gebhart/patrepeval huggingface dataset:
Cloning and Sequencing of Human PEX from a Bone cDNA Library: Evidence for Its Developmental Stage-Specific Regulation in Osteoblasts (1997)

Inactivating mutations of the neutral endopeptidase, PEX, have been identified as the cause of X-linked hypophosphatemia (XLH). Though the function of PEX is unknown, current information suggests that impaired renal phosphate conservation in XLH is due to the failure of PEX to either degrade an undefined phosphaturic factor or activate a novel phosphate-conserving hormone. The physiologically relevant target tissue for the XLH mutation has not been identified. An apparent intrinsic defect of osteoblast function in XLH implicates bone as a possible site of PEX expression. In the current investigation, we employed a polymerase chain reaction (PCR) strategy to amplify a PEX cDNA from a human bone cell cDNA library. We found that the human PEX cDNA encodes a 749 amino acid protein belonging to the type II integral membrane zinc-dependent endopeptidase family. The predicted PEX amino acid sequence shares 96.0% identify to the recently cloned mouse Pex cDNA and has 27-38% identity to other members of the metalloendopeptidase family. Using reverse transcriptase (RT)-PCR with PEX-specific primers, we detected PEX transcripts in both human osteosarcoma-derived MG-63 osteoblasts and in differentiated mouse MC3T3-E1 clonal osteoblasts but not in immature MC3T3-E1 preosteoblasts. The association of impaired mineralization of bone in XLH and the apparent developmental stage-specific expression of PEX in osteoblasts suggest that bone is a physiologically relevant site of PEX expression and that PEX may play an active role in osteoblast-mediated mineralization.
Immunogenicity in humans of an edible vaccine for hepatitis B (2005)

A double-blind placebo-controlled clinical trial evaluated the immunogenicity of hepatitis B surface antigen (HBsAg) expressed in potatoes and delivered orally to previously vaccinated individuals. The potatoes accumulated HBsAg at approximately 8.5 microg/g of potato tuber, and doses of 100 g of tuber were administered by ingestion. The correlate of protection for hepatitis B virus, a nonenteric pathogen, is blood serum antibody titers against HBsAg. After volunteers ate uncooked potatoes, serum anti-HBsAg titers increased in 10 of 16 volunteers (62.5%) who ate three doses of potatoes; in 9 of 17 volunteers (52.9%) who ate two doses of transgenic potatoes; and in none of the volunteers who ate nontransgenic potatoes. These results were achieved without the coadministration of a mucosal adjuvant or the need for buffering stomach pH. We conclude that a plant-derived orally delivered vaccine for prevention of hepatitis B virus should be considered as a viable component of a global immunization program.
Abelson Interactor Protein-1 Positively Regulates Breast Cancer Cell Proliferation, Migration, and Invasion (2007)

Abelson interactor protein-1 (ABI-1) is an adaptor protein involved in actin reorganization and lamellipodia formation. It forms a macromolecular complex containing Hspc300/WASP family verprolin-homologous proteins 2/ABI-1/nucleosome assembly protein 1/PIR121 or Abl/ABI-1/WASP family verprolin-homologous proteins 2 in response to Rho family-dependent stimuli. Due to its role in cell mobility, we hypothesized that ABI-1 has a role in invasion and metastasis. In the present study, we found that weakly invasive breast cancer cell lines (MCF-7, T47D, MDA-MB-468, SKBR3, and CAMA1) express lower levels of ABI-1 compared with highly invasive breast cancer cell lines (MDA-MB-231, MDA-MB-157, BT549, and Hs578T), which exhibit high ABI-1 levels. Using RNA interference, ABI-1 was stably down-regulated in MDA-MB-231, which resulted in decreased cell proliferation and anchorage-dependent colony formation and abrogation of lamellipodia formation on fibronectin. Down-regulation of ABI-1 decreased invasiveness and migration ability and decreased adhesion on collagen IV and actin polymerization in MDA-MB-231 cells. Additionally, compared with control parental cells, ABI-1 small interfering RNA-transfected cells showed decreased levels of phospho-PDK1, phospho-Raf, phospho-AKT, total AKT, and AKT1. These data suggest that ABI-1 plays an important role in the spread of breast cancer and that this role may be mediated via the phosphatidylinositol 3-kinase pathway.
Tris (Dibenzylideneacetone) Dipalladium, aN-Myristoyltransferase-1 Inhibitor, Is Effective against Melanoma GrowthIn vitroandIn vivo (2008)

Tris DBA is thus a novel inhibitor of N-myristoyltransferase-1 with significant antitumor activity and is well tolerated in vivo. Further preclinical evaluation of Tris DBA and related complexes is warranted.
Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media (2012)

Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.
Isolation, characterization and evolutionary retatedness of three members from the soybean multigene family encoding chlorophyll a/b binding proteins (1988)

The soybean light-harvesting complex II (LHC II) was composed of one major and three minor chlorophyll a/b (Cab) binding proteins. This study demonstrated that the soybean genome contained at least 11 genes that code for these Cab proteins. Three members of the soybean Cab gene family were characterized. Cab 3 coded for a 25.7 kD mature apoprotein with a 32 amino acid transit peptide. Comparisons with previously published Cab protein sequences indicated that Cab 3 coded for the major Cab protein of LHC II. Cab 2 coded for a novel Cab protein with an apparent molecular weight of 24.6 kD. Cab 2 retained a high degree of similarity with Cab 3, but distinguished itself from previously reported minor photosystem II type II Cab genes and products. Finally, Cab 1 was determined to be a pseudogene that had two deletions relative to Cab 2 and Cab 3.
New opportunities by synthetic biology for biopharmaceutical production in Pichia pastoris (2013)

Biopharmaceuticals are an integral part of modern medicine and pharmacy. Both, the development and the biotechnological production of biopharmaceuticals are highly cost-intensive and require suitable expression systems. In this review we discuss established and emerging tools for reengineering the methylotrophic yeast Pichia pastoris for biopharmaceutical production. Recent advancements of this industrial expression system through synthetic biology include synthetic promoters to avoid methanol induction and to fine-tune protein production. New platform strains and molecular cloning tools as well as in vivo glycoengineering to produce humanized glycoforms have made P. pastoris an important host for biopharmaceutical production.
Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development (2004)

Tbx2 is a member of the T-box transcription factor gene family,and is expressed in a variety of tissues and organs during embryogenesis. In the developing heart, Tbx2 is expressed in the outflow tract, inner curvature, atrioventricular canal and inflow tract, corresponding to a myocardial zone that is excluded from chamber differentiation at 9.5 days post coitus (dpc). We have used targeted mutagenesis in mice to investigate Tbx2 function. Mice heterozygous for a Tbx2 null mutation appear normal but homozygous embryos reveal a crucial role for Tbx2 during cardiac development. Morphological defects are observed in development of the atrioventricular canal and septation of the outflow tract. Molecular analysis reveals that Tbx2 is required to repress chamber differentiation in the atrioventricular canal at 9.5 dpc. Analysis of homozygous mutants also highlights a role for Tbx2 during hindlimb digit development. Despite evidence that TBX2 negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in cultured cells, there is no evidence that loss of Tbx2 function during mouse development results in increased levels of p19ARF, p16INK4a,p15INK4b or p21 expression in vivo, nor is there evidence for a genetic interaction between Tbx2 and p53.
The Use of a Mini-Bioreactor Fermentation System as a Reproducible, High-Throughput ex vivo Batch Model of the Distal Colon (2018)

<i>Ex vivo</i> colon fermentation systems are highly versatile as models for analyzing gastrointestinal tract microbiota composition and functionality. <i>Ex vivo</i> colon models range in size and functionality from bench-top micro fermenters to large units housed in individualized cabinets. The length of set-up time (including stabilization periods) for each fermentation system can range from hours to weeks to months. The aim of this study was to investigate a single-use cassette mini-fermentation system as a reproducible batch model of the colon. The online data log from the cassettes (triplicate wells across four different cassettes, <i>n</i> = 12) was sensitive enough to identify real-time changes in pH, temperature, dissolved oxygen or liquid addition (sodium hydroxide) during the runs which could be addressed if an alarm set-point was triggered. The alpha diversity indices also showed little variation between cassettes with the samples clustering around the mean. The weighted beta diversity PCoA analysis illustrated that 95% of the variance between the samples was accounted for by the time-point and not the fermentation run/cassette used. The variation in taxonomic diversity between cassettes was limited to less than 20 out of 115 genera. This study provides evidence that micro-bioreactors provide some very attractive advantages as batch models for the human colon. We show for the first time the use of the micro-Matrix a 24-well sophisticated parallel controlled cassette-based bioreactors as a batch colon model. We demonstrated a high level of reproducibility across fermentation cassettes when used in conjunction with a standardized fecal microbiota. The machine can operate 24 individual fermentations simultaneously and are relatively cost effective. Based on next generation sequencing analysis, the micro-bioreactors offer a high degree of reproducibility together with high-throughput capacity. This makes it a potential system for large screening projects that can then be scaled up to large fermenters or human/animal <i>in vivo</i> experiments.
mik1+ encodes a tyrosine kinase that phosphorylates p34cdc2 on tyrosine 15. (1994)

mik1+ and wee1+ function to regulate the tyrosine phosphorylation of p34cdc2 in Schizosaccharomyces pombe (Lundgren, K., Walworth, N., Booher, R., Dembski, M., Kirschner, M., and Beach, D. (1991) Cell 64, 1111-1122). wee1+ encodes a tyrosine kinase that directly phosphorylates p34cdc2 on tyrosine 15, resulting in the inactivation of the cyclin B/p34cdc2 complex. We have overproduced the mik1+ gene product in insect cells and in S. pombe in order to characterize it biochemically. Immunoprecipitates of Mik1 from both sources catalyzed the phosphorylation of p34cdc2 on tyrosine 15 whereas immunoprecipitates of a kinase-deficient mutant of Mik1 were negative in this assay. Mik1 overproduced in insect cells was partially purified by column chromatography, and column fractions were assayed for their ability to phosphorylate p34cdc2 on tyrosine 15. Two major peaks of Mik1 protein were detected by gel filtration chromatography. One peak eluted in the void volume, and a second peak eluted with an apparent molecular mass expected for monomeric Mik1 (approximately 68 kDa). The tyrosine 15 kinase activity co-eluted with the 68 kDa form of Mik1. These results indicate that mik1+ encodes a tyrosine kinase that directly phosphorylates p34cdc2 on tyrosine 15.
Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3. (1992)

Experiments using recombinant vaccinia viruses expressing rat proinsulin I coinfected into COS-7 cells with recombinant vaccinia virus expressing human furin, human PC2, mouse PC3 (subtilisin-related proprotein convertases 1-3, respectively), or yeast Kex2 indicate that in this system both Kex2 and furin produce mature insulin, whereas PC2 selectively cleaves proinsulin at the C-peptide-A-chain junction. This is a property consistent with its probable identity with the rat insulinoma granule type II proinsulin processing activity as described by Davidson et al. [Davidson, H. W., Rhodes, C. J. & Hutton, J. C. (1988) Nature (London) 333, 93-96]. PC3 generates mature insulin but cleaves preferentially at the proinsulin B-chain-C-peptide junction. This pattern of cleavage by PC3 is similar, but not identical, to that of the highly B-chain-C-peptide junction-selective type I activity as described by Davidson et al., perhaps due to the presence of a P4 arginine residue near the C-peptide-A-chain junction unique to the rat proinsulins. These results along with data presented on the expression of both PC2 and PC3 in islet beta cells strongly support the conclusion that these proteases are involved in the conversion of proinsulin to insulin in vivo.
Influenza Viruses Select Ordered Lipid Domains during Budding from the Plasma Membrane (1999)

During the budding of enveloped viruses from the plasma membrane, the lipids are not randomly incorporated into the envelope, but virions seem to have a lipid composition different from the host membrane. Here, we have analyzed lipid assemblies in three different viruses: fowl plague virus (FPV) from the influenza virus family, vesicular stomatitis virus (VSV), and Semliki Forest virus (SFV). Analysis of detergent extractability of proteins, cholesterol, phosphoglycerolipids, and sphingomyelin in virions showed that FPV contains high amounts of detergent-insoluble complexes, whereas such complexes are largely absent from VSV or SFV. Cholesterol depletion from the viral envelope by methyl-beta-cyclodextrin results in increased solubility of sphingomyelin and of the glycoproteins in the FPV envelope. This biochemical behavior suggests that so-called raft-lipid domains are selectively incorporated into the influenza virus envelope. The "fluidity" of the FPV envelope, as measured by the fluorescence polarization of diphenylhexatriene, was significantly lower than compared with VSV or SFV. Furthermore, influenza virus hemagglutinin incorporated into the envelope of recombinant VSV was largely detergent-soluble, indicating the depletion of raft-lipid assemblies from this membrane. The results provide a model for lipid selectivity during virus budding and support the view of lipid rafts as cholesterol-dependent, ordered domains in biological membranes.
How the Fanconi Anemia Pathway Guards the Genome (2009)

Fanconi Anemia (FA) is an inherited genomic instability disorder, caused by mutations in genes regulating replication-dependent removal of interstrand DNA crosslinks. The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. To this end, the Fanconi Anemia pathway employs a unique nuclear protein complex that ubiquitinates FANCD2 and FANCI, leading to formation of DNA repair structures. Lack of obvious enzymatic activities among most FA members has made it challenging to unravel its precise modus operandi. Here we review the current understanding of how the Fanconi Anemia pathway components participate in DNA repair and discuss the mechanisms that regulate this pathway to ensure timely, efficient, and correct restoration of chromosomal integrity.
Transcription-Dependent Degradation of Topoisomerase I-DNA Covalent Complexes (2003)

Topoisomerase I (Top I)-DNA covalent complexes represent a unique type of DNA lesion whose repair and processing remain unclear. In this study, we show that Top I-DNA covalent complexes transiently arrest RNA transcription in normal nontransformed cells. Arrest of RNA transcription is coupled to activation of proteasomal degradation of Top I and the large subunit of RNA polymerase II. Recovery of transcription occurs gradually and depends on both proteasomal degradation of Top I and functional transcription-coupled repair (TCR). These results suggest that arrest of the RNA polymerase elongation complex by the Top I-DNA covalent complex triggers a 26S proteasome-mediated signaling pathway(s) leading to degradation of both Top I and the large subunit of RNA polymerase II. We propose that proteasomal degradation of Top I and RNA polymerase II precedes repair of the exposed single-strand breaks by TCR.
Induction of tumorigenicity and lack of in vitro growth requirement for 12-O-tetradecanoylphorbol-13-acetate by transfection of murine melanocytes with v-Ha-ras. (1989)

A nontumorigenic line of murine melanocytes, Mel-ab, has been transfected with the v-Ha-ras gene under transcriptional control of the Moloney murine leukemia virus long terminal repeat. Transfectants produced rapidly growing undifferentiated melanomas in recipient mice. The inhibition of melanin production in transformed cells, observable both in vitro and in vivo, suggests that ras may affect melanocyte cytodifferentiation. Mel-ab cells require the continual presence of 12-O-tetradecanoylphorbol-13-acetate, or other activators of protein kinase C, for in vitro growth. Transfectants expressing v-Ha-ras no longer manifested this requirement and were actually growth inhibited by the addition of protein kinase C activators. These results are consistent with the notion that ras acts via the protein kinase C pathway in conferring autonomous growth on Mel-ab cells.
Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential (2003)

For reasons that are not apparent, it has been difficult to isolate and expand the adult stem cells referred to as mesenchymal stem cells or marrow stromal cells (MSCs) from murine bone marrow. We developed a protocol that provides rapidly expanding MSCs from 5 strains of inbred mice. The MSCs obtained from 5 different strains of mice were similar to human and rat MSCs in that they expanded more rapidly if plated at very low density, formed single-cell-derived colonies, and readily differentiated into either adipocytes, chondrocytes, or mineralizing cells. However, the cells from the 5 strains differed in their media requirements for optimal growth, rates of propagation, and presence of the surface epitopes CD34, stem cell antigen-1 (Sca-1), and vascular cell adhesion molecule 1 (VCAM-1). The protocol should make it possible to undertake a large number of experiments with MSCs in transgenic mice that have previously not been possible. The differences among MSCs from different strains may explain some of the conflicting data recently published on the engraftment of mouse MSCs or other bone marrow cells into nonhematopoietic tissues.
Highly Luminescent Silicon Nanocrystals with Discrete Optical Transitions (2001)

A new synthetic method was developed to produce robust, highly crystalline, organic-monolayer passivated silicon (Si) nanocrystals in a supercritical fluid. By thermally degrading the Si precursor, diphenylsilane, in the presence of octanol at 500 degrees C and 345 bar, relatively size-monodisperse sterically stabilized Si nanocrystals ranging from 15 to 40 A in diameter could be obtained in significant quantities. Octanol binds to the Si nanocrystal surface through an alkoxide linkage and provides steric stabilization through the hydrocarbon chain. The absorbance and photoluminescence excitation (PLE) spectra of the nanocrystals exhibit a significant blue shift in optical properties from the bulk band gap energy of 1.2 eV due to quantum confinement effects. The stable Si clusters show efficient blue (15 A) or green (25-40 A) band-edge photoemission with luminescence quantum yields up to 23% at room temperature, and electronic structure characteristic of a predominantly indirect transition, despite the extremely small particle size. The smallest nanocrystals, 15 A in diameter, exhibit discrete optical transitions, characteristic of quantum confinement effects for crystalline nanocrystals with a narrow size distribution.
Novel Adsorption Process for Co-Production of Hydrogen and CO2 from a Multicomponent Stream—Part 2: Application to Steam Methane Reforming and Autothermal Reforming Gases (2020)

ISSN:1520-5045
In search of an understandable consensus algorithm (2014)

Raft is a consensus algorithm for managing a replicated log. It produces a result equivalent to (multi-)Paxos, and it is as efficient as Paxos, but its structure is different from Paxos; this makes Raft more understandable than Paxos and also provides a better foundation for build-ing practical systems. In order to enhance understandabil-ity, Raft separates the key elements of consensus, such as leader election, log replication, and safety, and it enforces a stronger degree of coherency to reduce the number of states that must be considered. Results from a user study demonstrate that Raft is easier for students to learn than Paxos. Raft also includes a new mechanism for changing the cluster membership, which uses overlapping majori-ties to guarantee safety. 1
Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro (2017)

The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology.