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Overview of mathematical approaches used to model bacterial chemotaxis I: the single cell
Mathematical modeling of bacterial chemotaxis systems has been influential and insightful in helping to understand experimental observations. We provide here a comprehensive overview of the range of mathematical approaches used for modeling, within a single bacterium, chemotactic processes caused by changes to external gradients in its environment. Specific areas of the bacterial system which have been studied and modeled are discussed in detail, including the modeling of adaptation in response to attractant gradients, the intracellular phosphorylation cascade, membrane receptor clustering, and spatial modeling of intracellular protein signal transduction. The importance of producing robust models that address adaptation, gain, and sensitivity are also discussed. This review highlights that while mathematical modeling has aided in understanding bacterial chemotaxis on the individual cell scale and guiding experimental design, no single model succeeds in robustly describing all of the basic elements of the cell. We conclude by discussing the importance of this and the future of modeling in this area
Protein Pattern Formation
Protein pattern formation is essential for the spatial organization of many
intracellular processes like cell division, flagellum positioning, and
chemotaxis. A prominent example of intracellular patterns are the oscillatory
pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological
function is to ensure precise cell division. Cell polarization, a prerequisite
for processes such as stem cell differentiation and cell polarity in yeast, is
also mediated by a diffusion-reaction process. More generally, these functional
modules of cells serve as model systems for self-organization, one of the core
principles of life. Under which conditions spatio-temporal patterns emerge, and
how these patterns are regulated by biochemical and geometrical factors are
major aspects of current research. Here we review recent theoretical and
experimental advances in the field of intracellular pattern formation, focusing
on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl
Thermal inactivation and conformational lock studies on glucose oxidase
In this study, the dissociative thermal inactivation
and conformational lock theories are applied for the
homodimeric enzyme glucose oxidase (GOD) in order to
analyze its structure. For this purpose, the rate of activity
reduction of glucose oxidase is studied at various temperatures
using b-D-glucose as the substrate by incubation of
enzyme at various temperatures in the wide range between
40 and 70 �C using UV–Vis spectrophotometry. It was
observed that in the two ranges of temperatures, the
enzyme has two different forms. In relatively low temperatures,
the enzyme is in its dimeric state and has normal
activity. In high temperatures, the activity almost disappears
and it aggregates. The above achievements are confirmed
by dynamic light scattering. The experimental
parameter ‘‘n’’ as the obvious number of conformational
locks at the dimer interface of glucose oxidase is obtained
by kinetic data, and the value is near to two. To confirm the
above results, the X-ray crystallography structure of the
enzyme, GOD (pdb, 1gal), was also studied. The secondary
and tertiary structures of the enzyme to track the thermal
inactivation were studied by circular dichroism and
fluorescence spectroscopy, respectively. We proposed a
mechanism model for thermal inactivation of GOD based
on the absence of the monomeric form of the enzyme by
circular dichroism and fluorescence spectroscopy
The interplay of intrinsic and extrinsic bounded noises in genetic networks
After being considered as a nuisance to be filtered out, it became recently
clear that biochemical noise plays a complex role, often fully functional, for
a genetic network. The influence of intrinsic and extrinsic noises on genetic
networks has intensively been investigated in last ten years, though
contributions on the co-presence of both are sparse. Extrinsic noise is usually
modeled as an unbounded white or colored gaussian stochastic process, even
though realistic stochastic perturbations are clearly bounded. In this paper we
consider Gillespie-like stochastic models of nonlinear networks, i.e. the
intrinsic noise, where the model jump rates are affected by colored bounded
extrinsic noises synthesized by a suitable biochemical state-dependent Langevin
system. These systems are described by a master equation, and a simulation
algorithm to analyze them is derived. This new modeling paradigm should enlarge
the class of systems amenable at modeling.
We investigated the influence of both amplitude and autocorrelation time of a
extrinsic Sine-Wiener noise on: the Michaelis-Menten approximation of
noisy enzymatic reactions, which we show to be applicable also in co-presence
of both intrinsic and extrinsic noise, a model of enzymatic futile cycle
and a genetic toggle switch. In and we show that the
presence of a bounded extrinsic noise induces qualitative modifications in the
probability densities of the involved chemicals, where new modes emerge, thus
suggesting the possibile functional role of bounded noises
Measurements of Deuteron Photodisintegration up to 4.0 GeV
The first measurements of the differential cross section for the d(gamma,p)n
reaction up to 4.0 GeV were performed at Continuous Electron Beam Accelerator
Facility (CEBAF) at Jefferson Lab. We report the cross sections at the proton
center-of-mass angles of 36, 52, 69 and 89 degrees. These results are in
reasonable agreement with previous measurements at lower energy. The 89 and 69
degree data show constituent-counting-rule behavior up to 4.0 GeV photon
energy. The 36 and 52 degree data disagree with the counting rule behavior. The
quantum chromodynamics (QCD) model of nuclear reactions involving reduced
amplitudes disagrees with the present data.Comment: 5 pages (REVTeX), 1 figure (postscript
Spin Structure of the Proton from Polarized Inclusive Deep-Inelastic Muon-Proton Scattering
We have measured the spin-dependent structure function in inclusive
deep-inelastic scattering of polarized muons off polarized protons, in the
kinematic range and . A
next-to-leading order QCD analysis is used to evolve the measured
to a fixed . The first moment of at is .
This result is below the prediction of the Ellis-Jaffe sum rule by more than
two standard deviations. The singlet axial charge is found to be . In the Adler-Bardeen factorization scheme, is
required to bring in agreement with the Quark-Parton Model. A
combined analysis of all available proton and deuteron data confirms the
Bjorken sum rule.Comment: 33 pages, 22 figures, uses ReVTex and smc.sty. submitted to Physical
Review
Two body photodisintegration of the deuteron up to 2.8 GeV
Measurements were performed for the photodisintegration cross section of the deuteron for photon energies from 1.6 to 2.8 GeV and center-of-mass angles from 37° to 90°. The measured energy dependence of the cross section at θ_(cm)=90° is in agreement with the constituent counting rules
Wild-Type Phosphoribosylpyrophosphate Synthase (PRS) from Mycobacterium tuberculosis: A Bacterial Class II PRS?
The 5-phospho-α-D-ribose 1-diphosphate (PRPP) metabolite plays essential roles in several biosynthetic pathways, including histidine, tryptophan, nucleotides, and, in mycobacteria, cell wall precursors. PRPP is synthesized from α-D-ribose 5-phosphate (R5P) and ATP by the Mycobacterium tuberculosis prsA gene product, phosphoribosylpyrophosphate synthase (MtPRS). Here, we report amplification, cloning, expression and purification of wild-type MtPRS. Glutaraldehyde cross-linking results suggest that MtPRS predominates as a hexamer, presenting varied oligomeric states due to distinct ligand binding. MtPRS activity measurements were carried out by a novel coupled continuous spectrophotometric assay. MtPRS enzyme activity could be detected in the absence of Pi. ADP, GDP and UMP inhibit MtPRS activity. Steady-state kinetics results indicate that MtPRS has broad substrate specificity, being able to accept ATP, GTP, CTP, and UTP as diphosphoryl group donors. Fluorescence spectroscopy data suggest that the enzyme mechanism for purine diphosphoryl donors follows a random order of substrate addition, and for pyrimidine diphosphoryl donors follows an ordered mechanism of substrate addition in which R5P binds first to free enzyme. An ordered mechanism for product dissociation is followed by MtPRS, in which PRPP is the first product to be released followed by the nucleoside monophosphate products to yield free enzyme for the next round of catalysis. The broad specificity for diphosphoryl group donors and detection of enzyme activity in the absence of Pi would suggest that MtPRS belongs to Class II PRS proteins. On the other hand, the hexameric quaternary structure and allosteric ADP inhibition would place MtPRS in Class I PRSs. Further data are needed to classify MtPRS as belonging to a particular family of PRS proteins. The data here presented should help augment our understanding of MtPRS mode of action. Current efforts are toward experimental structure determination of MtPRS to provide a solid foundation for the rational design of specific inhibitors of this enzyme
Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study
Research on tuberous sclerosis complex (TSC) to date has focused mainly on the physical manifestations of the disease. In contrast, the psychosocial impact of TSC has received far less attention. The aim of this study was therefore to examine the impact of TSC on health, quality of life (QoL), and psychosocial well-being of individuals with TSC and their families. Questionnaires with disease-specific questions on burden of illness (BOI) and validated QoL questionnaires were used. After completion of additional informed consent, we included 143 individuals who participated in the TOSCA (TuberOus SClerosis registry to increase disease Awareness) study. Our results highlighted the substantial burden of TSC on the personal lives of individuals with TSC and their families. Nearly half of the patients experienced negative progress in their education or career due to TSC (42.1%), as well as many of their caregivers (17.6% employed; 58.8% unemployed). Most caregivers (76.5%) indicated that TSC affected family life, and social and working relationships. Further, well-coordinated care was lacking: a smooth transition from pediatric to adult care was mentioned by only 36.8% of adult patients, and financial, social, and psychological support in 21.1, 0, and 7.9%, respectively. In addition, the moderate rates of pain/discomfort (35%) and anxiety/depression (43.4%) reported across all ages and levels of disease demonstrate the high BOI and low QoL in this vulnerable population
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