Guidelines for model adaptation: A study of the transferability of a general seagrass ecosystem Dynamic Bayesian Networks model

In general, it is not feasible to collect enough empirical data to capture the entire range of processes that define a complex system, either intrinsically or when viewing the system from a different geographical or temporal perspective. In this context, an alternative approach is to consider model transferability, which is the act of translating a model built for one environment to another less well‐known situation. Model transferability and adaptability may be extremely beneficial—approaches that aid in the reuse and adaption of models, particularly for sites with limited data, would benefit from widespread model uptake. Besides the reduced effort required to develop a model, data collection can be simplified when transferring a model to a different application context. The research presented in this paper focused on a case study to identify and implement guidelines for model adaptation. Our study adapted a general Dynamic Bayesian Networks (DBN) of a seagrass ecosystem to a new location where nodes were similar, but the conditional probability tables varied. We focused on two species of seagrass (Zostera noltei and Zostera marina) located in Arcachon Bay, France. Expert knowledge was used to complement peer‐reviewed literature to identify which components needed adjustment including parameterization and quantification of the model and desired outcomes. We adopted both linguistic labels and scenario‐based elicitation to elicit from experts the conditional probabilities used to quantify the DBN. Following the proposed guidelines, the model structure of the general DBN was retained, but the conditional probability tables were adapted for nodes that characterized the growth dynamics in Zostera spp. population located in Arcachon Bay, as well as the seasonal variation on their reproduction. Particular attention was paid to the light variable as it is a crucial driver of growth and physiology for seagrasses. Our guidelines provide a way to adapt a general DBN to specific ecosystems to maximize model reuse and minimize re‐development effort. Especially important from a transferability perspective are guidelines for ecosystems with limited data, and how simulation and prior predictive approaches can be used in these contexts.     

Exercise increases the release of NAMPT in extracellular vesicles and alters NAD + activity in recipient cells

Aging is associated with a loss of metabolic homeostasis, with cofactors such as nicotinamide adenine dinucleotide (NAD⁺) declining over time. The decrease in NAD⁺ production has been linked to the age‐related loss of circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT), the rate‐limiting enzyme in the NAD⁺ biosynthetic pathway. eNAMPT is found almost exclusively in extracellular vesicles (EVs), providing a mechanism for the distribution of the enzyme in different tissues. Currently, the physiological cause for the release of eNAMPT is unknown, and how it may be affected by age and physical exercise. Here, we show that release of small EVs into the bloodstream is stimulated following moderate intensity exercise in humans. Exercise also increased the eNAMPT content in EVs, most prominently in young individuals with higher aerobic fitness. Both mature fit and young unfit individuals exhibited a limited increase in EV‐eNAMPT release following exercise, indicating that this mechanism is related to both the age and physical fitness of a person. Notably, unfit mature individuals were unable to increase the release of eNAMPT in EVs after exercise, suggesting that lower fitness levels and aging attenuate this important signalling mechanism in the body. EVs isolated from exercising humans containing eNAMPT were able to alter the abundance of NAD⁺ and SIRT1 activity in recipient cells compared to pre‐exercise EVs, indicating a pathway for inter‐tissue signalling promoted through exercise. Our results suggest a mechanism to limit age‐related NAD⁺ decline, through the systemic delivery of eNAMPT via EVs released during exercise.     

Epidemic management and control through risk-dependent individual contact interventions

Testing, contact tracing, and isolation (TTI) is an epidemic management and control approach that is difficult to implement at scale because it relies on manual tracing of contacts. Exposure notification apps have been developed to digitally scale up TTI by harnessing contact data obtained from mobile devices; however, exposure notification apps provide users only with limited binary information when they have been directly exposed to a known infection source. Here we demonstrate a scalable improvement to TTI and exposure notification apps that uses data assimilation (DA) on a contact network. Network DA exploits diverse sources of health data together with the proximity data from mobile devices that exposure notification apps rely upon. It provides users with continuously assessed individual risks of exposure and infection, which can form the basis for targeting individual contact interventions. Simulations of the early COVID-19 epidemic in New York City are used to establish proof-of-concept. In the simulations, network DA identifies up to a factor 2 more infections than contact tracing when both harness the same contact data and diagnostic test data. This remains true even when only a relatively small fraction of the population uses network DA. When a sufficiently large fraction of the population (≳ 75%) uses network DA and complies with individual contact interventions, targeting contact interventions with network DA reduces deaths by up to a factor 4 relative to TTI. Network DA can be implemented by expanding the computational backend of existing exposure notification apps, thus greatly enhancing their capabilities. Implemented at scale, it has the potential to precisely and effectively control future epidemics while minimizing economic disruption.     

高寒草甸土壤昆虫的数量与生物量及其影响因素

昆虫数量变动包括“数”和“量”两方面,“数”即密度,人们早已惯用;“量”即生物量和能量,尚很少应用。因为相同数目的个体不一定具有相同的生物量或能量,所以从群落的食物链索关系或生态系统的能量流来看,单纯的个体数不足以表示所起的作用。因此,如何从“数”的概念过渡到“量”的概念,从更切实的基础上了解这种动态的实质是非常重要的。本文仅就土壤昆虫的数量与生物量作一初步探讨,以便结合其它有关研究最终阐明草甸生态系统的结构和功能,从而把草甸的生产和管理建立在合理的基础之上。     

Human C1orf27 protein interacts with α2A-adrenergic receptor and regulates its anterograde transport

The molecular mechanisms underlying the anterograde surface transport of G protein–coupled receptors (GPCRs) after their synthesis in the endoplasmic reticulum (ER) are not well defined. In C. elegans, odorant response abnormal 4 has been implicated in the delivery of olfactory GPCRs to the cilia of chemosensory neurons. However, the function and regulation of its human homolog, C1orf27, in GPCR transport or in general membrane trafficking remain unknown. Here, we demonstrate that siRNA-mediated knockdown of C1orf27 markedly impedes the ER-to-Golgi export kinetics of newly synthesized α_2A-adrenergic receptor (α_2A-AR), a prototypic GPCR, with the half-time being prolonged by more than 65%, in mammalian cells in retention using the selective hooks assays. Using modified bioluminescence resonance energy transfer assays and ELISAs, we also show that C1orf27 knockdown significantly inhibits the surface transport of α_2A-AR. Similarly, C1orf27 knockout by CRISPR-Cas9 markedly suppresses the ER–Golgi-surface transport of α_2A-AR. In addition, we demonstrate that C1orf27 depletion attenuates the export of β₂-AR and dopamine D2 receptor but not of epidermal growth factor receptor. We further show that C1orf27 physically associates with α_2A-AR, specifically via its third intracellular loop and C terminus. Taken together, these data demonstrate an important role of C1orf27 in the trafficking of nascent GPCRs from the ER to the cell surface through the Golgi and provide novel insights into the regulation of the biosynthesis and anterograde transport of the GPCR family members.     

Hemin with Peroxidase Activity Can Inhibit the Oxidative Damage Induced by Ultraviolet A

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H₂O₂). Catalysis was found to effectively reduce or eliminate oxidative damage to cells induced by H₂O₂ or UVA. The scavenging effects of hemin for other free-radical ROS were also evaluated through pyrogallol autoxidation, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)-scavenging assays, and phenanthroline–Fe²⁺ assays. The results show that a mixture of hemin and tyrosine exhibits strong scavenging activities for H₂O₂, superoxide anion (O₂⁻·), DPPH·, and the hydroxyl radical (·OH). Furthermore, the inhibition of oxidative damage to human skin keratinocyte (HaCaT) cells induced by H₂O₂ or UVA was evaluated. The results show that catalysis can significantly reduce the ratio of cell apoptosis and death and inhibit the release of lactate dehydrogenase (LDH), as well as accumulation of malondialdehyde (MDA). Furthermore, the resistance to apoptosis was found to be enhanced. These results show that the mixture of hemin and tyrosine has a significantly protective effect against oxidative damage to HaCaT cells caused by UVA, suggesting it as a protective agent for combating UVA damage.     

The mode of action of thidiazuron: auxins,indoleamines, and ion channels in the regeneration of <Emphasis Type="Italic">Echinacea purpurea</Emphasis> L.

The biochemical mechanisms underlying thidiazuron (TDZ)-induced regeneration in plant cells have not been clearly elucidated. Exposure of leaf explants of Echinacea purpurea to a medium containing TDZ results in undifferentiated cell proliferation and differentiated growth as mixed shoot organogenesis and somatic embryogenesis. The current studies were undertaken to determine the potential roles of auxin, indoleamines, and ion signaling in the dedifferentiation and redifferentiation of plant cells. E. purpurea leaf explants were found to contain auxin and the related indoleamine neurotransmitters, melatonin, and serotonin. The levels of these endogenous indoleamines were increased by exposure to TDZ associated with the induction of regeneration. The auxin-transport inhibitor 2,3,5-triiodobenzoic acid and auxin action inhibitor, p-chlorophenoxyisobutyric acid decreased the TDZ-induced regeneration but increased concentrations of endogenous serotonin and melatonin. As well, inhibitors of calcium and sodium transport significantly reduced TDZ-induced morphogenesis while increasing endogenous indoleamine content. These data indicate that TDZ-induced regeneration is the manifestation of a metabolic cascade that includes an initial signaling event, accumulation, and transport of endogenous plant signals such as auxin and melatonin, a system of secondary messengers, and a concurrent stress response.     

锦天牛属阳茎内囊结构

采用显微解剖和冰冻组织切片方法研究锦天牛属Acalolepta三种天牛阳茎内囊的结构,发现内囊骨化结构物,尤其端部骨化结构物,及其控制内囊伸缩的加厚侧带和有聚集精子作用的射精管壶腹结构,在探讨天牛科分类和系统发育上均具有重要意义。     

Protein kinase C delta null mice exhibit structural alterations in articular surface,intra-articular and subchondral compartments

IntroductionStructural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta (PKC-δ) plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known.MethodsHistological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone–cartilage interface in PKC-δ knockout (KO) mice. The morphology and organization of chondrocytes were studied using confocal microscopy. Glycosaminoglycan content was studied by micromass culture of chondrocytes of PKC-δ KO mice.ResultsWe uncovered atypical structural demarcation between articular cartilage and subchondral bone of PKC-δ KO mice. Histology analyses revealed a thickening of the articular cartilage and calcified bone–cartilage interface, and decreased safranin O staining accompanied by an increase in the number of hypertrophic chondrocytes in the articular cartilage of PKC-δ KO mice. Interestingly, loss of demarcation between articular cartilage and bone was concomitant with irregular chondrocyte morphology and arrangement. Consistently, in vivo calcein labeling assay showed an increased intensity of calcein labeling in the interface of the growth plate and metaphysis in PKC-δ KO mice. Furthermore, in vitro culture of chondrocyte micromass showed a decreased alcian blue staining of chondrocyte micromass in the PKC-δ KO mice, indicative of a reduced level of glycosaminoglycan production.ConclusionsOur data imply a role for PKC-δ in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0720-4) contains supplementary material, which is available to authorized users.     

不同细胞周期大鼠肝实质细胞癌细胞粘弹特性研究

以胸腺嘧啶核苷和秋水仙碱顺序阻断法及胸腺嘧啶核苷双阻断法分别获得同步化Ｇ１期和Ｓ期细胞,从细胞周期角度出发,采用微管吸吮技术对大鼠肝实质细胞癌细胞的粘弹特性进行了测定并以标准线性固体模型对实验数据进行了拟合,结果表明：该细胞具有高弹性和低粘性的总体特征;Ｇ１期细胞与Ｓ期细胞相比具有高Ｋ１值和低μ值的特点,从而显示Ｇ１期细胞比Ｓ期细胞具有更大的强度和更快的被动变形能力。这些结果不仅反映了同步化细胞存在的细胞骨架状态的周期性差异,也提示Ｇ１期细胞可能比Ｓ期细胞更适于在血流中存活和转移。