1,115 research outputs found
Dataset for the proteomic inventory and quantitative analysis of the breast cancer hypoxic secretome associated with osteotropism
The cancer secretome includes all of the macromolecules secreted by cells into their microenvironment. Cancer cell secretomes are significantly different to that of normal cells reflecting the changes that normal cells have undergone during their transition to malignancy. More importantly, cancer secretomes are known to be active mediators of both local and distant host cells and play an important role in the progression and dissemination of cancer. Here we have quantitatively profiled both the composition of breast cancer secretomes associated with osteotropism, and their modulation under normoxic and hypoxic conditions. We detect and quantify 162 secretome proteins across all conditions which show differential hypoxic induction and association with osteotropism. Mass Spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000397 and the complete proteomic, bioinformatic and biological analyses are reported in Cox et al. (2015) [1]
Development of deep Vs profiles and site periods for the Canterbury region
Recent field investigations were carried out to define the shear wave
velocity (VS) profile and site periods across the Canterbury region, supplementing earlier
efforts in urban Christchurch. Active source surface wave testing, ambient wave field
(passive) and H/V spectral ratio methods were used to characterise the soil profile in the
region. H/V spectral ratio peaks indicate site periods in the range of 5-7 seconds across
much of the Canterbury Plains, broadly consistent with those based on a 1D velocity
model for the region. Site periods decrease rapidly in the vicinity of the Canterbury
foothills and the Banks Peninsula outcrops. In Christchurch, the Riccarton Gravels result
in a significant mode of vibration that has a much shorter period than the site period of
the entire soil column down to basement rock
Annual Research Review: interparental conflict and youth psychopathology: an evidence review and practice focused update
The quality of the interparental relationship is recognized as an important influence on child and adolescent psychopathology. Historically, clinically-oriented research on this topic has focused on the impacts of parental divorce and domestic violence as primary interparental relationship influences on child outcomes, to the relative neglect of dimensional or qualitative features of the couple/interparental relationship for youth (child and adolescent) psychopathology. Recent research has highlighted that children are affected by attributes of interparental conflict, specifically how parents express and manage conflicts in their relationship, across a continuum of expressed severity and negativity â ranging from silence to violence. Further, new evidence highlights that childrenâs emotional, behavioral, social, academic outcomes and future interpersonal relationships are adversely affected by conflict between parents/carers whether adults are living together or not (i.e. married or separated), or where children are or are not genetically related to their rearing parents (e.g. adoption). We review evidence and present an integrated theoretical model, highlighting how children are affected by interparental conflict and what this evidence base means for effective intervention and prevention program development, as well as the development of possible cost-benefit models. Additionally, we review policy implications of this research and highlight some very recent examples of UK-based policy focusing on addressing the interparental relationship and its impact on youth psychopathology
Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein
Although metallocofactors are ubiquitous in enzyme catalysis, how metal binding specificity arises remains poorly understood, especially in the case of metals with similar primary ligand preferences such as manganese and iron. The biochemical selection of manganese over iron presents a particularly intricate problem because manganese is generally present in cells at a lower concentration than iron, while also having a lower predicted complex stability according to the IrvingâWilliams series (MnII ZnII). Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein ligands in both metal sites self-assembles from MnII and FeII in vitro, thus diverging from the IrvingâWilliams series without requiring auxiliary factors such as metallochaperones. Crystallographic, spectroscopic, and computational data demonstrate that one of the two metal sites preferentially binds FeII over MnII as expected, whereas the other site is nonspecific, binding equal amounts of both metals in the absence of oxygen. Oxygen exposure results in further accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least a two-step process governed by both the intrinsic metal specificity of the protein scaffold and additional effects exerted during oxygen binding or activation. We further show that the mixed-metal cofactor catalyzes a two-electron oxidation of the protein scaffold, yielding a tyrosineâvaline ether cross-link. Theoretical modeling of the reaction by density functional theory suggests a multistep mechanism including a valyl radical intermediate
Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone
BACKGROUND
New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype.
AIM
To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England.
METHODS
Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains.
FINDINGS
By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 Ă 10(-6), Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006.
CONCLUSIONS
Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms
INSIG1 influences obesity-related hypertriglyceridemia in humans
In our analysis of a quantitative trait locus (QTL) for plasma triglyceride (TG) levels [logarithm of odds (LOD) = 3.7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region. Insulin-induced genes (INSIGs) are feedback mediators of cholesterol and fatty acid synthesis in animals, but their role in human lipid regulation is unclear. In our cohort, the INSIG1 promoter SNP rs2721 was associated with TG levels (P = 2 Ă 10â3 in 1,560 individuals of the original linkage cohort, P = 8 Ă 10â4 in 920 unrelated individuals of the replication cohort, combined P = 9.9 Ă 10â6). Individuals homozygous for the T allele had 9% higher TG levels and 2-fold lower expression of INSIG1 in surgical liver biopsy samples when compared with individuals homozygous for the G allele. Also, the T allele showed additional binding of nuclear proteins from HepG2 liver cells in gel shift assays. Finally, the variant rs7566605 in INSIG2, the only homolog of INSIG1, enhances the effect of rs2721 (P = 0.00117). The variant rs2721 alone explains 5.4% of the observed linkage in our cohort, suggesting that additional, yet-undiscovered genes and sequence variants in the QTL interval also contribute to alterations in TG levels in humans
Charge-density wave formation in Sr_{14}Cu_{24}O_{41}
The electrodynamic response of the spin-ladder compound
SrCaCuO () has been studied from
radiofrequencies up to the infrared. At temperatures below 250 K a pronounced
absorption peak appears around 12 cm in SrCuO for
the radiation polarized along the chains/ladders ().
In addition a strongly temperature dependent dielectric relaxation is observed
in the kHz - MHz range. We explain this behavior by a charge density wave which
develops in the ladders sub-system and produces a mode pinned at 12 cm.
With increasing Ca doping the mode shifts up in frequency and eventually
disappears for because the dimensionality of the system crosses over from
one to two dimensions, giving way to the superconducting ground state under
pressure.Comment: One name added to author list 4 pages, 2 figures, email:
[email protected]
Landau Theory of the Phase Transitions in Half Doped Manganites: Interplay of Magnetic, Charge and Structural Orders
The order parameters of the magnetic, charge and structural orders at
half-doped manganites are identified. A corresponding Landau theory of the
phase transitions is formulated. Many structural and thermodynamical behaviors
are accounted for and clarified within the framework. In particular, the theory
provides a unified picture for the scenario of the phase transitions and their
nature with respect to the variation of the tolerance factor of the manganites.
It also accounts for the origin of the incommensurate nature of the orbital
order and its subsequently accompanying antiferromagnetic order.Comment: 4 pages, 3 eps figures, Revtex, Phys. Rev. B61, 200
The Local Bubble and Interstellar Material Near the Sun
The properties of interstellar matter (ISM) at the Sun are regulated by our
location with respect to the Local Bubble (LB) void in the ISM. The LB is
bounded by associations of massive stars and fossil supernovae that have
disrupted natal ISM and driven intermediate velocity ISM into the LB interior
void. The Sun is located in such a driven ISM parcel. The Local Fluff has a
bulk velocity of 19 km/s in the LSR, and an upwind direction towards the center
of the gas and dust ring formed by the Loop I supernova remnant interaction
with the LB. When the ram pressure of the LIC is included in the total LIC
pressure, and if magnetic thermal and cosmic ray pressures are similar, the LIC
appears to be in pressure equilibrium with the local hot bubble plasma.Comment: Proceedings of Symposium on the Composition of Matter, honoring
Johannes Geiss on the occasion of his 80th birthday. Space Science Reviews
(in press
Parity nonconserving cold neutron-parahydrogen interactions
Three pion dominated observables of the parity nonconserving interactions
between the cold neutrons and parahydrogen are calculated. The transversely
polarized neutron spin rotation, unpolarized neutron longitudinal polarization,
and photon-asymmetry of the radiative polarized neutron capture are considered.
For the numerical evaluation of the observables, the strong interactions are
taken into account by the Reid93 potential and the parity nonconserving
interactions by the DDH model along with the two-pion exchange.Comment: 17 pages, 2 figure
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