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    Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades

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    The mammalian visual system relies upon light detection by outer-retinal rod/cone photoreceptors and melanopsin-expressing retinal ganglion cells. Gnat1(-/-); Cnga3(-/-); Opn4(-/-) mice lack critical elements of each of these photoreceptive mechanisms via targeted disruption of genes encoding rod alpha transducin (Gnat1); the cone-specific alpha 3 cyclic nucleotide gated channel subunit (Cnga3); and melanopsin (Opn4). Although assumed blind, we show here that these mice retain sufficiently widespread retinal photoreception to drive a reproducible flash electroretinogram (ERG). The threshold sensitivity of this ERG is similar to that of cone-based responses, however it is lost under light adapted conditions. Its spectral efficiency is consistent with that of rod opsin, but not cone opsins or melanopsin, indicating that it originates with light absorption by the rod pigment. The TKO light response survives intravitreal injection of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone alpha transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence. Visual responses in TKO mice extend beyond the retina to encompass the lateral margins of the lateral geniculate nucleus and components of the visual cortex. Our data thus suggest that a Gnat1-independent phototransduction mechanism downstream of rod opsin can support relatively widespread responses in the mammalian visual system. This anomalous rod opsin-based vision should be considered in experiments relying upon Gnat1 knockout to silence rod phototransduction

    Finite groups whose commuting graph is split

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    As a contribution to the study of graphs defined on groups, we show that for a finite group G the following statements are equivalent: the commuting graph of G is a split graph; the commuting graph of G is a threshold graph; either G is abelian, or G is a generalized dihedral group D(A)=⟨A,t:(∀a∈A)(at)2=1⟩ where A is an abelian group of odd order.Peer reviewe

    Nonexistence of Certain Skew-symmetric Amorphous Association Schemes

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    An association scheme is amorphous if it has as many fusion schemes as possible. Symmetric amorphous schemes were classified by A. V. Ivanov [A. V. Ivanov, Amorphous cellular rings II, in Investigations in algebraic theory of combinatorial objects, pages 39--49. VNIISI, Moscow, Institute for System Studies, 1985] and commutative amorphous schemes were classified by T. Ito, A. Munemasa and M. Yamada [T. Ito, A. Munemasa and M. Yamada, Amorphous association schemes over the Galois rings of characteristic 4, European J. Combin., 12(1991), 513--526]. A scheme is called skew-symmetric if the diagonal relation is the only symmetric relation. We prove the nonexistence of skew-symmetric amorphous schemes with at least 4 classes. We also prove that non-symmetric amorphous schemes are commutative.Comment: 10 page

    Automatic correction of hand pointing in stereoscopic depth

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    In order to examine whether stereoscopic depth information could drive fast automatic correction of hand pointing, an experiment was designed in a 3D visual environment in which participants were asked to point to a target at different stereoscopic depths as quickly and accurately as possible within a limited time window (≤300 ms). The experiment consisted of two tasks: "depthGO" in which participants were asked to point to the new target position if the target jumped, and "depthSTOP" in which participants were instructed to abort their ongoing movements after the target jumped. The depth jump was designed to occur in 20% of the trials in both tasks. Results showed that fast automatic correction of hand movements could be driven by stereoscopic depth to occur in as early as 190 ms.This work was supported by the Grants from the National Natural Science Foundation of China (60970062 and 61173116) and the Doctoral Fund of Ministry of Education of China (20110072110014)

    Model selection and prediction of outcomes in recent onset schizophrenia patients who undergo cognitive training.

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    Predicting treatment outcomes in psychiatric populations remains a challenge, but is increasingly important in the pursuit of personalized medicine. Patients with schizophrenia have deficits in cognition, and targeted cognitive training (TCT) of auditory processing and working memory has been shown to improve some of these impairments; but little is known about the baseline patient characteristics predictive of cognitive improvement. Here we use a model selection and regression approach called least absolute shrinkage and selection operator (LASSO) to examine predictors of cognitive improvement in response to TCT for patients with recent onset schizophrenia. Forty-three individuals with recent onset schizophrenia randomized to undergo TCT were assessed at baseline on measures of cognition, symptoms, functioning, illness duration, and demographic variables. We carried out 10-fold cross-validation of LASSO for model selection and regression. We followed up on these results using linear models for statistical inference. No individual variable was found to correlate with improvement in global cognition using a Pearson correlation approach, and a linear model including all variables was also found not to be significant. However, the LASSO model identified baseline global cognition, education, and gender in a model predictive of improvement on global cognition following TCT. These findings offer guidelines for personalized approaches to cognitive training for patients with schizophrenia

    Change in knee flexor torque after fatiguing exercise identifies previous hamstring injury in football players

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    Muscular fatigue and interlimb strength asymmetry are factors known to influence hamstring injury risk; however, limb‐specific exacerbation of knee flexor (hamstrings) torque production after fatiguing exercise has previously been ignored. To investigate changes in muscular force production before and after sport‐specific (repeated‐sprint) and non‐specific (knee extension‐flexion) fatiguing exercise, and explore the sensitivity and specificity of isokinetic endurance (ie, muscle‐specific) and single‐leg vertical jump (ie, whole limb) tests to identify previous hamstring injury. Twenty Western Australia State League footballers with previous unilateral hamstring injury and 20 players without participated. Peak concentric knee extensor and flexor (180°∙s−1) torques were assessed throughout an isokinetic endurance test, which was then repeated alongside a single‐leg vertical jump test before and after maximal repeated‐sprint exercise. Greater reductions in isokinetic knee flexor torque (−16%) and the concentric hamstring:quadriceps peak torque ratio (−15%) were observed after repeated‐sprint running only in the injured (kicking) leg and only in the previously injured subjects. Changes in (1) peak knee flexor torque after repeated‐sprint exercise, and (2) the decline in knee flexor torque during the isokinetic endurance test measured after repeated‐sprint exercise, correctly identified the injured legs (N = 20) within the cohort (N = 80) with 100% specificity and sensitivity. Decreases in peak knee flexor torque and the knee flexor torque during an isokinetic endurance test after repeated‐sprint exercise identified previous hamstring injury with 100% accuracy. Changes in knee flexor torque, but not SLVJ, should be tested to determine its prospective ability to predict hamstring injury in competitive football players

    sFlt-1 and NTproBNP independently predict mortality in a cohort of heart failure patients.

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    Objective: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a circulating receptor for VEGF-A. Recent reports of elevated plasma levels of sFlt-1 in coronary heart disease and heart failure (HF) motivated our study aimed at investigating the utility of sFlt-1 as a prognostic biomarker in heart failure patients. Methods: ELISA assays for sFlt-1 and NTproBNP were performed in n=858 patients from a prospective multicentre, observational study (the PEOPLE study) of outcome among patients after appropriate treatment for an episode of acute decompensated HF in New Zealand. Plasma was sampled at a baseline visit and stored at -80°C. Statistical tests were adjusted for patient age at baseline visit, skewed data were log-adjusted and the endpoint for clinical outcome analysis was all-cause death. Patients were followed for a median of 3.63 (range 0.74-5.50) years. Results: Mean baseline plasma sFlt-1 was 125 +/- 2.01 pg/ml. sFlt-1 was higher in patients with HF with reduced ejection fraction (HFrEF) (130 +/- 2.62 pg/ml, n=553) compared to those with HF with preserved EF (HFpEF) (117 +/-3.59 pg/ml, n=305; p=0.005). sFlt-1 correlated with heart rate (r=0.148, p<0.001), systolic blood pressure (r=-0.139, p<0.001) and LVEF (r=-0.088, p=0.019). A Cox proportional hazards model showed sFlt-1 was a predictor of all-cause death (HR=6.30, p<0.001) in the PEOPLE cohort independent of age, NTproBNP, ischaemic aetiology, and NYHA class (n=842, 274 deaths), established predictors of mortality in the PEOPLE cohort. Conclusion: sFlt-1 levels at baseline should be investigated further as a predictor of death; complementary to established prognostic biomarkers in heart failure
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