趋磁细菌及磁小体在肿瘤治疗中的应用

提高抗肿瘤药物的靶向性是肿瘤治疗、降低药物副作用的重要手段。在肿瘤组织内部由于癌细胞的快速增殖致使其形成低氧区,低氧区会对多种肿瘤治疗方案产生耐受。趋磁细菌 (Magnetotactic bacteria, MTB) 是一类能在细胞内产生外包生物膜、纳米尺寸、单磁畴磁铁矿 (Fe3O4) 或硫铁矿 (Fe3S4) 晶体颗粒-磁小体的微生物的统称。在磁场的作用下,趋磁细菌可凭借鞭毛运动至厌氧区。趋磁细菌在动物体内毒性较低且生物相容性良好,其磁小体与人工合成的磁性纳米材料相比优势显著。文中在介绍趋磁细菌及其磁小体生物学特点、理化性能的基础上,综述了趋磁细菌作为载体偶联药物进入肿瘤内部,并通过感受低氧信号定位于肿瘤低氧区,以及趋磁细菌竞争肿瘤细胞铁源的研究进展,总结了磁小体运载化疗药物、抗体、DNA疫苗靶向结合肿瘤的研究进展,分析了趋磁细菌及磁小体肿瘤治疗中面临的问题,并对趋磁细菌和磁小体在肿瘤治疗中的应用进行了展望。     

趋磁细菌磁小体合成机制研究进展

趋磁细菌可在环境中吸收大量铁并在细胞内合成纳米级磁性颗粒—磁小体。比较几种趋磁细菌基因组特征,针对磁小体岛及与磁小体合成相关基因功能特点等方面,综述了当前磁小体合成机制的研究进展。     

趋磁细菌及磁小体的生物医学应用研究进展

近年来,趋磁细菌及其生物自身合成的磁小体由于良好的生物安全性逐渐被人们所认识,并被用于生物工程和医学应用研究。与人工化学合成磁性纳米颗粒相比,从趋磁细菌中提取的磁小体具有生物膜包被、生物相容性高、粒径均一及磁性高等优势。趋磁细菌因磁小体在其胞内呈链状排列,具有沿磁场方向泳动的能力,也被应用于各种应用研究。因此,综述了趋磁细菌及磁小体特性,并就最近的研究进展重点综述趋磁细菌和磁小体在生物工程及医学应用等领域的最新研究进展。     

趋磁细菌的磁小体

趋磁细菌是一类对磁场有趋向性反应的细菌,其菌体能吸收外界环境中铁元素并在体内合成包裹有膜的纳米磁性颗粒Fe₃O₄或Fe₃O_{3S4晶体即磁小体。综述了趋磁细菌的磁小体生物矿化的条件,以及趋磁细菌的铁离子吸收、磁小体囊泡的形成、铁离子的转运到磁小体囊泡及囊泡中受控的Fe3O4生物矿化的分子生物学和生物化学等方面的研究进展,重点介绍了趋磁细菌磁小体合成机制的研究进展及未来研究磁小体的发展方向。}     

趋磁细菌及其应用于生物导航的研究进展

趋磁性细菌是一种由于体内含有对磁场具有敏感性的磁小体,而能够沿着磁力线运动的特殊细菌,本文综述了趋磁细菌的分布、分类、特性、磁小体研究以及趋磁细菌在生物导航方面的研究进展。     

趋磁细菌及其应用于生物导航的研究进展

趋磁性细菌是一种由于体内含有对磁场具有敏感性的磁小体,而能够沿着磁力线运动的特殊细菌,本文综述了趋磁细菌的分布、分类、特性、磁小体研究以及趋磁细菌在生物导航方面的研究进展.     

趋磁细菌多样性与应用研究进展 *

趋磁细菌是一类可以沿磁场方向进行运动的微生物统称,在细胞内合成由生物膜包被、链状排列、纳米级、单磁畴的磁铁矿 (Fe₃O₄) 或胶黄铁矿 (Fe₃S₄) 的磁小体颗粒。趋磁细菌在自然界分布广泛且多样性丰富,不仅在水环境和沉积环境的铁、硫、碳、氮、磷等元素生物地球化学循环中发挥重要作用,而且在污染治理、疾病诊断和治疗等方面有较好的应用。趋磁细菌磁小体由生物膜包被并在细胞调控下合成,是一类新型的生物源磁性纳米材料。相比常规化学合成的磁性纳米颗粒,磁小体具有大小均一、生物相容性高、兼具化学修饰和基因工程修饰功能等特点,在磁性分离、固定化酶、食品检测、环境监测、医学诊断、磁共振成像、磁热疗和靶向治疗等方面具有广阔的应用前景。在介绍趋磁细菌多样性研究的基础上,综述了趋磁细菌和磁小体的制备、修饰及其应用的最新进展,并对未来的研究进行了展望。     

趋磁细菌概述及应用进展

趋磁细菌是一类具有趋磁行为的革兰氏阴性茵的统称,其趋磁特性是由于菌体内含有磁小体。磁小体是由膜包被的纳米尺寸单磁畴颗粒,在菌体内多呈链状排列。自被发现以来,趋磁细菌及磁小体已逐步成为新的生物资源被广泛研究于材料学、医学、生物学、物理学、地质学等多个学科领域,并在仿生学、生态学、医学、地质学、工业处理、卫生检验等多个领域得到应用。主要介绍了趋磁细菌的生物特征、研究发展进程,以及近年来在多个学科领域的研究与应用。     

趋磁螺菌中磁小体链装配相关基因及其功能

趋磁细菌(MTB)依赖于体内磁小体结构在磁场中取向,多个磁小体以一定的组 织形式排列是形成菌体内生物磁罗盘的重要环节．多数趋磁细菌中磁小体成链排列,有效增加了细胞磁偶极矩,从而使菌体表现出在环境磁场中定向的能力．趋磁螺菌M. magneticum AMB－1和M. gryphiswaldense MSR－1中磁小体均沿细胞长轴形成一条磁 小体链．通过对相关基因突变体表型的研究,结合对磁小体链形成过程的实时动态观 察,人们已初步了解MamJ、MamK和MamA等基因在磁小体链装配和维护过程中的功能．本文介绍了近年来趋磁螺菌磁小体链装配过程中重要功能性基因的研究进展,并重点分析了AMB-1和MSR-1中磁小体链装配的差异．     

趋磁细菌纳米磁小体的培养与分离及其在医学上的应用进展和前景

趋磁细菌是一种对磁场有趋向性反应的细菌,其原因是它们体内能合成一种特殊的细胞器-磁小体;由于磁小体有着大小合适,磁性强,表面易修饰等诸多优点,在诸多领域,尤其是医学领域有广泛的应用和广阔的前景.本文主要就从环境中区分和分离趋磁细菌;对其不同培养条件的优化与选择;从细菌体内提取磁小体并加以纯化;将不同药物偶联于磁小体之上的方法及其在医学上如,制造磁性细胞,磁分离技术,生物传感与检测技术,并将其作为靶向药物的载体,肿瘤治疗,基因治疗等方面的应用现状和前景作简要论述.     

Estimation and confidence regions for multi-dimensional effective dose

The problem of finding confidence regions for multiple predictor variables corresponding to given expected values of a response variable has not been adequately resolved. Motivated by an example from a study on hyperbaric exposure using a logistic regression model, we develop a conceptual framework for the estimation of the multi-dimensional effective dose for binary outcomes. The k -dimensional effective dose can be determined by conditioning on k - 1 components and solving for the last component as a conditional univariate effective dose. We consider various approaches for calculating confidence regions for the multi-dimensional effective dose and compare them via a simulation study for a range of possible designs. We analyze data related to decompression sickness to illustrate our procedure. Our results provide a practical approach to finding confidence regions for predictor variables for a given response value.     

Timing, memory for intervals, and memory for untimed stimuli: the role of instructional ambiguity

Theories of animal timing have had to account for findings that the memory for the duration of a timed interval appears to be dramatically shorted within a short time of its termination. This finding has led to the subjective shortening hypothesis and it has been proposed to account for the poor memory that animals appear to have for the initial portion of a timed interval when a gap is inserted in the to-be-timed signal. It has also been proposed to account for the poor memory for a relatively long interval that has been discriminated from a shorter interval. I suggest here a simpler account in which ambiguity between the gap or retention interval and the intertrial interval results in resetting the clock, rather than forgetting the interval. The ambiguity hypothesis, together with a signal salience mechanism that determines how quickly the clock is reset at the start of the intertrial interval can account for the results of the reported timing experiments that have used the peak procedure. Furthermore, instructional ambiguity rather than memory loss may account for the results of many animal memory experiments that do not involve memory for time.     

A reference business process for ecological niche modelling

Ecological niche modelling combines species occurrence points with environmental raster layers in order to obtain models for describing the probabilistic distribution of species. The process to generate an ecological niche model is complex. It requires dealing with a large amount of data, use of different software packages for data conversion, for model generation and for different types of processing and analyses, among other functionalities. A software platform that integrates all requirements under a single and seamless interface would be very helpful for users. Furthermore, since biodiversity modelling is constantly evolving, new requirements are constantly being added in terms of functions, algorithms and data formats. This evolution must be accompanied by any software intended to be used in this area. In this scenario, a Service-Oriented Architecture (SOA) is an appropriate choice for designing such systems. According to SOA best practices and methodologies, the design of a reference business process must be performed prior to the architecture definition. The purpose is to understand the complexities of the process (business process in this context refers to the ecological niche modelling problem) and to design an architecture able to offer a comprehensive solution, called a reference architecture, that can be further detailed when implementing specific systems. This paper presents a reference business process for ecological niche modelling, as part of a major work focused on the definition of a reference architecture based on SOA concepts that will be used to evolve the openModeller software package for species modelling. The basic steps that are performed while developing a model are described, highlighting important aspects, based on the knowledge of modelling experts. In order to illustrate the steps defined for the process, an experiment was developed, modelling the distribution of Ouratea spectabilis (Mart.) Engl. (Ochnaceae) using openModeller. As a consequence of the knowledge gained with this work, many desirable improvements on the modelling software packages have been identified and are presented. Also, a discussion on the potential for large-scale experimentation in ecological niche modelling is provided, highlighting opportunities for research. The results obtained are very important for those involved in the development of modelling tools and systems, for requirement analysis and to provide insight on new features and trends for this category of systems. They can also be very helpful for beginners in modelling research, who can use the process and the experiment example as a guide to this complex activity.     

Predicted accuracy of and response to genomic selection for new traits in dairy cattle

Genomic selection relaxes the requirement of traditional selection tools to have phenotypic measurements on close relatives of all selection candidates. This opens up possibilities to select for traits that are difficult or expensive to measure. The objectives of this paper were to predict accuracy of and response to genomic selection for a new trait, considering that only a cow reference population of moderate size was available for the new trait, and that selection simultaneously targeted an index and this new trait. Accuracy for and response to selection were deterministically evaluated for three different breeding goals. Single trait selection for the new trait based only on a limited cow reference population of up to 10 000 cows, showed that maximum genetic responses of 0.20 and 0.28 genetic standard deviation (s.d.) per year can be achieved for traits with a heritability of 0.05 and 0.30, respectively. Adding information from the index based on a reference population of 5000 bulls, and assuming a genetic correlation of 0.5, increased genetic response for both heritability levels by up to 0.14 genetic s.d. per year. The scenario with simultaneous selection for the new trait and the index, yielded a substantially lower response for the new trait, especially when the genetic correlation with the index was negative. Despite the lower response for the index, whenever the new trait had considerable economic value, including the cow reference population considerably improved the genetic response for the new trait. For scenarios with a zero or negative genetic correlation with the index and equal economic value for the index and the new trait, a reference population of 2000 cows increased genetic response for the new trait with at least 0.10 and 0.20 genetic s.d. per year, for heritability levels of 0.05 and 0.30, respectively. We conclude that for new traits with a very small or positive genetic correlation with the index, and a high positive economic value, considerable genetic response can already be achieved based on a cow reference population with only 2000 records, even when the reliability of individual genomic breeding values is much lower than currently accepted in dairy cattle breeding programs. New traits may generally have a negative genetic correlation with the index and a small positive economic value. For such new traits, cow reference populations of at least 10 000 cows may be required to achieve acceptable levels of genetic response for the new trait and for the whole breeding goal.     

Inference in Randomized Studies with Informative Censoring and Discrete Time-to-Event Endpoints

In this article, we present a method for estimating and comparing the treatment-specific distributions of a discrete time-to-event variable from right-censored data. Our method allows for (1) adjustment for informative censoring due to measured prognostic factors for time to event and censoring and (2) quantification of the sensitivity of the inference to residual dependence between time to event and censoring due to unmeasured factors. We develop our approach in the context of a randomized trial for the treatment of chronic schizophrenia. We perform a simulation study to assess the practical performance of our methodology.     

A reduced muscle model and planar musculoskeletal model fit for the simulation of whole-body movements

Musculoskeletal models are made to reflect the capacities of the human body in general, and often a specific subject in particular. It remains challenging to both model the musculoskeletal system and then fit the modelled muscles to a specific human subject. We present a reduced muscle model, a planar musculoskeletal model, and a fitting method that can be used to find a feasible set of active and passive muscle parameters for a specific subject. At a minimum, the fitting method requires inverse dynamics data of the subject, a scalar estimate of the peak activation reached during the movement, and a plausible initial estimate for the strength and flexibility of that subject. While additional data can be used to result in a more accurate fit, this data is not required for the method solve for a feasible fit. The minimal input requirements of the proposed fitting method make it well suited for subjects who cannot undergo a maximum voluntary contraction trial, or for whom recording electromyographic data is not possible. To evaluate the model and fitting method we adjust the musculoskeletal model so that it can perform an experimentally recorded stoop-lift of a 15 kg box.     

Economic Feasibility of Recycling Photovoltaic Modules

The market for photovoltaic (PV) electricity generation has boomed over the last decade, and its expansion is expected to continue with the development of new technologies. Taking into consideration the usage of valuable resources and the generation of emissions in the life cycle of photovoltaic technologies dictates proactive planning for a sound PV recycling infrastructure to ensure its sustainability. PV is expected to be a “green” technology, and properly planning for recycling will offer the opportunity to make it a “double‐green” technology—that is, enhancing life cycle environmental quality. In addition, economic feasibility and a sufficient level of value‐added opportunity must be ensured, to stimulate a recycling industry. In this article, we survey mathematical models of the infrastructure of recycling processes of other products and identify the challenges for setting up an efficient one for PV. Then we present an operational model for an actual recycling process of a thin‐film PV technology. We found that for the case examined with our model, some of the scenarios indicate profitable recycling, whereas in other scenarios it is unprofitable. Scenario SC4, which represents the most favorable scenario by considering the lower bounds of all costs and the upper bound of all revenues, produces a monthly profit of $107,000, whereas the least favorable scenario incurs a monthly loss of $151,000. Our intent is to extend the model as a foundation for developing a framework for building a generalized model for current‐PV and future‐PV technologies.     

Evaluation of the validity of a maximum likelihood adaptive staircase procedure for measurement of olfactory detection threshold in mice

Threshold is defined as the stimulus intensity necessary for a subject to reach a specified percent correct on a detection test. MLPEST (maximum likelihood parameter estimation by sequential testing) is a method that is able to determine threshold accurately and more rapidly than many other methods. Originally developed for human auditory and visual tasks, it has been adapted for human olfactory and gustatory tests. In order to utilize this technique for olfactory testing in mice, we have adapted MLPEST methodology for use with computerized olfactometry as a tool to estimate odor detection thresholds. Here we present Monte Carlo simulations and operant conditioning data that demonstrate the potential utility of this technique in mice, we explore the ramifications of altering MLPEST test parameters on performance, and we discuss the advantages and disadvantages of using MLPEST compared to other methods for the estimation of thresholds in rodents. Using MLPEST, we find that olfactory detection thresholds in mice deficient for the cyclic nucleotide-gated channel subunit A2 are similar to those of wild-type animals for odorants the knockout animals are able to detect.     

Repetitive mating and female fitness in Dysdercus cardinalis (Hemiptera: Pyrrhocoridae)

Using three mating-treatment groups–pairing with a male for life, pairing with a male from adult emergence to first oviposition, and no pairing (virgin)–of Dysdercus cardinalis females in a laboratory study, the following results were obtained. Most of the virgin females did not lay eggs; those that did oviposited for the first time at a considerably older age than females in the other two groups. In a lifetime, females pairing with a male for life and those pairing with a male up to first oviposition produced essentially the same number of eggs, and this was more than 3.5 times the number of eggs laid by a virgin female. Virgin females produced an average of 1.3 clutches in a lifetime, compared with about 4.5 clutches produced by females in the other two groups. Reproductive span was significantly shorter, and fecundity per day of reproductive span significantly greater, for females pairing with males for life than for those pairing with a male up to first oviposition. Age at death was significantly different amongst females in different mating-treatment groups. Virgin females had the longest life, followed by females pairing with a male up to first oviposition and females pairing with a male for life, in that order. There was a positive correlation between lifetime gross reproduction and age at death for females pairing with a male for life. There was no relationship between these two characters for females pairing with a male up to first oviposition. Both females pairing with a male for life and those pairing with a male to first oviposition exhibited a significant inverse relationship between fecundity per day and age at death. The results obtained indicate that (1) mating is a prerequisite for normal gonadal activity in Dysdercus cardinalis , and (2) repetitive mating increases the rate of reproduction. This would reduce the mean age of parenthood which is inversely related to the intrinsic rate of increase.