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Protein Regge Trajectories, Phase Coexistence and Loop Aetiology in Alzheimers Disease 17
Antti Niemi; Andrey Krokhotin.
Alzheimer's disease has a devastating impact on its victims by causing severe neurodegeneration in the brain that leads to a certain death. Only in a small number of cases can the origin be traced to a variety of genetic mutations, for the greater part the reasons for its onset are unclear.The defining factor is the formation of extracellular senile amyloid plaques in the brain, but therapeutic approaches to remove them remain to be shown effective in humans. Here we investigate physical processes that are involved in the release of the extracellular amyloid, by scrutinizing the intracellular domain of its precursor protein. We identify a phenomenon that has never before been discussed in the context of protein research: Like ice and water...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Neuroscience; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6030/version/1
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Endothelin-Induced Sarcoplasmic Reticulum Calcium Depletion Waves in Vascular Smooth Muscle Cells 17
Mitra Esfandiarei; Yohan Choi; Arash Y. Tehrani; Jeremy G. Hoskins; Nicola Fameli; Cornelis van Breemen.
Agonist-stimulated waves of elevated cytoplasmic Ca2+ concentration ([Ca2+]i ) regulate blood vessel tone and vasomotion in vascular smooth muscle. Previous studies employing cytoplasmic Ca2+ indicators revealed that these Ca2+ waves were generated by a combination of inositol 1,4,5-trisphosphate (IP3) and Ca2+ induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR); although, some of the mechanistic details remain uncertain. However, these findings were derived indirectly from observing agonist-induced [Ca2+]i fluctuations in the cytoplasm.
Here, for the first time, we have recorded Endothelin-1 (ET-1) induced waves of Ca2+ depletion from the SR lumen in vascular smooth muscle cells (VSMCs) using a calsequestrin-targeted Ca2+...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Pharmacology.
Ano: 2011 URL: http://precedings.nature.com/documents/6280/version/1
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Visual Molecular Dynamics Investigations of the Impact of Hydrophobic Nanoparticles on Prognosis of Alzheimer’s Disease and Cancers 17
I. C. Baianu; M Charles; V. I. Prisecaru.
The possible impact of hydrophobic lectin nanoparticles on the prognosis and progression of Alzheimer's disease (AD) and cancers was investigated by Visual Molecular Dynamics (VMD) computer modeling programs available from the Beckmann Advanced Research Institute at the University of Illinois at Urbana. Our results indicate the possibility of impeding pathological aggregation of certain proteins such as modified tau- or beta-amyloid that are currently being considered as possible causes of Alzheimer's disease. VMD programs serve as useful tools for investigation hydrophobic protein aggregation that may play a role in aging of human populations.
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry; Developmental Biology; Genetics & Genomics; Molecular Cell Biology; Neuroscience; Pharmacology; Bioinformatics; Data Standards.
Ano: 2012 URL: http://precedings.nature.com/documents/7111/version/2
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Pancreas islets in metabolic signaling - focus on the β-cell 17
Jakob Suckale; Michele Solimena.
Taken together the Islets of Langerhans form a nutrient sensing network spread throughout the pancreas. They are tightly connected to the source organ - the intestine - and the target organs - liver, muscle, and fat cells. The expression of a unique set of proteins enables [beta] cells, the most frequent islet cell type, to detect elevated blood glucose levels and secrete insulin accordingly. Neighbouring [beta]-cells achieve tighter regulation of glucose-induced insulin secretion by coordination through cell surface proteins. They also adjust their secretory pathway capacity and flow to avoid being damaged. The immediate reaction of the [beta] cell to nutrients is regulated by translational mechanisms, while longer term adaptations involve...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/1724/version/2
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Without magic bullets: the biological basis for public health interventions against protein folding disorders 17
Rodrick Wallace.
Protein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces...
Tipo: Manuscript Palavras-chave: Biotechnology; Developmental Biology; Molecular Cell Biology; Neuroscience; Pharmacology.
Ano: 2010 URL: http://precedings.nature.com/documents/4847/version/1
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Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice 17
Mei Chi; Yingbi Zhou; Srikanth Vedamoorthyrao; Gopal Babu; Muthu Periasamy.
The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (_SM2^-/-^_) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (_SM2^+/-^_) mice appeared normal...
Tipo: Manuscript Palavras-chave: Developmental Biology; Genetics & Genomics; Molecular Cell Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/1643/version/1
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Rabbit Muscle Actin Polymerization changes by Ultraviolet –B radiation 17
Anita Mukherjee; Arun Kumar Attri.
Increase in Ultraviolet-B flux from the Sun has the potential to alter the protein in mammals. Rabbit muscle was processed and filtered to extract G-actin, which was tested for its protein concentration before exposing to UV-B. It was found that polymerization of actin does get affected exposure of actin monomers to UV-B radiation. Inside the cell, there are many actin binding proteins which might be playing crucial role in G-actin to F-actin formation.
Tipo: Manuscript Palavras-chave: Molecular Cell Biology.
Ano: 2009 URL: http://precedings.nature.com/documents/2766/version/1
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Suppression of TNF-α induced NFκB activity by gallic acid and its semi-synthetic alkyl-gallates: Possible role in cancer chemoprevention 17
Suaib Luqman; Mauro C. C. Morais; Tamara P. Kondratyuk; Maicon S. Petronio; Luis O. Regasini; Dulce H. S. Silva; Vanderlan S. Bolzani; Christiane P. Soares; John M. Pezzuto.
NFκB, a transcription factor, regulates the expression of a number of genes involved in carcinogenesis. Thus, agents that can suppress NFκB activation have the potential to suppress carcinogenesis. In the present investigation, gallic acid was isolated from Alchornea glandulosa (Euphorbiaceae) and eight semi-synthetic alkyl gallates were prepared from the reaction of the corresponding alcohols with gallic acid at 80oC for 48 h in good yields (70-97%). All the compounds were evaluated against TNF-α-induced NFκB activation with stable transfected 293/NFκB-Luc human embryonic kidney cells. Treatment of cells with gallic acid and the gallate esters (20 µg/ml) significantly reduced TNF-α...
Tipo: Poster Palavras-chave: Cancer; Chemistry; Molecular Cell Biology; Pharmacology.
Ano: 2012 URL: http://precedings.nature.com/documents/6922/version/1
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BioenergyProduction From Plant Biomass: Bioethanol From Concept To Reality 17
Israr Khan; Muhammad Waheed Akhtar.
Natural energy reserves like petrol and diesel etc are depleting. As such, it is of paramount importance to find alternative fuels. Solar energy is trapped as biomass in plants. Biomass provide an excellent reserve for trapping solar energy on field. Complex enzymatic machinery comprising of hydrolytic reactions and consolidated bioprocessing is needed to make viable bioenergy, mostly biofuels like bioethanol for locomotives, industries and general use in the future.
Tipo: Manuscript Palavras-chave: Biotechnology; Chemistry; Molecular Cell Biology; Plant Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6286/version/1
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The biotechnological perspective of Beta-Glucosidases 17
Israr Khan; Muhammad waheed Akhtar.
Biotechnology is the art and science of making and technology to process biological materials for the welfare of human being. This discussion includes the beta glucosidase classification, its structure, application, and recent research interests in relation to its significance and comparison with eukaryotic Beta glucosidases including plant, animal and yeast as well. The study also comprise of the various stress factors and modifications thereby the organism to cope it. The focus of the study is on the various kinetics principles and their full potential exploitation to increase the activity of the enzyme. As such making the enzyme a potent vehicle for various industrial, pharmaceutical and research purposes. It also include the various glycosylhydrolases...
Tipo: Manuscript Palavras-chave: Biotechnology; Molecular Cell Biology; Plant Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4945/version/1
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity 17
Asuka Suzuki-Hirano; Tatsuya Sato; Harukazu Nakamura.
In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation of this pathway. 'Prolonged' activation of ERK by misexpression of _Fgf8b_ and dominant-negative _Sprouty2_ (_dnSprouty2_) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using a MEK inhibitor, U0126, or by tetracycline dependent Tet-off system after co-expression of _Fgf8b_ and _dnSprouty2_, forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of _dnMkp3_ and _Fgf8b_, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon...
Tipo: Manuscript Palavras-chave: Developmental Biology; Molecular Cell Biology; Neuroscience.
Ano: 2008 URL: http://precedings.nature.com/documents/2089/version/1
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Invariant mRNA content and mitotic protein breakdown as a solution to the Russian Doll problem of the mammalian cell cycle 17
Stephen Cooper; Kerby Shedden; Dang Vu-Phan.
It is widely accepted that numerous genes are expressed in a cell-cycle dependent manner, with cycle-specific variations in mRNA content or peaks of protein content during the cell cycle. These proposed variations raise the problem of how varying cell cycle gene expression is regulated. This is the "infinite regression" problem or Russian Doll problem where postulating a cell-cycle specific control element merely pushes the explanation of cell-cycle variation back one step to the problem of how that control element itself appears and disappears at particular times during the cell cycle. We present evidence that cyclin mRNA content is invariant during the cell cycle and calculations reveal that mRNA variation does not account for observed...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology.
Ano: 2007 URL: http://precedings.nature.com/documents/1218/version/1
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"Dark Mediators" of Proteins as Revealed by NMR in Water: Residue-selective Anion Bindings that are Masked by Pre-existing Buffer 17
Jianxing Song; Linlin Miao; Haina Qin.
Ions are commonly believed to impose their effects on proteins by unspecific electrostatic screening. Here, by NMR we reveal that in water sulfate, chloride and thiocyanate are able to bind a well-folded WW domain at distinctive residues and affinities, which is surprisingly masked by the pre-existing buffer. Our study reveals that the specific anion binding is so ubiquitous and consequently no longer negligible in establishing "postreductionist framework" for protein biochemistry.
Tipo: Manuscript Palavras-chave: Chemistry; Molecular Cell Biology; Earth & Environment; Evolutionary Biology.
Ano: 2012 URL: http://precedings.nature.com/documents/6769/version/1
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Cocaine self-administration in the mouse: A low-cost, chronic catheter preparation 17
Matthew B. Pomrenze; Michael V. Baratta; Brian A. Cadle; Donald C. Cooper.
Intravenous drug self-administration is the most valid animal model of human addiction because it allows volitional titration of the drug in the blood based on an individual’s motivational state together with the pharmacokinetic properties of the drug. Here we describe a reliable low-cost mouse self-administration catheter assembly and protocol that that can be used to assess a variety of drugs of abuse with a variety of protocols. We describe a method for intravenous catheter fabrication that allows for efficient and long-lasting intravenous drug delivery. The intravenous catheters remained intact and patent for several weeks allowing us to establish stable maintenance of cocaine acquisition. This was followed by a dose response study in the...
Tipo: Manuscript Palavras-chave: Biotechnology; Genetics & Genomics; Molecular Cell Biology; Neuroscience; Pharmacology.
Ano: 2012 URL: http://precedings.nature.com/documents/7040/version/1
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Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase 2 (IKK2, IKK-beta, IKBKB) and TRAF2 indicating a dose dependent regulatory function of TRAF1 for NF-kappa B signaling 17
Johannes A. Schmid; Andreas Birbach.
IKK2 is one of the most crucial signaling kinases for activation of the transcription factor NF-kappa B. Since many NF-kappa B activating pathways converge at the level of IKK2, we searched for interaction partners of this kinase using the C-terminal part (aa 466-756) as bait in a yeast two-hybrid system. We identified the N-terminal part (aa 1-228) of the TNF-receptor associated factor TRAF1 as putative interaction partner, which was subsequently confirmed in mammalian cells by coimmunoprecipitation experiments. However, this interaction seemed weaker than the interaction between TRAF1 and TRAF2, an important activating adapter molecule of NF-kappa B signaling indicating that relative levels of IKK2, TRAF1 and TRAF2 might be important for the final...
Tipo: Manuscript Palavras-chave: Immunology; Molecular Cell Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4153/version/1
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Valid and efficient formula for free energy difference from nonequilibrium work 17
Liao Y. Chen.
Atomic force microscopes and optical tweezers afford direct probe into the inner working of single biomolecules by mechanically unfolding them.^1-15^ Critical to the success of this type of probe is to correctly extract the free energy differences between the various conformations of a protein/nucleic acid along its forced unfolding pathways. Current studies rely on the Jarzynski equality^16^ (JE) or its undergirding Crooks fluctuation theorem^17^ (CFT), even though questions remain on its validity^17-19^ and on its accuracy.^13,20-21^ The validity of JE relies on the assumption of microscopic reversibility.^17,18^ The dynamics of biomolecules, however, is Langevin stochastic in nature. The frictional force in the Langevin equation breaks the time reversal...
Tipo: Manuscript Palavras-chave: Chemistry; Molecular Cell Biology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1911/version/1
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The Roles of Membrane Rafts in CD32A-Mediated Phagocytosis 17
Timothy P. Tolentino; Periasamy Selvaraj; Cheng Zhu.
Membrane rafts are highly dynamic heterogeneous sterol- and sphingolipid-rich micro-domains on cell surfaces. They are generally believed to provide residency for cell surface molecules (e.g., adhesion and signaling molecules) and scaffolding to facilitate the functions of these molecules such as membrane trafficking, receptor transport, cell signaling, and endocytosis.
The governing, or overall hypothesis, for this project is that membrane rafts provide residency for Fc[gamma]RIIA (CD32A) on K562 cells, and that by doing so they provide a platform from which Fc[gamma]RIIA initiate or carry out their functions, which include migration, signaling, phagocytic synapse formation, and internalization of IgG opsonized...
Tipo: Manuscript Palavras-chave: Immunology; Molecular Cell Biology.
Ano: 2007 URL: http://precedings.nature.com/documents/1191/version/1
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Two 'protein folding codes' can be inferred from empirical classifications using Tlusty's topological approach 17
Rodrick Wallace.
Tlusty's topological arguments regarding the genetic code are applied to the classification of tertiary irregular protein symmetries. Unlike the genetic case, two protein folding codes are found, a 'normal' globular and a 'pathological' amyloid version. The underlying normal 'protein folding code error network' is found to have one major, highly dominant, 'spherical' component, a minor attachment handle in the Morse Theory sense, and as many as three additional subminor handles. The basic amyloid folding code error network appears to be more complicated, of genus two, giving the eightfold symmetry of the steric zipper. Like many before us, we conjecture that the elaborate...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Bioinformatics; Evolutionary Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4665/version/1
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Myosin II isoforms with separate but linked functions determine the fate of lamellipodia extension during cell spreading 17
Venkaiah Betapudi.
Non-muscle myosin II role has been implicated in the extension of lamellipodia, a critical step in the initiation of directed cell migration, invasion and other cellular processes, but the mechanistic details are limited to driving retrograde actin filaments. The present study reveals distinct localization of myosin IIA and IIB with an unexpected opposite mechanical roles in mediating lamellipodia extension during spreading. Attachment of cells to matrix is impaired in the absence of either isoforms, but differential regulation of focal contacts formation occurs in myosin IIA^-^; and IIB^-^; cells. Spreading cells expressing both isoforms display an organized actin network consisting of retrograde filaments, arcs and central filaments. Loss of actin arcs...
Tipo: Manuscript Palavras-chave: Cancer; Microbiology; Molecular Cell Biology.
Ano: 2009 URL: http://precedings.nature.com/documents/2868/version/1
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An optimized energy potential can predict SH2 domain-peptide interactions 17
Zeba Wunderlich; Leonid Mirny.
Peptide recognition modules (PRMs) are used throughout biology to mediate protein-protein interactions, and many PRMs are members of large protein domain families. Members of these families are often quite similar to each other, but each domain recognizes a distinct set of peptides, raising the question of how peptide recognition specificity is achieved using similar protein domains. The analysis of individual protein complex structures often gives answers that are not easily applicable to other members of the same PRM family. Bioinformatics-based approaches, one the other hand, may be difficult to interpret physically. Here we integrate structural information with a large, quantitative data set of SH2-peptide interactions to study the physical origin...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1881/version/1
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