gebhart/patrepeval huggingface dataset:
Fetal origins of developmental plasticity: Animal models of induced life history variation (2004)

The interaction of the genetic program with the environment shapes the development of an individual. Accumulating data from animal models indicate that prenatal and early-postnatal events (collectively called "early-life events") can initiate long-term changes in the expression of the genetic program which persist, or may only become apparent, much later in the individual's life. Researchers working with humans or animal models of human diseases often view the effects of early-life events through the lens of pathology, with a focus on whether the events increase the risk for a particular disease. Alternatively, comparative biologists often view the effects of early-life events through the lens of evolution and adaptation by natural selection; they investigate the processes by which environmental conditions present early in life may prompt the adoption of different developmental pathways leading to alternative life histories. Examples of both approaches are presented in this article. This article reviews the concepts of phenotypic plasticity, natural selection, and evidence from animal models that early-life events can program the activity of the neuroendocrine system, at times altering life history patterns in an adaptive manner. Data from seasonally breeding rodents are used to illustrate the use of maternally derived information to alter the life history of young. In several species, the maternal system transfers photoperiodic information to the young in utero. This maternally derived information alters the response of young to photoperiods encountered later and life, producing seasonally distinct life histories.
Correlative Immunohistochemical and Reverse Transcriptase Polymerase Chain Reaction Analysis of Somatostatin Receptor Type 2 in Neuroendocrine Tumors of the Lung (2000)

Somatostatin receptors type 2 (sst2) have been frequently detected in neuroendocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, antisst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different techniques the presence of sst2 in a series of 26 neuroendocrine tumors of the lung in which fresh frozen tissue and paraffin sections were available. It was possible, therefore, to compare, in individual cases, RNA analysis studied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry. A series of 20 nonneuroendocrine lung carcinoma samples served as controls. RT-PCR was positive for sst2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypical carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obtained by RT-PCR was strong in the majority (87%) of typical carcinoids and of variable intensity in atypical carcinoids and small-cell carcinomas. A weakly positive signal was observed in 5 of 20 control samples. In immunohistochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA (as detected by RT-PCR) and sst2 protein expression (as detected by immunohistochemistry) was observed. However, one atypical carcinoid and one small-cell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniques. A low sst2 expression was associated with high grade neuroendocrine tumors and with aggressive behavior. It is concluded that 1) neuroendocrine tumors of the lung express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identification in tissue sections may provide information on the diagnostic or therapeutic usefulness of somatostatin analogues in individual patients with neuroendocrine tumors.
Ethanol-Induced Apoptotic Neurodegeneration and Fetal Alcohol Syndrome (2000)

The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.
High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells. (2000)

Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 micromol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.
NFκB activation is required for interferon regulatory factor‐1‐mediated interferon β induction (1999)

The interferon regulatory factor 1 (IRF-1) acts as a transcriptional inducer of the interferon beta (IFN-beta) gene and interferon-stimulated genes. Here we report that IRF-1-mediated IFN-beta induction depends on NFkappaB activity. IRF-1 by itself initiates NFkappaB activation by inducing a reduction in cellular MAD3/IkappaBalpha, an inhibitor of NFkappaB. After nuclear translocation, NFkappaB synergizes with IRF-1 on the cis-elements positive regulatory domain (PRD)II and PRDI/III to induce transcription of the IFN-beta gene. In contrast with IFN-beta transcription induced by dsRNA or virus, c-Jun/ATF-2 binding to PRDIV is not involved. Recombinant MAD3/IkappaBalpha is phosphorylated in vitro by extracts from IRF-1-expressing cells. IRF-1-dependent MAD3/IkappaBalpha degradation is not detectable in cells expressing a dominant negative mutant of the protein kinase PKR, suggesting that PKR mediates MAD3/IkappaBalpha degradation.
Trapped-oligonucleotide nucleotide incorporation (TONI) assay, a simple method for screening point mutations (1992)

We present a simple screening method for detecting a known point mutation, using only one 5'-biotinylated oligonucleotide primer, with its 3' end adjacent to the mutation site. In parallel reactions, an amplified DNA template encompassing the biotinylated oligonucleotide and mutation site undergoes 40 step-cycles of single nucleotide incorporation using Taq thermostable DNA polymerase and only one radioactive [alpha-32P]dNTP, specified by either the normal or mutant sequence. The oligonucleotides, now radioactively labelled at the 3' end according to the template sequence, are then trapped by streptavidin-coated magnetic beads, and the percent of radiolabel incorporated is determined directly by the Cerenkov method in a scintillation counter. The trapped-oligonucleotide nucleotide incorporation (TONI) assay has been used for the screening of a mitochondrial polymorphism, and has also been shown to distinguish the genotypes of hemoglobin A/C, A/A, A/S, and S/S. It is reproducible over at least a 100-fold range of radioisotope and a 10-fold range of oligonucleotide primer. This method is particularly useful for diagnosing mutations which do not produce alterations detectable by restriction enzyme analysis, since optimization of conditions is rarely necessary. In addition, it requires only a single oligonucleotide, and no electrophoretic separation of the allele-specific products. It thus represents an improved and simplified modification of the existing allele-specific primer extension methods (Kuppuswamy et al., Proc Natl Acad Sci USA 88:1143-1147, 1991; Sokolov, Nucl Acids Res 18:3671, 1989; Syvanen et al., Genomics 8:684-692, 1990).
Epidurography and therapeutic epidural injections: technical considerations and experience with 5334 cases. (1999)

Epidurography in conjunction with epidural steroid injections provides for safe and accurate therapeutic injection and is associated with an exceedingly low frequency of untoward sequelae. It can be performed safely on an outpatient basis and does not require sedation or special monitoring.
Potential Biomedical Applications of The Scanned Nanopipette (2006)

One grand challenge in current biology is to understand how individual cellular molecules interact together to form a functioning living cell. This requires new methods to image a live cell on the nanoscale. The scanned nanopipette can be used to obtain high resolution noncontact images of the surface of live cells under physiological conditions and has been used to develop a family of related methods that allow mapping of cell function on the nanoscale, and hence allow the relationship between cell structure and function to be probed. This is a powerful method to bridge the current gap between high resolution structures of individual molecular complexes and low resolution imaging of live cell structure and function.
Interferon Synthesis by Micro-organisms (1984)

Description des differentes classes d'interferon, methodes de clonage des genes et de synthese chez les microorganismes; techniques de production d'analogues: structure et proprietes therapeutiques eventuelles
Somatic mosaicism in Wiskott–Aldrich syndrome suggestsin vivoreversion by a DNA slippage mechanism (2001)

Somatic mosaicism caused by in vivo reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. In most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott--Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism.
Current gain collapse in microwave multifinger heterojunction bipolar transistors operated at very high power densities (1993)

The rapid development of heterojunction bipolar transistor (HBT) technologies has led to the demonstration of high power single-chip microwave amplifiers. Because HBTs are operated at high power densities, the ultimate limits on the performance of HBTs are imposed by thermal considerations. The authors address a thermal phenomenon observed when a multifinger power HBT is operating at high power densities. This phenomenon, referred to as the collapse (of current gain), occurs when suddenly one finger of the HBT draws most of the collector current, leading to an abrupt decrease of current gain. A quantitative model and the condition separating the normal operation region and the collapse are presented. Critical difference of the collapse in the constant l/sub b/ and constant V/sub be/ modes of operation is discussed for the common-emitter l-V characteristics. The collapse in the common-base l-V characteristics and its relationship with avalanche breakdown are also described. A solution to eliminate the collapse is experimentally verified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Waves on interfaces (1959)

In wave propagation along plane or cylindrical interfaces a distinction is made between truly guided waves (surface waves) and partially guided waves (radiating waves). When dissipation losses are involved, surface waves no longer represent the asymptotic field near the interfaces at large distances from the source. In order to separate them from the total field it is necessary to have a criterion for radiating waves which are free of any surface wave components. Such a criterion exists in the form of orthogonality relations which are the mathematical formulation of the concept that an ideal antenna which excites only a surface wave should not receive a radiating wave.
CD44v10 interaction with Rho‐kinase (ROK) activates inositol 1,4,5‐triphosphate (IP3) receptor‐mediated Ca2+ signaling during hyaluronan (HA)‐induced endothelial cell migration (2002)

Aortic endothelial cells (GM7372A) express a major cell adhesion molecule, CD44v10, which binds the extracellular matrix component, hyaluronan (HA), at its external domain and interacts with various signaling molecules at its cytoplasmic domain. In this study, we have determined that CD44v10 and Rho-Kinase (ROK) are physically associated as a complex in vivo. Using a recombinant fragment of ROK (in particular, the pleckstrin homology [PH] domain) and in vitro binding assays, we have detected a specific binding interaction between the PH domain of ROK and the cytoplasmic domain of CD44. Scatchard plot analysis indicates that there is a single high-affinity CD44 binding site in the PH domain of ROK with an apparent dissociation constant (Kd) of 1.76 nM, which is comparable to CD44 binding (Kd approximately 1.56 nM) to intact ROK. These findings suggest that the PH domain is the primary ROK binding region for CD44. Furthermore, HA binding to GM7372A cells promotes RhoA-mediated ROK activity, which, in turn, increases phosphorylation of three different inositol 1, 4, 5-trisphosphate receptors (IP(3)Rs) [in particular, subtype 1 (IP(3)R1), and to a lesser extent subtype 2 (IP(3)R2) and subtype 3 (IP(3)R3)] all known as IP(3)-gated Ca(2+) channels. The phosphorylated IP(3)R1 (but not IP(3)R2 or IP(3)R3) is enhanced in its binding to IP(3) which subsequently stimulates IP(3)-mediated Ca(2+) flux. Transfection of the endothelial cells with ROK's PH cDNA significantly reduces ROK association with CD44v10, and effectively inhibits ROK-mediated phosphorylation of IP(3)Rs and IP(3)R-mediated Ca(2+) flux in vitro. The PH domain of ROK also functions as a dominant-negative mutant in vivo to block HA-dependent, CD44v10-specific intracellular Ca(2+) mobilization and endothelial cell migration. Taken together, we believe that CD44v10 interaction with ROK plays a pivotal role in IP(3)R-mediated Ca(2+) signaling during HA-mediated endothelial cell migration.
Factors associated with bronchial hyperresponsiveness in Australian adults and children (1992)

To accurately assess putative risk factors for bronchial hyperresponsiveness (BHR), we have used multivariate models to analyse data from 4,366 children living in four regions and from 878 adults. A standard protocol was used to measure bronchial responsiveness to histamine. The prevalence of BHR was high at 7-9 yrs (16-18%), decreased significantly at 11-14 yrs (7-8%), and then increased in adults (12-14%). Atopy was the most important risk factor for BHR at all ages. In children, parental asthma, early respiratory illness and being born in Australia also had a significant influence, and eating fish more than once a week had a protective effect. No effect of parental smoking, gender or race was found. In adults, BHR was associated with being female and with smoking history. It appears that many factors have a significant influence on the presence of BHR, with environmental factors, particularly atopy, birthplace and diet, being the most important.
Attenuated vasodilatation in lambs with endogenous and exogenous activation of cGMP signaling: Role of protein kinase G nitration (2011)

Pulmonary vasodilation is mediated through the activation of protein kinase G (PKG) via a signaling pathway involving nitric oxide (NO), natriuretic peptides (NP), and cyclic guanosine monophosphate (cGMP). In pulmonary hypertension secondary to congenital heart disease, this pathway is endogenously activated by an early vascular upregulation of NO and increased myocardial B-type NP expression and release. In the treatment of pulmonary hypertension, this pathway is exogenously activated using inhaled NO or other pharmacological agents. Despite this activation of cGMP, vascular dysfunction is present, suggesting that NO-cGMP independent mechanisms are involved and were the focus of this study. Exposure of pulmonary artery endothelial or smooth muscle cells to the NO donor, Spermine NONOate (SpNONOate), increased peroxynitrite (ONOO(-) ) generation and PKG-1α nitration, while PKG-1α activity was decreased. These changes were prevented by superoxide dismutase (SOD) or manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) and mimicked by the ONOO(-) donor, 3-morpholinosydnonimine N-ethylcarbamide (SIN-1). Peripheral lung extracts from 4-week old lambs with increased pulmonary blood flow and pulmonary hypertension (Shunt lambs with endogenous activation of cGMP) or juvenile lambs treated with inhaled NO for 24 h (with exogenous activation of cGMP) revealed increased ONOO(-) levels, elevated PKG-1α nitration, and decreased kinase activity without changes in PKG-1α protein levels. However, in Shunt lambs treated with L-arginine or lambs administered polyethylene glycol conjugated-SOD (PEG-SOD) during inhaled NO exposure, ONOO(-) and PKG-1α nitration were diminished and kinase activity was preserved. Together our data reveal that vascular dysfunction can occur, despite elevated levels of cGMP, due to PKG-1α nitration and subsequent attenuation of activity.
The disulfide bridge pattern of snake venom disintegrins, flavoridin and echistatin (1992)

Flavoridin and echistatin, isolated from the venom of Trimeresurus flavoviridis and Echis carinatus, respectively, belong to the disintegrin family of integrin beta 1 and beta 3 inhibitors of low molecular weight RGD-containing, cysteine-rich peptides. Since disulfide bonds are critical for expression of biological activity, we sought to determine their location in these two proteins. In flavoridin, direct evidence for the existence of linkage between Cys4-Cys19 and between Cys45 and Cys64 was obtained by analysis of proteolytic products, and indirect evidence suggests links between Cys6-Cys14 and Cys13-Cys36. In echistatin, links between Cys8-Cys37 and Cys20-Cys39 were identified by direct chemical analysis.
Prostate-Specific Antigen-Activated Thapsigargin Prodrug as Targeted Therapy for Prostate Cancer (2003)

Further development of PSA-activated thapsigargin prodrugs as therapy for metastatic prostate cancer is warranted.
A protective monoclonal antibody recognizes a linear epitope in the precursor to the major merozoite antigens of Plasmodium chabaudi adami. (1989)

The monoclonal antibody 5C10/66 was shown to afford strong protection in mice against fulminating Plasmodium chabaudi adami infection. This was remarkable, as immunity to this organism is regarded to be mainly T-cell mediated. This antibody identified a 250-kDa molecule in schizonts and an 83-kDa fragment in merozoites. A cDNA clone selected by 5C10/66 was the homologue of the Plasmodium falciparum precursor to the major merozoite surface antigen (PMMSA). Comparison with the P. falciparum sequence showed that the P. chabaudi adami clone encoded the middle portion of the gene and that it can also be divided into variable and conserved blocks. Screening of a set of all possible octamer peptides predicted by the cDNA clone revealed that the core epitope of 5C10/66 was Glu-Thr-Thr-Glu-Thr. This region resides in a variable block of PMMSA.
Phage Display Shot-Gun Cloning of Ligand-Binding Domains of Prokaryotic Receptors Approaches 100% Correct Clones (1996)

We recently presented an application of the phage display technique enabling cloning of DNA encoding ligand-binding domain(s) of prokaryotic receptors directly from chromosomal DNA. Here we show that the use of a gene VIII-based, instead of a gene III-based, phagemid vector system results in a much more efficient selection for phage displaying a binding capacity. A phagemid library was made by insertion of randomly fragmented chromosomal DNA from Staphylococcus aureus strain 8325-4 into gene VIII in the constructed phagemid vector pG8H6. The library, which in theory should express parts of all proteins encoded by the bacterial genome, was affinity panned against the ligands IgG, fibronectin and fibrinogen, respectively. After a second panning against the same ligand, a significant increase in the number of eluted phagemid particles was observed, and 75%–100% of randomly picked clones contained inserts derived from genes encoding proteins with a binding affinity for the respective ligand. The results show that this technique can be used for cloning prokaryotic receptor genes without any prior knowledge of the receptor, thus eliminating the need for probes in the identification of receptor genes.
Cell Membrane Lipid Rafts Mediate Caveolar Endocytosis of HIV-1 Tat Fusion Proteins (2003)

The transactivator protein of human immunodeficiency virus type 1 Tat has the unique property of mediating the delivery of large protein cargoes into the cells when present in the extracellular milieu. Here we show that Tat fusion proteins are internalized by the cells through a temperature-dependent endocytic pathway that originates from cell membrane lipid rafts and follows caveolar endocytosis. These conclusions are supported by the study of the slow kinetics of the internalization of Tat endosomes, by their resistance to nonionic detergents, the colocalization of internalized Tat with markers of caveolar endocytosis, and the impairment of the internalization process by drugs that disrupt lipid rafts or disturb caveolar trafficking. These results are of interest for all those who exploit Tat as a vehicle for transcellular protein delivery.