Neuroleukin (NLK) is a protein of relative molecular mass (Mr) 56,000 (56K) secreted by denervated rat muscle and found in large amounts in muscle, brain, heart and kidneys. The protein is a neurotrophic factor for spinal and sensory neurons and a lymphokine product of lectin-stimulated T-cells. It also induces immunoglobulin secretion by human mononuclear cells. Molecular clones of NLK have been expressed in monkey COS cells and the product was shown to have the same biological and biochemical properties as the extracted protein. NLK is abundant in muscle, brain and kidney, but is active at concentrations of 10(-9) to 10(-11) M, similar to those for other polypeptide factors. We have cloned the gene for pig muscle phosphohexose isomerase (PHI) (EC 5.3.1.9) which catalyses the conversion of glucose-6-phosphate to fructose-6-phosphate, an obligatory step in glycolysis, and determined its amino-acid sequence. Surprisingly, it is 90% homologous to the sequence of mouse neuroleukin.

This explorative study indicates that older adults are willing to incorporate contactless monitoring in later life or when their health declines. They agree to share collected information with professional caregivers and clearly demand for participation in decisions about the technology. Various concerns and requirements provide implications for clinical practice and future research. Thereby, technology developpers, policy makers and professional caregivers can promote the implementation of contactless monitoring in the care for older adults.

Circadian clock mechanisms are far-from-equilibrium dissipative structures. Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta, and gamma) play a key role in metabolic regulatory processes, particularly in heart muscle. Links between circadian rhythms (CRs) and PPARs have been established. Mammalian CRs involve at least two critical transcription factors, CLOCK and BMAL1 (Gekakis et al., 1998; Hogenesch et al., 1998). PPAR gamma plays a major role in both glucose and lipid metabolisms and presents circadian properties which coordinate the interplay between metabolism and CRs. PPAR gamma is a major component of the vascular clock. Vascular PPAR gamma is a peripheral regulator of cardiovascular rhythms controlling circadian variations in blood pressure and heart rate through BMAL1. We focused our review on diseases with abnormalities of CRs and with primary or secondary cardiac dysfunction. Moreover, these diseases presented changes in the Wnt/beta-catenin pathway and PPARs, according to two opposed profiles. Profile 1 was defined as follows: inactivation of the Wnt/beta-catenin pathway with increased expression of PPAR gamma. Profile 2 was defined as follows: activation of the Wnt/beta-catenin pathway with decreased expression of PPAR gamma. A typical profile 1 disease is arrhythmogenic right ventricular cardiomyopathy, a genetic cardiac disease which presents mutations of the desmosomal proteins and is mainly characterized by fatty acid accumulation in adult cardiomyocytes mainly in the right ventricle. The link between PPAR gamma dysfunction and desmosomal genetic mutations occurs via inactivation of the Wnt/beta-catenin pathway presenting oscillatory properties. A typical profile 2 disease is type 2 diabetes, with activation of the Wnt/beta-catenin pathway and decreased expression of PPAR gamma. CRs abnormalities are present in numerous pathologies such as cardiovascular diseases, sympathetic/parasympathetic dysfunction, hypertension, diabetes, neurodegenerative diseases, cancer which are often closely inter-related.

This study was designed to determine the effects of PPARalpha lack on cardiac mechanical performance and to identify potential intracellular mechanisms linking PPARalpha pathway deficiency to cardiac contractile dysfunction. Echocardiography, ex vivo papillary muscle assays, and in vitro motility assays were used to assess global, intrinsic ventricular muscle performance and myosin mechanical properties, respectively, in PPARalpha(-/-) and age-matched wild-type mice. Three-nitrotyrosine formation and 4-hydroxy-2-nonenal protein-adducts, both markers of oxidative damage, were analyzed by Western blot analysis and immunolabeling. Radical scavenging capacity was analyzed by measuring protein levels and/or activities of the main antioxidant enzymes, including catalase, glutathione peroxidase, and manganese and copper-zinc superoxide dismutases. Echocardiographic left ventricular fractional shortening in PPARalpha(-/-) was 16% lower than that in wild-type. Ex vivo left ventricular papillary muscle exhibited reduced shortening velocity and isometric tension (three- and twofold, respectively). In vitro myosin-based velocity was approximately 20% slower in PPARalpha(-/-), indicating that myosin itself was involved in the contractile dysfunction. Staining of 3-nitrotyrosine was more pronounced in PPARalpha(-/-), and myosin heavy chain was the main nitrated protein. Formation of 3-nitrotyrosine myosin heavy chain was twofold higher in PPARalpha(-/-) and 4-hydroxy-2-nonenal protein-adducts were threefold higher. The expression and activity of manganese superoxide dismutase were respectively 33% and 50% lower in PPARalpha(-/-), with no changes in copper-zinc superoxide dismutase, catalase, or glutathione peroxidase. These findings demonstrate that PPARalpha pathway deficiency impairs cardiac function and also identify oxidative damage to myosin as a link between PPARalpha deficiency and contractile dysfunction.

A new technique permits removal of the resting force from the muscle during the course of shortening and study of the maximum velocity of shortening with almost zero load at physiological initial muscle lengths. This unloading has been performed as a sudden unloading to zero total load (zero load clamping), or according to the resting length-tension relations, or according to an arbitrary unloading intermediate between both former modes of unloading. Using these various modes of unloading to zero load during shortening, it has been demonstrated that the maximum velocity of shortening V mflI remains constant between maximum length (\ max ) and a length 12.5% shorter than l mai . This unique force (zero load)-velocity (V mnx )-length (up to 12.5* below l mQI ) relation is independent of the initial muscle length over this range of lengths, independent of the time after the stimulus over the largest portion of the shortening phase, and independent of the sequence of length change and mode of unloading through which it arrived at zero load within this range of lengths. KEY WORDScat papillary muscle force-velocity-length relation myocardium V mnx quick release load clamping contractility calcium• In single skeletal muscle fibers, the velocity of shortening of lightly loaded fibers has been shown to be independent of sarcomere length until relatively short sarcomere lengths (i.e., < 1.9/A) are reached (1). On the other hand, force development depends greatly on the degree of thick and thin filament overlap and remains constant only between sarcomere lengths of 2.0 to 2.2/LI (1). In heart muscle, the problem is somewhat more complex. The muscle length where actively developed tension is maximum (l mni ) is claimed to be associated with a substantial resting force, and a significant resting force would persist as the initial muscle length is shortened below this length and developed force falls. Moreover, it has been asserted that the maximum velocity of shortening (V max ) of the unloaded muscle obtained by extrapolaFrom the

Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta‐catenin pathway and peroxisome proliferator‐activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta‐catenin pathway, while the activation of the canonical WNT/beta‐catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta‐catenin pathway is upregulated. In cancer cells, upregulation of the WNT/beta‐catenin signaling induces dramatic changes in key metabolic enzymes that modify their thermodynamic behavior. This leads to activation of pyruvate dehydrogenase kinase1 (PDK‐1) and monocarboxylate lactate transporter. Consequently, phosphorylation of PDK‐1 inhibits the pyruvate dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot be converted into acetyl‐coenzyme A (acetyl‐CoA) in mitochondria and only a part of acetyl‐CoA can enter the tricarboxylic acid cycle. This leads to aerobic glycolysis in spite of the availability of oxygen. This phenomenon is referred to as the Warburg effect. Cytoplasmic pyruvate is converted into lactate. The WNT/beta‐catenin pathway induces the transcription of genes involved in cell proliferation, i.e., MYC and CYCLIN D1. This ultimately promotes the nucleotide, protein and lipid synthesis necessary for cell growth and multiplication. In cancer, activation of the PI3K‐AKT pathway induces an increase of the aerobic glycolysis. Moreover, prostaglandin E2 by activating the canonical WNT pathway plays also a role in cancer. In addition in many cancer cells, PPAR gamma is downregulated. Moreover, PPAR gamma contributes to regulate some key circadian genes. In cancers, abnormalities in the regulation of circadian rhythms (CRs) are observed. CRs are dissipative structures which play a key‐role in far‐from‐equilibrium thermodynamics. In cancers, metabolism, thermodynamics and CRs are intimately interrelated.

Aim:To assess nurse-reported organizational readiness for implementing change in acute care hospitals.

SUMMARY1. Abrupt alterations in load (load-clamping) have been imposed on cat papillary muscles during the course of isotonic shortening, between the onset of shortening and peak shortening.2. For any given total load, whether imposed during the course of shortening or before stimulation, the velocity of shortening is determined solely by the instantaneous length, and not by the sequence of length and tension changes through which it arrived at that length.3. This unique force-velocity-length relation is independent oftime from just after the onset of shortening until just prior to peak shortening.4. These results suggest that a steady state exists for the maximum intensity of active state in heart muscle over a major portion of the time during which isometric force is rising, and that heart muscle always senses total load while shortening.