gebhart/patrepeval huggingface dataset:
Architecture of the Outer Membrane of Escherichia coli III. Protein-Lipopolysaccharide Complexes in Intramembraneous Particles (1978)

In a previous paper (A. Verkleij, L. van Alphen, J. Bijvelt, and B. Lugtenberg, Biochim. Biophys. Acta 466:269-282, 1977) we have hypothesized that particles on the outer fracture face of the outer membrane ([Formula: see text]), with corresponding pits on the inner fracture face of the outer membrane ([Formula: see text]), consist of lipopolysaccharide (LPS) aggregates stabilized by divalent cations and that they might contain protein and/or phospholipid. In the present paper the roles of LPS, cations, and proteins in these [Formula: see text] particles are described more extensively, using a strain that lacks the major outer membrane proteins, b, c, and d (b(-) c(-) d(-)), and has a reduction in the number of [Formula: see text] particles of 75%. To study the role of divalent cations in the formation of [Formula: see text] particles, these b(-) c(-) d(-) cells were grown or incubated with Ca(2+), Mg(2+), or putrescine. The presence of Ca(2+) resulted in the appearance of many [Formula: see text] particles and [Formula: see text] pits. Mg(2+) and putrescine were less effective than Ca(2+). Introduction of these particles was not accompanied by alterations in the relative amounts of LPS and cell envelope proteins. Ca(2+) treatment of a heptoseless derivative of a b(-) c(-) d(-) strain did not result in morphological changes. Incubation of Ca(2+)-treated cells with ethylenediaminetetraacetate caused the disappearance of the introduced particles as well as the release of more than 60% of the cellular LPS. These results strongly support the hypothesis that LPS is involved in the formation of [Formula: see text] particles and [Formula: see text] pits. The roles of various outer membrane proteins in the formation of [Formula: see text] particles were studied by comparing the freeze-fracture morphology of b(-) c(-) d(-) cells with that of cells which contain one of the outer membrane proteins b, c, d, and e or the receptor protein for bacteriophage lambda. The results showed that the presence of any of these five proteins in a b(-) c(-) d(-) background resulted in a large increase in the number of [Formula: see text] particles and [Formula: see text] pits, indicating that these proteins are, independent of each other, involved in the formation of [Formula: see text] particles and [Formula: see text] pits. The simplest explanation for the results is that in wild-type cells each particle consists of LPS complexed with some molecules of a single protein species, stabilized by either divalent cations or polyamines. It is hypothesized that the outer membrane of the wild-type cell contains a heterogeneous population of particles, of which 75% consists of protein b-LPS, protein c-LPS, and protein d-LPS particles. A function of these particles as aqueous pores is proposed.
Recent advances in the research and development of CB1 antagonists. (2005)

The worldwide prevalence of obesity has dramatically increased over the last 30 years, yet due to modest efficacy and side effects, current treatments for obesity are inadequate. Antagonists of the cannabinoid receptor type 1 (CB(1)) have emerged as a highly promising therapeutic strategy for obesity, with the 1,5-diaryl-pyrazole rimonabant (Sanofi-Aventis) being the most characterized and the furthest advanced agent in the clinic. This review focuses on recent publications (2002 to 2004) that describe the effects of CB(1) antagonists both on feeding behavior and in models of obesity, and the identification and characterization of new structure classes as CB(1) antagonists.
Clinical trials involving multidrug resistance transcription units in retroviral vectors. (1999)

Cowan et al. [(1)][1] have reported in this issue of Clinical Cancer Research the results of a clinical trial that was designed to evaluate the feasibility of using retroviral vectors to transfer the MDR-1 [2][2] chemotherapy resistance genes to normal hematopoietic cells to protect them from the
Frequent transcriptional inactivation of Kallikrein 10 gene by CpG island hypermethylation in non‐small cell lung cancer (2009)

The role of Kallikrein 10 gene (KLK10) in non-small cell lung cancer (NSCLC) remains largely unknown. We determined the frequency and functional significance of KLK10 hypermethylation in NSCLC. The mRNA expression and methylation status of KLK10 in 78 pairs NSCLC specimens was explored. The biological effects of KLK10 were analyzed by transfection. The results showed that, KLK10 was significantly downregulated in NSCLC (57.7%, 45/78) as compared to non-cancer samples (P = 0.010). CpG island hypermethylation of KLK10 was detected in 46.2% (36/78) NSCLC tissues and was closely correlated with loss of transcript (P < 0.001). KLK10 methylation was associated with advanced stage (P = 0.013) and lymph metastasis (P = 0.015). Furthermore, demethylation treatment restored the expression of KLK10 in two lung adencarcinoma cell lines (A549, SPC-A1). Forced expression of KLK10 in A549 and SPC-A1 remarkably suppressed cells proliferation, migration in vitro and oncogenicity in vivo. Additionally, methylated KLK10 was detected in 38.7% (30/78) of plasma samples from cancer patients but rare in cancer-free controls (P < 0.001). In conclusion, KLK10 acts as a functional tumor suppressor gene in NSCLC, epigenetic inactivation of KLK10 is a common event contributing to NSCLC pathogenesis and may be used as a potential biomarker.
Purification and properties of Saccharomyces cerevisiae acetolactate synthase from recombinant Escherichia coli (1989)

The yeast ilv2 gene, encoding acetolactate synthase, was subcloned in an Escherichia coli expression vector. Although a major part of the acetolactate synthase synthesized by E. coli cells harbouring this vector was packaged into protein inclusion bodies, we used these recombinant E. coli cells to produce large quantities of the yeast enzyme. The yeast acetolactate synthase was purified to homogeneity using first streptomycin and ammonium sulfate precipitations, followed by T-gel thiophilic interaction, Sephacryl S-300 gel filtration, Mono Q anion exchange, and Superose 12 gel filtration chromatography. SDS/PAGE and gel filtration of the purified enzyme showed that it is a dimer composed of two subunits, each with the molecular mass of 75 kDa. The purified yeast acetolactate synthase was further characterized with respect to pH optimum, dependence of the substrate, pyruvate, and requirements of the cofactors, thiamin diphosphate, Mg2+, and FAD.
A Mental Retardation-linked Nonsense Mutation in Cereblon Is Rescued by Proteasome Inhibition (2013)

A nonsense mutation in cereblon (CRBN) causes autosomal recessive nonsyndromic mental retardation. Cereblon is a substrate receptor for the Cullin-RING E3 ligase complex and couples the ubiquitin ligase to specific ubiquitination targets. The CRBN nonsense mutation (R419X) results in a protein lacking 24 amino acids at its C terminus. Although this mutation has been linked to mild mental retardation, the mechanism by which the mutation affects CRBN function is unknown. Here, we used biochemical and mass spectrometric approaches to explore the function of this mutant. We show that the protein retains its ability to assemble into a Cullin-RING E3 ligase complex and catalyzes the ubiquitination of CRBN-target proteins. However, we find that this mutant exhibits markedly increased levels of autoubiquitination and is more readily degraded by the proteasome than the wild type protein. We also show that the level of the mutant protein can be restored by a treatment of cells with a clinically utilized proteasome inhibitor, suggesting that this agent may be useful for the treatment of mental retardation associated with the CRBN R419X mutation. These data demonstrate that enhanced autoubiquitination and degradation account for the defect in CRBN activity that leads to mental retardation.
Acid sphingomyelinase involvement in tumor necrosis factor α-regulated vascular and steroid disruption during luteolysis in vivo (2008)

TNF is well known for its role in inflammation, including direct effects on the vasculature. TNF also is implicated in the regulation of reproduction by its actions to affect ovarian steroidogenic cells and to induce apoptosis of corpus luteum (CL)-derived endothelial cells in vitro. We hypothesized that the disruption of TNF signaling would postpone the regression of the highly vascularized CL in vivo, and this effect could be replicated in mutant mouse models lacking TNF receptor (TNFRI(-/-)) and/or a critical enzyme of TNF signaling, acid sphingomyelinase (ASMase(-/-)). In the current study, the treatment of pseudopregnant mice with the luteolytic mediator prostaglandin F2-alpha (PGF) significantly increased TNF in the ovaries when compared with saline-treated controls. Treatment with PGF also reduced serum progesterone (P4) concentrations and caused involution of the CL. However, pretreatment of pseudopregnant mice with Etanercept (ETA), a TNF-neutralizing antibody, inhibited the PGF-induced decrease in P4 and delayed luteal regression. A similar outcome was evident in pseudopregnant TNFRI(-/-) animals. Treatment of luteal microvascular endothelial cells (MVECs) with TNF provoked a significant increase in ASMase activity when compared with the corresponding controls. Furthermore, TNF-induced MVEC death was inhibited in the ASMase(-/-) mice. The ASMase(-/-) mice displayed no obvious evidence of luteal regression 24 h after treatment with PGF and were resistant to the PGF-induced decrease in P4. Together these data provide evidence that TNF plays an active role in luteolysis. Further studies are required to determine the deleterious effects of anti-inflammatory agents on basic ovarian processes.
The Aging Voice (1997)

A number of studies have found that listeners are often able to differentiate the voices of young and old speakers accurately. Following an overview of structural and functional changes found in studies of aging larynges, this article examines current findings on maximum phonation duration, voice quality, vocal jitter/shimmer, spectral noise, and fundamental frequency. Aging can affect vocal pitch, loudness, and quality, but such effects are highly variable across the aging population. Therefore, a thorough voice and medical examination is needed to isolate voice problems caused by vocal abuse or pathology from those due to normal aging. Pushing exercises may be a viable treatment option for those with age-related voice problems.
Snipping Away at Genome Patenting (1997)

Genetic markers called single nucleotide polymorphisms (SNPs or snips) are becoming a hot commercial property. They offer unique and efficient signposts that can be used by researchers scanning an entire genome for significant mutations, and they are piling up in growing numbers as public and private institutions churn out more and more human DNA sequence data. But some companies--and, according to rumors, some research groups--are staking proprietary claims on SNPs. Last week, a group of researchers urged the National Institutes of Health to undermine such claims by creating a public repository of SNPs. They got a sympathetic response from Human Genome Project chief Francis Collins.
Lipid binding-induced conformational changes in the N-terminal domain of human apolipoprotein E (1999)

The N-terminal domain of human apolipoprotein E3 (apoE3) adopts an elongated, globular four helix bundle conformation in the lipid-free state. Upon lipid binding, the protein is thought to undergo a significant conformational change that is essential for manifestation of its low density lipoprotein receptor recognition properties. We have used fluorescence resonance energy transfer (FRET) to characterize helix repositioning which accompanies lipid interaction of this protein. ApoE3(1-183) possesses a single cysteine at position 112 and four tryptophan residues (positions 20, 26, 34, and 39). Modification of Cys112 with the chromophore, N-iodoacetyl-N'-(5-sulfo-1-naphthyl)etheylenediamine (AEDANS) was specific and did not alter the secondary structure content of the protein. The efficiency of energy transfer from donor Trp residues to the AEDANS moiety was 49% in buffer, consistent with close proximity of the chromophores. Guanidine HCl titration experiments induced characteristic changes in the efficiency of energy transfer, indicating that FRET data faithfully reports on the conformational status of the protein. Interaction of AEDANS-apoE3(1-183) with dimyristoylphosphatidylcholine to form disk particles, or with detergent micelles, resulted in large decreases in the efficiency of energy transfer. Distance calculations based on the FRET measurements revealed that lipid binding increases the average distance between the four Trp donors and the AEDANS acceptor from 23 A to 44 A. The results obtained demonstrate the utility of FRET to investigate conformational adaptations of exchangeable apolipoproteins and are consistent with the hypothesis that, upon lipid binding, apoE3(1-183) undergoes conformational opening, repositioning helix 1 and 3 to adopt a receptor-active conformation.
<title>Overview of passive and active vision techniques for hand-held 3D data acquistion</title> (2003)

The digitization of the 3D shape of real objects is a rapidly expanding discipline, with a wide variety of applications, including shape acquisition, inspection, reverse engineering, gauging and robot navigation. Developments in computer product design techniques, automated production, and the need for close manufacturing tolerances will be facts of life for the foreseeable future. A growing need exists for fast, accurate, portable, non-contact 3D sensors. However, in order for 3D scanning to become more commonplace, new methods are needed for easily, quickly and robustly acquiring accurate full geometric models of complex objects using low cost technology. In this paper, a brief survey is presented of current scanning technologies available for acquiring range data. An overview is provided of current 3D-shape acquisition using both active and passive vision techniques. Each technique is explained in terms of its configuration, principle of operation, and the inherent advantages and limitations. A separate section then focuses on the implications of scannerless scanning for hand held technology, after which the current status of 3D acquisition using handheld technology, together with related issues concerning implementation, is considered more fully. Finally, conclusions for further developments in handheld devices are discussed. This paper may be of particular benefit to new comers in this field.
Trigeminal neuralgia: Pathology and pathogenesis (2001)

There is now persuasive evidence that trigeminal neuralgia is usually caused by demyelination of trigeminal sensory fibres within either the nerve root or, less commonly, the brainstem. In most cases, the trigeminal nerve root demyelination involves the proximal, CNS part of the root and results from compression by an overlying artery or vein. Other causes of trigeminal neuralgia in which demyelination is involved or implicated include multiple sclerosis and, probably, compressive space-occupying masses in the posterior fossa. Examination of trigeminal nerve roots from patients with compression of the nerve root by an overlying blood vessel has revealed focal demyelination in the region of compression, with close apposition of demyelinated axons and an absence of intervening glial processes. Similar foci of nerve root demyelination and juxtaposition of axons have been demonstrated in multiple sclerosis patients with trigeminal neuralgia. Experimental studies indicate that this anatomical arrangement favours the ectopic generation of spontaneous nerve impulses and their ephaptic conduction to adjacent fibres, and that spontaneous nerve activity is likely to be increased by the deformity associated with pulsatile vascular indentation. Decompression of the nerve root produces rapid relief of symptoms in most patients with vessel-associated trigeminal neuralgia, probably because the resulting separation of demyelinated axons and their release from focal distortion reduce the spontaneous generation of impulses and prevent their ephaptic spread. The role of remyelination in initial symptomatic recovery after decompression is unclear. However, remyelination may help to ensure that relief of symptoms is sustained after decompression of the nerve root and may also be responsible for the spontaneous remission of the neuralgia in some patients. In addition to causing symptomatic relief, vascular decompression leads to rapid recovery of nerve conduction across the indented root, a phenomenon that, we suggest, is likely to reflect the reversal of compression-induced conduction block in larger myelinated fibres outside the region of demyelination. Trigeminal neuralgia can occur in association with a range of other syndromes involving vascular compression and hyperactivity of cranial nerves. Clinical observations and electrophysiological studies support the concept that demyelination and ephaptic spread of excitation underlie most, if not all, of these conditions.
Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors. (1994)

Xanomeline [3(3-hexyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1- methylpyridine] has been evaluated as a muscarinic receptor agonist. In vitro, xanomeline had high affinity for muscarinic receptors in brain homogenates, but had substantially less or no affinity for a number of other neurotransmitter receptors and uptake sites. In cells stably expressing genetic m1 receptors, xanomeline increased phospholipid hydrolysis in CHO, BHK and A9 L cells to 100, 72 and 55% of the nonselective agonist carbachol. In isolated tissues, xanomeline had high affinity for M1 receptors in the rabbit vas deferens (IC50 = 0.006 nM), low affinity for M2 receptors in guinea pig atria (EC50 = 3 microM), was a weak partial agonist in guinea pig ileum and was neither an agonist nor antagonist in guinea pig bladder. In vivo, xanomeline increased striatal levels of dopamine metabolites, presumably by acting at M1 heteroreceptors on dopamine neurons to increase dopamine release. In contrast, xanomeline had only a relatively small effect on acetylcholine levels in brain, indicating that it is devoid of actions at muscarinic autoreceptors. In the gastrointestinal tract, xanomeline inhibited small intestinal and colonic motility, but increased small intestinal transmural potential difference. In contrast to the nonselective muscarinic agonist oxotremorine, xanomeline did not produce salivation, tremor nor hypothermia; it did, however, increase heart rate. The present data are consistent with the interpretation that xanomeline is a novel muscarinic receptor agonist with functional selectivity for M1 muscarinic receptors both in vitro and in vivo.
Selective movpe growth and its application to semiconductor photonic integrated circuits (1993)

Abstract Considerable research and development have been done on semiconductor photonic integrated circuits in which various components such as a laser diode and other photonic devices were integrated. In this paper, a 1.55‐μm band wavelength division multiplexing (WDM) integrated light source for optical communication is developed and the results of the evaluation are described. Four‐channel laser sources were fabricated by integrating tunable semiconductor lasers and semiconductor optical modulators plus multiplexers, and the possibility of using a 2.5‐Gbit/s high‐density WDM optical transmission system is discussed. After analyzing the problems encountered in the fabrication of these photonic integrated components, the development of a bandgap energy‐controlling technique of quantum well structure using the selective metal oxide vapor‐phase epitaxial (MOVPE) growth, which is a better fabrication technique, is described. By using this technique, the difficult process of combining the waveguide with a different bandgap energy can be accomplished only by a one‐step crystal growing. This simplifies the components fabrication, and a high‐coupling efficiency of the waveguide between the integrated elements can be obtained. As an application example, the integrated light source was fabricated by integrating a tunable laser, distributed feedback (DFB) laser, and semiconductor optical modulator. Then the tunable characteristic and the extinction characteristic were verified. This simplifies the fabrication method of the previously difficult method of semiconductor photonic integrated circuits and clarifies the possibility of developing a high‐density integrated element.
Stromal cell‐derived factor‐1 stimulates vasculogenesis and enhances Ewing's sarcoma tumor growth in the absence of vascular endothelial growth factor (2008)

Stromal cell-derived Factor-1alpha (SDF-1alpha) stimulates the migration of bone marrow (BM) cells, similar to vascular endothelial growth factor (VEGF). We previously demonstrated that inhibition of VEGF(165) by small interfering RNA inhibited Ewing's sarcoma tumor growth, tumor vessel formation and recruitment of BM cells to the tumor. To determine the importance of BM cells in tumor vessel development, we investigated the effects of SDF-1alpha on VEGF-inhibited TC/siVEGF(7-1) Ewing's tumor neovasculature formation and growth. The effect of SDF-1alpha on CD34(+) progenitor cell chemotaxis was determined in vivo. Using a BM transplantation model with GFP(+) transgenic mice as BM donors and nude mice as recipients, we evaluated the effect of SDF-1alpha on the recruitment of BM-derived cells to VEGF(165)-inhibited TC/siVEGF(7-1) tumors, as well as its effect on neovasculature development, vessel morphology and tumor growth. SDF-1alpha stimulated the migration of CD34(+) progenitor cells to Matrigel plugs in vivo and promoted the retainment of BM-derived pericytes in close association with perfused, functional tumor vessels. Intratumor inoculation of Ad-SDF-1alpha into TC/siVEGF(7-1) tumors resulted in increased SDF-1 and PDGF-BB expression, augmented tumor growth, an increase in the number of large, lumen-bearing vascular structures, and enhanced vessel pericyte coverage, with no change in VEGF(165). SDF-1alpha stimulates BM cell chemotaxis and the association of these cells with functional tumor vessels. Furthermore, SDF-1alpha enhances tumor neovascularization and growth with no alteration in VEGF(165). Our work suggests that SDF-1-mediated vasculogenesis may represent an alternate pathway that could potentially be utilized by tumors to sustain growth and neovasculature expansion after anti-VEGF therapy.
4-Amino-3-alkylbutanoic acids as substrates for gamma-aminobutyric acid aminotransferase. (1990)

A variety of alkyl-substituted 4-aminobutanoic acid derivatives, including a homologous series of 3-alkyl-4-aminobutanoic acid analogues, 4-methyl isomer analogues, the 3,3-dimethyl analogue, and (E)-4-amino-3-methyl-2-butenoic acid, were synthesized and tested as alternate substrates for purified gamma-aminobutyric acid aminotransferase from pig brain. All of the compounds were substrates, but their activities diminished as the size and bulk of the 3-alkyl substituent increased. Several differences were observed between the alkyl-substituted analogues and the corresponding aryl-substituted compounds previously reported (Silverman, R. B., Invergo, B. J., and Levy, M. A. (1987) J. Biol. Chem. 262, 3192-3195). These findings will be important in future designs of inhibitors of gamma-aminobutyric acid aminotransferase.