gebhart/patrepeval huggingface dataset:
Age‐associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging (2005)

Mitochondrial dysfunction and the accumulation of oxidative damage to macromolecules are believed to play key roles in the aging process. Characterization of age-related changes to cardiac mitochondria has been complicated by the fact that two distinct populations of mitochondria exist in the myocardium: subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). We investigated whether differences in hydrogen peroxide production (H2O2) and oxidative stress existed between cardiac SSM and IFM isolated from young (6 mo) and old (24 mo) male Fischer-344 rats. There was a significant increase in oxidative stress levels (4-hydroxy-2-nonenal-modified proteins, protein carbonyls, and malondialdehyde) in IFM with age. In contrast, only protein carbonyls were elevated in SSM with age. Significant age-related increases in MnSOD, GPX, and CAT activities were detected in IFM, while in SSM, MnSOD, and GPX activities increased with age and CAT activity declined. These increases in antioxidant enzyme activity likely occurred in response to increased mitochondrial production of superoxide and hydrogen peroxide. Indeed, SSM produced more H2O2 with age, while the increase in IFM was not significant, but this may be due to the higher antioxidant enzyme activity observed in IFM compared with SSM. Finally, reduced glutathione levels were significantly lower in IFM compared with SSM in both young and old rats, while glutathione reductase activity was not different with age or mitochondrial subpopulations, indicating increased consumption of glutathione. The accumulation of oxidant-induced damage in IFM may be a major contributing factor to the age-related alterations in myocardial function. Our results emphasize the importance of studying both mitochondrial populations when attempting to elucidate the contribution of mitochondrial dysfunction to myocardial aging.
Videomicroscopic Comparison of Bull Sperm and Leukocyte Chromosome Areas as Related to Gender (1990)

Chromosomal areas from metaphase spreads of male bovine leukocytes were digitized and sex chromosomes identified using videomicroscopy. Autosomal areas were ranked in descending order within a cell and assigned to two categories based on alternating rank. X and Y chromosome areas were assigned to respective categories. Areas were divided by 4 to make their sum equivalent to sperm DNA content. Data were analyzed before and after inclusion of sex chromosomal areas. Before X and Y inclusion, rank contributed to difference in chromosomal areas. Rank by category interaction and category effects did not contribute to area variation. After X and Y inclusion, area variation was due to rank by category interaction, rank, and category. Differences between sums of chromosomal areas across categories was 3.57%. Head areas of morphologically normal sperm with intact acrosomes were digitized using the same optics as chromosomal areas. Sum of corrected chromosomal areas per category was used in discriminant analysis to assign sperm head areas to two categories with .5 prior probabilities. Assignment resulted in 1037 sperm in one category and 1177 in the other. Difference between largest sperm head area classes across categories was 3.2%. Discrimination of sperm head areas, based on sum of chromosomal area and measured with computerized videomicroscopy, may be used to evaluate sex of bovine spermatozoa.
The Bacterial Glycocalyx in Nature and Disease (1981)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Adenovirus Vector-Induced Immune Responses in Nonhuman Primates: Responses to Prime Boost Regimens (2009)

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.
The Conformation of Adenosine Diphosphoribose and 8-Bromoadenosine Diphosphoribose when Bound to Liver Alcohol Dehydrogenase (1975)

8-Bromo-adenosine diphosphoribose (br8 ADP-Rib) and nicotinamide 8-bromoadenine dinucleotide (Nbr8AD+) which are analogues of the coenzyme NAD+, were prepared and their liver alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in hydrogen transport and br8ADP-Rib is a coenzyme competitive inhibitor for the enzymes liver alcohol dehydrogenase and yeast alcohol dehydrogenase. X-ray data were obtained for the complex between liver alcohol dehydrogenase and br8ADP-Rib to 0.45 nm resolution and for the liver alcohol dehydrogenase-adenosine diphosphoribose complex to 0.29-nm resolution. The conformations of these analogues were determined from the X-ray data. It was found that ADP-Rib had a conformation very similar to the corresponding part of NAD+, when NAD+ is bound to lactate and malate dehydrogenase. br8ADP-Rib had the same anti conformation of the adenine ring with respect to the ribose as ADP-Rib and NAD+, in contrast to the syn conformation found in 8-bromo-adenosine. The overcrowding at the 8-position is relieved in br8ADP-Rib by having the ribose in the 2' endo condormation instead of the usual 3' endo as in ADP-Rib and NAD+.
A Solution To The Inverse Problem: A Method For Determining The Driving Currents For Focused Stimulation (2005)

ABsmAcT Focused stimulation of distinct neural populations is desired for accurate reproduction of sound by a cochlear prosthesis. Varying the magnitude and alternating the phase of the input currents to a multielectrode array should focus stimulating waveforms [l]. A method is needed which will determine the complex current values required to achieve distinct peak responses. The least squares approach has been implemented to solve this inverse problem. The method has been validated with theoretical data. The solution and the results are described.
Intralesional Immunotherapy with Candida Antigen for the Treatment of Molluscum Contagiosum in Children (2011)

Intralesional injection of Candida and other antigens is an established and useful therapy for warts; a cutaneous immune response can induce improvement and or clearance of warts, often with response in anatomically distinct lesions other than those injected. Molluscum contagiosum virus is a common cutaneous infection seen primarily in pediatric dermatology clinics. Treatment is often unsatisfactory, painful, and time consuming. A retrospective chart review was conducted to examine the efficacy of intralesional injection of Candida antigen into a maximum of three individual molluscum lesions. Twenty-nine patients were treated with this therapy; 55% had complete resolution. In addition, 37.9% experienced partial resolution, yielding an overall response rate of 93%. Only two patients failed to respond (6.9%). In addition, only four patients reported a single adverse effect of pain with injection. No other adverse effects were reported or noted clinically. Scarring was absent. No recurrences were reported at the time of publication. This report establishes the efficacy of intralesional injection of Candida for molluscum contagiosum.
Immunocytochemical localization of the N‐acetyl‐aspartyl‐glutamate (NAAG) hydrolyzing enzyme N‐acetylated α‐linked acidic dipeptidase (NAALADase) (1992)

N-acetylated alpha-linked acidic dipeptidase (NAALADase) is a membrane bound enzyme that cleaves glutamate from the endogenous neuropeptide N-acetyl-aspartyl-glutamate (NAAG). We report the immunocytochemical localization of NAALADase in rat brain and kidney by using specific anti-NAALADase antiserum. NAALADase-immunoreactivity (NAALADase-IR) was widely distributed, abundant in neuropil, absent from neuronal cytoplasm, and displayed regional heterogeneity. Staining was selectively enriched in several structures previously reported to contain NAAG-immunoreactivity (NAAG-IR) including the amygdala, caudate-putamen, central gray, dorsal raphe, globus pallidus, hippocampus, hypothalamus, locus coerulus, medial and lateral geniculate, olfactory bulb, periaqueductal gray, solitary nucleus, spinal trigeminal nucleus, substantia nigra, superior colliculus, and thalamus. Staining within these structures was enriched in neuropil; no intracellular staining was detected, even after colchicine treatment. In addition, NAALADase-IR was observed in some NAAG-containing fiber tracts including the corpus callosum, fornix, habenular commissure, solitary tract, stria medularis, and stria terminalis. The co-localization of NAALADase-IR and NAAG-IR support the hypothesis that NAALADase is responsible for the catabolism of NAAG in vivo. NAALADase-IR was also detected in brain regions that, to date, have not revealed NAAG-IR, including the bed nucleus of the stria terminalis and the median eminence. In addition, NAALADase-IR was detected in the rat kidney cortex, specifically in the brush border of the proximal convoluted tubules. The observation that NAALADase-IR was more widespread than NAAG-IR suggests that NAALADase may also be involved in the catabolism of other structurally related neural and renal peptides.
Propionate as a health-promoting microbial metabolite in the human gut (2011)

Propionate is a major microbial fermentation metabolite in the human gut with putative health effects that extend beyond the gut epithelium. Propionate is thought to lower lipogenesis, serum cholesterol levels, and carcinogenesis in other tissues. Steering microbial propionate production through diet could therefore be a potent strategy to increase health effects from microbial carbohydrate fermentation. The present review first discusses the two main propionate-production pathways and provides an extended gene-based list of microorganisms with the potential to produce propionate. Second, it evaluates the promising potential of arabinoxylan, polydextrose, and L-rhamnose to act as substrates to increase microbial propionate. Third, given the complexity of the gut microbiota, propionate production is approached from a microbial-ecological perspective that includes interaction processes such as cross-feeding mechanisms. Finally, it introduces the development of functional gene-based analytical tools to detect and characterize propionate-producing microorganisms in a complex community. The information in this review may be helpful for designing functional food strategies that aim to promote propionate-associated health benefits.
Dimerization of an intermediate during the sodium in liquid ammonia reduction of l-thiazolidine-4-carboxylic acid (1967)

Reduction with sodium in liquid ammonia of l-thiazolidine-4-carboxylic acid (II) leads, depending on the reaction procedure followed, to N-methyl-l-cysteine (I) or a mixture of N-methyl-l-cysteine (I) (30%) and a dimer (50%), the structure of which is shown to be VI. Contrary to what has been expressed in the literature, the reaction of 1,2-dichloroethane with cysteine (III) at a pH of 8–10 does not lead to compound VI but to compound VIII.
Coupling of Biocomputing Systems with Electronic Chips: Electronic Interface for Transduction of Biochemical Information (2009)

Electronic transduction of biochemical signals processed by the enzyme-based OR-Reset/AND-Reset logic systems was achieved using field-effect Si chips. The developed enzyme logic systems produced pH changes as the result of biochemical reactions activated by different combinations of the chemical input signals. Signal transduction was performed by pH-responding gold nanoparticles associated with the chip interface. The transformation of the nanoparticle shells between the dissociated (negatively charged) and protonated (neutral) states was determined using capacitance−voltage or impedance spectroscopy measurements, resulting in an electronic signal that reflects the state of the system corresponding to the logic output produced by the enzymes. The developed systems are the first examples of enzyme-based biocomputing systems interfaced with ordinary Si-based electronics.
Intron splicing: a conserved internal signal in introns of animal pre-mRNAs. (1984)

Splicing of introns of yeast pre-mRNAs requires an internal conserved sequence T-A-C-T-A-A-C that is located 20-55 nucleotides from the 3' intron boundary. Sequences differing only in certain positions from this yeast signal have now been identified in the corresponding internal region of pre-mRNA introns of a variety of animal genes. A computer program that searches for homologues to a consensus structure and calculates the accuracy of match of each homologue is used to locate these sequences. We list here the signals found by this search in introns of sea urchin, mouse, rat, and human genes and give the consensus for each species. We also give the consensus found for Drosophila and chicken and duck signals. We then discuss the accumulating evidence that these internal signals are required for splicing in animals. It is also noted that a single-stranded region of small nuclear RNA U2 contains sequences complementary both to the proposed mammalian internal signal and to the neighboring CT-A-G at the 3' intron boundary. A role for U2 ribonucleoprotein in intron splicing is thus suggested.
Effects of bromohomoibotenate on metabotropic glutamate receptors (1994)

(S)-Bromohomoibotenic acid [(S)-BrHIbo] stereoselectively antagonized glutamate-stimulated phosphoinositide (PI) hydrolysis in baby hamster kidney (BHK) cells expressing mGluR1a in a competitive manner with an IC50 of 250 microM. However, (S)-BrHIbo did not inhibit (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced PI hydrolysis in rat hippocampal slices (S)- or (R)-BrHIbo did not show any effects on forskolin-stimulated cAMP-formation in BHK cells expressing mGluR2 or mGluR4 but did displace [3H]2-amino-4-phosphonobutyrate ([3H]AP4) binding from rat corticalmembranes with high affinities (IC50 = 1.0 microM and 1.1 microM, respectively). These data suggest that (S)-BrHIbo may interest with multiple PI-coupled glutamate receptors, however, at concentrations that are several fold higher than for displacement of [3H]AP4 binding from rat cortical membranes.
Activation of tyrosine kinase p60fyn following T cell antigen receptor cross-linking. (1992)

Activation of T cells by specific antigens in the context of major histocompatibility complex encoded proteins is mediated by the T cell antigen receptor (TcR), consisting of a variable (Ti) and an invariant (CD3) subunits. Tyrosine phosphorylation is considered to be one of the earliest steps in TcR-mediated signal transduction. There are indications that the p60fyn protein tyrosine kinase is involved in signaling via TcR. However, enzymatic activation of the Src-related tyrosine kinases upon TcR triggering has not been shown yet, therefore the identity of TcR-activated tyrosine kinase(s) remains unclear. We demonstrate that cross-linking of CD3 activates p60fyn and induces tyrosine phosphorylation of cellular proteins in human T cells (resting peripheral T cells, a helper T cell clone, a helper T cell clone immortalized with Herpesvirus saimiri, and a leukemic T cell line). Activation of p60fyn was fast, and its maximum (2-4-fold activation as compared with the basal activity) was followed by a decline. The amount of p60fyn in the cells remained unchanged. None of the other T cell Src-related tyrosine kinases was activated after cross-linking of CD3. Activation of p60fyn was induced by anti-CD3, but not by anti-CD4, anti-CD2, or anti-CD28. The activation was correlated with an increase of the phosphotyrosine content of p60fyn. These studies provide direct proof for the functional association between p60fyn and the TcR.
Magnesium and Vascular Changes in Hypertension (2012)

Many factors have been implicated in the pathogenesis of hypertension, including changes in intracellular concentrations of calcium, sodium, potassium, and magnesium. There is a significant inverse correlation between serum magnesium and incidence of cardiovascular diseases. Magnesium is a mineral with important functions in the body such as antiarrhythmic effect, actions in vascular tone, contractility, glucose metabolism, and insulin homeostasis. In addition, lower concentrations of magnesium are associated with oxidative stress, proinflammatory state, endothelial dysfunction, platelet aggregation, insulin resistance, and hyperglycemia. The conflicting results of studies evaluating the effects of magnesium supplements on blood pressure and other cardiovascular outcomes indicate that the action of magnesium in the vascular system is present but not yet established. Therefore, this mineral supplementation is not indicated as part of antihypertensive treatment, and further studies are needed to better clarify the role of magnesium in the prevention and treatment of cardiovascular diseases.
Limited Effect of Systemic β-Blockade on Sympathetic Outflow (2001)

Central beta-adrenoreceptors may augment sympathetic outflow. We tested the hypothesis that beta-blockade attenuates central sympathetic outflow by inhibiting central adrenoreceptors. We studied 18 healthy controls (4 female, 14 male; age, 26+/-6 years, body mass index, 23+/-3 kg/m(2)). ECG, brachial, and finger arterial blood pressure, muscle sympathetic nerve activity, and respiration were measured continuously before and during complete beta-blockade. Subjects received a total intravenous dose of 0.21 mg/kg of propranolol in 15 minutes. Spontaneous baroreflex slopes were calculated using the sequence technique (BRSup, BRSdown). The sympathetic baroreflex slope was determined at baseline using phenylephrine and sodium nitroprusside infusions. The subjects underwent cold pressor testing before and during beta-blockade. The R-R interval increased from 861+/-119 ms at baseline to 952+/-141 ms during beta-blockade (P<0.01). Blood pressure was 117+/-9/65+/-8 mm Hg at baseline and 117+/-10/67+/-8 mm Hg during beta-Blockade (P=NS). beta-Blockade did not affect baroreflex sensitivity (BRSup: 21+/-10 versus 28+/-11 ms/mmHg, P<0.1; BRSdown: 17+/-8 versus 20+/-8 ms/mmHg, P=NS). Muscle sympathetic nerve activity increased significantly during beta-blockade (number of bursts/100 beats: 32+/-9 versus 40+/-14, P<0.05), compared with baseline. However, the operating points of the parasympathetic and sympathetic baroreflex during beta-blockade were on the baroreflex curves obtained at baseline. beta-Blockade blunted the heart rate response to cold pressor testing; blood pressure and muscle sympathetic nerve activity responses were similar. Our study demonstrates that propranolol does not cause an acute decrease in sympathetic activity in normotensive young subjects. This, observation is not consistent with an important tonic stimulatory effect of beta-adrenoreceptors in the brain.
Binding of Human Immunodeficiency Virus Type 1 to CD4 Induces Association of Lck and Raf-1 and Activates Raf-1 by a Ras-Independent Pathway (1996)

We have analyzed CD4-mediated signaling during the early stages of human immunodeficiency virus type 1 (HIV-1) infection. Binding of purified HIV-1 virions or recombinant HIV-1 glycoprotein gp120 to CD4 receptors resulted in association and tyrosine phosphorylation and activation of tyrosine kinase Lck and serine/threonine kinase Raf-1. The association between Lck and Raf-1 was mediated by stimulation of the CD4 receptors, since it was abolished by preincubation of the virus with soluble CD4 and was not detected in CD4-negative A201 T cells. However, the Lck-Raf-1 association was restored in A201 cells permanently transfected with human CD4 cDNA and stimulated with anti-CD4 antibodies. In addition, a catalytically active Lck was required for the association of Lck and Raf-1. Surprisingly, the CD4-mediated signaling, induced by the HIV-1 binding, did not result in stimulation of the Ras GTP-binding activity or its association with Raf-1, indicating that the signaling pathway generated by the HIV-1 binding is not identical to the classical Ras/Raf-1 pathway. Furthermore, overexpression of activated Raf-1 in Jurkat T cells stimulated the HIV long terminal repeat promoter activity and significantly enhanced HIV-1 replication. This suggests that the Lck-Raf-1 pathway, rapidly stimulated by the binding of HIV-1 or gp120 to CD4 receptors, may play an essential role in the transcriptional activation of the integrated HIV-1 provirus as well as in its pathogenicity.
Human immunodeficiency virus-like particles produced by a vaccinia virus expression vector. (1989)

Infectious retrovirus particles consist of a core structure containing RNA and gag-pol polypeptides surrounded by a lipid membrane studded with env proteins. A recombinant vaccinia virus was designed to express the entire gag-pol precursor protein of the human immunodeficiency virus type 1. Synthesis and processing of gag proteins occurred in mammalian cells infected with this live recombinant virus, and reverse transcriptase was detected largely in the medium. Electron micrographs revealed immature retrovirus-like particles budding from the plasma membrane and extracellular particles with morphological characteristics of immature and mature human immunodeficiency virus. The latter contained functional reverse transcriptase as well as processed p24 and p17 gag polypeptides. Thus, assembly and maturation of human immunodeficiency virus-like particles can occur in the absence of either infectious RNA molecules or env proteins. The production of noninfectious virus-like particles by expression vectors should be useful for biochemical studies and could provide a safe source of material for the development of vaccines.
Interaction of the Immunosuppressant Deoxyspergualin with a Member of the Hsp70 Family of Heat Shock Proteins (1992)

Deoxyspergualin (DSG) is a potent immunosuppressant whose mechanism of action remains unknown. To elucidate its mechanism of action, an intracellular DSG binding protein was identified. DSG has now been shown to bind specifically to Hsc70, the constitutive or cognate member of the heat shock protein 70 (Hsp70) protein family. The members of the Hsp70 family of heat shock proteins are important for many cellular processes, including immune responses, and this finding suggests that heat shock proteins may represent a class of immunosuppressant binding proteins, or immunophilins, distinct from the previously identified cis-trans proline isomerases. DSG may provide a tool for understanding the function of heat shock proteins in immunological processes.