gebhart/patrepeval huggingface dataset:
Vascular endothelial growth factor prevents G93A‐SOD1‐induced motor neuron degeneration (2009)

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by selective loss of motor neurons (MNs). Twenty percent of familial ALS cases are associated with mutations in Cu(2+)/Zn(2+) superoxide dismutase (SOD1). To specifically understand the cellular mechanisms underlying mutant SOD1 toxicity, we have established an in vitro model of ALS using rat primary MN cultures transfected with an adenoviral vector encoding a mutant SOD1, G93A-SOD1. Transfected cells undergo axonal degeneration and alterations in biochemical responses characteristic of cell death such as activation of caspase-3. Vascular endothelial growth factor (VEGF) is an angiogenic and neuroprotective growth factor that can increase axonal outgrowth, block neuronal apoptosis, and promote neurogenesis. Decreased VEGF gene expression in mice results in a phenotype similar to that seen in patients with ALS, thus linking loss of VEGF to the pathogenesis of MN degeneration. Decreased neurotrophic signals prior to and during disease progression may increase MN susceptibility to mutant SOD1-induced toxicity. In this study, we demonstrate a decrease in VEGF and VEGFR2 levels in the spinal cord of G93A-SOD1 ALS mice. Furthermore, in isolated MN cultures, VEGF alleviates the effects of G93A-SOD1 toxicity and neuroprotection involves phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Overall, these studies validate the usefulness of VEGF as a potential therapeutic factor for the treatment of ALS and give valuable insight into the responsible signaling pathways and mechanisms involved.
The nucleotide and partial amino acid sequence of toxic shock syndrome toxin-1. (1986)

The nucleotide sequence of toxic shock syndrome toxin-1 (TSST-1) has been determined. In addition, one-third of the predicted amino acid sequence was confirmed by amino acid sequence analysis of cyanogen bromide-generated TSST-1 protein fragments. The DNA sequencing results identified a 708-base pair open reading frame starting with an ATG, 7 base pairs downstream from a Shine-Dalgarno sequence, and terminating at a UAA stop codon. Amino acid analysis of the intact protein defined the NH2 terminus of the mature protein and located the cleavage point for the signal peptide (Ala/Ser). The signal peptide contained the first 40 amino acids and had characteristic structural similarities with other bacterial signal peptides. The coding sequence of the mature protein was 585 base pairs (194 amino acids) in length, and the molecular weight of the predicted protein was 22,049. This is in good agreement with the previously reported molecular weight of TSST-1 (22,000), as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NH2-terminal amino acid sequence analysis performed on isolated TSST-1 CNBr fragments determined the position of the peptides in the TSST-1 sequence and verified the predicted amino acid sequence in those positions. Computer analyses of the amino acid sequence showed that TSST-1 has little or no sequence homology with biologically related toxins, streptococcal pyrogenic exotoxin A, and staphylococcal enterotoxins B and C.
RNAi analysis of Deformed, proboscipedia and Sex combs reduced in the milkweed bug Oncopeltus fasciatus: novel roles for Hox genes in the Hemipteran head (2000)

Insects have evolved a large variety of specialized feeding strategies, with a corresponding variability in mouthpart morphology. We have, however, little understanding of the developmental mechanisms that underlie this diversity. Until recently it was difficult to perform any analysis of gene function outside of the genetic model insects Drosophila melanogaster and Tribolium castaneum. In this paper, we report the use of dsRNA-mediated interference (RNAi) to dissect gene function in the development of the milkweed bug Oncopeltus fasciatus, which has specialized suctorial mouthparts. The Hox genes Deformed (Dfd), proboscipedia (pb) and Sex combs reduced (Scr) have previously been shown to be expressed in the gnathal appendages of this species. Strikingly, the milkweed bug was found to have an unusual expression pattern of pb. Here, by analyzing single and combination RNAi depletions, we find that Dfd, pb and Scr are used in the milkweed bug to specify the identity of the mouthparts. The exact roles of the genes, however, are different from what is known in the two genetic model insects. The maxillary appendages in the bug are determined by the activities of the genes Dfd and Scr, rather than Dfd and pb as in the fly and beetle. The mandibular appendages are specified by Dfd, but their unique morphology in Oncopeltus suggests that Dfd's target genes are different. As in flies and beetles, the labium is specified by the combined activities of pb and Scr, but again, the function of pb appears to be different. Additionally, the regulatory control of pb by the other two genes seems to be different in the bug than in either of the other species. These novelties in Hox function, expression pattern and regulatory relationships may have been important for the evolution of the unique Hemipteran head.
Nerve regeneration along bioengineered scaffolds (2007)

Tissue engineering has recently seen great advancements in many medical fields, including peripheral nerve reconstruction. In the rat median nerve model, we investigated nerve repair by means of bioengineered tissue scaffolds (muscle-vein-combined tubes) focusing on changes in the neuregulin-1/ErbB-receptor system which represents one of the main regulatory systems of axo-glial interaction in peripheral nerves. Repaired nerves were withdrawn at 5, 15, and 30 days postoperative and processed for morphological and retro-transcriptase polymerase chain reaction (RT-PCR) analysis. Results revealed an early and progressive increase in the expression of NRG1alpha isoform only, while the appearance of the beta isoform of NRG1, which is normally present in peripheral nerves, was delayed. In regards to ErbB2 and ErbB3 receptors, their expression increased progressively inside the muscle-vein-combined scaffolds, though with different kinetics. Taken together, these results suggest that variations in neuregulin-1/ErbB system activation play a key role in peripheral nerve regeneration along bioengineered muscle-vein-combined scaffolds. Since similar variations are also detectable in denervated skeletal muscles, it can be hypothesized that the existence of a NRG1's autocrine/paracrine trophic loop shared by both glial and muscle fibers could be responsible for the effectiveness of muscle-vein-combined conduits for repairing nerve defects.
Estrogen induction of growth factors specific for hormone-responsive mammary, pituitary, and kidney tumor cells. (1978)

The problem of estrogen-promoted tumor cell growth has been studied extensively in an attempt to establish the direct mitogenic role of these steroid hormones. We have developed cell lines from three estrogen-responsive tumors or cell populations: the H-301 kidney tumor cells established from a parent estrogen-dependent hamster kidney tumor, the GH3/C14 rat pituitary tumor cell line established as a subline of the original GH3 population, and the MTW9/PL mammary cell line developed from a parent estrogen- and prolactin-responsive MT-W9A carcinogen-induced rat tumor. With all three of these cell lines, we have encountered a paradox: although estrogens are obligatory for tumor formation in vivo, no direct mitogenic effect of estrogens can be shown in culture when assayed by an increase in cell number. We have thus considered the possibility that estrogens may induce growth factors in vivo that are then responsible for tumor formation by the three cell lines described. Experiments presented in this report show that extracts of rodent uterus, kidney, or liver contain growth activity for these three tumor cell lines, that estrogen treatment causes an increase in tissue content of these activities, and that the estrogen-induced activities are specific for the estrogen-responsive cells. These studies suggest that estrogen-responsive tumor growth in vivo includes the mechanism of estrogen leads to uterus, kidney, or liver leads to specific growth factors leads to estrogen-responsive tumor cells.
Resveratrol induces apoptosis and inhibits adipogenesis in 3T3‐L1 adipocytes (2008)

Resveratrol, a phytoallexin, has recently been reported to slow aging by acting as a sirtuin activator. Resveratrol also has a wide range of pharmacological effects on adipocytes. In this study, we investigated the effects of resveratrol on adipogenesis and apoptosis using 3T3-L1 cells. In mature adipocytes, 100 and 200 microM resveratrol decreased cell viability dose-dependently by 23 +/- 2.7%, and 75.3 +/- 2.8% (p < 0.0001), respectively, after 48 h treatment, and 100 microM resveratrol increased apoptosis by 76 +/- 8.7% (p < 0.0001). Resveratrol at 25 and 50 microM decreased lipid accumulation in maturing preadipocytes significantly by 43 +/- 1.27% and 94.3 +/- 0.3% (p < 0.0001) and decreased cell viability by 25 +/- 1.3% and 70.4 +/- 1.6% (p < 0.0001), respectively. In order to understand the anti-adipogenic effects of resveratrol, maturing 3T3-L1 preadipocytes were treated with 25 microM resveratrol and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Resveratrol down-regulated the expression of PPAR gamma, C/EBP alpha, SREBP-1c, FAS, HSL, LPL and up-regulated the expression of genes regulating mitochondrial activity (SIRT3, UCP1 and Mfn2). These results indicate that resveratrol may alter fat mass by directly affecting cell viability and adipogenesis in maturing preadipocytes and inducing apoptosis in adipocytes and thus may have applications for the treatment of obesity.
Acute Liver Failure Associated with Levetiracetam and Lacosamide Combination Treatment for Unspecified Epileptic Disorder (2013)

Background and Aim. Levetiracetam is a second-generation antiepileptic drug. It is approved as an adjunctive treatment of partial onset seizures with or without secondary generalization. It is considered safe with less than 1% of patients with transient elevations of liver enzymes. Methods. We report a case of acute liver failure secondary to Levetiracetam in combination with Lacosamide documented with a liver biopsy. Results. Liver biopsy demonstrated acute liver injury with a predominant submassive necrosis pattern and features of a drug-induced hepatitis. Conclusions. This is the first published case of acute liver failure due to antiepileptic therapy with Levetiracetam in combination with Lacosamide.
Click Chemistry as a Macrocyclization Tool in the Solid-Phase Synthesis of Small Cyclic Peptides (2007)

Despite the vast number of techniques developed for the cyclization of small peptides, cyclization efficiency remains problematic in peptides that lack turn-promoting structures. Here we demonstrate the utility of click chemistry as a macrocyclization tool in the solid-phase synthesis of cyclic tetra-, penta-, hexa-, and heptapeptides. On-resin cyclization is completed at room temperature within 6 h, resulting in predominantly monomer with small amounts of cyclomultimer byproducts.
Novel cationic dye and crosslinkable surfactant for DNA biophotonics (2012)

Biopolymers such as DNA can be used as a host material for nonlinear optical dyes for photonic applications. In previous work by Heckman et al. (Proc. SPIE 6401, 640108-2), the chromophore Disperse Red 1 (DR1) was combined with CTMA-DNA (a water-insoluble DNA/surfactant complex) to produce an electro-optic waveguide modulator. However, DR1 does not bind strongly to DNA and has a low first hyperpolarizability (&beta;). We have used theory-aided design to develop and synthesize a novel chromophore with strong affinity for DNA and higher &beta; than DR1. We have also developed a surfactant containing a photocrosslinkable moiety that can be used to harden thin films of the DNA/surfactant/dye composite under ultraviolet light. The optical and thermal properties of these materials and outlook for device applications will be discussed.
Effect of condensed tannins on egg hatching and larval development of Trichostrongylus colubriformis in vitro (2002)

The effects of condensed tannins extracted from seven forages on the viability of the eggs and first stage (L1) larvae of the sheep nematode Trichostrongylus colubriformis were evaluated in in vitro assays. The extracts of condensed tannins were obtained from Lotus pedunculatus (LP), Lotus corniculatus (LC), sulla (Hedysarum coronarium), sainfoin (Onobrychus viciifolia), Dorycnium pentaphylum (DP), Dorycnium rectum (DR) and dock (Rumex obtusifolius). Extracts containing 200 to 500 microg/ml reduced the proportion of eggs that hatched. The larval development assay was used to evaluate the effect of the extracts on the development of either eggs or L1 larvae to L3 infective larvae. Development was allowed to proceed for seven days by which time the larvae in control incubations had reached the infective L3 stage. Extracts containing 200 microg/ml from LP, DP, DR or dock prevented egg development, and only 11, 8 and 2 per cent of the eggs developed to L3 larvae with extracts from LC, sulla and sainfoin, respectively. When the concentration was 400 microg/ml no eggs developed to L3 larvae. The addition of the extracts after hatching also inhibited the development of L1 to L3 larvae; 200 microg/ml extracted from LP, LC, sulla, sainfoin, DP, DR and dock resulted in only 14, 18, 17, 15, 14, 16 and 4 per cent of L1 larvae developing to the L3 stage compared with 85 per cent for controls, and 400 microg/ml further reduced the development of L1 larvae. Statistical analyses showed that when the extracts were added before hatching they were significantly (P<0.001) more effective at inhibiting the larval development than when they were added after hatching. The condensed tannins from dock had the greatest inhibitory effect on egg development followed by the tannins from DR, sainfoin, DP, LP, sulla and LC.
1.7-ps, microwave, integrated-circuit-compatible InAs/AlSb resonant tunneling diodes (1993)

Microwave integrated-circuit-compatible InAs/AlSb resonant tunneling diodes (RTDs) have been fabricated. The resulting devices have peak current densities of 3.3*10/sup 5/ A/cm/sup 2/ with peak-to-valley ratios of 3.3. Switching transition times of 1.7 ps are measured using electrooptic sampling techniques.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Detection, isolation, and capture of circulating breast cancer cells with photoacoustic flow cytometry (2013)

According to the CDC, breast cancer is the most common cancer and the second leading cause of cancer related deaths among women. Metastasis, or the presence of secondary tumors caused by the spread of cancer cells via the circulatory or lymphatic systems, significantly worsens the prognosis of any breast cancer patient. In this study, a technique is developed to detect circulating breast cancer cells in human blood using a photoacoustic flow cytometry method. A Q-switched laser with a 5 ns pulse at 532 nm is used to interrogate thousands of cells with one pulse as they flow through the beam path. Cells which are pigmented, either naturally or artificially, emit an ultrasound wave as a result of the photoacoustic (PA) effect. Breast cancer cells are targeted with chromophores through immunochemistry in order to provide pigment. After which, the device is calibrated to demonstrate a single-cell detection limit. Cultured breast cancer cells are added to whole blood to reach a biologically relevant concentration of about 25-45 breast cancer cells per 1 mL of blood. An in vitro photoacoustic flow cytometer is used to detect and isolate these cells followed by capture with the use of a micromanipulator. This method can not only be used to determine the disease state of the patient and the response to therapy, it can also be used for genetic testing and in vitro drug trials since the circulating cell can be captured and studied.
The Pathogenic Role of Macrophage Migration Inhibitory Factor in Immunologically Induced Kidney Disease in the Rat (1997)

Macrophage migration inhibitory factor (MIF) plays a pivotal role in the inflammatory response in endotoxemia and in the delayed-type hypersensitivity response, but its potential as a regulator of immunologically induced disease is unknown. We have addressed this issue by administering a neutralizing anti-MIF antibody in a rat model of immunologically induced crescentic anti-glomerular basement membrane (GBM) glomerulonephritis. Six individual experiments using paired inbred littermates were performed. Rats were primed with rabbit immunoglobulin on day -5 and then injection with rabbit anti-rat GBM serum on day 0. Pairs of animals were treated with anti-MIF or a control monoclonal antibody from the time of anti-GBM serum administration until being killed 14 d later. Control antibody-treated animals developed severe proteinuria and renal function impairment with severe histological damage due to marked leukocytic infiltration and activation within the kidney. In contrast, anti-MIF treatment substantially reduced proteinuria, prevented the loss of renal function, significantly reduced histological damage including glomerular crescent formation, and substantially inhibited renal leukocytic infiltration and activation (all P <0.001 compared with control treatment). Inhibition of renal disease by anti-MIF treatment was attributed to preventing the marked upregulation of interleukin-1beta, leukocyte adhesion molecules including intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and inducible nitric oxide synthase expression seen in the control antibody-treated animals. This inhibition of progressive renal injury was mirrored by the complete suppression of the skin delayed-type hypersensitivity response to the challenge antigen (rabbit IgG). Interestingly, anti-MIF treatment did not effect the secondary antibody response or immune deposition within the kidney, indicating that MIF participates in cellular-based immunity in this primed macrophage-dependent anti-GBM glomerulonephritis. In conclusion, this study has demonstrated a key regulatory role for MIF in the pathogenesis of immunologically induced kidney disease. These results argue that blocking MIF activity may be of benefit in the treatment of human rapidly progressive glomerulonephritis, and suggest that MIF may be important in immune-mediated disease generally.
Directed polymerase evolution (2013)

Polymerases evolved in nature to synthesize DNA and RNA, and they underlie the storage and flow of genetic information in all cells. The availability of these enzymes for use at the bench has driven a revolution in biotechnology and medicinal research; however, polymerases did not evolve to function efficiently under the conditions required for some applications and their high substrate fidelity precludes their use for most applications that involve modified substrates. To circumvent these limitations, researchers have turned to directed evolution to tailor the properties and/or substrate repertoire of polymerases for different applications, and several systems have been developed for this purpose. These systems draw on different methods of creating a pool of randomly mutated polymerases and are differentiated by the process used to isolate the most fit members. A variety of polymerases have been evolved, providing new or improved functionality, as well as interesting new insight into the factors governing activity.
Off‐label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study (2011)

According to this data, fumarates may represent a new approach in the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. For the first time, the successful treatment of LP and CDLE with fumarates is reported. Side-effects are not limiting in most cases, but can hamper a dose escalation.
ADVANCES IN CHEMICAL GENETICS (2005)

Chemical genetics is an emerging approach for studying biological systems using chemical tools. This strategy aims to reveal the macromolecules responsible for regulating biological systems; thus, the approach shares much in common with genetics. In both strategies, one must (a) develop an assay that reports on a biological process of interest, (b) perturb this process systematically (with mutations or small molecules), and (c) determine the target of each perturbation to reveal macromolecules (i.e., proteins and genes) regulating the process of interest. In this review, we discuss advances and challenges in this field that have emerged over the past four years. Several technologies have converged, raising the hope that it may be possible to systematically apply chemical probes to biological processes.
Hospital Deaths in Patients With Sepsis From 2 Independent Cohorts (2014)

Hospital Deaths in Patients With Sepsis From 2 Independent CohortsSepsis, the inflammatory response to infection, affects millions of patients worldwide. 1However, its effect on overall hospital mortality has not been measured.We quantified the contribution of sepsis to mortality in 2 complementary inpatient cohorts from Kaiser Permanente Northern California (KPNC) and the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS).Methods | The KPNC cohort included 482 828 adults (aged ≥18 years) with overnight, nonobstetrical hospitalizations at 21 KPNC hospitals between 2010 and 2012. 2 Compared with all Northern California patients, KPNC patients have broadly similar health characteristics but higher income and educational attainment. 3The NIS, a nationally representative sample of 1051 hospitals, included 6.5 million unweighted adult hospitalizations in 2010. 4e used 2 approaches to identify patients with sepsis from International Statistical Classification of Diseases, Ninth Revision, Clinical Modification codes.The explicit approach identified those with codes 038 (septicemia), 995.91 (sepsis), 995.92 (severe sepsis), or 785.52 (septic shock).Because of the known underrecognition of sepsis, we also used an implicit approach adding patients with evidence of both infection and acute organ failure using the Angus implementation 5 of sepsis consensus criteria.Within KPNC data, we delineated diagnoses when coded as present on admission, an important consideration for improving identification and treatment efforts.Furthermore, we linked 97.9% (n = 19 621) of all explicit sepsis cases present on admission in 2012 to KPNC quality improvement data, permitting stratification of patients by com-