Zebrafish Vascular Quantification (ZVQ): a tool for quantification of three-dimensional zebrafish cerebrovascular architecture by automated image analysis

Zebrafish transgenic lines and light sheet fluorescence microscopy allow in-depth insights into three-dimensional vascular development in vivo. However, quantification of the zebrafish cerebral vasculature in 3D remains highly challenging. Here, we describe and test an image analysis workflow for 3D quantification of the total or regional zebrafish brain vasculature, called zebrafish vasculature quantification “ZVQ”. It provides the first landmark- or object-based vascular inter-sample registration of the zebrafish cerebral vasculature, producing Population Average Maps allowing rapid assessment of intra- and inter-group vascular anatomy. ZVQ also extracts a range of quantitative vascular parameters from a user-specified Region of Interest including volume, surface area, density, branching points, length, radius, and complexity. Application of ZVQ to thirteen experimental conditions, including embryonic development, pharmacological manipulations and morpholino induced gene knockdown, shows ZVQ is robust, allows extraction of biologically relevant information and quantification of vascular alteration, and can provide novel insights into vascular biology. To allow dissemination, the code for quantification, a graphical user interface, and workflow documentation are provided. Together, ZVQ provides the first open-source quantitative approach to assess the 3D cerebrovascular architecture in zebrafish.

Decision prioritization and causal reasoning in decision hierarchies

From cooking a meal to finding a route to a destination, many real life decisions can be decomposed into a hierarchy of sub-decisions. In a hierarchy, choosing which decision to think about requires planning over a potentially vast space of possible decision sequences. To gain insight into how people decide what to decide on, we studied a novel task that combines perceptual decision making, active sensing and hierarchical and counterfactual reasoning. Human participants had to find a target hidden at the lowest level of a decision tree. They could solicit information from the different nodes of the decision tree to gather noisy evidence about the target’s location. Feedback was given only after errors at the leaf nodes and provided ambiguous evidence about the cause of the error. Despite the complexity of task (with 107 latent states) participants were able to plan efficiently in the task. A computational model of this process identified a small number of heuristics of low computational complexity that accounted for human behavior. These heuristics include making categorical decisions at the branching points of the decision tree rather than carrying forward entire probability distributions, discarding sensory evidence deemed unreliable to make a choice, and using choice confidence to infer the cause of the error after an initial plan failed. Plans based on probabilistic inference or myopic sampling norms could not capture participants’ behavior. Our results show that it is possible to identify hallmarks of heuristic planning with sensing in human behavior and that the use of tasks of intermediate complexity helps identify the rules underlying human ability to reason over decision hierarchies.

Structure and Branching of Unstable Modes in a Swirling Flow

Swirling has a significant effect on the main characteristics of flow and can lead to its fundamental restructuring. On the flow axis, a stagnation point with zero velocity is possible, behind which a return flow zone is formed. The apparent instability leads to the formation of secondary vortex motions and can also be the cause of vortex breakdown. In the paper, a swirling flow with a velocity profile of the Batchelor vortex type has been studied on the basis of the linear hydrodynamic stability theory. An effective numerical method for solving the spectral problem has been developed. This method includes the asymptotic solutions at artificial and irregular singular points. The stability of flows was considered for the values of the Reynolds number in the range 10≤Re≤5×106. The calculations were carried out for the value of the azimuthal wavenumber parameter n=−1. As a result of the analysis of the solutions, the existence of up to eight simultaneously occurring unstable modes has been shown. The paper presents a classification of the detected modes. The critical parameters are calculated for each mode. For fixed values of the Reynolds numbers 60≤Re≤5000, the curves of neutral stability are plotted. Branching points of unstable modes are found. The maximum growth rates for each mode are determined. A new viscous instability mode is found. The performed calculations reveal the instability of the Batchelor vortex at large values of the swirl parameter for long-wave disturbances.

An Effectively Dynamic Path Optimization Approach for the Tree Skeleton Extraction from Portable Laser Scanning Point Clouds

One key step to the tree structure study is skeleton processing. Although there are lots of extraction approaches, the existing methods have paid less attention to extraction effectiveness, which highly use redundant points to formulate the skeleton and bring difficulties to the subsequent 3D modeling. This work proposes a four-step framework for the purpose of skeleton extraction. Firstly, candidate skeleton points are filtered from input data based on the spatial slice projection and grouped using the Euclidean distance analysis. Secondly, a key dynamic path optimization step is used to formulate a tree skeleton using the candidate point information. Thirdly, the optimized path is filled by interpolating points to achieve complete skeletons. Finally, short skeletons are removed based on the distance between branching points and ending points, and then, the extraction skeletons are smoothed for improving the visual quality. Our main contribution lies in that we find the global minimization cost path from every point to the root using a novel energy function. The formulated objective function contains a data term to constrain the distance between points and paths, and a smoothness term to constrain the direction continuities. Experimental scenes include three different types of trees, and input point clouds are collected by a portable laser scanning system. Skeleton extraction results demonstrate that we achieved completeness and correctness of 81.10% and 99.21%. respectively. Besides, our effectiveness is up to 79.26%, which uses only 5.82% of the input tree points in the skeleton representation, showing a promising effective solution for the tree skeleton and structure study.

Neuroprotective effect of and ascorbic acid in brain against high fat diet and stress induced neurotoxicity

Chronic exposure to stress and diet rich in saturated fat is one of the major reasons for the development of dementia and neurodegenerative disorders. The present study aims to examine the neuroprotective potential of and Ascorbic acid against high fat diet and stress induced neurotoxicity in brain. Animals were randomly divided into five groups. Group I received normal diet, Group II received high fat diet along with stress, Group III were treated with 100mg/kg body weight, and Group IV were treated with Ascorbic acid 100mg/kg body weight, Group V were treated with 100mg/kg body weight and Ascorbic acid 100mg/kg body weight. After the treatment all rats were sacrificed and brains were removed. Golgi staining was done and dendritic branching points and dendritic intersections were quantified with the help of cameralucida.There was a significant increase in dendritic length and branching points was observed in brain in rats treated with and Ascorbic acid.Present study concludes that and Ascorbic acid have neuroprotective role against high fat diet and stress induced Wistar rats.

Three-dimensional morphological analysis of spermatogenesis in aged mouse testes

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.

TAMI-52. NEURONAL MECHANISMS OF BRAIN TUMOR INVASION

Incurable gliomas are characterized by their infiltration into the whole brain. Recently, we described tumor microtubes as a novel structure contributing to glioma cell invasion and uncovered synaptic contacts on glioma cells that drive brain tumour progression. However, the exact effects of neuronal activity on glioma cell motility are yet unclear. Here, we show how a recently described neuronal-like cellular transcription state of glioblastoma cells is correlated to glioma cell invasion in vivo. To unravel the details of neuronal features of glioma invasion in space and time, we established a novel approach of intravital imaging for brain tumor cells with a membrane-bound GFP combined with deep learning algorithms that are used to track glioma cell processes with a high temporal resolution over several hours. This approach uncovers how invading tumor microtubes use Levy-like movement patterns indicative of efficient search patterns often employed by animal predators searching for scarce resources such as food. Neuronal activity is able to accelerate the tumor microtube dynamics, accelerate the Levy-like movement patterns and increase the overall invasion speed of glioma cells. These processes are mediated by local calcium transients in glioma cell somata and tumor microtubes. In accordance, genetic manipulation and pharmacological perturbation of AMPA receptors reduces tumor microtube length, number and branching points by interfering with intracellular calcium transients. All in all, the work here uncovers novel neuronal activity-mediated mechanisms of glioma cell invasion, a hallmark of this yet fatal disease.

On the nature of the sustainability of the process in time

Introduction. Why do the ideas about time in ‘The Iliad’ and in the conditions of modern transmission speeds of large flows of information unexpectedly converge, and the key point is the study of the forms of stability of the process in time? What do we really mean by ingrained thinking and sustainable development, and how do they relate to the evolutionary nature of sustainable processes? The purpose of this paper is to present the form of a sustainable process, its constructive deployment in time by means of a natural science analysis. Materials and Methods. Based on the materials and methods of measuring time-varying quantities, as well as set-theoretic prerequisites for branching the process, it is proposed to look for natural scientific grounds for analyzing the sustainable development of trends in culture in general, in information processes and the education system, in particular. Here we will also try to take a well-known point of view (K. Lorentz, I. Prigozhin), when time, irreversibility, randomness in some constructive process relate to inanimate matter, to life, and to human. Results. Based on the analysis carried out by the author, the answer to the question of whether there are natural conditions for the sustainability of the object-process, in what aspect we can discuss the constructiveness of time, the evolutionary rooting of sustainable processes, branching points and the ‘stretching’ of a sustainable educational process into the future is presented. Conclusions. Our ideas about the processes in time and the conditions of their sustainability in the broadest cultural aspect, including the education system, need to be clarified. The constructive deployment of the process in time has its own structure that ensures the evolutionary rooting of the process and, in particular, the educational process.

TwinCons: Conservation score for uncovering deep sequence similarity and divergence

We have developed the program TwinCons, to detect noisy signals of deep ancestry of proteins or nucleic acids. As input, the program uses a composite alignment containing pre-defined groups, and mathematically determines a ‘cost’ of transforming one group to the other at each position of the alignment. The output distinguishes conserved, variable and signature positions. A signature is conserved within groups but differs between groups. The method automatically detects continuous characteristic stretches (segments) within alignments. TwinCons provides a convenient representation of conserved, variable and signature positions as a single score, enabling the structural mapping and visualization of these characteristics. Structure is more conserved than sequence. TwinCons highlights alternative sequences of conserved structures. Using TwinCons, we detected highly similar segments between proteins from the translation and transcription systems. TwinCons detects conserved residues within regions of high functional importance for the ribosomal RNA (rRNA) and demonstrates that signatures are not confined to specific regions but are distributed across the rRNA structure. The ability to evaluate both nucleic acid and protein alignments allows TwinCons to be used in combined sequence and structural analysis of signatures and conservation in rRNA and in ribosomal proteins (rProteins). TwinCons detects a strong sequence conservation signal between bacterial and archaeal rProteins related by circular permutation. This conserved sequence is structurally colocalized with conserved rRNA, indicated by TwinCons scores of rRNA alignments of bacterial and archaeal groups. This combined analysis revealed deep co-evolution of rRNA and rProtein buried within the deepest branching points in the tree of life.

Neuroprotective role of Ginkgobiloba and Rosuvastatin in CA1 region of Hippocampus against high fat diet induced neurotoxicity

Diet rich in fat is one of the main risk factor for the development of Alzheimer’s disease. Studies have shown that diet rich in fat disrupts memory and learning. The present study evaluates the ameliorative role of Ginkgobiloba and Rosuvastatin against high fat diet induced neurotoxicity in CA1 (Corona Ammonis) region of hippocampus. Animals were randomly divided into six groups. Group I received normal diet, Group II received high fat diet, Group III & IV were treated with Ginkgobiloba 50mg/kg and 100mg/kg body weight, and Group V & VI were treated with Rosuvastatin 10mg/kg and 20 mg/kg body weight. All the rats were subjected to spatial learning (Morris water maze). Subsequently, rats were sacrificed and brains were removed. Golgi staining was done and CA1 neurons of hippocampus were traced using camera lucida. Dendritic branching points and dendritic intersections were quantified. Lipid profile and Super oxide (SOD) was also estimated.There was enhancement of spatial learning in treatment group rats. Furthermore, a significant increase in dendritic length and branching points was observed in CA1 region along with significant decrease in the Superoxide dismutase in rats treated with higher dose of Ginkgobiloba and Rosuvastatin. Present study concludes that Ginkgobiloba and Rosuvastatin in higher dose have protective role against high fat diet induced neurotoxicity in CA1 region.