scholarly journals Receptor selectivity from minimal backbone modification of a polypeptide agonist

2018 ◽  
Vol 115 (49) ◽  
pp. 12383-12388 ◽  
Author(s):  
Shi Liu ◽  
Ross W. Cheloha ◽  
Tomoyuki Watanabe ◽  
Thomas J. Gardella ◽  
Samuel H. Gellman
Keyword(s):  
Sequence Similarity ◽  
The Other ◽  
Side Chain ◽  
General Strategy ◽  
Human Parathyroid Hormone ◽  
Receptor Selectivity ◽  
Wide Range ◽  
Methylene Unit ◽  
Backbone Modification ◽  
Selective Agonists

Human parathyroid hormone (PTH) and N-terminal fragments thereof activate two receptors, hPTHR1 and hPTHR2, which share ∼51% sequence similarity. A peptide comprising the first 34 residues of PTH is fully active at both receptors and is used to treat osteoporosis. We have used this system to explore the hypothesis that backbone modification of a promiscuous peptidic agonist can provide novel receptor-selective agonists. We tested this hypothesis by preparing a set of variants of PTH(1–34)-NH2 that contained a single β-amino-acid residue replacement at each of the first eight positions. These homologs, each containing one additional backbone methylene unit relative to PTH(1–34)-NH2 itself, displayed a wide range of potencies in cell-based assays for PTHR1 or PTHR2 activation. The β-scan series allowed us to identify two homologs, each containing two α→β replacements, that were highly selective, one for PTHR1 and the other for PTHR2. These findings suggest that backbone modification of peptides may provide a general strategy for achieving activation selectivity among polypeptide-modulated receptors, and that success requires consideration of both β2- and β3-residues, which differ in terms of side-chain location.

scholarly journals Use of recA as an alternative phylogenetic marker in the family Vibrionaceae

2004 ◽  
Vol 54 (3) ◽  
pp. 919-924 ◽  
Author(s):  
C. C. Thompson ◽  
F. L. Thompson ◽  
K. Vandemeulebroecke ◽  
B. Hoste ◽  
P. Dawyndt ◽  
...  
Keyword(s):  
16S Rdna ◽  
Sequence Similarity ◽  
The Other ◽  
Vibrio Splendidus ◽  
Gene Sequences ◽  
Vibrio Tubiashii ◽  
Wide Range ◽  
The Family ◽  
Vibrio Mimicus ◽  
Taxonomic Studies

This study analysed the usefulness of recA gene sequences as an alternative phylogenetic and/or identification marker for vibrios. The recA sequences suggest that the genus Vibrio is polyphyletic. The high heterogeneity observed within vibrios was congruent with former polyphasic taxonomic studies on this group. Photobacterium species clustered together and apparently nested within vibrios, while Grimontia hollisae was apart from other vibrios. Within the vibrios, Vibrio cholerae and Vibrio mimicus clustered apart from the other genus members. Vibrio harveyi- and Vibrio splendidus-related species formed compact separated groups. On the other hand, species related to Vibrio tubiashii appeared scattered in the phylogenetic tree. The pairs Vibrio coralliilyticus and Vibrio neptunius, Vibrio nereis and Vibrio xuii and V. tubiashii and Vibrio brasiliensis clustered completely apart from each other. There was a correlation of 0·58 between recA and 16S rDNA pairwise similarities. Strains of the same species have at least 94 % recA sequence similarity. recA gene sequences are much more discriminatory than 16S rDNA. For 16S rDNA similarity values above 98 % there was a wide range of recA similarities, from 83 to 99 %.

2D Color-Intensity Representation of Ultrasonic Thickness Gauge Measurements

2020 ◽  
pp. 1192-1198
Author(s):  
M.S. Mohammad ◽  
Tibebe Tesfaye ◽  
Kim Ki-Seong
Keyword(s):  
Cost Effective ◽  
The Other ◽  
Thickness Gauge ◽  
Color Intensity ◽  
Digital Readout ◽  
Flat Surfaces ◽  
Video Cameras ◽  
Wide Range ◽  
Cost Effective Alternative ◽  
Ultrasonic Thickness

Ultrasonic thickness gauges are easy to operate and reliable, and can be used to measure a wide range of thicknesses and inspect all engineering materials. Supplementing the simple ultrasonic thickness gauges that present results in either a digital readout or as an A-scan with systems that enable correlating the measured values to their positions on the inspected surface to produce a two-dimensional (2D) thickness representation can extend their benefits and provide a cost-effective alternative to expensive advanced C-scan machines. In previous work, the authors introduced a system for the positioning and mapping of the values measured by the ultrasonic thickness gauges and flaw detectors (Tesfaye et al. 2019). The system is an alternative to the systems that use mechanical scanners, encoders, and sophisticated UT machines. It used a camera to record the probe’s movement and a projected laser grid obtained by a laser pattern generator to locate the probe on the inspected surface. In this paper, a novel system is proposed to be applied to flat surfaces, in addition to overcoming the other limitations posed due to the use of the laser projection. The proposed system uses two video cameras, one to monitor the probe’s movement on the inspected surface and the other to capture the corresponding digital readout of the thickness gauge. The acquired images of the probe’s position and thickness gauge readout are processed to plot the measured data in a 2D color-coded map. The system is meant to be simpler and more effective than the previous development.

p-Sulfonic acid calix[n]arene catalyzed synthesis of bioactive heterocycles: A review

2020 ◽  
Vol 24 ◽  
Author(s):  
Bubun Banerjee ◽  
Gurpreet Kaur ◽  
Navdeep Kaur
Keyword(s):  
Supramolecular Chemistry ◽  
Sulfonic Acid ◽  
Catalytic Efficiency ◽  
The Other ◽  
Reaction Conditions ◽  
Metal Free ◽  
Bioactive Scaffolds ◽  
Wide Range ◽  
Efficient Alternative ◽  
Bioactive Heterocycles

: Metal-free organocatalysts are becoming an important tool for the sustainable developments of various bioactive heterocycles. On the other hand, during last two decades, calix[n]arenes have been gaining considerable attention due to their wide range of applicability in the field of supramolecular chemistry. Recently, sulfonic acid functionalized calix[n] arenes are being employed as an efficient alternative catalyst for the synthesis of various bioactive scaffolds. In this review we have summarized the catalytic efficiency of p-sulfonic acid calix[n]arenes for the synthesis of diverse biologically promising scaffolds under various reaction conditions. There is no such review available in the literature showing the catalytic applicability of p-sulfonic acid calix[n]arenes. Therefore, we strongly believe that this review will surely attract those researchers who are interested about this fascinating organocatalyst.

Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

1994 ◽  
Vol 59 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Zdenko Procházka
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Basic Amino Acid ◽  
The Other ◽  
Side Chain ◽  
Inhibitory Potency ◽  
Phase Synthesis ◽  
Other Hand ◽  
Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

scholarly journals Independent pseudogenizations and losses of sox15 during amniote diversification following asymmetric ohnolog evolution

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yusaku Ogita ◽  
Kei Tamura ◽  
Shuuji Mawaribuchi ◽  
Nobuhiko Takamatsu ◽  
Michihiko Ito
Keyword(s):  
Sequence Similarity ◽  
The Other ◽  
Vertebrate Evolution ◽  
Skeletal Muscle Regeneration ◽  
Cns Development ◽  
Placental Development ◽  
Relaxed Selection ◽  
Significant Sequence Similarity ◽  
Anuran Amphibians ◽  
Divergent Gene

Abstract Background Four ohnologous genes (sox1, sox2, sox3, and sox15) were generated by two rounds of whole-genome duplication in a vertebrate ancestor. In eutherian mammals, Sox1, Sox2, and Sox3 participate in central nervous system (CNS) development. Sox15 has a function in skeletal muscle regeneration and has little functional overlap with the other three ohnologs. In contrast, the frog Xenopus laevis and zebrafish orthologs of sox15 as well as sox1-3 function in CNS development. We previously reported that Sox15 is involved in mouse placental development as neofunctionalization, but is pseudogenized in the marsupial opossum. These findings suggest that sox15 might have evolved with divergent gene fates during vertebrate evolution. However, knowledge concerning sox15 in other vertebrate lineages than therian mammals, anuran amphibians, and teleost fish is scarce. Our purpose in this study was to clarify the fate and molecular evolution of sox15 during vertebrate evolution. Results We searched for sox15 orthologs in all vertebrate classes from agnathans to mammals by significant sequence similarity and synteny analyses using vertebrate genome databases. Interestingly, sox15 was independently pseudogenized at least twice during diversification of the marsupial mammals. Moreover, we observed independent gene loss of sox15 at least twice during reptile evolution in squamates and crocodile-bird diversification. Codon-based phylogenetic tree and selective analyses revealed an increased dN/dS ratio for sox15 compared to the other three ohnologs during jawed vertebrate evolution. Conclusions The findings revealed an asymmetric evolution of sox15 among the four ohnologs during vertebrate evolution, which was supported by the increased dN/dS values in cartilaginous fishes, anuran amphibians, and amniotes. The increased dN/dS value of sox15 may have been caused mainly by relaxed selection. Notably, independent pseudogenizations and losses of sox15 were observed during marsupial and reptile evolution, respectively. Both might have been caused by strong relaxed selection. The drastic gene fates of sox15, including neofunctionalization and pseudogenizations/losses during amniote diversification, might be caused by a release from evolutionary constraints.

scholarly journals Limitation of current probe design for oligo-cross-FISH, exemplified by chromosome evolution studies in duckweeds

Chromosoma ◽  
2021 ◽  
Vol 130 (1) ◽  
pp. 15-25
Author(s):  
Phuong T. N. Hoang ◽  
Jean-Marie Rouillard ◽  
Jiří Macas ◽  
Ivona Kubalová ◽  
Veit Schubert ◽  
...  
Keyword(s):  
Growth Rate ◽  
Chromosome Number ◽  
Chromosome Evolution ◽  
Sequence Similarity ◽  
Flowering Plants ◽  
The Other ◽  
Probe Design ◽  
Congeneric Species ◽  
Specific Design ◽  
Spirodela Polyrhiza

AbstractDuckweeds represent a small, free-floating aquatic family (Lemnaceae) of the monocot order Alismatales with the fastest growth rate among flowering plants. They comprise five genera (Spirodela, Landoltia, Lemna, Wolffiella, and Wolffia) varying in genome size and chromosome number. Spirodela polyrhiza had the first sequenced duckweed genome. Cytogenetic maps are available for both species of the genus Spirodela (S. polyrhiza and S. intermedia). However, elucidation of chromosome homeology and evolutionary chromosome rearrangements by cross-FISH using Spirodela BAC probes to species of other duckweed genera has not been successful so far. We investigated the potential of chromosome-specific oligo-FISH probes to address these topics. We designed oligo-FISH probes specific for one S. intermedia and one S. polyrhiza chromosome (Fig. 1a). Our results show that these oligo-probes cross-hybridize with the homeologous regions of the other congeneric species, but are not suitable to uncover chromosomal homeology across duckweeds genera. This is most likely due to too low sequence similarity between the investigated genera and/or too low probe density on the target genomes. Finally, we suggest genus-specific design of oligo-probes to elucidate chromosome evolution across duckweed genera.

scholarly journals Density Guarantee on Finding Multiple Subgraphs and Subtensors

2021 ◽  
Vol 15 (5) ◽  
pp. 1-32
Author(s):  
Quang-huy Duong ◽  
Heri Ramampiaro ◽  
Kjetil Nørvåg ◽  
Thu-lan Dam
Keyword(s):  
Lower Bound ◽  
State Of The Art ◽  
The State ◽  
The Other ◽  
Exact Methods ◽  
Practical Solution ◽  
Novel Approach ◽  
Wide Range ◽  
Real World Datasets ◽  
Tensor Data

Dense subregion (subgraph & subtensor) detection is a well-studied area, with a wide range of applications, and numerous efficient approaches and algorithms have been proposed. Approximation approaches are commonly used for detecting dense subregions due to the complexity of the exact methods. Existing algorithms are generally efficient for dense subtensor and subgraph detection, and can perform well in many applications. However, most of the existing works utilize the state-or-the-art greedy 2-approximation algorithm to capably provide solutions with a loose theoretical density guarantee. The main drawback of most of these algorithms is that they can estimate only one subtensor, or subgraph, at a time, with a low guarantee on its density. While some methods can, on the other hand, estimate multiple subtensors, they can give a guarantee on the density with respect to the input tensor for the first estimated subsensor only. We address these drawbacks by providing both theoretical and practical solution for estimating multiple dense subtensors in tensor data and giving a higher lower bound of the density. In particular, we guarantee and prove a higher bound of the lower-bound density of the estimated subgraph and subtensors. We also propose a novel approach to show that there are multiple dense subtensors with a guarantee on its density that is greater than the lower bound used in the state-of-the-art algorithms. We evaluate our approach with extensive experiments on several real-world datasets, which demonstrates its efficiency and feasibility.

scholarly journals Grasp to See—Object Classification Using Flexion Glove with Support Vector Machine

Sensors ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 1461
Author(s):  
Shun-Hsin Yu ◽  
Jen-Shuo Chang ◽  
Chia-Hung Dylan Tsai
Keyword(s):  
Support Vector Machine ◽  
Daily Life ◽  
Object Classification ◽  
Target Object ◽  
The Other ◽  
Support Vector ◽  
Wide Range ◽  
Dark Space ◽  
Flex Sensors ◽  
Shape And Size

This paper proposes an object classification method using a flexion glove and machine learning. The classification is performed based on the information obtained from a single grasp on a target object. The flexion glove is developed with five flex sensors mounted on five finger sleeves, and is used for measuring the flexion of individual fingers while grasping an object. Flexion signals are divided into three phases, and they are the phases of picking, holding and releasing, respectively. Grasping features are extracted from the phase of holding for training the support vector machine. Two sets of objects are prepared for the classification test. One is printed-object set and the other is daily-life object set. The printed-object set is for investigating the patterns of grasping with specified shape and size, while the daily-life object set includes nine objects randomly chosen from daily life for demonstrating that the proposed method can be used to identify a wide range of objects. According to the results, the accuracy of the classifications are achieved 95.56% and 88.89% for the sets of printed objects and daily-life objects, respectively. A flexion glove which can perform object classification is successfully developed in this work and is aimed at potential grasp-to-see applications, such as visual impairment aid and recognition in dark space.

scholarly journals Natural Science and Supernatural Thought Experiments

Religions ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 389
Author(s):  
James Robert Brown
Keyword(s):  
Natural Science ◽  
Thought Experiment ◽  
Thought Experiments ◽  
The Other ◽  
Space And Time ◽  
Wide Range ◽  
The Difference ◽  
Theological Thought

Religious notions have long played a role in epistemology. Theological thought experiments, in particular, have been effective in a wide range of situations in the sciences. Some of these are merely picturesque, others have been heuristically important, and still others, as I will argue, have played a role that could be called essential. I will illustrate the difference between heuristic and essential with two examples. One of these stems from the Newton–Leibniz debate over the nature of space and time; the other is a thought experiment of my own constructed with the aim of making a case for a more liberal view of evidence in mathematics.

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