322 research outputs found
Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways
Amyotrophic lateral sclerosis (ALS) is a devastating
neurological disease with no effective treatment
available. An increasing number of genetic causes of ALS
are being identified, but how these genetic defects lead to
motor neuron degeneration and to which extent they affect
common cellular pathways remains incompletely understood.
To address these questions, we performed an interactomic
analysis to identify binding partners of wild-type
(WT) and ALS-associated mutant versions of ATXN2,
C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal
cells. This analysis identified several known but also many
novel binding partners of these proteins
Good Random Matrices over Finite Fields
The random matrix uniformly distributed over the set of all m-by-n matrices
over a finite field plays an important role in many branches of information
theory. In this paper a generalization of this random matrix, called k-good
random matrices, is studied. It is shown that a k-good random m-by-n matrix
with a distribution of minimum support size is uniformly distributed over a
maximum-rank-distance (MRD) code of minimum rank distance min{m,n}-k+1, and
vice versa. Further examples of k-good random matrices are derived from
homogeneous weights on matrix modules. Several applications of k-good random
matrices are given, establishing links with some well-known combinatorial
problems. Finally, the related combinatorial concept of a k-dense set of m-by-n
matrices is studied, identifying such sets as blocking sets with respect to
(m-k)-dimensional flats in a certain m-by-n matrix geometry and determining
their minimum size in special cases.Comment: 25 pages, publishe
Грунти як об’єкт науки
Висвітлюються деякі аспекти розвитку наших уявлень про ґрунтознавство як науковий напрямок природознавства та про ґрунти як об’єкт науки.Освещаются некоторые аспекты развития наших представлений о почвоведении как научном направлении природоведения и о почвах как объекте науки.The author highlights several aspects of human knowledge about soil research as a field of natural science, and about soils as a research object
Single Molecule Statistics and the Polynucleotide Unzipping Transition
We present an extensive theoretical investigation of the mechanical unzipping
of double-stranded DNA under the influence of an applied force. In the limit of
long polymers, there is a thermodynamic unzipping transition at a critical
force value of order 10 pN, with different critical behavior for homopolymers
and for random heteropolymers. We extend results on the disorder-averaged
behavior of DNA's with random sequences to the more experimentally accessible
problem of unzipping a single DNA molecule. As the applied force approaches the
critical value, the double-stranded DNA unravels in a series of discrete,
sequence-dependent steps that allow it to reach successively deeper energy
minima. Plots of extension versus force thus take the striking form of a series
of plateaus separated by sharp jumps. Similar qualitative features should
reappear in micromanipulation experiments on proteins and on folded RNA
molecules. Despite their unusual form, the extension versus force curves for
single molecules still reveal remnants of the disorder-averaged critical
behavior. Above the transition, the dynamics of the unzipping fork is related
to that of a particle diffusing in a random force field; anomalous,
disorder-dominated behavior is expected until the applied force exceeds the
critical value for unzipping by roughly 5 pN.Comment: 40 pages, 18 figure
Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques
<p>Abstract</p> <p>Background</p> <p>Human killer immunoglobulin-like receptors (KIRs) play a critical role in governing the immune response to neoplastic and infectious disease. Rhesus macaques serve as important animal models for many human diseases in which KIRs are implicated; however, the study of KIR activity in this model is hindered by incomplete characterization of <it>KIR </it>genetics.</p> <p>Results</p> <p>Here we present a characterization of <it>KIR </it>genetics in rhesus macaques (<it>Macaca mulatta)</it>. We conducted a survey of <it>KIRs </it>in this species, identifying 47 novel full-length <it>KIR </it>sequences. Using this expanded sequence library to build upon previous work, we present evidence supporting the existence of 22 <it>Mamu-KIR </it>genes, providing a framework within which to describe macaque <it>KIRs</it>. We also developed a novel pyrosequencing-based technique for <it>KIR </it>genotyping. This method provides both comprehensive <it>KIR </it>genotype and frequency estimates of transcript level, with implications for the study of <it>KIRs </it>in all species.</p> <p>Conclusions</p> <p>The results of this study significantly improve our understanding of macaque <it>KIR </it>genetic organization and diversity, with implications for the study of many human diseases that use macaques as a model. The ability to obtain comprehensive KIR genotypes is of basic importance for the study of KIRs, and can easily be adapted to other species. Together these findings both advance the field of macaque KIRs and facilitate future research into the role of KIRs in human disease.</p
Surface induced disorder in body-centered cubic alloys
We present Monte Carlo simulations of surface induced disordering in a model
of a binary alloy on a bcc lattice which undergoes a first order bulk
transition from the ordered DO3 phase to the disordered A2 phase. The data are
analyzed in terms of an effective interface Hamiltonian for a system with
several order parameters in the framework of the linear renormalization
approach due to Brezin, Halperin and Leibler. We show that the model provides a
good description of the system in the vicinity of the interface. In particular,
we recover the logarithmic divergence of the thickness of the disordered layer
as the bulk transition is approached, we calculate the critical behavior of the
maxima of the layer susceptibilities, and demonstrate that it is in reasonable
agreement with the simulation data. Directly at the (110) surface, the theory
predicts that all order parameters vanish continuously at the surface with a
nonuniversal, but common critical exponent. However, we find different
exponents for the order parameter of the DO3 phase and the order parameter of
the B2 phase. Using the effective interface model, we derive the finite size
scaling function for the surface order parameter and show that the theory
accounts well for the finite size behavior of the DO3 ordering but not for that
of B2 ordering. The situation is even more complicated in the neighborhood of
the (100) surface, due to the presence of an ordering field which couples to
the B2 order.Comment: To appear in Physical Review
The mosaic of KIR haplotypes in rhesus macaques
To further refine and improve biomedical research in rhesus macaques, it is necessary to increase our knowledge concerning both the degree of allelic variation (polymorphism) and diversity (gene copy number variation) in the killer cell immunoglobulin-like receptor (KIR) gene cluster. Pedigreed animals in particular should be studied, as segregation data will provide clues to the linkage of particular KIR genes/alleles segregating on a haplotype and to its gene content as well. A dual strategy allowed us to screen the presence and absence of genes and the corresponding transcripts, as well as to track differences in transcription levels. On the basis of this approach, 14 diverse KIR haplotypes have been described. These haplotypes consist of multiple inhibitory and activating Mamu-KIR genes, and any gene present on one haplotype may be absent on another. This suggests that the cost of accelerated evolution by recombination may be the loss of certain framework genes on a haplotype
Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity
Background: T-cell tolerance of allergic cutaneous contact
sensitivity (CS) induced in mice by high doses of reactive hapten
is mediated by suppressor cells that release antigen-specific
suppressive nanovesicles.
Objective: We sought to determine the mechanism or
mechanisms of immune suppression mediated by the
nanovesicles.
Methods: T-cell tolerance was induced by means of intravenous
injection of hapten conjugated to self-antigens of syngeneic
erythrocytes and subsequent contact immunization with the same
hapten. Lymph node and spleen cells from tolerized or control
donors were harvested and cultured to produce a supernatant
containing suppressive nanovesicles that were isolated from the
tolerized mice for testing in active and adoptive cell-transfer
models of CS.
Results: Tolerance was shown due to exosome-like nanovesicles
in the supernatants of CD81 suppressor T cells that were not
regulatory T cells. Antigen specificity of the suppressive
nanovesicles was conferred by a surface coat of antibody light
chains or possibly whole antibody, allowing targeted delivery of
selected inhibitory microRNA (miRNA)–150 to CS effector T
cells. Nanovesicles also inhibited CS in actively sensitized mice
after systemic injection at the peak of the responses. The role of
antibody and miRNA-150 was established by tolerizing either
panimmunoglobulin-deficient JH2/2 or miRNA-1502/2 mice
that produced nonsuppressive nanovesicles. These nanovesicles
could be made suppressive by adding antigen-specific antibody
light chains or miRNA-150, respectively.
Conclusions: This is the first example of T-cell regulation
through systemic transit of exosome-like nanovesicles delivering
a chosen inhibitory miRNA to target effector T cells in an
antigen-specific manner by a surface coating of antibody light
chains
- …