Recent Biophysical Issues About the Preparation of Solute-Filled Lipid Vesicles

Here we report some recent biophysical issues on the preparation of solute-filled lipid vesicles and their relevance to the construction of “synthetic cells.” First, we introduce the “semi-synthetic minimal cells” as the liposome-based cell-like systems, which contain a minimal number of biomolecules required to display simple and complex biological functions. Next, we focus on recent aspects related to the construction of synthetic cells. Emphasis is given to the interplay between the methods of synthetic cell preparation and the physics of solute encapsulation. We briefly introduce the notion of structural and compositional “diversity” in synthetic cell populations.     

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

Neutrophils in Tuberculosis: Cell Biology,Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.     

Perfluorocarbons in Chemical Biology

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, and ¹⁹F NMR studies in complex environments. Herein, we describe how the unique properties of perfluorocarbons have been employed to understand and manipulate biological systems.     

Change detection in synthetic aperture radar images based on unsupervised artificial immune systems

In this paper, we propose a novel change detection method for synthetic aperture radar images based on unsupervised artificial immune systems. After generating the difference image from the multitemporal images, we take each pixel as an antigen and build an immune model to deal with the antigens. By continuously stimulating the immune model, the antigens are classified into two groups, changed and unchanged. Firstly, the proposed method incorporates the local information in order to restrain the impact of speckle noise. Secondly, the proposed method simulates the immune response process in a fuzzy way to get an accurate result by retaining more image details. We introduce a fuzzy membership of the antigen and then update the antibodies and memory cells according to the membership. Compared with the clustering algorithms we have proposed in our previous works, the new method inherits immunological properties from immune systems and is robust to speckle noise due to the use of local information as well as fuzzy strategy. Experiments on real synthetic aperture radar images show that the proposed method performs well on several kinds of difference images and engenders more robust result than the other compared methods.     

Intersecting Xenobiology and Neometabolism To Bring Novel Chemistries to Life

The diversity of life relies on a handful of chemical elements (carbon, oxygen, hydrogen, nitrogen, sulfur and phosphorus) as part of essential building blocks; some other atoms are needed to a lesser extent, but most of the remaining elements are excluded from biology. This circumstance limits the scope of biochemical reactions in extant metabolism – yet it offers a phenomenal playground for synthetic biology. Xenobiology aims to bring novel bricks to life that could be exploited for (xeno)metabolite synthesis. In particular, the assembly of novel pathways engineered to handle nonbiological elements (neometabolism) will broaden chemical space beyond the reach of natural evolution. In this review, xeno-elements that could be blended into nature's biosynthetic portfolio are discussed together with their physicochemical properties and tools and strategies to incorporate them into biochemistry. We argue that current bioproduction methods can be revolutionized by bridging xenobiology and neometabolism for the synthesis of new-to-nature molecules, such as organohalides.     

Quantum Sensing in a Physiological‐Like Cell Niche Using Fluorescent Nanodiamonds Embedded in Electrospun Polymer Nanofibers

Fluorescent nanodiamonds (fNDs) containing nitrogen vacancy (NV) centers are promising candidates for quantum sensing in biological environments. This work describes the fabrication and implementation of electrospun poly lactic‐co‐glycolic acid (PLGA) nanofibers embedded with fNDs for optical quantum sensing in an environment, which recapitulates the nanoscale architecture and topography of the cell niche. A protocol that produces uniformly dispersed fNDs within electrospun nanofibers is demonstrated and the resulting fibers are characterized using fluorescent microscopy and scanning electron microscopy (SEM). Optically detected magnetic resonance (ODMR) and longitudinal spin relaxometry results for fNDs and embedded fNDs are compared. A new approach for fast detection of time varying magnetic fields external to the fND embedded nanofibers is demonstrated. ODMR spectra are successfully acquired from a culture of live differentiated neural stem cells functioning as a connected neural network grown on fND embedded nanofibers. This work advances the current state of the art in quantum sensing by providing a versatile sensing platform that can be tailored to produce physiological‐like cell niches to replicate biologically relevant growth environments and fast measurement protocols for the detection of co‐ordinated endogenous signals from clinically relevant populations of electrically active neuronal circuits.     

基于两层均匀媒质的GPEN SAR地下目标成像方法及其性能分析

地表穿透合成孔径雷达(Ground PENetration SAR,GPEN SAR)为了探测掩埋在地下的目标,通常工作在多层媒质的环境中。传统成像模型是建立在同一均匀媒质的假设上,不再适合于GPEN SAR的实际情况。本文首先建立了两层分区均匀媒质中的成像模型,然后利用后向投影(BP)算法定量分析了成像几何参数、土壤参数等对成像的影响,进而提出了一种修正的后向投影(MBP)算法。MBP算法不仅能够校正两层分区均匀媒质对成像定位的影响,还能估计目标的掩埋深度,提供目标三维位置坐标。仿真结果验证了MBP算法在不同信噪比环境下,对多目标的三维定位精度能满足实际的需要。     

电子显微学在结构生物学研究中的新进展

电子显微学是结构生物学的重要分支，已经成为一种公认的研究生物大分子、超分子复合体及亚细胞结构的有力手段。本文先回顾了近期电子显微学在技术上的新进展，后概述了生物电子显微学的三个组成部分——电子晶体学，单颗粒技术，电子断层成像术的基本原理，技术方法与研究现状。最后，对电子显微学与其他结构生物学研究手段的结合以及电子显微学的未来发展做了简单的展望。