DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all ...rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DETQ reversed the locomotor depression caused by a low dose of reserpine. DETQ also acted synergistically with L-DOPA to reverse the strong hypokinesia seen with a higher dose of reserpine. These results indicate potential as both monotherapy and adjunct treatment in Parkinson's disease. DETQ markedly increased release of both acetylcholine and histamine in the prefrontal cortex, and increased levels of histamine metabolites in the striatum. In the hippocampus, the combination of DETQ and the cholinesterase inhibitor rivastigmine increased ACh to a greater degree than either agent alone. DETQ also increased phosphorylation of the AMPA receptor (GluR1) and the transcription factor CREB in the striatum, consistent with enhanced synaptic plasticity. In the Y-maze, DETQ increased arm entries but (unlike a D1 agonist) did not reduce spontaneous alternation between arms at high doses. DETQ enhanced wakefulness in EEG studies in hD1 mice and decreased immobility in the forced-swim test, a model for antidepressant-like activity. In rhesus monkeys, DETQ increased spontaneous eye-blink rate, a measure that is known to be depressed in Parkinson's disease. Together, these results provide support for potential utility of D1 potentiators in the treatment of several neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, cognitive impairment in schizophrenia, and major depressive disorder.
•The dopamine D1 potentiator DETQ was tested in humanized D1 mice and rhesus monkeys.•Actions of DETQ were dependent on endogenous dopaminergic tone.•DETQ displayed a behavioral profile consistent with central D1 receptor activation.•Neurochemical actions of DETQ support potential pro-cognitive effects.•D1 potentiators show promise for Parkinson's disease and other CNS disorders.
This study sought to examine the efficacy and safety of 3 novel devices to recanalize coronary chronic total occlusions (CTOs).
Successful percutaneous coronary intervention (PCI) of CTOs improves ...clinical outcome in appropriately selected patients. CTO PCI success, however, remains suboptimal.
A new crossing catheter and re-entry system was evaluated in a prospective, multicenter, single-arm trial of CTO lesions refractory to standard PCI techniques. The primary efficacy endpoint was the frequency of true lumen guidewire placement distal to the CTO (technical success).
Enrollment included 147 patients with 150 CTOs. The mean lesion length was 41 ± 17 mm. A crossing catheter crossed 56 lesions into the distal true lumen, and a re-entry catheter facilitated tapered-wire cannulation of the distal lumen in 59 CTOs initially crossed subintimally (77% technical success). Success in the first 75 CTOs was 67%, rising to 87% in the last 75 CTOs. Mean fluoroscopy and procedure times were 45 ± 16 min and 90 ± 12 min, respectively, each significantly shorter than in historical controls (p < 0.0001 for both). Coronary perforation occurred in 14 cases (9.3%), requiring treatment in 3 cases (prolonged balloon inflation, with additional coil embolization in 1 case). No tamponade or hemodynamic instability occurred. Six patients had periprocedural non-ST-segment elevation myocardial infarction. No emergency surgery, ST-segment elevation myocardial infarction, or cardiac reintervention occurred. Two deaths occurred within 30 days, neither as a direct result of the procedure. The 30-day major adverse cardiac event rate was 4.8%.
In CTOs failing standard techniques, use of a new crossing and re-entry system results in a high success rate without increasing complications.
Spirit began operations in Gusev Crater in January 2004 and has returned data on three seasons of dust devil (DD) activity. Total DDs observed were 533 in season one, 101 in season two, and 127 in ...season three. Their general characteristics are the same within factors of 2 among the seasons, with median diameters of 19 m in season one, 24 m in season two, and 39 m in season three, and dust flux values for individual vortices ranging from 4.0 × 10−9 to 4.6 × 10−4 kg m−2 s−1 in season one, 5.2 × 10−7 to 6.2 × 10−5 kg m−2 s−1 in season two, and 1.5 × 10−7 to 1.6 × 10−4 kg m−2 s−1 in season three. All three seasons were initiated with the onset of southern Martian spring within 14 sols of the same Ls (181°) and their frequency increased to the period corresponding to late southern spring. The occurrences decreased monotonically in seasons one and three but apparently ended abruptly in season two when a large dust storm occurred; although the dusty atmosphere might have precluded the detection of active DDs, the abrupt cessation could result from conditions such as thermal stability of the atmosphere due to the presence of dust which could halt DD formation. Dust devils can contribute significant quantities of dust to the atmosphere, although it is unclear as to whether this dust stays locally or is injected into higher‐altitude winds and is distributed elsewhere. In the three DD seasons observed through Spirit, DDs in Gusev Crater injected a minimum average of ∼18 × 106 kg of material into the atmosphere each season.
Abstract Aim Animals couple habitats by three types of movement: dispersal, migration, and foraging, which dynamically link populations, communities, and ecosystems. Across these types, movement ...distances tend to correlate with each other, potentially reflecting allometric scaling with body mass, but ecological and evolutionary species' traits may constrain movement distances and weaken these correlations. Here, we investigate multivariate “movement profiles” to better understand patterns in movement across movement types, with the aim of improving predictions in ecology from populations to ecosystems. Location Global. Time period 1945–2019. Major taxa studied Vertebrates. Methods We synthesized distances of all three movement types (dispersal, migration, and foraging) across 300+ vertebrate species and investigated how the relationships between movement types and body mass were modified by evolutionary history and trophic guild. Results We found that the strength of relationships between movement types and body mass varied among taxa and trophic guilds, for example, strongly positive for mammals but weak for birds, or positive across trophic guilds for foraging and dispersal but not migration. Notably, movement profiles interacted with the effects of shared evolutionary history and trophic guild to diminish covariance between movement types. Main conclusions Overall, we find that movement types with distinct ecological consequences (foraging, migration) are often correlated, although some species seem able to overcome biomechanical, evolutionary, and metabolic constraints by reducing correlations among movement types. This integrative assessment of movement can improve ecological prediction by allowing estimation of unobserved movement distances for parameterization of models based on estimation of other movement types.
Abstract Marine protected areas (MPAs) are increasingly common worldwide, typically restricting fishing activities. However, MPAs may also limit scientific surveys that impact benthic habitat. We ...combine a historical data degradation approach and simulation to investigate the effects on population indices of excluding surveys from MPAs. Our approach quantifies losses in precision, inter-annual accuracy, trend accuracy, and power to detect trends, as well as correlates of these effects. We apply this approach to a proposed MPA network off western Canada, examining 43 groundfish species observed by four surveys. Survey exclusion particularly impacted less precise indices, species well-represented in MPAs, and those whose density shifted in or out of MPAs. Redistributing survey effort outside MPAs consistently improved precision but not accuracy or trend detection—sometimes making estimates more precise about the ‘wrong’ index. While these changes may not qualitatively alter stock assessment for many species, in some cases, ∼30 percentage point reductions in power to detect simulated 50% population declines suggest meaningful impacts are possible. If survey restrictions continue expanding, index integrity could further degrade, eventually compromising the management of exploited populations. Regulating surveys within MPA boundaries therefore requires careful consideration to balance MPA objectives with the need for reliable monitoring.
Species distribution models (SDMs) have been widely used to project terrestrial species' responses to climate change and are increasingly being used for similar objectives in the marine realm. These ...projections are critically needed to develop strategies for resource management and the conservation of marine ecosystems. SDMs are a powerful and necessary tool; however, they are subject to many sources of uncertainty, both quantifiable and unquantifiable. To ensure that SDM projections are informative for management and conservation decisions, sources of uncertainty must be considered and properly addressed. Here we provide ten overarching guidelines that will aid researchers to identify, minimize, and account for uncertainty through the entire model development process, from the formation of a study question to the presentation of results. These guidelines focus on correlative models and were developed at an international workshop attended by over 50 researchers and practitioners. Although our guidelines are broadly applicable across biological realms, we provide particular focus to the challenges and uncertainties associated with projecting the impacts of climate change on marine species and ecosystems.
Definitions: Spatial insurance: Improvement of maintenance of species diversity and ecosystem functioning in heterogeneous environments because species can track their optimal environments by ...dispersing between habitat patches. Betweenness centrality: Value of an individual habitat patch in adding to the connectivity of the metacommunity by being a stepping-stone for dispersing individuals. Robustness: The proportion of patches that must be removed to change each response variable beyond a given threshold. Question: In fragmented landscapes, how do spatial patterns of habitat loss affect the robustness of the insurance effects on biodiversity? Does the underlying pattern of habitat connectivity in metacommunities play a role in maintaining biodiversity and ecosystem function in the face of habitat loss? Mathematical method: Using a spatially explicit version of a resource competition metacommunity model, we simulated habitat loss in metacommunity networks composed of habitat patches connected by links for dispersal. Key assumptions: Species differ in their environmental preferences. Local environmental conditions fluctuate asynchronously so that species must disperse in order to persist and maintain productivity. Habitat patches are lost sequentially, resulting in gradual fragmentation of the metacommunity. Results: Habitat loss reduces the amount of spatial insurance conferred by the habitat structure on biodiversity by preventing species from dispersing to environmentally suitable areas. The robustness of metacommunities to habitat loss decreases dramatically when the patches with high betweenness centrality are lost. Metacommunities are generally most robust when the pattern of habitat connectivity is random and when the habitat patches that are lost have low betweenness centrality.
Purpose.
This study was designed (1) to examine the effects of a 10,000 steps·d−1 exercise prescription on sedentary, overweight/obese adults, and (2) to examine the effects of adherence on body ...composition and cardiovascular risk factors.
Methods.
Fifty-six overweight/obese adults participated in the study. Body composition and cardiovascular risk factors were determined at baseline, 20 weeks, and 36 weeks. Adherence was defined as averaging ≥ 9500 steps·d−1 from week 4 to week 36.
Results.
38 participants (68%) wore pedometers daily for 36 weeks and were available for posttesting. Significant improvements were noted in mean values for walking volume (3994 steps·d−1), body weight (–2.4 kg), body mass index (–0.8 kg·m−2), percentage body fat (–1.9%), fat mass (–2.7 kg), waist circumference (–1.8 cm), hip circumference (–1.9 cm) and high-density lipoprotein (3 mg/dl). The adherers had large improvements in body composition measures, whereas the nonadherers showed little or no change in these variables.
Discussion.
A 10,000 steps·d−1 exercise prescription resulted in weight loss over 36 weeks in previously sedentary, overweight/obese adults. Adherence to the step goal had a marked effect on the outcome.
The Northwest Atlantic cod stocks collapsed in the early 1990s and have yet to recover, despite the subsequent establishment of a continuing fishing moratorium. Efforts to understand the collapse and ...lack of recovery have so far focused mainly on the dynamics of commercially harvested species. Here, we use data from a 33-year scientific trawl survey to determine to which degree the signatures of the collapse and recovery of the cod are apparent in the spatial and temporal dynamics of the broader groundfish community. Over this 33-year period, the groundfish community experienced four phases of change: (i) a period of rapid, synchronous biomass collapse in most species, (ii) followed by a regime shift in community composition with a concomitant loss of functional diversity, (iii) followed in turn by periods of slow compositional recovery, and (iv) slow biomass growth. Our results demonstrate how a community-wide perspective can reveal new aspects of the dynamics of collapse and recovery unavailable from the analysis of individual species or a combination of a small number of species. Overall, we found evidence that such community-level signals should be useful for designing more effective management strategies to ensure the persistence of exploited marine ecosystems.
Geomorphic features such as drifts, sediment waves and channels have been documented in the Upper Cretaceous of north‐west Europe. These features are interpreted to result from bottom currents and ...have been used to refine chalk depositional models and quantify palaeocirculation patterns. Chalk was first deposited as calcareous nannofossil ooze and geomorphic features are the result of sediment reworking after deposition. There is limited knowledge on the processes that govern nannofossil ooze mobility, thus forcing uncertainty onto numerical models based on sedimentological observations. This article provides an extensive view of the erosional and depositional behaviour of calcareous nannofossil ooze based on experimental work using annular flumes. A fundamental observation of this study is the significant decrease of nannofossil ooze mobility with decreasing bed porosity. Erosion characteristics, labelled as erosion types, vary with total bed porosity (φ) and applied shear stress (τ0). High‐porosity ooze (φ >80%) is characterized by constant erosion rates (Em). At φ <77%, however, erosion characteristics showed greater variance. Surface erosion was typically followed by transitional erosion (with asymptotically decreasing Em), and stages of erosion with constant, and exponential erosion rates. The estimated erosion thresholds (τc) vary from ca 0·05 to 0·08 Pa for the onset of surface erosion and up to ca 0·19 Pa for the onset of constant erosion (φ of 60 to 85%). Variability of deposition thresholds (τcd) from ca 0·04 to 0·13 Pa reflects the influence of variable suspended sediment concentration and τ0 on settling particle size due to the identified potential for chalk ooze aggregation and flocculation. Additionally, deposition thresholds seem to be affected by the size of eroded aggregates whose size correlates with bed porosity. Lastly, slow sediment transport without resuspension occurred in high‐porosity ooze as surface creep, forming low‐relief sedimentary features resembling ripples. This process represents a previously undescribed mode of fine‐grained nannofossil ooze transport.
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