The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation.

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination

Urinary protein profiling in hyperactive delirium and non-delirium cardiac surgery ICU patients

Contains fulltext : 92532.pdf (publisher's version ) (Open Access

Surfactant status and respiratory outcome in premature infants receiving late surfactant treatment.

BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p < 0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r = 0.50, p < 0.00001) and inversely related to total protein (r = 0.39, p < 0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant. CONCLUSIONS:We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant

Robot rights? Towards a social-relational justification of moral consideration \ud

Should we grant rights to artificially intelligent robots? Most current and near-future robots do not meet the hard criteria set by deontological and utilitarian theory. Virtue ethics can avoid this problem with its indirect approach. However, both direct and indirect arguments for moral consideration rest on ontological features of entities, an approach which incurs several problems. In response to these difficulties, this paper taps into a different conceptual resource in order to be able to grant some degree of moral consideration to some intelligent social robots: it sketches a novel argument for moral consideration based on social relations. It is shown that to further develop this argument we need to revise our existing ontological and social-political frameworks. It is suggested that we need a social ecology, which may be developed by engaging with Western ecology and Eastern worldviews. Although this relational turn raises many difficult issues and requires more work, this paper provides a rough outline of an alternative approach to moral consideration that can assist us in shaping our relations to intelligent robots and, by extension, to all artificial and biological entities that appear to us as more than instruments for our human purpose

Pinning quantum phase transition for a Luttinger liquid of strongly interacting bosons

One of the most remarkable results of quantum mechanics is the fact that many-body quantum systems may exhibit phase transitions even at zero temperature. Quantum fluctuations, deeply rooted in Heisenberg's uncertainty principle, and not thermal fluctuations, drive the system from one phase to another. Typically, the relative strength of two competing terms in the system's Hamiltonian is changed across a finite critical value. A well-known example is the Mott-Hubbard quantum phase transition from a superfluid to an insulating phase, which has been observed for weakly interacting bosonic atomic gases. However, for strongly interacting quantum systems confined to lower-dimensional geometry a novel type of quantum phase transition may be induced for which an arbitrarily weak perturbation to the Hamiltonian is sufficient to drive the transition. Here, for a one-dimensional (1D) quantum gas of bosonic caesium atoms with tunable interactions, we observe the commensurate-incommensurate quantum phase transition from a superfluid Luttinger liquid to a Mott-insulator. For sufficiently strong interactions, the transition is induced by adding an arbitrarily weak optical lattice commensurate with the atomic granularity, which leads to immediate pinning of the atoms. We map out the phase diagram and find that our measurements in the strongly interacting regime agree well with a quantum field description based on the exactly solvable sine-Gordon model. We trace the phase boundary all the way to the weakly interacting regime where we find good agreement with the predictions of the 1D Bose-Hubbard model. Our results open up the experimental study of quantum phase transitions, criticality, and transport phenomena beyond Hubbard-type models in the context of ultracold gases

A review for clinical outcomes research: hypothesis generation, data strategy, and hypothesis-driven statistical analysis

In recent years, more and more large, population-level databases have become available for clinical research. The size and complexity of these databases often present a methodological challenge for investigators. We propose that a “protocol” may facilitate the research process using these databases. In addition, much like the structured History and Physical (H&P) helps the audience appreciate the details of a patient case more systematically, a formal outcomes research protocol can also help in the systematic evaluation of an outcomes research manuscript

Th17 Cells and IL-17 in Protective Immunity to Vaginal Candidiasis

Background: Th17 cells play a major role in coordinating the host defence in oropharyngeal candidiasis. In this study we investigated the involvement of the Th17 response in an animal model of vulvovaginal candidiasis (VVC). Methods: To monitor the course of infection we exploited a new in vivo imaging technique. Results: i) The progression of VVC leads to a strong influx of neutrophils in the vagina soon after the challenge which persisted despite the resolution of infection; ii) IL-17, produced by vaginal cells, particularly CD4 T cells, was detected in the vaginal wash during the infection, reaching a maximum 14 days after the challenge; iii) The amount and kinetics of IL-23 in vaginal fluids were comparable to those in vaginal cells; iv) The inhibition of Th17 differentiation led to significant inhibition of IL-17 production with consequent exacerbation of infection; v) An increased production of bdefensin 2 was manifested in cells of infected mice. This production was strongly reduced when Th17 differentiation was inhibited and was increased by rIL-17 treatment. Conclusions: These results imply that IL-17 and Th17, along with innate antimicrobial factors, have a role in the immune response to vaginal candidiasis

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

Protégé: A Tool for Managing and Using Terminology in Radiology Applications

The development of standard terminologies such as RadLex is becoming important in radiology applications, such as structured reporting, teaching file authoring, report indexing, and text mining. The development and maintenance of these terminologies are challenging, however, because there are few specialized tools to help developers to browse, visualize, and edit large taxonomies. Protégé (http://protege.stanford.edu) is an open-source tool that allows developers to create and to manage terminologies and ontologies. It is more than a terminology-editing tool, as it also provides a platform for developers to use the terminologies in end-user applications. There are more than 70,000 registered users of Protégé who are using the system to manage terminologies and ontologies in many different domains. The RadLex project has recently adopted Protégé for managing its radiology terminology. Protégé provides several features particularly useful to managing radiology terminologies: an intuitive graphical user interface for navigating large taxonomies, visualization components for viewing complex term relationships, and a programming interface so developers can create terminology-driven radiology applications. In addition, Protégé has an extensible plug-in architecture, and its large user community has contributed a rich library of components and extensions that provide much additional useful functionalities. In this report, we describe Protégé’s features and its particular advantages in the radiology domain in the creation, maintenance, and use of radiology terminology