High Density Lipoprotein Protects Mesenchymal Stem Cells from Oxidative Stress-Induced Apoptosis via Activation of the PI3K/Akt Pathway and Suppression of Reactive Oxygen Species

The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS

Selective synaptic remodeling of amygdalocortical connections associated with fear memory

Neural circuits underlying auditory fear conditioning have been extensively studied. Here we identified a previously unexplored pathway from the lateral amygdala (LA) to the auditory cortex (ACx) and found that selective silencing of this pathway using chemo- and optogenetic approaches impaired fear memory retrieval. Dual-color in vivo two-photon imaging of mouse ACx showed pathway-specific increases in the formation of LA axon boutons, dendritic spines of ACx layer 5 pyramidal cells, and putative LA-ACx synaptic pairs after auditory fear conditioning. Furthermore, joint imaging of pre- and postsynaptic structures showed that essentially all new synaptic contacts were made by adding new partners to existing synaptic elements. Together, these findings identify an amygdalocortical projection that is important to fear memory expression and is selectively modified by associative fear learning, and unravel a distinct architectural rule for synapse formation in the adult brain

Petrogenesis of the granitoids related to skarn-type mineralization in the Nyainqentanglha Metallogenic Belt, Tibet

The Nyainqentanglha Metallogenic Belt (NMB) is an economically important lead-zinc ore province located in the Central and Southern Lhasa subterrane, Tibet. The NMB consists mainly of skarn-type lead-zinc polymetallic deposits that form at the contact between Late Cretaceous-Eocene intrusive rocks and carbonatite/volcanic-sedimentary strata. These deposits are generally considered to be related to S-type granites formed by the Indo-Asian continental collision. However, the εHf(t) (ave. −1.6) of zircons from the mineralization-related granitoids indicates that it is crust-mantle mixing products. In addition, the volcanic rocks of the Dianzhong Formation, which have a close spatio-temporal relationship with the skarn-type deposits, typically show mantle-derived features. Therefore, the occurrence of AFC processes in mantle-derived material passing through the thick basement of the Lhasa Terrane may better explain the genesis of the mineralization-related granitoids. In this study, we present results on zircon U–Pb ages, major and trace elements of the granitoids associated with skarn-type mineralization from the Narusongduo district. LA-ICP-MS zircon U–Pb dating shows that the granite formed in the Paleocene (58.6 ± 0.5 Ma). Combined with published regional data, we propose the mineralization age of the skarn-type deposits in the NMB ranges from the Late Cretaceous to Eocene. Detailed petrology and geochemistry of mineralization-related granitoids are evaluated to constrain the magmatic evolution process. The granitoids have high contents of SiO2 (mean 72.8 %), K2O (mean 4.0 %), Rb (mean 186.9 ppm), DI (differentiation index) 84.7, A/CNK (mean 1.3), and low contents of MgO, TFe, suggesting that the granitoids have undergone strong differentiation. In addition, the continuous decrease of P2O5 with progressive differentiation and the lower average P2O5 abundance suggest that the mineralization-related granitoids belong to the I-type granite. The results suggest that the mineralization-related granitoids in the NMB originated from the mantle and is the fractionated I-type granite formed by the process of AFC (Assimilation and Fractional Crystallization). Considering that Pb and Zn often coexist in deposits, we suggest that magmatic differentiation may play an important role in the formation of the granite-related Pb and Zn mineralization

CARD8 rs2043211 Polymorphism is Associated with Gout in a Chinese Male Population

Background &Aim: Previous studies have suggested genetic factors are involved in the development of gout. We performed a case-control study to investigate the genetic association between CARD8 rs2043211 polymorphism and gout. Methods: A total of 396 male patients with gout and 403 age- and sex- matched healthy controls were included in this study. Genotyping was performed using TaqMan SNP Genotyping Assays. An association analysis was carried out using the χ2 test. The genotype-phenotype analysis was also conducted. Results: The genotype distribution of CARD8 rs2043211 polymorphism confirmed to HWE in the controls (P = 0.27). There was an obvious difference in the genotype distribution of CARD8 rs2043211 polymorphism between cases and controls (P = 0.017). In addition, there was an obvious association between CARD8 rs2043211 polymorphism and gout under the recessive comparison model (AA vs. TT/TA: OR = 0.65, 95%CI 0.47-0.88, P = 0.006). Patients carrying genotype TT of CARD8 rs2043211 polymorphism had higher triglycerides levels compared to those carrying the AA genotype (2.77±2.08 mmol/L vs. 2.07±1.15 mmol/L, P = 0.01). Patients with the TT genotype also had significantly higher systolic blood pressure compared with those with the AA genotype (142.11±21.10 mmHg vs. 135.38±14.66 mmHg, P = 0.03). Patients carrying TT genotype also had an increased risk of renal calculus compared with those carrying the AA genotype. Conclusion: CARD8 rs2043211 polymorphism is significantly associated with susceptibility to gout in Chinese Han males

Identification of Two Novel Mutations of ABCD1 Gene in Pedigrees with X-Linked Adrenoleukodystrophy and Review of the Literature

Background. X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal metabolism disorder, resulting from the loss-of-function mutation of ATP-binding cassette protein subfamily D1 (ABCD1) gene. The dysfunction of ALD protein, a peroxisomal ATP-binding cassette transporter, results in the excessive saturated very long-chain fatty acids (VLCFAs) accumulation in organs including the brain, spine, and adrenal cortex. X-ALD is characterized as the childhood, adolescent, adult cerebral ALD, adrenomyeloneuropathy (AMN), adrenal insufficiency, and asymptomatic phenotypes, exhibiting a high variety of clinical neurological manifestations with or without adrenocortical insufficiency. Results. In this study, we reported two cases of X-ALD, which were first diagnosed as adrenal insufficiency (Addison’s disease) and treated with adrenocortical supplement. However, both of the cases progressed as neurological symptoms and signs after decades. Elevated VLCFAs level, brain MRI scan, and genetic analysis confirmed final diagnosis. In addition, we identified two novel mutations of ABCD1 gene, NM_000033.3 (ABCD1): c.874_876delGAG (p.Glu292del) and NM_000033.3 (ABCD1): c.96_97delCT (p.Tyr33Profs∗161), in exon 1 of ABCD1 gene. Sanger sequencing confirmed that the proband’s mother of the first case was heterozygous carrying the same variant. Adrenal insufficiency-only type is very rare; however, it may be the starting performance of X-ALD. In addition, we summarized reported mutation sites and clinical manifestations to investigate the correlationship of phenotype-genotype of X-ALD. Conclusions. The early warning manifestations should be noticed, and the probability of X-ALD should be considered. This report could be beneficial for the early diagnosis and genetic counseling for patients with X-ALD

The Sunway TaihuLight supercomputer: system and applications

The Sunway TaihuLight supercomputer is the world's first system with a peak performance greater than 100 PFlops. In this paper, we provide a detailed introduction to the TaihuLight system. In contrast with other existing heterogeneous supercomputers, which include both CPU processors and PCIe-connected many-core accelerators (NVIDIA GPU or Intel Xeon Phi), the computing power of TaihuLight is provided by a homegrown many-core SW26010 CPU that includes both the management processing elements (MPEs) and computing processing elements (CPEs) in one chip. With 260 processing elements in one CPU, a single SW26010 provides a peak performance of over three TFlops. To alleviate the memory bandwidth bottleneck in most applications, each CPE comes with a scratch pad memory, which serves as a user-controlled cache. To support the parallelization of programs on the new many-core architecture, in addition to the basic C/C++ and Fortran compilers, the system provides a customized Sunway OpenACC tool that supports the OpenACC 2.0 syntax. This paper also reports our preliminary efforts on developing and optimizing applications on the TaihuLight system, focusing on key application domains, such as earth system modeling, ocean surface wave modeling, atomistic simulation, and phase-field simulation

The Sunway TaihuLight supercomputer: system and applications

The Sunway TaihuLight supercomputer is the world's first system with a peak performance greater than 100 PFlops. In this paper, we provide a detailed introduction to the TaihuLight system. In contrast with other existing heterogeneous supercomputers, which include both CPU processors and PCIe-connected many-core accelerators (NVIDIA GPU or Intel Xeon Phi), the computing power of TaihuLight is provided by a homegrown many-core SW26010 CPU that includes both the management processing elements (MPEs) and computing processing elements (CPEs) in one chip. With 260 processing elements in one CPU, a single SW26010 provides a peak performance of over three TFlops. To alleviate the memory bandwidth bottleneck in most applications, each CPE comes with a scratch pad memory, which serves as a user-controlled cache. To support the parallelization of programs on the new many-core architecture, in addition to the basic C/C++ and Fortran compilers, the system provides a customized Sunway OpenACC tool that supports the OpenACC 2.0 syntax. This paper also reports our preliminary efforts on developing and optimizing applications on the TaihuLight system, focusing on key application domains, such as earth system modeling, ocean surface wave modeling, atomistic simulation, and phase-field simulation

thesunwaytaihulightsupercomputersystemandapplications

The Sunway TaihuLight supercomputer is the world's first system with a peak performance greater than 100 PFlops. In this paper, we provide a detailed introduction to the TaihuLight system. In contrast with other existing heterogeneous supercomputers, which include both CPU processors and PCIe-connected many-core accelerators (NVIDIA GPU or Intel Xeon Phi), the computing power of TaihuLight is provided by a homegrown many-core SW26010 CPU that includes both the management processing elements (MPEs) and computing processing elements (CPEs) in one chip. With 260 processing elements in one CPU, a single SW26010 provides a peak performance of over three TFlops. To alleviate the memory bandwidth bottleneck in most applications, each CPE comes with a scratch pad memory, which serves as a user-controlled cache. To support the parallelization of programs on the new many-core architecture, in addition to the basic C/C++ and Fortran compilers, the system provides a customized Sunway OpenACC tool that supports the OpenACC 2.0 syntax. This paper also reports our preliminary efforts on developing and optimizing applications on the TaihuLight system, focusing on key application domains, such as earth system modeling, ocean surface wave modeling, atomistic simulation, and phase-field simulation