Cholesteryl ester transfer protein TaqIB polymorphism and its association with serum lipid levels and longevity in Chinese Bama Zhuang population

<p>Abstract</p> <p>Background</p> <p><it>Taq</it>IB polymorphism in the cholesteryl ester transfer protein (CETP) gene has been reported to be associated with serum high-density lipoprotein cholesterol (HDL-C) levels and longevity in several populations, but controversial results also arose probably due to racial/ethnic diversity. Bama is a remote and mountainous county located in the northwest of Guangxi, People's Republic of China, which has been well known for its longevity for centuries. The current study was to investigate the possible association of CETP <it>Taq</it>IB polymorphism with serum lipid levels and longevity in the Bama Zhuang population.</p> <p>Methods</p> <p>The CETP <it>Taq</it>IB genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in 523 long-lived inhabitants (long-lived group, LG; aged 90-107 years) and 498 healthy controls without longevity family history (non-long-lived group, non-LG; aged 40-69 years) residing in Bama County.</p> <p>Results</p> <p>The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were higher but TG, HDL-C/LDL-C ratio and the prevalence of dyslipidemia were lower in LG than in non-LG (<it>P </it>< 0.001 for all). There were no differences in the allelic and genotypic frequencies between the two groups (<it>P </it>> 0.05). Serum HDL-C levels and HDL-C/LDL-C ratio in LG were different among the genotypes (<it>P </it>< 0.01 for each), the subjects with B2B2 and B1B2 genotyes had higher HDL-C levels and HDL-C/LDL-C ratio than the subjects with B1B1genotye, whereas the levels of TC and HDL-C in non-LG were different among/between the genotypes (<it>P </it>< 0.01 for each), the B2 allele carriers had lower TC and higher HDL-C levels than the B2 allele noncarriers. Serum TG and HDL-C levels and HDL-C/LDL-C ratio were correlated with genotypes in LG, whereas serum TC and HDL-C levels were associated with genotypes in non-LG (<it>P </it>< 0.05-0.001).</p> <p>Conclusions</p> <p>The association of CETP <it>Taq</it>IB polymorphism and serum lipid profiles is different between LG and non-LG in the Chinese Bama Zhuang population. CETP <it>Taq</it>IB polymorphism might be one of the longevity-related genetic factors in this population.</p

DrM: Mastering Visual Reinforcement Learning through Dormant Ratio Minimization

Visual reinforcement learning (RL) has shown promise in continuous control tasks. Despite its progress, current algorithms are still unsatisfactory in virtually every aspect of the performance such as sample efficiency, asymptotic performance, and their robustness to the choice of random seeds. In this paper, we identify a major shortcoming in existing visual RL methods that is the agents often exhibit sustained inactivity during early training, thereby limiting their ability to explore effectively. Expanding upon this crucial observation, we additionally unveil a significant correlation between the agents' inclination towards motorically inactive exploration and the absence of neuronal activity within their policy networks. To quantify this inactivity, we adopt dormant ratio as a metric to measure inactivity in the RL agent's network. Empirically, we also recognize that the dormant ratio can act as a standalone indicator of an agent's activity level, regardless of the received reward signals. Leveraging the aforementioned insights, we introduce DrM, a method that uses three core mechanisms to guide agents' exploration-exploitation trade-offs by actively minimizing the dormant ratio. Experiments demonstrate that DrM achieves significant improvements in sample efficiency and asymptotic performance with no broken seeds (76 seeds in total) across three continuous control benchmark environments, including DeepMind Control Suite, MetaWorld, and Adroit. Most importantly, DrM is the first model-free algorithm that consistently solves tasks in both the Dog and Manipulator domains from the DeepMind Control Suite as well as three dexterous hand manipulation tasks without demonstrations in Adroit, all based on pixel observations

Salmon Calcitonin Exerts an Antidepressant Effect by Activating Amylin Receptors

Depressive disorder is defined as a psychiatric disease characterized by the core symptoms of anhedonia and learned helplessness. Currently, the treatment of depression still calls for medications with high effectiveness, rapid action, and few side effects, although many drugs, including fluoxetine and ketamine, have been approved for clinical usage by the Food and Drug Administration (FDA). In this study, we focused on calcitonin as an amylin receptor polypeptide, of which the antidepressant effect has not been reported, even if calcitonin gene-related peptides have been previously demonstrated to improve depressive-like behaviors in rodents. Here, the antidepressant potential of salmon calcitonin (sCT) was first evaluated in a chronic restraint stress (CRS) mouse model of depression. We observed that the immobility duration in CRS mice was significantly increased during the tail suspension test and forced swimming test. Furthermore, a single administration of sCT was found to successfully rescue depressive-like behaviors in CRS mice. Lastly, AC187 as a potent amylin receptor antagonist was applied to investigate the roles of amylin receptors in depression. We found that AC187 significantly eliminated the antidepressant effects of sCT. Taken together, our data revealed that sCT could ameliorate a depressive-like phenotype probably via the amylin signaling pathway. sCT should be considered as a potential therapeutic candidate for depressive disorder in the future

Plasma Levels of Amino Acids Related to Urea Cycle and Risk of Type 2 Diabetes Mellitus in Chinese Adults

Objective: This study aimed to test associations between type 2 diabetes mellitus (T2DM) and metabolites in urea cycle including arginine, citrulline and ornithine.Methods:This study used a hospital-based cross-sectional study design. We retrieved medical notes of 401 in-patients with onset of T2DM within 2 years and 1,522 healthy subjects who attended annual physical examination. All cases were admitted to a tertiary care center in Jinzhou, China from May 2015 to August 2016. Binary logistic regression analyses were performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs).Results:Patients with T2DM had higher arginine, and lower ornithine than control subjects. Levels of citrulline were similar in two groups. Arginine was positively associated with T2DM (ORs: 1.20, 1.17–1.23) while ornithine was negatively associated with T2DM (OR: 0.89, 0.88–0.91). After adjustment for other amino acids and traditional risk factors, these associations were still significant and persistent for arginine and ornithine. The association between citrulline and T2DM was not significant. Their ratios of pairs of two amino acids were associated with increased risk of T2DM. After adjustment for other ratios of amino acids, effect size for T2DM remained significant. Further adjustment for traditional risk factors did not lead to large changes (ORs: 1.78, 1.20–2.65 for the ratio of arginine to ornithine; ORs: 1.59, 1.37–1.86 for the ratio of citrulline to ornithine, respectively) except the ratio of arginine to citrulline.Conclusions: Plasma levels of amino acids related to urea cycle and their ratios of these amino-acids were associated with T2DM in Chinese adults

Uniparental Genetic Analyses Reveal the Major Origin of Fujian Tanka from Ancient Indigenous Daic Populations

The Fujian Tanka people are officially classified as a southern Han ethnic group while they have customs similar to Daic and Austronesion people. Whether they originated in Han or Daic people, there is no consensus. Three hypotheses have been proposed to explain the origin of this group: 1) the Han Chinese origin, 2) the ancient Daic origin, 3) and the admixture between Daic and Han. In this study, we address this issue by analyzing the paternal Y chromosome and maternal mtDNA variation of 62 Fujian Tanka and 25 neighboring Han in Fujian. We found that the southern East Asian predominant haplogroups, e.g. O1a1a-P203 and O1b1a1a-M95 of Y chromosome and F2a, M7c1, and F1a1 of mtDNA, reach relatively high frequencies in Tanka. The interpopulation comparison reveals that the Tanka have a closer affinity with Daic populations than with Han Chinese in paternal lineages while are closely clustered with southern Han populations such as Hakka and Chaoshanese in maternal lineages. Network and haplotype-sharing analyses also support the admixture hypothesis. The Fujian Tanka mainly originate from the ancient indigenous Daic people and have only limited gene flows from Han Chinese populations. Notably, the divergence time inferred by the Tanka-specific haplotypes indicates that the formation of Fujian Tanka was a least 1033.8-1050.6 years before present (the early Northern Song Dynasty), indicating that they are indigenous population, not late Daic migrants from southwestern China

Uniparental Genetic Analyses Reveal the Major Origin of Fujian Tanka from Ancient Indigenous Daic Populations

The Fujian Tanka people are officially classified as a southern Han ethnic group while they have customs similar to Daic and Austronesion people. Whether they originated in Han or Daic people, there is no consensus. Three hypotheses have been proposed to explain the origin of this group: 1) the Han Chinese origin, 2) the ancient Daic origin, 3) and the admixture between Daic and Han. In this study, we address this issue by analyzing the paternal Y chromosome and maternal mtDNA variation of 62 Fujian Tanka and 25 neighboring Han in Fujian. We found that the southern East Asian predominant haplogroups, e.g. O1a1a-P203 and O1b1a1a-M95 of Y chromosome and F2a, M7c1, and F1a1 of mtDNA, reach relatively high frequencies in Tanka. The interpopulation comparison reveals that the Tanka have a closer affinity with Daic populations than with Han Chinese in paternal lineages while are closely clustered with southern Han populations such as Hakka and Chaoshanese in maternal lineages. Network and haplotype-sharing analyses also support the admixture hypothesis. The Fujian Tanka mainly originate from the ancient indigenous Daic people and have only limited gene flows from Han Chinese populations. Notably, the divergence time inferred by the Tanka-specific haplotypes indicates that the formation of Fujian Tanka was a least 1033.8-1050.6 years before present (the early Northern Song Dynasty), indicating that they are indigenous population, not late Daic migrants from southwestern China

The Hidden Nematic Fluctuations in the Triclinic (Ca0.85La0.15)10(Pt3As8)(Fe2As2)5 Superconductor Revealed by Ultrafast Optical Spectroscopy

We reported the quasiparticle relaxation dynamics of an optimally doped triclinic iron-based superconductor (Ca$_{0.85}$La$_{0.15}$)$_{10}$(Pt$_3$As$_8$)(Fe$_2$As$_2$)$_5$ with bulk $T_c$ = 30 K using polarized ultrafast optical pump-probe spectroscopy. Our results reveal anisotropic transient reflectivity induced by nematic fluctuations develops below $T_{nem}$ $\approx$ 120 K and persists in the superconducting states. Measurements under high pump fluence reveal three distinct, coherent phonon modes at frequencies of 1.6, 3.5, and 4.7 THz, corresponding to $A_{1g}(1)$, $E_g$, and $A_{1g}(2)$ modes, respectively. The high-frequency $A_{1g}(2)$ mode corresponds to the $c$-axis polarized vibrations of FeAs planes with a nominal electron-phonon coupling constant $\lambda _{A_{1g}(2)}$ $\approx$ 0.139 $\pm$ 0.02. Our findings suggest that the superconductivity and nematic state are compatible but competitive at low temperatures, and the $A_{1g}$ phonons play an important role in the formation of Cooper pairs in (Ca$_{0.85}$La$_{0.15}$)$_{10}$(Pt$_3$As$_8$)(Fe$_2$As$_2$)$_5$.Comment: 6 pages, 3 figures and Supplemental Material