Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

Space-time sketching of character animation

International audienceWe present a space-time abstraction for the sketch-based design of character animation. It allows animators to draft a full coordinated motion using a single stroke called the space-time curve (STC). From the STC we compute a dynamic line of action (DLOA) that drives the motion of a 3D character through projective constraints. Our dynamic models for the line's motion are entirely geometric, require no pre-existing data, and allow full artistic control. The resulting DLOA can be refined by over-sketching strokes along the space-time curve, or by composing another DLOA on top leading to control over complex motions with few strokes. Additionally , the resulting dynamic line of action can be applied to arbitrary body parts or characters. To match a 3D character to the 2D line over time, we introduce a robust matching algorithm based on closed-form solutions, yielding a tight match while allowing squash and stretch of the character's skeleton. Our experiments show that space-time sketching has the potential of bringing animation design within the reach of beginners while saving time for skilled artists

Cardiovascular effects of calcium supplementation

Peer reviewedPostprin

Neuromuscular control of aerodynamic forces and moments in the blowfly, Calliphora vicina

Flies are among the most agile of flying insects, a capacity that ultimately results from their nervous system's control over steering muscles and aerodynamic forces during flight. In order to investigate the relationships among neuromuscular control, musculo-skeletal mechanics and flight forces, we captured high-speed, three-dimensional wing kinematics of the blowfly, Calliphora vicina, while simultaneously recording electromyogram signals from prominent steering muscles during visually induced turns. We used the quantified kinematics to calculate the translational and rotational components of aerodynamic forces and moments using a theoretical quasi-steady model of force generation, confirmed using a dynamically scaled mechanical model of a Calliphora wing. We identified three independently controlled features of the wingbeat trajectory – downstroke deviation, dorsal amplitude and mode. Modulation of each of these kinematic features corresponded to both activity in a distinct steering muscle group and a distinct manipulation of the aerodynamic force vector. This functional specificity resulted from the independent control of downstroke and upstroke forces rather than the independent control of separate aerodynamic mechanisms. The predicted contributions of each kinematic feature to body lift, thrust, roll, yaw and pitch are discussed

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

The Line of Action: an Intuitive Interface for Expressive Character Posing

International audienceThe line of action is a conceptual tool often used by cartoonists and illustrators to help make their figures more consistent and more dramatic. We often see the expression of characters--may it be the dynamism of a super hero, or the elegance of a fashion model--well captured and amplified by a single aesthetic line. Usually this line is laid down in early stages of the drawing and used to describe the body's principal shape. By focusing on this simple abstraction, the person drawing can quickly adjust and refine the overall pose of his or her character from a given viewpoint. In this paper, we propose a mathematical definition of the line of action (LOA), which allows us to automatically align a 3D virtual character to a user specified LOA by solving an optimization problem. We generalize this framework to other types of lines found in the drawing literature, such as secondary lines used to place arms. Finally, we show a wide range of poses and animations that were rapidly created using our system

Interactive Sketching of Mannequin Poses

It can be easy and even fun to sketch humans in different poses. In contrast, creating those same poses on a 3D graphics 'mannequin' is comparatively tedious. Yet 3D body poses are necessary for various downstream applications. We seek to preserve the convenience of 2D sketching while giving users of different skill levels the flexibility to accurately and more quickly pose/refine a 3D mannequin. At the core of the interactive system, we propose a machine-learning model for inferring the 3D pose of a CG mannequin from sketches of humans drawn in a cylinder-person style. Training such a model is challenging because of artist variability, a lack of sketch training data with corresponding ground truth 3D poses, and the high dimensionality of human pose-space. Our unique approach to synthesizing vector graphics training data underpins our integrated ML-and-kinematics system. We validate the system by tightly coupling it with a user interface, and by performing a user study, in addition to quantitative comparisons

From Parallel Sequence Representations to Calligraphic Control: A Conspiracy of Neural Circuits

Calligraphic writing presents a rich set of challenges to the human movement control system. These challenges include: initial learning, and recall from memory, of prescribed stroke sequences; critical timing of stroke onsets and durations; fine control of grip and contact forces; and letter-form invariance under voluntary size scaling, which entails fine control of stroke direction and amplitude during recruitment and derecruitment of musculoskeletal degrees of freedom. Experimental and computational studies in behavioral neuroscience have made rapid progress toward explaining the learning, planning and contTOl exercised in tasks that share features with calligraphic writing and drawing. This article summarizes computational neuroscience models and related neurobiological data that reveal critical operations spanning from parallel sequence representations to fine force control. Part one addresses stroke sequencing. It treats competitive queuing (CQ) models of sequence representation, performance, learning, and recall. Part two addresses letter size scaling and motor equivalence. It treats cursive handwriting models together with models in which sensory-motor tmnsformations are performed by circuits that learn inverse differential kinematic mappings. Part three addresses fine-grained control of timing and transient forces, by treating circuit models that learn to solve inverse dynamics problems.National Institutes of Health (R01 DC02852

Biomechanics of Pediatric Manual Wheelchair Mobility

Currently, there is limited research of the biomechanics of pediatric manual wheelchair mobility. Specifically, the biomechanics of functional tasks and their relationship to joint pain and health is not well understood. To contribute to this knowledge gap, a quantitative rehabilitation approach was applied for characterizing upper extremity biomechanics of manual wheelchair mobility in children and adolescents during propulsion, starting, and stopping tasks. A Vicon motion analysis system captured movement, while a SmartWheel simultaneously collected three-dimensional forces and moments occurring at the handrim. A custom pediatric inverse dynamics model was used to evaluate three-dimensional upper extremity joint motions, forces, and moments of 14 children with spinal cord injury (SCI) during the functional tasks. Additionally, pain and health-related quality of life outcomes were assessed. This research found that joint demands are significantly different amongst functional tasks, with greatest demands placed on the shoulder during the starting task. Propulsion was significantly different from starting and stopping at all joints. We identified multiple stroke patterns used by the children, some of which are not standard in adults. One subject reported average daily pain, which was minimal. Lower than normal physical health and higher than normal mental health was found in this population. It can be concluded that functional tasks should be considered in addition to propulsion for rehabilitation and SCI treatment planning. This research provides wheelchair users and clinicians with a comprehensive, biomechanical, mobility assessment approach for wheelchair prescription, training, and long-term care of children with SCI