gebhart/patrepeval huggingface dataset:
Multiple RNA binding domains (RBDs) just don't add up (1995)

One of the most common motifs for binding RNA in eukaryotes is the RNA binding domain (RBD) or RNA Recognition Motif (RRM). One of the more intriguing aspects of these proteins is their modular nature. Proteins have been found containing from one to four RRMs. In most instances, these domains have some basal level of non-sequence specific RNA binding affinity. In addition, many also have a higher affinity for a specific structure or sequence of RNA. In the cases of heterogenous nuclear ribonucleoprotein A1 (hnRNP A1), yeast poly-A binding protein and splicing factor U2AF65, the individual free energy of binding of the RBDs for RNA are not strictly additive. By invoking a model in which the amino acids connecting adjoining RBDs are considered to be flexible linkers with an interresidue spacing of about 3.5 A, it is possible to predict the apparent association constants for at least some multi-RBD proteins to single-stranded RNA. We have surveyed the literature and found that individual RBDs are separated by 'linker' sequences of highly variable length. These linkers provide a critical determinant of binding affinity and may modulate cis versus trans binding. A clearer understanding of multi-RBD binding is essential to critically evaluating the role of these proteins in RNA splicing, packaging and transport.
Modern corneal and refractive procedures (2011)

Recent advances in technology and our understanding of corneal physiology have led to a rapid progression in available corneal and refractive surgical procedures. In contrast to the past, penetrating keratoplasty is no longer the only intervention of choice. Lamellar keratoplasty has gained a renewed interest and newer approaches, such as phototherapeutic keratectomy, laser-assisted in situ keratomileusis, intrastromal corneal ring segments, corneal collagen crosslinking, deep anterior lamellar keratoplasty and endothelial keratoplasty, are improving and becoming increasingly popular. This article is intended to be an overview of the modern corneal procedures, divided into three categories: anterior cornea, including those involving the epithelium, Bowman's layer and anterior stroma; stromal; and posterior cornea, including those involving the posterior stroma, Descemet's membrane and endothelium. Newer and experimental corneal procedures are also discussed.
Experimental radioimmunotherapy of a xenografted human colonic tumor (GW-39) producing carcinoembryonic antigen. (1981)

Experiments were undertaken to evaluate the antitumor effects of 131I-labeled goat antibody immunoglobulin G prepared against carcinoembryonic antigen in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma. At a single injection of 1 mCi 131I and higher, a marked growth inhibition of GW-39 tumors, as well as a considerable increase in the survival time of the tumor-bearing hamsters, could be achieved. At a dose of 1 mCi, the radioactive affinity-purified antibody appeared to be superior to radioactive normal goat immunoglobulin G in influencing tumor growth and survival time, but no significant difference could be seen at the higher dose of 2 mCi given. Radiobiological calculations indicated that the tumors received, at up to 20 days after therapy, 1325 rads for the specific antibody and only 411 rads for the normal immunoglobulin G preparation. These findings encourage the further evaluation of antibodies to tumor markers for isotopic cancer therapy.
Hyaluronic acid gel fillers in the management of facial aging (2008)

Time affects facial aging by producing cellular and anatomical changes resulting in the consequential loss of soft tissue volume. With the advent of new technologies, the physician has the opportunity of addressing these changes with the utilization of dermal fillers. Hyaluronic acid (HA) dermal fillers are the most popular, non-permanent injectable materials available to physicians today for the correction of soft tissue defects of the face. This material provides an effective, non invasive, non surgical alternative for correction of the contour defects of the face due to its enormous ability to bind water and easiness of implantation. HA dermal fillers are safe and effective. The baby-boomer generation, and their desire of turning back the clock while enjoying an active lifestyle, has expanded the popularity of these fillers. In the US, there are currently eight HA dermal fillers approved for commercialization by the Food and Drug Administration (FDA). This article reviews the innate properties of FDA-approved HA fillers and provides an insight on future HA products and their utilization for the management of the aging face.
High Prevalence of Fatty Acid Synthase Expression in Colorectal Cancers in Middle Eastern Patients and Its Potential Role as a Therapeutic Target (2009)

These data identify FASN as a potential biomarker and a novel therapeutic target in distinct molecular subtypes of CRC.
Graphene-based biosensor for on-chip detection of bio-orthogonally labeled proteins to identify the circulating biomarkers of aging during heterochronic parabiosis (2018)

Studies of heterochronic parabiosis, where two animals of different ages are joined surgically, provided proof-of-principle results that systemic proteins have broad age-specific effects on tissue health and repair. In an effort to identify these systemic proteins, we previously developed a method to selectively label the proteome of only one animal joined in parabiosis utilizing bio-orthogonal non-canonical amino acid tagging (BONCAT), which can metabolically label proteins during their de novo synthesis by incorporating a methionine substitute, azido-nor-leucine (ANL), in cells expressing a mutant methionyl-tRNA synthetase (MetRSL274G). Once labeled, we can selectively identify the proteins produced by the MetRSL274G transgenic mouse in the setting of heterochronic parabiosis. This approach enabled the detection of several rejuvenating protein candidates from the young parabiont, which were transferred to the old mammalian tissue through their shared circulation. Although BONCAT is a very powerful technology, the challenges associated with its complexity including large starting material requirements and cost of ANL-labeled protein detection, such as modified antibody arrays and mass spectrometry, limit its application. Herein, we propose a lab-on-a-chip technology, termed Click-A+Chip for facile and rapid digital detection of ANL-labeled proteomes present in minute amount of sample, to replace conventional assays. Click-A+Chip is a graphene-based field effect biosensor (gFEB) which utilizes novel on-chip click-chemistry to specifically bind to ANL-labeled biomolecules. In this study, Click-A+Chip is utilized for the capture of ANL-labeled proteins transferred from young to old parabiotic mouse partners. Moreover, we were able to identify the young-derived ANL-labeled Lif-1 and leptin in parabiotic systemic milieu, confirming previous data as well as providing novel findings on the relative levels of these factors in young versus old parabionts. Summarily, our results demonstrate that Click-A+Chip can be used for rapid detection and identification of ANL-labeled proteins, significantly reducing the sample size, complexity, cost and time associated with BONCAT analysis.
Cloning, nucleotide sequencing, and expression of tetanus toxin fragment C in Escherichia coli (1986)

The amino acid sequence of the first 30 residues of fragment C of tetanus toxin was determined, and a mixture of 32 complementary oligonucleotides, each 17 bases long, was synthesized. A 2-kilobase (kb) EcoI fragment of Clostridium tetani DNA was identified by Southern blotting and was cloned into the Escherichia coli plasmid vector pAT153 with the 32P-labeled oligonucleotide mixture as a probe. A second 3.2-kb Bg/II fragment was identified and cloned with the 2-kb EcoRI fragment as a probe. The nucleotide sequence of 1.8 kb of this DNA was determined and was shown to encode the entire fragment C and a portion of fragment B of tetanus toxin. The tetanus DNA was expressed in E. coli with pWRL507, a plasmid vector containing the trp promoter and a portion of the trpE gene. The trpE-tetanus fusion proteins were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were shown to react with anti-fragment C antibody.
Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer (2020)

FOLFOXIRI + bevacizumab significantly and meaningfully improves survival of patients with metastatic colorectal cancer compared with doublets + bevacizumab and provides advantage in PFS, ORR, and R0 resection rate at the price of a moderate increase in toxicity. No increased benefit is observed among patients with <i>BRAF</i>-mutant tumors.
Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine (1988)

The R-(-) and S-(+) enantiomers of 11-hydroxy-N-n-propylnoraporphine, (R)-3 and (S)-3, were synthesized in six steps from 1-(3-methoxy-2-nitrobenzyl)isoquinoline. Neuropharmacological evaluation of the R and S isomers (by affinity to dopamine receptor sites in rat brain tissues, induction of stereotyped behavior, and interaction with motor arousal induced by (R)-apomorphine in the rat) indicated that, similar to the 10,11-dihydroxy congener 2, both enantiomers can bind to dopamine receptors but that only (R)-3 activates them, whereas (S)-3 shows activity as a dopaminergic antagonist.
Tiagabine is associated with sustained attention during sleep restriction: evidence for the value of slow-wave sleep enhancement? (2006)

To our knowledge these findings are the first to be consistent with the hypothesis that pharmacologic SWS enhancement reduces selective aspects of the behavioral, psychological, and physiologic impact of sleep restriction.
Interviewing "Ronald Wilson Reagan" (1982)

As a rule, VIPs are likely to be interviewed only by other equal or lesser VIPs. But there is an even stronger rule, little known and indubitably of less consequence, that only VUPs are ever observed interviewing a Big Name in the literal sense, and like all bizarre aberrations in nature it is observed only rarely. I am not speaking of interviewing a Big Name in the figurative sense as Barbara Walters would do, which really means interviewing the actual person. No, I speak of interviewing only the Name itself, which in the present instance is composed of eleven distinct letters of the alphabet: A, D, E, G, I, L, N, O, R, S, and W. For the benefit of those who want a technical name for this kind of wordplay, the interviewee's half of this interview is called a lipogram on the name RONALD WILSON REAGAN, which means that the interviewee utters no words except those which can be spelled using the alphabetical letters in his name.
Modular organization of inteins and C‐terminal autocatalytic domains (1998)

Analysis of the conserved sequence features of inteins (protein "introns") reveals that they are composed of three distinct modular domains. The N-terminal (N) and C-terminal (C) domains are predicted to perform different parts of the autocatalytic protein splicing reaction. An optional endonuclease domain (EN) is shown to correspond to different types of homing endonucleases in different inteins. The N domain contains motifs predicted to catalyze the first steps of protein splicing, leading to the cleavage of the intein N terminus from its protein host. Intein N domain motifs are also found in C-terminal autocatalytic domains (CADs) present in hedgehog and other protein families. Specific residues in the N domain of intein and CADs are proposed to form a charge relay system involved in cleaving their N-termini. The intein C domain is apparently unique to inteins and contains motifs that catalyze the final protein splicing steps: ligation of the intein flanks and cleavage of its C terminus to release the free intein and spliced host protein. All intein EN domains known thus far have dodecapeptide (DOD, LAGLI-DADG) type homing endonuclease motifs. This work identifies an EN domain with an HNH homing-endonuclease motif and two new small inteins with no EN domains. One of these small inteins might be inactive or a "pseudo intein." The results suggest a modular architecture for inteins, clarify their origin and relationship to other protein families, and extend recent experimental findings on the functional roles of intein N, C, and EN motifs.
Nanoparticle PEGylation for Imaging and Therapy (2011)

Nanoparticles are an essential component in the emerging field of nanomedical imaging and therapy. When deployed in vivo, these materials are typically protected from the immune system by polyethylene glycol (PEG). A wide variety of strategies to coat and characterize nanoparticles with PEG has established important trends on PEG size, shape, density, loading level, molecular weight, charge and purification. Strategies to incorporate targeting ligands are also prevalent. This article presents a background to investigators new to stealth nanoparticles, and suggests some key considerations needed prior to designing a nanoparticle PEGylation protocol and characterizing the performance features of the product.
Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. (1993)

Deficient hydroxylation of debrisoquine is an autosomal recessive trait that affects approximately 7% of the Caucasian population. These individuals (poor metabolizers) carry deficient CYP2D6 gene variants and have an impaired metabolism of severely commonly used drugs. The opposite phenomenon also exists, and certain individuals metabolize the drugs very rapidly, resulting in subtherapeutic plasma concentrations at normal doses. In the present study, we have investigated the molecular genetic basis for ultrarapid metabolism of debrisoquine. Restriction fragment length polymorphism analysis of the CYP2D locus in two families with very rapid metabolism of debrisoquine [metabolic ratio (MR) for debrisoquine = 0.01-0.1] revealed the variant CYP2D6 gene CYP2D6L. Eco RI RFLP and Xba I pulsed-field gel electrophoresis analyses showed that this gene had been amplified 12-fold in three members (father and his two children) of one of the families, and two copies were present among members of the other family. The CYP2D6L gene had an open reading frame and carried two mutations causing amino acid substitutions: one in exon 6, yielding an Arg-296-->Cys exchange and one in exon 9 causing Ser-486-->Thr. The MR of subjects carrying one copy of the CYP2D6L gene did not significantly differ from that of those with the wild-type gene, indicating that the structural alterations were not of importance of the catalytic properties of the gene product. Examination of the MR among subjects carrying wild-type CYP2D6, CYP2D6L, or deficient alleles revealed a relationship between the number of active genes and MR. The data show the principle of inherited amplification of an active gene. Furthermore, the finding of a specific haplotype with two or more active CYP2D6 genes allows genotyping for ultrarapid drug metabolizers. This genotyping could be of predictive value for individualized and more efficient drug therapy.
Epidemiology of allergic conjunctivitis (2011)

Little focus has been set on the impact of allergic conjunctivitis as comorbidity to asthma and rhinitis in atopic patients. Conjunctivitis symptoms are at least as severe as rhinitis symptoms in patients with 'hay fever' and some have even generated the term of conjunctivorhinitis stressing the ocular symptoms. Prevalence studies should be specifically addressed to ocular allergy symptoms.
The role of constitutively activated STAT3 in B16 melanoma cells (2010)

Constitutively activated STAT3 is found frequently in a wide variety of human tumors, including melanoma. Moreover, constitutive STAT3 activation actively participates in tumor formation and progression, making STAT3 an attractive target for cancer therapy. We report here that in murine B16 melanoma cells, which have been previously shown to express constitutively active STAT3, the expression of a mutant form of STAT3 with the canonical tyrosine phosphorylation site (residue 705) mutated to phenylanaine has dominant-negative properties (STAT3-DN). STAT3-DN inhibits STAT3 tyrosine phosphorylation and STAT3-dependent DNA binding activity. Most importantly, STAT3-DN expression in B16 cells inhibits their invasiveness, as well as their melanogenesis by down-regulation of tyrosinase mRNA and protein expression as well as tyrosinase activity. These results suggest that STAT3 signaling plays a critical role in regulating melanoma behavior, and may represent a druggable target for melanoma therapy.
RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models (2010)

The BRAF(V600E) mutation is common in several human cancers, especially melanoma. RG7204 (PLX4032) is a small-molecule inhibitor of BRAF(V600E) kinase activity that is in phase II and phase III clinical testing. Here, we report a preclinical characterization of the antitumor activity of RG7204 using established in vitro and in vivo models of malignant melanoma. RG7204 potently inhibited proliferation and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and ERK phosphorylation in a panel of tumor cell lines, including melanoma cell lines expressing BRAF(V600E) or other mutant BRAF proteins altered at codon 600. In contrast, RG7204 lacked activity in cell lines that express wild-type BRAF or non-V600 mutations. In several tumor xenograft models of BRAF(V600E)-expressing melanoma, we found that RG7204 treatment caused partial or complete tumor regressions and improved animal survival, in a dose-dependent manner. There was no toxicity observed in any dose group in any of the in vivo models tested. Our findings offer evidence of the potent antitumor activity of RG7204 against melanomas harboring the mutant BRAF(V600E) gene.
Exogenous siRNA Mediates Sequence-Independent Gene Suppression by Signaling through Toll-Like Receptor 3 (2004)

RNA interference (RNAi) is a powerful method that specifically suppresses gene expression in a sequence-dependent manner whose machinery is found in organisms from fungi to mammals. Mammalian cells have developed a sequence-independent system of gene suppression often induced by viral replication that includes the recognition of double-stranded RNA (dsRNA) through Toll-like receptor 3 (TLR3) and induction of type I interferon synthesis. Interferon activates the transcription of a set of genes including dsRNA-activated protein kinase that suppresses protein synthesis and 2'-5'-oligoadenylate synthetase, which generates a product that activates RNase L to cleave RNA in a sequence-independent manner. We observed that 21-bp dsRNA, a key mediator of RNAi, not only induces sequence-specific gene suppression, but also signals TLR3 to induce type I interferon and activates sequence-independent suppression of protein synthesis and enhancement of mRNA degradation. This sequence-independent suppression was demonstrated for both an exogenously administered reporter gene as well as during the targeting of viral genes in the course of acute herpes simplex virus type I infection of keratinocytes. As TLR3 is expressed by many primary cell types and cell lines, this sequence-independent suppression should be considered in the design of experiments using small interfering RNA-mediated gene suppression.
Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease (2007)

IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFNgamma production.
MolecularâGenetic Imaging: A Nuclear MedicineâBased Perspective (2002)

Molecular imaging is a relatively new discipline, which developed over the past decade, initially driven by in situ reporter imaging technology. Noninvasive in vivo molecular-genetic imaging developed more recently and is based on nuclear (positron emission tomography [PET], gamma camera, autoradiography) imaging as well as magnetic resonance (MR) and in vivo optical imaging. Molecular-genetic imaging has its roots in both molecular biology and cell biology, as well as in new imaging technologies. The focus of this presentation will be nuclear-based molecular-genetic imaging, but it will comment on the value and utility of combining different imaging modalities. Nuclear-based molecular imaging can be viewed in terms of three different imaging strategies: (1) "indirect" reporter gene imaging; (2) "direct" imaging of endogenous molecules; or (3) "surrogate" or "bio-marker" imaging. Examples of each imaging strategy will be presented and discussed. The rapid growth of in vivo molecular imaging is due to the established base of in vivo imaging technologies, the established programs in molecular and cell biology, and the convergence of these disciplines. The development of versatile and sensitive assays that do not require tissue samples will be of considerable value for monitoring molecular-genetic and cellular processes in animal models of human disease, as well as for studies in human subjects in the future. Noninvasive imaging of molecular-genetic and cellular processes will complement established ex vivo molecular-biological assays that require tissue sampling, and will provide a spatial as well as a temporal dimension to our understanding of various diseases and disease processes.
Structure-Function Relationship in a Winter Flounder Antifreeze Polypeptide (1989)

Using synthetic analogs of an alpha-helical winter flounder antifreeze polypeptide (AFP) we investigated some important molecular details of the mechanism of action of this AFP. Of the seven peptides synthesized, all but one were amino-terminal deletions of the native AFP. Three of the seven synthetic analogs possessed the same antifreeze activity as the native polypeptide; the other analogs were devoid of antifreeze activity. The growth rates along the a and c axes of ice in solutions of varying concentrations of the three active AFP analogs were examined. The a axis growth rates of ice were inversely proportional to the concentration of the active peptides. The c-axis growth rates of ice were also dependent on peptide concentration. The active peptides enhanced c-axis growth at lower concentrations, while at higher concentrations they inhibited c axis growth. The ability of the peptides to develop antifreeze activity and to alter the a and c axis growth rates of ice depended on the presence of appropriately positioned amino acid residues with hydrogen bonding side chains. From these observations we propose that at low concentrations the AFP, through dipolar interactions and hydrogen bonding, interact with the prism faces of ice retarding a axis growth. At these concentrations, the electrical field of the AFP helix-dipole, like an externally applied field (Bartlett, J.T., van der Heuval, A.P., and Mason, B.J. (1963) Z. Angew. Math. Phys. 14, 599-610), can enhance ice c axis growth. At higher concentrations, the AFP interact with all ice crystal planes and retard both a and c axis growth.
A report on the occurrence of Antidesma thwaitesianum Muell.: Arg. (Euphorbiaceae) from south Andamans (1995)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.