374 research outputs found

    A Functional Architecture of Optic Flow in the Inferior Parietal Lobule of the Behaving Monkey

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    The representation of navigational optic flow across the inferior parietal lobule was assessed using optical imaging of intrinsic signals in behaving monkeys. The exposed cortex, corresponding to the dorsal-most portion of areas 7a and dorsal prelunate (DP), was imaged in two hemispheres of two rhesus monkeys. The monkeys actively attended to changes in motion stimuli while fixating. Radial expansion and contraction, and rotation clockwise and counter-clockwise optic flow stimuli were presented concentric to the fixation point at two angles of gaze to assess the interrelationship between the eye position and optic flow signal. The cortical response depended upon the type of flow and was modulated by eye position. The optic flow selectivity was embedded in a patchy architecture within the gain field architecture. All four optic flow stimuli tested were represented in areas 7a and DP. The location of the patches varied across days. However the spatial periodicity of the patches remained constant across days at ∼950 and 1100 µm for the two animals examined. These optical recordings agree with previous electrophysiological studies of area 7a, and provide new evidence for flow selectivity in DP and a fine scale description of its cortical topography. That the functional architectures for optic flow can change over time was unexpected. These and earlier results also from inferior parietal lobule support the inclusion of both static and dynamic functional architectures that define association cortical areas and ultimately support complex cognitive function

    Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass - a cross sectional study

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    <p>Abstract</p> <p>Background</p> <p>As many patients with rheumatoid arthritis (RA) have increased fat mass (FM) and increased frequency of cardiovascular diseases we evaluated if total physical activity (MET-hours) had impact on body composition and cardiovascular risk factors in women with RA.</p> <p>Methods</p> <p>Sixty-one out-ward RA women, 60.8 (57.3-64.4) years, answered a self-administered questionnaire, to estimate total daily physical activity during the previous year. Physical activity level was given as metabolic equivalents (MET) × h/day. Diet content was assessed by a food frequency questionnaire and body composition by whole-body dual-energy X-ray absorptiometry. Blood lipids and antibodies against phosphorylcholine (anti-PC) were determined.</p> <p>Results</p> <p>Forty-one percent of the women had BMI > 25, 6% were centrally obese and 80% had FM% > 30%. The median (IQR) total physical activity was 40.0 (37.4-47.7), i.e. the same activity level as healthy Swedish women in the same age. Total physical activity did not significantly correlate with disease activity, BMI or FM%. Disease activity, BMI and FM% did not differ between those in the lowest quartile of total physical activity and those in the highest quartile. However, the women in the lowest quartile of physical activity had lower HDL (p = 0.05), Apo A1 (p = 0.005) and atheroprotective natural anti-PC (p = 0.016) and higher levels of insulin (p = 0.05) and higher frequency of insulin resistance than those in the highest quartile. Women in the lowest quartile consumed larger quantities of saturated fatty acids than those in the highest quartile (p = 0.042), which was associated with high oxidized low-density lipoprotein (oxLDL).</p> <p>Conclusion</p> <p>This cross sectional study demonstrated that RA women with fairly low disease activity, good functional capacity, high FM and high frequency of central obesity had the same total physical activity level as healthy Swedish women in the same age. The amount of total physical activity was not associated with functional capacity or body composition. However, low total physical activity was associated with dyslipidemia, insulin resistance, low levels of atheroprotective anti-PC and consumption of saturated fatty acids, which is of interest in the context of increased frequency of cardiovascular disease in RA.</p

    In Heart Failure Patients with Left Bundle Branch Block Single Lead MultiSpot Left Ventricular Pacing Does Not Improve Acute Hemodynamic Response To Conventional Biventricular Pacing. A Multicenter Prospective, Interventional, Non-Randomized Study.

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    Introduction Recent efforts to increase CRT response by multiSPOT pacing (MSP) from multiple bipols on the same left ventricular lead are still inconclusive. Aim The Left Ventricular (LV) MultiSPOTpacing for CRT (iSPOT) study compared the acute hemodynamic response of MSP pacing by using 3 electrodes on a quadripolar lead compared with conventional biventricular pacing (BiV). Methods Patients with left bundle branch block (LBBB) underwent an acute hemodynamic study to determine the %change in LV+dP/dtmax from baseline atrial pacing compared to the following configurations: BiV pacing with the LV lead in a one of lateral veins, while pacing from the distal, mid, or proximal electrode and all 3 electrodes together (i.e. MSP). All measurements were repeated 4 times at 5 different atrioventricular delays. We also measured QRS-width and individual Q-LV durations. Results Protocol was completed in 24 patients, all with LBBB (QRS width 171±20 ms) and 58% ischemic aetiology. The percentage change in LV+dP/dtmax for MSP pacing was 31.0±3.3% (Mean±SE), which was not significantly superior to any BiV pacing configuration: 28.9±3.2% (LV-distal), 28.3±2.7% (LV-mid), and 29.5±3.0% (LV-prox), respectively. Correlation between LV+dP/dtmax and either QRS-width or Q-LV ratio was poor. Conclusions In patients with LBBB MultiSPOT LV pacing demonstrated comparable improvement in contractility to best conventional BiV pacing. Optimization of atrioventricular delay is important for the best performance for both BiV and MultiSPOT pacing configurations. Trial Registration ClinicalTrials.gov NTC0188314

    Imprinted CDKN1C Is a Tumor Suppressor in Rhabdoid Tumor and Activated by Restoration of SMARCB1 and Histone Deacetylase Inhibitors

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    SMARCB1 is deleted in rhabdoid tumor, an aggressive paediatric malignancy affecting the kidney and CNS. We hypothesized that the oncogenic pathway in rhabdoid tumors involved epigenetic silencing of key cell cycle regulators as a consequence of altered chromatin-remodelling, attributable to loss of SMARCB1, and that this hypothesis if proven could provide a biological rationale for testing epigenetic therapies in this disease. We used an inducible expression system to show that the imprinted cell cycle inhibitor CDKN1C is a downstream target for SMARCB1 and is transcriptionally activated by increased histone H3 and H4 acetylation at the promoter. We also show that CDKN1C expression induces cell cycle arrest, CDKN1C knockdown with siRNA is associated with increased proliferation, and is able to compete against the anti-proliferative effect of restored SMARCB1 expression. The histone deacetylase inhibitor (HDACi), Romidepsin, specifically restored CDKN1C expression in rhabdoid tumor cells through promoter histone H3 and H4 acetylation, recapitulating the effect of SMARCB1 on CDKNIC allelic expression, and induced cell cycle arrest in G401 and STM91-01 rhabdoid tumor cell lines. CDKN1C expression was also shown to be generally absent in clinical specimens of rhabdoid tumor, however CDKN1A and CDKN1B expression persisted. Our observations suggest that maintenance of CDKN1C expression plays a critical role in preventing rhabdoid tumor growth. Significantly, we report for the first time, parallels between the molecular pathways of SMARCB1 restoration and Romidepsin treatment, and demonstrate a biological basis for the further exploration of histone deacetylase inhibitors as relevant therapeutic reagents in the treatment of rhabdoid tumor

    Activity in perceptual classification networks as a basis for human subjective time perception

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    Despite being a fundamental dimension of experience, how the human brain generates the perception of time remains unknown. Here, we provide a novel explanation for how human time perception might be accomplished, based on non-temporal perceptual classification processes. To demonstrate this proposal, we build an artificial neural system centred on a feed-forward image classification network, functionally similar to human visual processing. In this system, input videos of natural scenes drive changes in network activation, and accumulation of salient changes in activation are used to estimate duration. Estimates produced by this system match human reports made about the same videos, replicating key qualitative biases, including differentiating between scenes of walking around a busy city or sitting in a cafe or office. Our approach provides a working model of duration perception from stimulus to estimation and presents a new direction for examining the foundations of this central aspect of human experience
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