N6-methyladenosine (m6A) is a dynamic and reversible RNA modification that has emerged as a crucial player in the life cycle of RNA, thus playing a pivotal role in various biological processes. In recent years, the potential involvement of RNA m6A modification in aging and age-related diseases has gained increasing attention, making it a promising target for understanding the molecular mechanisms underlying aging and developing new therapeutic strategies. This Perspective article will summarize the current advances in aging-related m6A regulation, highlighting the most significant findings and their implications for our understanding of cellular senescence and aging, and the potential for targeting RNA m6A regulation as a therapeutic strategy. We will also discuss the limitations and challenges in this field and provide insights into future research directions. By providing a comprehensive overview of the current state of the field, this Perspective article aims to facilitate further advances in our understanding of the molecular mechanisms underlying aging and to identify new therapeutic targets for aging-related diseases. 相似文献
PtdIns and PtdInsP kinases from normal erythrocyte (AA) membranes and sickle cell anaemia erythrocyte (SS) membranes have been characterized. PtdIns kinase was studied in native membranes under conditions in which PtdInsP kinase and PtdInsP phosphatase do not express any activity. Kinetic analysis of the AA and SS PtdIns kinases indicate similar Km values for PtdIns and ATP but higher Vmax values for SS PtdIns kinase. PtdInsP kinase was partially purified from erythrocyte ghosts by NaCl extraction. The kinetic parameters of PtdInsP kinase determined under these conditions were similar in AA and SS NaCl extracts. These data suggest the presence of some effector of PtdIns kinase in SS cell membranes, resulting in a greater activity of the enzyme. This leads consequently, to increase the PtdInsP pool and to activate PtdInsP kinase, in agreement with our previous observations of a greater [32P]Pi incorporation in both polyphosphoinositides in SS cells relatively to AA cells. 相似文献
Using both chromosomal in situ hybridization and molecular techniques, we report the genetic localization of the gene coding for the alpha 1 subunit of the skeletal slow Ca2+ current channel/DHP receptor gene (Cchl1a3) on human Chromosome (Chr) 1 (1q31–1q32 region) and on mouse Chr 1 region (F-G). On the basis of single-strand conformation polymorphism (SSCP-PCR) analysis in an interspecific backcross, we have determined that the Cchl1a3=mdg (muscular dysgenesis) locus is very closely linked to the myogenin (Myog) locus. 相似文献
The garnet-type phase Li7La3Zr2O12 (LLZO) attracts significant attention as an oxide solid electrolyte to enable safe and robust solid-state batteries (SSBs) with potentially high energy density. However, while significant progress has been made in demonstrating compatibility with Li metal, integrating LLZO into composite cathodes remains a challenge. The current perspective focuses on the critical issues that need to be addressed to achieve the ultimate goal of an all-solid-state LLZO-based battery that delivers safety, durability, and pack-level performance characteristics that are unobtainable with state-of-the-art Li-ion batteries. This perspective complements existing reviews of solid/solid interfaces with more emphasis on understanding numerous homo- and heteroionic interfaces in a pure oxide-based SSB and the various phenomena that accompany the evolution of the chemical, electrochemical, structural, morphological, and mechanical properties of those interfaces during processing and operation. Finally, the insights gained from a comprehensive literature survey of LLZO–cathode interfaces are used to guide efforts for the development of LLZO-based SSBs. 相似文献
The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV.
The protooncogene protein, Bcl-2, protects cells from apoptosis and ensures their survival in vitro by inhibiting the action
of the apoptosis-inducer, Bax. Its expression in proliferative and long-lived cells in vivo also indicates that it protects
against cell death. The chondrocytes of the epiphyseal plate cartilage undergo a series of maturation steps and deposit mineral
in the cartilage matrix before dying. The possibility that Bcl-2 helps protect chondrocytes until mineral deposition is completed
was investigated by determining the distribution of Bcl-2 immunoreactivity in the epiphyseal plate cartilage of growing rats
and its subcellular localization, using a specific antibody. The involvement of Bax in the triggering of chondrocyte death
was checked by immunocytochemistry. Bcl-2 expression in the osteoblasts and the final result of their evolution, the osteocytes,
was also examined in trabecular bone. Bcl-2 immunoreactivity was non-uniformly distributed throughout the epiphyseal cartilage.
It was maximal in proliferative chondrocytes, decreased in mature chondrocytes, and low in hypertrophic chondrocytes, whereas
there was Bax immunoreactivity in all chondrocytes examined. Immunolabeling was intense in osteoblasts but considerably lower
in fully differentiated osteocytes. Bcl-2 immunoreactivity was mainly in the cytoplasm of chondrocytes, osteoblasts, and early
osteocytes; the nuclei appeared clear. The subcellular distribution of Bcl-2 immunolabeling in chondrocytes, revealed by gold
particles in the electron microscope, showed that gold particles were frequently concentrated in the mitochondria in all the
cartilage zones and lay mainly within the organelles, not at their periphery. The endoplasmic reticulum contained moderate
immunoreactivity and there were few gold particles in the cytoplasm and nuclei. The number of gold particles decreased in
all the subcellular compartments from proliferative to hypertrophic chondrocytes. In contrast, Bax immunoreactivity changed
little during chondrocyte terminal evolution, and its subcellular distribution mirrored that of Bcl-2. These immunocytochemical
data indicate that Bcl-2 helps maintain chondrocytes and osteoblasts until their terminal maturation.
Accepted: 19 February 1997 相似文献