Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

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Nearest Neighbor Classification Rule for Mixtures of Discrete and Continuous Random Variables

In this paper very simple nonparametric classification rule for mixtures of discrete and continuous random variables is described. It is based on the method of nearest neighbor proposed by Cover and Hart (1967). The bounds on the limit of the nearest neighbor rule risks are given. Both lower and upper bound depend on the Bayes risk and the loss function. Finally the method is compared with other existing methods on some practical data set.     

A Cross-linking Mass Spectrometry Approach Defines Protein Interactions in Yeast Mitochondria

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Highlights

• •XL-MS reveals new PPIs in yeast mitochondria under glycerol and glucose condition.
• •Significant but limited results from quantitative XL-MS experiments.
• •Ndi1 participates in a CIII₂CIV₂ respiratory supercomplex.
• •Min8 promotes assembly of Cox12 into an intermediate complex IV.

     

Targeting age‐specific changes in CD4+ T cell metabolism ameliorates alloimmune responses and prolongs graft survival

Age impacts alloimmunity. Effects of aging on T‐cell metabolism and the potential to interfere with immunosuppressants have not been explored yet. Here, we dissected metabolic pathways of CD4⁺ and CD8⁺ T cells in aging and offer novel immunosuppressive targets. Upon activation, CD4⁺ T cells from old mice failed to exhibit adequate metabolic reprogramming resulting into compromised metabolic pathways, including oxidative phosphorylation (OXPHOS) and glycolysis. Comparable results were also observed in elderly human patients. Although glutaminolysis remained the dominant and age‐independent source of mitochondria for activated CD4⁺ T cells, old but not young CD4⁺ T cells relied heavily on glutaminolysis. Treating young and old murine and human CD4⁺ T cells with 6‐diazo‐5‐oxo‐l‐norleucine (DON), a glutaminolysis inhibitor resulted in significantly reduced IFN‐γ production and compromised proliferative capacities specifically of old CD4⁺ T cells. Of translational relevance, old and young mice that had been transplanted with fully mismatched skin grafts and treated with DON demonstrated dampened Th1‐ and Th17‐driven alloimmune responses. Moreover, DON diminished cytokine production and proliferation of old CD4⁺ T cells in vivo leading to a significantly prolonged allograft survival specifically in old recipients. Graft prolongation in young animals, in contrast, was only achieved when DON was applied in combination with an inhibition of glycolysis (2‐deoxy‐d‐glucose, 2‐DG) and OXPHOS (metformin), two alternative metabolic pathways. Notably, metabolic treatment had not been linked to toxicities. Remarkably, immunosuppressive capacities of DON were specific to CD4⁺ T cells as adoptively transferred young CD4⁺ T cells prevented immunosuppressive capacities of DON on allograft survival in old recipients. Depletion of CD8⁺ T cells did not alter transplant outcomes in either young or old recipients. Taken together, our data introduce an age‐specific metabolic reprogramming of CD4⁺ T cells. Targeting those pathways offers novel and age‐specific approaches for immunosuppression.     

Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma

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Highlights

• •Flow cytometry analysis is used to isolate ASC speck⁽⁺⁾ NPC cells.
• •Proteome analysis of ASC speck⁽⁺⁾ NPC cells reveals enriched mitochondrial OxPhos proteins.
• •OxPhos proteins mediate NLRP3 inflammasome activation through mtROS.
• •OxPhos proteins, NDUFB8 and ATP5B are correlated with NPC local recurrence.

     

Evolutionary assembly of cooperating cell types in an animal chemical defense system

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Animal models for respiratory chain disease

Elucidation of the pathogenesis in respiratory chain diseases is of great importance for developing specific treatments. The limitations inherent to the use of patient material make studies of human tissues often difficult and the mouse has therefore emerged as a suitable model organism for studies of respiratory chain diseases. In this review, we present an overview of the field and discuss in depth a few examples of animal models reproducing pathology of human disease with primary and secondary respiratory chain involvement.     

N-糖蛋白去糖基化酶（PNGase）的研究进展

N-糖蛋白去糖基化酶（PNGase）是一种广泛存在于真菌、植物、哺乳动物中的去糖基化酶，可以水解N-糖蛋白或 N-糖肽上天冬酰胺与寡糖链连接的化学键，并释放出完整的N-寡糖。PNGase在生物体内参与蛋白质降解、器官发育、个体生长等过程。人PNGase基因功能缺陷会导致先天性去糖基化障碍，小鼠PNGase缺陷会导致胚胎致死性，线虫PNGase缺陷使其寿命下降。本文对PNGase在不同物种的分布、蛋白质结构、酶学功能及生物学功能进行阐述，为PNGase的生理病理功能及致病机制的基础研究提供思路，为PNGase作为糖生物学工具酶或药物开发的创新应用研究奠定基础。     

Respiratory components in acidophilic bacteria that respire on iron

Abstract

Microorganisms capable of aerobic respiration on ferrous ions are spread throughout eubacterial and archaebacterial phyla. Phylogenetically distinct organisms were shown to express spectrally distinct redox‐active biomolecules during autotrophic growth on soluble iron. A new iron‐oxidizing eubacterium, designated as strain Funis, was investigated. Strain Funis was judged to be different from other known iron‐oxidizing bacteria on the bases of comparative lipid analyses, 16S rRNA sequence analyses, and cytochrome composition studies. When grown autotrophically on ferrous ions, Funis produced conspicuous levels of a novel acid‐stable, acid‐soluble yellow cytochrome with a distinctive absorbance peak at 579 nm in the reduced state.

Stopped‐flow spectrophotometric kinetic studies were conducted on respiratory chain components isolated from cell‐free extracts of Thiobacillus ferrooxidans. Experimental results were consistent with a model where the primary oxidant of ferrous ions is a highly aggregated c‐type cytochrome that then reduces the periplasmic rusticyanin. The Fe(II)‐dependent, cytochrome c‐catalyzed reduction of the rusticyanin possessed three kinetic properties in common with corresponding intact cells that respire on iron: the same anion specificity, a similar dependence of the rate on the concentration of ferrous ions, and similar rates at saturating concentrations of ferrous ions     

Sex differences in leg dexterity are not present in elite athletes

We studied whether the time-varying forces that control unstable foot–ground interactions provide insight into the neural control of dynamic leg function. Twenty elite (10 F, 26.4 ± 3.5 yrs) and 20 recreational (10 F, 24.8 ± 2.4 yrs) athletes used an isolated leg to maximally compress a slender spring designed to buckle at low forces while seated. The foot forces during the compression at the edge of instability quantify the maximal sensorimotor ability to control dynamic foot–ground interactions. Using the nonlinear analysis technique of attractor reconstruction, we characterized the spatial (interquartile range IQR) and geometric (trajectory length TL, volume V, and sum of edge lengths SE) features of the dynamical behavior of those force time series. ANOVA confirmed the already published effect of sex, and a new effect of athletic ability, respectively, in TL (p = 0.014 and p < 0.001), IQR (p = 0.008 and p < 0.001), V (p = 0.034 and p = 0.002), and SE (p = 0.033 and p < 0.001). Further analysis revealed that, for recreational athletes, females exhibited weaker corrective actions and greater stochasticity than males as per their greater mean values of TL (p = 0.003), IQR (p = 0.018), V (p = 0.017), and SE (p = 0.025). Importantly, sex differences disappeared in elite athletes. These results provide an empirical link between sex, athletic ability, and nonlinear dynamical control. This is a first step in understanding the sensorimotor mechanisms for control of unstable foot–ground interactions. Given that females suffer a greater incidence of non-contact knee ligament injuries, these non-invasive and practical metrics of leg dexterity may be both indicators of athletic ability, and predictors of risk of injury.