Abildgaardbering4699

Finally, we show that the ∼9-My cycle faded during the Pliensbachian, which could either reflect major paleoenvironmental disturbances or a chaotic transition affecting this cycle.An appealing definition of the term "molecule" arises from consideration of the nature of fluorescence, with discrete molecular entities emitting a stream of single photons. We address the question of how large a molecular object may become by growing deterministic aggregates from single conjugated polymer chains. Even particles containing dozens of individual chains still behave as single quantum emitters due to efficient excitation energy transfer, whereas the brightness is raised due to the increased absorption cross-section of the suprastructure. Excitation energy can delocalize between individual polymer chromophores in these aggregates by both coherent and incoherent coupling, which are differentiated by their distinct spectroscopic fingerprints. Coherent coupling is identified by a 10-fold increase in excited-state lifetime and a corresponding spectral red shift. Exciton quenching due to incoherent FRET becomes more significant as aggregate size increases, resulting in single-aggregate emission characterized by strong blinking. This mesoscale approach allows us to identify intermolecular interactions which do not exist in isolated chains and are inaccessible in bulk films where they are present but masked by disorder.Neuronal responses to sensory stimuli are not only driven by feedforward sensory pathways but also depend upon intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation. To understand how these factors together regulate cortical dynamics, we recorded simultaneously spontaneous and somatosensory-evoked multiunit activity from primary somatosensory cortex and from the locus coeruleus (LC) (the neuromodulatory nucleus releasing norepinephrine) in urethane-anesthetized rats. We found that bursts of ipsilateral-LC firing preceded by few tens of milliseconds increases of cortical excitability, and that the 1- to 10-Hz rhythmicity of LC discharge appeared to increase the power of delta-band (1-4 Hz) cortical synchronization. To investigate quantitatively how LC firing might causally influence spontaneous and stimulus-driven cortical dynamics, we then constructed and fitted to these data a model describing the dynamical interaction of stimulus drive, ongoing synchronized cortical activity, and noradrenergic neuromodulation. The model proposes a coupling between LC and cortex that can amplify delta-range cortical fluctuations, and shows how suitably timed phasic LC bursts can lead to enhanced cortical responses to weaker stimuli and increased temporal precision of cortical stimulus-evoked responses. Thus, the temporal structure of noradrenergic modulation may selectively and dynamically enhance or attenuate cortical responses to stimuli. Finally, using the model prediction of single-trial cortical stimulus-evoked responses to discount single-trial state-dependent variability increased by ∼70% the sensory information extracted from cortical responses. This suggests that downstream circuits may extract information more effectively after estimating the state of the circuit transmitting the sensory message.Advances in nanomedicine are providing sophisticated functions to precisely control the behavior of nanoscale drugs and diagnostics. Strategies that coopt protease activity as molecular triggers are increasingly important in nanoparticle design, yet the pharmacokinetics of these systems are challenging to understand without a quantitative framework to reveal nonintuitive associations. We describe a multicompartment mathematical model to predict strategies for ultrasensitive detection of cancer using synthetic biomarkers, a class of activity-based probes that amplify cancer-derived signals into urine as a noninvasive diagnostic. Using a model formulation made of a PEG core conjugated with protease-cleavable peptides, we explore a vast design space and identify guidelines for increasing sensitivity that depend on critical parameters such as enzyme kinetics, dosage, and probe stability. According to this model, synthetic biomarkers that circulate in stealth but then activate at sites of disease have the theoretical capacity to discriminate tumors as small as 5 mm in diameter-a threshold sensitivity that is otherwise challenging for medical imaging and blood biomarkers to achieve. This model may be adapted to describe the behavior of additional activity-based approaches to allow cross-platform comparisons, and to predict allometric scaling across species.Many biological and physiological processes depend upon directed migration of cells, which is typically mediated by chemical or physical gradients or by signal relay. Here we show that cells can be guided in a single preferred direction based solely on local asymmetries in nano/microtopography on subcellular scales. These asymmetries can be repeated, and thereby provide directional guidance, over arbitrarily large areas. The direction and strength of the guidance is sensitive to the details of the nano/microtopography, suggesting that this phenomenon plays a context-dependent role in vivo. We demonstrate that appropriate asymmetric nano/microtopography can unidirectionally bias internal actin polymerization waves and that cells move with the same preferred direction as these waves. This phenomenon is observed both for the pseudopod-dominated migration of the amoeboid Dictyostelium discoideum and for the lamellipod-driven migration of human neutrophils. The conservation of this mechanism across cell types and the asymmetric shape of many natural scaffolds suggest that actin-wave-based guidance is important in biology and physiology.What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.Federal lands across the conterminous United States (CONUS) account for 23.5% of the CONUS terrestrial area but have received no systematic studies on their ecosystem carbon (C) dynamics and contribution to the national C budgets. The methodology for US Congress-mandated national biological C sequestration potential assessment was used to evaluate ecosystem C dynamics in CONUS federal lands at present and in the future under three Intergovernmental Panel on Climate Change Special Report on Emission Scenarios (IPCC SRES) A1B, A2, and B1. The total ecosystem C stock was estimated as 11,613 Tg C in 2005 and projected to be 13,965 Tg C in 2050, an average increase of 19.4% from the baseline. The projected annual C sequestration rate (in kilograms of carbon per hectare per year) from 2006 to 2050 would be sinks of 620 and 228 for forests and grasslands, respectively, and C sources of 13 for shrublands. The federal lands' contribution to the national ecosystem C budget could decrease from 23.3% in 2005 to 20.8% in 2050. The C sequestration potential in the future depends not only on the footprint of individual ecosystems but also on each federal agency's land use and management. The results presented here update our current knowledge about the baseline ecosystem C stock and sequestration potential of federal lands, which would be useful for federal agencies to decide management practices to achieve the national greenhouse gas (GHG) mitigation goal.Single cardiomyocytes contain myofibrils that harbor the sarcomere-based contractile machinery of the myocardium. selleck Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart activity. However, their fetal-like misalignment of myofibrils limits their usefulness for modeling contractile activity. We analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered hPSC-CMs. Single hPSC-CMs were cultured on polyacrylamide substrates of physiological stiffness (10 kPa), and Matrigel micropatterns were used to generate physiological shapes (2,000-µm(2) rectangles with lengthwidth aspect ratios of 51-71) and a mature alignment of myofibrils. Translation of sarcomere shortening to mechanical output was highest in 71 hPSC-CMs. Increased substrate stiffness and applied overstretch induced myofibril defects in 71 hPSC-CMs and decreased mechanical output. Inhibitors of nonmuscle myosin activity repressed the assembly of myofibrils, showing that subcellular tension drives the improved contractile activity in these engineered hPSC-CMs. Other factors associated with improved contractility were axially directed calcium flow, systematic mitochondrial distribution, more mature electrophysiology, and evidence of transverse-tubule formation. These findings support the potential of these engineered hPSC-CMs as powerful models for studying myocardial contractility at the cellular level.Leiomodin (Lmod) is a class of potent tandem-G-actin-binding nucleators in muscle cells. Lmod mutations, deletion, or instability are linked to lethal nemaline myopathy. However, the lack of high-resolution structures of Lmod nucleators in action severely hampered our understanding of their essential cellular functions. Here we report the crystal structure of the actin-Lmod2162-495 nucleus. The structure contains two actin subunits connected by one Lmod2162-495 molecule in a non-filament-like conformation. Complementary functional studies suggest that the binding of Lmod2 stimulates ATP hydrolysis and accelerates actin nucleation and polymerization. The high level of conservation among Lmod proteins in sequence and functions suggests that the mechanistic insights of human Lmod2 uncovered here may aid in a molecular understanding of other Lmod proteins. Furthermore, our structural and mechanistic studies unraveled a previously unrecognized level of regulation in mammalian signal transduction mediated by certain tandem-G-actin-binding nucleators.