An algorithm for estimation of chromosome motion in Four-Dimensional microscopic images

1994 ◽  
Vol 52 ◽  
pp. 930-931
Author(s):  
Wallace Marshall ◽  
David Agard ◽  
John Sedat
Keyword(s):  
Nuclear Organization ◽  
Three Dimensional ◽  
Estimation Algorithm ◽  
Structural Features ◽  
Random Motion ◽  
Structural Representation ◽  
Functional Roles ◽  
The Face ◽  
Chromosome Motion

Analysis of the three-dimensional organization of chromosomes within the nucleus has revealed a number of characteristic structural features. Yet imaging of living nuclei indicate that chromosomes undergo considerable random motion. Maintenance of nuclear organization in the face of such motion is thought to involve the attachment of chromosomes to the nuclear envelope or matrix. Yet while such attachments have been proposed to play a variety of functional roles as well as maintain nuclear organization, direct evidence for the existence of these mechanical interactions in vivo has been lacking. One way to demonstrate such attachment directly would be to estimate the motion of chromosomes and attempt thereby to demonstrate the presence of fixed points, which would indicate attachment of chromatin to some fixed superstructure.We have previously presented a motion estimation algorithm that is designed for tracking the motion of nonrigid and featureless objects such as chromosomes. This algorithm starts with a structural representation for the set of chromosomes at each time point, and then finds a correspondence between elements of the representations at successive time points.

FLUOROSCOPIC ANALYSIS FOR THE ESTIMATION OF IN VIVO ELBOW KINEMATICS: INFLUENCE OF 3D MODEL

2012 ◽  
Vol 12 (03) ◽  
pp. 1250046 ◽  
Author(s):  
LUCA TERSI ◽  
SILVIA FANTOZZI ◽  
RITA STAGNI ◽  
ANGELO CAPPELLO
Keyword(s):  
Cost Function ◽  
Three Dimensional ◽  
Elbow Flexion ◽  
Estimation Algorithm ◽  
Healthy Male Subject ◽  
Distance Map ◽  
3D Fluoroscopy ◽  
Flexion Extension ◽  
Single Bone

The reliable knowledge that model-based three-dimensional (3D) fluoroscopy can provide about in vivo joints kinematics is essential to diagnose orthopedic pathologies, develop new prosthesis, and evaluate clinical procedures. To exploit 3D fluoroscopy for the analysis of elbow kinematics, its use was evaluated considering a single model for the forearm or two different models for the ulna and radius. Active elbow flexion-extension and prono-supination motor tasks of a healthy male subject were acquired by means of fluoroscopy. The 3D bone models were automatically aligned to the relevant projections. The pose estimation algorithm sought the tangency condition of the projection rays with the model surface, minimizing a cost function and exploiting an adaptive distance map. Five iterative guided alignments were performed to avoid the final convergence to a local minimum. The results highlighted the critical alignment of the ulna/radius model, particularly when prono-supination is performed. From the physiological motion patterns and given the values of the cost function, 3D fluoroscopy was proven to be applicable to the analysis of the elbow kinematics when single bone models for the ulna and radius are used.

scholarly journals Micro-Structured Patches for Dermal Regeneration Obtained via Electrophoretic Replica Deposition

2020 ◽  
Vol 10 (14) ◽  
pp. 5010
Author(s):  
Arash Ghalayani Esfahani ◽  
Lina Altomare ◽  
Lorenzo Bonetti ◽  
Fereshteh Nejaddehbashi ◽  
Francesca Boccafoschi ◽  
...  
Keyword(s):  
Normal Skin ◽  
Three Dimensional ◽  
Experimental Period ◽  
Structural Features ◽  
Skin Wound ◽  
Hair Follicles ◽  
Artificial Substrates ◽  
Lattice Structures ◽  
Random Porosity

Artificial substrates supporting the healing of skin wounds require specific structural and chemical architectures that promote a recapitulation of the complexity of the native organ. Bottom-up fabrication technologies are emerging as effective strategies to fine tune biochemical, morphological, and structural features intended for regenerative applications. Here, we proposed an electrophoretic replica deposition (EPrD) approach to realize chitosan three-dimensional structures specifically designed to treat patients with serious cutaneous damages or losses. The EPrD process has been optimized to consistently obtain random porosity vs. hierarchical lattice structures, showing mechanical properties in the range of skin tissue (E = 0.2–20 MPa). The obtained patches were tested in vivo via a one-stage grafting procedure in a full thickness skin wound rat model. Chitosan patches showed no adverse reactions throughout the experimental period (14 days). Hair follicles and sebaceous glands were observed in histological sections, indicating the regeneration of a thin epidermal layer with more skin appendages. Immunohistochemistry results demonstrated that keratin 10 was mostly expressed in basal and suprabasal layers, like normal skin, in structures with random porosity and with smaller lattice structures. The obtained results show the potential of EPrD to innovate the design of artificial substrates in skin healing therapies.

scholarly journals Virtual Screening of Natural Products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2)

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2271 ◽  
Author(s):  
Noor Rahman ◽  
Zarrin Basharat ◽  
Muhammad Yousuf ◽  
Giuseppe Castaldo ◽  
Luca Rastrelli ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Three Dimensional ◽  
Natural Compounds ◽  
Structural Features ◽  
Host Cells ◽  
Dimensional Structure ◽  
Active Site Residues ◽  
Transmembrane Serine Protease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused about 2 million infections and is responsible for more than 100,000 deaths worldwide. To date, there is no specific drug registered to combat the disease it causes, named coronavirus disease 2019 (COVID-19). In the current study, we used an in silico approach to screen natural compounds to find potent inhibitors of the host enzyme transmembrane protease serine 2 (TMPRSS2). This enzyme facilitates viral particle entry into host cells, and its inhibition blocks virus fusion with angiotensin-converting enzyme 2 (ACE2). This, in turn, restricts SARS-CoV-2 pathogenesis. A three-dimensional structure of TMPRSS2 was built using SWISS-MODEL and validated by RAMPAGE. The natural compounds library Natural Product Activity and Species Source (NPASS), containing 30,927 compounds, was screened against the target protein. Two techniques were used in the Molecular Operating Environment (MOE) for this purpose, i.e., a ligand-based pharmacophore approach and a molecular docking-based screening. In total, 2140 compounds with pharmacophoric features were retained using the first approach. Using the second approach, 85 compounds with molecular docking comparable to or greater than that of the standard inhibitor (camostat mesylate) were identified. The top 12 compounds with the most favorable structural features were studied for physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties. The low-molecular-weight compound NPC306344 showed significant interaction with the active site residues of TMPRSS2, with a binding energy score of −14.69. Further in vitro and in vivo validation is needed to study and develop an anti-COVID-19 drug based on the structures of the most promising compounds identified in this study.

scholarly journals Thrombin-derived C-terminal fragments aggregate and scavenge bacteria and their proinflammatory products

2020 ◽  
Vol 295 (11) ◽  
pp. 3417-3430 ◽  
Author(s):  
Jitka Petrlova ◽  
Ganna Petruk ◽  
Roland G. Huber ◽  
Eilish W. McBurnie ◽  
Mariena J. A. van der Plas ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Lipid A ◽  
Lipoteichoic Acid ◽  
Structural Features ◽  
Human Neutrophil Elastase ◽  
Gram Negative ◽  
Functional Roles ◽  
Cellular Assays

Thrombin-derived C-terminal peptides (TCPs), including a major 11-kDa fragment (TCP96), are produced through cleavage by human neutrophil elastase and aggregate lipopolysaccharide (LPS) and the Gram-negative bacterium Escherichia coli. However, the physiological roles of TCP96 in controlling bacterial infections and reducing LPS-induced inflammation are unclear. Here, using various biophysical methods, in silico molecular modeling, microbiological and cellular assays, and animal models, we examined the structural features and functional roles of recombinant TCP96 (rTCP96) in the aggregation of multiple bacteria and the Toll-like receptor (TLR) agonists they produce. We found that rTCP96 aggregates both Gram-negative and Gram-positive bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa, and their cell-wall components LPS, lipid A, and lipoteichoic acid (LTA). The Gram-negative bacteria E. coli and P. aeruginosa were particularly sensitive to aggregation-induced bacterial permeabilization and killing. As a proof of concept, we show that rTCP96 reduces LPS-induced NF-κB activation in human monocytes, as well as in mouse models of LPS-induced subcutaneous inflammation. Moreover, in a mouse model of subcutaneous inoculation with P. aeruginosa, rTCP96 reduced bacterial levels. Together, these results link TCP-mediated aggregation of endotoxins and bacteria in vitro to attenuation of inflammation and bacterial levels in vivo.

scholarly journals A Novel Mercuric Reductase from the Unique Deep Brine Environment of Atlantis II in the Red Sea

2013 ◽  
Vol 289 (3) ◽  
pp. 1675-1687 ◽  
Author(s):  
Ahmed Sayed ◽  
Mohamed A. Ghazy ◽  
Ari J. S. Ferreira ◽  
João C. Setubal ◽  
Felipe S. Chambergo ◽  
...  
Keyword(s):  
Red Sea ◽  
Three Dimensional ◽  
Structural Features ◽  
Amino Acid Sequences ◽  
Site Directed Mutagenesis ◽  
Mercuric Reductase ◽  
Three Dimensional Modeling ◽  
High Concentrations ◽  
Convective Layer

A unique combination of physicochemical conditions prevails in the lower convective layer (LCL) of the brine pool at Atlantis II (ATII) Deep in the Red Sea. With a maximum depth of over 2000 m, the pool is characterized by acidic pH (5.3), high temperature (68 °C), salinity (26%), low light levels, anoxia, and high concentrations of heavy metals. We have established a metagenomic dataset derived from the microbial community in the LCL, and here we describe a gene for a novel mercuric reductase, a key component of the bacterial detoxification system for mercuric and organomercurial species. The metagenome-derived gene and an ortholog from an uncultured soil bacterium were synthesized and expressed in Escherichia coli. The properties of their products show that, in contrast to the soil enzyme, the ATII-LCL mercuric reductase is functional in high salt, stable at high temperatures, resistant to high concentrations of Hg2+, and efficiently detoxifies Hg2+in vivo. Interestingly, despite the marked functional differences between the orthologs, their amino acid sequences differ by less than 10%. Site-directed mutagenesis and kinetic analysis of the mutant enzymes, in conjunction with three-dimensional modeling, have identified distinct structural features that contribute to extreme halophilicity, thermostability, and high detoxification capacity, suggesting that these were acquired independently during the evolution of this enzyme. Thus, our work provides fundamental structural insights into a novel protein that has undergone multiple biochemical and biophysical adaptations to promote the survival of microorganisms that reside in the extremely demanding environment of the ATII-LCL.

scholarly journals Knocking-out the human face genes TBX15 and PAX1 in mice alters facial and other physical morphology

2021 ◽  
Author(s):  
Yu Qian ◽  
ziyi Xiong ◽  
Yi Li ◽  
haibo Zhou ◽  
Manfred Kayser ◽  
...  
Keyword(s):  
Association Studies ◽  
Three Dimensional ◽  
Mutant Mice ◽  
Genome Wide Association Studies ◽  
Facial Morphology ◽  
Morphological Alterations ◽  
Functional Roles ◽  
Adult Mice ◽  
Phenotype Analysis ◽  
The Face

DNA variants in or closed to the human TBX15 and PAX1 genes have been repeatedly associated with facial morphology in independent genome-wide association studies, while their functional roles in determining facial morphology remains to be understood. We generated Tbx15 knockout ( Tbx15 -/- ) and Pax1 knockout ( Pax1 -/- ) mice by applying the one-step CRISPR/Cas9 method. A total of 75 adult mice were used for subsequent phenotype analysis, including 38 Tbx15 mice (10 homozygous Tbx15 -/- , 18 heterozygous Tbx15 +/- , 10 wild-type WT) and 37 Pax1 mice (12 homozygous Pax1 -/- , 15 heterozygous Pax1 +/- , 10 WT mice). Facial and other physical morphological phenotypes were obtained from three-dimensional (3D) images acquired with the HandySCAN BLACK scanner. Compared to WT mice, the Tbx15 -/- mutant mice had significantly shorter faces ( P =1.08E-8, R2=0.61) and their ears were in a significantly lower position ( P =3.54E-8, R2=0.62) manifesting an “ear dropping” characteristic. Besides these face alternations, Tbx15 -/- mutant mice displayed significantly lower weight as well as shorter body and limb length. Pax1 -/- mutant mice showed significantly longer noses ( P =1.14E-5, R2=0.46) relative to WT mice, but otherwise displayed less obvious morphological alterations than Tbx15 -/- mutant mice did. Because the Tbx15 and Pax1 effects on facial morphology we revealed here in mice are largely consistent with previously reported TBX15 and PAX1 face associations in humans, we suggest that the functional role these two genes play on determining the face of mice is similar to the functional impact their human homologues have on the face of humans.

Estimation and analysis of 3-D chromosome motion

1995 ◽  
Vol 53 ◽  
pp. 652-653
Author(s):  
W.F. Marshall ◽  
D.A. Agard ◽  
J.W. Sedat
Keyword(s):  
Motion Estimation ◽  
Motion Vector ◽  
3D Structure ◽  
Quantitative Description ◽  
Three Dimensional ◽  
Axial Direction ◽  
Aperture Problem ◽  
Motion Vector Field ◽  
Chromosome Motion

The mechanical properties of chromosomes in vivo are at present poorly characterized, yet an understanding of such properties is likely to be important for understanding both the behavior of chromosomes during mitosis as well as the establishment and maintenance of specific chromosome configurations in the nucleus. In order to better investigate the mechanics of chromosomes inside living cells we have developed algorithms for quantitative analysis of chromosome motion. This allows us to directly determine chromosome mobility, and to visualize the trajectories of specific regions, such as telomeres or centromeres. Previously developed tools for analysis of 3D structure can then be extended to 4 dimensions, allowing quantitative description of chromosome behavior. The motion vector field itself can also be analyzed for specific patterns of motion.Three dimensional motion estimation is difficult in fluorescence microscopic images, due to limited spatial resolution, particularly in the axial direction, which result in a significant aperture problem because each part of a chromosome looks identical to any other part of any other chromosome, such that intensity patterns are not useful in motion estimation.

scholarly journals SELF-REGULATION OF GROWTH IN THREE DIMENSIONS

1973 ◽  
Vol 138 (4) ◽  
pp. 745-753 ◽  
Author(s):  
Judah Folkman ◽  
Mark Hochberg
Keyword(s):  
Surface Area ◽  
Self Regulation ◽  
Three Dimensional ◽  
Two Dimensions ◽  
Three Dimensions ◽  
Cell Populations ◽  
Simple Diffusion ◽  
The Face

Multi-cell spheroids were grown in soft agar. When each spheroid was cultured in a large volume of medium, frequently renewed, all spheroids eventually reached a dormant phase at a diameter of approximately 3–4 mm and a population of approximately 106 cells. In the dormant spheroid, newly generated cells at the periphery balanced those lost by necrosis in the center. We propose that this dormant phase is due to a gradual reduction in the ratio of surface area to volume: a size is achieved beyond which there is insufficient surface area for the spheroid to eliminate catabolites and absorb nutrients. Thus, in the face of unlimited space and of new medium, three-dimensional cell populations become self-regulating. This phenomenon contrasts with standard tissue culture in which cell populations, living on a flat plane in two dimensions, will not stop growing in the face of unlimited space and new medium because the ratio of surface area to volume remains constant. These experiments provide a mechanism for our observations in vivo: before vascularization, solid tumors live by simple diffusion as three-dimensional spheroids or ellipsoids. They become dormant at a diameter of only a few millimeters; once vascularized, they are released from this dormant phase and begin exponential growth. Thus, tumor dormancy resulting from absence of angiogenesis in vivo, may operate by the same mechanism responsible for dormancy of spheroids in vitro.

scholarly journals Pharmacophore-driven Identification of N-Methyl-D-Receptor Antagonists as Potent Neuroprotective Agents Validated Using In-Vivo Studies

2018 ◽  
Author(s):  
Mukta Sharma ◽  
Anupama Mittal ◽  
Aarti Singh ◽  
Ashwin K. Jainarayanan ◽  
Swapnil Sharma ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Virtual Screening ◽  
Learning And Memory ◽  
Three Dimensional ◽  
Scoring Function ◽  
The Elderly ◽  
Structural Features ◽  
In Vivo Studies ◽  
Receptor Antagonists

AbstractAlzheimer’s disease (AD), the most widespread cause of dementia is delineated by progressive cognitive impairment in the elderly people. During its progression, N-Methyl-D-Aspartate receptor antagonists are known to play a key role in the mechanisms of learning and memory. Extensive side effects alongside other effects on learning and memory have limited the therapeutic significance of various blockers and antagonists of the NMDA receptor. In this study, we identify potential compounds targeted against NMDA. In order to reveal the essential structural features for NMDA receptor, three-dimensional pharmacophore models are constructed based on a set of known NMDA inhibitors. This is followed by virtual screening which results in novel chemical compounds having the potential to inhibit NMDA. The lead compounds are then subjected to molecular docking and assessed by a scoring function, which results in two compounds with high Libdock scores. These compounds also show interactions with important residues at the active site. The compounds are shortlisted on the basis of high estimated activity, fit values, LibDock score, no violation to Lipinski’s and availability for procuring.Of the shortlisted compounds, one compound satisfying the entire aforementioned criterion is further tested using in-vivo studies on mice with the help of an eight-arm radial maze. The pharmacophore-based virtual screening protocol presented in this study pave the way forward to address the unmet medical need of Alzheimer disease.

Reconstructed Human Epidermis In Vitro: An Alternative to Animal Testing

1995 ◽  
Vol 23 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Maria Ponec
Keyword(s):  
Human Skin ◽  
Three Dimensional ◽  
Structural Features ◽  
Animal Testing ◽  
Normal Human Skin ◽  
Normal Human ◽  
Biochemical Mechanisms ◽  
Human Skin Models

Various three-dimensional human skin models, in which the epidermis exhibits in vivo-like morphological and functional characteristics, have recently been developed. Such models are currently being used to study the development and physiology of the skin, the processes involved in wound healing, and the reactivity of skin to environmental and chemical insults. Since these models reproduce to a large extent the barrier function properties of normal human skin, they can be used for screening potential skin irritants. These substances can be applied topically and their irritant potential can be evaluated using various endpoints, such as the induction of tissue damage or the release of various pro-inflammatory mediators. Studies with human skin equivalents can therefore contribute to our knowledge of the basic biochemical mechanisms underlying irritant reactions, and can be used to understand the structural features of molecules which may be responsible for eliciting an irritant reaction. In addition”, the generation of epidermal equivalents populated with melanocytes, as well as keratinocytes, makes it possible to study the regulation of melanogenesis, melanocyte–keratinocyte interactions, and how these are affected by UV irradiation. Such a model can also be used for testing the phototoxic or photoprotective potentials of various compounds and sunscreens.

Sign in / Sign up

Export Citation Format

Share Document