The effect of spatial orientation on detecting motion trajectories in noise

A series of experiments investigated the extent to which the spatial orientation of a signal line affects discrimination of its trajectory from the random trajectories of background noise lines. The orientation of the signal line was either parallel (iso-) or orthogonal (ortho-) to its motion direction and it was identical in all respects to the noise (orientation, length and speed) except for its motion direction, rendering the signal line indistinguishable from the noise on a frame-to-frame basis. We found that discrimination of ortho-trajectories was generally better than iso-trajectories. Discrimination of ortho-trajectories was largely immune to the effects of spatial jitter in the trajectory, and to variations in step size and line-length. Discrimination of iso-trajectories was reliable provided that step-size was not too short and did not exceed line length, and that the trajectory was straight. The new result that trajectory discrimination in moving line elements is modulated by line orientation suggests that ortho- and iso-trajectory discrimination rely upon two distinct mechanisms: iso-motion discrimination involves a ‘motion-streak’ process that combines motion information with information about orientation parallel to the motion trajectory, while ortho-motion discrimination involves extended trajectory facilitation in a network of receptive fields with orthogonal orientation tuning.     

Distinct position assignment mechanisms revealed by cross-order motion

Motion perception influences perceived position. It has been shown that first-order (luminance defined) motion shifts perceived position across a wide range of spatial and temporal frequencies. On the other hand, second-order (contrast defined) motion shifts perceived position over a narrow range of temporal frequencies, regardless of spatial frequency [Bressler, D. W., & Whitney, D. (2006). Second-order motion shifts perceived position. Vision Research, 46(6-7), 1120-1128]. These results suggest the presence of distinct position assignment mechanisms for first- and second-order motion. We investigated whether the first- and second-order systems independently encode and assign the position of a moving stimulus. To measure motion induced position shift we presented two horizontally offset Gabors placed above and below a central fixation point, with sine wave carriers drifting in opposite directions. Subjects judged the position of the top Gabor relative to the bottom one. We used both first-order Gabors (sinusoidal luminance modulation of a dynamic noise carrier enveloped by a static Gaussian) and second-order Gabors (sinusoidal contrast modulation of a dynamic noise carrier enveloped by a static Gaussian). Results showed a strong position shift in the direction of the carrier motion when both Gabors were first-order, a weak position shift when both Gabors were second-order, and no appreciable position shift when one Gabor was first-order and the other was second-order (cross-order motion). The absence of a position shift using cross-order motion supports the hypothesis that the two motion systems independently encode and assign the position of a moving object. These results are consistent with those of experiments investigating global spatial interactions between static first-order and second-order Gabor patches, indicating a commonality in the underlying spatial integration processes.     

mTOR Signaling Regulates Metabolic Function in Oligodendrocyte Precursor Cells and Promotes Efficient Brain Remyelination in the Cuprizone Model

In demyelinating diseases, such as multiple sclerosis, primary loss of myelin and subsequent neuronal degeneration throughout the CNS impair patient functionality. While the importance of mechanistic target of rapamycin (mTOR) signaling during developmental myelination is known, no studies have yet directly examined the function of mTOR signaling specifically in the oligodendrocyte (OL) lineage during remyelination. Here, we conditionally deleted Mtor from adult oligodendrocyte precursor cells (OPCs) using Ng2-Cre^ERT in male adult mice to test its function in new OLs responsible for remyelination. During early remyelination after cuprizone-induced demyelination, mice lacking mTOR in adult OPCs had unchanged OL numbers but thinner myelin. Myelin thickness recovered by late-stage repair, suggesting a delay in myelin production when Mtor is deleted from adult OPCs. Surprisingly, loss of mTOR in OPCs had no effect on efficiency of remyelination after lysophosphatidylcholine lesions in either the spinal cord or corpus callosum, suggesting that mTOR signaling functions specifically in a pathway dysregulated by cuprizone to promote remyelination efficiency. We further determined that cuprizone and inhibition of mTOR cooperatively compromise metabolic function in primary rat OLs undergoing differentiation. Together, our results support the conclusion that mTOR signaling in OPCs is required to overcome the metabolic dysfunction in the cuprizone-demyelinated adult brain.SIGNIFICANCE STATEMENT Impaired remyelination by oligodendrocytes contributes to the progressive pathology in multiple sclerosis, so it is critical to identify mechanisms of improving remyelination. The goal of this study was to examine mechanistic target of rapamycin (mTOR) signaling in remyelination. Here, we provide evidence that mTOR signaling promotes efficient remyelination of the brain after cuprizone-mediated demyelination but has no effect on remyelination after lysophosphatidylcholine demyelination in the spinal cord or brain. We also present novel data revealing that mTOR inhibition and cuprizone treatment additively affect the metabolic profile of differentiating oligodendrocytes, supporting a mechanism for the observed remyelination delay. These data suggest that altered metabolic function may underlie failure of remyelination in multiple sclerosis lesions and that mTOR signaling may be of therapeutic potential for promoting remyelination.     

Endothelin limits insulin action in obese/insulin-resistant humans

The normal action of insulin to vasodilate and redistribute blood flow in support of skeletal muscle metabolism is impaired in insulin-resistant states. Increased endogenous endothelin contributes to endothelial dysfunction in obesity and diabetes. Here, we test the hypothesis that increased endogenous endothelin action also contributes to skeletal muscle insulin resistance via impairments in insulin-stimulated vasodilation. We studied nine lean and seven obese humans, measuring the metabolic and hemodynamic effects of insulin (300 mU . m(-2) . min(-1)) alone and during femoral artery infusion of BQ123 (an antagonist of type A endothelin receptors, 1 micromol/min). Endothelin antagonism augmented skeletal muscle responses to insulin in obese subjects through changes in both leg blood flow (LBF) and glucose extraction. Insulin-stimulated LBF was significantly increased in obese subjects only. These changes, combined with differential effects on glucose extraction, resulted in augmented insulin-stimulated leg glucose uptake in obese subjects (54.7 +/- 5.7 vs. 107.4 +/- 18.9 mg/min with BQ123), with no change in lean subjects (103.7 +/- 11.4 vs. 88.9 +/- 16.3, P = 0.04 comparing BQ123 across groups). BQ123 allowed augmented leg glucose extraction in obese subjects even in the face of NOS antagonism. These findings suggest that increased endogenous endothelin action contributes to insulin resistance in skeletal muscle of obese humans, likely through both vascular and tissue effects.     

Novel Michael Addition Networks Containing Poly(propylene glycol) Telechelic Oligomers

Summary: Poly(propylene glycol) oligomers with molecular weights ranging from 1 000 to 8 000 g · mol^?1 were end‐functionalized with acetoacetate groups and subsequently crosslinked using carbon‐Michael addition with PEG diacrylate. Gel fraction analysis, DMA, TGA, tensile, and swelling measurements were utilized to characterize the networks. The thermomechanical properties of the networks were analyzed with respect to the molecular weight between crosslink points (M_c) and the critical molecular weight for entanglement (M_e). Sampling experiments during crosslinking revealed the evolution of molecular weight with time and monomer conversion. Kinetic analyses of the Michael additions were performed using ¹H NMR spectroscopy, and the influence of basic catalyst and concentration was elucidated.

Synthesis of acetoacetate networks from acetoacetate‐functionalized PPG using DBU as a basic catalyst.     

Evaluating satellite sensor-derived indices for Lyme disease risk prediction

The wetness and greenness indices created using Landsat Thematic Mapper (TM) data from June 1995 and 1997 and July 2002 were tested for their ability to predict the location of sites with different levels of nymphal blacklegged tick, Ixodes scapularis Say, abundance in Rhode Island. In 1995, there were statistically significant differences in the mean of greenness and wetness indices between sites classified as low and moderate tick abundance areas (P = 0.005 and P = 0.041, respectively). In 1997, there also were statistically significant differences in the mean of the greenness and wetness indices, but these differences were between the grouping of low/moderate tick abundance and the high tick abundance category (P = 0.023 and P = 0.015, respectively). The same indices from the 2002 image were not significant predictors of tick abundance. It may be that Landsat TM-derived indices can be used to predict nymphal blacklegged tick abundance in years (e.g., 1995 and 1997) when tick abundance is lower than average but not in years when it is higher (e.g., 2002). Thus, it seems unlikely that these remotely sensed indices will be very useful for modeling nonperidomestic Lyme disease risk over a large region in Rhode Island.     

Relationship of dysglycemia to acute myocardial infarct size and cardiovascular outcome as determined by cardiovascular magnetic resonance

Background

Improved outcomes for normoglycemic patients suffering acute myocardial infarction (AMI) over the last decade have not been matched by similar improvements in mortality for diabetic patients despite similar levels of baseline risk and appropriate medical therapy. Two of the major determinants of poor outcome following AMI are infarct size and left ventricular (LV) dysfunction.

Methods

Ninety-three patients with first AMI were studied. 22 patients had diabetes mellitus (DM) based on prior history or admission blood glucose ≥11.1 mmol/l. 13 patients had dysglycemia (admission blood glucose ≥7.8 mmol/l but <11.1 mmol/l) and 58 patients had normoglycemia (admission blood glucose <7.8 mmol/l). Patients underwent cardiac magnetic resonance (CMR) imaging at index presentation and median follow-up of 11 months. Cine imaging assessed LV function and late gadolinium contrast-enhanced imaging was used to quantify infarct size. Clinical outcome data were collected at 18 months median follow-up.

Results

Patients with dysglycemia and DM had larger infarct sizes by CMR than normoglycemic patients; at baseline percentage LV scar (mean (SD)) was 23.0% (10.9), 25.6% (12.9) and 15.8% (10.3) respectively (p = 0.001), and at 11 months percentage LV scar was 17.6% (8.9), 19.1% (9.6) and 12.4% (7.8) (p = 0.017). Patients with dysglycemia and DM also had lower event-free survival at 18 months (p = 0.005).

Conclusions

Patients with dysglycemia or diabetes mellitus sustain larger infarct sizes than normoglycemic patients, as determined by CMR. This may, in part, account for their adverse prognosis following AMI.