text:
Persistence of Serotonergic Enhancement of Airway Response
in a Model of Childhood Asthma
Brian D. Moore
, Dallas M. Hyde
, Lisa A. Miller
, Emily M. Wong
, and Edward S. Schelegle
University of the Pacific, Stockton, California; and
California National Primate Research Center, Respiratory Diseases Unit, University of
California Davis, Davis, California
The persistence of airway hyperresponsiveness (AHR) and
serotonergic enhancement of airway smooth muscle (ASM)
contraction induced by ozone (O
) plus allergen has not been
evaluated. If this mechanism persists after a prolonged recovery, it
would indicate that early-life exposure to O
plus allergen induces
functional changes predisposing allergic individuals to asthma-
related symptoms throughout life, even in the absence of
environmental insult. A persistent serotonergic mechanism in
asthma exacerbations may offer a novel therapeutic target, widening
treatment options for patients with asthma. The objective of this
study was to determine if previously documented AHR and
serotonin-enhanced ASM contraction in allergic monkeys exposedto
plus house dust mite allergen (HDMA) persist after prolonged
recovery. Infant rhesus monkeys sensitized to HDMA were exposed
to filtered air (FA) (n = 6) or HDMA plus O
(n = 6) for 5 months.
Monkeys were then housed in a FA environment for 30 months. At
3 years, airway responsiveness was assessed. Airway rings were then
harvested, and ASM contraction was evaluated using electrical fi eld
stimulation with and without exogenous serotonin and serotonin-
subtype receptor antagonists. Animals exposed to O
plus HDMA
exhibited persistent AHR. Serotonin exacerbated the ASM
contraction in the exposure group but not in the FA group.
Serotonin subtype receptors 2, 3, and 4 appear to drive the response.
Our study shows that AHR and serotonin-dependent exacerbation of
cholinergic-mediated ASM contraction induced by early-life
exposure to O
plus allergen persist for at least 2.5 years and may
contribute to a persistent asthma phenotype.
Keywords: serotonin; ozone; antigens; hyperresponsiveness;
Macaca mulatta
Clinical Relevance
Airway hyperresponsiveness and serotonin-dependent
exacerbation of cholinergic-mediated airway smooth muscle
contraction induced by early-life exposure to ozone plus allergen
persist for at least 2.5 years and may contribute to a persistent
asthma phenotype. These findings substantiate the need to
minimize exposure of young individuals to known environmental
contributors to asthma during critical periods of lung maturation
because damage inflicted during these times can contribute to
prolonged asthma symptoms. The identification of a persistent
5-HT–mediated enhanced airway smooth muscle contraction
mayidentifynoveltherapeutic targets for pharmacological
intervention in the treatment of childhood asthma.
Asthma is one of the most common chronic
childhood conditions in the United States.
In 2011, z 7 million children suffered from
asthma (1). The most frequent reason for
school absences is asthma, accounting for
one third of school days missed, and the
severity of symptoms is negatively
correlated with achievement (2).
The link between ozon e (O
dust mite allergen (HDMA) exposure and
childhood asthma has been supported by
a wealth of research (3–9). In the latest State
of the Air report, almost half of United States
citizens—over 148 million people—live in
areas with unhealthy O
levels (6).
Although the mechanisms responsible
for asthma symptoms are debatable,
research shows that O
and HDMA
( Received in original form September 6, 2013; accepted in final form January 23, 2014 )
This research was supported by a National Institute of Health Sciences Program Project grant P01ES000628–33.
Author Contributions: Conception and design: D.H., L.M., E.S., B.M. Analysis and interpretation: E.S., B.M., E.W. Drafting the manuscript for important
intellectual content: B.M., E.S.
Correspondence and requests for reprints should be addressed to Edward Schelegle, Ph.D., Anatomy, Physiology & Cell Biology, University of California–Davis,
Davis, CA 95616. E-mail: firstname.lastname@example.com
This article has an online supplement, which is acces sible from this issue's table of contents at www.atsjournals.org
Am J Respir Cell Mol Biol Vol 51, Iss 1, pp 77–85, Jul 2014
Copyright © 2014 by the American Thoracic Society
Originally Published in Press as DOI: 10.1165/r cmb.2013-0387OC on January 31, 2014
Internet address: www.atsjournals.org
Moore, Hyde, Miller, et al.: Persistent Response to Allergen and O
Page 1
exposure leads to functional, structural,
neural, vascular, and immunological
alterations in airways (10–16). This airway
remodeling indicates that environmental
insults early in life can have life-long
deleterious effects on lung function and
may lead to chronic asthma symptoms.
Airway hyperresponsiveness (AHR),
a functional hallmark of asthma, is assessed
with a bronchoprovocation test (17). The
presence of AHR after O
and HDMA
exposure indicates that airway function has
been compromised. In humans, nonhuman
primates, and other models of asthma, O
and HDMA exposure has been shown to
increase AHR (18–21).
Recent literature suggests that
serotonin (5-HT) plays a role in the asthma
response (22–24). Animal studies show that
5-HT increases airway resistance and O
HDMA exposure of infant monkeys results
in 5-HT–positive cells within airway
epithelia (25–27). Patients with asthma
have higher 5-HT plasma levels, which are
inversely correlated with lung function, and
drug treatments that lower plasma 5-HT
decrease symptom severity and improve
lung function (6, 28, 29). Our lab has
shown that exposure of O
induces AHR and exacerbates 5-
HT–mediated airway smooth muscle
(ASM) contraction in a model of childhood
asthma (18) and that the combined
exposure of O
1 HDMA results in
alterations in 9 of 10 immune, structural,
and functional end points, with six of the
end points demonstrating greater than
additive effects of O
or HDMA exposure
alone (10). Studies have epidemiologically
confirmed asthma persistence from
childhood through adulthood, linking
persistent symptoms to atopy, smoking, air
pollution (including O
), early age at onset of
asthma, and airway remodeling (30–34).
To date, no study has examined the
persistence of AHR and 5-HT enhancement
of ASM contraction in a controlled setting
using a model of childhood asthma. The
aims of this project are (1) to determine
if AHR and 5-HT–enhanced ASM
contraction induced by O
exposure persist after a prolonged recovery
period in a filtered air (FA) environment
and (2) to identify which 5-HT subtype
receptors are responsible for driving the 5-
HT response. Confirming the persistence of
AHR caused by early-life exposure to O
HDMA will help guide environmental
policy and substantiate the need to mitigate
exposure, especially in young populations.
Associating a 5-HT–mediated mechanism
with persistent AHR offers a novel
therapeutic target for asthma treatment.
Rhesus monkeys were used because
they have similar lung cellular morphology,
airway architecture, and immunology
and undergo a similar extensive period
of postnatal development compared
with humans (35–39). In addition to
possessing all of the components of the
intrapulmonary conducting airways that
are altered in humans with asthma, rhesus
monkeys display a similar progression of
asthma pathophysiology and symptoms
(11, 40). The sensitization protocol used
induces the functional, immunologic,
histological, and clinical characteristics that
are used to diagnose allergic asthma (40).
Materials and Methods
Care of animals complied with the Institute
of Laboratory Animal Resources and the
American Association for Accreditation of
Laboratory Animal Care (AAALAC).
Procedures were approved by the University
of California - Davis Institutional Animal
Care and Use Committee (41). The
University of California - Davis and the
California National Primate Research
Center are accredited by AAALAC.
General Protocol
Twelve 30-day-old, captive-born rhesus
monkeys were randomly assigned to one of
two groups: FA or O
plus HDMA (O
HDMA). All animals were sensitized to
HDMA and exposed to 11 episodes of FA
or O
1 HDMA as previously described
(10, 18) (Figure 1). Exposures had a HDMA
mass concentration averaging 7.05 6
0.73 mg/m
and a mean O
concentration of
0.500 6 0.005 ppm. Monkeys were killed
with sodium pentobarbital (15 ml/kg). A
distal tracheal portion was harvested and
placed in modified Kreb's solution.
Airway Responsiveness Testing
At 3 years of age, airway resistance (R
was measured during a histamine challenge
and expressed as the concentration of
histamine causing a 200% increase in Raw
) (40).
Electrical Field Stimulation
Airway rings were suspended between
platinum wire electrodes in tissue baths
(Myobath; WPI Inc., Sarasota, FL) as
previously described (18). Tension was
measured via Fort 10 g transducers (WPI
Inc.) and recorded with Powerlab Chart 5.1
software (ADInstruments, Colorado
Springs, CO). Monophasic square-wave
impulses (50 V, 4 Hz, 0.5 ms) were
delivered for 30 seconds every 4 minutes
until three consecutive stable responses
were observed. Pulses were induced via S88
Stimulators (Grass Technologies, West
Warwick, RI).
5-HT Concentration-Response
Six rings from each animal were used to
perform 5-HT concentration-response
curves during electric field stimulation
(EFS)-induced contractions.
Antagonist Concentration-
Response Curves
5-HT concentration-response curves were
performed in the presence of antagonists
(Table 1).
The Effect of 5-HT
R Activation
Previous research identified an inhibitory
pathway mediated through 5-HT
receptors (18). These analyses were
Baseline Responses
Acetylcholine (ACh) concentration-
response curves were performed (one
control and one preincubated with 10 mM
5-HT). Voltage-response curves and
frequency-response curves were performed
on tracheal rings.
Concluding Experiments
Airway rings were exposed to 10 mM ACh
to compare tension with the initial ACh
concentration-response curves. The effect of
atropine (1 mM) was evaluated to ensure
muscarinic-mediated contractions. To
verify that the responses were neurogenic,
tissue was incubated in 3 mM tetrodotoxin
before EFS. All drugs were purchased from
Sigma-Aldrich Co. (St. Louis, MO).
Statistical Analysis
Results are expressed as mean 6 SEM.
Airway responsiveness data; between-group
; and 5-HT direct effect
values were analyzed using Student's t tests.
Within-group 5-HT direct effects and the
direct effect of 8-OH-DPAT were analyzed
with paired-samples t tests.
78 American Journal of Respiratory Cell and Molecular Biology Volume 51 Number 1
July 2014
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Concentration-responses were compared
using repeated-measures ANOVAs. Tukey
post hoc testing was used to identify the source
of significance. The a level was set at 0.05.
Significance was based on the adjusted
P value. A one-way t test was used to assess
the direct effect of 5-HT on ASM
contraction based on previous findings that
5-HT constricts ASM.
Airway Responsiveness
1 HDMA exposure induced
a significant increase in airway
responsiveness when compared with FA
controls, even with a prolonged 2.5-year
recovery period in FA (EC200R
14.43 6 3.89 mg/ml; O
0.60 mg/ml; P = 0.04) (Figure 2).
5-HT Concentration Response
1 HDMA exposure resulted in
enhanced airway contractility in the
presence of 5-HT, indicated by significantly
increased EFS-induced ASM tension
production when compared with FA
animals at 100 mM 5-HT (FA = 308.5 6
0.008). All 5-HT concentrations in the
1 HDMA group produced significantly
greater tension than the EFS-induced
tension produced during their control
response (EFS-induced contraction in the
absence of 5-HT; P , 0.05), which was not
the case in the FA group. In the FA group,
none of the 5-HT concentrations elicited
a contraction significantly greater than its
control response (P . 0.05) (Figure 3).
There was also an overall group effect, with
the O
1 HDMA group producing a
significantly higher mean tension (as % of
control EFS response) than the FA group
Antagonist Concentration Response
In the O
1 HDMA group, incubation with
increasing concentrations of 5-HT
(ketanserin), 5-HT
(ondansetron), or
(GR 113808) subtype receptor
antagonists attenuated the tension induced
by EFS at all 5-HT concentrations,
indicating that these three receptors are
involved in the ASM response to 5-HT
(Figure 4).
The Effect of 5-HT
Receptor Activation
Addition of the 5-HT
receptor agonist
8-OH-DPAT significantly attenuated
EFS-induced ASM contraction in
a concentration-dependent manner
(Figure 5A). This effect was seen in both
the FA and O
1 HDMA groups,
indicating that exposure had no effect. The
direct effect of 5-HT
receptor activation
on ASM tension induced by 100 mM
exogenous ACh was also evaluated.
Concentrations of 10 and 100 mM 8-OH-
DPAT significantly attenuated ACh-
induced tension in both the FA and O
HDMA groups. There was no between-
group difference in the response, indicating
that exposure had no effect on 5-HT
receptor activation (Figure 5B).
Direct Effect of 5-HT on ASM Tension
The addition of 10 mM 5-HT produced
a small, but consistent, increase in ASM
tension in the FA and O
groups. In the FA group, tension increased
from 0.992 6 0.007 g to 1.204 6 0.229 g
(P = 0.037). This increase was just over 6%
of the maximal response to ACh. In the
1 HDMA group, 10 mM 5-HT caused
a tension increase amounting to 12.75% of
the maximal ACh response (Figure 6A).
When comparing the change in absolute
tension between the FA and O
groups, O
1 HDMA exposure produced
a significantly greater 5-HT–induced
tension increase compared with the FA
group (0.549 6 0.146 g versus 0.211 6
0.094 g) (Figure 6B). This indicates that 5-
HT directly induces ASM contraction and
that O
1 HDMA exposure exacerbates
this response.
Baseline ASM Response
Before 5-HT addition, frequency-response
and voltage-response curves were
performed. There was no difference in the
voltage needed to induce 50% of maximum
EFS tension (EV
) between groups (EV
4.4 V; P . 0.05). There was no significant
difference in the frequency necessary to
induce 50% of maximum EFS tension
) between groups (EV
2.4 Hz; O
1 HDMA = 7.1 6 0.7 Hz;
Figure 1. Timeline of exposure protocol. FA, filtered air; HDMA, house dust mite allergen.
Table 1. Summary of Antagonists
Drug Receptor Concentration Range (mM) References
Ketanserin 5-HT2A 1, 10, 100 61, 62
Ondansetron 5-HT3 1, 10, 100 63, 64
Moore, Hyde, Miller, et al.: Persistent Response to Allergen and O
Page 3
P . 0.05). This indicates that without
exogenous 5-HT added to the tissue baths,
the airway rings from the O
animals and the FA animals responded
similarly to EFS.
Concluding Experiments
Tissue response to 10 mM ACh at the
conclusion of the experiment produced over
93% (1.442 g versus 1.541 g) of the tension
seen at the beginning of the protocol,
indicating adequate tissue viability
throughout the testing. Atropine and
tetrodotoxin completely attenuated EFS
response, confirming that EFS-induced
contractions were neurogenic of origin and
induced by activation of cholinergic
receptors on the ASM.
Although persistent asthma symptoms have
been linked to environmental O
allergen exposure, no study to date has
examined the persistent effect of O
HDMA exposure in a model of childhood
asthma. Our previous research showed that
cyclical exposure to O
1 HDMA from 1 to
6 months of life in allergic rhesus monkeys
results in a hyperresponsive airway and in
a 5-HT–mediated enhancement of ASM
contraction (18). With the wealth of
epidemiologic data supporting the negative
effects of early-life exposure to O
allergens, it makes sense to question
whether or not the functional decrements
seen with O
1 HDMA exposure in our
model of childhood asthma would persist if
the animals were allowed a prolonged
recovery in a FA environment (6, 42–44).
This study confirms that O
exposure induces persistent AHR and
exacerbated 5-HT–mediated ASM
contraction, even after a prolonged recovery
period, in a model of childhood asthma.
Airway Responsiveness
AHR is a functional indicator of asthma.
When comparing EC200R
between the
1 HDMA exposure and FA groups, the
exposure group required a significantly
lower dose (Figure 2). The AHR seen in the
1 HDMA group closely resembles that
of our previous work using the same
exposure protocol that did not allow for
a prolonged recovery (18). This signifies
that the functional decrement induced by
1 HDMA exposure seen after 5 months
of exposure persists even after 2.5 years
of recovery in a FA environment. The
persistence of AHR after a prolonged
recovery period underscores the deleterious
effects of early-life exposure to O
HDMA and that such exposure not only
leads to acute pulmonary dysfunction in
allergic individuals but induces chronic
changes in airway function that remain
after a long recovery period even when the
environmental insult is no longer present.
Unlike previous studies (25, 45, 46) in
which sensitivity to HDMA was maintained
in the O
1 HDMA group during recovery,
persistent functional alterations were found
in this study even though there was no
attempt to ensure maintained HDMA
sensitivity and the recovery period was
extended from 6 to 30 months. The impact
of this observation is even more significant
when one considers that the exposure
occurred during a period of rapid postnatal
lung development and that the detrimental
effects were still present at an age
equivalent to preadolescence in humans.
This reinforces the need to minimize
children's exposures to air pollution and
allergens during the extended postnatal
maturation of the lungs, otherwise risking
decrements in lung function lasting into
adulthood, regardless of the presence of
environmental insults.
5-HT Concentration-Response
Not only did the pulmonary functional
decrements induced by O
exposure persist after the prolonged
recovery p eriod, but the 5-HT– mediated
exacerbation of ASM contraction did
as well (Figure 3 ). The persistence of
a 5-HT mechanism with the functional
decrements indi cates that altered
serotonergic signaling at the postganglionic
in the persistent AHR induced by O
HDMA exposure. 5-HT has been
implicated in asthma from clinical,
inflammatory, immunologic, and
neurogenic points of view (23, 28, 29,
47–52). It is well subst antiated that
5-HT can enhance the neuronal release
of ACh at nerve endings (53). Mechanistically,
it is possible that an increase in the
presence of 5-HT or an up-regulation
of 5-HT receptors at the postganglionic
HT–mediated ASM contraction, leading
to AHR and contribut ing to chronic
asthma symptoms. 5-HT has bee n shown
to up-regulate thromboxane release,
HDMA induces the proliferation of
5-HT–containing cells in the airway
epithelia (25), and 5-HT levels are
increased in the bronchoalveolar lavage
fluid of patients with asthma after allergen
challenge (23). In mice, allergen challenge
induces 5-HT release from platelets
(23). These studies indicate a plausible
mechanism for 5-HT contributing to AHR
Figure 2. Airway responsiveness during
histamine challenge. *The O
1 HDMA group
exhibited a significant increase in airway
responsiveness when compared with FA (P =
0.04; n = 6). EC200R
is the effective
concentration of histamine needed to induce
a 200% increase in airway resistance. The lower
the effective concentration, the more responsive
the airway.
Figure 3. Effect of serotonin (5-HT)
concentration on airway contractility during
electric field stimulation (EFS). *Tension
production in O
1 HDMA group is significantly
greater than in the FA group at 100 mM 5-HT.
the O
1 HDMA group, tension production at
each 5-HT concentration was greater than the
control response. Control response is defined as
the amount of tension produced via EFS before
addition of 5-HT. There was no within-group
effect seen in the FA group (P . 0.05; n = 6).
80 American Journal of Respiratory Cell and Molecular Biology Volume 51 Number 1
July 2014
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and offer possible sources of 5-HT in the
asthmatic airway.
Antagonist Concentration-
Response Curves
To identify the specific 5-HT subtype
receptors involved in the 5-HT response in
the O
1 HDMA group, 5-HT
concentration response curves where
conducted in the presence of 5-HT
, and 5-HT
subtype receptor
antagonists. These receptors were targeted
due to previous experiments run by this
group and an extensive review of literature
(18, 27, 49, 54, 55). Separate incubation
with 5-HT
, and 5-HT
receptor antagonists significantly
attenuated the ASM contractile response
to 5-HT, indicating that these receptors
play a prominent role in the O
HDMA–induced enhancement of ASM
The Effect of 5-HT
As noted in our previous exposure study,
a counterbalancing inhibitory 5-HT effect
was seen, mediated through 5-HT
receptors (18). The 5-HT
agonist 8-OH-DPAT attenuated any tissue
response to EFS and was able to diminish
the tension produced by exogenous ACh,
indicating that these receptors exert their
effect at the ASM, as opposed to inducing
postganglionic neural inhibition. This
inhibitory effect was seen in both the FA
and O
1 HDMA groups, with exposure
having no effect. Although dysregulation of
an inhibitory pathway could lead to AHR
and enhanced ASM contraction, these
results suggest that increased ASM
contraction with 5-HT is due to up-
regulation of an excitatory pathway rather
than the down-regulation of an inhibitory
Direct Effect of 5-HT on ASM Tension
1 HDMA exposure enhanced the direct
effect of 5-HT on ASM (Figure 6). 5-HT
has been shown to directly contract ASM
in multiple species (56, 56 –58). The
Figure 4. Effect of 5-HT concentration on airway contractility during EFS in the presence of 5-HT subtype receptor antagonists. (A) The 5-HT
antagonist ketanserin (Ket). (B) The 5-HT
receptor antagonist ondansetron (Ond). (C) The 5-HT
receptor antagonist, GR 113808. *All concentrations
of the receptor antagonist induced a significant reduction in tension at each 5-HT concentration when compared with concentration-respon se curve with
5-HT alone.
Administration of 10 and 100 mM of antagonist significantly reduced tension compared with the concentration-response curve with 5-HT
alone. "% of control" response is defined as the amount of tension produced via EFS before addition of 5-HT or 5-HT receptor antagonist (P , 0.05; n = 6).
Moore, Hyde, Miller, et al.: Persistent Response to Allergen and O
Page 5
enhancement of 5-HT's ability to contract
ASM is consistent with recent research
identifying that a similar exposure protocol
in rhesus monkeys induces an up-
regulation of 5-HT receptor expression
on ASM (59).
Although a functional study of this
nature using EFS on whole excised airway
tissue allows insight into the role of 5-HT in
ASM function and AHR in a model of
childhood allergic asthma, the limitations of
such an experimental preparation must be
acknowledged. Pharmacologic identification
of receptor subtypes is common practice,
but one must be careful when drawing
conclusions. We attempted to use the most
selective antagonists available, but, due to
the variance of published receptor affinities,
quantitative rank-order comparison of the
contributions of each receptor subtype could
not be established. Therefore, it was deemed
imprudent to make assumptions regarding
the relative contribution of each identified
5-HT receptor subtype (2–4) that was
shown to be involved in the serotonergic
enhancement of ASM contraction in
the exposed animals. Current
immunohistochemical studies are
underway to identify which receptor
subtypes are present at the ganglia and
terminal axon of cholinergic nerves in
FA and exposed monkeys.
This study focused on a conducting
airway site located in the middle to lower
trachea. Previous research shows that
vascular remodeling in HDMA-exposed
airways is generation specific (60). It is
possible that O
1 HDMA exposure may
have differential effects along segments
of the tracheobronchial tree. Studies
evaluating ASM function at alternate
airway generations could assess whether
Figure 5. (A) Effect of the 5-HT
agonist 8-OH-DPAT on airway contractility during EFS. *EFS-induced tension is significantly less than within-group
EFS control contraction before agonist addition. "% of control response" is defined as the amount of tension produced via EFS before addition of 5-HT
or 5-HT receptor agonist. There was no difference in response between groups. (B) Direct effect of 8-OH-DPAT on airway smooth muscle (ASM)
precontracted with 100 mM ACh. *ASM tension is significantly less than within-group control after 10 minutes of incubation with agonist.
Tension at
100 mM 5-HT is significantly less than within-group tension at 10 mM 5-HT. There was no difference in ASM tension between groups (P . 0.05; n = 6).
Figure 6. Direct effect of 5-HT on ASM tension. (A) *Addition of 10 mM 5-HT induced a significant increase in ASM compared with the within-group
baseline tension. PRE 5-HT, tissue at baseline tension of 1.0 g before addition of 5-HT; POST 5-HT, tissue tension after addition of 10 mM 5-HT. (B)
5-HT–induced tension increase was significantly greater in the O
1 HDMA group than in the FA group (P , 0.05; n = 6).
82 American Journal of Respiratory Cell and Molecular Biology Volume 51 Number 1
July 2014
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exposure effects are widespread and
consistent throughout conducting airways.
Also, studies examining the intensity and
longevity of the persistence of AHR and
enhanced ASM contraction at different
time points of exposure and recovery could
help identify a critical window during
postnatal lung development in which the
airway is most susceptible to environmental
toxicant damage.
This study did not use strategies to
differentiate between responses due to
HDMA-associated immune responses or
reactive oxygen species formation via O
exposure. Previous research has shown
a synergistic effect of O
exposure, with O
amplifying the allergic,
structural, and neural remodeling effects of
HDMA sensitization and inhalation (10, 14,
25). Also, previous work has shown that
immediately after 6 months of exposure
to HDMA, O
1 HDMA, similar
5-HT–induced increases in neurally
mediated ASM contractions were seen in all
the groups (18). The common factor in all
of these exposures is inflammation, whether
it was induced via an HDMA-driven
immune response or reactive oxygen
species production via O
exposure. This
experimental design did not allow us to
differentiate between immune versus
oxidant-induced inflammation, but this is
a viable avenue for future research.
Further evaluation linking histological
and structural changes to alterations in
airway function and 5-HT handling will
bridge a critical gap in our proposed model.
Future research could also evaluate the
effectiveness of 5-HT receptor antagonists at
reversing AHR in whole animal studies. This
study focused on the persistence of the
combined effect of O
1 HDMA exposure
on AHR and 5-HT enhancement of ASM
contraction and did not investigate the
effect of exposure to each environmental
insult separately, so the individual
contributions of O
or HDMA to
persistence cannot be addressed.
In conclusion, this study verifies for the
first time that combined exposure to two
recognized environmental contributors to
asthma, O
and HDMA, induce prolonged
decrements in lung function and lead to
a 5-HT–mediated exacerbation of ASM
contraction in a model of childhood
asthma. These hallmarks of asthma—AHR
and enhanced ASM contraction—persisted
even after exposure to O
1 HDMA had
been discontinued for 2.5 years. This study
also identified three 5-HT subtype receptors
that contribute to the enhanced ASM
contractile response (5-HT
, and
). These findings substantiate the
need to minimize exposure of young
individuals to known environmental
contributors to asthma during critical
periods of lung maturation because
damage inflicted during these times
can contribute to prolonged asthma
symptoms. The identification of
a persistent 5-HT–mediated enhanced
ASM contraction may identify novel
therapeutic targets for pharmacological
intervention in the treatment of childhood
asthma. n
Author disclosures are available with the text
of this article at www.atsjournals.org.
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Page 9
- CitationsCitations1
- ReferencesReferences71
Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs[Show abstract] [Hide abstract] ABSTRACT: In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in lung parenchyma would be permanent following a long-term recovery in filtered (FA) housing. Forty-eight infant rhesus macaques (30days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O3) or HDMA/ozone (HDMA+O3) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes,interalveolar capillary density . After 30months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. . These alveoli also had higher capillary densities as compare with FA controls. These results indicate that early life exposure to HDMA alone or HDMA+O3 alters the development process in lung alveoli. Copyright © 2014. Published by Elsevier Inc.


text:
Serena Williams
Tennis player
Here's your morning roundup of the biggest marketing, advertising and media industry news and happenings.
'Who Shot Sports,' a new exhibition at the Brooklyn Museum, shows that capturing the perfect sports photo entails much more than just snapping the winning shot.
In 'Who Shot Sports,' images cover a wide range of countries and sports, ranging from an 1840s portrait of a Scottish tennis player to contemporary views of women playing basketball in Somalia.
The winners of this year's U.S. Open men's and women's singles tournaments will each earn $3.5 million, up from $3.3 million last year.
Winning 22 Grand Slam singles titles is a brilliant accomplishment, because it's incredibly hard to do. Even if you are Serena Williams.
Serena Williams claimed her 22nd major singles victory by defeating Angelique Kerber in the Wimbledon final, tying Steffi Graf for the most major titles in tennis's Open era.
Serena Williams will face Angelique Kerber in Wimbledon final seeking to win her elusive 22nd major singles title.
After destroying a racket, everything has clicked at Wimbledon for Serena Williams.
After a week of rain delays, canceled matches and scheduling chaos, there was a miracle at Wimbledon on Sunday: The sun came out and the tournament got back on track.
Before match is suspended, American Sam Querrey puts the world's No. 1 in a two-set hole; Serena Williams survives a scare.
Garbiñe Muguruza, ranked 2nd in the world, was beaten by Jana Cepelova, a qualifier, in the second round of Wimbledon.
As garish colors and regrettable patterns invade the pro-tennis circuit, designers are rediscovering classic whites—and investing them with retro charm
Ralph Gardner Jr. tries out to be a ball boy at this summer's U.S. Open. He might have had a better shot last year.
In photos chosen Tuesday by Wall Street Journal editors, a fire destroys hundreds of houses in the Philippines, Ikea recalls dressers, London demonstrators show solidarity with the EU and more.
Novak Djokjovic is a runaway favorite at Wimbledon, the No. 1 seed, the world No. 1, both the smart and the lazy person's pick.
As the seemingly unbeatable world's No. 1 player continues his march toward a Grand Slam, here's how he could actually lose.
Writer Jason Gay and photographer Maciek Kobielski contributed to this issue of WSJ. Magazine.
From a cameo appearance in Beyoncé's "Lemonade" to defending her titles and competing at the Rio Olympics, Serena Williams is working hard as ever to stay on top.
Garbiñe Muguruza, a 22-year-old from Spain, achieved a rare feat at the French Open: She overpowered Serena Williams in a Grand Slam final.
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Garbine Muguruza defeats Serena Williams to win the women's French Open title
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subset: commoncrawl


text:
the DA was never after mbpoa. they were sent there by vic z with false allegations. they were proven false and vic has never gotten over it. get the FACTS<quoted text>
The DA has been after them twice.. liar
21 - 32 of 32 Comments Last updated Jun 6, 2013
#22 May 17, 2013
#23 May 17, 2013
OK. MB POA hasn't done anything to the village. They have no control what gets approved or voted on. They have no voting controller the board members or power of any kind in this government. Why are they such a big deal to you? Is it just the club house? Do you want their club for your own? THEY ARE A CIVIC! They are no threat to you but you act like they are the enemy! What ever happens, the Village did it to themselves.
#24 May 18, 2013
Get the FACTS it wasnt Vic Z. The guy who did it told DeBonna it was him at a meeting in front of lots of people there . YOU get the facts straight. I hate liars. In FACT DEBonna accused him of it the month before the election of their Board which Vic ran for. FACT. Another FACT, you are a hateful liar willing to spew whatever nonsense just to spread that seed of hate. FACT you are a disgusting person to be filled with so much hate and lies.
Since: May 13
Location hidden
#25 May 18, 2013
Isnt vic suing the MBPOA?
#26 May 18, 2013
Yes I sm , and I didn't turn them in it was a guy from shirley
#27 May 18, 2013
That guy is probably also an organized criminal.
#28 May 18, 2013
fact..... MBPOA is a civic and not a layer of government. FACT FACT FACT
FACT. D A doesn't care about the MBPOA, they DO care about what the village is doing. FACT FACT FACT
#29 May 18, 2013
hahahahaha how's that lawsuit working out? Has it been tossed yet? How many people left Franks lawsuit saying they had no idea that they were part of that suit? A least two people that I know of that Frank lied to. Maybe you can refill that suit! Hahahahahahaha
#30 May 18, 2013
bs,nice try. I heard the cops are tired of your BS also.
#31 May 18, 2013
fact. If Gary did noting wrong or hire family members, then he has nothing to worry about.
#32 May 18, 2013
Fact u r an idiot .the lawsuit is going fine its in federal court , this is not that bs stick dock crap so bod of mbpoa grab your ankles
#33 Jun 6, 2013
I'm waiting to see if the Police actually stole my Previously Owned Hard Drives and put illegal stuff on them to try and Set Me Up with.
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Excelsior Energy's exemptions renewed
There are 2 comments on the TwinCities.com story from May 22, 2011, titled Excelsior Energy's exemptions renewed. In it, TwinCities.com reports that:The proposed Excelsior Energy power plant, which has tapped into millions of state and federal dollars over the past decade but has been stuck in the starting blocks, has a new lease on life.
Join the discussion below, or Read more at TwinCities.com.
United States
#1 May 23, 2011
"Were trying to make the best of a bad situation here,'' said Beard, who says Gov. Mark Dayton backs the effort.
This is a travesty! This project should have never been started and is not viable. It should get no special exemptions from the government, and instead should be killed. We have wasted enough government money on it, benfitting a few wealthy interests and hurting the movement toward clean energy a great deal.
Mark Dayton ought to be ashamed of his support fot this. He knows that "clean coal" isn't, and that this plant was poorly conceived and will never produce clean energy for Minnesota. It was, and is a boondoggle!
#2 May 23, 2011
What Pat said. Beard is obviously an idiot and is a perfect example of business as usual. Furthermore he's name dropping the governor who doesn't know jack about ****. Clean coal, natural gas, whatever those two principles for Excelsior are peddling is BS. The people have simply been paying them for trying to create a powerplant no one needs or wants. Free money for 10 years to do nothing. Gotta love this country.
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US, Polish Aviators Practice Air Assault
U.S. and Polish forces participated in an air assault exercise called Anakonda 2016 in Poland last...
Leonardo-Finmeccanica Unveils US Navy Trainer
Leonardo-Finmeccanica introduced an AgustaWestland AW119 single-engine helicopter, called the...
NTSB Eyes Traffic Pattern Data in Maryland Midair
Conflicting information on airport traffic procedures and private-company operating rules appear to...
FAA to Hold Safety Conference in Texas
July 22, 2016 |The FAA will host the 2016 International Rotorcraft Safety Conference Oct. 25 to 27 at the Hurst Conference Center in Hurst, Texas.
Frasca, Grob Sim on Display at Farnborough
July 12, 2016 |
Frasca's Grob G120TP-SIM flight training device will be on display in the Grob Aircraft booth at the Farnborough Air Show, held until July 18....
Helicentre Aviation Offers 2017 Scholarships
July 11, 2016 |Helicentre Aviation Academy said its scholarship program would run for a fifth year in 2017. This year's applications are due by Sep. 30, 2016.
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ARGUS, PSAAC Enter Sponsorship Agreement
September 30, 2014 | ARGUS International has entered into a sponsorship agreement with the Public Safety Aviation Accreditation Commission (PSAAC), also known has the Airborne Law Enforcement Accreditation Commission, that recognizes ARGUS's support of PSAAC as the official...
Coptersafety AW139 FFS Receives EASA Certification
September 29, 2014 | Coptersafety's AW139 full flight simulator (FFS) has received EASA Level D certification from the Finnish CAA (Trafi) and is...
FAA, EASA Approve CAE Training Tools
September 23, 2014 | The FAA and EASA have granted certification for two CAE products: the CAE-built A350 XWB full-flight simulator (FFS) has achieved Interim Level C qualification, and the company's flight training device (FTD) achieved FAA Level 6 and EASA Level 2...


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The Muskego-Norway School District hit another record high in results for the ACT college entrance exam.
The results, released this week, show a 23.9 composite score, a significant jump from last year's previous record of 23.2, school officials said.
Boosting the district to that record were the highest scores ever for the district in English, reading and science. Those subscores were 23.6 for English and reading and 23.8 for science.
The math subscore showed a sixth straight year of improvement with a composite of 24.1, they said.
"Overall, these ACT results are very encouraging and the result of many hands involved in making this happen," Superintendent of Schools Joe Schroeder said in a press release.
More from News and Features
- Muskego gets a $500,000 state grant for Parkland Mall redevelopment
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- Questions must be answered before Muskego Youth Football can use park
- Muskego soccer parents, Kurth Park neighbors might be on same side
- Dog park idea takes step backward in Muskego
- Local lake districts, statewide programs persist in battle against invasive species
- Pickleball tickles Muskego seniors who flock to new courts


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Sounds Like: Method Man, Jadakiss, Drake, J.Cole
Label: TillmyDeath
Manager: OutSpoken
Bio: Yo Whut Up? Truskilz is my name,till my death I'll spit flames! Basically I go hard in everything I do.my music explains it all,check out my shit,message me,collab with me or like most ppl do is hate on me..but fuck it, i'm cool with that,cause that means ya paying attention! so continue to liste...See Full Bio


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I know that headphones can get very expensive, but my question is: for you personally, what is the best budget for a set of headphones? What i mean by that is how much do you have to spend to get the best value. i hope this is making sense. for example. I asked a question about expensive iem's earlier this month and in response someone gave me this. It makes sense! but the question i am asking is what price range is best in terms of value? I hope this makes sense!
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Question about Budgets
Gear mentioned in this thread:
- "Luxurious midrange, full and extended bass, smooth treble, comfortable.""Pros : Sound quality, comfort, build, modularity (parts), balance, naturalness, clarity, detail"
- "Smooth Presentation, a linear, stout sound at louder volumes. ""Sensational Excursion Factor , Exquisite Bass Extension , Almost perfect Mid-Range , Classic HE-60/90 Design , Potential Upper Treble Extension "
- "Good across the frequency range, Live Sounding, Full ""Balanced, Decent Bass Body, Not much Plastic"
- Nirvana Woman
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200-300. You can get for example sennheiser hd600 and hd650 in that range, either used or new if you're lucky, and I think they're about the best deals.
- MattTCG
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For me, $300-400 is the sweet spot. The puts the hd650, he400 and maddogs within reach.
Yea, i kinda want a pair of hd650's or maybe some hd598's. just dont have the money right now. haha. thanks for the info!
Edited by bcd127 - 1/30/13 at 6:45pm
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I'd definately say $200-$400. Thats where all the former flagships are.
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In terms of the best value for money: one model lower than the best a company has to offer. Top models always have a big markup.
In terms of absolute money, I agree with others. $3-400 is good enough.
Hm. Good point! thanks!
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Yeah, the jump from nothing/$10 headphones to the $300-400 range is infinitely more noticeable/drastic/worth your money than the jump from $300-400 to $700-$2000-onward.
- Question about Budgets
Gear mentioned in this thread:
- "Luxurious midrange, full and extended bass, smooth treble, comfortable.""Pros : Sound quality, comfort, build, modularity (parts), balance, naturalness, clarity, detail"
- "Smooth Presentation, a linear, stout sound at louder volumes. ""Sensational Excursion Factor , Exquisite Bass Extension , Almost perfect Mid-Range , Classic HE-60/90 Design , Potential Upper Treble Extension "
- "Good across the frequency range, Live Sounding, Full ""Balanced, Decent Bass Body, Not much Plastic"
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A fan-fiction take on the legendary series!
weebl and bob
It's the everyday happenings of weebl and sometimes weebl's friend bob!
Aqua Life
Crazy antics from under the sea!
Dude sweet
It reminded me of the things you can get when using windows media player, only yours was MUCH better. I could have watched that all day and not got bored with. Nice one.
u know part of that looked like it was an abbey national advert. lol. it was great.
very cool, but i dont think many people watch this and others is because of the generic names. Better names!
the music was very fitting for this! OoooOoooOooo!
this is awesome and very fluid-like!


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Back to Main...
BWW Reviews: Doug Varone and Dancers Further the Art
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MOonhORsE Dance Theatre Presents 36th Edition of OLDER & RECKLESS This Weekend
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The devastating outcomes of lessons learned from the Holocaust are revealed in a landmark, original ballet coming to the Raymond F. Kravis Center for the Performing Arts in Ballet Austin - LIGHT/The Holocaust & Humanity Project. Presented by inSIGHT Through Education, in collaboration with the Kravi... (more...)
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BWW Book Review: A CHANCE TO DANCE, by Betsy Bradley
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Verizon Communications Inc will announce plans to buy Yahoo's core assets for a bit more than $4.8 billion, said two people with direct knowledge of the situation who asked not to be identified.
China will continue to upgrade its manufacturing industry and boost its intelligent manufacturing, as well as cut down its excessive capacity, the country's industry watchdog said
The Shanghai Futures Exchange has vowed it won't tolerate any abuse of trading rules after the unprecedented boom-bust episode in Chinese commodities markets earlier this year.
China continues support for high-tech manufacturing: Official
Lower headline credit growth, still strong overall credit impulse
Booming Chinese robotics industry a good sign
New age, new balance and new breakthroughs
Is China running out of policy options?
Hello Huawei, Xiaomi, bye-bye big brands
Opening-up the service sector key for reform
Market economy status not a bilateral negotiation
Tibet came top of 25 Chinese provinces and municipalities that had released their half-year GDP growth figure as of Monday, thanks to investment in infrastructure and local industries.
China nuclear giant CGN said Monday that it had partnered with French new-energy firm Eolfi on a winning tender for a floating wind power project in France.
The delegation from the China Academy of Chinese Medical Sciences paid a visit to Hanover Medical School for TCM cooperation with Germany where they discussed academic research and clinical practice in areas.
Zhou Lei, an independent auto analyst in Beijing, said the rise in the number of cars recalled did not necessarily mean that more cars are shoddily made.
Chinese internet search company Baidu Inc said on Monday an offer it received in February to buy its stake in online video unit iQiyi has been withdrawn.


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How We Thinkby John Dewey
View All Available Formats & Editions
The dean of American philosophers shares his views on methods of training students to think well. His considerations include inductive and deductive logic, interpreting facts, concrete and abstract thinking, the roles of activity, language, and observation, and many other aspects of thought training. This volume is essential reading for teachers and other education


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Long popular among Israelis, yoga is gaining ground among Palestinians seeking inner peace in a land marred by war. But can it actually 'empower' them?4
Ballots for the upcoming Israeli election are printed in a West Bank settlement — so do leftists who want to fight the occupation need to stay home on voting day?16
Why would a group of young British Jews want to hire a West Bank lawyer? Jessica Belle Weiss explains that someone needs to make sure Palestinian kids get a fair trial in military court.22
Other religions offer spiritual practices that Judaism lacks — so why not adopt multiple traditions simultaneously? Jay Michaelson argues that being a hybrid Jew is an opportunity, not a problem.38
Nine years after vocally opposing same-sex commitment ceremonies, Conservative Rabbi Philip Scheim officiated at one. It ended up being the highlight of his career.36
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Written on: 29/06/2013
Insured my Bandit 1250 fo £89, two weeks later I part exd it for a
650 vstrom, I rang from the showroom because I forgot to change the insurance, they charged me £127 which included £50 admin charges. It took two days to get back in touch to complain and was told it would cost another £50 to cancel policy and a proportion of the amount for being insured. I decided to stay with them but hoipefully never have to make a claim. Learnt from my experience.
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|Page 7 of 14:
|[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
|132 reviews in total
Sean (Josh Hutcherson, the only returning original cast member)
reappears as a rebellious, book-loving teenager who is trying to put
together clues to find The Mysterious Island, where he believes his
grandfather Alexander Anderson (Michael Caine) is stranded. Initially
resistant to his new stepfather, Sean reluctantly agrees to let Hank
(Dwayne "The Rock" Johnson), a former Navy code-breaker, assist in
deciphering the signal that ultimately leads them to the coordinates of
the island. Hank desperately trying to form a relationship with his new
stepson, takes Sean to Palau where they meet up with Gabato (Luis
Guzman, who plays a comic-relief helicopter pilot) and his beautiful
daughter Kailani (Vanessa Hudgens). Hank shares his strong motivation
for developing his relationship with Sean, when he speaks of his own
"bad dad" experience. "My father left when I was eight and I haven't
seen him since," Hank later tells his new stepson, which becomes the
turning point in their relationship.
In flight to the destination's coordinates, the helicopter loses control and is sucked into a major hurricane. After a terrifying ride, the storm leads them right to an island with gigantic lizards, tiny elephants, and gold-filled volcanoes. In search of a way off of the island, they discover many great artifacts and create a bond with each other like no other. They eventually find their way off the island by way of the sunken submarine, which they find by reading the chapters in Verne's eccentric story. This makes a great opportunity to reinforce reading to your kids.
Examples like the giant insects and a submarine that has been under water for a hundred years that starts with just the push of a button, makes the plot of the film appear somewhat frivolous and child-like. In watching this movie, you must remember that this is a PG rated film, with the primary audience intended to be children and families with children. I loved that in watching this movie over and over again with my kids, we discovered something new each time that we had missed in the previous viewing. Each time was like going to the enchanted island yourself as it draws you in to the storyline, joining the characters in their adventure. As Daniel Eagan states in his review, "If you want to fault Journey 2 for being too far-fetched, Verne's novel had just as much balderdash. Both film and book move quickly and slyly enough to skim over mere logic." This reminds us that yes the plot is crazy, but that it was the original intention of Verne, the author of the book the movie is based on. This movie brings his imagination to life with excitement and fantasy.
Director, Brad Peyton (Cats & Dogs 2, Evelyn: The Cutest Evil Dead Girl), creates a beautiful visual experience of tropical plants and waterfalls. Even though it is very obvious that the majority of the film is shot in front of a green-screen, it does manage to give us amazing graphics and cinematography with vibrant colors and quirky special effects. I'm not going to lie when I say the entire movie was a little bit over the top, and a tad hokey. With its computer generated overgrown lizards and ants, and tiny elephants you can pick up and carry, it forces one to use their child-like imaginations and try to forget what we know to be "real" and "make-believe". If you are a fan of special effects, this movie although fun to watch, was definitely no Rise of the Planet of the Apes, which is up for an Oscar nomination this year. Is this another Avatar? Not by any stretch of the imagination was this movie intended to win any major awards that much is clear. However when they all board giant flying bees, we are able to see just how much work went into generating the computer animation, and how they used it in such a fun, imaginative way.
The silliness of the storyline would have been a little too much to handle, if the actors didn't manage to ground it. As is written in Wikipedia's review, "It isn't a good movie in the usual sense (or most senses), but it is jolly and good-natured, and Michael Caine and Dwayne Johnson are among the most likable of actors." Johnson and Caine add a great dynamic to the film as the dueling father figures in Hutcherson's life. Their rivalry-based banter carries the film, and adds a dynamic camaraderie between relatives, that most families can relate to.
I think overall this film is a wonderful blend of comedy, adventure, and fantasy. Recently released into Redbox for just a $1.50, I think everyone should at least give it a try. Whether you have kids or not, this is a fun, carefree film that will make you smile at the end of a hard day. You will find yourself anxiously waiting for the release of Journey 3 From the Earth to the Moon, coming to theaters 2014. If you do have kids, be prepared to just purchase the DVD. This is one of those films they will watch on a hundred different occasions and love it every time!
I found this movie to be quite cute! Being a fan of the Rock, he never fails to surprise me. The story line is fun and engaging by enlisting the book titles for Jules Verne. The special effects are very well done and deliver a wonderful visual marriage of the real and the imagined. There are some weak points, but what movie doesn't have them. I felt the speed of the movie was just about perfect for the young audience. The ending left the viewer wanting more. I think the older child, 10 and up, would find this a fun and exciting adventure. If it encouraged a young one to read the classic books it would be an extra bonus. I do so hope they do another movie about another adventure.
Jules Verne wrote several notable novels in his time. I truly believe he would have been astonished by what modern movie magic has done to his work. With director Brad Payton at the helm, the core book is now the movie called " The Mysterious Island: The Journey. " Obstencibly written by Verne, it's been adapted by Brian and Mark Gunn for the silver screen. The film is one beautiful and wondrous adaption of the book and becomes an extraordinary college of excitement. The story begins with the Grandson (Josh Hutcherson) who discovers a mysterious code left for him by his Grandfather (Michael Caine). Now with the help of his Step-Father (Dwayne Johnson) they decide to travel to the Pacfic Ocean and seek out the fantastic island. Along the way they enlist the aid of a helicopter pilot (Luis Guzmán) and his daughter (Vanessa Hudgens). From beginning to end, the film is a fast-paced, action-oriented, fantasy adventure. The movie is well worth the time and the cast is a wonderful. I easily recommend it to one and all. ****
Oh, I know. That's the whole point. It's not meant to be taken
seriously. But really? Journey 2 goes out of its way to be so far
beyond ridiculous that it is, at times, painful to watch.
Yeah, little kids will love it. Adults will hate it. I guess I must be (mentally, at least) somewhere in the middle, but since I couldn't stop laughing at the stupid, it is difficult to tell.
Usually when I watch a kid's film, I'm mostly interested in whether it is actually suitable for kids or not. In this case , as I said above, little kids will find it bright and entertaining.
Slightly older kids I'm not so sure. I don't think there is anything remotely like common sense anywhere in the plot and smart kids will see through it like last night's fish and chip's wrapper.
There are questionable scenes (enjoyable for an adult!) of Vanessa Hudgens butt (mostly covered) which I wasn't sure about. Nothing nasty, but just a few too many lingering bum-shots. Maybe they gave the cameraman carte-blanche, who knows? It's really not a very good film and the wackiness is, at times, overwhelming, hence why I laughed a lot - not at the intended jokes, but the stupidity of it all. But it was pleasant laughter, all the same, just not what the writer and director had imagined, I'm sure.
It's all kinds of stupid and you will be glad when its over, trust me. But for small kids its a passable diversion, I guess.
The one section that comes across far nastier than it was intended, I'm sure, were the initial scenes between The Rock and Michael Cain. There is some really unpleasant dialogue between the two as the rivalry for the step-sons affections takes hold. I mean a real bitter undercurrent between them. You actually begin to hate Caine's character for his snide comments.
They make up in the end, of course, and all is well. But for those opening scenes. Ouch! All in all though, not really worth the effort.
*** This review may contain spoilers ***
If I'm to be totally honest about this movie, I liked it. Definitely the kind of thing I would have watched when I was younger. The thing I did NOT like though, was how fast the beginning was, and how they all of a sudden knew exactly what to do next, or what this means, or what this is. Such as, when Sean (Josh Hutcherson) knew exactly what the riddles meant, and exactly where the books would be in the beginning, and also when he knew the name of the birds that were chasing them on the bees. I understand that he's supposed to be playing a "straight A" student who's a science goof, but come on. Overall, though, I enjoyed it. The visual effects were very cool. Also, I really enjoyed seeing The Rock popping his pecks. At that point I nearly died (death by laughter ;D). 8/10 from me :)
The first time I read the title of this movie while it was in
development I laughed and cried at the same time. The first movie was
called "Journey to the center of the earth" which is directly the title
of the book. But this movie is called "Journey 2 the mysterious island"
which is based off of the book "Mysterious Island"... this is too
funny. That means we are now pretending that the first movie was really
"Journey: to the center of the earth" and this movie should be "Journey
2: the mysterious island" but they never fixed that problem so it just
looks sloppy. (note that some places say "Journey 2: the mysterious
island" and automatically corrected that grammar problem)
Journey 2 has a lot of problems in it, but you probably would've guessed what the problems were from the first time you watched the trailer. The Rock is in this movie, replacing Fraser which is a little bit annoying since Fraser is a much more enjoyable character and actor. You can tell from this movie that it is going to be heavily family oriented with little creativity or originality. This movie was just made to be an easy cash-grab and that's it. The Rock doesn't do anything overly original in this movie and there is a joke about his pecs and deflecting fruit which was honestly rather stupid and kind of annoying. Really he is dull. Luis Guzmán was entirely a comedy relief in this movie and was entirely stereotypical... which was rather disappointing. I don't blame him so much, it's more of his script that sucks.
But there are two actors here which I can respect a little bit more ion this movie: Michael Caine and Josh Hutcherdad. Josh Hutchernephew actually attempts to do a good job at acting in this movie, and I actually kind of enjoyed some of his dialogue. Michael Caine wasn't over the top in this movie, but he didn't do a bad job. If there was a problem I had with Josh Hutcherdaughter it wasn't his acting but it was his dialogue. In the movie Josh Hutchergreatgrandpa has the whole "I'm a super intelligent, self efficient teenager who says stuff that sounds smart but actually makes no sense". It bothers me when you're in a movie and you understand their "smart" dialogue but you can tell it makes no sense. If you have the time to pretend that something far fetched could happen, at least try and make a reasonable explanation.
Visual is another issue this movie has. The visuals... are repulsive and awful. There is an entire lack of creativity for the whole mysterious island scenario which is probably one of the biggest problems this film has. If a family movie is all about the visual experience then at least put some work into them. All of the animals/monsters in this movie are about as dull as it gets. I'm not even joking here, no effort at all went into making the animals. On the mysterious island all of the animal sizes are reversed: Elephants are punt sized and lizards are giant behemoths. Now even I could've taken some creative liberties with this one, but this movie takes no creativity. Animal sizes are reversed... but with no visual changes. Basically a tiny elephant looks identical to a large elephant, and large Bees look identical to tiny bees except for size. This makes me even more mad than the actors and the entire scenario. The makers could've at least made the animals look a bit visually different than their normal counterparts since they evolved bigger wouldn't that mean that they should've changed even slightly? Oh yeah and the CGI is probably at least 6 years out of date which also adds to the visuals being dull in appearance and in creativity. At least the first movie had some creativity which makes me wonder why this movie couldn't have been as creative as the last.
The plot isn't interesting, basically it throws in every plot device from the book into the movie such as Atlantis, the Nautilus, captain Nemo and other stuff like that. Not terrible but not intriguing. Of course there is a love interest for Josh Hutchermom but nobody really cares about it because it seemed forced.
In summary: this movie may be good for younger audiences but it has nothing to offer for any movie-goer. Personally, I think all sequels need to be watched just so that you know for a fact whether it was good or not. I rarely avoid bad sequels because I will always have that feeling that I missed a part of what the creators wanted me to see. So if you have seen the first, you might as well watch this movie.
Could have been a great movie, but the writers for this movie are
absolutely horrid. There is suppose to be some sort of witty banter
going on between characters, and it's just painful to watch.
An absolute waste of time. If you have kids, they will probably still enjoy it, and you may even be able to stand watching it for the entire movie if you know you're doing it for the kids. Unfortunately I watched this without kids, so I didn't get any sort of meaningful pleasure out of this torture.
I regret watching this movie, and wish I never did. Please for the good of all humanity, I hope whoever wrote the scripts for this movie to never write again.
Journey 2: The Mysterious Island CATCH IT (B) Journey2 is surprisingly funny and entertaining. Even though it seems like a bad 3D movie from the promos but when you start watching it and understand that it's a family adventure movie. You'll actually thoroughly enjoy the movie. Every movie doesn't have to please the critics there should be movies which are simply fun. I'm not a huge fan of Josh Hutcherson; I think he is a one note actor since bridge to Terabithia till now. Even though the Kids are Alright and The Hunger Games has put him in better position but I still I feel if these movies had someone else. He would have been considered a superstar giving both indie and commercial blockbusters. Anyways he does a good job and matched well with Vanessa Hudgens. Vanessa the X-Disney child is fun to watch. Dwayne The Rock Johnson is a brilliant man, he can sing, dance and punches darn good. This man is always good in everything; good thing is he never shy or hesitates from doing anything. Michael Cain is a legendary actor, his fun teases with Dwayne are really funny. Luiz Guzman is hilarious & Kristin Davis is beautiful. Overall, I had great fun watching Big Lizards, Big Elfish, Big Bees & Big Birds fights and small sharks & elephants. It's a complete Family entertainer.
I did not see it in 3-D, perhaps that might have been something. I'm willing to suspend my disbelief pretty readily, but this pile of trash was so full of plot holes and unbelievable character motivation that I felt physically Ill throughout the screening. If not for my girlfriend and her two kids I would have left the theater. Instead I put up with the torture of a bad script, horrific acting acting, and the lamest, borderline sexist, comedy (calling an old man grandmother, I find that offensive) I've seen in a long while. I spent most of the movie feeling sorry and embarrassed for Michael Caine. The kids seemed to like it (as well as some of the adults in the audience)... I fear for the future of our civilization.
*** This review may contain spoilers ***
They say there is nothing stranger than folk, and reading some truly
negative reviews on here proves it.
I thought this movie was delightful, the special effects were superb.
This film had humour and adventure, and the cast played it well.
I am not a reader of books, but am now tempted to read the titles mentioned in this film.
The great writers of the past, lent to the imagination, just as this movie does.
Its basically a light heart frothy romp, centered round Jules Verne's 19th-century novel Twenty Thousand Leagues Under the Sea and The Mysterious Island again a novel by Jules Verne, published in 1874.
Take your kids to see this film, you wont regret it.
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text:
InterMot 2010 includes lots of electric motorcycles
Thu, 09/30/2010 - 07:30
Here's an invitation message filmed by Mavizen featuring Jennifer Bromme of Werkstatt SF. It was recorded at the TTXGP race at VIR in August. I understand there's a German version that's playing in Germany (she's originally from Germany).
Information here: http://www.intermot-koeln.com/thefair/electric_mobility.php
Are any V members planning to attend?
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The Transition Companion: Making Your Community More Resilient in Uncertain Times
Bottled Lightning: Superbatteries, Electric Cars, and the New Lithium Economy Essential to understanding the economic importance of lithium batteries
Resilient Cities: Responding to Peak Oil and Climate Change
Transportation in a Climate-Constrained World
JOLT!: The Impending Dominance Of The Electric Car And Why America Must Take Charge