Neutron Scattering and Its Application to Strongly Correlated Systems

Neutron scattering is a powerful probe of strongly correlated systems. It can directly detect common phenomena such as magnetic order, and can be used to determine the coupling between magnetic moments through measurements of the spin-wave dispersions. In the absence of magnetic order, one can detect diffuse scattering and dynamic correlations. Neutrons are also sensitive to the arrangement of atoms in a solid (crystal structure) and lattice dynamics (phonons). In this chapter, we provide an introduction to neutrons and neutron sources. The neutron scattering cross section is described and formulas are given for nuclear diffraction, phonon scattering, magnetic diffraction, and magnon scattering. As an experimental example, we describe measurements of antiferromagnetic order, spin dynamics, and their evolution in the La(2-x)Ba(x)CuO(4) family of high-temperature superconductors.Comment: 31 pages, chapter for "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancin

Guyon's canal syndrome due to tortuous ulnar artery with DeQuervain stenosing tenosynovitis, ligamentous injuries and dorsal intercalated segmental instability syndrome, a rare presentation: a case report

The Guyon's canal syndrome is a well known clinical entity and may have significant impact on patient's quality of life. We report a case of 43-year-old male who presented with complaints of pain and numbness in right hand and difficulty in writing for past one month. On imaging diagnosis of Guyon's canal syndrome because of tortuous ulnar artery was made with additional findings of DeQuervain's stenosing tenosynovitis and dorsal intercalated segmental instability syndrome with ligamentous injury and subsequently these were confirmed on surgery

Spatially modulated "Mottness" in La2-xBaxCuO4

Stripe phases were predicted to arise in doped antiferromagnets through competition between magnetism and the kinetic energy of mobile carriers (typically holes). In copper-oxides the main experimental evidence for stripes is neutron scattering from La1.48Nd0.4Sr0.12CuO4 (LNSCO) and La1.875Ba0.125CuO4 (LBCO) which reveals coexisting static spin and charge order whose wavelengths differ by a factor of two, reminiscent of charged rivers separating regions of oppositely-phased antiferromagnetism. A neutron is an electrically neutral object, however, so does not detect charge but rather its associated lattice distortion ; it is not known if the "stripe" phase in LNSCO and LBCO actually involves ordering of the doped holes. Here we present a study of the charge order in LBCO with resonant soft x-ray scattering (RSXS). We observe giant resonances at both the mobile carrier and upper-Hubbard band features in the OK edge. These demonstrate a substantial modulation in the doped hole density as well as the amount of spectral weight near the correlated gap, i.e. the degree of "Mottness". The peak-to-trough amplitude of the valence modulation is estimated to be 0.063 holes, which if interpreted with a model of the stripe form factor suggests an integrated area of 0.59 holes under a single stripe. While only an estimate, this number agrees with what is expected for half-filled stripes.Comment: 12 pages, 4 figures, to appear in Nature Physic

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG

Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1-Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer–heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1–VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy

New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options

Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can be surgically repaired, joint injury triggers a chronic remodeling process in cartilage and other joint tissues that ultimately manifests as osteoarthritis in a majority of cases. The objective of the present review is to summarize information on pathogenetic mechanisms involved in the acute and chronic consequences of joint trauma and discuss potential pharmacological interventions. The focus of the review is on the early events that follow joint trauma since therapies for posttraumatic joint inflammation are not available and this represents a unique window of opportunity to limit chronic consequences

The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses

Abstract Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are dynamic modules enriched in subset of lipids and specialized proteins that determine their structure and functions. The MERCs regulate lipid transfer, autophagosome formation, mitochondrial fission, Ca2+ homeostasis and apoptosis. Since these functions are essential for cell biology, it is therefore not surprising that MERCs also play a critical role in organ physiology among which the immune system stands by its critical host defense function. This defense system must discriminate and tolerate host cells and beneficial commensal microorganisms while eliminating pathogenic ones in order to preserve normal homeostasis. To meet this goal, the immune system has two lines of defense. First, the fast acting but unspecific innate immune system relies on anatomical physical barriers and subsets of hematopoietically derived cells expressing germline-encoded receptors called pattern recognition receptors (PRR) recognizing conserved motifs on the pathogens. Second, the slower but very specific adaptive immune response is added to complement innate immunity. Adaptive immunity relies on another set of specialized cells, the lymphocytes, harboring receptors requiring somatic recombination to be expressed. Both innate and adaptive immune cells must be activated to phagocytose and process pathogens, migrate, proliferate, release soluble factors and destroy infected cells. Some of these functions are strongly dependent on lipid transfer, autophagosome formation, mitochondrial fission, and Ca2+ flux; this indicates that MERCs could regulate immunity

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700