Transcriptional diversity during lineage commitment of human blood progenitors.

Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.The work described in this article was primarily supported by the European Commission Seventh Framework Program through the BLUEPRINT grant with code HEALTH-F5-2011-282510 (D.H., F.B., G.C., J.H.A.M., K.D., L.C., M.F., S.C., S.F., and S.P.G.). Research in the Ouwehand laboratory is further supported by program grants from the National Institute for Health Research (NIHR, www.nihr.ac.uk; to A.A., M.K., P.P., S.B.G.J., S.N., and W.H.O.) and the British Heart Foundation under nos. RP-PG-0310-1002 and RG/09/12/28096 (www.bhf.org.uk; to A.R. and W.J.A.). K.F. and M.K. were supported by Marie Curie funding from the NETSIM FP7 program funded by the European Commission. The laboratory receives funding from the NHS Blood and Transplant for facilities. The Cambridge BioResource (www.cambridgebioresource.org.uk), the Cell Phenotyping Hub, and the Cambridge Translational GenOmics laboratory (www.catgo.org.uk) are supported by an NIHR grant to the Cambridge NIHR Biomedical Research Centre (BRC). The BRIDGE-Bleeding and Platelet Disorders Consortium is supported by the NIHR BioResource—Rare Diseases (http://bioresource.nihr.ac.uk/; to E.T., N.F., and Whole Exome Sequencing effort). Research in the Soranzo laboratory (L.V., N.S., and S. Watt) is further supported by the Wellcome Trust (Grant Codes WT098051 and WT091310) and the EU FP7 EPIGENESYS initiative (Grant Code 257082). Research in the Cvejic laboratory (A. Cvejic and C.L.) is funded by the Cancer Research UK under grant no. C45041/A14953. S.J.S. is funded by NIHR. M.E.F. is supported by a British Heart Foundation Clinical Research Training Fellowship, no. FS/12/27/29405. E.B.-M. is supported by a Wellcome Trust grant, no. 084183/Z/07/Z. Research in the Laffan laboratory is supported by Imperial College BRC. F.A.C., C.L., and S. Westbury are supported by Medical Research Council Clinical Training Fellowships, and T.B. by a British Society of Haematology/NHS Blood and Transplant grant. R.J.R. is a Principal Research Fellow of the Wellcome Trust, grant no. 082961/Z/07/Z. Research in the Flicek laboratory is also supported by the Wellcome Trust (grant no. 095908) and EMBL. Research in the Bertone laboratory is supported by EMBL. K.F. and C.v.G. are supported by FWO-Vlaanderen through grant G.0B17.13N. P.F. is a compensated member of the Omicia Inc. Scientific Advisory Board. This study made use of data generated by the UK10K Consortium, derived from samples from the Cohorts arm of the project.This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 26/9/14 in volume 345, number 6204, DOI: 10.1126/science.1251033. This version will be under embargo until the 26th of March 2015

Impact of Time Delay in Perceptual Decision-Making: Neuronal Population Modeling Approach

Contains fulltext : 187462.pdf (publisher's version ) (Open Access)15 p

Delay can stabilize: Love affairs dynamics

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Porosty na terenach pogórniczych rud cynkowo-ołowiowych

A list of lichens from areas of zinc-lead ores in Southern Poland and a review of the characteristic lichen biota of these sites is provided. In spite of the devastated and heavy metal contaminated environment, a highly diverse epigeic and epilithic lichen biota was found, including species characteristic of various anthropogenic habitats, particularly zinc and lead enriched substrates (Diploschistes muscorum, Steinia geophana, Sarcosagium campestre, Vezdaea aestivalis and V. leprosa). Also, the high-mountain species Leucocarpia biatorella, as well as very rare in Europe Thelocarpon imperceptum, and several species categorized as very rare, endangered and protected in Poland were recorded. Crustose lichens are the most abundant; among fruticose forms Cladonia spp. predominate and Stereocaulon incrustatum is commonPraca prezentuje wyniki badań lichenologicznych przeprowadzonych na wybranych powierzchniach Wyżyny Śląsko-Krakowskiej związanych z eksploatacją rud cynkowo-ołowiowych. Lista porostów tego terenu liczy 89 taksonów, z których 76 zawartych jest w tabeli 1. Pomimo trudnych warunków siedliskowych (brak wody oraz niektórych składników pokarmowych, wysoka zawartość metali ciężkich – głównie cynku, ołowiu i kadmu, - silna insolacja oraz silne działania wiatrów), występuje tu bardzo zróżnicowana i specyficzna biota porostów. Porosty były badane na wszystkich dostępnych substratach. Najmniej liczne są epifity i epiksylity, ograniczone do kilku najpospolitszych, toksytolerancyjnych gatunków. Dominują gatunki naziemne i naskalne, z których te ostatnie rosną głównie na kamieniach i drobnych kamykach. Wśród form morfologicznych zdecydowanie liczebną przewagę mają porosty skorupiaste, choć o fizjonomii zbiorowisk decydują porosty krzaczkowate, zwłaszcza Cladonia spp., które występują obficie i tworzą duże populacje. Z nielicznych form listkowatych obecne są Peltigera rufescens i P. didactyla, które poprzez zdolność wiązania wolnego azotu przez symbiotyczne sinice, są ważnym ogniwem łańcucha troficznego. Występują gatunki związane z substratami zawierającymi cynk i ołów, które mogą być wskaźnikami ich obecności w podłożu: Diploschistes muscorum, Sarcosagium campestre, Steinia geophana, Vezdaea aestivalis i V. leprosa. Wiele spośród odnotowanych porostów to gatunki rzadkie lub bardzo rzadkie w Polsce, pięć z nich podlega ochronie prawnej, a siedem – znajduje się na krajowej czerwonej liście. Badany teren jest również ostoją rzadkich porostów górskich, na przykład Leucocarpia biatorella oraz bardzo rzadkiego w E E uropie Thelocarpon imperceptum. Analizowana lichenobiota jest porównywalna ze składem gatunkowym porostów z innych terenów pogórniczych Europy

Time-delay model of perceptual decision making in cortical networks

Contains fulltext : 201199.pdf (publisher's version ) (Open Access)It is known that cortical networks operate on the edge of instability, in which oscillations can appear. However, the influence of this dynamic regime on performance in decision making, is not well understood. In this work, we propose a population model of decision making based on a winner-take-all mechanism. Using this model, we demonstrate that local slow inhibition within the competing neuronal populations can lead to Hopf bifurcation. At the edge of instability, the system exhibits ambiguity in the decision making, which can account for the perceptual switches observed in human experiments. We further validate this model with fMRI datasets from an experiment on semantic priming in perception of ambivalent (male versus female) faces. We demonstrate that the model can correctly predict the drop in the variance of the BOLD within the Superior Parietal Area and Inferior Parietal Area while watching ambiguous visual stimuli.18 p

SMIM1 underlies the Vel blood group and influences red blood cell traits

<p>The blood group Vel was discovered 60 years ago(1), but the underlying gene is unknown. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel(2). To identify the responsible gene, we sequenced the exomes of five individuals negative for the Vel antigen and found that four were homozygous and one was heterozygous for a low-frequency 17-nucleotide frameshift deletion in the gene encoding the 78-amino-acid transmembrane protein SMIM1. A follow-up study showing that 59 of 64 Vel-negative individuals were homozygous for the same deletion and expression of the Vel antigen on SMIM1-transfected cells confirm SMIM1 as the gene underlying the Vel blood group. An expression quantitative trait locus (eQTL), the common SNP rs1175550 contributes to variable expression of the Vel antigen (P = 0.003) and influences the mean hemoglobin concentration of red blood cells (RBCs; P = 8.6 x 10(-15))(3). In vivo, zebrafish with smim1 knockdown showed a mild reduction in the number of RBCs, identifying SMIM1 as a new regulator of RBC formation. Our findings are of immediate relevance, as the homozygous presence of the deletion allows the unequivocal identification of Vel-negative blood donors.</p>