Dynamical Adaptation in Photoreceptors

Adaptation is at the heart of sensation and nowhere is it more salient than in early visual processing. Light adaptation in photoreceptors is doubly dynamical: it depends upon the temporal structure of the input and it affects the temporal structure of the response. We introduce a non-linear dynamical adaptation model of photoreceptors. It is simple enough that it can be solved exactly and simulated with ease; analytical and numerical approaches combined provide both intuition on the behavior of dynamical adaptation and quantitative results to be compared with data. Yet the model is rich enough to capture intricate phenomenology. First, we show that it reproduces the known phenomenology of light response and short-term adaptation. Second, we present new recordings and demonstrate that the model reproduces cone response with great precision. Third, we derive a number of predictions on the response of photoreceptors to sophisticated stimuli such as periodic inputs, various forms of flickering inputs, and natural inputs. In particular, we demonstrate that photoreceptors undergo rapid adaptation of response gain and time scale, over ∼ 300 ms—i. e., over the time scale of the response itself—and we confirm this prediction with data. For natural inputs, this fast adaptation can modulate the response gain more than tenfold and is hence physiologically relevant

Nonlinear circuits for naturalistic visual motion estimation

Many animals use visual signals to estimate motion. Canonical models suppose that animals estimate motion by cross-correlating pairs of spatiotemporally separated visual signals, but recent experiments indicate that humans and flies perceive motion from higher-order correlations that signify motion in natural environments. Here we show how biologically plausible processing motifs in neural circuits could be tuned to extract this information. We emphasize how known aspects of Drosophila's visual circuitry could embody this tuning and predict fly behavior. We find that segregating motion signals into ON/OFF channels can enhance estimation accuracy by accounting for natural light/dark asymmetries. Furthermore, a diversity of inputs to motion detecting neurons can provide access to more complex higher-order correlations. Collectively, these results illustrate how non-canonical computations improve motion estimation with naturalistic inputs. This argues that the complexity of the fly's motion computations, implemented in its elaborate circuits, represents a valuable feature of its visual motion estimator. DOI: http://dx.doi.org/10.7554/eLife.09123.00

The role of the AFD neuron in C. elegans thermotaxis analyzed using femtosecond laser ablation

BACKGROUND: Caenorhabditis elegans actively crawls down thermal gradients until it reaches the temperature of its prior cultivation, exhibiting what is called cryophilic movement. Implicit in the worm's performance of cryophilic movement is the ability to detect thermal gradients, and implicit in regulating the performance of cryophilic movement is the ability to compare the current temperature of its surroundings with a stored memory of its cultivation temperature. Several lines of evidence link the AFD sensory neuron to thermotactic behavior, but its precise role is unclear. A current model contends that AFD is part of a thermophilic mechanism for biasing the worm's movement up gradients that counterbalances the cryophilic mechanism for biasing its movement down gradients. RESULTS: We used tightly-focused femtosecond laser pulses to dissect the AFD neuronal cell bodies and the AFD sensory dendrites in C. elegans to investigate their contribution to cryophilic movement. We establish that femtosecond laser ablation can exhibit submicrometer precision, severing individual sensory dendrites without causing collateral damage. We show that severing the dendrites of sensory neurons in young adult worms permanently abolishes their sensory contribution without functional regeneration. We show that the AFD neuron regulates a mechanism for generating cryophilic bias, but we find no evidence that AFD laser surgery reduces a putative ability to generate thermophilic bias. In addition, although disruption of the AIY interneuron causes worms to exhibit cryophilic bias at all temperatures, we find no evidence that laser killing the AIZ interneuron causes thermophilic bias at any temperature. CONCLUSION: We conclude that laser surgical analysis of the neural circuit for thermotaxis does not support a model in which AFD opposes cryophilic bias by generating thermophilic bias. Our data supports a model in which the AFD neuron gates a mechanism for generating cryophilic bias

March 1964

Turf and Lawn Grass Association Better turf through research and Educatio

Sensitive screening of single nucleotide polymorphisms in cell free DNA for diagnosis of gestational tumours

Tumours expressing human chorionic gonadotropin (hCG), the majority of which are difficult to biopsy due to their vascularity, have disparate prognoses depending on their origin. As optimal management relies on accurate diagnosis, we aimed to develop a sensitive cell free DNA (cfDNA) assay to non-invasively distinguish between cases of gestational and non-gestational origin. Deep error-corrected Illumina sequencing of 195 common single nucleotide polymorphisms (SNPs) in cfDNA and matched genomic DNA from 36 patients with hCG-secreting tumours (serum hCG 5 to 3,042,881 IU/L) and 7 controls with normal hCG levels (≤ 4 IU/L) was performed. cfDNA from confirmed gestational tumours with hCG levels ranging from 1,497 to 700,855 IU/L had multiple (n ≥12) ‘non-host’ alleles (i.e. alleles of paternal origin). In such cases the non-host fraction of cfDNA ranged from 0.3% - 40.4% and correlated with serum hCG levels. At lower hCG levels the ability to detect non-host cfDNA was variable, with the detection limit dependent on the type of causative pregnancy. Patients with non-gestational tumours were identifiable by the absence of non-host cfDNA, with copy number alterations detectable in the majority of cases. Following validation in a larger cohort, our sensitive assay will enable clinicians to better inform patients, for whom biopsy is inappropriate, of their prognosis and provide optimum management

Young children's research: children aged 4-8 years finding solutions at home and at school

Children's research capacities have become increasingly recognised by adults, yet children remain excluded from the academy, with reports of their research participation generally located in adults' agenda. Such practice restricts children's freedom to make choices in matters affecting them, underestimates children’s capabilities and denies children particular rights. The present paper reports on one aspect of a small-scale critical ethnographic study adopting a constructivist grounded approach to conceptualise ways in which children's naturalistic behaviours may be perceived as research. The study builds on multi-disciplinary theoretical perspectives, embracing 'new' sociology, psychology, economics, philosophy and early childhood education and care (ECEC). Research questions include: 'What is the nature of ECEC research?' and 'Do children’s enquiries count as research?' Initially, data were collected from the academy: professional researchers (n=14) confirmed 'finding solutions' as a research behaviour and indicated children aged 4-8 years, their practitioners and primary carers as 'theoretical sampling'. Consequently, multi-modal case studies were constructed with children (n=138) and their practitioners (n=17) in three ‘good’ schools, with selected children and their primary carers also participating at home. This paper reports on data emerging from children aged 4-8 years at school (n=17) and at home (n=5). Outcomes indicate that participating children found diverse solutions to diverse problems, some of which they set themselves. Some solutions engaged children in high order thinking, whilst others did not; selecting resources and trialing activities engaged children in 'finding solutions'. Conversely, when children's time, provocations and activities were directed by adults, the quality of their solutions was limited, they focused on pleasing adults and their motivation to propose solutions decreased. In this study, professional researchers recognised 'finding solutions' as research behaviour and children aged 4-8 years naturalistically presented with capacities for finding solutions; however, the children's encounters with adults affected the solutions they found

Dopamine Signaling Is Essential for Precise Rates of Locomotion by C. elegans

Dopamine is an important neuromodulator in both vertebrates and invertebrates. We have found that reduced dopamine signaling can cause a distinct abnormality in the behavior of the nematode C. elegans, which has only eight dopaminergic neurons. Using an automated particle-tracking system for the analysis of C. elegans locomotion, we observed that individual wild-type animals made small adjustments to their speed to maintain constant rates of locomotion. By contrast, individual mutant animals defective in the synthesis of dopamine made larger adjustments to their speeds, resulting in large fluctuations in their rates of locomotion. Mutants defective in dopamine signaling also frequently exhibited both abnormally high and abnormally low average speeds. The ability to make small adjustments to speed was restored to these mutants by treatment with dopamine. These behaviors depended on the D2-like dopamine receptor DOP-3 and the G-protein subunit GOA-1. We suggest that C. elegans and other animals, including humans, might share mechanisms by which dopamine restricts motor activity levels and coordinates movement

A curvilinear effect of height on reproductive success in human males

Human male height is associated with mate choice and intra-sexual competition, and therefore potentially with reproductive success. A literature review (n = 18) on the relationship between male height and reproductive success revealed a variety of relationships ranging from negative to curvilinear to positive. Some of the variation in results may stem from methodological issues, such as low power, including men in the sample who have not yet ended their reproductive career, or not controlling for important potential confounders (e.g. education and income). We investigated the associations between height, education, income and the number of surviving children in a large longitudinal sample of men (n = 3,578; Wisconsin Longitudinal Study), who likely had ended their reproductive careers (e.g. > 64 years). There was a curvilinear association between height and number of children, with men of average height attaining the highest reproductive success. This curvilinear relationship remained after controlling for education and income, which were associated with both reproductive success and height. Average height men also married at a younger age than shorter and taller men, and the effect of height diminished after controlling for this association. Thus, average height men partly achieved higher reproductive success by marrying at a younger age. On the basis of our literature review and our data, we conclude that men of average height most likely have higher reproductive success than either short or tall men

High-intensity exercise to promote accelerated improvements in cardiorespiratory fitness (HI-PACE): study protocol for a randomized controlled trial

Background: African Americans have a disproportionate prevalence and incidence of type 2 diabetes compared with Caucasians. Recent evidence indicates that low cardiorespiratory fitness (CRF) level, an independent risk factor for type 2 diabetes, is also more prevalent in African Americans than Caucasians. Numerous studies in Caucasian populations suggest that vigorous exercise intensity may promote greater improvements in CRF and other type 2 diabetes risk factors (e.g., reduction of glucose/insulin levels, pulse wave velocity, and body fat) than moderate intensity. However, current evidence comparing health benefits of different aerobic exercise intensities on type 2 diabetes risk factors in African Americans is negligible. This is clinically important as African Americans have a greater risk for type 2 diabetes and are less likely to meet public health recommendations for physical activity than Caucasians. The purpose of the HI-PACE (High-Intensity exercise to Promote Accelerated improvements in CardiorEspiratory fitness) study is to evaluate whether high-intensity aerobic exercise elicits greater improvements in CRF, insulin action, and arterial stiffness than moderate-intensity exercise in African Americans. Methods/Design: A randomized controlled trial will be performed on overweight and obese (body mass index of 25–45 kg/m2) African Americans (35–65 years) (n = 60). Participants will be randomly assigned to moderate-intensity (MOD-INT) or high-intensity (HIGH-INT) aerobic exercise training or a non-exercise control group (CON) for 24 weeks. Supervised exercise will be performed at a heart rate associated with 45–55% and 70–80% of VO2 max in the MOD-INT and HIGH-INT groups, respectively, for an exercise dose of 600 metabolic equivalents of task (MET)-minutes per week (consistent with public health recommendations). The primary outcome is change in CRF. Secondary outcomes include change in insulin sensitivity (measured via an intravenous glucose tolerance test), skeletal muscle mitochondrial oxidative capacity (via near-infrared spectroscopy), skeletal muscle measurements (i.e., citrate synthase, COX IV, GLUT-4, CPT-1, and PGC1-α), arterial stiffness (via carotid-femoral pulse wave velocity), body fat, C-reactive protein, and psychological outcomes (quality of life/exercise enjoyment). Discussion: The anticipated results of the HI-PACE study will provide vital information on the health effects of high-intensity exercise in African Americans. This study will advance health disparity research and has the potential to influence future public health guidelines for physical activity