61 research outputs found
A Subconscious Interaction Between Fixation and Anticipatory Pursuit
Ocular smooth pursuit and fixation are typically viewed as separate systems, yet there is evidence that the brainstem fixation system inhibits pursuit. Here we present behavioral evidence that the fixation system modulates pursuit behavior outside of conscious awareness. Human observers (male and female) either pursued a small spot that translated across a screen, or fixated it as it remained stationary. As shown previously, pursuit trials potentiated the oculomotor system, producing anticipatory eye velocity on the next trial before the target moved that mimicked the stimulus-driven velocity. Randomly interleaving fixation trials reduced anticipatory pursuit, suggesting that a potentiated fixation system interacted with pursuit to suppress eye velocity in upcoming pursuit trials. The reduction was not due to passive decay of the potentiated pursuit signal because interleaving “blank” trials in which no target appeared did not reduce anticipatory pursuit. Interspersed short fixation trials reduced anticipation on long pursuit trials, suggesting that fixation potentiation was stronger than pursuit potentiation. Furthermore, adding more pursuit trials to a block did not restore anticipatory pursuit, suggesting that fixation potentiation was not overridden by certainty of an imminent pursuit trial but rather was immune to conscious intervention. To directly test whether cognition can override fixation suppression, we alternated pursuit and fixation trials to perfectly specify trial identity. Still, anticipatory pursuit did not rise above that observed with an equal number of random fixation trials. The results suggest that potentiated fixation circuitry interacts with pursuit circuitry at a subconscious level to inhibit pursuit. SIGNIFICANCE STATEMENT When an object moves, we view it with smooth pursuit eye movements. When an object is stationary, we view it with fixational eye movements. Pursuit and fixation are historically regarded as controlled by different neural circuitry, and alternating between invoking them is thought to be guided by a conscious decision. However, our results show that pursuit is actively suppressed by prior fixation of a stationary object. This suppression is involuntary, and cannot be avoided even if observers are certain that the object will move. The results suggest that the neural fixation circuitry is potentiated by engaging stationary objects, and interacts with pursuit outside of conscious awareness
Illusory Motion Reveals Velocity Matching, Not Foveation, Drives Smooth Pursuit of Large Objects
When small objects move in a scene, we keep them foveated with smooth pursuit eye movements. Although large objects such as people and animals are common, it is nonetheless unknown how we pursue them since they cannot be foveated. It might be that the brain calculates an object’s centroid, and then centers the eyes on it during pursuit as a foveation mechanism might. Alternatively, the brain merely matches the velocity by motion integration. We test these alternatives with an illusory motion stimulus that translates at a speed different from its retinal motion. The stimulus was a Gabor array that translated at a fixed velocity, with component Gabors that drifted with motion consistent or inconsistent with the translation. Velocity matching predicts different pursuit behaviors across drift conditions, while centroid matching predicts no difference.We also tested whether pursuit can segregate and ignore irrelevant local drifts when motion and centroid information are consistent by surrounding the Gabors with solid frames. Finally, observers judged the global translational speed of the Gabors to determine whether smooth pursuit and motion perception share mechanisms. We found that consistent Gabor motion enhanced pursuit gain while inconsistent, opposite motion diminished it, drawing the eyes away from the center of the stimulus and supporting a motion-based pursuit drive. Catch-up saccades tended to counter the position offset, directing the eyes opposite to the deviation caused by the pursuit gain change. Surrounding the Gabors with visible frames canceled both the gain increase and the compensatory saccades. Perceived speed was modulated analogous to pursuit gain. The results suggest that smooth pursuit of large stimuli depends on the magnitude of integrated retinal motion information, not its retinal location, and that the position system might be unnecessary for generating smooth velocity to large pursuit targets
Tolerance without clonal expansion: Self-antigen-expressing B cells program self-reactive T cells for future deletion
B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells
A Covered Eye Fails To Follow an Object Moving in Depth
To clearly view approaching objects, the eyes rotate inward (vergence), and the intraocular lenses focus (accommodation). Current ocular control models assume both eyes are driven by unitary vergence and unitary accommodation commands that causally interact. The models typically describe discrete gaze shifts to non-accommodative targets performed under laboratory conditions. We probe these unitary signals using a physical stimulus moving in depth on the midline while recording vergence and accommodation simultaneously from both eyes in normal observers. Using monocular viewing, retinal disparity is removed, leaving only monocular cues for interpreting the object\u27s motion in depth. The viewing eye always followed the target\u27s motion. However, the occluded eye did not follow the target, and surprisingly, rotated out of phase with it. In contrast, accommodation in both eyes was synchronized with the target under monocular viewing. The results challenge existing unitary vergence command theories, and causal accommodation-vergence linkage
Motion Integration for Ocular Pursuit Does Not Hinder Perceptual Segregation of Moving Objects
When confronted with a complex moving stimulus, the brain can integrate local element velocities to obtain a single motion signal, or segregate the elements to maintain awareness of their identities. The integrated motion signal can drive smooth-pursuit eye movements (Heinen and Watamaniuk, 1998), whereas the segregated signal guides attentive tracking of individual elements in multiple-object tracking tasks (MOT; Pylyshyn and Storm, 1988). It is evident that these processes can occur simultaneously, because we can effortlessly pursue ambulating creatures while inspecting disjoint moving features, such as arms and legs, but the underlying mechanism is unknown. Here, we provide evidence that separate neural circuits perform the mathematically opposed operations of integration and segregation, by demonstrating with a dual-task paradigm that the two processes do not share attentional resources. Human observers attentively tracked a subset of target elements composing a small MOT stimulus, while pursuing it ocularly as it translated across a computer display. Integration of the multidot stimulus yielded optimal pursuit. Importantly, performing MOT while pursuing the stimulus did not degrade performance on either task compared with when each was performed alone, indicating that they did not share attention. A control experiment showed that pursuit was not driven by integration of only the nontargets, leaving the MOT targets free for segregation. Nor was a predictive strategy used to pursue the stimulus, because sudden changes in its global velocity were accurately followed. The results suggest that separate neural mechanisms can simultaneously segregate and integrate the same motion signals
New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3
aHUS (atypical haemolytic uraemic syndrome), AMD (age-related macular degeneration) and other diseases are associated with defective AP (alternative pathway) regulation. CFH (complement factor H), CFI (complement factor I), MCP (membrane cofactor protein) and C3 exhibited the most disease-associated genetic alterations in the AP. Our interactive structural database for these was updated with a total of 324 genetic alterations. A consensus structure for the SCR (short complement regulator) domain showed that the majority (37%) of SCR mutations occurred at its hypervariable loop and its four conserved Cys residues. Mapping 113 missense mutations onto the CFH structure showed that over half occurred in the C-terminal domains SCR-15 to -20. In particular, SCR-20 with the highest total of affected residues is associated with binding to C3d and heparin-like oligosaccharides. No clustering of 49 missense mutations in CFI was seen. In MCP, SCR-3 was the most affected by 23 missense mutations. In C3, the neighbouring thioester and MG (macroglobulin) domains exhibited most of 47 missense mutations. The mutations in the regulators CFH, CFI and MCP involve loss-of-function, whereas those for C3 involve gain-of-function. This combined update emphasizes the importance of the complement AP in inflammatory disease, clarifies the functionally important regions in these proteins, and will facilitate diagnosis and therapy
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe
Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants
Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks
Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions
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