Radiation-induced kidney injury: a role for chronic oxidative stress?

Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant glomerulosclerosis and/or tubulointerstitial fibrosis. However, the particular cell types, mediators and/or mechanisms involved in the development and progression of radiation nephropathy remain ill defined. Angiotensin II (Ang II) plays a major pathogenic role; administration of Ang II blockers markedly abrogates the severity of radiation nephropathy in experimental models. Both ionizing radiation and Ang II signal via generation of reactive oxygen species (ROS). Thus, we hypothesized that localized kidney irradiation might lead to a chronic oxidative stress. In view of the difficulty in measuring ROS in vivo we adopted an indirect immunohistochemical approach in which we used a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most commonly used markers of DNA oxidation.The right kidney of 7-8 week-old male Sprague-Dawley rats was removed. Five to 6 weeks later the remaining hypertrophied kidney was irradiated with single doses of 0-20.0 Gy X-rays. Groups of rats, three per dose, were killed at 4, 8, 16 and 24 weeks post-irradiation, their kidneys fixed, and sections stained with the 8-OHdG-specific antibody N45.1.For quantitation of glomerular DNA oxidation with the N45.1 antibody stained sections, 50 glomeruli/animal were counted. The presence of any intensely stained nuclei within the glomerular tuft was scored as positive. Quantitation of tubular DNA oxidation employed a 10 x 10 point ocular grid. Sections were examined at 400 magnification; 250 tubular profiles were counted. All tubules with any nuclear staining were scored as positive.Sham-irradiated kidneys showed little evidence of DNA oxidation over the experimental period. In contrast, localized kidney irradiation led to a marked, dose-independent increase in glomerular and tubular cell nuclear DNA oxidation. This increase was evident at the first time point studied, i.e. 4 weeks after irradiation, and persisted for up to 24 weeks postirradiation. DNA oxidation in the irradiated kidney was only seen in apparently viable glomerular and tubular cells. Thus, while from 16 to 24 weeks post-irradiation structural alterations had progressed to glomerular sclerosis and tubular atrophy, positive staining for 8-OHdG was not observed in severely atrophic tubules. Similarly, fewer positive staining cells were noted in glomeruli undergoing sclerosis, while none were seen in totally sclerotic glomeruli. These data support the hypothesis that renal irradiation is associated with a chronic and persistent oxidative stress.     

Cardiovascular magnetic resonance for the assessment of pulmonary arterial hypertension: toward a comprehensive CMR exam

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by abnormally increased blood pressure of the pulmonary circulation. The clinical course of the untreated PAH involves rapid progression to right ventricular (RV) failure and death. Right heart catheterization is the gold-standard method for confirming PAH. However, the technique's invasiveness and associated risks preclude its use on a regular basis. Different imaging techniques have been implemented for evaluating PAH, including echocardiography, computed tomography and nuclear medicine. However, these techniques have their own limitations. During the past decade, cardiovascular magnetic resonance (CMR) has been increasingly used for the evaluation of different cardiovascular diseases, including PAH, due to its high resolution, high tissue contrast, and the plethora of anatomical and physiological parameters that can be measured with this modality. This article presents an up-to-date review of the implementation of CMR for evaluating PAH. This is achieved by describing a comprehensive CMR protocol that includes several imaging sequences for assessing different cardiovascular parameters pertaining to PAH. In contrast to the previously published articles, the presented CMR protocol evaluates both RV function and pulmonary artery hemodynamics, which are both affected in PAH. Each imaging sequence is explained along with the image analysis steps required for deriving the cardiovascular parameters of interest. Then, based on an extensive literature review, the article illustrates the significance of the derived cardiovascular parameters and their association with PAH. The article concludes with a discussion of the advantages of the proposed CMR exam for better understanding of the disease pathophysiology and treatment planning.     

Video fluorescence microscopic techniques to monitor local lipid and phospholipid molecular order and organization in cell membranes during hypoxic injury

Digitized video microscopy is rapidly finding uses in a number of fields of biological investigation because it allows quantitative assessment of physiological functions in intact cells under a variety of conditions. In this review paper, we focus on the rationale for the development and use of quantitative digitized video fluorescence microscopic techniques to monitor the molecular order and organization of lipids and phospholipids in the plasma membrane of single living cells. These include (1) fluorescence polarization imaging microscopy, used to measure plasma membrane lipid order, (2) fluorescence resonance energy transfer (FRET) imaging microscopy, used to detect and monitor phospholipid domain formation, and (3) fluorescence quenching imaging microscopy, used to spatially map fluid and rigid lipid domains. We review both the theoretical as well as practical use of these different techniques and their limits and potential for future developments, and provide as an illustrative example their application in studies of plasma membrane lipid order and topography during hypoxic injury in rat hepatocytes. Each of these methods provides complementary information; in the case of hypoxic injury, they all indicated that hypoxic injury leads to a spatially and temporally heterogeneous alteration in lipid order, topography, and fluidity of the plasma membrane. Hypoxic injury induces the formation of both fluid and rigid lipid domains; the formation of these domains is responsible for loss of the plasma membrane permeability barrier and the onset of irreversible injury (cell death). By defining the mechanisms which lead to alterations in lipid and phospholipid order and organization in the plasma membrane of hypoxic cells, potential sites of intervention to delay, prevent, or rescue cells from hypoxic injury have been identified. Finally, we briefly discuss fluorescence lifetime imaging microscopy (FLIM) and its potential application for studies monitoring local lipid and phospholipid molecular order and organization in cell membranes.     

Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes

Group A streptococcus (GAS) or Streptococcus pyogenes causes various diseases ranging from self-limiting sore throat to deadly invasive diseases. The genome size of GAS is 1.85–1.9 Mb, and genomic rearrangement has been demonstrated. GAS possesses various surface-associated substances such as hyaluronic capsule, M proteins, and fibronectin/laminin/immunoglobulin-binding proteins. These are related to the virulence and play multifaceted and mutually reflected roles in the pathogenesis of GAS infections. Invasion of GAS into epithelial cells and deeper tissues provokes immune and non-immune defense or inflammatory responses including the recruitment of neutrophils, macrophages, and dendritic cells in hosts. GAS frequently evades host defense mechanisms by using its virulence factors. Extracellular products of GAS may perturb cellular and subcellular functions and degrade tissues enzymatically, which leads to the aggravation of local and/or systemic disorders in the host. In this review, we summarize some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these.     

超声粒子图像测速技术及应用

心血管疾病的产生与动脉血流的流动状况密切相关。然而,目前普遍应用的超声多普勒成像技术不能精确测量复杂血流流场信息。本文提出了一种基于超声造影微泡的超声全流场粒子图像测速技术,能够获得多维流速速度信息,且不依赖于声束与速度向量之间的夹角。本文首先着重阐述了超声全流场粒子测速技术的基本原理以及系统组成,并对直管流和旋转流场流体动力学特性进行了实验测试研究,实验结果表明本技术能够测量全流场速度,并可作为表征复杂血流流场的有力手段。      

What is preferred about the preferred basis?

I introduce and review the most recent and most promising model of state vector reduction, that of Ghirardi, Rimini, Weber, and Pearle. This model requires the specification of a reduction basis. At least two questions therefore arise: Are there physical reasons to choose one basis rather than another? Does the choice made lead to any undesirable consequences? I argue that there arephysical reasons to choose from a certain class of reduction bases (a class which includes the choice made by the authors mentioned above), and that such a choice does not lead to problems, contra an argument by Albert and Vaidman.     

Magnetic anisotropy,exchange coupling and Dzyaloshinskii–Moriya interaction of two-dimensional magnets

The two-dimensional (2D) magnets provide novel opportunities for understanding magnetism and investigating spin related phenomena in several atomic thickness. Multiple features of 2D magnets, such as critical temperatures, magnetoelectric/magneto-optic responses, and spin configurations, depend on the basic magnetic terms that describe various spins interactions and cooperatively determine the spin Hamiltonian of studied systems. In this review, we present a comprehensive survey of three types of basic terms, including magnetic anisotropy that is intimately related with long-range magnetic order, exchange coupling that normally dominates the spin interactions, and Dzyaloshinskii−Moriya interaction (DMI) that favors the noncollinear spin configurations, from the theoretical aspect. We introduce not only the physical features and origin of these crucial terms in 2D magnets but also many correlated phenomena, which may lead to the advance of 2D spintronics.     

Agreement dynamics on interaction networks with diverse topologies

We review the behavior of a recently introduced model of agreement dynamics, called the "Naming Game." This model describes the self-organized emergence of linguistic conventions and the establishment of simple communication systems in a population of agents with pairwise local interactions. The mechanisms of convergence towards agreement strongly depend on the network of possible interactions between the agents. In particular, the mean-field case in which all agents communicate with all the others is not efficient, since a large temporary memory is requested for the agents. On the other hand, regular lattice topologies lead to a fast local convergence but to a slow global dynamics similar to coarsening phenomena. The embedding of the agents in a small-world network represents an interesting tradeoff: a local consensus is easily reached, while the long-range links allow to bypass coarsening-like convergence. We also consider alternative adaptive strategies which can lead to faster global convergence.     

Visualizing iron in multiple sclerosis

Magnetic resonance imaging (MRI) protocols that are designed to be sensitive to iron typically take advantage of (1) iron effects on the relaxation of water protons and/or (2) iron-induced local magnetic field susceptibility changes. Increasing evidence sustains the notion that imaging iron in brain of patients with multiple sclerosis (MS) may add some specificity toward the identification of the disease pathology. The present review summarizes currently reported in vivo and post mortem MRI evidence of (1) iron detection in white matter and gray matter of MS brains, (2) pathological and physiological correlates of iron as disclosed by imaging and (3) relations between iron accumulation and disease progression as measured by clinical metrics.     

荧光碳点在脊椎类模式动物斑马鱼中的活体成像与毒理学研究

将荧光碳点引入透明斑马鱼胚胎中,研究了荧光碳点在斑马鱼中的活体成像和对斑马鱼的毒副作用。通过对水中添加荧光碳纳米颗粒,从形态上观察其对于斑马鱼个体发育的生物学效应,实时观察其在斑马鱼体内富集代谢的情况,为荧光碳点及其复合物在生物活体成像方面的研究应用奠定基础。结果表明,荧光碳点对斑马鱼生长发育无明显的毒副作用,不会导致胚胎发育异常(通过观察尾巴弯曲情况、色素深浅、血管发育速度、鱼鳔发育速度来确定对胚胎发育的影响),并且对斑马鱼无明显致死现象。荧光碳点进入斑马鱼体内的时间非常迅速,并且可以在48 h之内经代谢排出体外。     

The big problems in star formation: The star formation rate,stellar clustering,and the initial mass function

Star formation lies at the center of a web of processes that drive cosmic evolution: generation of radiant energy, synthesis of elements, formation of planets, and development of life. Decades of observations have yielded a variety of empirical rules about how it operates, but at present we have no comprehensive, quantitative theory. In this review I discuss the current state of the field of star formation, focusing on three central questions: What controls the rate at which gas in a galaxy converts to stars? What determines how those stars are clustered, and what fraction of the stellar population ends up in gravitationally-bound structures? What determines the stellar initial mass function, and does it vary with star-forming environment? I use these three questions as a lens to introduce the basics of star formation, beginning with a review of the observational phenomenology and the basic physical processes. I then review the status of current theories that attempt to solve each of the three problems, pointing out links between them and opportunities for theoretical and numerical work that crosses the scale between them. I conclude with a discussion of prospects for theoretical progress in the coming years.     

Observation of angiotensin II-induced changes in fixed and live mesangial cells by atomic force microscopy

Glomerular mesangial cells (MCs) are centrally located in the glomerulus. MCs control not only glomerular filtration, but also the response to local injury, including cell proliferation and basement membrane remodeling. Angiotensin II (Ang II) plays an important role in kidney function regulation, and participates in the progression of renal damage, as well as mesangial injury. However, studies on Ang II effects on MCs have used indirect methods, such as gene and protein expression after MC injury. In this study, we visually observed structural and mechanical changes to MC after Ang II treatment using atomic force microscopy (AFM). We obtained AFM topography and deflection images of live MCs, as well as fixed MCs in liquid, before and after Ang II treatment. Real-time imaging showed the dynamic movement of live MCs induced by Ang II. Changes in MC elastic property after Ang II treatment were measured using force–distance curves. AFM images of fixed and live MCs showed that cells contracted after Ang II exposure, with the nucleus height increasing within 20 min of Ang II stimulation. Force–distance analysis showed that Ang II caused MCs to stiffen (p < 0.0001). In conclusion, we demonstrated that AFM is an effective tool for real-time monitoring of live cell responses to drugs and stimuli.     

Autofluorescence endoscopy for the gastrointestinal tract

This review focuses on our basic study results and clinical experience of fluorescence endoscopy for the gastrointestinal (GI) tract. Collagen, which fluoresces in the green wavelength range, is one of the major sources of tissue autofluorescence (AF) and AF imaging systems are now available. With their use, however, it is important to take into account tissue changes other than, or in addition to, changes in gross tissue morphology. These may include alterations in the local blood volume, tissue metabolic activity, and relative fluorophore concentrations. New AF imaging systems are very easy to use, because white light endoscopy can be changed to AF at the push of a button, and hold great promise for diagnosis of early carcinomas and premalignant lesions in the GI tract. In particular, AF endoscopy has potential for identification of small or flat tumors, tumor margins and premalignant lesions in Barrett’s esophagus, as well as for assessing tumor grade and response to therapy. However, large-scale studies are needed to clarify the clinical impact of this new diagnostic approach.     

Lattice Boltzmann method simulating hemodynamics in the three-dimensional stenosed and recanalized human carotid bifurcations

By using the lattice Boltzmann method(LBM)pulsatile blood flows were simulated in three-dimensional moderate stenosed and recanalized carotid bifurcations to understand local hemodynamics and its relevance in arterial atherosclerosis formation and progression.The helical flow patterns,secondary flow and wall dynamical pressure spatiotemporal distributions were investigated,which leads to the disturbed shear forces in the carotid artery bifurcations.The wall shear stress distributions indicated by time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI),and the relative residence time(RRT)in a cardiac cycle revealed the regions where atherosclerotic plaques are prone to form,extend or rupture.This study also illustrates the point that locally disturbed flow may be considered as an indicator for early atherosclerosis diagnosis.Additionally the present work demonstrates the robust and highly efficient advantages of the LBM for the hemodynamics study of the human blood vessel system.     

Alzheimer's disease: biological aspects, therapeutic perspectives and diagnostic tools

Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person's ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (Aβ) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of Aβ misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.     

Simultaneous imaging of total cerebral hemoglobin concentration,oxygenation, and blood flow during functional activation

A simple instrument is demonstrated for high-resolution simultaneous imaging of total hemoglobin concentration and oxygenation and blood flow in the brain by combining rapid multiwavelength imaging with laser speckle contrast imaging. The instrument was used to image changes in oxyhemoglobin and deoxyhemoglobin and blood flow during cortical spreading depression and single whisker stimulation in rats through a thinned skull. The ability to image blood flow and hemoglobin concentration changes simultaneously with high resolution will permit detailed quantitative analysis of the spatiotemporal hemodynamics of functional brain activation, including imaging of oxygen metabolism. This is of significance to the neuroscience community and will lead to a better understanding of the interrelationship of neural, metabolic, and hemodynamic processes in normal and diseased brains.     

Emerging spectroscopic techniques for prostate cancer diagnosis

ABSTRACT

Over the past several decades, large efforts have been made to diagnose and overcome prostate cancer. Among all screening methods, the measurement of prostate-specific antigen (PSA) threshold has been stood out and contributed to diagnose prostate cancer (PCa) in a large number of men. Nevertheless, the early detection of prostate carcinoma and its focal imaging is remaining crucial to diminish the elevated number of PCa-related deaths. Because of the multifocal behavior of PCa development, a whole gland ablation has been practiced during previous years. Furthermore, there is an evidence of the likelihood of high-risk PCa that proves once again the importance of early diagnosis and accurate staging of the disease. So far, numerous advanced spectroscopic methods with different approaches have been reported as the alternative tools to conventional techniques of PCa diagnosis and imaging. In this review, we introduce innovative emerging techniques utilizing spectroscopic methods such as photoluminescence, surface-enhanced Raman spectroscopy, and surface plasmon resonance to measure the ultralow level of PSA. In addition, we review novel and alternative approaches of diagnosis such as imaging methods through photoluminescence, magnetic resonance imaging, and positron emission tomography.     

Kelvin probe force microscopy and its application

Kelvin probe force microscopy (KPFM) is a tool that enables nanometer-scale imaging of the surface potential on a broad range of materials. KPFM measurements require an understanding of both the details of the instruments and the physics of the measurements to obtain optimal results. The first part of this review will introduce the principles of KPFM and compare KPFM to other surface work function and potential measurement tools, including the Kelvin probe (KP), photoemission spectroscopy (PES), and scanning electron microscopy (SEM) with an electron beam induced current (EBIC) measurement system. The concept of local contact potential difference (LCPD), important for understanding atomic resolution KPFM, is discussed. The second part of this review explores three applications of KPFM: metallic nanostructures, semiconductor materials, and electrical devices.     

Modeling structural metastability of irradiated thin films

The nucleation of crystalline or amorphous phases in irradiated binary metallic, as well as non-metallic compound thin films is interpreted using the atomistic interface migration-charge transfer (IMCT) model. The space and time evolution of dense collision cascades, which form upon ion bombardment of the target, lead to non-equilibrium compositional and electronic density profiles at the interface between each cascade and the surrounding crystalline matrix. This occurs because one of film constituents preferentially migrates to the interface, which becomes enriched in it. Cascade relaxation to metastable equilibrium is simulated by local charge transfer reactions (CTR), each involving a pair of dissimilar atoms of the initial compound, which constitute a dimer of an effective compound. The energy cost to introduce an effective compound dimer into the matrix, the difference of formation enthalpy between effective and initial compound and the local strain suffered by the film as a consequence of ion formation by a CTR are evaluated. Threshold values are found in the above structure stability parameters that allow for a qualitative separation of amorphised from crystalline compounds, both metallic and non-metallic.     

Workflow sensitivity of post-processing methods in renal DCE-MRI

Objective: Estimation of renal filtration using dynamic contrast-enhanced imaging (DCE-MRI) requires a series of analysis steps. The possible number of distinct post-processing chains is large and grows rapidly with increasing number of processing steps or options. In this study we introduce a framework for systematic evaluation of the post-processing chains. The framework is later used to highlight the workflow processing chain sensitivity towards accuracy in estimation of glomerular filtration rate (GFR).Methods: Twenty healthy volunteers underwent DCE-MRI examinations as well as iohexol clearance for reference GFR measurements. In total, 692 different combinations of post-processing steps were explored for analysis, including options for kidney segmentation, B1 inhomogeneity correction, placement of arterial input function, gadolinium concentration estimation as well as handling of motion-corrupted volumes and breathing motion. The evaluation of various processing chains is presented using a classification tree framework and random forest ensemble learning.Results: Among the processing steps subject to testing, methods for calculating the gadolinium concentration as well as B1 inhomogeneity correction had the largest impact on accuracy of GFR estimations. Different segmentation methods did not play an important role in the post-processing of the MR data except from one processing chain where the automated segmentation outperformed the manual segmentation.Conclusion: The proposed classification trees were efficiently used as a statistical tool for visualization and communication of results to distinguish between important and less influential processing steps in renal DCE-MRI. We also identified several crucial factors in the processing chain.