gebhart/patrepeval huggingface dataset:
Comparison of the immune response to recombinant gp120 in humans and chimpanzees (1994)

While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies over-estimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.
Role of ATF4 in skeletal muscle atrophy (2017)

In skeletal muscle fibers, ATF4 is critical component of a complex and incompletely understood molecular signaling network that causes muscle atrophy during aging, fasting, and immobilization.
Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. (1996)

Oral administration of antigen is a long recognized method of inducing systemic immune tolerance. In animals with experimental autoimmune disease, a major mechanism of oral tolerance triggered by oral administration of antigen involves the induction of regulatory T cells that mediate active suppression by secreting the cytokine TGF-beta 1. Multiple sclerosis (MS) is a presumed T cell-mediated Th1 type autoimmune disease. Here, we investigated whether in MS patients oral myelin treatment, containing both myelin basic protein (MBP) and proteolipid protein (PLP), induced antigen specific MBP or PLP reactive T cells that either secreted IL4, TGF-beta1, or alternatively did Th1 type sensitization occur as measured by IFN-gamma secretion. Specifically, 4,860 short-term T cell lines were generated to either MBP, PLP, or tetanus toxoid (TT) from 34 relapsing-remitting MS patients: 17 orally treated with bovine myelin daily for a minimum of 2 yr as compared to 17 nontreated patients. We found a marked increase in the relative frequencies of both MBP and PLP specific TGF-beta1-secreting T cell lines in the myelin treated MS patients as compared to non-treated MS patients (MBP P < 0.001, PLP P < 0.003). In contrast, no change in the frequency of MBP or PLP specific IFN-gamma or TT specific TGF-beta1 secreting T cells were observed. These results suggest that the oral administration of antigens generates antigen specific TGF-beta1 secreting Th3 cells of presumed mucosal origin that represent a distinct lineage of T cells. Since antigen-specific TGF-beta1 secreting cells localize to the target organ and then suppress inflammation in the local microenvironment, oral tolerization with self antigens may provide a therapeutic approach for the treatment of cell-mediated autoimmune disease which does not depend upon knowledge of the antigen specificity of the original T cell clone triggering the autoimmune cascade.
Sequential Autophosphorylation Steps in the Interleukin-1 Receptor-associated Kinase-1 Regulate its Availability as an Adapter in Interleukin-1 Signaling (2004)

The interleukin-1 receptor-associated kinase 1 (IRAK-1) is an important adapter in the signaling complex of the Toll/interleukin-1 (IL-1) receptor family. Formation of the signaling IL-1 receptor complex results in the activation and hyperphosphorylation of IRAK-1, which leads to a pronounced shift of its apparent molecular mass in gel electrophoresis. Presently, the individual residues phosphorylated in IRAK-1 and the consequences for IRAK-1 function are unknown. We define sequential phosphorylation steps in IRAK-1, which are, in vitro, autophosphorylation. First, IRAK-1 is phosphorylated at Thr209. By fluorescence energy transfer experiments, we demonstrate that Thr209 phosphorylation results in a conformational change of the kinase domain, permitting further phosphorylations to take place. Substitution of Thr209 by alanine results in a kinase-inactive IRAK-1. Second, Thr387 in the activation loop is phosphorylated, leading to full enzymatic activity. Third, IRAK-1 autophosphorylates several times in the proline-, serine-, and threonine-rich ProST region between the N-terminal death domain and kinase domain. Hyperphosphorylation of this region leads to dissociation of IRAK-1 from the upstream adapters MyD88 and Tollip but leaves its interaction with the downstream adapter TRAF6 unaffected. This identifies IRAK-1 as a novel type of adapter protein, which employs its own kinase activity to introduce negative charges adjacent to the protein interaction domain, which anchors IRAK-1 at the active receptor complex. Thus, IRAK-1 regulates its own availability as an adapter molecule by sequential autophosphorylation.
ChemInform Abstract: Inorganic Semiconductor Nanowires: Rational Growth, Assembly, and Novel Properties (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Polarization- and wavelength-insensitive guided-wave optical switch with semiconductor Y junction (1990)

A polarization- and wavelength-insensitive semiconductor guided-wave optical switch with a Y junction is proposed. The switch exhibits a digital response with respect to current, allowing its use as a wavelength-insensitive 1*2 optical switch. The switching characteristics are analyzed by using the beam propagation method, and a design example is given. The polarization- and wavelength-insensitive switching operation has been confirmed with a fabricated GaAs/GaAlAs switch at wavelengths of 1.3 and 1.55 mu m, and the on/off ratio exceeded 20 dB at an injection current of 250 mA at these wavelengths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
<title>Smart prosthetics based on magnetorheological fluids</title> (2001)

One of the most exciting new applications for magnetorheological fluid technology is that of real-time controlled dampers for use in advanced prosthetic devices. In such systems a small magnetorheological fluid damper is used to control, in real-time, the motion of an artificial limb based on inputs from a group of sensors. A 'smart' prosthetic knee system based on a controllable magnetorheological fluid damper was commercially introduced to the orthopedics and prosthetics market in 2000. The benefit of such an artificial knee is a more natural gait that automatically adapts to changing gait conditions.
The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation of 5′ HoxD genes during limb pattern formation (1995)

Mutations in the murine limb deformity (ld) gene disrupt differentiation of the Apical Ectodermal Ridge (AER) and patterning of distal limb structures. However, initial outgrowth of the limb bud is not affected, suggesting that early and late functions of the AER are uncoupled. Similarly, activation of the 5' members of the HoxD gene cluster (Hoxd-11 to Hoxd-13) is not affected in ld mutant posterior limb bud mesenchyme, but the subsequent anteriorization of 5' HoxD domains is delayed by about 12 hours and is associated with reduced levels of polarising activity. These results indicate that the ld gene products act upstream of 5' HoxD genes during patterning of the autopod. Expression of the signalling molecule Sonic hedgehog (Shh) in the posterior limb bud mesenchyme is initiated normally, but ceases prematurely indicating a defect in maintenance of Shh by the ld mutant AER. Furthermore, no Fgf-4 transcripts are detected in the ld mutant AER, whereas Fgf-8 transcripts remain expressed. However, Shh expression can be rescued by heterospecific grafting of ld mutant posterior mesenchyme under a wild-type chicken AER. These studies show that the AER defect in ld homozygous limb buds causes disruption of the FGF-4/SHH feedback loop and support the proposed essential role for FGF-4 in maintaining Shh expression during limb pattern formation.
Human neutralizing human immunodeficiency virustype 2-specific Fab molecules generated by phage display (1999)

A panel of human immunodeficiency virus type 2 (HIV-2)-neutralizing, recombinant Fab fragments was generated by using the phage display technique. The combinatorial library was derived from an asymptomatic, HIV-2-seropositive individual and constructed on the surface of filamentous phage by using the pComb3 phagemid vector and then screened against native HIV-2 envelope glycoprotein (gp125). Ten of 30 Fab fragments generated displayed strong reactivity in an ELISA and were therefore selected for further study. Six of these possessed neutralizing capacity, with titres varying from 20 to 80 against the homologous HIV-2 strain, and one also had a weak neutralizing capacity against a heterologous HIV-2 isolate, K135. Sequencing of the heavy chain CDR3 regions showed that the gp125-specific Fabs represented individual clones. These reagents may be useful for studies on the conformational structures of the HIV-2 envelope antigens and their immunogenicity, which may help in vaccine design. Furthermore, the cloned Fab genes may be transformed into whole IgG for eukaryotic expression, and as such used for therapeutic and immunoprophylactic studies in HIV-2-infected macaques and, possibly, for human immunoprophylaxis against HIV-2.
Generation of antigen-specific CD8+ CTLs from naive precursors. (1994)

Class I MHC-restricted CTLs are an important component of the host immune response against viral infections, and CTL effectors can often be isolated from infected individuals. However, the mechanism responsible for the induction of CTLs is incompletely understood because, in part, of the difficulty in generating such cells in vitro from naive precursors. In the present study we have used human peripheral blood dendritic cells (DCs), devoid of CD4+ T cells, to sensitize naive CD8+ T cells to exogenous Ags, resulting in the generation of Ag specific CTL effectors. With this system, Ag-specific CTL lines were generated to a complex glycoprotein, keyhole limpet hemocyanin, and to multiple small (9-15 amino acids) synthetic peptides derived from conserved regions of the HIV-1 gag and envelope proteins. The HIV-1-specific CTLs demonstrated potent HLA class I restricted killing of both Ag pulsed and virally infected target cells. In contrast to Ag-pulsed DCs, Ag-pulsed monocytes failed to sensitize CTL precursors although they could be used as feeders for purposes of CTL expansion and as target cells in cytolytic assays. With the use of the system described herein, a detailed analysis of the primary human T cell response to foreign Ags is now feasible, and CTL of desired specificity can be generated for potential clinical use in adoptive immunotherapy protocols.
One-step assembly and targeted integration of multigene constructs assisted by the I-SceI meganuclease inSaccharomyces cerevisiae (2013)

In vivo assembly of overlapping fragments by homologous recombination in Saccharomyces cerevisiae is a powerful method to engineer large DNA constructs. Whereas most in vivo assembly methods reported to date result in circular vectors, stable integrated constructs are often preferred for metabolic engineering as they are required for large-scale industrial application. The present study explores the potential of combining in vivo assembly of large, multigene expression constructs with their targeted chromosomal integration in S. cerevisiae. Combined assembly and targeted integration of a ten-fragment 22-kb construct to a single chromosomal locus was successfully achieved in a single transformation process, but with low efficiency (5% of the analyzed transformants contained the correctly assembled construct). The meganuclease I-SceI was therefore used to introduce a double-strand break at the targeted chromosomal locus, thus to facilitate integration of the assembled construct. I-SceI-assisted integration dramatically increased the efficiency of assembly and integration of the same construct to 95%. This study paves the way for the fast, efficient, and stable integration of large DNA constructs in S. cerevisiae chromosomes.
In Vitro Selection of RNA Ligands to Substance P (1995)

RNA ligands to the tachykinin substance P have been selected from a large pool of random sequence RNA molecules. Substance P is an undecapeptide that plays a variety of roles as a neurotransmitter and neuromodulator in the central and peripheral nervous system of mammals. A systematic evolution of ligands by exponential enrichment (SELEX) procedure was used to isolate RNAs that bind substance P immobilized on a solid support. RNAs that also bind substance P in solution were identified, and the tightest binder was subjected to mutagenesis in a second SELEX procedure to evolve ligands with a higher affinity for the peptide. A comparative analysis of 36 ligands isolated from the second SELEX experiment revealed two main sequence classes with highly conserved secondary structures within each class. Dissociation constants for the interaction of these ligands with substance P in solution were determined by equilibrium dialysis. The amino acid residues involved in the interaction with the highest affinity ligand (190 nM Kd) were mapped by determining which of a set of overlapping fragments of substance P can compete with the intact peptide for binding. A binding competition experiment also demonstrated the ability of the same ligand to discriminate between substance P and the reverse orientation of the same amino acid sequence. The results from this study demonstrate that SELEX can yield high affinity RNA ligands to small nonconstrained peptides.
Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein. (1990)

The low density lipoprotein receptor-related protein (LRP) from rat liver membranes binds apoprotein E (apoE)-enriched rabbit beta-migrating very low density lipoproteins (beta-VLDL) in a ligand blotting assay on nitrocellulose membranes. Binding was markedly activated when the beta-VLDL was preincubated with recombinant human apoE-3, native human apoE-3 or E-4, or native rabbit apoE. Human apoE-2, which binds poorly (1-2% of apo E-3 binding) to low density lipoprotein receptors, was approximately 40% as effective as apoE-3 or apoE-4 in binding to LRP. Stimulation of apoE-dependent binding to LRP was blocked by the inclusion of a mixture of human apoC proteins, but not apoA-I or A-II, in the preincubation reaction. High concentrations of apoE did not overcome the apoC inhibition. The effects of apoE and apoC on the ligand blotting assay were paralleled by similar effects in the ability of beta-VLDL to stimulate cholesteryl ester synthesis in mutant human fibroblasts that lack low density lipoprotein receptors. These properties of LRP are consistent with the known effects of apoE and apoC on uptake of chylomicron and very low density lipoprotein remnants in the liver and raise the possibility that LRP functions as a receptor for apoE-enriched forms of these lipoproteins in intact animals.
Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple sclerosis (1999)

Relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL mouse is a Th1-mediated autoimmune demyelinating disease model for human multiple sclerosis and is characterized by infiltration of the central nervous system (CNS) by Th1 cells and macrophages. Disease relapses are mediated by T cells specific for endogenous myelin epitopes released during acute disease, reflecting a critical role for epitope spreading in the perpetuation of chronic central CNS pathology. We asked whether blockade of the CD40-CD154 (CD40L) costimulatory pathway could suppress relapses in mice with established R-EAE. Anti-CD154 antibody treatment at either the peak of acute disease or during remission effectively blocked clinical disease progression and CNS inflammation. This treatment blocked Th1 differentiation and effector function rather than expansion of myelin-specific T cells. Although T-cell proliferation and production of interleukin (IL)-2, IL-4, IL-5, and IL-10 were normal, antibody treatment severely inhibited interferon-gamma production, myelin peptide-specific delayed-type hypersensitivity responses, and induction of encephalitogenic effector cells. Anti-CD154 antibody treatment also impaired the expression of clinical disease in adoptive recipients of encephalitogenic T cells, suggesting that CD40-CD154 interactions may be involved in directing the CNS migration of these cells and/or in their effector ability to activate CNS macrophages/microglia. Thus, blockade of CD154-CD40 interactions is a promising immunotherapeutic strategy for treatment of ongoing T cell-mediated autoimmune diseases.
Identification of Immunogenic and Serum Binding Proteins of Staphylococcus epidermidis (2005)

Staphylococcus epidermidis is a commensal of human skin and a leading cause of nosocomial bloodstream infections. Limited information is available about S. epidermidis proteins that are expressed upon transition to the bloodstream or those involved in host-pathogen interactions. A cell surface fraction from S. epidermidis 0-47 grown in rabbit serum to mimic environmental signals encountered during a bloodstream infection was separated by two-dimensional (2D) gel electrophoresis. Following 2D separation, the proteins were transferred to nitrocellulose and detected with either pooled sera generated in rabbits immunized with live S. epidermidis 0-47 or with biotin-labeled serum proteins eluted from the surface of bacteria grown in rabbit serum. Twenty-nine immunoreactive or serum binding proteins of S. epidermidis were identified by mass spectrometry. Twenty-seven of the corresponding genes were expressed in Escherichia coli, and the purified recombinant proteins were used to immunize mice. In a preliminary screen, 12 of the 27 recombinant proteins induced a response that reduced the number of bacteria recovered from the spleen or bloodstream of infected mice. In subsequent vaccination studies, 5 of the 12 proteins resulted in a statistically significant reduction in the number of bacteria. The identification of five candidate vaccine antigens from the initial screen of only 29 proteins demonstrates the utility of this approach.
Lymphocyte Responses to Chemokines (1998)

Today, almost three dozen human chemokines have been identified. The main function of these soluble proteins is the recruitment of leukocytes to sites of infection and inflammation. This review emphasizes the new developments in the field of lymphocyte responses to chemokines. Notably, it was shown that lymphocytes require stimulation to become responsive to chemokines, a process that is closely linked to chemokine receptor expression. As an exception, one chemokine, SDF-1, is a highly effective chemoattractant for non-activated T lymphocytes and progenitor B cells. Of particular interest are the chemokines IP10 and Mig which bind to a receptor with selective expression in activated T lymphocytes and, therefore, may be critical mediators of T lymphocyte migration in T cell-dependent immune-responses. All other chemokines with activities in lymphocytes do also induce responses in monocytes and granulocytes. The involvement of chemokine receptors in HIV infection is briefly mentioned, while other interesting areas in chemokine research, such as hematopoiesis and angiogenesis, are not discussed.
Using Ion Channel-Forming Peptides to Quantify Protein−Ligand Interactions (2008)

This paper proposes a method for sensing affinity interactions by triggering disruption of self-assembly of ion channel-forming peptides in planar lipid bilayers. It shows that the binding of a derivative of alamethicin carrying a covalently attached sulfonamide ligand to carbonic anhydrase II (CA II) resulted in the inhibition of ion channel conductance through the bilayer. We propose that the binding of the bulky CA II protein (MW approximately 30 kD) to the ion channel-forming peptides (MW approximately 2.5 kD) either reduced the tendency of these peptides to self-assemble into a pore or extracted them from the bilayer altogether. In both outcomes, the interactions between the protein and the ligand lead to a disruption of self-assembled pores. Addition of a competitive inhibitor, 4-carboxybenzenesulfonamide, to the solution released CA II from the alamethicin-sulfonamide conjugate and restored the current flow across the bilayer by allowing reassembly of the ion channels in the bilayer. Time-averaged recordings of the current over discrete time intervals made it possible to quantify this monovalent ligand binding interaction. This method gave a dissociation constant of approximately 2 microM for the binding of CA II to alamethicin-sulfonamide in the bilayer recording chamber: this value is consistent with a value obtained independently with CA II and a related sulfonamide derivative by isothermal titration calorimetry.
Towards the Definition of a Chimpanzee and Human Conserved CD6 Domain 1 Epitope Recognized by T1 Monoclonal Antibody (2008)

Scavenger receptor cysteine-rich (SRCR) domains are evolutionally conserved modules that display complex structures stabilized by key amino acids, while some other residues have evolved with a relative independence, thus allowing the functional diversity of these receptors. CD6, a highly glycosylated membrane protein predominantly expressed on lymphocytes, contains three SRCR domains. The lack of CD6 domain crystal structure has limited the characterization of the binding sites for the interacting molecules. The interaction between CD6 and its ligand, activated leukocyte-cell adhesion molecule (ALCAM)/CD166, through the membrane-proximal SRCR3 domain, has low affinity and involves conserved sites in both molecules mediating a cross-species binding. The CD6-ALCAM interaction has been involved in cell adhesion, maturation, regulation of activation, and survival processes, suggesting the potential relevance of this target for therapeutic interventions. Several anti-CD6 monoclonal antibodies (MAb) have been described but their affinity and epitope definition remain unclear. We found the murine and humanized T1 MAb versions have similar CD6 recognition profiles and affinity constants of about 6 x 10(8). These antibodies do not block the CD6-ALCAM interaction and recognize a conformational epitope independent of the CD6 N-glycosylation. This epitope was additionally found in the chimpanzee and contains an RXE/Q consensus motif located in the membrane-distal SRCR1. These results, together with the therapeutic evidence previously obtained with these MAbs, suggest a differential contribution of CD6 domains to lymphocyte biology. Potential mechanisms for T1 MAb therapeutic effect different from CD6-CD166 interaction blocking would be dissected.
Hepatitis C Virus-Like Particles Induce Virus–Specific Humoral and Cellular Immune Responses in Mice (2001)

We have recently described the production of hepatitis C virus-like particles (HCV-LPs) in insect cells that resemble the putative virions. Here we evaluate the humoral and cellular immunogenicity of the virus-like particles with or without viral p7 protein, a small viral polypeptide that resides between the structural and nonstructural regions of the HCV polyprotein and whose function has not been defined. Immunized BALB/c mice developed high titers of anti-E2 antibodies and virus-specific cellular immune responses including cytotoxic T lymphocytes and T helper responses with gamma interferon production. The virus-like particles without p7 generated a higher cellular immune response with a more T(H)1 profile than the particles with p7. Immunization of heat-denatured particles resulted in substantially lower humoral and cellular responses, suggesting that the immunogenicity is strongly dependent on particle formation. Administration of CpG oligonucleotide or cationic lipid 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol), two potent adjuvants, did not significantly enhance the immunogenicity of HCV-LPs. Our results indicate that HCV-LPs can induce humoral and cellular immune responses and offer a promising approach to vaccine development.