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https://www.readbyqxmd.com/read/28314191/robust-detection-and-segmentation-of-cell-nuclei-in-biomedical-images-based-on-a-computational-topology-framework
#1
Rodrigo Rojas-Moraleda, Wei Xiong, Niels Halama, Katja Breitkopf-Heinlein, Steven Dooley, Luis Salinas, Dieter W Heermann, Nektarios A Valous
The segmentation of cell nuclei is an important step towards the automated analysis of histological images. The presence of a large number of nuclei in whole-slide images necessitates methods that are computationally tractable in addition to being effective. In this work, a method is developed for the robust segmentation of cell nuclei in histological images based on the principles of persistent homology. More specifically, an abstract simplicial homology approach for image segmentation is established. Essentially, the approach deals with the persistence of disconnected sets in the image, thus identifying salient regions that express patterns of persistence...
March 6, 2017: Medical Image Analysis
https://www.readbyqxmd.com/read/28299743/computational-approaches-to-matrix-metalloprotease-drug-design
#2
Tanya Singh, B Jayaram, Olayiwola Adedotun Adekoya
Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes required for homeostasis. These enzymes are an important class of drug targets as their over expression is associated with many disease states. Most of the inhibitors reported against this class of proteins have failed in clinical trials due to lack of specificity. In order to assist in drug design endeavors for MMP targets, a computationally tractable pathway is presented, comprising, (1) docking of small molecule inhibitors against the target MMPs, (2) derivation of quantum mechanical charges on the zinc ion in the active site and the amino acids coordinating with zinc including the inhibitor molecule, (3) molecular dynamics simulations on the docked ligand-MMP complexes, and (4) evaluation of binding affinities of the ligand-MMP complexes via an accurate scoring function for zinc containing metalloprotein-ligand complexes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28292839/the-physics-of-organoids-a-biophysical-approach-to-understanding-organogenesis
#3
Svend Dahl-Jensen, Anne Grapin-Botton
Organoids representing a diversity of tissues have recently been created, bridging the gap between cell culture and experiments performed in vivo Being small and amenable to continuous monitoring, they offer the opportunity to scrutinize the dynamics of organ development, including the exciting prospect of observing aspects of human embryo development live. From a physicist's perspective, their ability to self-organize - to differentiate and organize cells in space - calls for the identification of the simple rules that underlie this capacity...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28288121/a-genetic-system-to-study-plasmodium-falciparum-protein-function
#4
Jakob Birnbaum, Sven Flemming, Nick Reichard, Alexandra Blancke Soares, Paolo Mesén-Ramírez, Ernst Jonscher, Bärbel Bergmann, Tobias Spielmann
Current systems to study essential genes in the human malaria parasite Plasmodium falciparum are often inefficient and time intensive, and they depend on the genetic modification of the target locus, a process hindered by the low frequency of integration of episomal DNA into the genome. Here, we introduce a method, termed selection-linked integration (SLI), to rapidly select for genomic integration. SLI allowed us to functionally analyze targets at the gene and protein levels, thus permitting mislocalization of native proteins, a strategy known as knock sideways, floxing to induce diCre-based excision of genes and knocking in altered gene copies...
March 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/28287527/examination-of-host-phenotypes-in-gambusia-affinis-following-antibiotic-treatment
#5
Jeanette M Carlson, Oscar Chavez, Sonali Aggarwal, Todd P Primm
The commonality of antibiotic usage in medicine means that understanding the resulting consequences to the host is vital. Antibiotics often decrease host microbiome community diversity and alter the microbial community composition. Many diseases such as antibiotic-associated enterocolitis, inflammatory bowel disease, and metabolic disorders have been linked to a disrupted microbiota. The complex interplay between host, microbiome, and antibiotics needs a tractable model for studying host-microbiome interactions...
February 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28285998/a-non-cell-autonomous-role-of-bec-1-becn1-beclin1-in-coordinating-cell-cycle-progression-and-stem-cell-proliferation-during-germline-development
#6
Kristina Ames, Dayse S Da Cunha, Brenda Gonzalez, Marina Konta, Feng Lin, Gabriel Shechter, Lev Starikov, Sara Wong, Hannes E Bülow, Alicia Meléndez
The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1-4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16...
March 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28285523/encoding-odorant-images
#7
Madeleine Marie Rochelle, Géraldine Julie Prévost, Terry Edward Acree
This perspective examines psychophysical methods that may reveal the algorithms that encode odor images by integrating current data from sensory measurement into a computational model of odor perception. There is evidence that algorithms used by the nervous system to process odor sensations require input from only a few odorants, between 3 and 8. Furthermore, the number of recognizable odors in foods that contribute anything to the aroma of all foods is approximately 250.8 This may imply that it is the ratio of a small number of key odorants (KOs) that create a multitude of food odor...
March 12, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28285105/tunable-preparation-of-ruthenium-nanoparticles-with-superior-size-dependent-catalytic-hydrogenation-properties
#8
Yuan Zhao, Yaodong Luo, Xuan Yang, Yaxin Yang, Qijun Song
Ruthenium (Ru) featured with an unusual catalytic behavior is of great significance in several heterogeneous and electro-catalytic reactions. The preparation of tractable Ru nanocatalysts and the building of highly active catalytic system at ambient temperature remains a grand challenge. Herein, a facile strategy is developed for the controllable preparation of Ru nanoparticles (NPs) with the sizes ranging from 2.6 to 51.5nm. Ru NPs show superior size-dependent catalytic performance with the best kinetic rate constant as high as -1...
March 6, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28278459/fast-randomized-singular-value-thresholding-for-low-rank-optimization
#9
Tae-Hyun Oh, Yasuyuki Matsushita, Yu-Wing Tai, In So Kweon
Rank minimization can be converted into tractable surrogate problems, such as Nuclear Norm Minimization (NNM) and Weighted NNM (WNNM). The problems related to NNM, or WNNM, can be solved iteratively by applying a closed-form proximal operator, called Singular Value Thresholding (SVT), or Weighted SVT, but they suffer from high computational cost of Singular Value Decomposition (SVD) at each iteration. We propose a fast and accurate approximation method for SVT, that we call fast randomized SVT (FRSVT), with which we avoid direct computation of SVD...
March 3, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28275681/gastrointestinal-organoids-understanding-the-molecular-basis-of-the-host-microbe-interface
#10
REVIEW
David R Hill, Jason R Spence
In recent years, increasing attention has been devoted to the concept that microorganisms play an integral role in human physiology and pathophysiology. Despite this, the molecular basis of host-pathogen and host-symbiont interactions in the human intestine remains poorly understood owing to the limited availability of human tissue, and the biological complexity of host-microbe interactions. Over the past decade, technological advances have enabled long-term culture of organotypic intestinal tissue derived from human subjects and from human pluripotent stem cells, and these in vitro culture systems already have shown the potential to inform our understanding significantly of host-microbe interactions...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28264903/longitudinal-quasi-static-stability-predicts-changes-in-dog-gait-on-rough-terrain
#11
Simon Wilshin, Michelle A Reeve, G Clark Haynes, Shai Revzen, Daniel E Koditschek, Andrew J Spence
Legged animals utilize gait selection to move effectively and must re-cover from environmental perturbations. We show that on rough terrain domestic dogs, Canis lupus familiaris, spend more time in longitudinal quasi-statically stable patterns of movement. Here longitudinal refers to the rostro-caudal, axis. We used an existing model in the literature to quantify the longitudinal quasi-static stability of gaits neighbouring the walk, and found that trot-like gaits are more stable. We thus hypothesized that when perturbed, the rate of return to a stable gait would depend on the direction of perturbation, such that perturbations towards less quasi-statically stable patterns of movement would be more rapid than those towards more stable patterns of movement...
March 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28261064/expression-of-sept3-sept5a-and-sept5b-in-the-developing-and-adult-nervous-system-of-the-zebrafish-danio-rerio
#12
Frederik Helmprobst, Christina Lillesaar, Christian Stigloher
Septins are a highly conserved family of small GTPases that form cytoskeletal filaments. Their cellular functions, especially in the nervous system, still remain largely enigmatic, but there are accumulating lines of evidence that septins play important roles in neuronal physiology and pathology. In order to further dissect septin function in the nervous system a detailed temporal resolved analysis in the genetically well tractable model vertebrate zebrafish (Danio rerio) is crucially necessary. To close this knowledge gap we here provide a reference dataset describing the expression of selected septins (sept3, sept5a and sept5b) in the zebrafish central nervous system...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28257444/mechanisms-of-fast-and-stringent-search-in-homologous-pairing-of-double-stranded-dna
#13
Amir Bitran, Wei-Yin Chiang, Erel Levine, Mara Prentiss
Self-organization in the cell relies on the rapid and specific binding of molecules to their cognate targets. Correct bindings must be stable enough to promote the desired function even in the crowded and fluctuating cellular environment. In systems with many nearly matched targets, rapid and stringent formation of stable products is challenging. Mechanisms that overcome this challenge have been previously proposed, including separating the process into multiple stages; however, how particular in vivo systems overcome the challenge remains unclear...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28256783/the-processive-kinetics-of-gene-conversion-in-bacteria
#14
Johan Paulsson, Meriem El Karoui, Monica Lindell, Diarmaid Hughes
Gene conversion, non-reciprocal transfer from one homologous sequence to another, is a major force in evolutionary dynamics, promoting co-evolution in gene families, and maintaining similarities between repeated genes. However, the properties of the transfer - where it initiates, how far it proceeds, and how the resulting conversion tracts are affected by mismatch repair - are not well understood. Here we use the duplicate tuf genes in Salmonella as a quantitatively tractable model system for gene conversion...
March 3, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28256192/the-insect-pathogens
#15
Brian Lovett, Raymond J St Leger
Fungi are the most common disease-causing agents of insects; aside from playing a crucial role in natural ecosystems, insect-killing fungi are being used as alternatives to chemical insecticides and as resources for biotechnology and pharmaceuticals. Some common experimentally tractable genera, such as Metarhizium spp., exemplify genetic diversity and dispersal because they contain numerous intraspecific variants with distinct environmental and insect host ranges. The availability of tools for molecular genetics and multiple sequenced genomes has made these fungi ideal experimental models for answering basic questions on the genetic and genomic processes behind adaptive phenotypes...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28252202/a-mouse-model-for-ocular-surface-staphylococcus-aureus-infection
#16
Zhiyong Zhang, Osama Abdel-Razek, Guirong Wang
Creation of an appropriate animal model that accurately reflects the disease and host immune response to bacterial infection in humans is a major challenge in ocular-surface infection research. For decades, mice have been the ideal small animal model for ocular-surface infection research because of the availability and relatively low cost of various genetic backgrounds, targeted defects, and immunologic reagents. By employing different combinations of mouse and bacterial strains, murine infection models can be used to explore a complete picture of bacterial infection and innate immunity of the ocular surface...
March 2, 2017: Current Protocols in Mouse Biology
https://www.readbyqxmd.com/read/28251462/genetic-technologies-for-extremely-thermophilic-microorganisms-of-sulfolobus-the-only-genetically-tractable-genus-of-crenarchaea
#17
REVIEW
Nan Peng, Wenyuan Han, Yingjun Li, Yunxiang Liang, Qunxin She
Archaea represents the third domain of life, with the information-processing machineries more closely resembling those of eukaryotes than the machineries of the bacterial counterparts but sharing metabolic pathways with organisms of Bacteria, the sister prokaryotic phylum. Archaeal organisms also possess unique features as revealed by genomics and genome comparisons and by biochemical characterization of prominent enzymes. Nevertheless, diverse genetic tools are required for in vivo experiments to verify these interesting discoveries...
February 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28250052/a-novel-mode-of-induction-of-the-humoral-innate-immune-response-in-drosophila-larvae
#18
Hiroyuki Kenmoku, Aki Hori, Takayuki Kuraishi, Shoichiro Kurata
Drosophila adults have been utilized as a genetically tractable model organism to decipher the molecular mechanisms of humoral innate immune responses. In an effort to promote the utility of Drosophila larvae as an additional model system, in this study, we describe a novel aspect of an induction mechanism for innate immunity in these larvae. By using a fine tungsten needle created for manipulating semi-conductor devices, larvae were subjected to septic injury. However, although Toll pathway mutants were susceptible to infection with Gram-positive bacteria as had been shown for Drosophila adults, microbe clearance was not affected in the mutants...
March 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28250017/the-use-of-next-generation-sequencing-for-research-and-diagnostics-for-intellectual-disability
#19
REVIEW
Ricardo Harripaul, Abdul Noor, Muhammad Ayub, John B Vincent
Genetic or genomic mutation is a major cause of intellectual disability (ID). However, despite the generally anticipated strong genotype/phenotype correlation for ID, there are huge obstacles to gene identification, except perhaps where very distinct syndromic features are observed, because of the high degree of genetic heterogeneity and wide variability of phenotype for different mutations or even with the same mutation within a single gene. A recent review estimates in excess of 2500 genes for ID. Fortunately for researchers and diagnosticians alike, the recent advent of massively parallel sequencing technologies, or next-generation sequencing (NGS) has made an apparently impossible task tractable...
March 1, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28249985/inference-of-the-distribution-of-selection-coefficients-for-new-nonsynonymous-mutations-using-large-samples
#20
Bernard Y Kim, Christian D Huber, Kirk E Lohmueller
The distribution of fitness effects (DFE) has considerable importance in population genetics. To date, estimates of the DFE come from studies using a small number of individuals. Thus, estimates of the proportion of moderately to strongly deleterious new mutations may be unreliable because such variants are unlikely to be segregating in the data. Additionally, the true functional form of the DFE is unknown, and estimates of the DFE differ significantly between studies. Here we present a flexible and computationally tractable method, called Fit∂a∂i, to estimate the DFE of new mutations using the site frequency spectrum from a large number of individuals...
March 1, 2017: Genetics
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