A stereotaxic atlas of the monkey frontal lobes.

A stereotaxic atlas of the frontal lobes of M. Arctoides is presented as a consecutive series of line drawings. It is based on six animals. Alternating serial coronal sections stained with cresyl violet or Luxol Fast Blue were produced for each brain. Representative sections were used to prepare line drawings at one-millimeter intervals at a magnification of 4x. The stereotaxic anterior to posterior range is +43 to +20. This line drawing format can be use to recorded electrode placement or document the extent of lesions.     

人脑和人血清胆碱酯酶三维结构的计算机模拟研究

本文以同源的电鳐胆碱酯酶（Ｔ．ＡＣｈＥ）的三维结构为模板,模拟预测了人脑和血清胆碱酯酶（Ｈ。ＡＣｈＥ和Ｈ．ＢｕＣｈＥ）的三维结构和活力中心的组成。指Ｔ．ＡＣｈＥ,Ｈ．ＡＣｈＥ和Ｈ．ＢｕＣｈＥ宁间结构差异,并讨论了ＡＣｈ和Ｈ。ＡＣｈＥ的对接（ｄｏｃｋｉｎｇ）。Ｈ。ＡＣｈＥ和Ｈ．ＢｕＣｈＥ三维结构的确定将为进一步深入研究它的中毒机理和合理药物设计提供靶子。     

Numerical simulation of local blood flow in the carotid and cerebral arteries under altered gravity

A computational fluid dynamics (CFD) approach was presented to model the blood flows in the carotid bifurcation and the brain arteries under altered gravity. Physical models required for CFD simulation were introduced including a model for arterial wall motion due to fluid-wall interactions, a shear thinning fluid model of blood, a vascular bed model for outflow boundary conditions, and a model for autoregulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models were solved iteratively using the pseudocompressibility method and dual time stepping. Gravity source terms were added to the Navier-Stokes equations to take the effect of gravity into account. For the treatment of complex geometry, a chimera overset grid technique was adopted to obtain connectivity between arterial branches. For code validation, computed results were compared with experimental data for both steady-state and time-dependent flows. This computational approach was then applied to blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other using an anatomical data set. A three-dimensional Circle of Willis configuration was reconstructed from subject-specific magnetic resonance images using an image segmentation method. Through the numerical simulation of blood flow in two model problems, namely, the carotid bifurcation and the brain arteries, it was observed that the altered gravity has considerable effects on arterial contraction/dilatation and consequent changes in flow conditions.     

Concept and development of an orthotropic FE model of the proximal femur

PURPOSE: In contrast to many isotropic finite-element (FE) models of the femur in literature, it was the object of our study to develop an orthotropic FE "model femur" to realistically simulate three-dimensional bone remodelling. METHODS: The three-dimensional geometry of the proximal femur was reconstructed by CT scans of a pair of cadaveric femurs at equal distances of 2mm. These three-dimensional CT models were implemented into an FE simulation tool. Well-known "density-determined" bony material properties (Young's modulus; Poisson's ratio; ultimate strength in pressure, tension and torsion; shear modulus) were assigned to each FE of the same "CT-density-characterized" volumetric group.In order to fix the principal directions of stiffness in FE areas with the same "density characterization", the cadaveric femurs were cut in 2mm slices in frontal (left femur) and sagittal plane (right femur). Each femoral slice was scanned into a computer-based image processing system. On these images, the principal directions of stiffness of cancellous and cortical bone were determined manually using the orientation of the trabecular structures and the Haversian system. Finally, these geometric data were matched with the "CT-density characterized" three-dimensional femur model. In addition, the time and density-dependent adaptive behaviour of bone remodelling was taken into account by implementation of Carter's criterion. RESULTS: In the constructed "model femur", each FE is characterized by the principal directions of the stiffness and the "CT-density-determined" material properties of cortical and cancellous bone. Thus, on the basis of anatomic data a three-dimensional FE simulation reference model of the proximal femur was realized considering orthotropic conditions of bone behaviour. CONCLUSIONS: With the orthotropic "model femur", the fundamental basis has been formed to realize realistic simulations of the dynamical processes of bone remodelling under different loading conditions or operative procedures (osteotomies, total hip replacements, etc).     

Individual variability of the human brain (putamen)

By means of microscopical cytoarchitectonical methods the borders of the putamen have been established and its volume has been measured in the brain of some persons of various sex and age (21 individuals, 27 hemispheres). The putamen variants are not connected with changes in the brain weight and age. The difference in the volume of the extreme variants is 3.7 times. The distribution of the variants does not contradict the hypothesis on its normality. The data obtained make to revise the principles on the proportional dependence between the external and internal structures of the brain which lie in the base for using stereotaxic atlases at any size of the human brain. An especially real threat for complications at surgical interventions performed in the human brain occurs when the most seldom variants of the putamen are present, since their parameters are not at all taken into consideration in the existing stereotaxic reference Moscow.     

A comparison of the restrained molecular dynamics and distance geometry methods for determining three-dimensional structures of proteins on the basis of interproton distances

A direct comparison of the metric matrix distance geometry and restrained molecular dynamics methods for determining three-dimensional structures of proteins on the basis of interproton distances is presented using crambin as a model system. It is shown that both methods reproduce the overall features of the secondary and tertiary structure (shape and polypeptide fold). The region of conformational space sampled by the converged structures generated by the two methods is similar in size, and in both cases the converged structures are distributed about mean structures which are closer to the X-ray structure than any of the individual structures. The restrained molecular dynamics structures are superior to those obtained from distance geometry as regards local backbone conformation, side chain positions and non-bonding energies.     

Synaptology of the claustrum in the rat

A great deal of information is available on the morphology of the claustrum in various animal species, as well as on its neuronal distribution and relationships with the cerebral cortex and other nuclei. However, no research has been performed on synaptic organization. Here we report an ultrastructural study performed on 7 male albino rats of the Wistar strain weighing 270-310 g. Five rats were sacrificed by prolonging general anesthesia with diethyl ether until death. Three of these rats were secured to the stereotaxic atlas coordinates of Paxinos and Watson (1982); the claustrum area was marked by injecting 1 microliter of a 10% Evans Blue solution into the nucleus. The brain was then removed from the skull, cut into 2-3 mm thick coronal sections, and tissue samples taken from the area immediately adjacent to the marked area were immersed in 2% OsO4 buffered with 2% potassium dichromate containing 0.2% CaCl2 at pH 7.7 (Gobel, 1968). After dehydration they were embedded in Durcupan and the ultrafine sections were stained with uranyl acetate and lead citrate and observed with either a Zeiss 9S2 or a Hitachi H 800 electron microscope. The samples from two other rats, taken with the stereotaxic techniques described, were fixed for 12 h in 0.6 potassium permanganate solution buffered with veronal-acetate at pH 7.4 (Luft, 1956). After processing for electron microscopy, a portion of the sections were used without any contrast medium and the remainder were stained with uranyl acetate and lead citrate.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢病毒介导的下丘脑中过表达miR-505小鼠模型的构建

目的:本文用慢病毒定点注射的方法构建了在下丘脑中过表达mi R-505的小鼠模型,并利用荧光原位杂交方法在冰冻切片组织上快速检测mi RNAs,以确认慢病毒载体介导的mi R-505在丘脑中的表达能力。方法:实验小鼠在脑立体定位仪下定位到下丘脑位置,采用原位注射的方式进行慢病毒注射,注射后采用实时荧光定量RCR和应用了LNA探针和TSA系统的FISH(fluorescence in situ hybridization)技术,完成在慢病毒介导的mi R-505过表达老鼠下丘脑区域细胞中的mi R-505检测和示踪。结果:mi R-505慢病毒注射未成年小鼠下丘脑区5、10、20和40天后,均可检测到mi R-505在下丘脑区域的表达,且实验结果表明在慢病毒介导的过表达小鼠下丘脑注射部位,mi R-505表达量有明显的提高。结论:利用慢病毒注射未成年小鼠下丘脑脑区的方法,成功的建立了下丘脑中过表达mi R-505的小鼠模型,使用LNA标记探针的FISH方法探索mi RNA表达规律较稳定,且重复率高。     

Three-dimensional periodic cubic membrane structure in the mitochondria of amoebaeChaos carolinensis

Summary Through computer simulation of images produced by the transmission electron microscope (TEM), we have identified three-dimensional periodic cubic membrane structures in giant amoebae (Chaos carolinensis) mitochondria. The cubic membranes are based on the highly curved three-dimensional periodic cubic surfaces, sharing the same geometry of mathematically defined periodic minimal surfaces. The double-membrane structures identified here divide space into three separate and convoluted subspaces. Specimen preparation, specifically the tendency to cut oblique sections, of this membrane crystal has added to the complexity of the resulting TEM projections and until now prevented researchers from recognizing them. It is the added complexity of the oblique sections, though, that allows us to match the TEM projection to a computer simulation of the same with confidence. In this study, formation of cubic membrane structures in amoeba mitochondria was found to be dependent on diet. The cubic structures only occurred in the absence of food, and disappeared in the presence of food, suggesting a structural adaptation and possible advantages for amoeba's survival in nature. The verification of mathematically well-defined structures in unfed amoeba mitochondria is also important to the understanding of the mitochondrial bioenergetics in relation to the topology of the inner membrane, where major cellular energy production as well as free-radical generation are taking place. This understanding may carry great impact upon human health as far as aging and age-related degenerative diseases are concerned, especially as mitochondrial disorders have been implicated in these processes.Abbreviations G gyroid - D double diamond - P primitive - TEM transmission electron microscopy - PCS periodic cubic surface     

棉铃虫幼虫脑和咽下神经节的三维结构构建

【目的】解剖棉铃虫Helicoverpa armigera (Hübner) 5龄幼虫脑和咽下神经节及其内部神经髓形态结构,并分析和构建幼虫脑和咽下神经节以及各神经髓的三维结构模型。【方法】采用免疫组织化学方法解剖脑和咽下神经节的内部神经髓结构,利用激光共聚焦显微镜获取脑和咽下神经节扫描图像,然后利用AMIRA 三维图像分析软件进行图像分析,从而构建脑和咽下神经节的三维结构模型,并测量脑和咽下神经节以及内部各神经髓的体积,并分析了相对比例。【结果】 棉铃虫5龄幼虫脑和咽下神经节由围咽神经索连接在一起。脑主要由前脑、中脑和后脑3部分组成。前脑内包括视叶、蕈形体和中央体等形态结构较明显的神经髓。此外,前脑还包括其他位于脑的左右两侧以及背侧和腹侧大量神经髓区域,约占脑总神经髓的59.65%。这些神经髓区域边界不明显。中脑主要包括1对触角叶;后脑位于脑的腹侧和触角叶的下方,体积较小。咽下神经节由3个神经节融合构成,从前到后分别为上颚神经节、下颚神经节和下唇神经节,由于融合的紧密程度高,3个神经节间的边界不明显。【结论】阐明了棉铃虫5龄幼虫脑和咽下神经节的神经髓形态结构,构建了脑和咽下神经节以及内部神经髓的三维结构模型。三维模型可以任意旋转,能从任何角度观察脑、咽下神经节和内部不同神经髓的结构及其它们之间的空间关系。本研究结果对研究棉铃虫脑和咽下神经节信息接收、处理及调控行为的机制奠定了解剖学基础。     

Stereotaxic Surgery for Excitotoxic Lesion of Specific Brain Areas in the Adult Rat

Many behavioral functions in mammals, including rodents and humans, are mediated principally by discrete brain regions. A common method for discerning the function of various brain regions for behavior or other experimental outcomes is to implement a localized ablation of function. In humans, patient populations with localized brain lesions are often studied for deficits, in hopes of revealing the underlying function of the damaged area. In rodents, one can experimentally induce lesions of specific brain regions.Lesion can be accomplished in several ways. Electrolytic lesions can cause localized damage but will damage a variety of cell types as well as traversing fibers from other brain regions that happen to be near the lesion site. Inducible genetic techniques using cell-type specific promoters may also enable site-specific targeting. These techniques are complex and not always practical depending on the target brain area. Excitotoxic lesion using stereotaxic surgery, by contrast, is one of the most reliable and practical methods of lesioning excitatory neurons without damaging local glial cells or traversing fibers.Here, we present a protocol for stereotaxic infusion of the excitotoxin, N-methyl-D-aspartate (NMDA), into the basolateral amygdala complex. Using anatomical indications, we apply stereotaxic coordinates to determine the location of our target brain region and lower an injection needle in place just above the target. We then infuse our excitotoxin into the brain, resulting in excitotoxic death of nearby neurons. While our experimental subject of choice is a rat, the same methods can be applied to other mammals, with the appropriate adjustments in equipment and coordinates.This method can be used on a variety of brain regions, including the basolateral amygdala^1-6, other amygdala nuclei^{6, 7}, hippocampus⁸, entorhinal cortex⁹ and prefrontal cortex¹⁰. It can also be used to infuse biological compounds such as viral vectors^{1, 11}. The basic stereotaxic technique could also be adapted for implantation of more permanent osmotic pumps, allowing more prolonged exposure to a compound of interest.     

Stereotaxic atlas of the brain of Octodon degus.

We present a stereotaxic atlas of the brain of the trumpet-tailed rat or degu (Octodon degus), an hystricomorph rodent native to Chile and one which has become increasingly popular as a research animal, among other things because of its use as a model for diabetic cataracts and its tendency to become hyperglycemic. The atlas contains 38 transverse and two sagittal sections of the brain covering pros-, mes-, and rhombencephalon, as well as diagrams of the brain's surface anatomy. It was constructed from brains of young adult male degus but can be used readily in studies of adult females, since there is no apparent sexual dimorphism in the brain size of this rodent. Ninety percent of 40 experimental lesions used to check the accuracy of the atlas were correctly placed. The fore- and midbrain of the degu are generally more compact than corresponding regions of the brain in the laboratory rat (suborder Myomorpha) and the guinea pig (another hystricomorph). The amygdaloid complex extends further forward in the telencephalon. Major mesencephalic nuclei and fiber tracts are more rostral in position. However, superior and inferior colliculi are much longer in degus than rats. The basic organization of the rhombencephalon is similar in degus and rats, although there are clearcut differences in the length or size of some hindbrain nuclei.     

Statistical geometry based prediction of nonsynonymous SNP functional effects using random forest and neuro-fuzzy classifiers

There is substantial interest in methods designed to predict the effect of nonsynonymous single nucleotide polymorphisms (nsSNPs) on protein function, given their potential relationship to heritable diseases. Current state-of-the-art supervised machine learning algorithms, such as random forest (RF), train models that classify single amino acid mutations in proteins as either neutral or deleterious to function. However, it is frequently the case that the functional effect of a polymorphism on a protein resides between these two extremes. The utilization of classifiers that incorporate fuzzy logic provides a natural extension in order to account for the spectrum of possible functional consequences. We generated a dataset of single amino acid substitutions in human proteins having known three-dimensional structures. Each variant was uniquely represented as a feature vector that included computational geometry and knowledge-based statistical potential predictors obtained though application of Delaunay tessellation of protein structures. Additional attributes consisted of physicochemical properties of the native and replacement amino acids as well as topological location of the mutated residue position in the solved structure. Classification performance of the RF algorithm was evaluated on a training set consisting of the disease-associated and neutral nsSNPs taken from our dataset, and attributes were ranked according to their relative importance. Similarly, we evaluated the performance of adaptive neuro-fuzzy inference system (ANFIS). The utility of statistical geometry predictors was compared with that of traditional structural and evolutionary attributes employed by other researchers, revealing an equally effective yet complementary methodology. Among all attributes in our feature set, the statistical geometry predictors were found to be the most highly ranked. On the basis of the AUC (area under the ROC curve) measure of performance, the ANFIS and RF models were equally effective when only statistical geometry features were utilized. Tenfold cross-validation studies evaluating AUC, balanced error rate (BER), and Matthew's correlation coefficient (MCC) showed that our RF model was at least comparable with the well-established methods of SIFT and PolyPhen. The trained RF and ANFIS models were each subsequently used to predict the disease potential of human nsSNPs in our dataset that are currently unclassified (http://rna.gmu.edu/FuzzySnps/).     

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.     

Temperature profiles with respect to inhomogeneity and geometry of the human body

Temperature profiles within the human body are highly dependent on the geometry and inhomogeneity of the body. Physical parameters such as density and heat conductivity of the various tissues and variables such as blood flow and metabolic heat production of different organs are spatially distributed and thereby influence the temperature profiles within the human body. Actual physiological knowledge allows one to take into account up to 54 different spatially distributed values for each parameter. An adequate representation of the anatomy of the body requires a spatial three-dimensional grid of at least 0.5-1.0 cm. This is achieved by photogrammetric treatment of three-dimensional anatomic models of the human body. As a first essential result, the simulation system has produced a realistic picture of the topography of temperatures under neutral conditions. Compatibility of reality and simulation was achieved solely on the basis of physical considerations and physiological data base. Therefore the simulation is suited to the extrapolation of temperature profiles that cannot be obtained experimentally.     

Antagonistic activity of one-joint muscles in three-dimensions using non-linear optimisation

Non-linear optimisation, such as the type presented by R.D. Crowninshield and R.A. Brand [The prediction of forces in joint structures: Distribution of intersegmental resultants, Exercise Sports Sci. Rev. 9 (1981) 159], has been frequently used to obtain a unique set of muscle forces during human or animal movements. In the past, analytical solutions of this optimisation problem have been presented for single degree-of-freedom models, and planar models with a specific number of muscles and a defined musculoskeletal geometry. Results of these studies have been generalised to three-dimensional problems and for general formulations of the musculoskeletal geometry without corresponding proofs. Here, we extend the general solution of the above non-linear, constrained, planar optimisation problem to three-dimensional systems of arbitrary geometry. We show that there always exists a set of intersegmental moments for which the given static optimisation formulation will predict co-contraction of a pair of antagonistic muscles unless they are exact antagonists. Furthermore, we provide, for a given three-dimensional system consisting of single joint muscles, a method that describes all the possible joint moments that give co-contraction for a given pair of antagonistic muscles.     

Morphological patterns of the intraparietal sulcus and the anterior intermediate parietal sulcus of Jensen in the human brain

Distinct parts of the intraparietal sulcal cortex contribute to sensorimotor integration and visual spatial attentional processing. A detailed examination of the morphological relations of the different segments of the complex intraparietal sulcal region in the human brain in standard stereotaxic space, which is a prerequisite for detailed structure-to-function studies, is not available. This study examined the intraparietal sulcus (IPS) and the related sulcus of Jensen in magnetic resonance imaging brain volumes registered in the Montreal Neurological Institute stereotaxic space. It was demonstrated that the IPS is divided into two branches: the anterior ramus and the posterior ramus of the IPS, often separated by a submerged gyral passage. The sulcus of Jensen emerges between the anterior and posterior rami of the IPS, and its ventral end is positioned between the first and second caudal branches of the superior temporal sulcus. In a small number of brains, the sulcus of Jensen may merge superficially with the first caudal branch of the superior temporal sulcus. The above morphological findings are discussed in relation to previously reported functional neuroimaging findings and provide the basis for future exploration of structure-to-function relations in the posterior parietal region of individual subjects.     

Laser scanning cytometry in human brain slices.

BACKGROUND: The Laser Scanning Cytometry (LSC) offers quantitative fluorescence analysis of cell suspensions and tissue sections. METHODS: We adapted this technique to immunohistochemical labelled human brain slices. RESULTS: We were able to identify neurons according to their labelling and to display morphological structures such as the lamination of the entorhinal cortex. Further, we were able to distinguish between neurons with and without cyclin B1 expression and we could assign the expression of cyclin B1 to the cell islands of layer II and the pyramidal neurons of layer V of the entorhinal cortex in Alzheimer's disease effected brain. In addition, we developed a method depicting the three-dimensional distribution of the cells in intact tissue sections. CONCLUSIONS: In this pilot experiments we could demonstrate the power of the LSC for the analysis of human brain sections.