578 research outputs found
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Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects
Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to
test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main
paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining
relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes
Solubilization of green plant thylakoid membranes with n-dodecyl-α,D-maltoside. Implications for the structural organization of the Photosystem II, Photosystem I, ATP synthase and cytochrome b6f complexes
Solubilization of green plant thylakoid membranes with n-dodecyl-α,D-maltoside. Implications for the structural organization of the Photosystem II, Photosystem I, ATP synthase and cytochrome b6f complexes
Solubilization of green plant thylakoid membranes with n-dodecyl-α,D-maltoside. Implications for the structural organization of the Photosystem II, Photosystem I, ATP synthase and cytochrome b6f complexes
A hot spot on interferon α/β receptor subunit 1 (IFNAR1) underpins its interaction with interferon-β and dictates signaling
The interaction of IFN-β with its receptor IFNAR1 (interferon α/β receptor subunit 1) is vital for host-protective anti-viral and anti-proliferative responses, but signaling via this interaction can be detrimental if dysregulated. Whereas it is established that IFNAR1 is an essential component of the IFNAR signaling complex, the key residues underpinning the IFN-β-IFNAR1 interaction are unknown. Guided by the crystal structure of the IFN-β-IFNAR1 complex, we used truncation variants and site-directed mutagenesis to investigate domains and residues enabling complexation of IFN-β to IFNAR1. We have identified an interface on IFNAR1-subdomain-3 that is differentially utilized by IFN-β and IFN-α for signal transduction. We used surface plasmon resonance and cell-based assays to investigate this important IFN-β binding interface that is centered on IFNAR1 residues Tyr240 and Tyr274 binding the C and N termini of the B and C helices of IFN-β, respectively. Using IFNAR1 and IFN-β variants, we show that this interface contributes significantly to the affinity of IFN-β for IFNAR1, its ability to activate STAT1, the expression of interferon stimulated genes, and ultimately to the anti-viral and anti-proliferative properties of IFN-β. These results identify a key interface created by IFNAR1 residues Tyr240 and Tyr274 interacting with IFN-β residues Phe63, Leu64, Glu77, Thr78, Val81, and Arg82 that underlie IFN-β-IFNAR1-mediated signaling and biological processes
Cervical cancer in 2 women with a Mirena®-pitfalls in the assessment of irregular bleeding: a case series
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The atomic structure of low-index surfaces of the intermetallic compound InPd
The intermetallic compound InPd (CsCl type of crystal structure with a broad compositional range) is considered as a candidate catalyst for the steam reforming of methanol. Single crystals of this phase have been grown to study the structure of its three low-index surfaces under ultra-high vacuum conditions, using low energy electron diffraction (LEED), X-ray photoemission spectroscopy (XPS), and scanning tunneling microscopy (STM). During surface preparation, preferential sputtering leads to a depletion of In within the top few layers for all three surfaces. The near-surface regions remain slightly Pd-rich until annealing to ∼580 K. A transition occurs between 580 and 660 K where In
segregates towards the surface and the near-surface regions become slightly In-rich above ∼660 K. This transition is accompanied by a sharpening of LEED patterns and formation of flat step-terrace morphology, as observed by STM. Several superstructures have been identified for the different surfaces associated with this process. Annealing to higher temperatures (≥750 K) leads to faceting via thermal etching as shown for the (110) surface, with a bulk In composition close to the In-rich limit of the existence domain of the cubic phase. The Pd-rich InPd(111) is found to be consistent with
a Pd-terminated bulk truncation model as shown by dynamical LEED analysis while, after annealing at higher temperature, the In-rich InPd(111) is consistent with an In-terminated bulk truncation, in agreement with density functional theory (DFT) calculations of the relative surface energies. More complex surface structures are observed for the (100) surface. Additionally, individual grains of a polycrystalline sample are characterized by micro-spot XPS and LEED as well as low-energy electron
microscopy. Results from both individual grains and “global” measurements are interpreted based on
comparison to our single crystals findings, DFT calculations and previous literature
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Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration.
Recent interest in astrocyte activation states has raised the fundamental question of how these cells, normally essential for synapse and neuronal maintenance, become pathogenic. Here, we show that activation of the unfolded protein response (UPR), specifically phosphorylated protein kinase R-like endoplasmic reticulum (ER) kinase (PERK-P) signaling-a pathway that is widely dysregulated in neurodegenerative diseases-generates a distinct reactivity state in astrocytes that alters the astrocytic secretome, leading to loss of synaptogenic function in vitro. Further, we establish that the same PERK-P-dependent astrocyte reactivity state is harmful to neurons in vivo in mice with prion neurodegeneration. Critically, targeting this signaling exclusively in astrocytes during prion disease is alone sufficient to prevent neuronal loss and significantly prolongs survival. Thus, the astrocyte reactivity state resulting from UPR over-activation is a distinct pathogenic mechanism that can by itself be effectively targeted for neuroprotection
White matter structure and myelin-related gene expression alterations with experience in adult rats
White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity measured by DTI. We combined DTI, immunohistochemistry and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. First, we observed experience-induced DTI differences in WM and in grey matter structure. C-Fos mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the MRI WM metrics, indicating that molecular correlates of cortical activity relate to macroscale measures of WM structure. Analysis of myelin-related genes revealed higher myelin basic protein (MBP) mRNA expression. Higher MBP protein expression was also found via immunohistochemistry in WM. Finally, unbiased RNA sequencing analysis identified 134 differentially expressed genes encoding proteins in- volved in functions related to cell proliferation and differentiation, regulation of myelination and neuronal activity modulation. In conclusion, macroscale measures of WM plasticity are supported by both molecular and cellular evidence and confirm that myelination is one of the underlying mechanisms
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