Foraging success under uncertainty: search tradeoffs and optimal space use

Understanding the structural complexity and the main drivers of animal search behaviour is pivotal to foraging ecology. Yet, the role of uncertainty as a generative mechanism of movement patterns is poorly understood. Novel insights from search theory suggest that organisms should collect and assess new information from the environment by producing complex exploratory strategies. Based on an extension of the first passage time theory, and using simple equations and simulations, we unveil the elementary heuristics behind search behaviour. In particular, we show that normal diffusion is not enough for determining optimal exploratory behaviour but anomalous diffusion is required. Searching organisms go through two critical sequential phases (approach and detection) and experience fundamental search tradeoffs that may limit their encounter rates. Using experimental data, we show that biological search includes elements not fully considered in contemporary physical search theory. In particular, the need to consider search movement as a non‐stationary process that brings the organism from one informational state to another. For example, the transition from remaining in an area to departing from it may occur through an exploratory state where cognitive search is challenged. Therefore, a more comprehensive view of foraging ecology requires including current perspectives about movement under uncertainty.     

运动应激介导线粒体DAMP对先天性免疫的调控作用研究进展

线粒体是先天性免疫的关键调控者,具体表现为:线粒体可以通过释放多种线粒体损伤相关分子模式(damage-associated molecular patterns,DAMPs)来诱发先天性免疫应答,如线粒体DNA(mitochondrial DNA,mtDNA)、线粒体转录因子 A(mitochondrial tran...     

Agglutination Activity of Fasciola gigantica DM9-1, a Mannose-Binding Lectin

The DM9 domain is a protein unit of 60–75 amino acids that has been first detected in the fruit fly Drosophila as a repeated motif of unknown function. Recent research on proteins carrying DM9 domains in the mosquito Anopheles gambiae and the oyster Crassostrea gigas indicated an association with the uptake of microbial organisms. Likewise, in the trematode Fasciola gigantica DM9-1 showed intracellular relocalization following microbial, heat and drug stress. In the present research, we show that FgDM9-1 is a lectin with a novel mannose-binding site that has been recently described for the protein CGL1 of Crassostrea gigas. This property allowed FgDM9-1 to agglutinate gram-positive and -negative bacteria with appropriate cell surface glycosylation patterns. Furthermore, FgDM9-1 caused hemagglutination across all ABO blood group phenotypes. It is speculated that the parenchymal located FgDM9-1 has a role in cellular processes that involve the transport of mannose-carrying molecules in the parenchymal cells of the parasite.     

Plasmin-sensitive dibasic sequences in the third fibronectin-like domain of L1-cell adhesion molecule (CAM) facilitate homomultimerization and concomitant integrin recruitment

L1 is a multidomain transmembrane neural recognition molecule essential for neurohistogenesis. While moieties in the immunoglobulin-like domains of L1 have been implicated in both heterophilic and homophilic binding, the function of the fibronectin (FN)-like repeats remains largely unresolved. Here, we demonstrate that the third FN-like repeat of L1 (FN3) spontaneously homomultimerizes to form trimeric and higher order complexes. Remarkably, these complexes support direct RGD-independent interactions with several integrins, including alpha(v)beta(3) and alpha(5)beta(1). A pep- tide derived from the putative C-C' loop of FN3 (GSQRKHSKRHIHKDHV(852)) also forms trimeric complexes and supports alpha(v)beta(3) and alpha(5)beta(1) binding. Substitution of the dibasic RK(841) and KR(845) sequences within this peptide or the FN3 domain limited multimerization and abrogated integrin binding. Evidence is presented that the multimerization of, and integrin binding to, the FN3 domain is regulated both by conformational constraints imposed by other domains and by plasmin- mediated cleavage within the sequence RK( downward arrow)HSK( downward arrow)RH(846). The integrin alpha(9)beta(1), which also recognizes the FN3 domain, colocalizes with L1 in a manner restricted to sites of cell-cell contact. We propose that distal receptor ligation events at the cell-cell interface may induce a conformational change within the L1 ectodomain that culminates in receptor multimerization and integrin recruitment via interaction with the FN3 domain.     

Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation

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BMP-9与骨代谢及糖代谢关系研究进展

骨形成蛋白-9(BMP-9)是从胚胎鼠的肝脏c DNA文库中克隆得到的新型细胞因子,属于转化生长因子β超家族的成员,由肝脏非实质细胞合成分泌,在体内以类激素的形式发挥广泛的生物学作用。BMP-9不仅具有强烈的骨诱导活性,促进成骨细胞分化,还可通过调控糖代谢过程中关键酶的表达、促进胰岛素合成及分泌、增加胰岛素敏感性等方式调节体内葡萄糖平衡。本文主要对BMP-9与骨代谢及糖代谢的关系进行综述,为深入认识糖尿病、代谢性骨病及糖尿病性骨质疏松的发生机理提供理论依据,为糖尿病和骨骼疾病的防治提供新的思路。     

Metabolism and activation of benzo[a]pyrene by mouse and rat skin in short-term organ culture and in vivo

The metabolic activation of BP was examined in mouse and rat skin in vivo and in short-term organ culture. In mouse skin, larger quantities of ether- and water-soluble metabolites were formed and more BP became bound covalently to DNA and protein than in rat skin. Qualitative differences in the formation of dihydrodiol metabolites and of BP-deoxyribonucleoside adducts between mouse and rat skin were also observed. Organ culture techniques may not provide a true model of metabolic activation in vivo because it was found that the covalent binding of BP to DNA and protein was reduced in skin maintained in culture despite an accumulation of dihydrodiol and other ether-soluble metabolites. In addition, the proportions of the syn- and anti-isomers of BP-7,8-diol 9,10-oxide involved in the formation of adducts with deoxyguanosine differed between skin treated in organ culture and in vivo.     

Recent advances in plasmid-based tools for establishing novel microbial chassis

A key challenge for domesticating alternative cultivable microorganisms with biotechnological potential lies in the development of innovative technologies. Within this framework, a myriad of genetic tools has flourished, allowing the design and manipulation of complex synthetic circuits and genomes to become the general rule in many laboratories rather than the exception. More recently, with the development of novel technologies such as DNA automated synthesis/sequencing and powerful computational tools, molecular biology has entered the synthetic biology era. In the beginning, most of these technologies were established in traditional microbial models (known as chassis in the synthetic biology framework) such as Escherichia coli and Saccharomyces cerevisiae, enabling fast advances in the field and the validation of fundamental proofs of concept. However, it soon became clear that these organisms, although extremely useful for prototyping many genetic tools, were not ideal for a wide range of biotechnological tasks due to intrinsic limitations in their molecular/physiological properties. Over the last decade, researchers have been facing the great challenge of shifting from these model systems to non-conventional chassis with endogenous capacities for dealing with specific tasks. The key to address these issues includes the generation of narrow and broad host plasmid-based molecular tools and the development of novel methods for engineering genomes through homologous recombination systems, CRISPR/Cas9 and other alternative methods. Here, we address the most recent advances in plasmid-based tools for the construction of novel cell factories, including a guide for helping with “build-your-own” microbial host.