CalDAG-GEFI deficiency protects mice from FcγRIIa-mediated thrombotic thrombocytopenia induced by CD40L and β2GPI immune complexes

Platelet activation via the Fcγ receptor IIa (FcγRIIa) is implicated in the pathogenesis of immune complex (IC)-mediated thrombocytopenia and thrombosis (ITT). We previously showed that ICs composed of antigen and antibodies targeting CD40 ligand (CD40L) or β2 Glycoprotein I (β2GPI) induce ITT in mice transgenic for human FcγRIIa (hFcR) but not wild-type controls (which lack FcγRIIa). Here we evaluated the contribution of the guanine nucleotide exchange factor, CalDAG-GEFI, and P2Y12, key regulators of Rap1 signaling in platelets, to ITT induced by these clinically relevant ICs

The fibrinogen γA/γ′ isoform does not promote acute arterial thrombosis in mice

Elevated plasma fibrinogen associates with arterial thrombosis in humans and promotes thrombosis in mice by increasing fibrin formation and thrombus fibrin content. Fibrinogen is composed of six polypeptide chains: (Aα, Bβ, and γ)2. Alternative splicing of the γ chain leads to a dominant form (γA/γA) and a minor species (γA/γ’). Epidemiologic studies have detected elevated γA/γ’ fibrinogen in patients with arterial thrombosis, suggesting this isoform promotes thrombosis. However, in vitro data show that γA/γ’ is anticoagulant due to its ability to sequester thrombin, and suggest its expression is upregulated in response to inflammatory processes

Sequence analysis of the cloned streptococcal cell surface antigen I/II

AbstractThe gene spa P (formerly designated as spa P1) encoding the Mr 185,000 surface antigen (I/II) of Streptococcus mutons, serotype c (NG5), has been sequenced. The gene (4683 bp) encodes a protein of 1561 amino acid residues including putative signal peptide (residues 1–38) and transmembrane (residues 1537–1556) sequences. The N-terminal region (60–550) has alanine-rich repeats and is predicted to be α-helical. However, the C-ternunal region (800–1540) is proline-rich and favours an extended structure. Except for a short central variable region the sequences appear to be highly conserved for S. mutans serotype c. N-Tenninal sequencing of separated antigen I and antigen II polypeptides suggests that the former represents the N-terminal and the latter the C-terminal portions of the intact antigen

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Platelet ITAM signaling is critical for vascular integrity in inflammation

Platelets play a critical role in maintaining vascular integrity during inflammation, but little is known about the underlying molecular mechanisms. Here we report that platelet immunoreceptor tyrosine activation motif (ITAM) signaling, but not GPCR signaling, is critical for the prevention of inflammation-induced hemorrhage. To generate mice with partial or complete defects in these signaling pathways, we developed a protocol for adoptive transfer of genetically and/or chemically inhibited platelets into thrombocytopenic (TP) mice. Unexpectedly, platelets with impaired GPCR signaling, a crucial component of platelet plug formation and hemostasis, were indistinguishable from WT platelets in their ability to prevent hemorrhage at sites of inflammation. In contrast, inhibition of GPVI or genetic deletion of Clec2, the only ITAM receptors expressed on mouse platelets, significantly reduced the ability of platelets to prevent inflammation-induced hemorrhage. Moreover, transfusion of platelets without ITAM receptor function or platelets lacking the adapter protein SLP-76 into TP mice had no significant effect on vascular integrity during inflammation. These results indicate that the control of vascular integrity is a major function of immune-type receptors in platelets, highlighting a potential clinical complication of novel antithrombotic agents directed toward the ITAM signaling pathway

Heterogeneous yet stable V delta 2((+)) T-cell profiles define distinct cytotoxic effector potentials in healthy human individuals

The Wellcome Trust [096954/Z/11/Z]; and Bloodwise; grant award 14026 (formally Leukaemia & Lymphoma Research)

Maternal feeding practices and fussy eating in toddlerhood: A discordant twin analysis

Background: Parental feeding practices are thought to play a causal role in shaping a child's fussiness; however, a child-responsive model suggests that feeding practices may develop in response to a child's emerging appetitive characteristics. We used a novel twin study design to test the hypothesis that mothers vary their feeding practices for twin children who differ in their 'food fussiness', in support of a child-responsive model. Methods: Participants were mothers and their 16 month old twin children (n=2026) from Gemini, a British twin birth cohort of children born in 2007. Standardized psychometric measures of maternal 'pressure to eat', 'restriction' and 'instrumental feeding', as well as child 'food fussiness', were completed by mothers. Within-family analyses examined if twin-pair differences in 'food fussiness' were associated with differences in feeding practices using linear regression models. In a subset of twins (n=247 pairs) who were the most discordant (highest quartile) on 'food fussiness' (difference score≥.50), Paired Samples T-test were used to explore the magnitude of differences in feeding practices between twins. Between-family analyses used Complex Samples General Linear Models to examine associations between feeding practices and 'food fussiness'. Results: Within-pair differences in 'food fussiness' were associated with differential 'pressure to eat' and 'instrumental feeding' (ps<.001), but not with 'restriction'. In the subset of twins most discordant on 'food fussiness', mothers used more pressure (p<.001) and food rewards (p<.05) with the fussier twin. Between-family analyses indicated that 'pressure to eat' and 'instrumental feeding' were positively associated with 'food fussiness', while 'restriction' was negatively associated with 'food fussiness' (ps<.001). Conclusions: Mothers appear to subtly adjust their feeding practices according to their perceptions of their toddler's emerging fussy eating behavior. Specifically, the fussier toddler is pressured more than their less fussy co-twin, and is more likely to be offered food rewards. Guiding parents on how to respond to fussy eating may be an important aspect of promoting feeding practices that encourage food acceptance

Classification of the Mediterranean lowland to submontane pine forest vegetation

Vegetation SurveyAim: Vegetation types of Mediterranean thermophilous pine forests dominated by Pinus brutia, Pinus halepensis, Pinus pinaster and Pinus pinea were studied in various areas. However, a comprehensive formal vegetation classification of these forests based on a detailed data analysis has never been developed. Our aim is to provide the first broad-scale classification of these pine forests based on a large data set of vegetation plots. Location: Southern Europe, North Africa, Levant, Anatolia, Crimea and the Caucasus. Methods: We prepared a data set of European and Mediterranean pine forest vegetation plots. We selected 7,277 plots dominated by the cold-sensitive Mediterranean pine species Pinus brutia, Pinus halepensis, Pinus pinaster and Pinus pinea. We classified these plots using TWINSPAN, interpreted the ecologically and biogeographically homogeneous TWINSPAN clusters as alliances, and developed an expert system for automatic vegetation classification at the class, order and alliance levels. Results: We described Pinetea halepensis as a new class for the Mediterranean lowland to submontane pine forests, included in the existing Pinetalia halepensis order, and distinguished 12 alliances of native thermophilous pine forests, including four newly described and three informal groups merging supposedly native stands and old-established plantations. The main gradients in species composition reflect elevational vegetation belts and the west–east, and partly north–south, biogeographical differences. Both temperature and precipitation seasonality co-vary with these gradients. Conclusions: We provide the first formal classification at the order and alliance levels for all the Mediterranean thermophilous pine forests based on vegetation-plot data. This classification includes traditional syntaxa, which have been critically revised, and a new class and four new alliances. We also outline a methodological workflow that might be useful for other vegetation classification syntheses. The expert system, which is jointly based on pine dominance and species composition, is a tool for applying this classification in research and nature conservation survey, monitoring and managementinfo:eu-repo/semantics/publishedVersio

Euro+Med-Checklist Notulae, 14

Abstract: This is the fourteenth of a series of miscellaneous contributions, by various authors, where hitherto unpublished data relevant to both the Med-Checklist and the Euro+Med (or Sisyphus) projects are presented. This instalment deals with the families Apocynaceae, Compositae, Crassulaceae, Cyperaceae, Euphorbiaceae, Gramineae, Leguminosae, Nyctaginaceae, Onagraceae, Orobanchaceae, Rubiaceae, Solanaceae and Umbelliferae. It includes new country and area records and taxonomic and distributional considerations for taxa in Acalypha, Bupleurum, Carex, Datura, Epilobium, Eragrostis, Galium, Leontodon, Mirabilis, Nerium, Orobanche, Phelipanche, Rhinanthus, Saccharum, Sedum, Trifolium, Tripleurospermum and Willemetia. Citation For the whole article: Raab-Straube E. von &amp; Raus Th. (ed.) 2021: Euro+Med-Checklist Notulae, 14.-Willdenowia 51: 355-369. For a single contribution (example): Bergmeier E. 2021: Leontodon longirostris (Finch &amp; P. D. Sell) Talavera-Pp. 356-357 in: Raab-Straube E. von &amp; Raus Th. (ed.), Euro+Med-Checklist Notulae, 14.-Willdenowia 51: 355-369. https://doi.org/10.3372/wi.51.51304 Version of record first published online on 30 November 2021 ahead of inclusion in December 2021 issue