted from Grubbs et al.) is confirmed by the present simulations. Starting from the observation that selective bond excitation is necessary to exhibit reactivity, the higher activity of the monophosphine system compared to bisphosphine complexes reported by Grubbs et al. can be understood. We stress that we have also found that the bisphosphine is active, which also agrees with the experimental data. Finally, the fact that ruthenium−carbene complexes based on sterically crowded phosphines give higher metathesis activity, can be rationalized by their intrinsically more labile Ru−P bonds as indicated by longer Ru−P bond lengths.
Physical and Chemical Aspects of Saliva as Indicators of Risk for Dental Caries in Humans (2001)

The etiology and pathogenesis of dental caries are known to be multifactorial, but the interplay between intrinsic and extrinsic factors is still not fully understood. As in other host/parasite interactions, there appear to be marked variations in individual susceptibility to the disease. It therefore is likely that intrinsic host factors play a key role in modulating the initiation and progression of caries. The objective of this systematic review was to evaluate critically the evidence supporting the role and effects of saliva in caries pathogenesis. The full-length evidence report, including evidence tables, and the structured abstract presented at the NIH/NIDCR Consensus Development Conference on the Diagnosis and Management of Dental Caries Throughout Life, March 26-28. 2001, can be accessed at the web site http://www.nidcr.nih.gov. The present abridged report is a summary of the main findings from our evidence-based review.
Imaging Odor-Induced Calcium Transients in Single Olfactory Cilia: Specificity of Activation and Role in Transduction (1998)

The possibility that odor stimuli trigger distinct Ca2+ elevations within the cilia of vertebrate olfactory receptor neurons (ORNs) is a widely proposed concept. However, because of the small size of the olfactory cilia, the existence and properties of such Ca2+ elevations and their role in odor transduction are still unknown. We investigate odor-induced Ca2+ changes in individual olfactory cilia from salamander using the Ca2+ indicator dye fluo-3 in combination with laser scanning confocal microscopy. Single brief applications of odor ligand produce highly localized Ca2+ elevations in individual cilia lasting for several seconds. These Ca2+ signals originate in the cilia and depend entirely on Ca2+ entry through ciliary cyclic nucleotide-gated ion channels. The odor specificity of the Ca2+ rises implies a receptor-operated mechanism underlying odor detection. Each of the cilia on a receptor neuron functions as an independent biochemical compartment that can detect odorants and produce a Ca2+ transient with remarkably uniform properties in terms of kinetics and odor specificity. The rate of recovery of the odor-induced Ca2+ transients matches recovery from a short-term form of odor adaptation. Application of the membrane-permeant intracellular Ca2+ chelator BAPTA AM eliminates this odor adaptation. The results indicate that an olfactory cilium serves as a basic functional unit at the input level of the olfactory system, controlling both the specificity and sensitivity of odor detection.
Continuous and Discontinuous Semiconductor-Metal Transition in Samarium Monochalcogenides Under Pressure (1970)

Resistivity and lattice-constant measurements under high pressure on SmS show that a $4f\ensuremath{\rightarrow}5d$ electronic transition in SmS occurs discontinuously at 6.5 kbar at room temperature, whereas such a transition takes place continuously over a broad pressure range in SmTe and SmSe. The pressure-induced semiconductor-to-metal transition in the Sm chalcogenides and their pressure-volume relationship are consistent with the conversion of ${\mathrm{Sm}}^{2+}$ to ${\mathrm{Sm}}^{3+}$. Optical-absorption measurements in these materials correlate well with the resistivity data under pressure. The semiconductor-to-metal transition in Sm chalcogenides appears to fit the model recently proposed by Falicov and Kimball for a system with a localized state and a conduction band.
Effects of Neighboring Glycans on Antibody–Carbohydrate Interaction (2011)

Who can? Glycan! Heterogeneous glycan microarrays were prepared for the study of antibody binding specificity and affinity. It was found that heterogeneous glycans provide better binding affinity compared to their individual components (see picture), thereby suggesting a new strategy for carbohydrate-based vaccine design. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A robust silicon photonic platform for multiparameter biological analysis (2009)

Silicon photonic technology has incredible potential to transform multiplexed bioanalysis on account of the scalability of device fabrication, which maps favorably to a myriad of medical diagnostic applications. The optical properties of CMOS-fabricated microring resonators are incredibly responsive to changes in the local dielectric environment accompanying a biological binding event near the ring surface. Arrays of high-Q microrings were designed to be individually addressable both in surface derivitization, using well-established microarraying technologies, and in optical evaluation. The optical response of each ring can be determined in near real time allowing multiple biomolecular interactions to be simultaneously monitored. We describe a stable and robust measurement platform that allows sensitive visualization of small molecule surface chemical derivitization as well as monitoring of biological interactions, including the detection of proteins and nucleic acids. We also present recent results demonstrating multiplexed measurement of cancer markers. These demonstrations establish a pathway to higher level multiparameter analysis from real-world patient samples; a development that will enable individualized disease diagnostics and personalized medicine.
On EXIT-chart analysis of coherent and noncoherent space-time codes (2005)

We propose a "turbo" coding scheme for the multiple-input-multiple-output (MIMO) Rayleigh fading channel consisting of the serially concatenation of outer channel codes and different coherent as well as noncoherent space-time codes as the inner code. At the receiver, we apply iterative space-time detection and decoding. We analyze the impact of different mapping strategies on the information transfer of the soft-input-soft-output (SISO) space-time detector for the case of orthogonal space-time codes (OSTBC) and derive some criteria for the optimum mapping strategy. We show that additional performance gains can be obtained by different mapping strategies. Furthermore, we use extrinsic information transfer characteristics (EXIT-charts) in order to predict the performance and the behaviour of the system.
Maternal Recognition of Pregnancy1 (1996)

Maternal recognition of pregnancy reflects the various ways in which the mother responds to the presence of a conceptus within her reproductive tract. A part of the biochemical information she senses may be irrelevant to pregnancy outcome, but some reflects the attempts by the conceptus to gain some measure of control over corpus luteum function, uterine blood supply, the mother's immune system, and other aspects of maternal physiology. Most probably as a result of ongoing genetic conflict between the mother and the conceptus, a bewildering range of placental structures and trophoblast signaling mechanisms are encountered in eutherian mammals despite the fact that the uterus and conceptus share a common interest, which is the successful outcome of the pregnancy. Here we review some of the ways that such mammals maintain luteal function in early pregnancy and briefly discuss the related topics of embryonic loss and maternal monitoring of conceptus fitness. We next address the view that the conceptus is an intruder, recognized as foreign by the mother, that likely survives by using strategies analogous to those employed by successful parasites. In this context, we describe the pregnancy-associated glycoproteins, multiple isoforms of which are released at the trophoblast-endometrial interface during pregnancy of ungulate species. These molecules, which are structurally related to pepsin, are proposed to bind and sequester antigenic peptides, thereby serving an immunoprotective role.
Sequences of E. coli O157:H7 detected by a PCR-acoustic wave sensor combination (2001)

In this paper, we report on the amplification by polymerase chain reaction (PCR) of a 509 base sequence unique to E. coli O157:H7. Immobilization of a probe for the bacterium on an acoustic wave sensor by the biotin-neutravidin interaction was employed to detect the on-line hybridization of the sequence with the sample obtained from PCR. The limit of detection was found to be 10(-8) M, which suggests that the method may be useful for detecting the organism in food, water and clinical samples. Finally, this approach lays the groundwork for incorporating the method into an integrated system for rapid PCR-based DNA analysis.
Lack of analgesic effect of systemically administered morphine or pethidine on labour pain (1996)

It is concluded that labour pain is not sensitive to systemically administered morphine or pethidine. These drugs only cause heavy sedation. It therefore seems unethical and medically incorrect to meet parturients' requests for pain relief by giving them sedation. Considering the well documented negative effects on newborn infants we also believe systemic pethidine should be avoided in labour.
Artocarpol A stimulation of superoxide anion generation in neutrophils involved the activation of PLC, PKC and p38 mitogen‐activated PK signaling pathways (2005)

1 Artocarpol A (ART), a natural phenolic compound isolated from Artocarpus rigida, stimulated a slow onset and long-lasting superoxide anion generation in rat neutrophils, whereas only slightly activated the NADPH oxidase in a cell-free system. 2 Pretreatment of neutrophils with pertussis toxin (1 microg ml(-1)), 50 microM 2'-amino-3'-methoxyflavone (PD 98059), or 1 microM 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126) had no effect on ART-stimulated superoxide anion generation. ART (30 microM) did not induce extracellular signal-regulated kinase (ERK) phosphorylation. 3 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB 203580) markedly attenuated the ART-stimulated superoxide anion generation (IC50 value of 4.3+/-0.3 microM). Moreover, ART induced p38 mitogen-activated PK (MAPK) phosphorylation and activation. 4 The superoxide anion generation in response to ART was also substantially inhibited in a Ca2+-free medium, and by pretreatment with 1 microM 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U-73122) and 100 microM 2-aminoethyldiphenyl borate (2-APB). ART (30 microM) stimulated the [Ca2+]i elevation in the presence or absence of external Ca2+, and also increased the D-myo-inositol 1,4,5-trisphosphate formation. 5 2-[1-(3-Dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide (GF 109203X) greatly inhibited the ART-stimulated superoxide anion generation (IC50 value of 7.8+/-1.0 nM). ART increased the recruitment of PKC-alpha, -betaI, and -betaII to the plasma membrane of neutrophils, and stimulated Ca2+-dependent PKC activation in the cytosol preparation. 6 ART induced the phosphorylation of p47phox, which was attenuated by GF 109203X. Moreover, ART evoked the membrane association of p47(phox), which was inhibited by GF 109203X and SB 203580. 7 These results indicate that the ART stimulation of superoxide anion generation involved the activation of p38 MAPK, PLC/Ca2+, and PKC signaling pathways in rat neutrophils.
A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors (2015)

The generation of a targeting agent that strictly binds to IL13Rα2 will significantly expand the therapeutic potential for the treatment of IL13Rα2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13Rα2 monoclonal antibody and tested its binding properties. Furthermore, to demonstrate the potential therapeutic applicability of scFv47, we engineered an adenovirus by incorporating scFv47 as the targeting moiety in the viral fiber and characterized its properties in vitro and in vivo. The scFv47 binds to human recombinant IL13Rα2, but not to IL13Rα1 with a high affinity of 0.9 · 10(-9) M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13Rα2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13Rα2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13Rα2-expressing glioma and other malignancies.
Progressive hypertrophy and heart failure in β 1 -adrenergic receptor transgenic mice (1999)

Stimulation of cardiac beta1-adrenergic receptors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac beta-adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of beta1-adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed marked myocyte hypertrophy (3.5-fold increase in myocyte area). This increase was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by approximately 50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of approximately 20%. We conclude that overexpression of beta1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased beta1-adrenergic receptor signalling is ultimately detrimental.
Metabolism of Citrate and Other Carboxylic Acids in Erythrocytes As a Function of Oxygen Saturation and Refrigerated Storage (2017)

State-of-the-art proteomics technologies have recently helped to elucidate the unanticipated complexity of red blood cell metabolism. One recent example is citrate metabolism, which is catalyzed by cytosolic isoforms of Krebs cycle enzymes that are present and active in mature erythrocytes and was determined using quantitative metabolic flux analysis. In previous studies, we reported significant increases in glycolytic fluxes in red blood cells exposed to hypoxia <i>in vitro</i> or <i>in vivo</i>, an observation relevant to transfusion medicine owing to the potential benefits associated with hypoxic storage of packed red blood cells. Here, using a combination of steady state and quantitative tracing metabolomics experiments with <sup>13</sup>C<sub>1,2,3</sub>-glucose, <sup>13</sup>C<sub>6</sub>-citrate, <sup>13</sup>C<sub>5</sub><sup>15</sup>N<sub>2</sub>-glutamine, and <sup>13</sup>C<sub>1</sub>-aspartate <i>via</i> ultra-high performance liquid chromatography coupled on line with mass spectrometry, we observed that hypoxia <i>in vivo</i> and <i>in vitro</i> promotes consumption of citrate and other carboxylates. These metabolic reactions are theoretically explained by the activity of cytosolic malate dehydrogenase 1 and isocitrate dehydrogenase 1 (abundantly represented in the red blood cell proteome), though moonlighting functions of additional enzymes cannot be ruled out. These observations enhance understanding of red blood cell metabolic responses to hypoxia, which could be relevant to understand systemic physiological and pathological responses to high altitude, ischemia, hemorrhage, sepsis, pulmonary hypertension, or hemoglobinopathies. Results from this study will also inform the design and testing of novel additive solutions that optimize red blood cell storage under oxygen-controlled conditions.