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Associations between the developmental trajectories of visual scanning and disengagement of attention in infants.

The relation between the developmental trajectories of visual scanning and disengagement of attention and gaze were examined throughout early infancy. A sample of 10 infants carried out a scanning and a disengagement task with the same visual stimuli six times between 6 and 26 weeks of age. Frequency and latency measures were analyzed using multivariate multilevel models and Monte Carlo analyses. The results suggest that the ability to scan a face or an abstract stimulus evolves slightly earlier than the ability to shift gaze to a newly appeared target in the periphery. This is consistent with the account that the parvocellular stream becomes functional slightly before the magnocellular stream. The study revealed no indications of a positive association between the development of scanning and disengagement on the level of the individual infant. Scanning and disengagement change scores contrasted more with one another than could be expected on the basis of chance. This implies that the magnocellular and the parvocellular stream develop rather independently up to the age of 26 weeks.

Attention↗

A novel real-time system to monitor cell aggregation and trajectories in rotating wall vessel bioreactors.

Rotating wall vessel bioreactors (RWVs) constitute dynamic suspension culture venues for tissue engineering. Quantitative real-time assessment of the kinetics of cell-cell aggregation in RWVs can yield mechanistic information about the initial steps leading to the assembly of individual cells into tissue-like constructs. In our imaging system, fluorescently labeled cells suspended in a HARV-type RWV were irradiated by a laser-beam. Emission was recorded by a camera mounted at 90 degrees to the excitation plane. Using macro lenses, the system identified approximately 5 microm particles from a 5 cm working distance, distinguished aggregated 20 microm microspheres from larger (45 and 90 microm) microspheres, and plotted local trajectories of microspheres and cells. Sizes of PC12 cells assessed by our system matched conventional measurements. We validated the system's ability to follow HepG2 and PC12 aggregation in real time over 24h of RWV culture. Taken together, our system provides the means to measure and analyze in real time the processes that lead to the 3D tissue-like assembly of diverse cell types into spheroids. Future studies include development of intelligent feedback algorithms, allowing automatic control over RWV rotational speed required to maintain aggregating cells and nascent tissue in continual free fall.

Animals↗

Effect of electrostatic, hydrodynamic, and Brownian forces on particle trajectories and sieving in normal flow filtration.

Particle deposition and fouling are critical factors governing the performance of microfiltration and ultrafiltration systems. Particle trajectories were evaluated by numerical integration of the Langevin equation, accounting for the combined effects of electrostatic repulsion, enhanced hydrodynamic drag, and Brownian diffusion. In the absence of Brownian forces, particles are unable to enter the membrane pores unless the drag associated with the filtration velocity can overcome the electrostatic repulsion. Brownian forces significantly alter this behavior, allowing some particles to enter the pore even at low filtration velocities. The average particle transmission, evaluated from the probability of having a particle enter the pore, increases with increasing filtration velocity due to the greater hydrodynamic drag force on the particle. These results provide important insights into particle behavior in membrane systems.

Journal Article↗

Scoring binding affinity of multiple ligands using implicit solvent and a single molecular dynamics trajectory: application to influenza neuraminidase.

We explore a perturbative approach to calculation of binding free energy of multiple ligands, based on a single molecular dynamics simulation of a reference ligand-receptor complex and analysis via a hybrid force field/continuum model potential. The methodology is applied to prediction of relative binding free energies of 10 Influenza neuraminidase inhibitors, using Poisson-Boltzmann and generalised Born models of implicit solvent. These single-step MM-PB/SA and MM-GB/SA approaches predict the experimentally most potent ligand as first- or second-ranked according to total binding free energy. Ranking of inhibitors displays only moderate sensitivity to the choice of reference trajectory and ligand partial charge scheme. When ranked according to total electrostatic binding free energy, correlation with experiment improves (r(2) of 0.72); this may be related to underestimated first solvation shell effects by the implicit water models. Therefore, to increase the generality of this single-step approach as part of a potential computational compound optimisation strategy, further development of the treatment of short-range solvent interactions is warranted.

Binding Sites↗

Feature point tracking and trajectory analysis for video imaging in cell biology.

This paper presents a computationally efficient, two-dimensional, feature point tracking algorithm for the automated detection and quantitative analysis of particle trajectories as recorded by video imaging in cell biology. The tracking process requires no a priori mathematical modeling of the motion, it is self-initializing, it discriminates spurious detections, and it can handle temporary occlusion as well as particle appearance and disappearance from the image region. The efficiency of the algorithm is validated on synthetic video data where it is compared to existing methods and its accuracy and precision are assessed for a wide range of signal-to-noise ratios. The algorithm is well suited for video imaging in cell biology relying on low-intensity fluorescence microscopy. Its applicability is demonstrated in three case studies involving transport of low-density lipoproteins in endosomes, motion of fluorescently labeled Adenovirus-2 particles along microtubules, and tracking of quantum dots on the plasma membrane of live cells. The present automated tracking process enables the quantification of dispersive processes in cell biology using techniques such as moment scaling spectra.

Adenoviridae↗

Behavioral trajectories as predictors in event history analysis: male calling behavior forecasts medfly longevity.

A recent study on wild male Mediterranean fruit flies [Papadopoulos, N.T., Katsoyannos, B.I., Kouloussis, N.A., Carey, J.R., Müller, H.-G., Zhang, Y., 2004. High sexual signalling rates of young individuals predict extended life span in male Mediterranean fruit flies. Oecologia 138, 127-134] provided evidence that intense sexual signalling (calling behavior) is associated with longer life span. We demonstrate here an approach based on functional data analysis methodology for predicting individual remaining longevity and the distribution of remaining lifetime from individual behavioral trajectories. A key methodological concept is the time evolution of mean functions and eigenfunctions. This methodology is applied to the event history of calling behavior of male medflies. The results demonstrate complex relationships between male calling behavior and subsequent longevity that complement previous biodemographic analyses of these data. A high level of recent calling activity is found to be associated with increased remaining lifetime for an individual male fly, while calling activity at early ages plays no role for remaining longevity.

Animals↗

Local inhibition guides the trajectory of early longitudinal tracts in the developing chick brain.

During development of the chick central nervous system, the trajectories of the descending medial and lateral longitudinal fascicles (MLF and LLF) are pioneered by axons originating from the interstitial nucleus of Cajal (INC) and the mesencephalic trigeminal nucleus (MTN), respectively. Both tracts cross rhombomere 1 at two specific locations in the basal plate. In this study, we have investigated the molecular properties of these crossing points and find that they are permissive regions situated in an otherwise inhibitory boundary region. We show that the dorsal part of rhombomere 1 is inhibitory for the growth of both MTN and INC axons. Ventrally, MLF and LLF axons are repelled from the midline by Slit proteins. Our results reveal the existence of a new repulsive/inhibitory mechanism for axons in the alar plate in addition to the ventral repulsion by Slit proteins. This suggests a model where MLF and LLF axons are channeled longitudinally within the neural tube by both dorsal and ventral constraints.

Animals↗

Influence of visual constraints in the trajectory formation of grasping movements.

The main objective of the present study is to show that the visual context can influence the trajectory formation of grasping movements. We asked participants to reach and grasp a cylinder disposed at three different positions: -20 degrees , 0 degrees and 20 degrees of eccentricity with respect to the midsagittal axis. Grasping movements were performed in a direct and in an indirect visual feedback condition (i.e., controlled through a vertical video display). Results revealed that for grasping movements directed toward objects located at -20 degrees and 0 degrees , path curvatures of the wrist, the thumb and the index finger were significantly straighter in the indirect visual feedback condition. However, no significant difference concerning hand path curvature was observed when the movement was directed toward the object located at 20 degrees . This suggests that grasping movements controlled through a remote visual feedback tend to be planned in extrinsic space and that the effect of the visual context on movement planning appears to be not isotropic over the workspace.

Adolescent↗

Chemorepulsion and cell adhesion molecules in patterning initial trajectories of sensory axons.

Research in the past decade has advanced our knowledge of the key role that diffusible cues play in axonal guidance during development. In higher vertebrates, dorsal root ganglion (DRG) neurons extend axons centrally to the spinal cord through the dorsal root entry zone and peripherally to muscle and skin targets. In this review, we focus on the role of proximate "non-target" tissues in the initial stages of DRG axonal growth. In the early stages of development, "non-target" tissues including the dermamyotome, the notochord, and the ventral spinal cord exert chemorepulsion for DRG axons. We describe how semaphorin 3A, chondroitin sulfate proteogrycans, and cell adhesion molecules participate in chemorepulsion and the way they provide spatio-temporal specificity to chemorepulsion. Axon chemorepulsion may act not only to shape DRG axonal trajectories but it also affects a variety of other axonal projections in the peripheral and central nervous system.

Axons↗

Time on my side? Life course trajectories of poverty and health.

This study examines the relationship between poverty and health in time. Following the argument that time is significant for shaping the experience of being poor or not poor and growing evidence of heterogeneity in long-term patterns of poverty, we investigate whether different kinds of poverty have distinct consequences for long-term health. Using data from the 1968-1996 annual waves of the United States Panel Study of Income Dynamics Data, we estimate a general growth mixture model to assess the relationship between the longitudinal courses of poverty and health. The model allows us to first estimate latent poverty classes in the data and then determine their effects on latent self-rated health. Four types of long-term poverty patterns characterized as stable nonpoor, exiting poverty, entering poverty and stable poor were evident in the data. These different kinds of poverty affected self-rated health trajectories in distinct ways, but worked in concert with age, education and race to create gaps in initial health status that were constant over time.

Adult↗

The social trajectory of illness: autism in the ultraorthodox community in Israel.

Severe or chronic illness-related events present patients and their family members with a physically and socially changed reality. In analyzing 30 open-ended interviews of ultraorthodox Jewish Israeli mothers of children with autism, this paper addresses the general question of one childhood disorder's social trajectory and examines in particular mothers' efforts to promote their children's re-inclusion into the community. The illness narratives reveal the mothers' role as mediators between the child and the community, educating the child in religious praxis on the one hand and striving to bend social norms regarding this praxis to permit inclusion on the other. Despite these daily efforts, the ultraorthodox community challenges these children's status, and mothers turn to religious discourse to establish the status of the child with autism as an able Jewish individual. In utilizing spiritual discourse in daily activities, mothers only employ those cultural elements that advance the child's integration, thus further constructing small changes in religious themes. The findings highlight not only the mothers' role as mediators, but also their potential ability to set in motion processes of change.

Autistic Disorder↗

The trajectory of biomarkers in symptom management for older adults with cancer.

OBJECTIVES: To provide an overview of the trajectory of select biomarkers and their potential usefulness in symptom management in the older individual with cancer. DATA SOURCES: Empirical data and literature review. CONCLUSION: Biomarkers offer significant opportunities to understand the biological impact of cancer and its treatment on older adults whose response is likely different from their younger counterparts. Large well-designed multi-site clinical trials with adequate numbers and power are necessary to create evidenced-based practice changes. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to understand the science and implications of biomarkers to develop interventions in response to the mechanisms of symptoms experienced by older adults with cancer.

Adrenal Cortex↗

Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.

6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the Mg(2+)-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). The reaction follows a bi-bi mechanism with ATP as the first substrate and AMP and HP pyrophosphate (HPPP) as the two products. HPPK is a key enzyme in the folate biosynthetic pathway and is essential for microorganisms but absent from mammals. For the HPPK-catalyzed pyrophosphoryl transfer, a reaction coordinate is constructed on the basis of the thermodynamic and transient kinetic data we reported previously, and the reaction trajectory is mapped out with five three-dimensional structures of the enzyme at various liganded states. The five structures are apo-HPPK (ligand-free enzyme), HPPK.MgATP(analog) (binary complex of HPPK with its first substrate) and HPPK.MgATP(analog).HP (ternary complex of HPPK with both substrates), which we reported previously, and HPPK.AMP.HPPP (ternary complex of HPPK with both product molecules) and HPPK.HPPP (binary complex of HPPK with one product), which we present in this study.

Adenosine Monophosphate↗

Subjective cognition trajectories, Alzheimer biomarkers, and incident mild cognitive impairment.

BACKGROUND: Subjective cognitive decline is common in older adults and may represent an early clinical signal along the Alzheimer's disease continuum. The clinical relevance of longitudinal changes in subjective cognitive decline remains unclear. OBJECTIVES: To determine whether trajectories of self- or study partner-reported cognitive decline predict progression to mild cognitive impairment and reflect Alzheimer's disease-specific biological patterns. DESIGN, SETTING, PARTICIPANTS: Data were pooled from two observational cohorts. Cognitively unimpaired participants with baseline amyloid status, repeated assessments of subjective cognitive decline, and clinical follow-up were included. The study included 770 participants with a median follow-up of 5.0 years (interquartile range 4.0-7.0). MEASUREMENTS: Subjective cognitive decline was assessed using the Everyday Cognition questionnaire completed by participants and study partners. Linear mixed-effects models examined associations with amyloid status and progression to mild cognitive impairment. Cox proportional hazards models tested whether one-year changes predicted progression. RESULTS: Amyloid-positive participants and those who progressed to mild cognitive impairment showed steeper increases in self- and study partner-reported cognitive difficulties over time. Among amyloid-positive participants, only increases in study partner-report differentiated progressors from non-progressors. One-year increases in study partner-report predicted a higher risk of mild cognitive impairment compared with unchanged scores (hazard ratio 3.24; 95% confidence interval 1.73-6.07]), with effects confined to amyloid-positive participants. CONCLUSIONS: Short-term increases in study partner-reported cognitive difficulties identify amyloid-positive cognitively unimpaired older adults at increased risk of near-term progression to mild cognitive impairment. Longitudinal monitoring using study partner reports may provide a low-burden and clinically relevant approach for early risk stratification and surveillance in aging populations.

Humans↗

The shape of things to come: using models with physiological structure to predict mortality trajectories.

If mortality rate is viewed as the outcome of processes of behavior, growth and reproduction, then it should be possible to predict mortality rate as a result of those processes. We provide two examples of how this may be done. In the first, we use the method of linear chains to treat mortality that is the result of multiple physiological processes, some of which may have delays. In the second, we assume that mortality is the result of damage associated with growth and metabolism. Both approaches lead to a rich diversity of predicted mortality trajectories. Although many of these look Gompertzian at young ages, the behavior at older ages depends upon the details of the physiological models.

Humans↗

Long-term adaptive life functioning in relation to initiation of treatment with antipsychotics over the lifetime trajectory of schizophrenia.

BACKGROUND: There is evidence that the stage of illness at which antipsychotic treatment is initiated in schizophrenia may have consequences for its subsequent course. How this might relate to impaired adaptive life functioning in the long-term is poorly understood. METHODS: Thirty-eight inpatients, many of whom had been admitted in the preneuroleptic era, were assessed using the Social-Adaptive Functioning Evaluation (SAFE); constituent clinical and medication phases of the lifetime trajectory of their illnesses were then analyzed to identify predictors of SAFE score using multiple regression modeling. RESULTS: The primary, independent predictor of SAFE score was duration of initially unmedicated psychosis, which accounted for 22% of variance (p<.001) therein. Conversely, duration of subsequently treated illness, although decades longer, failed to predict SAFE score. CONCLUSIONS: These findings are consistent with some form of "progressive" process, particularly over the first several years following the emergence of psychosis, which is associated with accrual of deficits in adaptive life functioning.

Adaptation, Psychological↗

The neurodevelopmental basis of schizophrenia: clinical clues from cerebro-craniofacial dysmorphogenesis, and the roots of a lifetime trajectory of disease.

A "read-back" analysis of schizophrenia, from chronic illness, through the first psychotic episode, to psychosocial and neurointegrative abnormalities of childhood and infancy, leads to the intrauterine period as a primary focus for etiological events. Evidence for a characteristic topography of cerebro-craniofacial dysmorphology in schizophrenia is reviewed, and interpreted to estimate: (i) the timing of dysmorphic event(s); (ii) the nature of early cellular and molecular mechanisms which might determine that topography of dysmorphogenesis; and (iii) the population homogeneity of these processes. It is argued that early cerebro-craniofacial dysmorphogenesis in schizophrenia should be conceptualized as a first stage not in a static but rather in a dynamic, lifetime trajectory of disease.

Brain↗

Direct measurements of multiple adhesive alignments and unbinding trajectories between cadherin extracellular domains.

Direct measurements of the interactions between antiparallel, oriented monolayers of the complete extracellular region of C-cadherin demonstrate that, rather than binding in a single unique orientation, the cadherins adhere in three distinct alignments. The strongest adhesion is observed when the opposing extracellular fragments are completely interdigitated. A second adhesive alignment forms when the interdigitated proteins separate by 70 +/- 10 A. A third complex forms at a bilayer separation commensurate with the approximate overlap of cadherin extracellular domains 1 and 2 (CEC1-2). The locations of the energy minima are independent of both the surface density of bound cadherin and the stiffness of the force transducer. Using surface element integration, we show that two flat surfaces that interact through an oscillatory potential will exhibit discrete minima at the same locations in the force profile measured between hemicylinders covered with identical materials. The measured interaction profiles, therefore, reflect the relative separations at which the antiparallel proteins adhere, and are unaffected by the curvature of the underlying substrate. The successive formation and rupture of multiple protein contacts during detachment can explain the observed sluggish unbinding of cadherin monolayers. Velocity-distance profiles, obtained by quantitative video analysis of the unbinding trajectory, exhibit three velocity regimes, the transitions between which coincide with the positions of the adhesive minima. These findings suggest that cadherins undergo multiple stage unbinding, which may function to impede adhesive failure under force.

Animals↗