Determining the Quantitative Principles of T Cell Response to Antigenic Disparity in Stem Cell Transplantation

Alloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft vs. host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 generally presenting a greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and determine the risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation

Bonding in Mercury-Alkali Molecules: Orbital-driven van der Waals Complexes

The bonding situation in mercury-alkali diatomics HgA (2Σ+) (A = Li, Na, K, Rb) has been investigated employing the relativistic all-electron method Normalized Elimination of the Small Component (NESC), CCSD(T), and augmented VTZ basis sets. Although Hg,A interactions are typical of van der Waals complexes, trends in calculated De values can be explained on the basis of a 3-electron 2-orbital model utilizing calculated ionization potentials and the De values of HgA+(1Σ+) diatomics. HgA molecules are identified as orbital-driven van der Waals complexes. The relevance of results for the understanding of the properties of liquid alkali metal amalgams is discussed

The Politics of Pleasure: Promenading on the Corniche and Beachgoing

Can the pleasures of young Palestinian women from refugee camps in promenading on the Beirut seaside Corniche on a warm summer evening be political? Or days spent at women-only beaches? If so, how do we understand such pleasure as everyday practices, as a politics of the present moment, or conversely (or simultaneously) as mechanisms of being co-opted into a broader apparatus of consumerist ideology and capitalist complacency? Drawing on ethnographic research over 2 years I argue that these moments of pleasure are caesuras in the massive apparatus of power – welded from strands of work, neoliberal practice, nationalist certitudes and political exclusion – which binds these women. These acts of pleasure cannot easily be categorised as ‘resistance’ but I argue that they should not facilely be considered reinforcements of hegemonic control either. They are momentary and ephemeral recognitions of ordinary life lived in hard times, attempts at clawing back an instant of joy from the drudgery of the everyday, and a surrender to the enjoyment of conviviality in public and urban spaces. If they are at all political, they are so because such conviviality is ever harder to sustain in the calamity of hopelessness that characterises so much politics today

Crustal structure of active deformation zones in Africa: Implications for global crustal processes

The Cenozoic East African rift (EAR), Cameroon Volcanic Line (CVL), and Atlas Mountains formed on the slow-moving African continent, which last experienced orogeny during the Pan-African. We synthesize primarily geophysical data to evaluate the role of magmatism in shaping Africa's crust. In young magmatic rift zones, melt and volatiles migrate from the asthenosphere to gas-rich magma reservoirs at the Moho, altering crustal composition and reducing strength. Within the southernmost Eastern rift, the crust comprises ~20% new magmatic material ponded in the lower crust sills, and intruded as sills and dikes at shallower depths. In the Main Ethiopian rift, intrusions comprise 30% of the crust below axial zones of dike-dominated extension. In the incipient rupture zones of the Afar rift, magma intrusions fed from crustal magma chambers beneath segment centers create new columns of mafic crust, as along slow-spreading ridges. Our comparisons suggest that transitional crust, including seaward-dipping sequences, is created as progressively smaller screens of continental crust are heated and weakened by magma intrusion into 15-20 km-thick crust. In the 30Ma-Recent CVL, which lacks a hotspot age-progression, extensional forces are small, inhibiting the creation and rise of magma into the crust. In the Atlas orogen, localized magmatism follows the strike of the Atlas Mountains from the Canary Islands hotspot towards the Alboran Sea. CVL and Atlas magmatism has had minimal impact on crustal structure. Our syntheses show that magma and volatiles are migrating from the asthenosphere through the plates, modifying rheology and contributing significantly to global carbon and water fluxes

Somatic ‘Soluble’ Adenylyl Cyclase Isoforms Are Unaffected in Sacytm1Lex/Sacytm1Lex ‘Knockout’ Mice

BACKGROUND: Mammalian Soluble adenylyl cyclase (sAC, Adcy10, or Sacy) represents a source of the second messenger cAMP distinct from the widely studied, G protein-regulated transmembrane adenylyl cyclases. Genetic deletion of the second through fourth coding exons in Sacy(tm1Lex)/Sacy(tm1Lex) knockout mice results in a male sterile phenotype. The absence of any major somatic phenotype is inconsistent with the variety of somatic functions identified for sAC using pharmacological inhibitors and RNA interference. PRINCIPAL FINDINGS: We now use immunological and molecular biological methods to demonstrate that somatic tissues express a previously unknown isoform of sAC, which utilizes a unique start site, and which 'escapes' the design of the Sacy(tm1Lex) knockout allele. CONCLUSIONS/SIGNIFICANCE: These studies reveal increased complexity at the sAC locus, and they suggest that the known isoforms of sAC play a unique function in male germ cells

Droppings From Captive Coturnix coturnix (Galliformes: Phasianidae) as a Fly Breeding Resource

The aim of this study was to describe the fauna of flies associated with captive Coturnix coturnix (L.) (Galliformes: Phasianidae) droppings. Samples of 150 g of quail droppings were exposed in the quail house for 48 h in plastic containers to promote eventual access of flies, and then placed in emergence traps. The number of adults and species emerging was recorded daily. This procedure was carried out in spring 2008 and spring and autumn 2009. In total, 2,138 adults belonging to Muscidae, Calliphoridae, Piophilidae, Phoridae, Fanniidae, and Milichiidae families were collected. The most numerous family was Muscidae (representing >82% of the total specimens), with Musca domestica L. being the most abundant species followed by Ophyra aenescens (Wiedemann) (both Diptera: Muscidae). Quail breeding should include adequate droppings management policies to avoid potential sanitary issues related to fly productionFil: Battan Horenstein, Moira. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Diversidad y Ecologia Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Lynch Ianello, I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (p). Grupo Vinculado Centro de Relevamiento y Evaluacion de Recursos Agricolas y Naturales; ArgentinaFil: de Dió, B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (p). Grupo Vinculado Centro de Relevamiento y Evaluacion de Recursos Agricolas y Naturales; ArgentinaFil: Gleiser, Raquel M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (p). Grupo Vinculado Centro de Relevamiento y Evaluacion de Recursos Agricolas y Naturales; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentin

Lees and Moonshine: Remembering Richard III, 1485-1635

Published version of article deposited in accordance with Sherpa Romeo guidelines. © University of Chicago Press, 2010publication-status: AcceptedNot long after Shakespeare’s birth (1564) the last witnesses to the reign of Richard III (1483-85) would have reached the end of their lives. Richard III (c. 1592) occupies a distinctive historical moment in relation to its subject – a period after the extinction of living memory, but still within the horizon of communicative memory, the period in which stories and recollections may be transmitted across multiple generations. This essay explores how memories and “postmemories” of Richard’s reign were preserved, transmitted and transformed over the course of the sixteenth century and into the seventeenth. Whilst reflecting the powerful influence of emerging contexts including the Reformation and, ultimately, Shakespeare’s play, these memories remained distinct from and sometimes at odds with textual history. They survived because they offered their bearers a resource for interpreting and resisting the predicaments of the present, from the problem of tyranny to the legacies of the Reformation

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Physiological Sensing of Carbon Dioxide/Bicarbonate/pH via Cyclic Nucleotide Signaling

Carbon dioxide (CO2) is produced by living organisms as a byproduct of metabolism. In physiological systems, CO2 is unequivocally linked with bicarbonate (HCO3−) and pH via a ubiquitous family of carbonic anhydrases, and numerous biological processes are dependent upon a mechanism for sensing the level of CO2, HCO3, and/or pH. The discovery that soluble adenylyl cyclase (sAC) is directly regulated by bicarbonate provided a link between CO2/HCO3/pH chemosensing and signaling via the widely used second messenger cyclic AMP. This review summarizes the evidence that bicarbonate-regulated sAC, and additional, subsequently identified bicarbonate-regulate nucleotidyl cyclases, function as evolutionarily conserved CO2/HCO3/pH chemosensors in a wide variety of physiological systems