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1.
Cell death can be divided into the anti-inflammatory process of apoptosis and the
pro-inflammatory process of necrosis. Necrosis, as apoptosis, is a regulated form of cell
death, and Poly-(ADP-Ribose) Polymerase-1 (PARP-1) and Receptor-Interacting Protein (RIP)
1/3 are major mediators. We previously showed that absence or inhibition of PARP-1
protects mice from nephritis, however only the male mice. We therefore hypothesized that
there is an inherent difference in the cell death program between the sexes. We show here
that in an immune-mediated nephritis model, female mice show increased apoptosis compared
to male mice. Treatment of the male mice with estrogens induced apoptosis to levels
similar to that in female mice and inhibited necrosis. Although PARP-1 was activated in
both male and female mice, PARP-1 inhibition reduced necrosis only in the male mice. We
also show that deletion of RIP-3 did not have a sex bias. We demonstrate here that male
and female mice are prone to different types of cell death. Our data also suggest that
estrogens and PARP-1 are two of the mediators of the sex-bias in cell death. We therefore
propose that targeting cell death based on sex will lead to tailored and better treatments
for each gender. 相似文献
2.
3.
The tiger beetle fauna of the Balkan Peninsula is one of the richest in Europe and includes 19 species or 41% of the European tiger beetle fauna. Assembled by their biogeographical origins, the Balkan tiger beetle species fall into 14 different groups that include, Mediterranean, Middle Oriental, Central Asiatic, Euro-Siberian, South and East European, Pannonian-Sarmatian, West Palaearctic, Turano-European and Afrotropico Indo-Mediterranean species. The Mediterranean Sclerophyl and the Pontian Steppe are the Balkan biogeographical provinces with the highest species richness, while the Balkan Highlands has the lowest Cicindelidae diversity. Most species are restricted to single habitat types in lowland areas of the Balkan Peninsula and only Calomera aulica aulica and Calomera littoralis nemoralis occur in respectively 3 and 4 different types of habitat. About 60% of all Balkan Cicindelidae species are found in habitats potentially endangered by human activity. 相似文献
4.
Jason D. Hoffert Chung-Lin Chou Mark A. Knepper 《The Journal of biological chemistry》2009,284(22):14683-14687
Vasopressin controls renal water excretion largely through actions to
regulate the water channel aquaporin-2 in collecting duct principal cells. Our
knowledge of the mechanisms involved has increased markedly in recent years
with the advent of methods for large-scale systems-level profiling such as
protein mass spectrometry, yeast two-hybrid analysis, and oligonucleotide
microarrays. Here we review this progress.Regulation of water excretion by the kidney is one of the most visible
aspects of everyday physiology. An outdoor tennis game on a hot summer day can
result in substantial water losses by sweating, and the kidneys respond by
reducing water excretion. In contrast, excessive intake of water, a frequent
occurrence in everyday life, results in excretion of copious amounts of clear
urine. These responses serve to exact tight control on the tonicity of body
fluids, maintaining serum osmolality in the range of 290–294 mosmol/kg
of H2O through the regulated return of water from the pro-urine in
the renal collecting ducts to the bloodstream.The importance of this process is highlighted when the regulation fails.
For example, polyuria (rapid uncontrolled excretion of water) is a sometimes
devastating consequence of lithium therapy for bipolar disorder. On the other
side of the coin are water balance disorders that result from excessive renal
water retention causing systemic hypo-osmolality or hyponatremia. Hyponatremia
due to excessive water retention can be seen with severe congestive heart
failure, hepatic cirrhosis, and the syndrome of inappropriate
antidiuresis.The chief regulator of water excretion is the peptide hormone
AVP,2 whereas the
chief molecular target for regulation is the water channel AQP2. In this
minireview, we describe new progress in the understanding of the molecular
mechanisms involved in regulation of AQP2 by AVP in collecting duct cells,
with emphasis on new information derived from “systems-level”
approaches involving large-scale profiling and screening techniques such as
oligonucleotide arrays, protein mass spectrometry, and yeast two-hybrid
analysis. Most of the progress with these techniques is in the identification
of individual molecules involved in AVP signaling and binding interactions
with AQP2. Additional related issues are addressed in several recent reviews
(1–4). 相似文献
5.
Saija Kiljunen Neeta Datta Svetlana V. Dentovskaya Andrey P. Anisimov Yuriy A. Knirel Jos�� A. Bengoechea Otto Holst Mikael Skurnik 《Journal of bacteriology》2011,193(18):4963-4972
φA1122 is a T7-related bacteriophage infecting most isolates of Yersinia pestis, the etiologic agent of plague, and used by the CDC in the identification of Y. pestis. φA1122 infects Y. pestis grown both at 20°C and at 37°C. Wild-type Yersinia pseudotuberculosis strains are also infected but only when grown at 37°C. Since Y. pestis expresses rough lipopolysaccharide (LPS) missing the O-polysaccharide (O-PS) and expression of Y. pseudotuberculosis O-PS is largely suppressed at temperatures above 30°C, it has been assumed that the phage receptor is rough LPS. We present here several lines of evidence to support this. First, a rough derivative of Y. pseudotuberculosis was also φA1122 sensitive when grown at 22°C. Second, periodate treatment of bacteria, but not proteinase K treatment, inhibited the phage binding. Third, spontaneous φA1122 receptor mutants of Y. pestis and rough Y. pseudotuberculosis could not be isolated, indicating that the receptor was essential for bacterial growth under the applied experimental conditions. Fourth, heterologous expression of the Yersinia enterocolitica O:3 LPS outer core hexasaccharide in both Y. pestis and rough Y. pseudotuberculosis effectively blocked the phage adsorption. Fifth, a gradual truncation of the core oligosaccharide into the Hep/Glc (l-glycero-d-manno-heptose/d-glucopyranose)-Kdo/Ko (3-deoxy-d-manno-oct-2-ulopyranosonic acid/d-glycero-d-talo-oct-2-ulopyranosonic acid) region in a series of LPS mutants was accompanied by a decrease in phage adsorption, and finally, a waaA mutant expressing only lipid A, i.e., also missing the Kdo/Ko region, was fully φA1122 resistant. Our data thus conclusively demonstrated that the φA1122 receptor is the Hep/Glc-Kdo/Ko region of the LPS core, a common structure in Y. pestis and Y. pseudotuberculosis. 相似文献
6.
The genus Planinasus Cresson is revised and includes 18 extant and one fossil species. We clarify the status of the three previously described species and describe 15 new species as follows (type locality in parenthesis): Planinasus aenigmaticus (Colombia. Bogota: Bogota (04°35.8''N, 74°08.8''W)), Planinasus neotropicus (Panama. Canal Zone: Barro Colorado Island (09°09.1''N, 79°50.8''W)), Planinasus kotrbae (Ecuador. Orellana: Rio Tiputini Biodiversity Station (0°38.2''S, 76°08.9''W)), Planinasus miradorus (Brazil. Maranhão: Parque Estadual Mirador, Base da Geraldina (06°22.2''S, 44°21.8''W)), Planinasus tobagoensis (Trinidad and Tobago. Tobago. St. John: Parlatuvier (11°17.9''N, 60°39''W)), Planinasus xanthops (Ecuador. Orellana: Rio Tiputini Biodiversity Station (0°38.2''S, 76°8.9''W)), Planinasus argentifacies (Peru. Madre de Dios: Río Manu, Pakitza (11°56.6''S, 71°16.9''W; 250 m)), Planinasus insulanus (Dominican Republic. La Vega: near Jarabacoa, Salto Guasara (19°04.4''N, 70°42.1''W, 680 m)), Planinasus nigritarsus (Guyana. Conservation of Ecological Interactions and Biotic Associations (CEIBA; ca. 40 km S Georgetown; 06°29.9''N, 58°13.1''W)), Planinasus atriclypeus (Brazil. Rio de Janeiro: Rio de Janeiro, Floresta da Tijuca (22°57.6''S, 43°16.4''W)), Planinasus atrifrons (Bolivia. Santa Cruz: Ichilo, Buena Vista (4-6 km SSE; Hotel Flora y Fauna; 17°29.95''S, 63°33.15''W; 4-500 m)), P. flavicoxalis (West Indies. Dominica. St. David: 1.6 km N of junction of roads to Rosalie and Castle Bruce (15°23.8''N, 61°18.6''W)), Planinasus mcalpineorum (Mexico. Chiapas: Cacahoatan (7 km N; 15°04.1''N, 92°07.4''W)), Planinasus nigrifacies (Brazil. São Paulo: Mogi das Cruzes, Serra do Itapeti (23°31.5''S, 46°11.2''W)), Planinasus obscuripennis (Peru. Madre de Dios: Río Manu, Erika (near Salvación; 12°50.7''S, 71°23.3''W; 550 m)). In addition to external characters, we also describe and illustrate structures of the male terminalia and for Planinasus kotrbae
sp. n., the internal female reproductive organs. Detailed locality data and distribution maps for all species are provided. For perspective and to facilitate genus-group and species-group recognition, the family Periscelididae and subfamily Stenomicrinae are diagnosed and for the latter, a key to included genera is provided. 相似文献
7.
Duvalius (sg. Neoduvalius) gejzadunayi
sp. n. from Pećina u Dubokom potoku cave ( Donje Biševo village near Rožaje, Montenegro), the first known representative of this subgenus from the territory of Montenegro is described, illustrated and compared with the related species of the subgenus Neoduvalius Müller, 1913. This new species is characterised by depigmented, medium sized body, totally reduced eyes, deep and complete frontal furrows, 3–4 pairs of discal setae in third elytral stria, as well as by the shape of aedeagus. Data on the distribution and the ecology of this remarkable species, as well as a check-list of the subgenus Neoduvalius are also provided. Recently described genera Serboduvalius Ćurčić, S. B. Pavićević & Ćurčić, B.P.M., 2001, Rascioduvalius Ćurčić, S. B. Brajković, Mitić & Ćurčić, B.P.M., 2003, Javorella Ćurčić, S. B. Brajković, Ćurčić, B.P.M. & Mitić, 2003 and Curcicia Ćurčić, S. B. & Brajković, 2003 are regarded as junior synonyms of the genus Duvalius Delarouzée. 相似文献
8.
Zhang L Kinkelaar D Huang Y Li Y Li X Wang HH 《Applied and environmental microbiology》2011,77(20):7134-7141
The rapid emergence of antibiotic resistance (AR) is a major public health concern. Recent findings on the prevalence of food-borne antibiotic-resistant (ART) commensal bacteria in ready-to-consume food products suggested that daily food consumption likely serves as a major avenue for dissemination of ART bacteria from the food chain to human hosts. To properly assess the impact of various factors, including the food chain, on AR development in hosts, it is important to determine the baseline of ART bacteria in the human gastrointestinal (GI) tract. We thus examined the gut microbiota of 16 infant subjects, from the newborn stage to 1 year of age, who fed on breast milk and/or infant formula during the early stages of development and had no prior exposure to antibiotics. Predominant bacterial populations resistant to several antibiotics and multiple resistance genes were found in the infant GI tracts within the first week of age. Several ART population transitions were also observed in the absence of antibiotic exposure and dietary changes. Representative AR gene pools including tet(M), ermB, sul2, and bla(TEM) were detected in infant subjects. Enterococcus spp., Staphylococcus spp., Klebsiella spp., Streptococcus spp., and Escherichia coli/Shigella spp. were among the identified AR gene carriers. ART bacteria were not detected in the infant formula and infant foods examined, but small numbers of skin-associated ART bacteria were found in certain breast milk samples. The data suggest that the early development of AR in the human gut microbiota is independent of infants' exposure to antibiotics but is likely impacted by exposure to maternal and environmental microbes during and after delivery and that the ART population is significantly amplified within the host even in the absence of antibiotic selective pressure. 相似文献
9.
Eugenijus ?imoliūnas Laura Kaliniene Lidija Truncait? Aurelija Zajan?kauskait? Juozas Staniulis Algirdas Kaupinis Marija Ger Mindaugas Valius Rolandas Me?kys 《PloS one》2013,8(4)
At 346 kbp in size, the genome of a jumbo bacteriophage vB_KleM-RaK2 (RaK2) is the largest Klebsiella infecting myovirus genome sequenced to date. In total, 272 out of 534 RaK2 ORFs lack detectable database homologues. Based on the similarity to biologically defined proteins and/or MS/MS analysis, 117 of RaK2 ORFs were given a functional annotation, including 28 RaK2 ORFs coding for structural proteins that have no reliable homologues to annotated structural proteins in other organisms. The electron micrographs revealed elaborate spike-like structures on the tail fibers of Rak2, suggesting that this phage is an atypical myovirus. While head and tail proteins of RaK2 are mostly myoviridae-related, the bioinformatics analysis indicate that tail fibers/spikes of this phage are formed from podovirus-like peptides predominantly. Overall, these results provide evidence that bacteriophage RaK2 differs profoundly from previously studied viruses of the Myoviridae family. 相似文献
10.
cDNA
corresponding to the GA4 gene of
Arabidopsis thaliana L. (Heynh.) was
expressed in Escherichia coli, from which cell lysates
converted [14C]gibberellin (GA)9 and
[14C]GA20 to radiolabeled GA4 and
GA1, respectively, thereby confirming that
GA4 encodes a GA 3β-hydroxylase. GA9 was
the preferred substrate, with a Michaelis value of 1 μm
compared with 15 μm for GA20. Hydroxylation
of these GAs was regiospecific, with no indication of
2β-hydroxylation or 2,3-desaturation. The capacity of the recombinant
enzyme to hydroxylate a range of other GA substrates was investigated.
In general, the preferred substrates contained a polar bridge between
C-4 and C-10, and 13-deoxy GAs were preferred to their 13-hydroxylated
analogs. Therefore, no activity was detected using
GA12-aldehyde, GA12, GA19,
GA25, GA53, or GA44 as the open
lactone (20-hydroxy-GA53), whereas GA15,
GA24, and GA44 were hydroxylated to
GA37, GA36, and GA38, respectively.
The open lactone of GA15 (20-hydroxy-GA12) was
hydroxylated but less efficiently than GA15. In contrast to
the free acid, GA25 19,20-anhydride was 3β-hydroxylated
to give GA13. 2,3-Didehydro-GA9 and
GA5 were converted by recombinant GA4 to the corresponding
epoxides 2,3-oxido-GA9 and GA6.Dwarf mutants with reduced biosynthesis of the GA plant hormones
have been valuable tools in studies of the function of these compounds
(Ross, 1994). In Arabidopsis thaliana, mutations
at six loci (GA1-GA6) that result in reduced GA
biosynthesis have been identified (Koorneef and van der Veen, 1980;
Sponsel et al., 1997), and three of these loci have recently been
cloned. The GA1 locus was isolated by genomic subtraction
(Sun et al., 1992) and shown by heterologous expression in
Escherichia coli to encode the enzyme that cyclizes
geranylgeranyl diphosphate to copalyl diphosphate (Sun and Kamiya,
1994). This enzyme was formerly referred to as ent-kaurene
synthase A but has been renamed copalyl diphosphate synthase
(Hedden and Kamiya, 1997; MacMillan, 1997). The GA5
locus was shown to correspond to one of the GA 20-oxidase genes (Xu et
al., 1995), the products of which catalyze the conversion of
GA12 to GA9 and
GA53 to GA20 (Phillips et
al., 1995; Xu et al., 1995). GA 20-oxidases are
2-oxoglutarate-dependent dioxygenases that are encoded by small
multigene families, members of which are differentially expressed in
plant tissues (Phillips et al., 1995; Garcia-Martinez et al., 1997).The GA4 locus was isolated by T-DNA tagging and, on the
basis of the derived amino acid sequence, was also shown to encode a
dioxygenase (Chiang et al., 1995). Several lines of evidence indicate
that the GA4 gene encodes a GA 3β-hydroxylase. Shoots of a
ga4 mutant, all alleles of which are semidwarf, contained
reduced concentrations of the 3β-hydroxy GAs
GA1, GA4, and
GA8 compared with the Landsberg erecta
wild type, whereas levels of immediate precursors to these GAs were
elevated (Talon et al., 1990). Furthermore, metabolism of
[13C]GA20 to
[13C]GA1 was
substantially less in the mutant than in the wild type (Kobayashi et
al., 1994). In the present paper we confirm by functional expression of
its cDNA in E. coli that GA4 encodes a GA
3β-hydroxylase. In addition, we determine the substrate specificity
of recombinant GA4 using a number of C20- and
C19-GAs and show by kinetic analysis that the enzyme
has a higher affinity for GA9 than for
GA20, which is consistent with the
non-13-hydroxylation pathway predominating in Arabidopsis (Talon et
al., 1990). 相似文献
11.
Probing the Conformation of the Fibronectin III1�C2
Domain by Fluorescence Resonance Energy
Transfer
Nancy W. Karuri Zong Lin Hays S. Rye Jean E. Schwarzbauer 《The Journal of biological chemistry》2009,284(6):3445-3452
Fibronectin (FN) matrix is crucial for cell and tissue functions during
embryonic development, wound healing, and oncogenesis. Assembly of FN matrix
fibrils requires FN domains that mediate interactions with integrin receptors
and with other FN molecules. In addition, regulation of FN matrix assembly
depends on the first two FN type III modules, III1 and
III2, which harbor FN-binding sites. We propose that interactions
between these two modules sequester FN-binding sites in soluble FN and that
these sites become exposed by FN conformational changes during assembly. To
test the idea that III1–2 has a compact conformation, we
constructed CIIIY, a conformational sensor of III1–2 based on
fluorescent resonance energy transfer between cyan and yellow fluorescent
proteins conjugated at its N and C termini. We demonstrate energy transfer in
CIIIY and show that fluorescent resonance energy transfer was eliminated by
proteolysis and by treatment with mild denaturants that disrupted
intramolecular interactions between the two modules. We also show that
mutations of key charged residues resulted in conformational changes that
exposed binding sites for the N-terminal 70-kDa FN fragment. Collectively,
these results support a conformation-dependent mechanism for the regulation of
FN matrix assembly by III1–2.Fibronectin (FN)3
is a 500-kDa modular dimeric protein and a major component of the
extracellular matrix. It exists in the blood and other body fluids as a
soluble compact molecule and undergoes cell-mediated assembly to form an
insoluble three-dimensional fibrillar matrix (reviewed in Ref.
1). The process of FN matrix
assembly has been implicated in embryonic development, wound healing, and
cancer
(2–4).
FN is composed of type I–III modules, and sets of these modules comprise
binding domains for cells and for other extracellular matrix components (see
Fig. 1A). Three of
these binding domains are essential for matrix assembly
(1). Integrin receptor
interactions with the cell-binding domain tether disulfide-bonded FN dimers to
the cell surface, where FN-FN interactions involving the N-terminal assembly
domain form dimers into fibrils. In addition to these essential domains, other
FN-binding sites have been implicated in assembly. In particular, the
III1–2 FN-binding domain plays a regulatory role in matrix
assembly. Within this domain reside a cryptic FN-binding site in
III1 and a site available for FN binding in the native form of
III2
(5–8).
Recombinant FN lacking III1 is assembled into a matrix at wild-type
levels, but that lacking the III1–2 domain results in short
immature FN fibrils (8).
Peptides derived from the III1–2 domain or antibodies against
III1–2 block matrix assembly by cultured cells
(9–11).
Furthermore, FN binding to this region is enhanced when FN is mechanically
stretched (12). Taken
together, these results suggest that conformational changes in the
III1–2 domain may control its interactions during FN
assembly.Open in a separate windowFIGURE 1.The FN III1–2 FRET conformational sensor.
A, representation of the domain structure of FN and major interaction
sites. FN is composed of repeating modules that form binding domains for other
FN molecules, cell receptors, and other extracellular matrix components as
indicated. The first two type III modules III1 and III2
(black), have FN-binding sites and regulate FN matrix assembly. The
N-terminal 70-kDa region contains a matrix assembly domain with FN-binding
activity. The cell-binding domain (cell), the heparin-binding domain
(heparin), the dimerization site (SS), and the alternatively
spliced type IIIA (A), IIIB (B), and variable regions
(V) are indicated. 70kD, N-terminal 70-kDa FN fragment.
B, schematic of proposed model of III1–2 domain
conformation. Panel i, in solution, the FN-binding sites in
III1 and III2 (hatched areas) are sequestered
through domain orientations that are facilitated by the linker between modules
(thin line). Panel ii, binding sites are exposed through
conformational changes resulting from cell-mediated extension of FN
(arrows). The length of the linker and the height and width of the
modules are drawn to scale for a linear peptide and published data on FN type
III modules, respectively. C, ribbon diagram representation of CIIIY,
a FRET sensor of the model in B (panel i), oriented with N
and C termini 50 Å apart. CIIIY consists of the III1–2
domain with CFP at the N terminus and YFP at the C terminus.To more fully understand the roles of native and cryptic FN-binding sites
in matrix assembly, the conformational dynamics of III1–2
must be characterized. One approach to this problem is to tag
III1–2 with fluorescent probes, which, in conjunction with
fluorescent resonance energy transfer (FRET), create a molecular
conformational sensor. FRET involves the radiationless transfer of energy from
an excited donor fluorophore to an acceptor fluorophore, a process that is
very sensitive to the distance between the two fluorophores
(13–15).
Two fluorescent protein variants, cyan fluorescent protein (CFP) and yellow
fluorescent protein (YFP), are highly related to green fluorescent protein
(GFP). Because the emission spectrum of CFP is well matched to the excitation
spectrum of YFP, these two fluorophores have been widely used as a
donor-acceptor pair in FRET studies
(13–15).In this study, we describe a FRET conformational sensor designed to test
the idea that intramolecular interactions between III1 and
III2 sequester key FN-binding and assembly sites. We show that
III1–2 with CFP and YFP fused to the N and C termini,
respectively, displays a clear FRET signal, indicating that the attached
fluorescent proteins and thus the ends of III1–2 are in close
proximity. FRET data from III1–2 mutants support the presence
of a stabilizing intermodule salt bridge that regulates FN-binding
activity. 相似文献
12.
Fernando Fonseca Val Vanderson Souza Sampaio Maria Belén Cassera Raquel Tapajós Andrade Pedro Luiz Tauil Wuelton Marcelo Monteiro Marcus Vinícius Guimar?es Lacerda 《Memórias do Instituto Oswaldo Cruz》2014,109(5):522-524
In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis
against malaria was considered to be a successful tool. However, with the development
of Plasmodium resistance in the Brazilian Amazon, this control
strategy was abandoned. More than 50 years later, asexual stage resistance can be
avoided by screening for antimalarial drugs that have a selective action against
gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old
methods should be tested as complementary tools for the elimination of malaria. 相似文献
13.
Hong Cao Jing Chen Eugene W. Krueger Mark A. McNiven 《Molecular and cellular biology》2010,30(3):781-792
The mechanisms by which epithelial cells regulate clathrin-mediated endocytosis (CME) of transferrin are poorly defined and generally viewed as a constitutive process that occurs continuously without regulatory constraints. In this study, we demonstrate for the first time that endocytosis of the transferrin receptor is a regulated process that requires activated Src kinase and, subsequently, phosphorylation of two important components of the endocytic machinery, namely, the large GTPase dynamin 2 (Dyn2) and its associated actin-binding protein, cortactin (Cort). To our knowledge these findings are among the first to implicate an Src-mediated endocytic cascade in what was previously presumed to be a nonregulated internalization process.Iron is an essential element for all mammalian organisms that plays essential roles in hemoglobin and myoglobin production (23). Altered iron transport can lead to disease states such as hemochromatosis (23), anemia (5, 23), and neuronal disorders (23). The transferrin receptor (TfR) is an important component of iron regulation in cells. There are two distinct TfRs in humans sharing 45% identity that are homodimeric and bind iron-associated transferrin (Tf) at markedly different affinities (26). While significant attention has been paid toward understanding the basic endocytic machinery that supports the efficient internalization and recycling of the TfR1 and its associated iron-bound ligand, it has been assumed that this transport process is constitutive in nature. This is in direct contrast to the highly regulated internalization pathway used by members of the receptor tyrosine kinase family (RTKs) and the family of G-coupled protein receptors (GPCRs) that utilize phosphorylation and/or ubiquination as signaling modules to regulate internalization.To test if TfR1 internalization might be regulated in a similar fashion, we focused on two essential components of the endocytic machinery: the large GTPase Dyn2 that mediates endocytic vesicle scission (35) and Cort that binds to Dyn2 via an SH3-PRD interaction and has been postulated to regulate actin dynamics to facilitate vesicle invagination and release (36, 40). Both Dyn2 and Cort have shown to be phosphorylated in vivo and in vitro by a variety of kinases (51, 58). Dyn1 interacts with (17) and is phosphorylated by Src in neuronal cells and in other excitable cells in response to activation of GPCRs and epidermal growth factor (EGF) (1, 2). While the Src phosphorylation motifs of dynamin are conserved in the epithelial expressed form of Dyn2, it is unclear if Dyn2 is phosphorylated in response to ligands that induce clathrin-based endocytosis.Cort possesses a series of C-terminal tyrosines that are heavily Src-phosphorylated and implicated in regulating actin remodeling during cell motility (20). In this study, we demonstrate that addition of Tf to cultured epithelial cells results in an internalization of the TfR1 mediated by a Src kinase-dependent phosphoactivation of the Dyn2-Cort-based endocytic machinery. In support of these findings, dominant negative forms of c-Src kinase, when expressed in a hepatocyte-derived cell line (Clone 9), attenuate Tf internalization. Remarkably, cells exposed to Tf showed a 3- to 4-fold increase in Dyn2 and Cort phosphorylation compared to that shown by untreated cells, an increase exceeding that observed in cells treated with EGF. These findings provide new insights into the regulation of what was thought to be a constitutive endocytic process. 相似文献
14.
The TonB system of Gram-negative bacteria uses the proton motive force (PMF) of the cytoplasmic membrane to energize active transport of nutrients across the outer membrane. The single transmembrane domain (TMD) anchor of TonB, the energy transducer, is essential. Within that TMD, His20 is the only TMD residue that is unable to withstand alanine replacement without a loss of activity. H20 is required for a PMF-dependent conformational change, suggesting that the importance of H20 lies in its ability to be reversibly protonated and deprotonated. Here all possible residues were substituted at position 20 (H20X substitutions). The His residue was also relocated throughout the TonB TMD. Surprisingly, Asn, a structurally similar but nonprotonatable residue, supported full activity at position 20; H20S was very weakly active. All the remaining substitutions, including H20K, H20R, H20E, and H20D, the obvious candidates to mimic a protonated state or support proton translocation, were inactive. A second-site suppressor, ExbB(A39E), indiscriminately reactivated the majority of H20 substitutions and relocations, including H20V, which cannot be made protonatable. These results suggested that the TonB TMD was not on a proton conductance pathway and thus only indirectly responds to PMF, probably via ExbD. 相似文献
15.
16.
Thor Veen M?rten B. Hjernquist Steven L. Van Wilgenburg Keith A. Hobson Eelke Folmer Laura Font Marcel Klaassen 《PloS one》2014,9(5)
Migratory routes and wintering grounds can have important fitness consequences, which can lead to divergent selection on populations or taxa differing in their migratory itinerary. Collared (Ficedula albicollis) and pied (F. hypoleuca) flycatchers breeding in Europe and wintering in different sub-Saharan regions have distinct migratory routes on the eastern and western sides of the Sahara desert, respectively. In an earlier paper, we showed that hybrids of the two species did not incur reduced winter survival, which would be expected if their migration strategy had been a mix of the parent species'' strategies potentially resulting in an intermediate route crossing the Sahara desert to different wintering grounds. Previously, we compared isotope ratios and found no significant difference in stable-nitrogen isotope ratios (δ
15N) in winter-grown feathers between the parental species and hybrids, but stable-carbon isotope ratios (δ
13C) in hybrids significantly clustered only with those of pied flycatchers. We followed up on these findings and additionally analyzed the same feathers for stable-hydrogen isotope ratios (δ
2H) and conducted spatially explicit multi-isotope assignment analyses. The assignment results overlapped with presumed wintering ranges of the two species, highlighting the efficacy of the method. In contrast to earlier findings, hybrids clustered with both parental species, though most strongly with pied flycatcher. 相似文献
17.
18.
19.
The DSM-IV major depression "bereavement exclusion" (BE), which recognizes that depressive symptoms are sometimes normal in recently bereaved individuals, is proposed for elimination in DSM-5. Evidence cited for the BE's invalidity comes from two 2007 reviews purporting to show that bereavement-related depression is similar to other depression across various validators, and a 2010 review of subsequent research. We examined whether the 2007 and 2010 reviews and subsequent relevant literature support the BE's invalidity. Findings were: a) studies included in the 2007 reviews sampled bereavement-related depression groups most of whom were not BE-excluded, making them irrelevant for evaluating BE validity; b) three subsequent studies cited by the 2010 review as supporting BE elimination did examine BE-excluded cases but were in fact inconclusive; and c) two more recent articles comparing recurrence of BE-excluded and other major depressive disorder cases both support the BE's validity. We conclude that the claimed evidence for the BE's invalidity does not exist. The evidence in fact supports the BE's validity and its retention in DSM-5 to prevent false positive diagnoses. We suggest some improvements to increase validity and mitigate risk of false negatives. 相似文献
20.
The New World species of Polytrichophora Cresson and Facitrichophora new genus, are revised. Fifteen new species are described (type locality in parenthesis): Facitrichophora atrella
sp. n. (Costa Rica. Guanacaste: Murciélago [10°56.9''N, 85°42.5''W; sandy mud flats around mangrove inlet]), Facitrichophora carvalhorum
sp. n. (Brazil. São Paulo: Praia Puruba [23°21''S, 44°55.6''W; beach]), Facitrichophora manza
sp. n. (Trinidad and Tobago. Trinidad. St. Andrew: Lower Manzanilla (12 km S; 10°24.5''N, 61°01.5''W), bridge over Nariva River), Facitrichophora panama
sp. n. (Panama. Darien: Garachine [8°04''N, 78°22''W]), Polytrichophora adarca
sp. n. (Barbados. Christ Church: Graeme Hall Nature Sanctuary [13°04.2''N, 59°34.7''W; swamp]), Polytrichophora arnaudorum
sp. n. (Mexico. Baja California. San Felipe [31°01.5''N, 114°50.4''W]), Polytrichophora barba
sp. n. (Cuba. Sancti Spiritus: Topes de Collantes [21°54.4''N, 80°01.4''W, 670 m]), Polytrichophora flavella
sp. n. (Peru. Madre de Dios: Rio Manu, Pakitza [11°56.6''S, 71°16.9''W; 250 m]), Polytrichophora marinoniorum
sp. n. (Brazil. Paraná: Antonina [25°28.4''S, 48°40.9''W; mangal]), Polytrichophora rostra
sp. n. (Peru. Madre de Dios: Rio Manu, Pakitza [11°56.6''S, 71°16.9''W; 250 m]), Polytrichophora sinuosa
sp. n. (Trinidad and Tobago. Trinidad. St. Andrew: Lower Manzanilla [12 km S; 10°24''N, 61°02''W]), Polytrichophora mimbres
sp. n. (United States. New Mexico. Grant: Mimbres River [New Mexico Highway 61 & Royal John Mine Road; 32°43.8''N, 107°52''W; 1665 m]), Polytrichophora salix
sp. n. (United States. Alaska. Matanuska-Susitna: Willow Creek [61°46.1''N, 150°04.2''W; 50 m]), Polytrichophora sturtevantorum
sp. n. (United States. Tennessee. Shelby: Meeman Shelby State Park [Mississippi River; 35°20.4''N, 90°2.1''W; 98 m]), Polytrichophora prolata
sp. n. (Belize. Stann Creek: Cockscomb Basin Wildlife Sanctuary [16°45''N, 88°30''W]). All known New World species of both genera are described with an emphasis on structures of the male terminalia, which are fully illustrated. Detailed locality data and distribution maps for all species are provided. For perspective and to facilitate recognition, the tribe Discocerinini is diagnosed and a key to included genera is provided. 相似文献