Signature of stripe pinning in optical conductivity

The response of charge stripes to an external electric field applied perpendicular to the stripe direction is studied within a diagrammatic approach for both weak and strong pinning by random impurities. The sound-like mode of the stripes described as elastic strings moves to finite frequency due to impurity pinning. By calculating the optical conductivity we determine this characteristic energy scale for both a single stripe and an array of interacting stripes. The results explain the anomalous far-infrared peak observed recently in optical-conductivity measurements on cuprates.Comment: Revised version, to appear in Phys. Rev.

Housing stability and diabetes among people living in New York city public housing

Public housing provides affordable housing and, potentially, housing stability for low-income families. Housing stability may be associated with lower incidence or prevalence and better management of a range of health conditions through many mechanisms. We aimed to test the hypotheses that public housing residency is associated with both housing stability and reduced risk of diabetes incidence, and the relationship between public housing and diabetes risk varies by levels of housing stability. Using 2004-16 World Trade Center Health Registry data, we compared outcomes (housing stability measured by sequence analysis of addresses, self-reported diabetes diagnoses) between 730 New York City public housing residents without prevalent diabetes at baseline and 730 propensity score-matched non-public housing residents. Sequence analysis found 3 mobility patterns among all 1460 enrollees, including stable housing (65%), limited mobility (27%), and unstable housing patterns (8%). Public housing residency was associated with stable housing over 12 years. Diabetes risk was not associated with public housing residency; however, among those experiencing housing instability, a higher risk of diabetes was found among public housing versus non-public housing residents. Of those stably housed, the association remained insignificant. These findings provide important evidence for a health benefit of public housing via housing stability among people living in public housing

Similarity of slow stripe fluctations between Sr-doped cuprates and oxygen-doped nickelates

Stripe fluctuations in La2NiO4.17 have been studied by 139La NMR using the field and temperature dependence of the linewidth and relaxation rates. In the formation process of the stripes the NMR line intensity is maximal below 230K, starts to diminish around 140K, disappears around 50K and recovers at 4K. These results are shown to be consistent with, but completely complementary to neutron measurements, and to be generic for oxygen doped nickelates and underdoped cuprates.Comment: 4 pages including 4 figure

GUIDANCE: a web server for assessing alignment confidence scores

Evaluating the accuracy of multiple sequence alignment (MSA) is critical for virtually every comparative sequence analysis that uses an MSA as input. Here we present the GUIDANCE web-server, a user-friendly, open access tool for the identification of unreliable alignment regions. The web-server accepts as input a set of unaligned sequences. The server aligns the sequences and provides a simple graphic visualization of the confidence score of each column, residue and sequence of an alignment, using a color-coding scheme. The method is generic and the user is allowed to choose the alignment algorithm (ClustalW, MAFFT and PRANK are supported) as well as any type of molecular sequences (nucleotide, protein or codon sequences). The server implements two different algorithms for evaluating confidence scores: (i) the heads-or-tails (HoT) method, which measures alignment uncertainty due to co-optimal solutions; (ii) the GUIDANCE method, which measures the robustness of the alignment to guide-tree uncertainty. The server projects the confidence scores onto the MSA and points to columns and sequences that are unreliably aligned. These can be automatically removed in preparation for downstream analyses. GUIDANCE is freely available for use at http://guidance.tau.ac.il

Mid-Infrared Conductivity from Mid-Gap States Associated with Charge Stripes

The optical conductivity of La(2-x)Sr(x)NiO(4) has been interpreted in various ways, but so far the proposed interpretations have neglected the fact that the holes doped into the NiO(2) planes order in diagonal stripes, as established by neutron and X-ray scattering. Here we present a study of optical conductivity in La(2)NiO(4+d) with d=2/15, a material in which the charge stripes order three-dimensionally. We show that the conductivity can be decomposed into two components, a mid-infrared peak that we attribute to transitions from the filled valence band into empty mid-gap states associated with the stripes, and a Drude peak that appears at higher temperatures as carriers are thermally excited into the mid-gap states. The shift of the mid-IR peak to lower energy with increasing temperature is explained in terms of the Franck-Condon effect. The relevance of these results to understanding the optical conductivity in the cuprates is discussed.Comment: final version of paper (minor changes from previous version

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society

Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment

Some mature natural killer (NK) cells cannot be inhibited by major histocompatibility complex (MHC) I molecules, either because they lack corresponding inhibitory receptors or because the host lacks the corresponding MHC I ligands for the receptors. Such NK cells nevertheless remain self-tolerant and exhibit a generalized hyporesponsiveness to stimulation through activating receptors. To address whether NK cell responsiveness is set only during the NK cell differentiation process, we transferred mature NK cells from wild-type (WT) to MHC I–deficient hosts or vice versa. Remarkably, mature responsive NK cells from WT mice became hyporesponsive after transfer to MHC I–deficient mice, whereas mature hyporesponsive NK cells from MHC I–deficient mice became responsive after transfer to WT mice. Altered responsiveness was evident among mature NK cells that had not divided in the recipient animals, indicating that the cells were mature before transfer and that alterations in activity did not require cell division. Furthermore, the percentages of NK cells expressing KLRG1, CD11b, CD27, and Ly49 receptors specific for H-2b were not markedly altered after transfer. Thus, the functional activity of mature NK cells can be reset when the cells are exposed to a changed MHC environment. These findings have important implications for how NK cell functions may be curtailed or enhanced in the context of disease

Promoting the use of Motor Function Measure (MFM) as outcome measure in patients with Duchenne Muscular Dystrophy (DMD) treated by corticosteroids

ObjectivesAssessing muscle function is a key step in measuring changes and evaluating the outcomes of therapeutic interventions in Duchenne Muscular Dystrophy (DMD). Regarding the large use of corticosteroids (CS) in this population to delay the loss of function, our goal was to monitor the evolution of motor function in patients with DMD treated by corticosteroids (CS) and to study the responsiveness of Motor Function Measure (MFM) in this population in order to provide an estimation of the number of subject needed for a clinical trial.MethodA total of 76 patients with DMD, aged 5.9 to 11.8 years, with at least 6 months of follow-up and 2 MFM were enrolled, 30 in the CS treated group (8±1.62 y) and 46 in the untreated group (7.91±1.50 y).ResultsThe relationship between MFM scores and age was studied in CS treated patients and untreated patients. The evolution of these scores was compared between groups, on a 6-, 12- and 24-month period by calculating slopes of change and standardized response mean. At 6, 12 and 24 months, significant differences in the mean score change were found, for all MFM scores, between CS treated patients and untreated patients. For D1 subscore specifically, at 6 months, the increase is significant in the treated group (11.3±14%/y; SRM 0.8) while a decrease is observed in the untreated group (–17.8±17.7%/y; SRM 1). At 12 and 24 months, D1 subscore stabilized for treated patients but declined significantly for untreated boys (–15.5±15.1%/y; SRM 1 at 12 mo and–18.8±7.1%/y; SRM 2.6 at 24 mo). 21 patients lost the ability to walk during the study: 6 in the CS treated group (25% at 24 months, mean age: 10.74±1.28 y) and 15 in the untreated group (64.71% at 24 months, mean age: 9.20±1.78 y).Discussion and conclusionPatients with DMD treated by CS present a different course of the disease described in this paper using the MFM. Based on these results, an estimation of the number of patients needed for clinical trial could be done

Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis

Background: Tamoxifen (TAM) is an important cancer therapeutic and an experimental tool for effecting genetic recombination using the inducible Cre-Lox technique. Despite its widespread use in the clinic and laboratory, we know little about its effects on the nervous system. This is of significant concern because TAM, via unknown mechanisms, induces cognitive impairment in humans. A hallmark of cellular stress is induction of Activating Transcription Factor 3 (Atf3), and so to determine whether TAM induces cellular stress in the adult nervous system, we generated a knock-in mouse in which Atf3 promoter activity drives transcription of TAM-dependent Cre recombinase (Cre-ERT2); when crossed with tdtomato reporter mice, Atf3 induction results in robust and permanent genetic labeling of cells in which it is up-regulated even transiently. Results: We found that granular neurons of the olfactory bulb and dentate gyrus, vascular cells and ependymal cells throughout the brain, and peripheral sensory neurons expressed tdtomato in response to TAM treatment. We also show that TAM induced Atf3 up-regulation through inhibition of cholesterol epoxide hydrolase (ChEH): reporter expression was mitigated by delivery in vitamin E-rich wheat germ oil (vitamin E depletes ChEH substrates), and was partially mimicked by a ChEH-specific inhibitor. Conclusions: This work demonstrates that TAM stresses cells of the adult central and peripheral nervous systems and highlights concerns about clinical and experimental use of TAM. We propose TAM administration in vitamin E-rich vehicles such as wheat germ oil as a simple remedy