gebhart/patrepeval huggingface dataset:
High yield overexpression and characterization of human recombinant proapolipoprotein A-I. (1996)

Human apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) where it defines the particle structure and stability and functions as the main activator of the enzyme lecithin:cholesterol acyltransferase (LCAT). ApoA-I is expressed in the liver as a preproprotein that is targeted to the endoplasmic reticulum for secretion; in plasma, an unknown protease removes the six amino acid long propeptide. In this study, the cDNA coding the human proapoA-I was cloned into an Escherichia coli vector; the overexpressed protein was purified to 99% homogeneity and was extensively characterized together with mature apoA-I purified from plasma. SDS-PAGE, mass spectrometry, and Edman sequence analysis showed that the initial Met residue needed for translation in E. coli is posttranslationally removed from the N-terminal sequence of the proapoA-I. The structural and functional analyses were carried out on the lipid-free and the lipid-bound proteins. ProapoA-I self associated, interacted with dimyristoyl phosphatidylcholine vesicles, and formed secondary structures very similar to the lipid-free apoA-I. Reconstituted HDL particles made with two initial molar ratios of palmitoyloleoyl phosphatidylcholine/cholesterol/apolipoprotein/Na-cholate had identical particle sizes and distributions when apoA-I or proapoA-I were used. Particles having diameters of 79 A and 98 A, containing two apoA-I or proapoA-I molecules per particle, were isolated and characterized. The particles contained the same amounts of alpha-helical structure, had very similar fluorescence properties, and activated LCAT equally well. We conclude that proapoA-I expressed and purified from E. coli is functionally and structurally indistinguishable from mature apoA-I purified from plasma when analyzed in vitro. Therefore, this recombinant proapoA-I and mutants derived from it will be important sources of protein for analyzing apoA-I structure and function, as well as for studies of proapoA-I processing.
Recognition of a 5‘-(A,T)GGG(A,T)2-3‘ Sequence in the Minor Groove of DNA by an Eight-Ring Hairpin Polyamide (1996)

The use of pyrrole−imidazole polyamides for the recognition of core 5‘-GGG-3‘ sequences in the minor groove of double stranded DNA is described. Two hairpin pyrrole−imidazole polyamides, ImImIm-γ-PyPyPy-β-Dp and ImImImPy-γ-PyPyPyPy-β-Dp (Im = N-methylimidazole-2-carboxamide, Py = N-methylpyrrole-2-carboxamide, β = β-alanine, γ = γ-aminobutyric acid, and Dp = ((dimethylamino)propyl)amide), as well as the corresponding EDTA affinity cleaving derivatives, were synthesized and their DNA binding properties analyzed. Quantitative DNase I footprint titrations demonstrate that ImImIm-γ-PyPyPy-β-Dp binds the formal match sequence 5‘-AGGGA-3‘ with an equilibrium association constant of Ka = 5 × 106 M-1 (10 mM Tris·HCl, 10 mM KCl, 10 mM MgCl2, and 5 mM CaCl2, pH 7.0 and 22 °C). ImImImPy-γ-PyPyPyPy-β-Dp binds the same site, 5‘-AGGGAA-3‘, approximately two orders of magnitude more tightly than the six ring polyamide, with an equilibrium association constant of Ka = 4 × 108 M-1. The eight-ring hairpin polyamide demonstrates greater specifity for single base pair mismatches than does the six ring hairpin. Polyamides with an EDTA·Fe(II) moiety at the carboxy terminus confirm that each hairpin binds in a single orientation. The high affinity recognition of a 5‘-GGG-3‘ core sequence by an eight ring polyamide containing three contiguous imidazole amino acids demonstrates the versatility of pyrrole−imidazole polyamides and broadens the sequence repertoire for DNA recognition.
Urinary and Serum Urea as Indicators of Protein Metabolism in Very Low Birthweight Infants Fed Varying Human Milk Protein Intakes (1990)

Urea concentrations in serum and urine were measured in 28 growing, very low birth weight, appropriate-for-gestational age infants fed varying human milk protein intakes (range 1.7 to 3.9 g/kg/day). We found a high correlation between serum urea values at the end of the study and mean protein intake (rs = 0.85, p less than 0.001) and between urinary urea concentrations in eight-hour urine collections and protein intake (rs = 0.81, p less than 0.001). All serum and urine urea values were below 1.6 and 18 mmol/l, respectively, at protein intakes less than 3 g/kg/day. Higher protein intakes caused higher serum and urinary urea concentrations. We also found a strong correlation between the individual serum and urinary urea values at the end of the study (rs = 0.90, p less than 0.001). The presented data are consistent with the growth data previously reported and indicate that inadequate or excessive protein intakes can be detected by measurement of urea concentrations in serum and/or urine. If urine urea samples alone can be used for estimating optimal protein intake, painful blood sampling procedures could be obviated.
Possible Involvement of Small Oligomers of Amyloid-β Peptides in 15-Deoxy-Δ12,14 Prostaglandin J2-Sensitive Microglial Activation (2003)

In Alzheimer’s disease, fibrillar amyloid-β (Aβ) peptides form senile plaques associated with microglia. However, the relationship between Aβ peptides and microglia is not fully understood. In this study, the incubation of Aβ1-40 (Aβ40) produced small oligomers, while incubation with Aβ1-42 (Aβ42) caused large molecular aggregates. Microglial production of nitrite, interleukin-6 and tumor necrosis factor-α was induced by Aβ40, but not Aβ42. This production was significantly reduced by 15-deoxy-Δ12,14 prostaglandin J2, and it was completely suppressed by β-sheet breaker peptide, Leu-Pro-Phe-Phe-Asp. These results suggest that small oligomers, rather than large molecular aggregates, mediate microglial activation induced by Aβ peptides.
Plasma cholesteryl ester transfer protein and high‐density lipoproteins: new insights from molecular genetic studies (1995)

Recent studies in transgenic mice provide strong evidence for a direct anti-atherogenic role of high-density lipoproteins (HDL) and highlight the importance of multiple gene interactions in the regulation of HDL levels. Plasma lipid transfer processes mediated by cholesteryl ester transfer protein (CETP) have a major impact on HDL levels, as revealed in studies of human genetic CETP deficiency and CETP transgenic mice. Subsequent to the discovery of an intron 14 CETP gene splicing defect, several new CETP gene mutations have been discovered recently in Japanese and other populations. One of these is an exon 15 missense mutation, changing amino acid 442 of CETP from aspartate to glycine. Population studies in Japan indicate that CETP gene mutations are sufficiently common to have a significant influence on HDL levels in the general population. Studies in transgenic mice show that CETP expression results in decreased levels of HDL cholesterol, but that the effects of CETP on HDL apolipoprotein A-I (apoA-I) content and size show important modulation by co-expression with transgenes encoding human apoA-I, apoC-III and apoA-II. In addition to the apparent antiatherogenic phenotype of human genetic CETP deficiency, high level expression of CETP in transgenic mice leads to accelerated atherosclerosis, illustrating the pro-atherogenic potential of CETP expression.
High voltage and high current density vertical GaN power diodes (2016)

The realisation of a GaN high voltage vertical p – n diode operating at &gt;3.9 kV breakdown with a specific on‐resistance &lt;0.9 mΩ cm 2 is reported. Diodes achieved a forward current of 1 A for on‐wafer, DC measurements, corresponding to a current density &gt;1.4 kA/cm 2 . An effective critical electric field of 3.9 MV/cm was estimated for the devices from analysis of the forward and reverse current–voltage characteristics. This suggests that the fundamental limit to the GaN critical electric field is significantly greater than previously believed.
Induction of the soxRS Regulon of Escherichia coli by Superoxide (1999)

The soxRS regulon orchestrates a multifaceted defense against oxidative stress, by inducing the transcription of approximately 15 genes. The induction of this regulon by redox agents, known to mediate O-2 production, led to the view that O-2 is one signal to which it responds. However, redox cycling agents deplete cellular reductants while producing O-2, and one may question whether the regulon responds to the depletion of some cytoplasmic reductant or to O-2, or both. We demonstrate that raising [O-2] by mutational deletion of superoxide dismutases and/or by addition of paraquat, both under aerobic conditions, causes induction of a member of the soxRS regulon and that a mutational defect in soxRS eliminates that induction. This establishes that O-2, directly or indirectly, can cause induction of this defensive regulon.
Thymic aging and T‐cell regeneration (1997)

Studies of T-cell regeneration using animal models have consistently shown the importance of the thymus for T-cell regeneration. In humans, recent studies have shown that declines in thymic T-cell regenerative capacity begins relatively early in life, resulting in a limited capacity for T-cell regeneration by young adulthood. As a result, adult humans who experience profound T-cell depletion regenerate T cells primarily via relatively inefficient thymic-independent pathways, resulting in prolonged CD4 depletion, CD4+ and CD8+ subset alterations, limited TCR repertoire diversity and a propensity for activation induced cell death. These limitations in T-cell regeneration have significant clinical implications in the setting of HIV infection and bone marrow transplantation and may also contribute to immunologic abnormalities associated with normal aging. While the mechanisms responsible for thymic aging are not well understood, current evidence suggests that changes within the thymus itself are primary, while age-related changes in marrow T-cell progenitors and inhibitory factors within the extrathymic host milieu contribute to a lesser extent. The development of therapies which can reverse thymic aging are critical for improving outcome in clinical settings of T-cell depletion, and could potentially improve immunologic function in normal aged hosts.
Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol (2001)

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine, which shows antioxidant and antiproliferative activities. In this study we have investigated whether these properties are dependent on similar or different structural determinants of the molecule. To this purpose, resveratrol derivatives, in which all or each single hydroxylic function were selectively substituted with methyl groups, were synthesized. Analogues with the stilbenic double bond reduced or with the stereoisometry modified were also investigated. The antioxidant activity of these compounds was evaluated by measuring the inhibition of citronellal thermo-oxidation, or the reduction of 2,2-diphenyl-1-picrylhydrazyl radical. In addition, the protection against lipid peroxidation was determined in rat liver microsomes, and in human primary cell cultures. The antiproliferative activity was evaluated by a clonogenic assay, and by analysis of cell cycle progression and DNA synthesis. The results showed that the hydroxyl group in 4' position is not the sole determinant for antioxidant activity. In contrast, the presence of 4'-OH together with stereoisometry in the trans-conformation (4'-hydroxystyryl moiety) was absolutely required for inhibition of cell proliferation. Enzymatic assays in vitro demonstrated that inhibition of DNA synthesis was induced by a direct interaction of resveratrol with DNA polymerases alpha and delta.
Use of flow cytometry for the adhesion analysis of Streptococcus pyogenes mutant strains to epithelial cells: investigation of the possible role of surface pullulanase and cysteine protease, and the transcriptional regulator Rgg (2006)

These results suggest that the flow cytometric assay is a valuable tool in the analysis of S. pyogenes adherence to host cells. It appears to be an efficient and sensitive tool for the characterization of interactions between the bacteria and the host at the molecular level. The results also suggest a role for Rgg regulated surface molecules, like PulA, in the adhesion of S. pyogenes to host cells.
Accumulation of Herpes Simplex Virus Type 1 Early and Leaky-Late Proteins Correlates with Apoptosis Prevention in Infected Human HEp-2 Cells (2001)

We previously reported that a recombinant ICP27-null virus stimulated, but did not prevent, apoptosis in human HEp-2 cells during infection (M. Aubert and J. A. Blaho, J. Virol. 73:2803-2813, 1999). In the present study, we used a panel of 15 recombinant ICP27 mutant viruses to determine which features of herpes simplex virus type 1 (HSV-1) replication are required for the apoptosis-inhibitory activity. Each virus was defined experimentally as either apoptotic, partially apoptotic, or nonapoptotic based on infected HEp-2 cell morphologies, percentages of infected cells with condensed chromatin, and patterns of specific cellular death factor processing. Viruses d27-1, d1-5, d1-2, M11, M15, M16, n504R, n406R, n263R, and n59R are apoptotic or partially apoptotic in HEp-2 cells and severely defective for growth in Vero cells. Viruses d2-3, d3-4, d4-5, d5-6, and d6-7 are nonapoptotic, demonstrating that ICP27 contains a large amino-terminal region, including its RGG box RNA binding domain, which is not essential for apoptosis prevention. Accumulations of viral TK, VP16, and gD but not gC, ICP22, or ICP4 proteins correlated with prevention of apoptosis during the replication of these viruses. Of the nonapoptotic viruses, d4-5 did not produce gC, indicating that accumulation of true late gene products is not necessary for the prevention process. Analyses of viral DNA synthesis in HEp-2 cells indicated that apoptosis prevention by HSV-1 requires that the infection proceeds to the stage in which viral DNA replication takes place. Infections performed in the presence of the drug phosphonoacetic acid confirmed that the process of viral DNA synthesis and the accumulation of true late (gamma(2)) proteins are not required for apoptosis prevention. Based on our results, we conclude that the accumulation of HSV-1 early (beta) and leaky-late (gamma(1)) proteins correlates with the prevention of apoptosis in infected HEp-2 cells.
Potentiation of angiotensin II-stimulated vascular contraction by lithium (1995)

Previous studies have suggested that lithium prolongs or enhances vascular contractions stimulated by alpha-adrenergic agents. The present study was performed to determine whether a similar phenomenon occurs with angiotensin II (ANG II)-stimulated contractions and whether this phenomenon results from interactions with the phosphoinositide signaling system. Contractions of rat aortic rings with 100 nM ANG II were 38% greater in the presence of 20 mM LiCl than in its absence (0.47 +/- 0.07 vs. 0.34 +/- 0.05 g tension/mg dry tissue wt, P < 0.01). The effects of lithium on inositol phosphate responses, diacylglycerol responses, and intracellular calcium concentration on single or repeated stimulations with ANG II were then examined in vascular smooth muscle cells cultured from rat aorta. Cells exposed twice to 100 nM ANG II contained 50% lower inositol trisphosphate levels (InsP3) and 10% lower diacylglycerol levels than cells exposed to ANG II only once. LiCl or lithium acetate abolished these desensitizations in a concentration-dependent manner. Similarly, InsP3 and diacylglycerol responses to a single exposure of ANG II were heightened by lithium (by 75 and 25%, respectively), and the duration of the responses was prolonged by lithium (5- and 2-fold, respectively). In contrast, ANG II-stimulated calcium transients were not enhanced or prolonged by lithium, nor was desensitization of ANG II-stimulated cytosolic calcium mobilization upon serial exposures abolished by lithium. When ring contraction studies were repeated in the presence of the protein kinase C inhibitor staurosporine (150 nM), lithium no longer potentiated ANG II contractions [0.38 +/- 0.03 (control) vs. 0.35 +/- 0.06 g tension/mg dry tissue wt (lithium)].(ABSTRACT TRUNCATED AT 250 WORDS)
Fampridine in multiple sclerosis (2007)

People with multiple sclerosis (MS) experience a wide variety of neurological symptoms such as weakness, impaired mobility, spasticity and bowel, bladder and sexual dysfunction due to slowed or blocked conduction where central nervous system (CNS) demyelination occurs. Over time, worsening symptoms increasingly compromise independence, quality of life, economic productivity and the ability to function and perform basic activities of daily living. The eventual physical, psychological, social and financial impact can be devastating for people with MS and their families. Although, clear advances have been made in available diseasemodifying therapies, in general, these do not benefit those residual symptoms consequent to existing lesions. Fampridine (4-aminopyridine, 4-AP) is a small-molecule potassium (K+) blocker (Figure 40.1) undergoing testing as an experimental symptomatic therapy for MS. This review considers briefly the pharmacology, history and early clinical studies, then focuses on the results of recent clinical trials of fampridine in MS.
Pile-up correction of pulse height spectrum measured by a Ge detector to a pulsed beam of high energy photons (2002)

A peak pile-up correction of the output pulses measured by a Ge detector is necessary for a quantitative measurement of a pulsed beam of high energy photons which are produced by Compton backscattering of pulsed laser light with relativistic electrons in a synchrotron storage ring. The peak pile-up causes not only a distortion of pulse height distribution measured by a Ge detector but also affects quantitative measurements based on integrating the area under the pulse height spectrum. In order to correct the peak pile-up, a Monte Carlo simulation has been applied to calculate the pile-up spectrum by superposing double pulse or triple pulse coincidences with different pulse heights and different time delays. It is assumed that the output pulses are randomly generated in time within one burst of the pulsed laser light. An undistorted pulse height spectrum necessary for the simulation has been obtained from a low counting rate experiment which has a negligible pile-up. A good agreement between the simulated spectrum and the experimental spectrum using different pile-up rates has been obtained. After fitting the experimental data by use of the simulated spectrum, the measured spectrum call be resolved into single, double and triple pile-up components. This results in a quantitatively corrected peak pile-up at different counting rates.
Wnt signaling as a therapeutic target for bone diseases (2009)

Neutralizing inhibitors of Wnt signaling have emerged as promising strategies. Small-molecule inhibitors of glycogen synthase kinase 3beta increase bone mass, lower adiposity and reduce fracture risk. Neutralizing antibodies to Dickkopf 1, secreted Frizzled-related protein 1 and sclerostin produce similar outcomes in animal models. These drugs are exciting breakthroughs but are not without risks. The challenges include tissue-specific targeting and consequently, long-term safety.
Voltage-induced perpendicular magnetic anisotropy change in magnetic tunnel junctions (2010)

A voltage-induced perpendicular magnetic anisotropy change in an ultrathin FeCo layer was observed in an epitaxial magnetic tunnel junction (MTJ) structure. A spin-transfer induced ferromagnetic resonance measurement technique was used under various bias voltage applications to evaluate the anisotropy change. From the peak frequency shifts, we could estimate that a surface magnetic anisotropy change of 15 μJ/m2 was induced by an electric field application of 400 mV/nm in the MTJ with a 0.5 nm thick FeCo layer. The realization of voltage-induced anisotropy changes in an MTJ structure should have a large impact on the development of electric-field driven spintronic devices.
Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin (2008)

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.
Chloroquine inhibits intracellular degradation but not secretion of Alzheimer beta/A4 amyloid precursor protein. (1992)

The metabolic fate of the Alzheimer beta/A4 amyloid precursor protein (APP) includes intraamyloid proteolysis that leads to the production of secreted N-terminal and cell-associated C-terminal fragments. The cellular sites at which this processing occurs are not known. We have examined the route of APP processing in metabolically labeled PC12 cells. The lysosomotropic drug chloroquine exerted inhibitory effects on the degradation of mature APP holoprotein. In addition, recovery of a C-terminal fragment resulting from normal intraamyloid cleavage was significantly increased in the presence of chloroquine, suggesting that further degradation of the C-terminal fragment was inhibited. Chloroquine had virtually no effect on APP maturation (N- and O-glycosylation and tyrosine sulfation) or secretion. Treatment with either monensin (which inhibits distal Golgi function) or brefeldin A (which causes resorption of the Golgi into the endoplasmic reticulum and fusion of the trans-Golgi network with the endosomal system) prevented normal APP maturation and abolished APP secretion and recovery of C-terminal fragments, indicating that intact Golgi function is necessary for APP maturation and processing. Our results suggest that a substantial proportion of APP is degraded in an intracellular acidic compartment but that the coupled APP cleavage/secretion event occurs in a chloroquine-insensitive compartment. The observations are consistent with the existence of multiple cellular routes for the trafficking and proteolysis of APP.