The maintenance of mitochondrial integrity is critical for muscle health. Mitochondria, indeed, play vital roles in a wide range of cellular processes, including energy supply, Ca2+ homeostasis, ...retrograde signaling, cell death, and many others. All mitochondria-containing cells, including skeletal muscle cells, dispose of several pathways to maintain mitochondrial health, including mitochondrial biogenesis, mitochondrial-derived vesicles, mitochondrial dynamics (fusion and fission process shaping mitochondrial morphology), and mitophagy—the process in charge of the removal of mitochondria though autophagy. The loss of skeletal muscle mass (atrophy) is a major health problem worldwide, especially in older people. Currently, there is no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging, a process termed sarcopenia. There is increasing data, including our own, suggesting that accumulation of dysfunctional mitochondria contributes to the development of sarcopenia. Impairments in mitochondrial dynamics and mitophagy were recently proposed to contribute to sarcopenia. This review summarizes the current state of knowledge on the role played by mitochondrial dynamics and mitophagy in skeletal muscle health and in the development of sarcopenia. We also highlight recent studies showing that enhancing mitophagy in skeletal muscle is a promising therapeutic target to prevent or even treat skeletal muscle dysfunction in the elderly.
Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even ...survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications.
The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD.
An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards.
We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality.
Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.
The common fixed point theorems, similar to those of Ćirić Lj.B. Ćirić, On a common fixed point theorem of a Gregus type, Publ. Inst. Math. (Beograd) (N.S.) 49 (1991) 174–178; Lj.B. Ćirić, On ...Diviccaro, Fisher and Sessa open questions, Arch. Math. (Brno) 29 (1993) 145–152; Lj.B. Ćirić, On a generalization of Gregus fixed point theorem, Czechoslovak Math. J. 50 (2000) 449–458, Fisher and Sessa B. Fisher, S. Sessa, On a fixed point theorem of Gregus, Internat. J. Math. Math. Sci. 9 (1986) 23–28, Jungck G. Jungck, On a fixed point theorem of Fisher and Sessa, Internat. J. Math. Math. Sci. 13 (1990) 497–500 and Mukherjee and Verma R.N. Mukherjee, V. Verma, A note on fixed point theorem of Gregus, Math. Japon. 33 (1988) 745–749, are proved for a Banach operator pair. As applications, common fixed point and approximation results for Banach operator pair satisfying Ćirić type contractive conditions are obtained without the assumption of linearity or affinity of either
T or
I. Our results unify and generalize various known results to a more general class of noncommuting mappings.
► Relations between Lmas,cr and energy savings potential (Δ) are obtained. ► Lmas,cr increases with increasing Δ. ► For given Lmas, cooling and heating energy-savings potentials are same. ► For Δ in ...the range 70–99%, Lmas,cr ranges between 6 and 30cm. ► Savings in loads are about 17% for cooling and 35% for heating.
Effects of varying amount and location of thermal mass on dynamic heat-transfer characteristics of insulated building walls with same nominal resistance (Rn-value) are investigated numerically under steady periodic conditions using climatic data of Riyadh. Concepts of “thermal-mass energy-savings potential” (Δ) and “critical thermal-mass thickness” (Lmas,cr) are developed and utilized in order to determine thermal mass thickness (Lmas) required for a selected desirable percentage of energy savings. Results show that daily transmission loads are not affected by Lmas for representative days of months in summer and winter. However, for moderate months, daily cooling and heating transmission loads decrease with increasing Lmas and either diminish to zero or be reduced asymptotically to constant values. For all months, peak transmission loads and decrement factor decrease, while time lag increases, with increasing Lmas. For a given Lmas, a wall with outside insulation gives better overall performance than a wall with inside insulation. While Rn-value is constant, wall dynamic resistance (Rd-value) changes and represents actual variations in transmission loads. For Δ in the range 70–99%, Lmas,cr ranges between 6 and 30cm by using heavyweight concrete. It is found that maximum savings in yearly cooling and heating transmission loads are about 17% and 35%, respectively, as a result of optimizing Lmas for same Rn-value. It is recommended that building walls should contain Lmas,cr that corresponds to high Δ (≈95%) and with insulation placed on outside for applications with continuously operating year-round AC.
Plasma HDL levels have a protective role in atherosclerosis, yet clinical therapies to raise HDL levels have remained elusive. Recent advances in the understanding of lipid metabolism have revealed ...that miR-33, an intronic microRNA located within the SREBF2 gene, suppresses expression of the cholesterol transporter ABC transporter A1 (ABCA1) and lowers HDL levels. Conversely, mechanisms that inhibit miR-33 increase ABCA1 and circulating HDL levels, suggesting that antagonism of miR-33 may be atheroprotective. As the regression of atherosclerosis is clinically desirable, we assessed the impact of miR-33 inhibition in mice deficient for the LDL receptor (Ldlr-/- mice), with established atherosclerotic plaques. Mice treated with anti-miR33 for 4 weeks showed an increase in circulating HDL levels and enhanced reverse cholesterol transport to the plasma, liver, and feces. Consistent with this, anti-miR33-treated mice showed reductions in plaque size and lipid content, increased markers of plaque stability, and decreased inflammatory gene expression. Notably, in addition to raising ABCA1 levels in the liver, anti-miR33 oligonucleotides directly targeted the plaque macrophages, in which they enhanced ABCA1 expression and cholesterol removal. These studies establish that raising HDL levels by anti-miR33 oligonucleotide treatment promotes reverse cholesterol transport and atherosclerosis regression and suggest that it may be a promising strategy to treat atherosclerotic vascular disease.
In this work we discuss some recent results about KKM mappings in cone metric spaces. We also discuss the fixed point existence results of multivalued mappings defined on such metric spaces. In ...particular we show that most of the new results are merely copies of the classical ones and do not necessitate the underlying Banach space nor the associated cone.
Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, ...redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles.
Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca(++) retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor.
We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis and increased autophagy compared with the ventilatory muscles and that autophagy in skeletal muscles during sepsis is regulated in part through the NFκB transcription factor.
KKM mappings in cone b -metric spaces Hussain, N.; Shah, M.H.
Computers & mathematics with applications (1987),
08/2011, Letnik:
62, Številka:
4
Journal Article
Recenzirano
Odprti dostop
In this paper we establish some topological properties of the cone
b
-metric spaces and then improve some recent results about KKM mappings in the setting of a cone
b
-metric space. We also prove ...some fixed point existence results for multivalued mappings defined on such spaces.