2,582 research outputs found
Early life stress alters expression of glucocorticoid stress response genes and trophic factor transcripts in the rodent basal ganglia
Early life stress shapes the developing brain and increases risk for psychotic disorders. Yet, it is not fully understood how early life stress impacts brain regions in dopaminergic pathways whose dysfunction can contribute to psychosis. Therefore, we investigated gene expression following early life stress in adult brain regions containing dopamine neuron cell bodies (substantia nigra, ventral tegmental area (VTA)) and terminals (dorsal/ventral striatum). Sprague–Dawley rats (14F, 10M) were separated from their mothers from postnatal days (PND) 2–14 for 3 h/day to induce stress, while control rats (12F, 10M) were separated for 15 min/day over the same period. In adulthood (PND98), brain regions were dissected, RNA was isolated and five glucocorticoid signalling-related and six brain-derived neurotrophic factor (Bdnf) mRNAs were assayed by qPCR in four brain regions. In the VTA, levels of glucocorticoid signalling-related transcripts differed in maternally separated rodents compared to controls, with the Fkbp5 transcript significantly lower and Ptges3 transcript significantly higher in stressed offspring. In the VTA and substantia nigra, maternally separated rodents had significantly higher Bdnf IIA and III mRNA levels than controls. By contrast, in the ventral striatum, maternally separated rodents had significantly lower expression of Bdnf I, IIA, IIC, IV and VI transcripts. Sex differences in Nr3c1, Bag1 and Fkbp5 expression in the VTA and substantia nigra were also detected. Our results suggest that early life stress has long-lasting impacts on brain regions involved in dopamine neurotransmission, changing the trophic environment and potentially altering responsiveness to subsequent stressful events in a sex-specific pattern
On quantum teleportation with beam-splitter-generated entanglement
Following the lead of Cochrane, Milburn, and Munro [Phys. Rev. A {\bf 62},
062307 (2000)], we investigate theoretically quantum teleportation by means of
the number-sum and phase-difference variables. We study Fock-state entanglement
generated by a beam splitter and show that two-mode Fock-state inputs can be
entangled by a beam splitter into close approximations of maximally entangled
eigenstates of the phase difference and the photon-number sum
(Einstein-Podolsky-Rosen -- EPR -- states). Such states could be experimentally
feasible with on-demand single-photon sources. We show that the teleportation
fidelity can reach near unity when such ``quasi-EPR'' states are used as the
quantum channel.Comment: 7 pages (two-column), 7 figures, submitted to Phys. Rev. A. Text
unmodified, postscript error correcte
Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control
DNA replication stress is a source of genomic instability. Here we identify changed mutation rate 1 (Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that Cmr1—together with Mrc1/Claspin, Pph3, the chaperonin containing TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to Cmr1, its human orthologue WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that Cmr1/WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins
Photoproduction of Theta baryon from the neutron
We study photoproduction reactions for Theta^+, which was recently observed
as a candidate of an exotic five quark state uudd(bar s). We employ effective
lagrangian interactions in the linear and non-linear formalism of chiral
symmetry and investigate two cases of spin and parity of Theta^+, J^P = 1/2^+
and 1/2^-. We calculate cross sections and discuss possibilities to
discriminate one from the other.Comment: 14 pages, 19 figure
Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2
The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic
QUBIC: The QU Bolometric Interferometer for Cosmology
One of the major challenges of modern cosmology is the detection of B-mode
polarization anisotropies in the CMB. These originate from tensor fluctuations
of the metric produced during the inflationary phase. Their detection would
therefore constitute a major step towards understanding the primordial
Universe. The expected level of these anisotropies is however so small that it
requires a new generation of instruments with high sensitivity and extremely
good control of systematic effects. We propose the QUBIC instrument based on
the novel concept of bolometric interferometry, bringing together the
sensitivity advantages of bolometric detectors with the systematics effects
advantages of interferometry. Methods: The instrument will directly observe the
sky through an array of entry horns whose signals will be combined together
using an optical combiner. The whole set-up is located inside a cryostat.
Polarization modulation will be achieved using a rotating half-wave plate and
interference fringes will be imaged on two focal planes (separated by a
polarizing grid) tiled with bolometers. We show that QUBIC can be considered as
a synthetic imager, exactly similar to a usual imager but with a synthesized
beam formed by the array of entry horns. Scanning the sky provides an
additional modulation of the signal and improve the sky coverage shape. The
usual techniques of map-making and power spectrum estimation can then be
applied. We show that the sensitivity of such an instrument is comparable with
that of an imager with the same number of horns. We anticipate a low level of
beam-related systematics thanks to the fact that the synthesized beam is
determined by the location of the primary horns. Other systematics should be
under good control thanks to an autocalibration technique, specific to our
concept, that will permit the accurate determination of most of the systematics
parameters.Comment: 12 pages, 10 figures, submitted to Astronomy and Astrophysic
Tight-binding parameters for charge transfer along DNA
We systematically examine all the tight-binding parameters pertinent to
charge transfer along DNA. The molecular structure of the four DNA bases
(adenine, thymine, cytosine, and guanine) is investigated by using the linear
combination of atomic orbitals method with a recently introduced
parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are
discussed and then used for calculating the corresponding wavefunctions of the
two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO
and LUMO energies of the bases are in good agreement with available
experimental values. Our results are then used for estimating the complete set
of charge transfer parameters between neighboring bases and also between
successive base-pairs, considering all possible combinations between them, for
both electrons and holes. The calculated microscopic quantities can be used in
mesoscopic theoretical models of electron or hole transfer along the DNA double
helix, as they provide the necessary parameters for a tight-binding
phenomenological description based on the molecular overlap. We find that
usually the hopping parameters for holes are higher in magnitude compared to
the ones for electrons, which probably indicates that hole transport along DNA
is more favorable than electron transport. Our findings are also compared with
existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table
Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach
Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally
- …