scholarly journals Evolution viewed from physics, physiology and medicine

2017 ◽  
Vol 7 (5) ◽  
pp. 20160159 ◽  
Author(s):  
Denis Noble
Keyword(s):  
Dna Sequences ◽  
Molecular Level ◽  
Medical Science ◽  
Functional Variation ◽  
Evolution And Development ◽  
Functional Development ◽  
Sensitive Organ ◽  
Highly Sensitive ◽  
Level Order ◽  
Development And Evolution

Stochasticity is harnessed by organisms to generate functionality. Randomness does not, therefore, necessarily imply lack of function or ‘blind chance’ at higher levels. In this respect, biology must resemble physics in generating order from disorder. This fact is contrary to Schrödinger's idea of biology generating phenotypic order from molecular- level order, which inspired the central dogma of molecular biology. The order originates at higher levels, which constrain the components at lower levels. We now know that this includes the genome, which is controlled by patterns of transcription factors and various epigenetic and reorganization mechanisms. These processes can occur in response to environmental stress, so that the genome becomes ‘a highly sensitive organ of the cell’ (McClintock). Organisms have evolved to be able to cope with many variations at the molecular level. Organisms also make use of physical processes in evolution and development when it is possible to arrive at functional development without the necessity to store all information in DNA sequences. This view of development and evolution differs radically from that of neo-Darwinism with its emphasis on blind chance as the origin of variation. Blind chance is necessary, but the origin of functional variation is not at the molecular level. These observations derive from and reinforce the principle of biological relativity, which holds that there is no privileged level of causation. They also have important implications for medical science.

scholarly journals The structure of ORC–Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiang Feng ◽  
Yasunori Noguchi ◽  
Marta Barbon ◽  
Bruce Stillman ◽  
Christian Speck ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Origin Recognition Complex ◽  
Molecular Level ◽  
Dna Recognition ◽  
Winged Helix ◽  
Replicative Helicase ◽  
The Core ◽  
Α Helix ◽  
Replication Initiator ◽  
Winged Helix Domain

AbstractThe Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. It has been unclear at the molecular level how Cdc6 activates ORC, converting it to an active recruiter of the Mcm2-7 hexamer, the core of the replicative helicase. Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC–Cdc6 bound to an 85-bp ARS1 origin DNA. The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins.

Quantifying genetic variation at the molecular level

2019 ◽  
pp. 34-66
Author(s):  
Asher D. Cutter
Keyword(s):  
Genetic Variation ◽  
Dna Sequences ◽  
Migration Rate ◽  
Population Genetic ◽  
Quantitative Methods ◽  
Molecular Level ◽  
Effective Population ◽  
Fundamental Properties ◽  
Site Frequency Spectrum ◽  
Population Genetic Variation

Chapter 3, “Quantifying genetic variation at the molecular level,” introduces quantitative methods for measuring variation directly in DNA sequences to help decipher fundamental properties of populations and what they can tell us about evolution. It provides an overview of the evolutionary factors that contribute to genetic variation, like mutational input, effective population size, genetic drift, migration rate, and models of migration. This chapter surveys the principal ways to measure and summarize polymorphisms within a single population and across multiple populations of a species, including heterozygosity, nucleotide polymorphism estimators of θ‎, the site frequency spectrum, and F ST, and by providing illustrative natural examples. Populations are where evolution starts, after mutations arise as the spark of population genetic variation, and Chapter 3 describes how to quantify the variation to connect observations to predictions about how much polymorphism there ought to be under different circumstances.

scholarly journals Feedback Inhibition of Chorismate Mutase/Prephenate Dehydrogenase (TyrA) of Escherichia coli: Generation and Characterization of Tyrosine-Insensitive Mutants

2005 ◽  
Vol 71 (11) ◽  
pp. 7224-7228 ◽  
Author(s):  
Tina Lütke-Eversloh ◽  
Gregory Stephanopoulos
Keyword(s):  
Escherichia Coli ◽  
Dna Sequences ◽  
Molecular Level ◽  
Feedback Inhibition ◽  
Feedback Regulation ◽  
The Other ◽  
Chorismate Mutase ◽  
Amino Acid Substitutions ◽  
Prephenate Dehydrogenase

ABSTRACT In order to get insights into the feedback regulation by tyrosine of the Escherichia coli chorismate mutase/prephenate dehydrogenase (CM/PDH), which is encoded by the tyrA gene, feedback-inhibition-resistant (fbr) mutants were generated by error-prone PCR. The tyrA fbr mutants were selected by virtue of their resistance toward m-fluoro-d,l-tyrosine, and seven representatives were characterized on the biochemical as well as on the molecular level. The PDH activities of the purified His6-tagged TyrA proteins exhibited up to 35% of the enzyme activity of TyrAWT, but tyrosine did not inhibit the mutant PDH activities. On the other hand, CM activities of the TyrAfbr mutants were similar to those of the TyrAWT protein. Analyses of the DNA sequences of the tyrA genes revealed that tyrA fbr contained amino acid substitutions either at Tyr263 or at residues 354 to 357, indicating that these two sites are involved in the feedback inhibition by tyrosine.

Nanotechnology: A Big Revolution from the Small World

2013 ◽  
Vol 80 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Matteo Bassi ◽  
Irene Santinello ◽  
Andrea Bevilacqua ◽  
Pierfrancesco Bassi
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Level ◽  
Medical Science ◽  
Small World ◽  
The Body ◽  
Superparamagnetic Nanoparticles ◽  
New Materials ◽  
Disease Treatment ◽  
History Of ◽  
Engineering Physics

Nanotechnology is a multidisciplinary field originating from the interaction of several different disciplines, such as engineering, physics, biology and chemistry. New materials and devices effectively interact with the body at molecular level, yielding a brand new range of highly selective and targeted applications designed to maximize the therapeutic efficiency while reducing the side effects. Liposomes, quantum dots, carbon nanotubes and superparamagnetic nanoparticles are among the most assessed nanotechnologies. Meanwhile, other futuristic platforms are paving the way toward a new scientific paradigm, able to deeply change the research path in the medical science. The growth of nanotechnology, driven by the dramatic advances in science and technology, clearly creates new opportunities for the development of the medical science and disease treatment in human health care. Despite the concerns and the on-going studies about their safety, nanotechnology clearly emerges as holding the promise of delivering one of the greatest breakthroughs in the history of medical science.

Freeze-Etch Replicas of the Mouse Proximal Tubule Cell

1972 ◽  
Vol 30 ◽  
pp. 300-301
Author(s):  
Ben O. Spurlock
Keyword(s):  
Fine Structure ◽  
Phosphate Buffer ◽  
Present Report ◽  
Specimen Preparation ◽  
Proximal Tubule Cell ◽  
Vascular Perfusion ◽  
Sensitive Organ ◽  
Highly Sensitive ◽  
Insight Into ◽  
Conventional Electron Microscopy

The fine structure of the mouse kidney has been studied in detail. Attempts at preserving this metabolically highly sensitive organ in the “closest to living state” have prompted some rather elaborate and involved methods of specimen preparation. Acknowledging that these techniques probably represent the best methods of preserving the integrity of this organ, it was felt that freeze-etch techniques might provide insight into structures heretofore unappreciated by conventional electron microscopy of thin sectioned material. The present report deals with the fine structure of the mouse renal proximal tubules as visualized in replicas of freeze-fractured and freeze-etched preparations.The left kidneys of lightly anesthesized mice were surgically exposed and fixed with 2% glutaraldehyde/0.1M phosphate buffer (pH 7. 2) by either the drip method (2) or by vascular perfusion (3). The kidneys were removed and stored in 0.1M phosphate buffer with 5% sucrose.

Dual signal-amplification electrochemical detection of DNA sequence based on molybdenum selenide nanorod and hybridization chain reaction

2016 ◽  
Vol 8 (26) ◽  
pp. 5234-5241 ◽  
Author(s):  
Liu Yang ◽  
Yanfu Li
Keyword(s):  
Dna Sequences ◽  
Signal Amplification ◽  
Hybridization Chain Reaction ◽  
Chain Reaction ◽  
Molybdenum Selenide ◽  
Highly Sensitive ◽  
Immunodeficiency Virus ◽  
Highly Sensitive Detection ◽  
Dual Signal Amplification

A new electrochemical biosensor based on the hybridization chain reaction and layered molybdenum selenide (MoSe2) stacked nanorod for dual-signal amplification is developed for the highly sensitive detection of the DNA sequences of Human Immunodeficiency Virus type 1 (HIV-1).

scholarly journals Aptamer Embedded Arch-Cruciform DNA Assemblies on 2-D VS2 Scaffolds for Sensitive Detection of Breast Cancer Cells

Biosensors ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 378
Author(s):  
Jinfeng Quan ◽  
Yihan Wang ◽  
Jialei Zhang ◽  
Kejing Huang ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Dna Sequences ◽  
Breast Cancer Cells ◽  
Limit Of Detection ◽  
Sensitive Detection ◽  
Highly Sensitive ◽  
Highly Sensitive Detection ◽  
Cruciform Dna ◽  
Mcf 7

Arch-cruciform DNA are self-assembled on AuNPs/VS2 scaffold as a highly sensitive and selective electrochemical biosensor for michigan cancer foundation-7 (MCF-7) breast cancer cells. In the construction, arch DNA is formed using two single-strand DNA sequences embedded with the aptamer for MCF-7 cells. In the absence of MCF-7 cells, a cruciform DNA labeled with three terminal biotin is bound to the top of arch DNA, which further combines with streptavidin-labeled horseradish peroxidase (HRP) to catalyze the hydroquinone-H2O2 reaction on the electrode surface. The presence of MCF-7 cells can release the cruciform DNA and reduce the amount of immobilized HRP, thus effectively inhibiting enzyme-mediated electrocatalysis. The electrochemical response of the sensor is negatively correlated with the concentration of MCF-7 cells, with a linear range of 10 − 1 × 105 cells/mL, and a limit of detection as low as 5 cells/mL (S/N = 3). Through two-dimensional materials and enzyme-based dual signal amplification, this biosensor may pave new ways for the highly sensitive detection of tumor cells in real samples.

scholarly journals Preparation of Large Conjugated Polybenzimidazole Fluorescent Materials and Their Application in Metal Ion Detection

Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3091
Author(s):  
Xi-Ying Cao ◽  
Chu-Ming Pang ◽  
Ying Xiao ◽  
Wan-Qing Xiao ◽  
Shi-He Luo ◽  
...  
Keyword(s):  
Metal Ion ◽  
Molecular Level ◽  
Logic Gate ◽  
Metal Catalysis ◽  
Good Solubility ◽  
Highly Sensitive ◽  
Fluorescent Materials ◽  
New Type ◽  
Metal Ion Detection ◽  
First Time

A new type of conjugated polybenzimidazole (CPBI) was synthesized through a simple polycondensation reaction without metal catalysis, and N-alkylation modification was carried out to solve the problems of solubility and fluorescence properties. A series of nano-microsphere polymers CPBIn with large conjugation, good solubility, and strong fluorescence has been successfully used as “turn-off” fluorescent probes for the first time. The results show that, under suitable N-alkylation conditions, the obtained CPBIn can be used as a highly sensitive and selective fluorescent probe for the detection of Cu2+ and Zn2+ at the same time, and their detection limits are both nM levels. In addition, CPBI2 can be designed as an ultra-sensitive IMPLICATION logic gate at the molecular level, cyclically detecting Cu2+. With the test paper containing CPBI2, easy and quick on-site detection can be achieved. This research provides a new idea for the brief synthesis of multifunctional materials.

Highly sensitive SERS assay of genetically modified organisms in maize via a nanoflowers substrate coupling with hybridization chain reaction amplification

2021 ◽  
Author(s):  
Xinyu Zhou ◽  
Shengjie Ge ◽  
Yue Sun ◽  
Menglin Ran ◽  
Yifan Liu ◽  
...  
Keyword(s):  
Research Methods ◽  
Dna Sequences ◽  
Genetically Modified Organisms ◽  
Dna Detection ◽  
Genetically Modified ◽  
Hybridization Chain Reaction ◽  
Chain Reaction ◽  
Substrate Coupling ◽  
Highly Sensitive ◽  
Reaction Amplification

The research methods for DNA detection have been widely extended since the application of nanotechnology, but it remains a challenge to detect specific DNA sequences or low abundance genes in...

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