249 research outputs found
A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc2 Disaccharide in Water
AbstractGlcNAc2 is the core disaccharide fragment present in Nâglycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because Nâglycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc2 by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methylâβâglycoside of GlcNAc2 in water with an unprecedented affinity of 160â
ÎźM, exceeding that of more structurally complex receptors reported in the literature. The tweezersâshaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between monoâ and disaccharides. Molecular modelling calculations supported by NOE data provided a threeâdimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor
Beneficial effect of sodium dichloroacetate in muscle cytochrome C oxidase deficiency
Beneficial Effect of Sodium Dichloroacetate in Muscle Cytochrome C Oxidase Deficienc
Quantum geometry and gravitational entropy
Most quantum states have wavefunctions that are widely spread over the
accessible Hilbert space and hence do not have a good description in terms of a
single classical geometry. In order to understand when geometric descriptions
are possible, we exploit the AdS/CFT correspondence in the half-BPS sector of
asymptotically AdS_5 x S^5 universes. In this sector we devise a
"coarse-grained metric operator" whose eigenstates are well described by a
single spacetime topology and geometry. We show that such half-BPS universes
have a non-vanishing entropy if and only if the metric is singular, and that
the entropy arises from coarse-graining the geometry. Finally, we use our
entropy formula to find the most entropic spacetimes with fixed asymptotic
moments beyond the global charges.Comment: 29 pages, 2 figures; references adde
RGS2 expression predicts amyloid-β sensitivity, MCI and Alzheimer's disease: genome-wide transcriptomic profiling and bioinformatics data mining
Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aβ neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aβ plaques. Here, we applied genome-wide transcriptomic profiling of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for identifying genes that predict sensitivity to Aβ. Real-time PCR validation identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling 2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Aβ sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with the patients' cognitive function. Lower RGS2 expression levels were also discovered in published expression data sets from postmortem AD brain tissues as well as in mild cognitive impairment and AD blood samples compared with controls. In conclusion, Aβ sensitivity phenotyping followed by transcriptomic profiling and published patient data mining identified reduced peripheral and brain expression levels of RGS2, a key regulator of G-protein-coupled receptor signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker (alongside other genes) toward early AD detection and future disease modifying therapeutics
Complex Matrix Model and Fermion Phase Space for Bubbling AdS Geometries
We study a relation between droplet configurations in the bubbling AdS
geometries and a complex matrix model that describes the dynamics of a class of
chiral primary operators in dual N=4 super Yang Mills (SYM). We show rigorously
that a singlet holomorphic sector of the complex matrix model is equivalent to
a holomorphic part of two-dimensional free fermions, and establish an exact
correspondence between the singlet holomorphic sector of the complex matrix
model and one-dimensional free fermions. Based on this correspondence, we find
a relation of the singlet holomorphic operators of the complex matrix model to
the Wigner phase space distribution. By using this relation and the AdS/CFT
duality, we give a further evidence that the droplets in the bubbling AdS
geometries are identified with those in the phase space of the one-dimensional
fermions. We also show that the above correspondence actually maps the
operators of N=4 SYM corresponding to the (dual) giant gravitons to the droplet
configurations proposed in the literature.Comment: 27 pages, 6 figures, some clarification, typos corrected, published
versio
The Library of Babel: On the origin of gravitational thermodynamics
We show that heavy pure states of gravity can appear to be mixed states to
almost all probes. For AdS_5 Schwarzschild black holes, our arguments are made
using the field theory dual to string theory in such spacetimes. Our results
follow from applying information theoretic notions to field theory operators
capable of describing very heavy states in gravity. For half-BPS states of the
theory which are incipient black holes, our account is exact: typical
microstates are described in gravity by a spacetime ``foam'', the precise
details of which are almost invisible to almost all probes. We show that
universal low-energy effective description of a foam of given global charges is
via certain singular spacetime geometries. When one of the specified charges is
the number of D-branes, the effective singular geometry is the half-BPS
``superstar''. We propose this as the general mechanism by which the effective
thermodynamic character of gravity emerges.Comment: LaTeX, 6 eps figures, uses young.sty and wick.sty; Version 2: typos
corrected, minor rewordings and clarifications, references adde
Isolated congenital heart block in undifferentiated connective tissue disease and in primary SjĂśgren's syndrome: a clinical study of 81 pregnancies in 41 patients
Objective: To study the incidence and the features of congenital heart block (CHB) in patients with undifferentiated connective tissue disease (UCTD) and primary SjĂśgren's syndrome (pSS). Methods: We studied 81 pregnancies of 41 women attending the Outpatients' Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61%) were affected with UCTD and 16 (39%) with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. Results: CHB was found in 2 out of the 46 (4,3%) pregnancies followed by our Staff and in 2 out of the 35 (5,7%) included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0,026). Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. Conclusion: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities
On dynamic network entropy in cancer
The cellular phenotype is described by a complex network of molecular
interactions. Elucidating network properties that distinguish disease from the
healthy cellular state is therefore of critical importance for gaining
systems-level insights into disease mechanisms and ultimately for developing
improved therapies. By integrating gene expression data with a protein
interaction network to induce a stochastic dynamics on the network, we here
demonstrate that cancer cells are characterised by an increase in the dynamic
network entropy, compared to cells of normal physiology. Using a fundamental
relation between the macroscopic resilience of a dynamical system and the
uncertainty (entropy) in the underlying microscopic processes, we argue that
cancer cells will be more robust to random gene perturbations. In addition, we
formally demonstrate that gene expression differences between normal and cancer
tissue are anticorrelated with local dynamic entropy changes, thus providing a
systemic link between gene expression changes at the nodes and their local
network dynamics. In particular, we also find that genes which drive
cell-proliferation in cancer cells and which often encode oncogenes are
associated with reductions in the dynamic network entropy. In summary, our
results support the view that the observed increased robustness of cancer cells
to perturbation and therapy may be due to an increase in the dynamic network
entropy that allows cells to adapt to the new cellular stresses. Conversely,
genes that exhibit local flux entropy decreases in cancer may render cancer
cells more susceptible to targeted intervention and may therefore represent
promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte
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