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101.
Relapsing polychondritis (RP) is an autoimmune disease that affects extra-articular cartilage. Matrilin-1-induced relapsing
polychondritis (MIRP) is a model for RP and is useful for studies of the pathogenic mechanisms in this disease. There are
indications that the major histocompatibility complex (MHC) class II plays a major role in RP, since DR4+ patients are more commonly affected than controls. We have now addressed the role of the MHC region, as well as the non-MHC
contribution, using congenic mouse strains. Of the MHC congenic strains, B10.Q (H2
q
) was the most susceptible, the B10.P (H2
p
) and B10.R (H2
r
) strains developed mild disease, while B10 strains carrying the v, b, f, or u H2 haplotypes were resistant. A slight variation
of susceptibility of H2
q
strains (B10.Q> C3H.Q> DBA/1) was observed and the (B10.Q × DBA/1)F1 was the most susceptible of all strains. Furthermore, macrophages and CD4+ T cells were the most prominent cell types in inflammatory infiltrates of the tracheal cartilage. Macrophages are the major
source of many cytokines, such as interleukin-10 (IL-10), which is currently being tested as a therapeutic agent in several
autoimmune diseases. We therefore investigated B10.Q mice devoid of IL-10 through gene deletion and found that they developed
a significantly more severe disease, with an earlier onset, than their heterozygous littermates. In conclusion, MHC genes,
as well as non-MHC genes, are important for MIRP induction, and IL-10 plays a major suppressive role in cartilage inflammation
of the respiratory tract. 相似文献
102.
The whole-cell patch-clamp technique was used to study the properties of inward ionic currents found in primary cultures of rat and mouse skeletal myotubes and in freshly dissociated fibers of the flexor digitorum brevis muscle of rats. In each of these cell types, test depolarizations from the holding potential (-80 or -90 mV) elicited three distinct inward currents: a sodium current (INa) and two calcium currents. INa was the dominant inward current: under physiological conditions, the maximum inward INa was estimated to be at least 30-fold larger than either of the calcium currents. The two calcium currents have been termed Ifast and Islow, corresponding to their relative rates of activation. Ifast was activated by test depolarizations to around -40 mV and above, peaked in 10-20 ms, and decayed to baseline in 50-100 ms. Islow was activated by depolarizations to approximately 0 mV and above, peaked in 50-150 ms, and decayed little during a 200-ms test pulse. Ifast was inactivated by brief, moderate depolarizations; for a 1-s change in holding potential, half-inactivation occurred at -55 to -45 mV and complete inactivation occurred at -40 to -30 mV. Similar changes in holding potential had no effect on Islow. Islow was, however, inactivated by brief, strong depolarizations (e.g., 0 mV for 2 s) or maintained, moderate depolarizations (e.g., -40 mV for 60 s). Substitution of barium for calcium had little effect on the magnitude or time course of either Ifast or Islow. The same substitution shifted the activation curve for Islow approximately 10 mV in the hyperpolarizing direction without affecting the activation of Ifast. At low concentrations (50 microM), cadmium preferentially blocked Islow compared with Ifast, while at high concentrations (1 mM), it blocked both Ifast and Islow completely. The dihydropyridine calcium channel antagonist (+)-PN 200-110 (1 microM) caused a nearly complete block of Islow without affecting Ifast. At a holding potential of -80 mV, the half-maximal blocking concentration (K0.5) for the block of Islow by (+)-PN 200-110 was 182 nM. At depolarized holding potentials that inactivated Islow by 35-65%, K0.5 decreased to 5.5 nM. 相似文献
103.
Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice 总被引:3,自引:0,他引:3
Nagamine CM; Shiroishi T; Miyashita N; Tsuchiya K; Ikeda H; Takao N; Wu XL; Jin ML; Wang FS; Kryukov AP 《Molecular biology and evolution》1994,11(6):864-874
When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is
replaced by the Y of certain strains of Mus musculus domesticus, testis
determination fails and all XY fetuses develop either as hermaphrodites or
XY females (XY sex reversal). This suggests the presence of at least two
alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6.
The B6 Y chromosome is derived from the Japanese house mouse, M. m.
molossinus and therefore carries a molossinus Sry allele. As a first step
to determine how the molossinus Sry allele evolved, its distribution
pattern was determined in wild mice. The cumulative data of 96 M. musculus
samples obtained from 58 geographical locations in Europe, North Africa,
and Asia show the molossinus Sry allele is restricted to Japan and the
neighboring Asian mainland and confirm that Japanese M. m. molossinus mice
were derived in part from a race of M. m. musculus from Korea or Manchuria.
Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve
as molecular markers for studies on the evolution of wild M. musculus
populations and can help determine the role sex determination plays in
speciation.
相似文献
104.
Members of the ZFY and ZNF6 gene families have been cloned from species
representing different taxa and different modes of sex determination.
Comparisons of these genes show the ZFY-like and ZNF6 sequences to be
strongly conserved across marsupials, birds, and lepidosaurians. Sequence
analyzed by neighbor-joining indicated that both gene families are
monophyletic with a high bootstrap value. Pairing of sequences from males
and females of nonmammalian species showed there to be no significant
difference between male and female sequences from a single species,
consistent with autosomal locations. The molecular distances between murine
Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have
undergone a period of rapid evolutionary change not seen in human ZFY.
相似文献
105.
The phylogenetic position of Rhopalura ophiocomae (Orthonectida) based on 18S ribosomal DNA sequence analysis 总被引:2,自引:0,他引:2
Hanelt B; Van Schyndel D; Adema CM; Lewis LA; Loker ES 《Molecular biology and evolution》1996,13(9):1187-1191
The Orthonectida is a small, poorly known phylum of parasites of marine
invertebrates. Their phylogenetic placement is obscure; they have been
considered to be multicellular protozoans, primitive animals at a
"mesozoan" grade of organization, or secondarily simplified flatworm- like
organisms. The best known species in the phylum, Rhopalura ophiocomae, was
collected on San Juan Island, Wash. and a complete 18S rDNA sequence was
obtained. Using the models of minimum evolution and parsimony, phylogenetic
analyses were undertaken and the results lend support to the following
hypotheses about orthonectids: (1) orthonectids are more closely aligned
with triploblastic metazoan taxa than with the protist or diploblastic
metazoan taxa considered in this analysis; (2) orthonectids are not derived
members of the phylum Platyhelminthes; and (3) orthonectids and rhombozoans
are not each other's closest relatives, thus casting further doubt on the
validity of the phylum Mesozoa previously used to encompass both groups.
相似文献
106.
Although invertebrate drift is an important ecological process in lotic ecosystems, very little is known about it in Kenyan rivers. The primary aim of this study was to investigate the effect of driftnet mesh size and exposure duration on drift density in 2017. Drift samples were dominated by Chironomidae, Baetidae, Simuliidae, Caenidae and Culicidae. The 100 µm mesh driftnet had the highest mean invertebrate density, followed by the 250 µm and 500 µm nets. Invertebrate drift densities decreased with increased exposure time. This study demonstrates that sampler mesh size and exposure time should be taken into account when characterising invertebrate drift in streams. Future studies should consider sampling different biotopes and during different seasons. 相似文献
107.
Transposable elements induce spontaneous mutations, promote genome
rearrangements, regulate gene expression, and participate in the horizontal
spread of genes encoding traits such as antibiotic resistance among
bacterial genera too distantly related to undergo homologous recombination.
Here we review the bacterial transposon Tn5 and focus on those aspects of
its functional organization and transposition which provide insights into
how it and other elements may have arisen, proliferated, and evolved.
相似文献
108.
A mathematical approach was developed to model and optimize selection on multiple known quantitative trait loci (QTL) and polygenic estimated breeding values in order to maximize a weighted sum of responses to selection over multiple generations. The model allows for linkage between QTL with multiple alleles and arbitrary genetic effects, including dominance, epistasis, and gametic imprinting. Gametic phase disequilibrium between the QTL and between the QTL and polygenes is modeled but polygenic variance is assumed constant. Breeding programs with discrete generations, differential selection of males and females and random mating of selected parents are modeled. Polygenic EBV obtained from best linear unbiased prediction models can be accommodated. The problem was formulated as a multiple-stage optimal control problem and an iterative approach was developed for its solution. The method can be used to develop and evaluate optimal strategies for selection on multiple QTL for a wide range of situations and genetic models. 相似文献
109.
Eric A Gaucher Logan G Graddy Tang Li Rosalia CM Simmen Frank A Simmen David R Schreiber David A Liberles Christine M Janis Steven A Benner 《BMC biology》2004,2(1):19
Background
Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. 相似文献110.
Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs 总被引:1,自引:0,他引:1
Metallothioneins are cysteine-rich, small metal-binding proteins present in various mammalian tissues. Of the four common
metallothioneins, MT-1 and MT-2 (MTs) are expressed in most tissues, MT-3 is predominantly present in brain, whereas MT-4
is restricted to the squamous epithelia. The expression of MT-1 and MT-2 in some organs exhibits sex, age, and strain differences,
and inducibility with a variety of stimuli. In adult mammals, MTs have been localized largely in the cell cytoplasm, but also
in lysosomes, mitochondria and nuclei. The major physiological functions of MTs include homeostasis of essential metals Zn
and Cu, protection against cytotoxicity of Cd and other toxic metals, and scavenging free radicals generated in oxidative
stress. The role of MTs in Cd-induced acute and chronic toxicity, particularly in liver and kidneys, is reviewed in more details.
In acute toxicity, liver is the primary target, whereas in chronic toxicity, kidneys are major targets of Cd. The intracellular
MTs bind Cd ions and form CdMT. In chronic intoxication, Cd stimulates de novo synthesis of MTs; it is assumed that toxicity
in the cells starts when loading with Cd ions exceeds the buffering capacity of intracellular MTs. CdMT, released from the
Cd-injured organs, or when applied parenterally for experimental purposes, reaches the kidneys via circulation, where it is
filtered, endocytosed in the proximal tubule cells, and degraded in lysosomes. Liberated Cd can immediately affect the cell
structures and functions. The resulting proteinuria and CdMT in the urine can be used as biomarkers of tubular injury. 相似文献