gebhart/patrepeval huggingface dataset:
High-Resolution Linkage Analyses to Identify Genes That Influence Varroa Sensitive Hygiene Behavior in Honey Bees (2012)

Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.
Polyethylene glycol-modified chimeric toxin composed of transforming growth factor alpha and Pseudomonas exotoxin. (1993)

Modification of proteins with monomethoxy-polyethylene glycol (mPEG) has been shown to prolong circulation time and to reduce immunogenicity. To make a mPEG-modified recombinant toxin that retained cytotoxic activity but had a longer residence time in circulation, we have constructed an altered form of TGF alpha-PE40, a recombinant toxin composed of human transforming growth factor alpha (TGF alpha) fused to a fragment of Pseudomonas exotoxin (PE38) devoid of its cell-binding domain. In the newly designed protein, termed TGF alpha R29-L2-CH2-PE38QQ delta (TCP), there are no lysine residues in the TGF alpha and PE38 portions. Human IgG4 constant region CH2 and a tetradecapeptide linker; L2, are inserted between TGF alpha and PE38. Together, L2 and CH2 contain 13 lysine residues as potential modification sites for mPEG. mPEG conjugates of TCP (PEG-TCP) were generated and the products were resolved by ion exchange chromatography. Two PEG-TCP species termed B4 and B6 retained 15 and 4% of cytotoxicity, respectively, and 26% of their receptor binding activity compared with the unmodified TCP. Both B4 and B6 had prolonged circulation times in the blood and reduced toxicity in animals. The mean residence times of B4 and B6 were 37 and 68 min, respectively, compared to 7 min for TCP. When administered i.v. to tumor bearing mice, both B4 and B6 produced marked antitumor effects whereas the unmodified TCP had none. Also, the immunogenicity of PEG-TCP was 5-10 times less than that of TCP. We suggest that the prolonged circulating time and reduced toxicity of PEG-TCP compensate for a diminished cytotoxic activity and enlarge significantly the therapeutic window of this chimeric toxin.
The Tyrosine Kinase Abl-Related Gene ARG Is Fused toETV6 in an AML-M4Eo Patient With a t(1;12)(q25;p13): Molecular Cloning of Both Reciprocal Transcripts (1999)

The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of patients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p13) that involves the ETV6 gene at 12p13. By 3′rapid amplification of cDNA ends-polymerase chain reaction (3′RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG. The reciprocal transcript ARG-ETV6 was also detected in the patient RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), although at a lower expression level. The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARGinvolvement in a human malignancy.
INCOMPOSITA: a MADS-box gene controlling prophyll development and floral meristem identity inAntirrhinum (2004)

INCOMPOSITA (INCO) is a MADS-box transcription factor and member of the functionally diverse StMADS11 clade of the MADS-box family. The most conspicuous feature of inco mutant flowers are prophylls initiated prior to first whorl sepals at lateral positions of the flower primordium. The developing prophylls physically interfere with subsequent floral organ development that results in aberrant floral architecture. INCO, which is controlled by SQUAMOSA, prevents prophyll formation in the wild type, a role that is novel among MADS-box proteins, and we discuss evolutionary implications of this function. Overexpression of INCO or SVP, a structurally related Arabidopsis MADS-box gene involved in the negative control of Arabidopsis flowering time, conditions delayed flowering in transgenic plants, suggesting that SVP and INCO have functions in common. Enhanced flowering of squamosa mutants in the inco mutant background corroborates this potential role of INCO as a floral repressor in Antirrhinum. One further, hitherto hidden, role of INCO is the positive control of Antirrhinum floral meristem identity. This is revealed by genetic interactions between inco and mutants of FLORICAULA, a gene that controls the inflorescence to floral transition, together with SQUAMOSA. The complex regulatory and combinatorial relations between INCO, FLORICAULA and SQUAMOSA are summarised in a model that integrates observations from molecular studies as well as analyses of expression patterns and genetic interactions.
Identification of MpaA, an Amidase in Escherichia coli That Hydrolyzes the γ- d -Glutamyl- meso- Diaminopimelate Bond in Murein Peptides (2003)

MpaA amidase was identified in Escherichia coli by its amino acid sequence homology with the ENP1 endopeptidase from Bacillus sphaericus. The enzymatic activity of MpaA, i.e., hydrolysis of the gamma-D-glutamyl-diaminopimelic acid bond in the murein tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelic acid, was demonstrated in the cell extract of a strain expressing mpaA from a multicopy plasmid. An mpaA mpl (murein peptide ligase) double mutant accumulated large amounts of murein tripeptide in its cytoplasm, consistent with the premise that MpaA degrades the tripeptide if its recycling via the peptidoglycan biosynthetic pathway is blocked.
Phenotypic and genotypic heterogeneity of glycopeptide resistance determinants in gram-positive bacteria (1990)

Gram-positive glycopeptide-resistant bacteria isolated in various hospitals in Europe and in the United States between 1986 and 1988 were collected. Three resistance phenotypes could be distinguished. Thirty-one enterococci were highly resistant to vancomycin and teicoplanin. Resistance was transferable to other enterococci by conjugation for 16 of the 22 isolates that were tested. Homology was detected by hybridization between a probe specific for the vanA gene, which encodes an inducible high-level glycopeptide resistance protein in Enterococcus faecium BM4147, and DNA of the 31 clinical isolates and the 16 corresponding transconjugants. This indicates that a single class of resistance determinants accounts for high-level glycopeptide resistance in enterococci. The strains differed in their biotypes and resistance phenotypes and harbored resistance plasmids of various sizes, suggesting that spread of this resistance phenotype is due to dissemination of a gene rather than of a bacterial clone or of a single plasmid. Four enterococcal isolates were resistant to low levels of vancomycin and susceptible to teicoplanin. Twenty-three coagulase-negative staphylococcal isolates were resistant to teicoplanin and susceptible to vancomycin. These two groups of strains did not hybridize with the vanA probe and did not transfer resistance at a detectable frequency. The vanA gene was not detected in the glycopeptide-producing strains of Amycolatopsis orientalis (vancomycin) and Actinoplanes teichomyceticus (teicoplanin) or in various gram-positive bacteria intrinsically resistant to glycopeptides.
CalDAG-GEFI deficiency protects mice in a novel model of FcγRIIA-mediated thrombosis and thrombocytopenia (2011)

Abstract Platelet activation via Fcγ receptor IIA (FcγRIIA) is a critical event in immune-mediated thrombocytopenia and thrombosis syndromes (ITT). We recently identified signaling by the guanine nucleotide exchange factor CalDAG-GEFI and the adenosine diphosphate receptor P2Y12 as independent pathways leading to Rap1 small GTPase activation and platelet aggregation. Here, we evaluated the contribution of CalDAG-GEFI and P2Y12 signaling to platelet activation in ITT. Mice transgenic for the human FcγRIIA (hFcR) and deficient in CalDAG-GEFI−/− (hFcR/CDGI−/−) were generated. Compared with controls, aggregation of hFcR/CDGI−/− platelets or P2Y12 inhibitor-treated hFcR platelets required more than 5-fold and approximately 2-fold higher concentrations of a FcγRIIA stimulating antibody against CD9, respectively. Aggregation and Rap1 activation were abolished in P2Y12 inhibitor-treated hFcR/CDGI−/− platelets. For in vivo studies, a novel model for antibody-induced thrombocytopenia and thrombosis was established. FcγRIIA-dependent platelet thrombosis was induced by infusion of Alexa750-labeled antibodies to glycoprotein IX (CD42a), and pulmonary thrombi were detected by near-infrared imaging technology. Anti-GPIX antibodies dose-dependently caused thrombocytopenia and pulmonary thrombosis in hFcR-transgenic but not wild-type mice. CalDAG-GEFI-deficient but not clopidogrel-treated hFcR-transgenic mice were completely protected from ITT. In summary, we established a novel mouse model for ITT, which was used to identify CalDAG-GEFI as a potential new target in the treatment of ITT.
Global Virtual Vault: Preventing unauthorized physical disclosure by the insider (2008)

Information providers on networks such as the global information grid need to share sensitive information while still protecting that information from misuse. We show how common information-sharing mechanisms encourage and allow high-bandwidth, hard-to-detect information exfiltration by malicious insiders, and by adversaries in the field. By leveraging netcentricity, modern stateless clients, and advances in distance visualization techniques, we can provide analysts and warfighters with highly-usable access to information that remains secured in high-availability, high-security data centers. We quantitatively analyze the intentional and inadvertent data exfiltration paths of several off-the-shelf secure computing solutions and demonstrate how to re-engineer these systems to greatly reduce residual risk by limiting access to human-interaction protocols. This approach eliminates large classes of insider attacks that are largely unaddressed in most systems and concentrates traditional insider access to manageable, well-defended physical security perimeters.
Transdifferentiation in developmental biology, disease, and in therapy (2007)

Transdifferentiation (or metaplasia) refers to the conversion of one cell type to another. Because transdifferentiation normally occurs between cells that arise from the same region of the embryo, understanding the molecular and cellular events in cell type transformations may help to explain the mechanisms underlying normal development. Here we review examples of transdifferentiation in nature focusing on the possible role of cell type switching in metamorphosis and regeneration. We also examine transdifferentiation in mammals in relation to disease and the use of transdifferentiated cells in cellular therapy.
A rearranged λ2 light gene chain retards but does not exclude x and λ1 expression (1991)

Mice transgenic for the lambda 2 light chain of MOPC315 were established. In newborn transgenics (TG), lambda 2 was the only light chain found on B cells. However, by day 21, lambda 2 high kappa low as well as lambda 2 low kappa high double expresser populations were emerging. lambda 2 was found on an increased fraction of serum immunoglobulins (Ig), this fraction declined with age. Correspondingly, kappa and lambda 1 expression was suppressed in young mice but increased with age. In adult mice kappa or lambda 1 were often co-expressed with lambda 2 in single serum Ig molecules. Most B cell hybridomas from and adult TG secreted lambda 2,kappa mixed molecules and had rearranged their kappa chain genes. One lambda 2,lambda 1 hybridoma and even a lambda 2,kappa,lambda 1 hybridoma were also found. In conclusion, isotypic exclusion in lambda 2 TG is complete in newborns but becomes increasingly leaky with age. Antigen probably expands the lambda 2 low kappa high B cell population; this population is most likely the major source of serum Ig in adult lambda 2 TG mice. In contrast, the lambda 2 high kappa low population, a major fraction of which is CD5+ Mu low delta low, appears only infrequently to develop into antibody-secreting plasma cells.
Genetic Profile of Insertion Mutations in Mouse Leukemias and Lymphomas (2000)

Murine leukemia retroviruses (MuLVs) cause leukemia and lymphoma in susceptible strains of mice as a result of insertional mutation of cellular proto-oncogenes or tumor suppressor genes. Using a novel approach to amplify and sequence viral insertion sites, we have sequenced &gt;200 viral insertion sites from which we identify &gt;35 genes altered by viral insertion in four AKXD mouse strains. The class of genes most frequently altered are transcription factors, however, insertions are found near genes involved in signal transduction, cell cycle control, DNA repair, cell division, hematopoietic differentiation, and near many ESTs and novel loci. Many of these mutations identify genes that have not been implicated in cancer. By isolating nearly all the somatic viral insertion mutations contributing to disease in these strains we show that each AKXD strain displays a unique mutation profile, suggesting strain-specific susceptibility to mutations in particular genetic pathways.
Curing of the killer deoxyribonucleic acid plasmids of Kluyveromyces lactis (1981)

Ultraviolet irradiation gave rise to frequent curing of killer plasmids pGKl1 and pGK12 of Kluyveromyces lactis. Almost all of the nonkillers obtained lost both plasmids, but one of them lost only pGKl1. The disappearance of pGKl1 was accompanied by the simultaneous loss of the killer activity and of the resistance to the killer factor. A new plasmid, pGKl1S, was obtained, which arose from a deletion in the central region of pGKl1. Genetic analysis suggested that pGKl1S has the killer gene lost by the deletion and the resistance gene intact and that pGKl1S shares the same replication control with pGKl1.
The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota (2012)

Breast-fed infant microbiota is typically rich in bifidobacteria. Herein, major human milk oligosaccharides (HMOS) are assessed for their ability to promote the growth of bifidobacteria and to acidify their environment, key features of prebiotics. During in vitro anaerobic fermentation of infant microbiota, supplementation by HMOS significantly decreased the pH even greater than supplementation by fructooligosaccharide (FOS), a prebiotic positive control. HMOS elevated lactate concentrations, increased the proportion of Bifidobacterium spp. in culture, and through their fermentation into organic acids, decreased the proportion of Escherichia and Clostridium perfringens. Three principal components of HMOS, 2'-fucosyllactose, lactodifucotetraose and 3-fucosyllactose, were consumed in these cultures. These three principal oligosaccharides of human milk were then individually tested as supplements for in vitro growth of four individual representative strains of infant gut microbes. Bifidobacterium longum JCM7007 and B. longum ATCC15697 efficiently consumed oligosaccharides and produced abundant lactate and short-chain fatty acids, resulting in significant pH reduction. The specificity of fermentation differed by microbe species and strain and by oligosaccharide structure. Escherichia coli K12 and C. perfringens did not utilize appreciable fucosylated oligosaccharides, and a typical mixture of organic acid fermentation products inhibited their growth. In summary, 2'-fucosyllactose, lactodifucotetraose, and 3-fucosyllactose, when cultured with B. longum JCM7007 and B. longum ATCC15697, exhibit key characteristics of a prebiotic in vitro. If these bifidobacteria are representative of pioneering or keystone species for human microbiota, fucosylated HMOS could strongly promote colonization and maintenance of a mutualist symbiotic microbiome. Thus, these simple glycans could mediate beneficial effects of human milk on infant health.
The Dimensions of Chain Molecules Containing Branches and Rings (1949)

Formulas for the mean square radii of various branched and ringed polymer molecules are developed under the usual assumptions regarding the statistics of chain configuration. For branched molecules, the mean square radii vary less rapidly with molecular weight than for strictly linear molecules, while for systems containing only rings and unbranched chains the variation is more rapid than for the linear case. These results show that in principle the quantity of branches or of rings can be determined from light-scattering measurements.
Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G (1987)

The structures of oligosaccharides of normal and pathological immunoglobulin G (IgG) are reported. Asparagine-linked neutral oligosaccharides were released by N-oligosaccharide glycopeptidase (almond) digestion. The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by reverse-phase high-performance liquid chromatography. It was possible to separate 15 out of the 16 kinds of oligosaccharides that have been suggested to exist in normal human IgG. High-resolution proton nuclear magnetic resonance spectroscopy was used along with chemical methods to determine the structures of the separated oligosaccharides. It has been shown that in normal IgG a biantennary complex-type oligosaccharide with a fucose residue (formula; see text) is predominant and four kinds of oligosaccharides, which are biantennary with bisecting N-acetylglucosamine and without fucose residues, exist only in a very small quantity. The results obtained for normal IgG were compared with those obtained for three myeloma IgG proteins. It has been found that the most abundant species that exist in the pathological proteins analyzed in the present work lack one or two galactose residues at the nonreducing terminal. We show that the fractions of fucose-containing oligosaccharides are markedly decreased in the heavy-chain disease protein Per. It is of particular interest that in this paraprotein the major component is a biantennary complex-type oligosaccharide that lacks a fucose residue and an oligosaccharide with the structure (Formula: see text) exists as one of the most abundant components.
An overview of the secondary structure of the V4 region of eukaryotic small-subunit ribosomal RNA (1991)

The V4 region of the small subunit (18S) ribosomal RNA was examined in 72 different sequences representing a broad sample eukaryotic diversity. This domain is the most variable region of the 18S rRNA molecule and ranges in length from ca. 230 to over 500 bases. Based upon comparative analysis, secondary structural models were constructed for all sequences and the resulting generalized model shows that most organisms possess seven helices for this region. The protists and two insects show from one to as many as four helices in addition to the above seven. In this report, we summarize secondary structure information presented elsewhere for the V4 region, describe the general features for helical and apical regions, and identify signature sequences useful in helix identification. Our model generally agrees with other current concepts; however, we propose modifications or alternative structures for the start of the V4 region, the large protist inserts, and the sector that may possibly contain a pseudoknot.
Processing and delivery of peptides presented by MHC class I molecules (1996)

Effective MHC class I peptide loading requires the proteolytic degradation of cytosolic proteins and the TAP-mediated translocation of peptides across the membrane of the endoplasmic reticulum. The proteasome is emerging as the main cytosolic protease generating class I binding peptides. The recent elucidation of the proteasome crystal structure, together with the use of functional inhibitors, has enhanced our understanding of proteasome function. Genetic analysis of a novel mutant cell line emphasizes the importance of the TAP-class I interaction in the assembly of mature class I heterotrimers, and suggests that additional MHC-encoded components are required.
Underwater Glider Model Parameter IdentiÞcation (2003)

An underwater glider is a buoyancy-propelled, Þxedwing vehicle with attitude controlled completely, or in part, by means of internal mass redistribution. We have developed a physics-based nonlinear model of the dynamics of an underwater glider and adapted it to model the SLOCUM glider’s geometry, rudder, ballast pump and internal movable mass. In this paper we identify the model parameters to match the steady glides in new sight test data from the SLOCUM glider. In the process we also estimate the
Structures of biological minerals in dental research (2001)

Structural features of some calcium phosphates of biological interest are described. Structure of hydroxyapatite (OHAp), considered as the prototype for the inorganic component of bones and teeth is discussed with respect to the kinds and locations of ionic substitutions. Octacalcium phosphate (OCP), is a probable precursor in biological mineralization. OCP has a layer type structure, with one layer quite similar to that of OHAp and the other, a hydrated layer consisting of more widely spaced Ca, and PO4 ions and the water molecules. The closeness of fit in the apatitic layers of OCP and OHAp accounts for the epitaxial, interlayered mixtures formed by these compounds and the in situ conversion of OCP to OHAp. Possible roles of OCP in biological mineralization are discussed.