gebhart/patrepeval huggingface dataset:
A STUDY OF PLASMA PROGESTERONE, OESTRADIOL‐l7β, PROLACTIN AND LH LEVELS, AND OF THE LUTEAL PHASE APPEARANCE OF THE OVARIES IN PATIENTS WITH ENDOMETRIOSIS AND INFERTILITY (1978)

Thirty-four infertile patients with regular cycles and endometriosis were studied and compared to a control group of 28 women. The endometriosis was classified as mild (n = 16), moderate (n = 9) and severe (n = 9) according to Acosta et al (1973). The interval between the LH peak and the onset of subsequent menstruation was shorter (P = 0.024) in patients with endometriosis than in the control group. In mild endometriosis, oestradiol-17beta levels fell on the day after the LH peak, but this was not the case in moderate and severe endometriosis. In mild, moderate and severe endometriosis the plasma progesterone concentration did not rise on the first day following the LH peak, and at laparoscopy significantly (P less than 0.005) less ovulation stigmata were present. We conclude that endometriosis is associated with luteinization in situ and that this may explain the associated infertility.
Vaccine Protocols (2003)

This extensively revised, updated, and expanded second edition of a classic laboratory manual applies new understanding of molecular mechanisms to the rational design and development of vaccines. Here the working researcher will find readily reproducible techniques for the development and production of live attenuated vaccines through the genetic manipulation of viruses and bacteria, vaccine vectors or inactivated toxins, and the production of synthetic peptides and conjugate vaccines. In addition, there are chapters describing more general techniques for vaccine formulation, delivery, and assessment of immune responses, and review discussions of scale-up to manufacture, vaccine quality assurance, and clinical trials. New to this second edition are cutting-edge chapters on two different viral vectors (Vaccinia and Semliki Forest), lactic acid bacteria for delivery of foreign antigens, incorporation of immunomodulators into plasmid DNA vaccines, construction of tetramer complexes to detect CMI responses, assessment of functional antibody responses, and the use of complete genome sequences for vaccine design. Each fully tested protocol is described in step-by-step detail by an established expert in the field and includes a background introduction outlining the principle behind the technique, equipment and reagent lists, tips on trouble shooting and avoiding known pitfalls, and, where needed, a discussion of the interpretation and use of results. State-of-the-art and highly practical, Vaccine Protocols, Second Edition, provides essential information for those seeking to produce improved or novel vaccines in the rapidly evolving field of vaccine research and development
Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing (2010)

MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure-function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer-small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. The ability of our ligand-responsive miRNA platform to respond to user-defined inputs, undergo regulatory performance tuning and display scalable combinatorial control schemes will help advance applications in biological research and applied medicine.
Management of undescended lingual and subhyoid thyroid glands (1974)

Abstract There are approximately 400 reported cases of undescended thyroid glands. Ninety percent of these are located in the base of the tongue, and 10 percent in the anterior neck superficial to the hyoid bone. The presumptive diagnosis is usually made by scintiphotography. These glands are probably quantitatively deficient and function at marginal levels. Apparently, TSH stimulation causes hypertrophy, usually at an early age, producing undesirable symptoms or local cosmetic change. The treatment varies, depending upon the problems that arise: observation, suppressive doses of thyroid, isotope suppression, surgical excision, and autotransplantation are methods used in attempting to benefit these patients. This communication deals with guidelines for therapy and attempts to evaluate allotransplantation based on the available data. To date, some degree of success has been obtained by autotransplantation; however, a more vigorous effort by the medical community is needed to obtain and report clinical and laboratory data to evaluate autotransplantation fully.
CARDIAC REGENERATION: Repopulating the Heart (2005)

Many forms of pediatric and adult heart disease result from a deficiency in cardiomyocyte number. Through repopulation of the heart with new cardiomyocytes (that is, induction of regenerative cardiac growth), cardiac disease potentially can be reversed, provided that the newly formed myocytes structurally and functionally integrate in the preexisting myocardium. A number of approaches have been utilized to effect regenerative growth of the myocardium in experimental animals. These include interventions aimed at enhancing the ability of cardiomyocytes to proliferate in response to cardiac injury, as well as transplantation of cardiomyocytes or myogenic stem cells into diseased hearts. Here we review efforts to induce myocardial regeneration. We also provide a critical review of techniques currently used to assess cardiac regeneration and functional integration of de novo cardiomyocytes.
Crystal structure of the BTB domain from PLZF (1998)

The BTB domain (also known as the POZ domain) is an evolutionarily conserved protein-protein interaction motif found at the N terminus of 5-10% of C2H2-type zinc-finger transcription factors, as well as in some actin-associated proteins bearing the kelch motif. Many BTB proteins are transcriptional regulators that mediate gene expression through the control of chromatin conformation. In the human promyelocytic leukemia zinc finger (PLZF) protein, the BTB domain has transcriptional repression activity, directs the protein to a nuclear punctate pattern, and interacts with components of the histone deacetylase complex. The association of the PLZF BTB domain with the histone deacetylase complex provides a mechanism of linking the transcription factor with enzymatic activities that regulate chromatin conformation. The crystal structure of the BTB domain of PLZF was determined at 1.9 A resolution and reveals a tightly intertwined dimer with an extensive hydrophobic interface. Approximately one-quarter of the monomer surface area is involved in the dimer intermolecular contact. These features are typical of obligate homodimers, and we expect the full-length PLZF protein to exist as a branched transcription factor with two C-terminal DNA-binding regions. A surface-exposed groove lined with conserved amino acids is formed at the dimer interface, suggestive of a peptide-binding site. This groove may represent the site of interaction of the PLZF BTB domain with nuclear corepressors or other nuclear proteins.
An adaptive hardware machine architecture and compiler for dynamic processor reconfiguration (2002)

Substantial gains can be achieved by allowing the configuration and fundamental operations of a processor to adapt to a user's program. A method is presented for improving the performance of many computationally intensive tasks by extracting information at compile-time to synthesize new operations that augment the functionality of a core processor. The newly synthesized operations are targeted to RAM-based reconfigurable logic located within the processor. A proof-of-concept system called PLADO, consisting of a C configuration compiler and a hardware platform, is presented. Computation and performance results confirm the concept viability, and demonstrate significant speed-up.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The N-X-S/T consensus sequence is required but not sufficient for bacterial N-linked protein glycosylation (2004)

In the Gram-negative bacterium Campylobacter jejuni there is a pgl (protein glycosylation) locus-dependent general N-glycosylation system of proteins. One of the proteins encoded by pgl locus, PglB, a homolog of the eukaryotic oligosaccharyltransferase component Stt3p, is proposed to function as an oligosaccharyltransferase in this prokaryotic system. The sequence requirements of the acceptor polypeptide for N-glycosylation were analyzed by reverse genetics using the reconstituted glycosylation of the model protein AcrA in Escherichia coli. As in eukaryotes, the N-X-S/T sequon is an essential but not a sufficient determinant for N-linked protein glycosylation. This conclusion was supported by the analysis of a novel C. jejuni glycoprotein, HisJ. Export of the polypeptide to the periplasm was required for glycosylation. Our data support the hypothesis that eukaryotic and bacterial N-linked protein glycosylation are homologous processes.
Binding of the herbicide trifluralin to Chlamydomonas flagellar tubulin (1977)

Colchicine-binding tubulin was isolated from the centre 2 axoneme microtubules from the flagella of the alga Chlamydomonas eugametos. Incubating this tubulin with 5-8 micron [14C]trifluralin resulted in significant and reproducible binding of trifluralin to tubulin. The specificity of binding was determined by demonstrating that limited or no binding occurred to flagellar membrane and matrix protein, higher plant proteins, or bovine serum albumin. It was concluded that trifluralin, at obtainable soluble concentrations, specifically inhibits microtubule-mediated processes in plants. To date no effect of trifluralin on animal microtubule systems has been reported; therefore, it is suggested that trifluralin has revealed a pharmacological difference between plant and animal tubulin.
HES-1 Repression of Differentiation and Proliferation in PC12 Cells: Role for the Helix 3-Helix 4 Domain in Transcription Repression (2000)

HES-1 is a Hairy-related basic helix-loop-helix protein with three evolutionarily conserved regions known to define its function as a transcription repressor. The basic region, helix-loop-helix domain, and WRPW motif have been characterized for their molecular function in DNA binding, dimer formation, and corepressor recruitment, respectively. In contrast, the function conferred by a fourth conserved region, the helix 3-helix 4 (H-3/4) domain, is not known. To better understand H-3/4 domain function, we expressed HES-1 variants under tetracycline-inducible control in PC12 cells. As expected, the induced expression of moderate levels of wild-type HES-1 in PC12 cells strongly inhibited nerve growth factor-induced differentiation. This repression was dependent on the H-3/4 domain. Unexpectedly, expression of HES-1 also arrested cell growth, an effect that could be reversed upon down regulation of HES-1. Concomitant with growth arrest, there was a strong reduction in bromodeoxyuridine incorporation and PCNA protein levels, although not in cyclin D1 expression. Expression of a HES-1 protein carrying the H-3/4 domain, but not the WRPW domain, still partially inhibited both proliferation and differentiation. Transcription assays in PC12 cells directly demonstrated that the H-3/4 domain can mediate DNA-binding-dependent transcription repression, even in the absence of corepressor recruitment by the WRPW motif. HES-1 expression strongly repressed transcription of the p21(cip1) promoter, a cyclin-cyclin-dependent kinase inhibitor up regulated during NGF-induced differentiation, and the H-3/4 domain is necessary for this repression. Thus, the H-3/4 domain of HES-1 contributes to transcription repression independently of WRPW function, inhibits neurite formation, and facilitates two distinct and previously uncharacterized roles for HES-1: the inhibition of cell proliferation and the direct transcriptional repression of the NGF-induced gene, p21.
Natural Product Biosynthetic Gene Diversity in Geographically Distinct Soil Microbiomes (2012)

The number of bacterial species estimated to exist on Earth has increased dramatically in recent years. This newly recognized species diversity has raised the possibility that bacterial natural product biosynthetic diversity has also been significantly underestimated by previous culture-based studies. Here, we compare 454-pyrosequenced nonribosomal peptide adenylation domain, type I polyketide ketosynthase domain, and type II polyketide ketosynthase alpha gene fragments amplified from cosmid libraries constructed using DNA isolated from three different arid soils. While 16S rRNA gene sequence analysis indicates these cloned metagenomes contain DNA from similar distributions of major bacterial phyla, we found that they contain almost completely distinct collections of secondary metabolite biosynthetic gene sequences. When grouped at 85% identity, only 1.5% of the adenylation domain, 1.2% of the ketosynthase, and 9.3% of the ketosynthase alpha sequence clusters contained sequences from all three metagenomes. Although there is unlikely to be a simple correlation between biosynthetic gene sequence diversity and the diversity of metabolites encoded by the gene clusters in which these genes reside, our analysis further suggests that sequences in one soil metagenome are so distantly related to sequences in another metagenome that they are, in many cases, likely to arise from functionally distinct gene clusters. The marked differences observed among collections of biosynthetic genes found in even ecologically similar environments suggest that prokaryotic natural product biosynthesis diversity is, like bacterial species diversity, potentially much larger than appreciated from culture-based studies.
A community of unknown, endophytic fungi in western white pine (2004)

The endophytic fungi of woody plants may be diverse as often claimed, and likewise, they may be functionally novel as demonstrated in a few studies. However, the endophyte taxa that are most frequently reported tend to belong to fungal groups composed of morphologically similar endophytes and parasites. Thus, it is plausible that endophytes are known (i.e., described) parasites in a latent phase within the host. If this null hypothesis were true, endophytes would represent neither additional fungal diversity distinct from parasite diversity nor a symbiont community likely to be novel ecologically. To be synonymous with parasites of the host, endophytes should at least be most closely related to those same parasites. Here we report that seven distinct parasites of Pinus monticola do not occur as endophytes. The majority of endophytes of P. monticola (90% of 2,019 cultures) belonged to one fungal family, the Rhytismataceae. However, not a single rhytismataceous endophyte was found to be most closely related by sequence homology to the three known rhytismataceous parasites of P. monticola. Similarly, neither endophytic Mycosphaerella nor endophytic Rhizosphaera isolates were most closely related to known parasites of P. monticola. Morphologically, the endophytes of P. monticola can be confounded with the parasites of the same host. However, they are actually most closely related to, but distinct from, parasites of other species of Pinus. If endophytes are generally unknown species, then estimates of 1 million endophytes (i.e., approximately 1 in 14 of all species of life) seem reasonable.
RU486 exerts antiestrogenic activities through a novel progesterone receptor A form-mediated mechanism. (1994)

The human progesterone receptor (hPR) exists in two distinct forms in most cells, hPR-A and hPR-B. Both receptor isoforms exhibit distinct biological functions and demonstrate a cell- and promoter-specific ability to regulate gene transcription. Interestingly, in cell contexts where PR-A is transcriptionally inactive, it acts as a progesterone-dependent inhibitor of estrogen receptor function. Coexpression of the human estrogen receptor with the A form (but not the B form) of the human progesterone receptor resulted in a ligand-dependent inhibition of estrogen receptor-mediated gene transcription. The antiprogestins RU486 (MIfepristone) and ZK98299 (Onapristone) and related antiprogestins were all effective "noncompetitive" inhibitors of the estrogen receptor in this assay as none of these compounds interacted directly with the estrogen receptor. This observation may explain in part the observed tissue-specific antiestrogenic effects of RU486 and further indicates that the antiestrogenic activities of antiprogestins may be intrinsic to their biological function. This important new information defines novel activities of progesterone receptor ligands and may alter the way in which we define progesterone receptor modulators for future clinical applications. In addition, these data reveal that the A form of the progesterone receptor plays a key role in modulating estrogen receptor function in cells where both receptors are expressed.
Intelligent RAM (IRAM): chips that remember and compute (2002)

It is time to reconsider unifying logic and memory. Since most of the transistors on this merged chip will be devoted to memory, it is called 'intelligent RAM'. IRAM is attractive because the gigabit DRAM chip has enough transistors for both a powerful processor and a memory big enough to contain whole programs and data sets. It contains 1024 memory blocks each 1kb wide. It needs more metal layers to accelerate the long lines of 600mm/sup 2/ chips. It may require faster transistors for the high-speed interface of synchronous DRAM. Potential advantages of IRAM include lower memory latency, higher memory bandwidth, lower system power, adjustable memory width and size, and less board space. Challenges for IRAM include high chip yield given processors have not been repairable via redundancy, high memory retention rates given processors usually need higher power than DRAMs, and a fast processor given logic is slower in a DRAM process.
Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation (2011)

Previously, we have shown that a heteroplasmic mutation in mitochondrial DNA-encoded complex I ND5 subunit gene resulted in an enhanced tumorigenesis through increased resistance to apoptosis. Here we report that the tumorigenic phenotype associated with complex I dysfunction could be reversed by introducing a yeast NADH quinone oxidoreductase (NDI1) gene. The NDI1 mediated electron transfer from NADH to Co-Q, bypassed the defective complex I and restored oxidative phosphorylation in the host cells. Alternatively, suppression of complex I activity by a specific inhibitor, rotenone or induction of oxidative stress by paraquat led to an increase in the phosphorylation of v-AKT murine thymoma viral oncogene (AKT) and enhanced the tumorigenesis. On the other hand, antioxidant treatment can ameliorate the reactive oxygen species-mediated AKT activation and reverse the tumorigenicity of complex I-deficient cells. Our results suggest that complex I defects could promote tumorigenesis through induction of oxidative stress and activation of AKT pathway.
A Comparison of Lipid Patterns in Photosynthesizing and Nonphotosynthesizing Cells of Euglena Gracilis* (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Comparison of Lipid Patterns in Photosynthesizing and Nonphotosynthesizing Cells of Euglena Gracilis*Abraham RosenbergCite this: Biochemistry 1963, 2, 5, 1148–1154Publication Date (Print):September 1, 1963Publication History Published online1 May 2002Published inissue 1 September 1963https://pubs.acs.org/doi/10.1021/bi00905a042https://doi.org/10.1021/bi00905a042research-articleACS PublicationsRequest reuse permissionsArticle Views246Altmetric-Citations85LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Aminoacridines, potent inhibitors of protein kinase C. (1988)

Acridine orange, acridine yellow G, and related compounds potently inhibited protein kinase C (Ca2+/phospholipid-dependent enzyme) activity and phorbol dibutyrate binding. Inhibition was investigated in vitro using Triton X-100 mixed micellar assays (Hannun, Y. A., Loomis, C. R., and Bell, R. M. (1985) J. Biol. Chem. 260, 10039-10043 and Hannun, Y. A., and Bell, R. M. (1986) J. Biol. Chem. 261, 9341-9347). Inhibition by the acridine derivatives was subject to surface dilution; therefore, the relevant concentration unit is mol % rather than the bulk molar concentration. Fifty percent inhibition of protein kinase C activity occurred at concentrations of these compounds comparable to concentrations of sn-1,2-diacylglycerol (DAG) and phosphatidylserine (PS) required for enzyme activation (i.e. 1-6 mol %). The mechanism of inhibition appeared to be complex: both the catalytic and regulatory sites of protein kinase C were affected. Acridine orange was a competitive inhibitor with respect to MgATP when the catalytic fragment of protein kinase C was employed. Inhibition at the active site was overcome by the addition of Triton X-100 micelles or phospholipid vesicles. When the activity of intact protein kinase C was measured, inhibition was noncompetitive with respect to MgATP. Further kinetic analysis suggested a competitive type of inhibition with respect to PS and DAG implying an interaction of acridine compounds with the regulatory lipid cofactors or with the regulatory domain of protein kinase C. This was further supported by demonstrating inhibition of phorbol dibutyrate binding to both protein kinase C and the lipid-binding domain generated by trypsin hydrolysis. Acridine orange and acridine yellow G also inhibited thrombin-induced 40-kDa phosphorylation in human platelets and phorbol dibutyrate binding to platelets. These effects were also subject to surface dilution. These results suggest that acridine derivatives have multiple interactions with protein kinase C with the predominant effect being inhibition of activation within the regulatory domain of the enzyme. Some of the biologic effects of acridine derivatives including anti-tumor action may occur as a consequence of protein kinase C inhibition.