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Proceedings of the National Academy of... Jul 2013It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long...
It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long charged polymer molecules. We have now fabricated nanopores in single-layer graphene that are closely matched to the diameter of a double-stranded DNA molecule. Ionic current signals during electrophoretically driven translocation of DNA through these nanopores were experimentally explored and theoretically modeled. Our experiments show that these nanopores have unusually high sensitivity (0.65 nA/Å) to extremely small changes in the translocating molecule's outer diameter. Such atomically short graphene nanopores can also resolve nanoscale-spaced molecular structures along the length of a polymer, but do so with greatest sensitivity only when the pore and molecule diameters are closely matched. Modeling confirms that our most closely matched pores have an inherent resolution of ≤ 0.6 nm along the length of the molecule.
Topics: DNA; Graphite; Microscopy, Electron; Nanopores
PubMed: 23836648
DOI: 10.1073/pnas.1220012110 -
Biomechanics and Modeling in... Oct 2020Mechanical loading-induced fluid flow in lacunar-canalicular space (LCS) of bone excites osteocyte cells to release signalling molecules which initiate osteo-activities....
Mechanical loading-induced fluid flow in lacunar-canalicular space (LCS) of bone excites osteocyte cells to release signalling molecules which initiate osteo-activities. Theoretical models considered canaliculi as a uniform and symmetrical space/channel in bone. However, experimental studies reported that canalicular walls are irregular and curvy resulting in inhomogeneous fluid motion which may influence the molecular transport. Therefore, a new mathematical model of LCS with curvy canalicular walls is developed to characterize cantilever bending-induced canalicular flow behaviour in terms of pore-pressure, fluid velocity, and streamlines. The model also analyses the mobility of signalling molecules involved in bone mechanotransduction as a function of loading frequency and permeability of LCS. Inhomogeneous flow is observed at higher loading frequency which amplifies mechanotransduction; nevertheless, it also promotes trapping of signalling molecules. The effects of shape and size of signalling molecules on transport behaviour are also studied. Trivially, signalling molecules larger in size and weight move slower as compared to molecules small in size and weight which validates the findings of the present study. The outcomes will ultimately be useful in designing better biomechanical exercise in combination with pharmaceutical agents to improve the bone health.
Topics: Adenosine Triphosphate; Animals; Biological Transport; Biomechanical Phenomena; Computer Simulation; Dinoprostone; Haversian System; Mice; Motion; Nitric Oxide; Porosity; Pressure; Signal Transduction; Tibia
PubMed: 32112154
DOI: 10.1007/s10237-020-01314-7 -
Applied Entomology and Zoology 2023Cockroaches are one of the hardiest insects that have survived on this planet for millions of years. They thrive in unhygienic environments, are able to survive without... (Review)
Review
Cockroaches are one of the hardiest insects that have survived on this planet for millions of years. They thrive in unhygienic environments, are able to survive without food for up to 30 days, without air for around 45 min and being submerged under water for 30 min. Cockroaches are omnivorous and feed on a variety of foods, including cellulose and plastic, to name a few. It is intriguing that cockroaches are able to endure and flourish under conditions that are harmful to . Given the importance of the gut microbiome on its' host physiology, we postulate that the cockroach gut microbiome and/or its metabolites, may be contributing to their "hardiness", which should be utilized for the discovery of biologically active molecules for the benefit of human health. Herein, we discuss the biology, diet/habitat of cockroaches, composition of gut microbiome, cellular senescence, and resistance to infectious diseases and cancer. Furthermore, current knowledge of the genome and epigenome of these remarkable species is considered. Being one of the most successful and diverse insects, as well as their extensive use in traditional and Chinese medicine, the lysates/extracts and gut microbial metabolites of cockroaches may offer a worthy resource for novel bioactive molecule(s) of therapeutic potential for the benefit of human health and may be potentially used as probiotics.
PubMed: 36536895
DOI: 10.1007/s13355-022-00810-9 -
Science (New York, N.Y.) Apr 1988The neural cell adhesion molecule (NCAM) can influence a number of diverse intercellular events, including junctional communication, the association of axons with... (Review)
Review
The neural cell adhesion molecule (NCAM) can influence a number of diverse intercellular events, including junctional communication, the association of axons with pathways and targets, and signals that alter levels of neurotransmitter enzymes. These pleiotropic effects appear to reflect the ability of NCAM to regulate membrane-membrane contact required to initiate specific interactions between other molecules. Such regulation can occur through changes in either NCAM expression or the molecule's content of polysialic acid (PSA). When NCAM with a low PSA content is expressed, adhesion is increased and contact-dependent events are triggered. In contrast, the large excluded volume of NCAM PSA can inhibit cell-cell interactions through hindrance of overall membrane apposition.
Topics: Animals; Antigens, Surface; Cell Adhesion; Cell Adhesion Molecules; Cell Communication; Cell Membrane; Membrane Glycoproteins; Sialic Acids
PubMed: 3281256
DOI: 10.1126/science.3281256 -
Cancer Chemotherapy and Pharmacology Nov 2017Despite advances in therapeutic interventions and supportive care, the morbidity and mortality associated with cancer have remained significant. Thus, there is a need... (Review)
Review
Despite advances in therapeutic interventions and supportive care, the morbidity and mortality associated with cancer have remained significant. Thus, there is a need for newer and more powerful anti-tumor agents. The search for new anti-tumor compounds originating from natural resources is a promising research area. Animals living in polluted environments are a potent source of anti-tumor agents. Under polluted milieus, species such as crocodiles, feed on rotten meat, are exposed to heavy metals, endure high levels of radiation, and are among the very few species to survive the catastrophic Cretaceous-Tertiary extinction event with a prolonged lifespan. Thus, it is reasonable to speculate that animals such as crocodiles have developed mechanisms to defend themselves against cancer. The discovery of antitumor activity in animals such as crocodiles, whales, sharks, etc. will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor compound(s) that may also overcome current drug resistance. Nevertheless, intensive research in the next few years will be required to realize these expectations.
Topics: Animals; Antineoplastic Agents; Environmental Microbiology; Environmental Pollutants; Humans; Neoplasms
PubMed: 28795217
DOI: 10.1007/s00280-017-3410-x -
Periodontology 2000 Jun 2011
Review
Topics: Animals; Female; Fibroblast Growth Factor 2; Guided Tissue Regeneration; Humans; Male; Mesenchymal Stem Cells; Periodontal Diseases; Periodontitis; Periodontium; Tissue Engineering; Wound Healing
PubMed: 21501244
DOI: 10.1111/j.1600-0757.2010.00365.x -
Current Opinion in Chemical Biology Feb 2005Transcriptional profiling with DNA microarrays can be used to measure the genome-wide transcriptional response to small molecules. Recent progress in the analysis of... (Review)
Review
Transcriptional profiling with DNA microarrays can be used to measure the genome-wide transcriptional response to small molecules. Recent progress in the analysis of gene-expression data has relied on the generation of databases of profiles documenting the transcriptional effects of various compound treatments and genetic perturbations. A positive correlation between the transcriptional response induced by a novel small molecule and a database profile can provide insight into the molecule's mechanism. Transcriptional profiling can also be used to assess a small molecule's specificity for its target and to facilitate analysis of pathways downstream of the target.
Topics: Gene Expression Profiling; Genomics; Humans; Oligonucleotide Array Sequence Analysis; Transcription, Genetic
PubMed: 15701449
DOI: 10.1016/j.cbpa.2004.10.009 -
Antibiotics (Basel, Switzerland) Dec 2019Over recent decades, the number and frequency of severe pathogen infections have been increasing. Pathogen mitigation strategies in human medicine or in livestock...
Over recent decades, the number and frequency of severe pathogen infections have been increasing. Pathogen mitigation strategies in human medicine or in livestock operations are vital to combat emerging arsenals of bacterial virulence and defense mechanisms. Since the emergence of antimicrobial resistance, the competitive nature of bacteria has been considered for the potential treatment or mitigation of pathogens. Previously, we identified a strong competitor with probiotic properties producing a diffusible antimicrobial molecule(s) that inhibited the growth of Shiga toxin-producing (STEC). Our current objective was to isolate and examine the properties of this antimicrobial molecule(s). Molecules were isolated by filter sterilization after 12 h incubation, and bacterial inhibition was compared to relevant controls. Isolated antimicrobial molecule(s) and controls were subjected to temperature, pH, or protease digestion treatments. Changes in inhibition properties were evaluated by comparing the incremental cell growth in the presence of treated and untreated antimicrobial molecule(s). No treatment affected the antimicrobial molecule(s) properties of STEC inhibition, suggesting that at least one molecule produced is an efficacious microcin. The molecule persistence to physiochemical and enzymatic treatments could open a wide window to technical industry-scale applications.
PubMed: 31877806
DOI: 10.3390/antibiotics9010006 -
Journal of Chemical Information and... Oct 2020Visual Molecular Dynamics (VMD) is one of the most widely used molecular graphics software in the community of theoretical simulations. So far, however, it still lacks a...
Visual Molecular Dynamics (VMD) is one of the most widely used molecular graphics software in the community of theoretical simulations. So far, however, it still lacks a graphical user interface (GUI) for molecular manipulations when doing some modeling tasks. For instance, translation or rotation of a selected molecule(s) or part(s) of a molecule currently only can be achieved using scripts. Here, we use the toolkit to develop a user-friendly GUI for VMD, named , which is featured by allowing users to quickly and conveniently perform various molecular manipulations. This GUI might be helpful for improving the modeling efficiency of VMD users.
Topics: Computer Graphics; Molecular Dynamics Simulation; Software; User-Computer Interface
PubMed: 32931272
DOI: 10.1021/acs.jcim.0c00754 -
Planta Apr 2008The phytohormone auxin is a potent regulator of plant development. Since its discovery in the beginning of the twentieth century many aspects of auxin biology have been... (Review)
Review
The phytohormone auxin is a potent regulator of plant development. Since its discovery in the beginning of the twentieth century many aspects of auxin biology have been extensively studied, ranging from biosynthesis and metabolism to the elucidation of molecular components of downstream signaling. With the identification of the F-box protein TIR1 as an auxin receptor a major breakthrough in understanding auxin signaling has been achieved and recent modeling approaches have shed light on the putative mechanisms underlying the establishment of auxin gradients and maxima essential for many auxin-regulated processes. Here, we review these and other recent advances in unraveling the entanglement of biosynthesis, polar transport and cellular signaling events that allow small auxinic molecules to facilitate their complex regulatory action.
Topics: Biological Transport; F-Box Proteins; Indoleacetic Acids; Models, Biological; Plant Proteins; Signal Transduction
PubMed: 18299888
DOI: 10.1007/s00425-008-0710-8