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.     

The Regulatory Status of Genome‐edited Crops

Genome editing with engineered nucleases (GEEN) represents a highly specific and efficient tool for crop improvement with the potential to rapidly generate useful novel phenotypes/traits. Genome editing techniques initiate specifically targeted double strand breaks facilitating DNA‐repair pathways that lead to base additions or deletions by non‐homologous end joining as well as targeted gene replacements or transgene insertions involving homology‐directed repair mechanisms. Many of these techniques and the ancillary processes they employ generate phenotypic variation that is indistinguishable from that obtained through natural means or conventional mutagenesis; and therefore, they do not readily fit current definitions of genetically engineered or genetically modified used within most regulatory regimes. Addressing ambiguities regarding the regulatory status of genome editing techniques is critical to their application for development of economically useful crop traits. Continued regulatory focus on the process used, rather than the nature of the novel phenotype developed, results in confusion on the part of regulators, product developers, and the public alike and creates uncertainty as of the use of genome engineering tools for crop improvement.     

Reduced hnRNPA3 increases C9orf72 repeat RNA levels and dipeptide‐repeat protein deposition

Intronic hexanucleotide (G₄C₂) repeat expansions in C9orf72 are genetically associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat RNA accumulates within RNA foci but is also translated into disease characterizing dipeptide repeat proteins (DPR). Repeat‐dependent toxicity may affect nuclear import. hnRNPA3 is a heterogeneous nuclear ribonucleoprotein, which specifically binds to the G₄C₂ repeat RNA. We now report that a reduction of nuclear hnRNPA3 leads to an increase of the repeat RNA as well as DPR production and deposition in primary neurons and a novel tissue culture model that reproduces features of the C9orf72 pathology. In fibroblasts derived from patients carrying extended C9orf72 repeats, nuclear RNA foci accumulated upon reduction of hnRNPA3. Neurons in the hippocampus of C9orf72 patients are frequently devoid of hnRNPA3. Reduced nuclear hnRNPA3 in the hippocampus of patients with extended C9orf72 repeats correlates with increased DPR deposition. Thus, reduced hnRNPA3 expression in C9orf72 cases leads to increased levels of the repeat RNA as well as enhanced production and deposition of DPR proteins and RNA foci.     

基于CRISPR/Cas9系统构建精准调控Wnt信号通路的表达载体及其效果的验证

目的:构建基于CRISPR/cas9系统调控Wnt信号通路的载体,并在细胞水平验证其调控基因表达的效率。方法:选取Wnt信号中负性调控分子,设计并合成能够表达靶向上述分子gRNA的互补DNA克隆序列,BsmBI限制性内切酶酶切载体后,采用分子克隆的方法将上述序列克隆至目的载体lenti-sgRNA-Ms2-zeo,测序正确的克隆通过Lipofectamine2000与lenti-Ms2-P65-HSF1-Hygro和lenti-dcas9-VP64-blastine共同转染入293细胞;转染24h后收集细胞,qRt-PCR检测目的基因的表达。结果:筛选了Wnt信号通路中已知的19个负性调控基因;针对每个基因设计了两对gRNA序列,并构建了能够表达gRNA和MS2融合序列的载体,测序结果显示重组质粒的DNA序列与预期完全相符。随机挑选了4个表达载体与lenti-Ms2-P65-HSF1-Hygro和lenti-dcas9-VP64-blastine共转进入细胞,qPCR结果显示构建的目的载体联合lenti-Ms2-P65-HSF1-Hygro和lenti-dcas9-VP64-blastine载体可以协同促进靶分子表达。结论:本研究成功构建了基于CRISPR/cas9基因编辑系统调控Wnt信号的载体。     

基质金属蛋白酶-9 基因单核苷酸多态性与肺结核病的相关性研究

目的:探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)基因多态性(single nucleotide polymorphism,SNP)与肺结核的相关性。方法:对符合纳入及排除标准的肺结核病例组224例及健康对照组249例进行血样收集与临床资料采集。采用飞行时间质谱分析方法对MMP-9基因rs17576、rs2236416、rs3787268、rs3918254共4个多态性位点进行基因分型,数据统计分析采用SPSS20.0和Haplo View 4.0软件进行。结果:我们首次发现,在病例及对照组中,rs17576基因型频率分布存在统计学差异(X~2=7.822,P=0.020)。与对照组相比,病例组G等位基因频率显著高于对照组(X~2=7.335,P=0.007,OR=1.463,95%CI=1.110-1.927)。病例组rs17576基因型分布中,GG和AG基因型患者吸烟史显著高于AA基因型患者;GG和AG基因型患者卡介苗接种史显著低于AA基因型患者。连锁不平衡分析发现一个单倍型(rs17576-rs3918254)高度连锁(D'0.7;r~20.8)。在病例组及对照组中,G-C和A-C单倍型频率分布存在显著性差异,病例组中G-C单倍型频率显著高于对照组(P=0.022),对照组中A-C单倍型频率显著高于疾病组(P=0.024)。结论:MMP-9基因rs17576多态性位点可能与肺结核有关,携带有rs17576位点G等位基因的个体更易发生肺结核。携带G-C(rs17576-rs3918254)单倍型的个体更易患肺结核病,携带A-C(rs17576-rs3918254)单倍型的个体相对不易患肺结核病。     

CpG methylation increases the DNA binding of 9-aminoacridine carboxamide Pt analogues

This study investigated the effect of CpG methylation on the DNA binding of cisplatin analogues with an attached aminoacridine intercalator. DNA-targeted 9-aminoacridine carboxamide Pt complexes are known to bind at 5′-CpG sequences. Their binding to methylated and non-methylated 5′-CpG sequences was determined and compared with cisplatin. The damage profiles of each platinum compound were quantified via a polymerase stop assay with fluorescently labelled primers and capillary electrophoresis. Methylation at 5′-CpG was shown to significantly increase the binding intensity for the 9-aminoacridine carboxamide compounds, whereas no significant increase was found for cisplatin. 5′-CpG methylation had the largest effect on the 9-ethanolamine-acridine carboxamide Pt complex, followed by the 9-aminoacridine carboxamide Pt complex and the 7-fluoro complex. The methylation state of a cell’s genome is important in maintaining normal gene expression, and is often aberrantly altered in cancer cells. An analogue of cisplatin which differentially targets methylated DNA may be able to improve its therapeutic activity, or alter its range of targets and evade the chemoresistance which hampers cisplatin efficacy in clinical use.