Uncertainty in the evolution of climate feedback traced to the strength of the Atlantic Meridional Overturning Circulation

In most coupled climate models, effective climate sensitivity increases for a few decades following an abrupt CO2 increase. The change in the climate feedback parameter between the first 20 years and the subsequent 130 years is highly model dependent. In this study, we suggest that the intermodel spread of changes in climate feedback can be partially traced to the evolution of the Atlantic Meridional Overturning Circulation. Models with stronger Atlantic Meridional Overturning Circulation recovery tend to project more amplified warming in the Northern Hemisphere a few decades after a quadrupling of CO2. Tropospheric stability then decreases as the Northern Hemisphere gets warmer, which leads to an increase in both the lapse‐rate and shortwave cloud feedbacks. Our results suggest that constraining future ocean circulation changes will be necessary for accurate climate sensitivity projections

The remote impacts of climate feedbacks on regional climate predictability

Uncertainty in the spatial pattern of climate change is dominated by divergent predictions among climate models. Model differences are closely linked to their representation of climate feedbacks, that is, the additional radiative fluxes that are caused by changes in clouds, water vapour, surface albedo, and other factors, in response to an external climate forcing. Progress in constraining this uncertainty is therefore predicated on understanding how patterns of individual climate feedbacks aggregate into a regional and global climate response. Here we present a simple, moist energy balance model that combines regional feedbacks and the diffusion of both latent and sensible heat. Our model emulates the relationship between regional feedbacks and temperature response in more comprehensive climate models; the model can therefore be used to understand how uncertainty in feedback patterns drives uncertainty in the patterns of temperature response. We find that whereas uncertainty in tropical feedbacks induces a global response, the impact of uncertainty in polar feedbacks remains predominantly regionally confined

Improving Precision Force Control With Low-Frequency Error Amplification Feedback: Behavioral and Neurophysiological Mechanisms

Although error amplification (EA) feedback has been shown to improve performance on visuomotor tasks, the challenge of EA is that it concurrently magnifies task-irrelevant information that may impair visuomotor control. The purpose of this study was to improve the force control in a static task by preclusion of high-oscillatory components in EA feedback that cannot be timely used for error correction by the visuomotor system. Along with motor unit behaviors and corticomuscular coherence, force fluctuations (Fc) were modeled with non-linear SDA to contrast the reliance of the feedback process and underlying neurophysiological mechanisms by using real feedback, EA, and low-frequency error amplification (LF-EA). During the static force task in the experiment, the EA feedback virtually potentiated the size of visual error, whereas the LF-EA did not channel high-frequency errors above 0.8 Hz into the amplification process. The results showed that task accuracy was greater with the LF-EA than with the real and EA feedback modes, and that LF-EA led to smaller and more complex Fc. LF-EA generally led to smaller SDA variables of Fc (critical time points, critical point of Fc, the short-term effective diffusion coefficient, and short-term exponent scaling) than did real feedback and EA. The use of LF-EA feedback increased the irregularity of the ISIs of MUs but decreased the RMS of the mean discharge rate, estimated with pooled MU spike trains. Beta-range EEG–EMG coherence spectra (13–35 Hz) in the LF-EA condition were the greatest among the three feedback conditions. In summary, amplification of low-frequency errors improves force control by shifting the relative significances of the feedforward and feedback processes. The functional benefit arises from the increase in the common descending drive to promote a stable state of MU discharges

Epidemiology of acute otitis media among young children: A multiple database study in Taiwan

Background/PurposeAcute otitis media (AOM) is a common complication of upper respiratory tract infection (URTI) among children. The purpose of this study was to evaluate the epidemiology of AOM among young children in Taiwan, including the age incidence and seasonality by combining multiple databases.MethodsTwo country-based questionnaire survey studies had been conducted to evaluate the experience of otitis media (OM) among young children: one in 2007 and the other between 2005 and 2010. The number of OM cases (5% of population younger than 7 years) in 2005 and annual visiting rates for URTI from 2005 to 2010 obtained from the National Health Insurance Research Database of Taiwan were collected and comprised the third database. The fourth database comprised ambulatory visits of children with OM to a medical center in central Taiwan between 2005 and 2010.ResultsData from a total of 1099 questionnaires were entered into Database I in 2007, and data from 9705 questionnaires between 2005 and 2010 comprised Database II. There were 86,702 children (younger than 7 years, representing 5% of the whole population for this age group) retrieved from Database III in 2007, and 5,904 cases of OM in children between 2005 and 2010 in a hospital. In Database I, 7.46% children experienced at least one episode of AOM compared with 9.21% in Database II for children aged 5 years and younger. In Database III, 13.2% children younger than 7 years had AOM in 2005. The peak season of AOM among children was from March to May (Databases III and IV).ConclusionAOM was thought to be a very common disease among children; however, this comparative analysis showed that the overall prevalence of AOM among children younger than 5 years was only 20%, much lower than in other countries. AOM was more prevalent during the spring season, and still was similarly common after age 2 years

Clonal dissemination of invasive and colonizing clonal complex 1 of serotype VI group B Streptococcus in central Taiwan

Background/PurposeThe aim of this study was to investigate clinical presentation, serotype distribution and genetic correlation of group B streptococcus (GBS) diseases. Since serotype VI prevalence far exceeded that reported in prior studies, genetic relationship of isolates was further analyzed.MethodsGBS isolates obtaining from patients with invasive diseases and pregnant women with colonization between June 2007 and December 2010 were analyzed. All isolates were tested for serotypes by multiplex PCR assay and pulsed-field gel electrophoresis (PFGE). Serotype VI isolates were further analyzed by multilocus sequence typing (MLST).ResultsA total of 134 GBS isolates were recovered from blood of 126 patients with invasive disease (94.0%) and anogenital swabs of 8 pregnant women (6.0%). Most common serotype was Ib (21.6%), followed by V (20.1%), VI (18.7%), III (15.7%), II (11.9 %), Ia (11.2%), and IX (0.7%). Serotype VI was also the leading type in infants with early onset disease (EOD; 3/8, 37.5%) and colonizing pregnant women (3/8, 37.5%). PFGE distinguished 33 pulsotypes, reflecting genetic diversity among GBS isolates. Among 25 serotype VI isolates tested, 14 were ST-1, seven were ST-679, three were ST-678, one was ST-681, and distributed into four PFGE pulsotypes. ST-678, ST-679, and ST-681 were novel sequence types; ST-678 and ST-679 are single-locus variants of ST-1 that belongs to clonal complex (CC) 1.ConclusionCC1 dissemination of serotype VI GBS thus emerges as an important invasive pathogen in infants and nonpregnant adults in central Taiwan. Serotype prevalence of GBS must be continuously monitored geographically to guide prevention strategy of GBS vaccines

Walker circulation response to extratropical radiative forcing

Walker circulation variability and associated zonal shifts in the heating of the tropical atmosphere have far-reaching global impacts well into high latitudes. Yet the reversed high latitude-to-Walker circulation teleconnection is not fully understood. Here, we reveal the dynamical pathways of this teleconnection across different components of the climate system using a hierarchy of climate model simulations. In the fully coupled system with ocean circulation adjustments, the Walker circulation strengthens in response to extratropical radiative cooling of either hemisphere, associated with the upwelling of colder subsurface water in the eastern equatorial Pacific. By contrast, in the absence of ocean circulation adjustments, the Walker circulation response is sensitive to the forcing hemisphere, due to the blocking effect of the northward-displaced climatological intertropical convergence zone and shortwave cloud radiative effects. Our study implies that energy biases in the extratropics can cause pronounced changes of tropical climate patterns

Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC50 values of 0.9 and 0.8 μ g/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control

FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway

BACKGROUND: Nasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development. METHODS: A bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation. RESULTS: We found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells. CONCLUSIONS: These findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake