To determine the proportion and physiological characteristics of nonobese patients with obstructive sleep apnea (OSA) and their response to prescribed therapy.
Data from 163 consecutive in-laboratory ...diagnostic sleep studies for participants referred to an academic teaching-hospital sleep clinic for suspected OSA were assessed. Sleep and anthropometric parameters at baseline and follow-up (up to 22 mo) were examined and compared between obese and nonobese patients with a diagnosis of OSA (apnea-hypopnea index > 5 events/h sleep). A key nonanatomical contributor to OSA pathogenesis, the respiratory arousal threshold, was compared between groups.
Twenty-five percent of the participants with a diagnosis of OSA had a body mass index (BMI) within the normal range (BMI < 25 kg/m
) and 54% had a BMI < 30 kg/m
(nonobese). Of the patients prescribed continuous positive airway pressure (CPAP), more nonobese patients reported not using their CPAP machine at all at follow-up (36% vs. 13%, p = 0.03). Objective CPAP compliance was also lower in the nonobese patients with OSA (5.1 ± 0.4 vs. 6.4 ± 0.4 h/night, p < 0.03). A higher proportion of the nonobese patients had a low respiratory arousal threshold compared to obese OSA patients (86% vs. 60%, p < 0.001).
A substantial proportion of patients with OSA are not obese. These patients are challenging to treat with existing therapies as they are less adherent and compliant with CPAP therapy. Nonanatomical contributors to OSA, such a low threshold for arousal, are likely to be particularly important in OSA pathogenesis in nonobese patients with OSA. These findings have important implications for the pathogenesis of OSA in nonobese patients and potential therapeutic targets for this group of patients.
1. A plant's growth rate is seen as a central element of its ecological strategy, and as determined by its traits. Yet the literature is inconsistent about the empirical correlation between ...functional traits and growth, casting doubt on the capacity of some prominent traits to influence growth rate. 2. We propose that traits should influence growth in a way that depends on the size of individual plants. We outline mechanisms and hypotheses based on new theoretical work and test these predictions in tree species using a meta-analysis of 103 studies (> 500 correlations) for five traits (specific leaf area, wood density, maximum height, seed mass and maximum assimilation rate). We also recorded data for 14 other traits commonly used in the trait literature. To capture the effects of plant size, we tested for a shift in the direction of correlation between growth rates and each trait across three ontogenetic stages: seedling, sapling and adult. 3. Results were consistent with predictions, although there were some limitations arising from unequal numbers of observation across ontogenetic stages. Specific leaf area was correlated with relative growth rate in seedlings but not in adult plants. Correlations of growth with wood density were not affected by ontogenetic stage. Seed mass, assimilation rate and maximum height were correlated with relative growth rate only in one ontogenetic stage category: seedlings, seedlings and adults, respectively. 4. Although we were able to confirm several of our theoretical predictions, major knowledge gaps still exist in the trait literature. For example, for one-third of the traits considered, the majority (> 75%) of reported correlations with growth came from the same ontogenetic stage. 5. Synthesis. We show for some traits, how trait–growth correlations change in a predictable way with plant size. Our understanding of plant strategies should shift away from describing species as having a fixed growth strategy throughout their life (on a continuous axis from slow to fast growth), in favour of a size-dependent growth trajectories.
The black-tailed dusky antechinus (Antechinus arktos) is an endangered, small carnivorous marsupial endemic to Australia, which occurs at low population density along with abundant sympatric ...populations of other small mammals: Antechinus stuartii, Rattus fuscipes and Melomys cervinipes. Using A. arktos as a model species, we aimed to evaluate the effectiveness of infrared digital camera traps for detecting and differentiating small mammals and to comment on the broad applicability of this methodology. We also sought to understand how the detection probabilities of our target species varied over time and characterize their activity patterns. We installed 11 infrared cameras at one of only three known sites where A. arktos occurs for five consecutive deployments. Cameras were fixed to wooden stakes and oriented vertically, 35 cm above ground, directly facing bait containers. Using this method, we successfully recorded and identified individuals from all four species of small mammal known previously in the area from live trapping, including A. arktos. This validates the effectiveness of the infrared camera type and orientation for small mammal studies. Periods of activity for all species were highly coincident, showing a strong peak in activity during the same two-hour period immediately following sunset. A. arktos, A. stuartii and M. cervinipes also displayed a strong negative linear relationship between detection probability and days since deployment. This is an important finding for camera trapping generally, indicating that routine camera deployment lengths (of one-to-two weeks) between baiting events may be too long when targeting some small mammals.
Background and aims
Root-released carboxylates enhance the availability of manganese (Mn), which enters roots through transporters with low substrate specificity. Leaf Mn concentration (Mn) has been ...proposed as a signature for phosphorus (P)-mobilising carboxylates in the rhizosphere. Here we test whether leaf Mn provides a signature for root functional types related to P acquisition.
Methods
Across 727 species at 66 sites in Australia and New Zealand, we measured leaf Mn as related to root functional type, while also considering soil and climate variables. To further assess the specific situations under which leaf Mn is a suitable proxy for rhizosphere carboxylate concentration, we studied leaf Mn along a strong gradient in water availability on one representative site. In addition, we focused on two systems where a species produced unexpected results.
Results
Controlling for background site-specific variation in leaf Mn with soil pH and mean annual precipitation, we established that mycorrhizal species have significantly lower leaf Mn than non-mycorrhizal species with carboxylate-releasing root structures, e.g., cluster roots. In exception to the general tendency, leaf Mn did not provide information about root functional types under seasonally waterlogged conditions, which increase iron availability and thereby interfere with Mn-uptake capacity. Two further exceptions were scrutinised, leading to the conclusion that they were ‘anomalous’ in not functioning like typical species in their families, as expected according to the literature.
Conclusions
Leaf Mn variation provides considerable insights on differences in belowground functioning among co-occurring species. Using this approach, we concluded that, within typical mycorrhizal families, some species actually depend on a carboxylate-releasing P-mobilising strategy. Likewise, within families that are known to produce carboxylate-releasing cluster roots, some do not produce functional cluster roots when mature. An analysis of leaf Mn can alert us to such ‘anomalous’ species.
Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. ...However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB–PTPIP51 interaction and ER–mitochondria associations. These disruptions are accompanied by perturbation of Ca2+ uptake by mitochondria following its release from ER stores, which is a physiological read‐out of ER–mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS‐expressing cells; mitochondrial ATP production is linked to Ca2+ levels. Finally, we demonstrate that the FUS‐induced reductions to ER–mitochondria associations and are linked to activation of glycogen synthase kinase‐3β (GSK‐3β), a kinase already strongly associated with ALS/FTD.
Synopsis
This study shows that FUS, by disrupting ER and mitochondria associations, regulates calcium uptake into and ATP production by mitochondria, with implications for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD).
FTD/ALS‐associated fused in sarcoma (FUS) disrupts ER–mitochondria associations and links calcium homoeostasis and mitochondrial ATP production.
FUS‐induced disruption of ER–mitochondria associations involves activation of GSK‐3β and breaking of the VAPB–PTPIP51 ER–mitochondria tethering proteins.
This study shows that FUS, by disrupting ER and mitochondria associations, regulates calcium uptake into and ATP production by mitochondria, with implications for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD).
Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. ...However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB-PTPIP51 interaction and ER-mitochondria associations. These disruptions are accompanied by perturbation of Ca2+ uptake by mitochondria following its release from ER stores, which is a physiological read-out of ER-mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS-expressing cells; mitochondrial ATP production is linked to Ca2+ levels. Finally, we demonstrate that the FUS-induced reductions to ER-mitochondria associations and are linked to activation of glycogen synthase kinase-3beta (GSK-3beta), a kinase already strongly associated with ALS/FTD. Synopsis This study shows that FUS, by disrupting ER and mitochondria associations, regulates calcium uptake into and ATP production by mitochondria, with implications for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). FTD/ALS-associated fused in sarcoma (FUS) disrupts ER-mitochondria associations and links calcium homoeostasis and mitochondrial ATP production. FUS-induced disruption of ER-mitochondria associations involves activation of GSK-3beta and breaking of the VAPB-PTPIP51 ER-mitochondria tethering proteins.
Basal‐like breast cancers typically correspond with increased enrichment of EpCAM‐/CD49f‐ cancer stem cells (CSC) and a propensity toward metastasis. However, the molecular mechanisms underlying ...these general characteristics are not well understood. To provide further insight concerning CSCs and their intrinsic metastatic mechanisms, we compared the 450K DNA methylation profile of EpCAM‐/CD49f‐ poor breast cancer cell lines to that of EpCAM‐/CD49f‐ enriched breast cancer cell lines. From our results, we were able to determine and highlight IL32 as a gene whose promoter is hypomethylated in EpCAM‐/CD49f‐ enriched cell lines. The hypomethylated IL32 promoter corresponded with increased IL32 expression in both cell lines and basal‐like breast cancer patients from The Cancer Genome Atlas (TCGA) database. Interestingly, increased IL32 expression preferentially occurred for the IL32‐beta transcript and corresponds with previous reports demonstrating that IL32‐beta is not secreted from the cell like other canonical interleukins and preferentially localizes to the mitochondria in breast cancer cells. Additionally, expression of the beta‐transcript could be suppressed when CSC‐enriched cells were treated with the BET‐bromodomain inhibitor JQ1. Because of this phenomenon, we sought to determine the effects of suppressing IL32 in the EpCAM‐/CD49f‐ enriched cell line SUM159PT via siRNA‐mediated knockdown and subsequent RNAseq differential expression analysis. From our results, we determined that transcripts involved in extracellular matrix (ECM) organization and collagen/integrin interaction were preferentially affected by IL32 silencing. Additionally, IL32 suppression decreased the invasiveness of SUM159PT based on an ECM‐matrix cell invasion assay. Collectively, our results reflect the notion that differential IL32 expression by promoter hypomethylation in breast CSCs plays a role in ECM remodeling for purposes of breast cancer cell invasion and metastasis.
Aim At a regional scale, across southern Africa, woody thickening of savannas is becoming increasingly widespread. Using coupled vegetation and faunal responses (ants), we explore whether major ...changes in woody cover in savannas represent an increase in the density of savanna trees (C4 grass layer remains intact) or a ‘regime shift’ in system state from savanna to thicket (=dry forest) where broad‐leaved, forest‐associated trees shade out C4 grasses. Location Hluhluwe Game Reserve, South Africa. Methods We sampled paired open (low woody cover) and closed (high cover that have undergone an increase in tree density) sites. Vegetation was sampled using belt transects, and a combination of pitfall trapping and Winkler sampling was used for ants. Results Closed habitats did not simply contain a higher density of woody savanna species, but differed significantly in structure, functional composition (high prevalence of broad‐leaved trees, discontinuous C4 grasses) and system properties (e.g. low flammability). Ant assemblage composition reflected this difference in habitat. The trophic structure of ant assemblages in the two habitats revealed a functional shift with much higher abundances of predatory species in the closed habitat. Main conclusions The predominance of species with forest‐associated traits and concomitant reduction of C4 grasses in closed sites indicate that vegetation has undergone a shift in fundamental system state (to thicket), rather than simply savanna thickening. This biome shift has cascading functional consequences and implications for biodiversity conservation. The potential loss of many specialist savanna plant species is especially concerning, given the spatial extent and speed of this vegetation switch. Although it is not clear how easily the habitat switch can be reversed and how stable the thicket habitats are, it is likely in the not‐too‐distant future that conservation managers will be forced to make decisions on whether to actively maintain savannas.
Objective:
Differences between adolescent self-reported and parent-reported emotional and behavioural difficulties may influence psychiatric epidemiological research. This study examined concordance ...between adolescents and their parents about mental health symptoms using the Strengths and Difficulties Questionnaire.
Methods:
The study comprised a randomly selected, nationally representative sample of adolescents aged 11–17 years who participated in the Second Australian Child and Adolescent Survey of Mental Health and Wellbeing (N = 2967). Matched adolescent and parent responses across the five Strengths and Difficulties Questionnaire subscales (emotional problems, hyperactivity, peer problems, conduct problems and prosocial behaviour), as well as total difficulties and total impact scores were examined to estimate concordance. Concordance patterns were analysed by sex, after stratifying the sample by age group (younger adolescents: 11–14 years; older adolescents: 15–17 years).
Results:
Concordance was 86.7% for total difficulties, 77.5% for total impact and ranged from 82.4% to 94.3% across the five Strengths and Difficulties Questionnaire subscales. There were no differences in concordance between sexes on the total difficulties score. Older females were more likely to disagree with their parents about emotional problems compared to males of the same age. Younger males were more likely to disagree with their parents compared to same-aged females about peer problems, hyperactivity, conduct problems and prosocial skills, as well as the impact of their problems. Older males were more likely to disagree with their parents about their prosocial skills compared to older females.
Conclusion:
Overall, concordance between adolescents and parents on the Strengths and Difficulties Questionnaire was largely driven by the high proportion of respondents who reported having no problems. Discordance on a subscale increased as the prevalence of problems in a sex and age demographic subgroup increased. These findings highlight the need for a multi-informant approach to detect emotional and behavioural difficulties in adolescents, particularly when assessing the impact of symptoms, as this subscale had the lowest concordance.
Understanding the mechanisms that control processing of the amyloid precursor protein (APP) to produce amyloid-β (Aβ) peptide represents a key area of Alzheimer's disease research. Here, we show that ...siRNA-mediated loss of calsyntenin-1 in cultured neurons alters APP processing to increase production of Aβ. We also show that calsyntenin-1 is reduced in Alzheimer's disease brains and that the extent of this reduction correlates with increased Aβ levels. Calsyntenin-1 is a ligand for kinesin-1 light chains and APP is transported through axons on kinesin-1 molecular motors. Defects in axonal transport are an early pathological feature in Alzheimer's disease and defective APP transport is known to increase Aβ production. We show that calsyntenin-1 and APP are co-transported through axons and that siRNA-induced loss of calsyntenin-1 markedly disrupts axonal transport of APP. Thus, perturbation to axonal transport of APP on calsyntenin-1 containing carriers induces alterations to APP processing that increase production of Aβ. Together, our findings suggest that disruption of calsyntenin-1-associated axonal transport of APP is a pathogenic mechanism in Alzheimer's disease.
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