BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

A review of the British Society for Histocompatibility and Immunogenetics (BSHI) "Guideline for selection and HLA matching of related, adult unrelated donors and umbilical cord units for haematopoietic progenitor cell transplantation" was undertaken by a BSHI appointed writing committee. Literature searches were performed, and the data extracted were presented as recommendations according to the GRADE nomenclature

Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport.

Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the serotonin reuptake transporter (SERT). Although some clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well understood mechanistically and useful in vitro data is limited. We sought to determine whether the inhibitory effects of citalopram on platelets are mediated via its pharmacological inhibition of 5-HT transport. We quantified the inhibitory potency of (RS)-, (R)- and (S)-citalopram on platelet function. If SERT blockade is the primary mechanism for citalopram-mediated platelet inhibition, these potencies should show quantitative congruence with inhibition of 5-HT uptake. Our data show that citalopram inhibits platelet aggregation, adhesion and thromboxane production with no difference in potency between (R)- and (S)-isomers. By contrast, citalopram had a eudysmic ratio of approximately 17 (S > R) for SERT blockade. Furthermore, nanomolar concentrations of citalopram inhibited 5-HT uptake into platelets but had no effect on other platelet functions, which were inhibited by micromolar concentrations. Our data indicate that citalopram-induced inhibition of platelets in vitro is not mediated by blockade of 5-HT transport. This raises a new question for future investigation: by what mechanism(s) does citalopram inhibit platelets

Hecke Groups, Dessins d’Enfants and the Archimedean Solids

Grothendieck’s dessins d’enfants arise with ever-increasing frequency in many areas of 21st century mathematical physics. In this paper, we review the connections between dessins and the theory of Hecke groups. Focussing on the restricted class of highly symmetric dessins corresponding to the so-called Archimedean solids, we apply this theory in order to provide a means of computing representatives of the associated conjugacy classes of Hecke subgroups in each case. The aim of this paper is to demonstrate that dessins arising in mathematical physics can point to new and hitherto unexpected directions for further research. In addition, given the particular ubiquity of many of the dessins corresponding to the Archimedean solids, the hope is that the computational results of this paper will prove useful in the further study of these objects in mathematical physics contexts

Virtual reconnection: The online spaces of alternative food networks in England

AbstractSpaces of ‘alternative’ food production and consumption have been the subject of considerable interest within agri-food research and policy-making circles in recent decades. Examples of these Alternative Food Networks (AFNs) include Farmers' Markets, Community Supported Agriculture (CSA) schemes and farm shops, where food products are embedded with social and spatial information that serves to differentiate them from conventional agri-food systems. These shorter, more transparent, localised supply chains that characterise AFNs are underpinned by the notion of reconnection – a fundamental set of biological, social and moral processes that enable agri-food stakeholders to participate in ethically minded, transparent systems, where they are better connected to one another and to the markets and environments in which they are immersed. Drawing on a range of eight AFN case studies in England and using a multi-method approach, we explore the notion of reconnection within online space to show how social relations have changed, and are changing as a result of online activity. In examining the websites and social media platforms of AFNs and primary data collected from the creators and users of these spaces, we uncover the notion of ‘virtual reconnection’. We found the embodied, socio-material reconnection processes that occur in-place also occur online. However, by extending AFN spaces, virtual reconnection cannot fully replicate the same embodied and tactile experiences associated with the material spaces of AFNs. As such, online spaces in the context of AFNs provide a useful additional realm for reconnection, but need to be understood as supplementary rather than as a substitution for socio-material reconnections. Future research should consider the moral dimensions of reconnection and the capacity that online spaces have for enhancing the inclusivity of Civic Food Networks (CFNs), and their transformative role in contributing to more sustainable behaviours

BtubA-BtubB Heterodimer Is an Essential Intermediate in Protofilament Assembly

BACKGROUND:BtubA and BtubB are two tubulin-like genes found in the bacterium Prosthecobacter. Our work and a previous crystal structure suggest that BtubB corresponds to alpha-tubulin and BtubA to beta-tubulin. A 1:1 mixture of the two proteins assembles into tubulin-like protofilaments, which further aggregate into pairs and bundles. The proteins also form a BtubA/B heterodimer, which appears to be a repeating subunit in the protofilament. METHODOLOGY/PRINCIPAL FINDINGS:We have designed point mutations to disrupt the longitudinal interfaces bonding subunits into protofilaments. The mutants are in two classes, within dimers and between dimers. We have characterized one mutant of each class for BtubA and BtubB. When mixed 1:1 with a wild type partner, none of the mutants were capable of assembly. An excess of between-dimer mutants could depolymerize preformed wild type polymers, while within-dimer mutants had no activity. CONCLUSIONS:An essential first step in assembly of BtubA + BtubB is formation of a heterodimer. An excess of between-dimer mutants depolymerize wild type BtubA/B by sequestering the partner wild type subunit into inactive dimers. Within-dimer mutants cannot form dimers and have no activity

Combined Inactivation of pRB and Hippo Pathways Induces Dedifferentiation in the Drosophila Retina

Functional inactivation of the Retinoblastoma (pRB) pathway is an early and obligatory event in tumorigenesis. The importance of pRB is usually explained by its ability to promote cell cycle exit. Here, we demonstrate that, independently of cell cycle exit control, in cooperation with the Hippo tumor suppressor pathway, pRB functions to maintain the terminally differentiated state. We show that mutations in the Hippo signaling pathway, wts or hpo, trigger widespread dedifferentiation of rbf mutant cells in the Drosophila eye. Initially, rbf wts or rbf hpo double mutant cells are morphologically indistinguishable from their wild-type counterparts as they properly differentiate into photoreceptors, form axonal projections, and express late neuronal markers. However, the double mutant cells cannot maintain their neuronal identity, dedifferentiate, and thus become uncommitted eye specific cells. Surprisingly, this dedifferentiation is fully independent of cell cycle exit defects and occurs even when inappropriate proliferation is fully blocked by a de2f1 mutation. Thus, our results reveal the novel involvement of the pRB pathway during the maintenance of a differentiated state and suggest that terminally differentiated Rb mutant cells are intrinsically prone to dedifferentiation, can be converted to progenitor cells, and thus contribute to cancer advancement

Residency and a broad feeding spectrum are related to extensive spatial exploration in parrots

Resident and nomadic species differ substantially in their mobility, with the former spending most of their lives in a restricted area and the latter encountering many areas while tracking spatiotemporal unpredictable resources. Earlier studies have shown that information gathering differs alongside this mobility axis—resident species pay more attention to changes in their familiar environment than nomadic ones. However, little is known about spatial exploration in resident and nomadic species. We investigated spatial exploration in 10 closely related parrot species that differed in their mobility by giving them access to two unfamiliar aviaries left and right of the familiar aviary. For analyses, mobility and some diet and habitat variables were related to spatial exploration. Nomadic species spent less time exploring the novel aviaries and also started tactile exploration later than resident/nomadic and pure resident species. Furthermore, diet specialists visited more new locations in relation to their overall movements than diet generalists. The variables were not correlated with the molecular phylogeny (mitochondrial cytochrome b) of the species. The results indicate that nomads invest less in spatial exploration than residents possibly because they stay only for limited periods of time in one particular area or use easier-to-assess cues. Residents, in contrast, assess a novel environment in detail as they may collect information about future breeding sites for which they need short- and long-term information. Finally, diet specialists may pay attention to fewer environmental cues than generalists, which allows them to move faster through a novel environment

Growth Hormone Promotes Hair Cell Regeneration in the Zebrafish (Danio rerio) Inner Ear following Acoustic Trauma

BACKGROUND: Previous microarray analysis showed that growth hormone (GH) was significantly upregulated following acoustic trauma in the zebrafish (Danio rerio) ear suggesting that GH may play an important role in the process of auditory hair cell regeneration. Our objective was to examine the effects of exogenous and endogenous GH on zebrafish inner ear epithelia following acoustic trauma. METHODOLOGY/PRINCIPAL FINDINGS: We induced auditory hair cell damage by exposing zebrafish to acoustic overstimulation. Fish were then injected intraperitoneally with either carp GH or buffer, and placed in a recovery tank for either one or two days. Phalloidin-, bromodeoxyuridine (BrdU)-, and TUNEL-labeling were used to examine hair cell densities, cell proliferation, and apoptosis, respectively. Two days post-trauma, saccular hair cell densities in GH-treated fish were similar to that of baseline controls, whereas buffer-injected fish showed significantly reduced densities of hair cell bundles. Cell proliferation was greater and apoptosis reduced in the saccules, lagenae, and utricles of GH-treated fish one day following trauma compared to controls. Fluorescent in situ hybridization (FISH) was used to examine the localization of GH mRNA in the zebrafish ear. At one day post-trauma, GH mRNA expression appeared to be localized perinuclearly around erythrocytes in the blood vessels of the inner ear epithelia. In order to examine the effects of endogenous GH on the process of cell proliferation in the ear, a GH antagonist was injected into zebrafish immediately following acoustic trauma, resulting in significantly decreased cell proliferation one day post-trauma in all three zebrafish inner ear end organs. CONCLUSIONS/SIGNIFICANCE: Our results show that exogenous GH promotes post-trauma auditory hair cell regeneration in the zebrafish ear through stimulating proliferation and suppressing apoptosis, and that endogenous GH signals are present in the zebrafish ear during the process of auditory hair cell regeneration

Chemistry with Controlled Ions

This chapter focuses on the application of controlled-molecule techniques for precise studies of ion-molecule reactions in the gas phase. It gives an overview of the most important techniques presently used for the control of the translational motion, internal quantum states, and structural properties of molecular ions and neutral molecules in the gas phase. Besides the control of the translational motion, preparation of the internal quantum state of molecular ions is a main prerequisite on the way to controlling chemical reactions. Since the 1980s, (multiphoton) photoionization has been a key method for preparing molecular ions in selected internal states. Various variants of this approach have been implemented. The chapter further gives a brief outline of salient concepts of ion-molecule reaction dynamics which are relevant for the present discussion. Finally, the chapter presents some illustrative examples in which cold- and controlled-molecule techniques have been used to study the mechanisms and dynamics of ionic reactions