分类: 生物学 >> 生物物理学 提交时间: 2016-05-05
摘要: Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing, and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability, and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca2+ dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca2+ leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: RNA binding protein is identified as an important mediator of aberrant alternative splicing in muscle atrophy. The altered splicing of calcium channels, such as ryanodine receptors (RyRs), plays an important role in impaired excitation-contraction (E-C) coupling in muscle atrophy; however, the regulatory mechanisms of ryanodine receptor 1 (RyR1) alternative splicing leading to skeletal muscle atrophy remains to be investigated. In this study we demonstrated that CUG binding protein 1 (CUG-BP1) was up-regulated and the alternative splicing of RyR1 ASI (exon70) was aberrant during the process of neurogenic muscle atrophy both in human patients and mouse models. The gain and loss of function experiments in vivo demonstrated that altered splicing pattern of RyR1 ASI was directly mediated by an up-regulated CUG-BP1 function. Furthermore, we found that CUG-BP1 affected the calcium release activity in single myofibers and the extent of atrophy was significantly reduced upon gene silencing of CUG-BP1 in atrophic muscle. These findings improve our understanding of calcium signaling related biological function of CUG-BP1 in muscle atrophy. Thus, we provide an intriguing perspective of involvement of mis-regulated RyR1 splicing in muscular disease.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: Type Ia Supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a brightness of -10.5 absolute AB magnitudes -- the lowest luminosity early Type Ia signals ever detected -- revealing a hitherto unseen plateau in the $B$-band that results in a rapid redward color evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing $B$-band flux is best-explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed $B-V$ color evolution of the SN also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colors are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended sub-sonic mixing processes in some normal Type Ia Supernova explosions.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: SN~2018aoz is a Type Ia SN with a $B$-band plateau and excess emission in the infant-phase light curves $\lesssim$ 1 day after first light, evidencing an over-density of surface iron-peak elements as shown in our previous study. Here, we advance the constraints on the nature and origin of SN~2018aoz based on its evolution until the nebular phase. Near-peak spectroscopic features show the SN is intermediate between two subtypes of normal Type Ia: Core-Normal and Broad-Line. The excess emission could have contributions from the radioactive decay of surface iron-peak elements as well as ejecta interaction with either the binary companion or a small torus of circumstellar material. Nebular-phase limits on H$\alpha$ and He~I favour a white dwarf companion, consistent with the small companion size constrained by the low early SN luminosity, while the absence of [O~I] and He~I disfavours a violent merger of the progenitor. Of the two main explosion mechanisms proposed to explain the distribution of surface iron-peak elements in SN~2018aoz, the asymmetric Chandrasekhar-mass explosion is less consistent with the progenitor constraints and the observed blueshifts of nebular-phase [Fe~II] and [Ni~II]. The helium-shell double-detonation explosion is compatible with the observed lack of C spectral features, but current 1-D models are incompatible with the infant-phase excess emission, $B_{\rm max}-V_{\rm max}$ color, and absence of nebular-phase [Ca~II]. Although the explosion processes of SN~2018aoz still need to be more precisely understood, the same processes could produce a significant fraction of Type Ia SNe that appear normal after $\sim$ 1 day.