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1.
We have broadly defined the DNA regions regulating esterase6 activity in
several life stages and tissue types of D. melanogaster using P-
element-mediated transformation of constructs that contain the esterase6
coding region and deletions or substitutions in 5' or 3' flanking DNA.
Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and
the primary sequences regulating its activity lie between -171 and -25 bp
relative to the translation initiation site: deletion of these sequences
decrease activity approximately 20-fold. Hemolymph activity is also
modulated by four other DNA regions, three of which lie 5' and one of which
lies 3' of the coding region. Of these, two have positive and two have
negative effects, each of approximately twofold. Esterase6 activity is
present also in two male reproductive tract tissues; the ejaculatory bulb,
which is another ancestral activity site, and the ejaculatory duct, which
is a recently acquired site within the melanogaster species subgroup.
Activities in these tissues are at least in part independently regulated:
activity in the ejaculatory bulb is conferred by sequences between -273 and
-172 bp (threefold decrease when deleted), while activity in the
ejaculatory duct is conferred by more distal sequences between -844 and
-614 bp (fourfold decrease when deleted). The reproductive tract activity
is further modulated by two additional DNA regions, one in 5' DNA (-613 to
-284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to
+2731 bp; threefold decrease when deleted) that probably overlaps the
adjacent esteraseP gene. Collating these data with previous studies
suggests that expression of EST6 in the ancestral sites is mainly regulated
by conserved proximal sequences while more variable distal sequences
regulate expression in the acquired ejaculatory duct site.
相似文献
2.
Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
3.
Monica K. Borucki Haiyin Chen-Harris Victoria Lao Gilda Vanier Debra A. Wadford Sharon Messenger Jonathan E. Allen 《PLoS neglected tropical diseases》2013,7(11)
One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change. 相似文献
4.
Schistosomiasis vector snails are subjected to extreme seasonal changes, particularly in ephemeral rivers and lentic waterbodies. In the tropics, aestivation is one of the adaptive strategies for survival and is used by snails in times of extremely high temperatures and desiccation. Aestivation therefore plays an important role in maintaining the transmission of schistosomiasis. This review assesses the possible impacts of climate change on the temporal and spatial distribution of schistosomiasis-transmitting snails with special emphasis on aestivation, and discusses the effect of schistosome infection on aestivation ability. The impacts of parasite development on snails, as well as physiological changes, are discussed with reference to schistosomiasis transmission. This review shows that schistosome-infected snails have lower survival rates during aestivation, and that those that survive manage to get rid of the infection. In general, snail aestivation ability is poor and survival chances diminish with time. Longer dry periods result in fewer, as well as uninfected, snails. However, the ability of the surviving snails to repopulate the habitats is high. 相似文献
5.
Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase
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Sharon C Mithoe Christina Ludwig Michiel JC Pel Mara Cucinotta Alberto Casartelli Malick Mbengue Jan Sklenar Paul Derbyshire Silke Robatzek Corné MJ Pieterse Ruedi Aebersold Frank LH Menke 《EMBO reports》2016,17(3):441-454
Pattern recognition receptors (PRRs) play a key role in plant and animal innate immunity. PRR binding of their cognate ligand triggers a signaling network and activates an immune response. Activation of PRR signaling must be controlled prior to ligand binding to prevent spurious signaling and immune activation. Flagellin perception in Arabidopsis through FLAGELLIN‐SENSITIVE 2 (FLS2) induces the activation of mitogen‐activated protein kinases (MAPKs) and immunity. However, the precise molecular mechanism that connects activated FLS2 to downstream MAPK cascades remains unknown. Here, we report the identification of a differentially phosphorylated MAP kinase kinase kinase that also interacts with FLS2. Using targeted proteomics and functional analysis, we show that MKKK7 negatively regulates flagellin‐triggered signaling and basal immunity and this requires phosphorylation of MKKK7 on specific serine residues. MKKK7 attenuates MPK6 activity and defense gene expression. Moreover, MKKK7 suppresses the reactive oxygen species burst downstream of FLS2, suggesting that MKKK7‐mediated attenuation of FLS2 signaling occurs through direct modulation of the FLS2 complex. 相似文献
6.
The hair follicle: a paradoxical androgen target organ 总被引:3,自引:0,他引:3
Randall VA Hibberts NA Thornton MJ Hamada K Merrick AE Kato S Jenner TJ De Oliveira I Messenger AG 《Hormone research》2000,54(5-6):243-250
Androgens are the main regulator of normal human hair growth. After puberty, they promote transformation of vellus follicles, producing tiny, unpigmented hairs, to terminal ones, forming larger pigmented hairs, in many areas, e.g. the axilla. However, they have no apparent effect on the eyelashes, but can cause the opposite transformation on the scalp leading to the replacement of terminal hairs by vellus ones and the gradual onset of androgenetic alopecia. This paradox appears to be an unique hormonal effect. Hair follicles are mainly epithelial tissues, continuous with the epidermis, which project into the dermis. A mesenchyme-derived dermal papilla enclosed within the hair bulb at the base controls many aspects of follicle function. In the current hypothesis for androgen regulation, the dermal papilla is also considered the main site of androgen action with androgens from the blood binding to receptors in dermal papilla cells of androgen-sensitive follicles and causing an alteration of their production of paracrine factors for target cells e.g. keratinocytes. Studies of cultured dermal papilla cells from sites with different responses to androgens in vivo have confirmed the paradoxical responses. All dermal papilla cells from androgen-sensitive sites contain low capacity, high affinity androgen receptors. However, only some cells formed 5alpha-dihydrotestosterone, e.g. beard but not axillary cells, in line with hair growth in 5alpha-reductase deficiency. Incubation with androgens also stimulated the mitogenic capacity of beard cell media, but inhibited that produced by scalp cells. This suggests that the paradoxical differences are due to differential gene expression within hair follicles, presumably caused during embryogenesis. 相似文献
7.
Tazi-Ahnini R di Giovine FS McDonagh AJ Messenger AG Amadou C Cox A Duff GW Cork MJ 《Human genetics》2000,106(6):639-645
Alopecia areata (AA) is a chronic inflammatory disease characterised by patchy hair loss with T cell infiltration of hair follicles. AA occurs in approximately 0.1% of the general population, but this is increased to 9% in Down syndrome (DS). DS is associated with an additional copy (full or partial) of chromosome 21, and the DS region may potentially include genes involved in the pathogenesis of AA. MX1 is the gene encoding the interferon-induced p78 protein (MxA). MxA protein confers resistance to influenza viruses, and we have previously shown that MxA protein is strongly expressed in lesional anagen hair bulbs from patients with AA but not in normal follicles. We therefore studied the possible involvement of MX1 in the pathogenesis of AA. To establish markers in the MX1 region which could be screened by PCR-based methods, we defined the human MX1 exon/intron organisation and screened the exons and the introns by conformation-sensitive gel electrophoresis. We found that the MX1 gene contains 17 exons extending over 33 kb. The size and sequence of the region from exon 6 to exon 16 are highly conserved between human and mouse. Screening of 4747 bp within the MX1 gene revealed four single nucleotide polymorphisms in intron 6. These polymorphisms are concentrated within 147 bp and show strong linkage disequilibrium. In a case-control association study for the MX1 (+9959) polymorphism in 165 AA patients and 510 controls we found a significant association of this marker with AA (odds ratio 1.79, 95% CI 1.21-2.66, chi2 = 8.464, P = 0.0036). The risk of disease was greater for patchy AA (mild disease) and with early age at onset (odds ratio 2.34, 95% CI 1.24-4.43, P = 0.0072), providing new evidence of genetic heterogeneity in AA. Our demonstration of genetic association between the MX1 gene and disease supports the hypothesis that this is a new candidate gene in AA. 相似文献
8.
1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors
Marino C; Marino K; Miletti L; Manso Alves MJ; Colli W; de Lederkremer RM 《Glycobiology》1998,8(9):901-904
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design
of inhibitors, since beta-D-galactofuranose is a constituent of important
parasite glycoconjugates but is not present in the host mammals. With this
aim, we have synthesized for the first time alkyl, benzyl and aryl
1-thio-beta-D-galactofuranosides by condensation of
penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols,
in the presence of SnCl4as catalyst. The complete chemical and
spectroscopical characterization of these compounds showed that the
reaction was stereoselective. Debenzoylation with sodium methoxide afforded
the beta-S-galactofuranosides in high yield. The thioglycosides were tested
as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum,
using for the first time 4-nitrophenyl-beta-D-galactofuranoside as
chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside,
obtained by catalytic hydrogenation of the nitrophenyl derivative, was the
best inhibitor being then an adequate ligand for the preparation of an
affinity phase aimed at the isolation of beta-d-galactofuranosidases from
different sources. Also the inhibitory activity of d-galactono-1, 4-lactone
was shown.
相似文献
9.
10.
Kelly A. Shipkowski Alexia J. Taylor Elizabeth A. Thompson Ellen E. Glista-Baker Brian C. Sayers Zachary J. Messenger Rebecca N. Bauer Ilona Jaspers James C. Bonner 《PloS one》2015,10(6)