12,186 research outputs found
Historical volcanism and within-island genetic divergence in the Tenerife skink (Squamata: Scincidae)
This study examines the genetic diversity of the Tenerife skink (Chalcides viridanus) within the context that Tenerife is now thought to have arisen as a single island as opposed to two/three precursor islands. DNA sequences were obtained from two mitochondrial regions and five nuclear loci. MtDNA divergence was substantial with four geographical clusters being detected. Two of these corresponded to two ancient areas that have undergone little recent eruptive activity (Anaga, Teno), while two further clusters were found within the more volcanically active central region. Nuclear divergence was low and revealed no strong geographical pattern. Estimated divergence of the Anaga group was 0.4-2.1 Ma ago (95% posterior interval), while the divergence time of the Teno cluster was 0.1-1.2 Ma ago. Phylogeographic distributions correspond well with ancient edifices, but divergence times postdate those expected under the previous ‘unification of ancient islands’ geological scenario. There is evidence of a major recent expansion of the central group following a decline in eruptive activity in this region, which also fits well with current geological hypotheses. Previously-described within-island evolutionary patterns in other Tenerife species also need to examined within this new geological context
Extracting the Groupwise Core Structural Connectivity Network: Bridging Statistical and Graph-Theoretical Approaches
Finding the common structural brain connectivity network for a given
population is an open problem, crucial for current neuro-science. Recent
evidence suggests there's a tightly connected network shared between humans.
Obtaining this network will, among many advantages , allow us to focus
cognitive and clinical analyses on common connections, thus increasing their
statistical power. In turn, knowledge about the common network will facilitate
novel analyses to understand the structure-function relationship in the brain.
In this work, we present a new algorithm for computing the core structural
connectivity network of a subject sample combining graph theory and statistics.
Our algorithm works in accordance with novel evidence on brain topology. We
analyze the problem theoretically and prove its complexity. Using 309 subjects,
we show its advantages when used as a feature selection for connectivity
analysis on populations, outperforming the current approaches
Hypoattenuated leaflet thickening associated with symptomatic thrombotic prosthetic valve obstruction: early complication following transcatheter aortic valve implantation
Locality in Theory Space
Locality is a guiding principle for constructing realistic quantum field
theories. Compactified theories offer an interesting context in which to think
about locality, since interactions can be nonlocal in the compact directions
while still being local in the extended ones. In this paper, we study locality
in "theory space", four-dimensional Lagrangians which are dimensional
deconstructions of five-dimensional Yang-Mills. In explicit ultraviolet (UV)
completions, one can understand the origin of theory space locality by the
irrelevance of nonlocal operators. From an infrared (IR) point of view, though,
theory space locality does not appear to be a special property, since the
lowest-lying Kaluza-Klein (KK) modes are simply described by a gauged nonlinear
sigma model, and locality imposes seemingly arbitrary constraints on the KK
spectrum and interactions. We argue that these constraints are nevertheless
important from an IR perspective, since they affect the four-dimensional cutoff
of the theory where high energy scattering hits strong coupling. Intriguingly,
we find that maximizing this cutoff scale implies five-dimensional locality. In
this way, theory space locality is correlated with weak coupling in the IR,
independent of UV considerations. We briefly comment on other scenarios where
maximizing the cutoff scale yields interesting physics, including theory space
descriptions of QCD and deconstructions of anti-de Sitter space.Comment: 40 pages, 11 figures; v2: references and clarifications added; v3:
version accepted by JHE
Insights Into the Effects of Mucosal Epithelial and Innate Immune Dysfunction in Older People on Host Interactions With Streptococcus pneumoniae
In humans, nasopharyngeal carriage of Streptococcus pneumoniae is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together, these kill over 500,000 people over the age of 70 years worldwide every year. Pneumococcal conjugate vaccines have been largely successful in reducing IPD in young children and have had considerable indirect impact in protection of older people in industrialized country settings (herd immunity). However, serotype replacement continues to threaten vulnerable populations, particularly older people in whom direct vaccine efficacy is reduced. The early control of pneumococcal colonization at the mucosal surface is mediated through a complex array of epithelial and innate immune cell interactions. Older people often display a state of chronic inflammation, which is associated with an increased mortality risk and has been termed ‘Inflammageing’. In this review, we discuss the contribution of an altered microbiome, the impact of inflammageing on human epithelial and innate immunity to S. pneumoniae, and how the resulting dysregulation may affect the outcome of pneumococcal infection in older individuals. We describe the impact of the pneumococcal vaccine and highlight potential research approaches which may improve our understanding of respiratory mucosal immunity during pneumococcal colonization in older individuals
Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer
Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer
c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation.
Sympathetic neurons depend on NGF binding to TrkA for their survival during vertebrate development. NGF deprivation initiates a transcription-dependent apoptotic response, which is suggested to require activation of the transcription factor c-Jun. Similarly, apoptosis can also be induced by selective activation of the p75 neurotrophin receptor. The transcriptional dependency of p75-mediated cell death has not been determined; however, c-Jun NH2-terminal kinase has been implicated as an essential component. Because the c-jun-null mutation is early embryonic lethal, thereby hindering a genetic analysis, we used the Cre-lox system to conditionally delete this gene. Sympathetic neurons isolated from postnatal day 1 c-jun-floxed mice were infected with an adenovirus expressing Cre recombinase or GFP and analyzed for their dependence on NGF for survival. Cre immunopositive neurons survived NGF withdrawal, whereas those expressing GFP or those uninfected underwent apoptosis within 48 h, as determined by DAPI staining. In contrast, brain-derived neurotrophic factor (BDNF) binding to p75 resulted in an equivalent level of apoptosis in neurons expressing Cre, GFP, and uninfected cells. Nevertheless, cycloheximide treatment prevented BDNF-mediated apoptosis. These results indicate that whereas c-jun is required for apoptosis in sympathetic neurons on NGF withdrawal, an alternate signaling pathway must be induced on p75 activation
The role of PET/CT in Cogan’s syndrome
We report on the case of a 60-year-old woman with complaints of fatigue, coughing, anorexia, atypical chest pain, recurrent fever, and also ear pain and hearing loss. A test for anti-neutrophil cytoplasmic antibody (ANCA) was myeloperoxidase positive with p-ANCA specificity. Laboratory acute phase parameters were increased. A 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography investigation showed pathological uptake in the aorta ascendens, with no other involvement of the large vessels. After therapy with methylprednisolon intravenously and later prednisolon orally with methothrexate, her general condition and hearing loss improved both subjectively and objectively. “Atypical” Cogan’s syndrome was diagnosed on the basis of sensorineural deafness with improvement on steroids and large-vessel vasculitis of the aortic arch
Direct high-precision measurement of the magnetic moment of the proton
The spin-magnetic moment of the proton is a fundamental property of
this particle. So far has only been measured indirectly, analysing the
spectrum of an atomic hydrogen maser in a magnetic field. Here, we report the
direct high-precision measurement of the magnetic moment of a single proton
using the double Penning-trap technique. We drive proton-spin quantum jumps by
a magnetic radio-frequency field in a Penning trap with a homogeneous magnetic
field. The induced spin-transitions are detected in a second trap with a strong
superimposed magnetic inhomogeneity. This enables the measurement of the
spin-flip probability as a function of the drive frequency. In each measurement
the proton's cyclotron frequency is used to determine the magnetic field of the
trap. From the normalized resonance curve, we extract the particle's magnetic
moment in units of the nuclear magneton . This
measurement outperforms previous Penning trap measurements in terms of
precision by a factor of about 760. It improves the precision of the forty year
old indirect measurement, in which significant theoretical bound state
corrections were required to obtain , by a factor of 3. By application
of this method to the antiproton magnetic moment the fractional
precision of the recently reported value can be improved by a factor of at
least 1000. Combined with the present result, this will provide a stringent
test of matter/antimatter symmetry with baryons.Comment: published in Natur
- …