共查询到20条相似文献,搜索用时 46 毫秒
1.
Aline Alves de Lima Silva Paulo Ricardo Criado Ricardo Spina Nunes Wellington Luiz Ferreira da Silva Luciane Kanashiro-Galo Maria Irma Seixas Duarte Mirian N. Sotto Carla Pagliari 《PLoS neglected tropical diseases》2014,8(9)
Background
Chromoblastomycosis is a chronic fungal infection that affects skin and subcutaneous tissue. Lesions can be classified in tumorous, verrucous, cicatricial and plaque type. The cellular immune response in the severe form of the disease seems to correlate with a Th2 pattern of cytokines. The humoral immune response also seems to play a role. We intended to explore the populations of regulatory T cells and the Th17 pattern.Methodology
Twenty-three biopsies of verrucous form were obtained from patients with clinical, culture and histopathological diagnostic of chromoblastomycosis, without treatment. It was performed an immunohistochemistry method to detect Foxp3, CD25, TGF-β, IL-6, IL-17 and IL-23.Principal findings
IL-17 was the only cytokine with high expression in CBM when compared to normal skin. The expression of Treg cells, TGF- β, IL-6 and IL-23 were similar to normal skin.Conclusions/Significance
The constitution of a local immune response with high expression of IL-17 and low expression of other cytokines could be at least in part, an attempt to help the immune system against fungal infection. On the other hand, high levels of local immune response mediated by Th17 profile could overcome the role of Treg cells. The inefficient immunomodulation as a consequence of the unbalance by Treg/Th17 cells seems to corroborate with the less effective immune response against fungi. 相似文献2.
3.
4.
5.
6.
Nidhi Ahuja Dmitry Korkin Rachna Chaba Brent O. Cezairliyan Robert T. Sauer Kyeong Kyu Kim Carol A. Gross 《The Journal of biological chemistry》2009,284(8):5403-5413
The Escherichia coli envelope stress response is controlled by the
alternative sigma factor, σE, and is induced when unfolded
outer membrane proteins accumulate in the periplasm. The response is initiated
by sequential cleavage of the membrane-spanning antisigma factor, RseA. RseB
is an important negative regulator of envelope stress response that exerts its
negative effects onσE activity through its binding to RseA.
In this study, we analyze the interaction between RseA and RseB. We found that
tight binding of RseB to RseA required intact RseB. Using programs that
performed global and local sequence alignment of RseB and RseA, we found
regions of high similarity and performed alanine substitution mutagenesis to
test the hypothesis that these regions were functionally important. This
protocol is based on the hypothesis that functionally dependent regions of two
proteins co-evolve and therefore are likely to be sequentially conserved. This
procedure allowed us to identify both an N-terminal and C-terminal region in
RseB important for binding to RseA. We extensively analyzed the C-terminal
region, which aligns with a region of RseA coincident with the major RseB
binding determinant in RseA. Both allele-specific suppression analysis and
cysteine-mediated disulfide bond formation indicated that this C-terminal
region of similarity of RseA and RseB identifies a contact site between the
two proteins. We suggest a similar protocol can be successfully applied to
pairs of non-homologous but functionally linked proteins to find specific
regions of the protein sequences that are important for establishing
functional linkage.The Escherichia coli σE-mediated envelope stress
response is the major pathway to ensure homeostasis in the envelope
compartment of the cell
(1-3).
σE regulon members encode periplasmic chaperones and
proteases, the machinery for inserting β-barrel proteins into the outer
membrane and components controlling the synthesis and assembly of LPS
(4-6).
This pathway is highly conserved among γ-proteobacteria
(6).The σE response is initiated when periplasmic protein
folding and assembly is compromised
(7-9).
During steady state growth, σE is inhibited by its antisigma
factor, RseA, a membrane-spanning protein whose cytoplasmic domain binds to
σE with picomolar affinity
(10-13).
Accumulation of unassembled porin monomers serves as a signal to activate the
DegS protease to cleave RseA in its periplasmic domain
(14,
15). This initiates a
proteolytic cascade in which RseP cleaves periplasmically truncated RseA near
or within the cytoplasmic membrane to release the
RseAcytoplasmic-σE complex, and cytoplasmic
ATP-dependent proteases complete the degradation of RseA thereby releasing
active σE
(16-19).RseB, a second negative regulator of the envelope stress response
(11,
20,
21), binds to the periplasmic
domain of RseA with nanomolar affinity. RseB is an important regulator of the
response (2,
22,
23). It prevents RseP from
degrading intact RseA, thereby ensuring that proteolysis is initiated only
when the DegS protease is activated by a stress signal
(21). Additionally, RseB
prevents activated DegS from cleaving RseA, suggesting that interaction of
RseB with RseA must be altered before the signal transduction cascade is
activated (23).The goal of the present studies was to explore how RseB binds to RseA. The
interaction partner of RseB is the unstructured periplasmic domain of RseA
(RseA-peri). Within RseA-peri, amino acids ∼169-186 constitute a major
binding determinant to RseB
(23,
24). This peptide alone binds
RseB with 6 μm affinity, and deleting this region abrogates
binding to RseB (23).
Additional regions of RseA-peri also contribute to RseB binding, as intact
RseA-peri binds with 20 nm affinity to RseB
(23). Much less is known about
the regions of RseB required for interaction with RseA. RseB is homodimeric
two-domain protein, whose large N-terminal domain shares structural homology
with LolA, a protein that transports lipoproteins to outer membrane
(24,
25). The smaller C-terminal
domain is connected to the N-terminal domain by a linker, and the two domains
share a large interface, which may facilitate interdomain signaling.
Glutaraldehyde cross-linking studies indicate that the C-terminal domain
interacts with RseA, but the regions of interaction were not identified
(25).In the present report, we study the interaction of RseB and RseA. We
establish that both domains of RseB interact with RseA-peri. Using a global
sequence alignment, we discovered several regions in RseA and RseB that had
high sequence similarity, despite the low overall sequence similarity between
these two proteins, a finding that was independently confirmed by a local
sequence similarity algorithm. This suggested that these regions were
functionally dependent, and we performed a set of mutagenesis experiments
designed to test this idea. Our studies of the binding properties of these
mutants revealed that regions in both the N terminus and C terminus of RseB
modulate interaction with RseA. Moreover, genetic suppression analysis and
cysteine-mediated disulfide bond formation suggest that the region of RseA/B
with highest similarity (RseA residues 165-191 (major binding determinant in
RseA) and RseB residues 233-258) are interacting partners. 相似文献
7.
8.
Hideki Watanabe Hiroyuki Matsumaru Ayako Ooishi YanWen Feng Takayuki Odahara Kyoko Suto Shinya Honda 《The Journal of biological chemistry》2009,284(18):12373-12383
Protein-protein interaction in response to environmental conditions enables
sophisticated biological and biotechnological processes. Aiming toward the
rational design of a pH-sensitive protein-protein interaction, we engineered
pH-sensitive mutants of streptococcal protein G B1, a binder to the IgG
constant region. We systematically introduced histidine residues into the
binding interface to cause electrostatic repulsion on the basis of a rigid
body model. Exquisite pH sensitivity of this interaction was confirmed by
surface plasmon resonance and affinity chromatography employing a clinically
used human IgG. The pH-sensitive mechanism of the interaction was analyzed and
evaluated from kinetic, thermodynamic, and structural viewpoints.
Histidine-mediated electrostatic repulsion resulted in significant loss of
exothermic heat of the binding that decreased the affinity only at acidic
conditions, thereby improving the pH sensitivity. The reduced binding energy
was partly recovered by “enthalpy-entropy compensation.” Crystal
structures of the designed mutants confirmed the validity of the rigid body
model on which the effective electrostatic repulsion was based. Moreover, our
data suggested that the entropy gain involved exclusion of water molecules
solvated in a space formed by the introduced histidine and adjacent tryptophan
residue. Our findings concerning the mechanism of histidine-introduced
interactions will provide a guideline for the rational design of pH-sensitive
protein-protein recognition.Molecular interactions govern a number of biological processes, including
metabolism, signal transduction, and immunoreaction. A better understanding of
the molecular basis for these interactions is crucial for a complete
elucidation of biological phenomena and redesign of interactions for drug
discovery and industrial biotechnology applications. Interactions between
biomolecules are generally characterized by their affinity, specificity, and
environmental responsiveness, such as sensitivity to pH. Such pH-dependent
ligand binding enables biological processes to function in an “on and
off” manner in response to environmental conditions, resulting in
sophisticated systems of regulation (e.g. pheromone production
(1,
2), immune systems
(3-5),
and mechanisms of virus survival
(6)).From an industrial perspective, pH sensitivity is advantageous to various
fields, such as drug delivery systems for medications
(7), biosensing techniques
(8,
9), and affinity chromatography
(10,
11). Although structure-based
protein design is a promising technique for improving molecular function
(12-15),
it is yet difficult to specifically modulate pH sensitivity of a
protein-protein interaction without an associated loss of inherent function
and/or structural stability. Some naturally occurring proteins undergo
substantial conformational change by pH shift, thereby achieving pH-dependent
binding for small molecules (2,
4,
16,
17). However, artificial
design of an equivalent mechanism involving conformational change is highly
problematic. Indeed, proteins have multiple degrees of freedom and consist of
a large number of atoms. Therefore, given that the resulting protein must
maintain both its innate binding ability and structural stability, the system
appears too complicated for rational design. By contrast to the method based
on conformational change, a rigid body-based model (i.e. introduction
of electrostatic repulsion or attraction into a binding interface between
rigid protein domains) could be a more promising approach for pH switching.
Naturally occurring proteins with pH sensitivity generally conserve histidine
residues
(18-21),
which function as a pH switch at slightly acidic conditions (pH ∼6.5) near
the pKa of the histidine side chain. In the presence of a
histidine residue at a binding interface, dissociation under acidic conditions
would be driven by electrostatic repulsion between rigid domains without
conformational change (Fig. 1).
This mechanism is rather simple and applicable to protein engineering
(22,
23). However, to our
knowledge, it still remains unclear how systematic design should be carried
out and, in particular, how histidine-mediated electrostatic repulsion
influences protein-protein interactions. Indeed, very little experimental data
are available for the molecular basis of histidine-introduced protein
binders.Open in a separate windowFIGURE 1.A schematic model for introduction of histidine-mediated electrostatic
repulsion into the binding interface between protein G (GB) and
Fc. Protein G residues positioned closely to basic side chains (depicted
as B) on Fc were systematically identified by distance calculations
and mutated into histidine to cause electrostatic repulsion under acidic
conditions. The inset shows an example of candidate positions for the
mutation.To better understand the design methodology for a pH-sensitive
protein-protein interaction, we generated a number of pH-sensitive
streptococcal protein G B1
(24) mutants by rationally
introducing histidine residues onto the binding surface. Protein G, a
bacterial Fc (fragment of crystallizable region) receptor to the constant
region of IgG, has been used as an affinity chromatography binder for antibody
immobilization and purification. Protein G has an acidic pH optimum for
binding relative to another bacterial Fc receptor, Staphylococcus
aureus protein A. The harsh elution conditions are likely to induce
acidic conformational changes in antibodies
(25,
26) during the purification
procedure, causing aggregation that is problematic for pharmaceutical
applications. The usefulness of the histidine-mediated electrostatic repulsion
for antibody purification was examined by constructing affinity chromatography
columns. Using the designed mutants, we analyzed the molecular basis of the
histidine-mediated interaction from a kinetic, thermodynamic, and structural
perspective. The observed data revealed functional and structural consequences
for the introduction of histidine residues. Analysis of our results provides a
guideline for the design of pH-dependent protein-protein interactions. 相似文献
9.
Ignacio Caballero Sumiah Al Ghareeb Shaghayegh Basatvat Javier A. Sánchez-López Mehrnaz Montazeri Nasim Maslehat Sarah Elliott Neil R. Chapman Alireza Fazeli 《PloS one》2013,8(1)
Background
Implantation is a complex process that requires a delicate cooperation between the immune and reproductive system. Any interference in the fine balance could result in embryo loss and infertility. We have recently shown that Toll-like receptor 5 activation results in a decrease of trophoblast cells binding to endometrial cells in an in vitro model of human implantation. However, little is known about the downstream signalling leading to the observed failure in implantation and the factors that modulate this immune response.Methods and Principal Findings
An in vitro model of embryo implantation was used to evaluate the effect of trophoblasts and flagellin on the activation of NF-κB in endometrial cells and whether TLR5-related in vitro implantation failure is signalled through NF-κB. We generated two different NF-κB reporting cell lines by transfecting either an immortalized endometrial epithelial cell line (hTERT-EECs) or a human endometrial carcinoma cell line (Ishikawa 3-H-12) with a plasmid containing the secreted alkaline phosphatase (SEAP) under the control of five NF-κB sites. The presence of trophoblast cells as well as flagellin increased NF-κB activity when compared to controls. The NF-κB activation induced by flagellin was further increased by the addition of trophoblast cells. Moreover, blocking NF-κB signalling with a specific inhibitor (BAY11-7082) was able to restore the binding ability of our trophoblast cell line to the endometrial monolayer.Conclusions
These are the first results showing a local effect of the trophoblasts on the innate immune response of the endometrial epithelium. Moreover, we show that implantation failure caused by intrauterine infections could be associated with abnormal levels of NF-κB activation. Further studies are needed to evaluate the target genes through which NF-κB activation after TLR5 stimulation lead to failure in implantation and the effect of the embryo on those genes. Understanding these pathways could help in the diagnosis and treatment of implantation failure cases. 相似文献10.
Nicoletta Loberto Maela Tebon Ilaria Lampronti Nicola Marchetti Massimo Aureli Rosaria Bassi Maria Grazia Giri Valentino Bezzerri Valentina Lovato Cinzia Cantù Silvia Munari Seng H. Cheng Alberto Cavazzini Roberto Gambari Sandro Sonnino Giulio Cabrini Maria Cristina Dechecchi 《PloS one》2014,9(8)
Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz-529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. 相似文献
11.
Kenshi Yamasaki Jun Muto Kristen R. Taylor Anna L. Cogen David Audish John Bertin Ethan P. Grant Anthony J. Coyle Amirhossein Misaghi Hal M. Hoffman Richard L. Gallo 《The Journal of biological chemistry》2009,284(19):12762-12771
Inflammation under sterile conditions is a key event in autoimmunity and
following trauma. Hyaluronan, a glycosaminoglycan released from the
extracellular matrix after injury, acts as an endogenous signal of trauma and
can trigger chemokine release in injured tissue. Here, we investigated whether
NLRP3/cryopyrin, a component of the inflammasome, participates in the
inflammatory response to injury or the cytokine response to hyaluronan. Mice
with a targeted deletion in cryopyrin showed a normal increase in Cxcl2 in
response to sterile injuries but had decreased inflammation and release of
interleukin-1β (IL-1β). Similarly, the addition of hyaluronan to
macrophages derived from cryopyrin-deficient mice increased release of Cxcl2
but did not increase IL-1β release. To define the mechanism of
hyaluronan-mediated activation of cryopyrin, elements of the hyaluronan
recognition process were studied in detail. IL-1β release was inhibited
in peritoneal macrophages derived from CD44-deficient mice, in an MH-S
macrophage cell line treated with antibodies to CD44, or by inhibitors of
lysosome function. The requirement for CD44 binding and hyaluronan
internalization could be bypassed by intracellular administration of
hyaluronan oligosaccharides (10–18-mer) in lipopolysaccharide-primed
macrophages. Therefore, the action of CD44 and subsequent hyaluronan
catabolism trigger the intracellular cryopyrin → IL-1β pathway.
These findings support the hypothesis that hyaluronan works through IL-1β
and the cryopyrin system to signal sterile inflammation.Inflammation, as defined by changes in vascular permeability and leukocyte
recruitment, is an essential step for the control of microbial invasion.
Specific microbial products trigger this process through a diverse array of
innate immune pattern recognition receptors. However, an inflammatory response
independent of infection is also an important process for maintenance of
biological homeostasis. For example, normal wound healing requires a
controlled inflammatory response to enable the recruitment of monocytes and
the release of growth factors required for repair. This response can occur in
the absence of microbial stimuli. Furthermore, inflammation and the release of
proinflammatory mediators is also associated with many diseases such as
rheumatoid arthritis and Crohn disease
(1). These diseases are not
well understood in terms of their triggers but rather are described by the
subsequent release of proinflammatory mediators. Identification of the
triggers of sterile inflammation represents an important goal with immediate
diagnostic and therapeutic significance.Recent work has begun to elucidate pathways of inflammation that occur in
the absence of microbial stimuli. Stress signals such as heat-shock proteins,
intracellular components of necrotic cells not normally seen by immune cells,
and components of the extracellular matrix have all been implicated as
endogenous triggers of injury
(2–4).
Among this group is the glycosaminoglycan hyaluronan
(HA),6 an important
structural component of the extracellular matrix that is also a common
component of bacterial surfaces. HA is synthesized at the cell surface and
typically exists as a high molecular mass polymer greater than 106
Da and composed of repeating disaccharide units of
N-acetylglucosamine and glucuronic acid
(5,
6). Unlike other
glycosaminoglycans such as heparan sulfate or chondroitin sulfates that encode
specific activity by use of a diverse disaccharide sequence, HA is not
sulfated or epimerized, and only changes in HA size, concentration, and
location affect function.We have previously developed murine models of sterile injury to identify
the innate elements that recognize and mediate sterile inflammation
(7). Our results demonstrated
that (a) the initiation of a sterile intrinsic inflammatory process
is dependent on TLR4 activation, (b) sterile injury induces HA
accumulation at the injured site, and (c) sterile intrinsic
inflammation resembles signaling events that are activated by HA. Furthermore,
we have defined a novel alternative recognition complex for HA that involves
TLR4, MD-2, and CD44 (7). Taken
together with other work associating HA and innate pattern recognition
(4,
8–10),
these observations have provided new insight into mechanisms responsible for
sterile inflammation.Recently, the NLR (nucleotide-binding domain and leucine rich
repeat-containing) family has been extensively analyzed as a group of
intracellular pattern recognition receptors
(11). NLRs have a leucine-rich
repeat that recognizes pathogen-associated molecular patterns including
bacterial cell wall components and viral nucleic acids. NOD2 and NLR family,
pyrin containing 3 (NLRP3)/cryopyrin are two of the best
characterized NLRs. NOD2 recognizes the bacterial peptidoglycan-derived
molecule muramyl dipeptide and activates the NF-κB pathway to induce
inflammatory responses (12).
Mutations of the NOD2 gene were identified in individuals with
chronic inflammatory disorders such as Crohn disease
(13,
14) and Blau syndrome
(15). Mouse knockin mutants of
NOD2, which have the same mutation in NOD2 as human patients
with Crohn disease, showed elevated proinflammatory cytokines following
muramyl dipeptide challenge or dextran sodium sulfate-induced bowel
inflammation (16).
NLRP3, also known as cyropyrin, CIAS1, NALP3, PYPAF1, forms
an “inflammasome” with ASC (apoptosis-associated speck-like
protein containing a CARD) and caspase-1 to convert pro-IL-1β to active
IL-1β (17). Mutations in
NLRP3 were identified in individuals with familial cold
autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and neonatal onset
multisystem inflammatory disease
(18–20).
These individuals have recurrent or chronic inflammatory symptoms, including
fever, arthritis, and a urticaria-like eruption characterized by neutrophilic
infiltration. In FCAS, symptoms can be elicited by cold provocation by a
mechanism that appears to be mediated through the skin
(15,
21).Because disorders associated with mutations in NLRP3 are examples
of inflammation under sterile conditions and HA has been shown to be a trigger
of sterile inflammation, we sought to further understand the mechanism of the
response to HA by examining the role of cryopyrin during injury and after
exposure to HA. Our results show that cryopyrin and IL-1β are integral to
sterile inflammation and the response to HA. These observations provide new
insight into the function of HA as a “danger signal” of
injury. 相似文献
12.
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
13.
14.
Pablo Tortosa Sylvain Charlat Pierrick Labbé Jean-Sébastien Dehecq Hélène Barré Mylène Weill 《PloS one》2010,5(3)
Background
Wolbachia bacteria have invaded many arthropod species by inducing Cytoplasmic Incompatibility (CI). These symbionts represent fascinating objects of study for evolutionary biologists, but also powerful potential biocontrol agents. Here, we assess the density dynamics of Wolbachia infections in males and females of the mosquito Aedes albopitcus, an important vector of human pathogens, and interpret the results within an evolutionary framework.Methodology/Principal Findings
Wolbachia densities were measured in natural populations and in age controlled mosquitoes using quantitative PCR. We show that the density dynamics of the wAlbA Wolbachia strain infecting Aedes albopictus drastically differ between males and females, with a very rapid decay of infection in males only.Conclusions/Significance
Theory predicts that Wolbachia and its hosts should cooperate to improve the transmission of infection to offspring, because only infected eggs are protected from the effects of CI. However, incompatible matings effectively lower the fertility of infected males, so that selection acting on the host genome should tend to reduce the expression of CI in males, for example, by reducing infection density in males before sexual maturation. The rapid decay of one Wolbachia infection in Aedes albopictus males, but not in females, is consistent with this prediction. We suggest that the commonly observed reduction in CI intensity with male age reflects a similar evolutionary process. Our results also highlight the importance of monitoring infection density dynamics in both males and females to assess the efficiency of Wolbachia-based control strategies. 相似文献15.
16.
17.
Adel Ben Ali 《Andrologie》2004,14(3):312-316
Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) represents an important health problem resulting in considerable morbidity and of health care expenditure. CP/CPPS is a multifactorial problem affecting men of all ages and all demographic characteristics. Over recent years, progress has been made in the epidemiology and diagnosis of CP/CPPS. A new universally accepted classification system has become the gold standard in the contemporary literature. Men with CP/CPPS have significantly higher leukocyte counts in all segmented urine samples and expressed prostatic secretion (EPS) but not in semen. In segmented cultures, the urethral culture (first 10 ml of urine), EPS and first 10 ml of urine avoided immediately after prostatic massage are the “optimal” samples to detect the microbial agent. According to the four-glass test with polymerase chain reaction testing (PCR), Chlamydia and/or Ureaplasma infection can be suspected in several cases, but their role in the pathogenesis of prostatitis remains speculative. However, testing for these infections is highly recommended in non-documented infections. Quantification, speed and specificity make real-time PCR a promising approach for the quantitative detection and identification of prostatic bacteria from CP/CPPS patients. Several antibiotics have a good correlation between pharmacokinetic/pharmacodynamic parameters and efficacy for antibiotics in the treatment of chronic prostatitis. Fluoroquinolones, cotrimoxazole and ceftriaxone have a bactericidal concentration to the main pathogens in the prostatic fluid of patients with subacute and chronic prostatitis and in prostatic tissue. 相似文献
18.
Future increases in oceanic carbon dioxide concentrations (CO2(aq)) may provide a benefit to submerged plants by alleviating photosynthetic carbon limitation. However, other environmental factors (for example, nutrient availability) may alter how seagrasses respond to CO2(aq) by regulating the supply of additional resources required to support growth. Thus, questions remain in regard to how other factors influence CO2(aq) effects on submerged vegetation. This study factorially manipulated CO2(aq) and nutrient availability, in situ, within a subtropical seagrass bed for 350 days, and examined treatment effects on leaf productivity, shoot density, above- and belowground biomass, nutrient content, carbohydrate storage, and sediment organic carbon (Corg). Clear, open-top chambers were used to replicate CO2(aq) forecasts for the year 2100, whereas nutrient availability was manipulated via sediment amendments of nitrogen (N) and phosphorus (P) fertilizer. We provide modest evidence of a CO2 effect, which increased seagrass aboveground biomass. CO2(aq) enrichment had no effect on nutrient content, carbohydrate storage, or sediment Corg content. Nutrient addition increased leaf productivity and leaf N content, however did not alter above- or belowground biomass, shoot density, carbohydrate storage, or Corg content. Treatment interactions were not significant, and thus NP availability did not influence seagrass responses to elevated CO2(aq). This study demonstrates that long-term carbon enrichment may alter the structure of shallow seagrass meadows, even in relatively nutrient-poor, oligotrophic systems. 相似文献
19.
20.
Yuki Ito Jose Luis Vela Fumiko Matsumura Hitomi Hoshino Aaron Tyznik Heeseob Lee Enrico Girardi Dirk M. Zajonc Robert Liddington Motohiro Kobayashi Xingfeng Bao Jeanna Bugaytsova Thomas Borén Rongsheng Jin Yinong Zong Peter H. Seeberger Jun Nakayama Mitchell Kronenberg Minoru Fukuda 《PloS one》2013,8(12)
Approximately 10–15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18−/−) or wild-type mice, bacterial recovery significantly increased in Jα18−/− compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18−/− compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis. 相似文献