1,211 research outputs found
Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice
Experimental allergic encephalomyelitis (EAE)' is an autoimmune inflammatory demyelinating disease in the central nervous system (CNS) of animals immunized
with myelin basic protein (MBP). The disease is directly mediated by Thelper cells that recognize MBP in the context ofclass II antigens of the MHC (1-3). In nude
mice, a single clone of adoptively transferred MBP-reactive T helper cells can cause EAE (4), suggesting that these are the only T cells required for disease induction.
As a prototypic model of T helper cell-mediated autoimmune disease, observations in EAE could likely be applicable to other T helper cell-mediated diseases such as
murine lupus (5), thyroiditis (6), collagen arthritis (7), and adjuvant arthritis (8), as well as human autoimmune diseases. The MBP epitope is determined in part by the MHC. Using proteolytic peptide fragments of MBP, SJL/J (H-2s) and BIO.T(6R) (H-2q) mice were found to develop
EAE to the COOH-terminal peptide of MBP, whereas PL/J (H-2u) and A/J (H-2k) mice developed EAE to the NH2-terminal peptide of MBP (9). Recently, by
using synthetic peptides that overcome the difficulties of obtaining pure uncontaminated proteolytic peptides, a single T cell encephalitogenic epitope for PL/J mice
has been identified . This epitope consists of the first nine NH2-terminal amino acid residues of MBP which must be acetylated at the a amino group to induce disease
(10). Similar fine mapping of the encephalitogenic T cell epitope(s) for SJL/J mice has not been done, in part because of the large size of the COOH-terminal peptic
fragment of MBP (residues 89-169 of rat MBP, reference 9).
MouseMBP consists offour major forms due to differential RNA splicing of exons II and VI (11), resulting in molecular masses of 21, 18.5, 17.5, and 14 kD, in the
relative amounts of 1 :10:3.5:35 . Since EAE can also be induced with the small form of rat MBP (14 kD), which has exons II and VI of the MBP gene deleted (12), the
COOH-terminal encephalitogenic determinant for SJL/J mice must be present within a segment ofonly 42 amino acid residues . Consistent withthis notion is the observation that this peptide sequence is identical among the MBPs of several mammalian species, including mouse, rat, bovine, guinea pig, and porcine, all of which can induce
EAE in SJL/mice (13, 14). To identify the SJL/J encephalitogenic T cell epitope(s), overlapping peptides to
the COOH-terminal region ofthe small form of mouse MBP were synthesized. Two overlapping peptides encompassing an 18-amino acid region were found to elicit EAE in SJL/J mice. The finding of a single peptide region of MBP that is responsible for encephalitogenic T cell epitopes in SJL/J mice is analogous to that of the PL/J mice and has implications for the development of specific therapy for T cell-mediated autoimmune diseases
Cell Wall and Protoplast Isoperoxidases in Tobacco Plants in Relation to Mechanical Injury and Infection with Tobacco Mosaic Virus
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A Mechanistic Analysis of Phase Evolution and Hydrogen Storage Behavior in Nanocrystalline Mg(BH4)2 within Reduced Graphene Oxide.
Magnesium borohydride (Mg(BH4)2, abbreviated here MBH) has received tremendous attention as a promising onboard hydrogen storage medium due to its excellent gravimetric and volumetric hydrogen storage capacities. While the polymorphs of MBH-alpha (α), beta (β), and gamma (γ)-have distinct properties, their synthetic homogeneity can be difficult to control, mainly due to their structural complexity and similar thermodynamic properties. Here, we describe an effective approach for obtaining pure polymorphic phases of MBH nanomaterials within a reduced graphene oxide support (abbreviated MBHg) under mild conditions (60-190 °C under mild vacuum, 2 Torr), starting from two distinct samples initially dried under Ar and vacuum. Specifically, we selectively synthesize the thermodynamically stable α phase and metastable β phase from the γ-phase within the temperature range of 150-180 °C. The relevant underlying phase evolution mechanism is elucidated by theoretical thermodynamics and kinetic nucleation modeling. The resulting MBHg composites exhibit structural stability, resistance to oxidation, and partially reversible formation of diverse [BH4]- species during de- and rehydrogenation processes, rendering them intriguing candidates for further optimization toward hydrogen storage applications
Identification of Intrahelical Bifurcated H‑Bonds as a New Type of Gate in K+ Channels
Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K+ channels, KcvS and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels.
Includes Supporting Informatio
Identification of Intrahelical Bifurcated H‑Bonds as a New Type of Gate in K+ Channels
Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K+ channels, KcvS and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels.
Includes Supporting Informatio
A Focused Sequent Calculus Framework for Proof Search in Pure Type Systems
Basic proof-search tactics in logic and type theory can be seen as the
root-first applications of rules in an appropriate sequent calculus, preferably
without the redundancies generated by permutation of rules. This paper
addresses the issues of defining such sequent calculi for Pure Type Systems
(PTS, which were originally presented in natural deduction style) and then
organizing their rules for effective proof-search. We introduce the idea of
Pure Type Sequent Calculus with meta-variables (PTSCalpha), by enriching the
syntax of a permutation-free sequent calculus for propositional logic due to
Herbelin, which is strongly related to natural deduction and already well
adapted to proof-search. The operational semantics is adapted from Herbelin's
and is defined by a system of local rewrite rules as in cut-elimination, using
explicit substitutions. We prove confluence for this system. Restricting our
attention to PTSC, a type system for the ground terms of this system, we obtain
the Subject Reduction property and show that each PTSC is logically equivalent
to its corresponding PTS, and the former is strongly normalising iff the latter
is. We show how to make the logical rules of PTSC into a syntax-directed system
PS for proof-search, by incorporating the conversion rules as in
syntax-directed presentations of the PTS rules for type-checking. Finally, we
consider how to use the explicitly scoped meta-variables of PTSCalpha to
represent partial proof-terms, and use them to analyse interactive proof
construction. This sets up a framework PE in which we are able to study
proof-search strategies, type inhabitant enumeration and (higher-order)
unification
Intra-aortic balloon counterpulsation in US and non-US centres: results of the Benchmark® Registry
Aims To examine differences in patient characteristics and outcomes in 19 636 patients enrolled in the USA and 3027 patients enrolled in other countries undergoing intra-aortic balloon pump (IABP) counterpulsation. Methods and results Indications for IABP use; a larger percentage of US patients were identified as ‘early support and stabilization for angiography or angioplasty' (21.1% US vs 11.8% non-US), and ‘pre-operative support for high-risk CABG' (15.9% vs 6.6%). A smaller percentage of US patients vs non-US patients were identified as ‘weaning from cardiopulmonary bypass' (14.3% vs 28.2%), and ‘refractory ventricular failure' (6.2% vs 9.8%). One out of five patients in both groups was listed as ‘cardiogenic shock' (18.9% US vs 20.2% non-US). All cause, risk-adjusted, in-hospital mortality (20.1% vs 28.7%; P<0.001), and mortality with IABP in place (10.8% vs 18.0%; P<0.001) were lower at US vs non-US sites. In both US and non-US institutions, IABP associated complication rates, such as IABP-related mortality (0.05% vs 0.07%), major limb ischaemia (0.9% vs 0.8%), and severe bleeding (0.9% vs 0.8%), were low. Conclusions IABP counterpulsation is deployed at an earlier clinical stage in US patients. Mortality rates are higher for non-US patients, particularly for patients with non-surgery cardiac interventions, even after adjusting for risk factors. Complication rates were low. Physicians should therefore not be reluctant to use IABP in high-risk patients undergoing cardiac procedure
A Machine Checked Model of Idempotent MGU Axioms For Lists of Equational Constraints
We present formalized proofs verifying that the first-order unification
algorithm defined over lists of satisfiable constraints generates a most
general unifier (MGU), which also happens to be idempotent. All of our proofs
have been formalized in the Coq theorem prover. Our proofs show that finite
maps produced by the unification algorithm provide a model of the axioms
characterizing idempotent MGUs of lists of constraints. The axioms that serve
as the basis for our verification are derived from a standard set by extending
them to lists of constraints. For us, constraints are equalities between terms
in the language of simple types. Substitutions are formally modeled as finite
maps using the Coq library Coq.FSets.FMapInterface. Coq's method of functional
induction is the main proof technique used in proving many of the axioms.Comment: In Proceedings UNIF 2010, arXiv:1012.455
Nesting biology of the bee Caupolicana yarrowi.
20 pages : illustrations (some color), color maps ; 26 cm.
Appendix: Use of nectar by the desert bee Caupolicana yarrowi (Colletidae) in cell construction / James H. Cane and Jerome G. Rozen, Jr.The first part of this publication, written by a group of participants in Bee Course 2018, results from the discovery of three nests of Caupolicana yarrowi (Cresson, 1875) at the base of the Chiricahua Mountains in southeastern Arizona. The nests are deep with branching laterals that usually connect to large vertical brood cells by an upward turn before curving downward and attaching to the top of the chambers. This loop of the lateral thus seems to serve as a "sink trap," excluding rainwater from reaching open cells during provisioning. Although mature larvae had not yet developed, an egg of C. yarrowi was discovered floating on the provisions allowing an SEM examination of its chorion, the first such study for any egg of the Diphaglossinae. Larval food for this species at this site came from Solanum elaeagnifolium Cav. (Solanaceae). Nests were parasitized by Triepeolus grandis (Friese, 1917) (Epeolini), which previously was known to attack only Ptiloglossa (Diphaglossinae: Caupolicanini). The subterranean nest cells of the desert bee Caupolicana yarrowi (Colletidae), which are enveloped by a casing of hardened soil that easily separates from the surrounding matrix, are discussed in a separate appendix. Chemical analysis revealed the casing to be rich in reducing sugars, indicating that the mother bee had regurgitated floral nectar onto the rough interior walls of the cell cavity before smoothing and waterproofing them. This novel use of nectar in nest construction is compared with that of other bee species that bring water to a nest site to soften soil for excavation
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