The Meissner effect in a strongly underdoped cuprate above its critical temperature

The Meissner effect and the associated perfect "bulk" diamagnetism together with zero resistance and gap opening are characteristic features of the superconducting state. In the pseudogap state of cuprates unusual diamagnetic signals as well as anomalous proximity effects have been detected but a Meissner effect has never been observed. Here we have probed the local diamagnetic response in the normal state of an underdoped La1.94Sr0.06CuO4 layer (up to 46 nm thick, critical temperature Tc' < 5 K) which was brought into close contact with two nearly optimally doped La1.84Sr0.16CuO4 layers (Tc \approx 32 K). We show that the entire 'barrier' layer of thickness much larger than the typical c axis coherence lengths of cuprates exhibits a Meissner effect at temperatures well above Tc' but below Tc. The temperature dependence of the effective penetration depth and superfluid density in different layers indicates that superfluidity with long-range phase coherence is induced in the underdoped layer by the proximity to optimally doped layers; however, this induced order is very sensitive to thermal excitation.Comment: 7 pages, 7 figures + Erratu

Assessment of surface roughness and blood rheology on local coronary hemodynamics: a multi-scale computational fluid dynamics study

The surface roughness of the coronary artery is associated with the onset of atherosclerosis. The study applies, for the first time, the micro-scale variation of the artery surface to a 3D coronary model, investigating the impact on haemodynamic parameters which are indicators for atherosclerosis. The surface roughness of porcine coronary arteries have been detailed based on optical microscopy and implemented into a cylindrical section of coronary artery. Several approaches to rheology are compared to determine the benefits/limitations of both single and multiphase models for multi-scale geometry. Haemodynamic parameters averaged over the rough/smooth sections are similar; however, the rough surface experiences a much wider range, with maximum wall shear stress greater than 6 Pa compared to the approximately 3 Pa on the smooth segment. This suggests the smooth-walled assumption may neglect important near-wall haemodynamics. While rheological models lack sufficient definition to truly encompass the micro-scale effects occurring over the rough surface, single-phase models (Newtonian and non-Newtonian) provide numerically stable and comparable results to other coronary simulations. Multiphase models allow for phase interactions between plasma and red blood cells which is more suited to such multi-scale models. These models require additional physical laws to govern advection/aggregation of particulates in the near-wall region

Motion in the north Iceland volcanic rift zone accommodated by bookshelf faulting

Along mid-ocean ridges the extending crust is segmented1 on length scales of 10–1,000 km. Where rift segments are offset from one another, motion between segments is accommodated by transform faults that are oriented orthogonally to the main rift axis. Where segments overlap, non-transform offsets with a variety of geometries2 accommodate shear motions. Here we use micro-seismic data to analyse the geometries of faults at two overlapping rift segments exposed on land in north Iceland. Between the rift segments, we identify a series of faults that are aligned sub-parallel to the orientation of the main rift. These faults slip through left-lateral strike-slip motion. Yet, movement between the overlapping rift segments is through right-lateral motion. Together, these motions induce a clockwise rotation of the faults and intervening crustal blocks in a motion that is consistent with a bookshelf-faulting mechanism, named after its resemblance to a tilting row of books on a shelf3. The faults probably reactivated existing crustal weaknesses, such as dyke intrusions, that were originally oriented parallel to the main rift and have since rotated about 15° clockwise. Reactivation of pre-existing, rift-parallel weaknesses contrasts with typical mid-ocean ridge transform faults and is an important illustration of a non-transform offset accommodating shear motion between overlapping rift segments

High Resolution Intravital Imaging of Subcellular Structures of Mouse Abdominal Organs Using a Microstage Device

Intravital imaging of brain and bone marrow cells in the skull with subcellular resolution has revolutionized neurobiology, immunology and hematology. However, the application of this powerful technology in studies of abdominal organs has long been impeded by organ motion caused by breathing and heartbeat. Here we describe for the first time a simple device designated ‘microstage’ that effectively reduces organ motions without causing tissue lesions. Combining this microstage device with an upright intravital laser scanning microscope equipped with a unique stick-type objective lens, the system enables subcellular-level imaging of abdominal organs in live mice. We demonstrate that this technique allows for the quantitative analysis of subcellular structures and gene expressions in cells, the tracking of intracellular processes in real-time as well as three-dimensional image construction in the pancreas and liver of the live mouse. As the aforementioned analyses based on subcellular imaging could be extended to other intraperitoneal organs, the technique should offer great potential for investigation of physiological and disease-specific events of abdominal organs. The microstage approach adds an exciting new technique to the in vivo imaging toolbox

Feedback Inhibition in the PhoQ/PhoP Signaling System by a Membrane Peptide

The PhoQ/PhoP signaling system responds to low magnesium and the presence of certain cationic antimicrobial peptides. It regulates genes important for growth under these conditions, as well as additional genes important for virulence in many gram-negative pathogens. PhoQ is a sensor kinase that phosphorylates and activates the transcription factor PhoP. Since feedback inhibition is a common theme in stress-response circuits, we hypothesized that some members of the PhoP regulon may play such a role in the PhoQ/PhoP pathway. We therefore screened for PhoP-regulated genes that mediate feedback in this system. We found that deletion of mgrB (yobG), which encodes a 47 amino acid peptide, results in a potent increase in PhoP-regulated transcription. In addition, over-expression of mgrB decreased transcription at both high and low concentrations of magnesium. Localization and bacterial two-hybrid studies suggest that MgrB resides in the inner-membrane and interacts directly with PhoQ. We further show that MgrB homologs from Salmonella typhimurium and Yersinia pestis also repress PhoP-regulated transcription in these organisms. In cell regulatory circuits, feedback has been associated with modulating the induction kinetics and/or the cell-to-cell variability in response to stimulus. Interestingly, we found that elimination of MgrB-mediated feedback did not have a significant effect on the kinetics of reporter protein production and did not decrease the variability in expression among cells. Our results indicate MgrB is a broadly conserved membrane peptide that is a critical mediator of negative feedback in the PhoQ/PhoP circuit. This new regulator may function as a point of control that integrates additional input signals to modulate the activity of this important signaling system

Five-year mortality in a cohort of people with schizophrenia in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is associated with a two to three fold excess mortality. Both natural and unnatural causes were reported. However, there is dearth of evidence from low and middle income (LAMIC) countries, particularly in Africa. To our knowledge this is the first community based report from Africa.</p> <p>Methods</p> <p>We followed a cohort of 307 (82.1% males) patients with schizophrenia for five years in Butajira, rural Ethiopia. Mortality was recorded using broad rating schedule as well as verbal autopsy. Standardized Mortality Ratio (SMR) was calculated using the mortality in the demographic and surveillance site as a reference.</p> <p>Result</p> <p>Thirty eight (12.4%) patients, 34 men (11.1%) and 4 women (1.3%), died during the five-year follow up period. The mean age (SD) of the deceased for both sexes was 35 (7.35). The difference was not statistically significant (p = 0.69). It was 35.3 (7.4) for men and 32.3 (6.8) for women. The most common cause of death was infection, 18/38 (47.4%) followed by severe malnutrition, 5/38 (13.2%) and suicide 4/38 (10.5%). The overall SMR was 5.98 (95% CI = 4.09 to7.87). Rural residents had lower mortality with adjusted hazard ratio (HR) of 0.30 (95% CI = 0.12-0.69) but insidious onset and antipsychotic treatment for less than 50% of the follow up period were associated with higher mortality, adjusted HR 2.37 (95% CI = 1.04-5. 41) and 2.66(1.054-6.72) respectively.</p> <p>Conclusion</p> <p>The alarmingly high mortality observed in this patient population is of major concern. Most patients died from potentially treatable conditions. Improving medical and psychiatric care as well as provision of basic needs is recommended.</p

Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672

Breast MRI: guidelines from the European Society of Breast Imaging

The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)

Structural genomics target selection for the New York consortium on membrane protein structure

The New York Consortium on Membrane Protein Structure (NYCOMPS), a part of the Protein Structure Initiative (PSI) in the USA, has as its mission to establish a high-throughput pipeline for determination of novel integral membrane protein structures. Here we describe our current target selection protocol, which applies structural genomics approaches informed by the collective experience of our team of investigators. We first extract all annotated proteins from our reagent genomes, i.e. the 96 fully sequenced prokaryotic genomes from which we clone DNA. We filter this initial pool of sequences and obtain a list of valid targets. NYCOMPS defines valid targets as those that, among other features, have at least two predicted transmembrane helices, no predicted long disordered regions and, except for community nominated targets, no significant sequence similarity in the predicted transmembrane region to any known protein structure. Proteins that feed our experimental pipeline are selected by defining a protein seed and searching the set of all valid targets for proteins that are likely to have a transmembrane region structurally similar to that of the seed. We require sequence similarity aligning at least half of the predicted transmembrane region of seed and target. Seeds are selected according to their feasibility and/or biological interest, and they include both centrally selected targets and community nominated targets. As of December 2008, over 6,000 targets have been selected and are currently being processed by the experimental pipeline. We discuss how our target list may impact structural coverage of the membrane protein space