825 research outputs found
Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs)
Fibroblasts can be directly reprogrammed to induced renal tubular epithelial cells (iRECs) using four transcription factors. These engineered cells may be used for disease modeling, cell replacement therapy or drug and toxicity testing. Direct reprogramming induces drastic changes in the transcriptional landscape, protein expression, morphological and functional properties of cells. However, how the metabolome is changed by reprogramming and to what degree it resembles the target cell type remains unknown. Using untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-MS, we characterized the metabolome of mouse embryonic fibroblasts (MEFs), iRECs, mIMCD-3 cells, and whole kidneys. Metabolic fingerprinting can distinguish each cell type reliably, revealing iRECs are most similar to mIMCD-3 cells and clearly separate from MEFs used for reprogramming. Treatment with the cytotoxic drug cisplatin induced typical changes in the metabolic profile of iRECs commonly occurring in acute renal injury. Interestingly, metabolites in the medium of iRECs, but not of mIMCD-3 cells or fibroblast could distinguish treated and non-treated cells by cluster analysis. In conclusion, direct reprogramming of fibroblasts into renal tubular epithelial cells strongly influences the metabolome of engineered cells, suggesting that metabolic profiling may aid in establishing iRECs as in vitro models for nephrotoxicity testing in the future
Treating clinical mastitis in dairy cows with essential oils
Clinical mastitis is the main concern in dairy farming today, but there are very few drugs that are compatible with organic specifications. Our study was conducted in order to evaluate the therapeutic efficiency of the intramammary infusion of three essential oils, Thymus vulgaris, Rosmarinus verbenone and Laurus nobilis. Fifty-five cases of mastitis were treated with 10 ml of a mixture of the three oils (1.5% each in sunflower oil). Forty-five others were treated with 10 ml of a mixture of Thymus vulgaris and Rosmarinus verbenone (6% of each in sunflower oil or in water). The recovery rate was only 40%, which is deemed unsatisfactory
Time-temperature superposition in viscous liquids
Dielectric relaxation measurements on supercooled triphenyl phosphite show
that at low temperatures time-temperature superposition (TTS) is accurately
obeyed for the primary (alpha) relaxation process. Measurements on 6 other
molecular liquids close to the calorimetric glass transition indicate that TTS
is linked to an high-frequency decay of the alpha loss, while
the loss peak width is nonuniversal.Comment: 4 page
Unconventional motional narrowing in the optical spectrum of a semiconductor quantum dot
Motional narrowing refers to the striking phenomenon where the resonance line
of a system coupled to a reservoir becomes narrower when increasing the
reservoir fluctuation. A textbook example is found in nuclear magnetic
resonance, where the fluctuating local magnetic fields created by randomly
oriented nuclear spins are averaged when the motion of the nuclei is thermally
activated. The existence of a motional narrowing effect in the optical response
of semiconductor quantum dots remains so far unexplored. This effect may be
important in this instance since the decoherence dynamics is a central issue
for the implementation of quantum information processing based on quantum dots.
Here we report on the experimental evidence of motional narrowing in the
optical spectrum of a semiconductor quantum dot broadened by the spectral
diffusion phenomenon. Surprisingly, motional narrowing is achieved when
decreasing incident power or temperature, in contrast with the standard
phenomenology observed for nuclear magnetic resonance
Energy landscape - a key concept for the dynamics of glasses and liquids
There is a growing belief that the mode coupling theory is the proper
microscopic theory for the dynamics of the undercooled liquid above a critical
temperature T_c. In addition, there is some evidence that the system leaves the
saddlepoints of the energy landscape to settle in the valleys at this critical
temperature. Finally, there is a microscopic theory for the entropy at the
calorimetric glass transition T_g by Mezard and Parisi, which allows to
calculate the Kauzmann temperature from the atomic pair potentials.
The dynamics of the frozen glass phase is at present limited to
phenomenological models. In the spirit of the energy landscape concept, one
considers an ensemble of independent asymmetric double-well potentials with a
wide distribution of barrier heights and asymmetries (ADWP or Gilroy-Phillips
model). The model gives an excellent description of the relaxation of glasses
up to about T_g/4. Above this temperature, the interaction between different
relaxation centers begins to play a role. One can show that the interaction
reduces the number of relaxation centers needed to bring the shear modulus down
to zero by a factor of three.Comment: Contribution to the III Workshop on Nonequilibrium Phenomena in
Supercooled Fluids, Glasses and Amorphous Materials, 22-27 September 2002,
Pisa; 14 pages, 3 figures; Version 3 takes criticque at Pisa into account;
final version 4 will be published in J.Phys.: Condens.Matte
The cellular prion protein increases the uptake and toxicity of tdp-43 fibrils
Cytoplasmic aggregation of the primarily nuclear TAR DNA-binding protein 43 (TDP-43) affects neurons in most amyotrophic lateral sclerosis (ALS) and approximately half of frontotemporal lobar degeneration (FTLD) cases. The cellular prion protein, PrPC, has been recognized as a common receptor and downstream effector of circulating neurotoxic species of several proteins involved in neurodegeneration. Here, capitalizing on our recently adapted TDP-43 real time quaking induced reaction, we set reproducible protocols to obtain standardized preparations of recombinant TDP-43 fibrils. We then exploited two different cellular systems (human SH-SY5Y and mouse N2a neuroblastoma cells) engineered to express low or high PrPC levels to investigate the link between PrPC expression on the cell surface and the internalization of TDP-43 fibrils. Fibril uptake was increased in cells overexpressing either human or mouse prion protein. Increased internalization was associated with detrimental consequences in all PrP-overexpressing cell lines but was milder in cells expressing the human form of the prion protein. As described for other amyloids, treatment with TDP-43 fibrils induced a reduction in the accumulation of the misfolded form of PrPC, PrPSc, in cells chronically infected with prions. Our results expand the list of misfolded proteins whose uptake and detrimental effects are mediated by PrPC, which encompass almost all pathological amyloids involved in neurodegeneration
Semiclassical approximations for Hamiltonians with operator-valued symbols
We consider the semiclassical limit of quantum systems with a Hamiltonian
given by the Weyl quantization of an operator valued symbol. Systems composed
of slow and fast degrees of freedom are of this form. Typically a small
dimensionless parameter controls the separation of time
scales and the limit corresponds to an adiabatic limit, in
which the slow and fast degrees of freedom decouple. At the same time
is the semiclassical limit for the slow degrees of freedom.
In this paper we show that the -dependent classical flow for the
slow degrees of freedom first discovered by Littlejohn and Flynn, coming from
an \epsi-dependent classical Hamilton function and an -dependent
symplectic form, has a concrete mathematical and physical meaning: Based on
this flow we prove a formula for equilibrium expectations, an Egorov theorem
and transport of Wigner functions, thereby approximating properties of the
quantum system up to errors of order . In the context of Bloch
electrons formal use of this classical system has triggered considerable
progress in solid state physics. Hence we discuss in some detail the
application of the general results to the Hofstadter model, which describes a
two-dimensional gas of non-interacting electrons in a constant magnetic field
in the tight-binding approximation.Comment: Final version to appear in Commun. Math. Phys. Results have been
strengthened with only minor changes to the proofs. A section on the
Hofstadter model as an application of the general theory was added and the
previous section on other applications was remove
Health services research into postnatal depression : results from a preliminary cross-cultural study
Background: Little is known about the
availability and uptake of health and
welfare services by women with postnatal
depression in different countries.
Aims: Within the context of a cross-
cultural research study, to develop and
test methods for undertaking quantitative
health services research in postnatal
depression.
Method: Interviews with service
planners and the collation of key health
indicators were used to obtain a profile of
service availability and provision. A service
use questionnaire was developed and
administered to a pilot sample in a number
of European study centres.
Results: Marked differences in service
access and use were observed between
the centres, including postnatal nursing
care and contacts with primary care
services.Rates of use of specialist services
were generally low.Common barriers to
access to care included perceived service
quality and responsiveness. On the basis of
the pilot work, a postnatal depression
version of the Service Receipt Inventory
was revised and finalised.
Conclusions: This preliminary study
demonstrated the methodological
feasibility of describing and quantifying
service use, highlighted the varied and
often limited use of care in this population,
and indicated the need for an improved
understanding of the resource needs and
implications of postnatal depression
Equilibration times in numerical simulation of structural glasses: Comparing parallel tempering and conventional molecular dynamics
Generation of equilibrium configurations is the major obstacle for numerical
investigation of the slow dynamics in supercooled liquid states. The parallel
tempering (PT) technique, originally proposed for the numerical equilibration
of discrete spin-glass model configurations, has recently been applied in the
study of supercooled structural glasses. We present an investigation of the
ability of parallel tempering to properly sample the liquid configuration space
at different temperatures, by mapping the PT dynamics into the dynamics of the
closest local potential energy minima (inherent structures). Comparing the PT
equilibration process with the standard molecular dynamics equilibration
process we find that the PT does not increase the speed of equilibration of the
(slow) configurational degrees of freedom.Comment: 5 pages, 3 figure
Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families
<p>Abstract</p> <p>Background</p> <p>Most rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen (CEA) gene family. To gain insights into evolutionary forces shaping the CEA gene family we have analysed this gene family in 27 mammalian species including monotreme and marsupial lineages.</p> <p>Results</p> <p>Phylogenetic analysis provided convincing evidence that the primordial CEA gene family in mammals consisted of five genes, including the immune inhibitory receptor-encoding <it>CEACAM1 </it>(CEA-related cell adhesion molecule) ancestor. Our analysis of the substitution rates within the nucleotide sequence which codes for the ligand binding domain of CEACAM1 indicates that the selection for diversification is, perhaps, a consequence of the exploitation of CEACAM1 by a variety of viral and bacterial pathogens as their cellular receptor. Depending on the extent of the amplification of an ancestral <it>CEACAM1</it>, the number of <it>CEACAM1</it>-related genes varies considerably between mammalian species from less than five in lagomorphs to more than 100 in bats. In most analysed species, ITAM (immunoreceptor tyrosine-based activation motifs) or ITAM-like motif-containing proteins exist which contain Ig-V-like, ligand binding domains closely related to that of CEACAM1. Human CEACAM3 is one such protein which can function as a CEACAM1 decoy receptor in granulocytes by mediating the uptake and destruction of specific bacterial pathogens via its ITAM-like motif. The close relationship between <it>CEACAM1 </it>and its ITAM-encoding relatives appears to be maintained by gene conversion and reciprocal recombination. Surprisingly, secreted CEACAMs resembling immunomodulatory CEACAM1-related trophoblast-specific pregnancy-specific glycoproteins (PSGs) found in humans and rodents evolved only in a limited set of mammals. The appearance of <it>PSG</it>-like genes correlates with invasive trophoblast growth in these species.</p> <p>Conclusions</p> <p>These phylogenetic studies provide evidence that pathogen/host coevolution and a possible participation in fetal-maternal conflict processes led to a highly species-specific diversity of mammalian CEA gene families.</p
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