Germline-specific dgcr8 knockout in zebrafish using a BACK approach

Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development. Our findings establish that Cre/loxP-mediated tissue-specific gene knockout could be achieved using this BACK strategy and that canonical microRNAs play important roles in early embryonic development in zebrafish.     

The stoichiometry of peptide-heparan sulfate binding as a determinant of uptake efficiency of cell-penetrating peptides

Binding to negatively charged heparan sulfates (HS) at the cell surface is considered the first step in the internalization of cationic cell-penetrating peptides (CPPs). However, little is known about the relation of the characteristics of the HS-CPP interaction such as affinity, stoichiometry, and clustering with uptake. In this study, we investigated a collection of mutants of a cyclic CPP derived from human lactoferrin with respect to HS binding and uptake. The thermodynamic parameters of HS binding were determined by isothermal titration calorimetry, clustering of HS was investigated by dynamic light scattering, and cellular uptake by flow cytometry and confocal microscopy. Whereas mutations of non-arginine amino acids that are conserved across lactoferrins of different mammalia only had a minor effect on uptake efficiency, changes in the number of arginine residues influenced the uptake significantly. In general, introduction of arginine residues and cyclization improved the HS affinity and the ability to cluster HS. In particular, there was a strong negative correlation between stoichiometry and uptake, indicating that crosslinking of HS is the driving force for the uptake of arginine-rich CPPs. Using glycan microarrays presenting a collection of synthetic HS, we show that a minimal chain length of HS is required for peptide binding.     

Cryptic subarctic diversity: a new bumblebee species from the Yukon and Alaska (Hymenoptera: Apidae)

It is nearly 90 years since a bumblebee species has been described for the first time from Canada or the USA that was previously unrecognised by science. We describe and illustrate Bombus(Alpinobombus) kluanensis sp. nov. and begin to map its distribution. This species was discovered through analysis of Cytochrome c Oxidase subunit I barcodes and had been unsuspected on the basis of morphological and colour characteristics. So far, 247 female specimens considered to belong to this species are known from the subarctic mountains associated with the Denali Fault running from the Alaska Range (Alaska, USA) to Kluane in the Saint Elias Mountains (Yukon, Canada). A checklist of all species of the subgenus Alpinobombus worldwide is provided.

http://zoobank.org/urn:lsid:zoobank.org:pub:78D524DD-FFBA-4BC4-8D39-3EF4F6BDD39E     

Swimming and bipedal bottom-running in the pig-nosed turtle Carettochelys insculpta Ramsay, 1886

The pig-nosed freshwater turtle Carettochelys insculpta Ramsay, 1886 has paddle-shaped foreflippers that resemble those of sea turtles. These turtles exhibit a wide range of swimming capabilities. As well as swimming by the action of synchronized foreflippers alone, they sometimes used alternate hindlimb action at the same time. They could swim by ipsilaterally synchronized action of all four limbs, or by hindlimb action alone (combined with stabilizer/lift function of the foreflippers). The turtles also showed flexibility in bottom-walking. Besides the ipsilaterally synchronized quadrupedal action characteristic of other freshwater turtles, they exhibited a bipedal walking mechanism never previously described. Propelled by alternate action of the hindlimbs, the animals held the head and plastron above the substratum, with the large foreflippers acting to provide anterior lift and stability against roll and yaw. Because both hindlimbs were sometimes off the substratum simultaneously during bipedal locomotion, their duty factors were < 0.5, implying a bipedal run.     

Effect of equal channel angular pressing on aging treatment of Al-7075 alloy

The effect of aging treatment on microstructure and mechanical properties of equal channel angular pressed Al-7075 alloy was examined.Commercial Al-7075 alloy in the solid solution heat-treated condition was processed by equal channel angular pressing through route BCat both the room temperature and 120 1C. Only three passes of equal channel angular pressing was possible due to the low ductility of the alloy at both temperatures. Followed by equal channel angular pressing, the specimens have been aged at 120 1C for different aging times. Mechanical properties were measured by Vickers microhardness and tensile tests and microstructural observations were undertaken using transmission electron microscopy, X-ray diffractometer as well as optical microscopy. Microstructural investigations showed that ultrafine-grained materials with grain size in the range of 200–350 nm and 300–500 nm could be obtained after three passes of equal channel angular pressing at room temperature and 120 1C, respectively. Equal channel angular pressing of solid solution heat-treated Al-7075 alloy accelerates precipitation rate and subsequently leads to a significant decrease in aging time to attain maximum mechanical properties. Furthermore, it is possible to achieve maximum mechanical properties during equal channel angular pressing at 120 1C as a result of dynamic aging and formation of small η′ phase.     

Command and control model based on complex information relation integration北大核心CSCD

In order to describe collaborative decision-making process, the command and control model is put forward based on complex information relation integrtion and OODA. The characteristics of individual decision-making are analyzed, the complex information relation is considered as the cause of OODA difficulty to describe collaborative decision-making exactly. From the perspective of armament system of systems combat, the information, data, intelligence and knowledge is defined based on knowledge management and Shannon's entropy theory. The basic element is confirmed and the information flow way is analyzed which in the physical, information, cognitive and social domains. From the perspective of information, the armament system of systems complex networks model framework is put forward based on the idea of using OODA to guide armament system of systems complex networks model design. The data, information, intelligence and knowledge flow is analyzed and the describing meta-model is put forward. Using the reticular structure of OODA to describe collaborative decision-making idea is proposed, the command and control model is put forward based on the idea, the simulating tool ExtendSim is used for simulation analysis and results show that our work offer a reference for innovate command and control thory. ©, 2015, The Journal Agency of Complex Systems and Complexity Science. All right reserved.     

行人下肢有限元模型的建立与验证研究

下肢损伤是行人与车辆碰撞事故中的主要损伤形式之一,建立具有较高生物逼真度的行人下肢有限元模型,可以为下肢保护提供有效的研究手段.在下肢长骨(股骨、胫骨、腓骨)、韧带(ACL,PCL,MCL,LCL)及膝关节得到全面验证的基础上,建立了包含骨骼、韧带、肌肉及皮肤等详细解剖学结构的行人下肢有限元模型,并定义了各组织间的接触.利用行人下肢弯曲的生物力学实验,对下肢有限元模型进行了整体弯曲验证.结果显示,下肢有限元模型的损伤形式、损伤发生时刻、膝关节弯矩和弯曲角度均与实验结果吻合较好,能够较真实地反映行人下肢的损伤和生物力学响应,具有较好的生物逼真度.     

Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.