Suchergebnisse

Abstract. We applied eddy-resolving ocean data assimilation to a cloud-resolving atmospheric simulation of a snow disaster and investigated the effects of mesoscale eddies on a heavy snowfall event in late December 2005. Ocean circulation model (OCM) data assimilation reproduces mesoscale sea surface temperature (SST) structures, which are smoothed out by optimum interpolation. This difference between OCM-assimilation and optimum-interpolation SSTs affects the atmospheric boundary layers over oceanic mesoscale eddies. The atmospheric response to the SST difference is complex at the cold tongue in the central Sea of Japan. Although the horizontal wind and turbulent mixing are quickly and locally affected by the low SST, the atmospheric temperature and water amounts are greatly affected by the upstream high SST via the northwesterly advection. In the heavy snowfall areas, the OCM assimilation greatly affects 10-day accumulated precipitation, though it does not largely influence 10-day mean vertical structures of wind, temperature and water vapor. Thus, we should recognize the significance of oceanic mesoscale eddies for heavy snowfall.

Thymic epithelial cells (TECs) provide key instructive signals for T-cell differentiation. Thymic cortical (cTECs) and medullary (mTECs) epithelial cells constitute two functionally distinct microenvironments for T-cell development, which derive from a common bipotent TEC progenitor. While seminal studies have partially elucidated events downstream of bipotent TECs in relation to the emergence of mTECs and their progenitors, the control and timing of the emergence of the cTEC lineage, particularly in relation to that of mTEC progenitors, has remained elusive. In this review, we describe distinct models that explain cTEC/mTEC lineage divergence from common bipotent progenitors. In particular, we summarize recent studies in mice providing evidence that mTECs, including the auto-immune regulator(+) subset, derive from progenitors initially endowed with phenotypic properties typically associated with the cTEC lineage. These observations support a novel "serial progression" model of TEC development, in which progenitors serially acquire cTEC lineage markers, prior to their commitment to the mTEC differentiation pathway. Gaining a better understanding of the phenotypic properties of early stages in TEC progenitor development should help in determining the mechanisms regulating cTEC/mTEC lineage development, and in strategies aimed at thymus reconstitution involving TEC therapy. ; N.L.A. is supported by program Ciencia2008 from the Foundation for Science and Technology (FCT, Portugal). N.L.A. is supported by grants from FCT, funds from the European Regional Development Fund (FEDER) through the Operational Competitiveness Program (COMPETE), by National Funds through the Foundation for Science and Technology (FCT, Portugal) under Project FCOMP-01-0124-FEDER-015803 (PTDC/SAU-IMU/110116/2009). A.R.R. is supported by Ph.D. fellowships from FCT (SFRH/BD/78380/2011). Y.T. is supported by Grants-in-Aid for Scientific Research from MEXT and JSPS (23249025 and 24111004), Japan. G.A. and Y.T. are supported by An International Exchange Scheme from The Royal Society, UK. S.B. is supported by a PhD studentship from the European Union ITN "NINA." G.A. is supported by a Medical Research Council Programme Grant, W.E.J. is supported by a New Investigator Award from the Medical Research Council, UK (G1001055).

Incluye material complementario ; The Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer's disease (AD). We have characterized the dark PITH domain-containing protein 1 (PITHD1) in olfactory metabolism using bioinformatics, proteomics, in vitro and in vivo studies, and neuropathology. PITHD1-/- mice exhibit olfactory bulb (OB) proteome changes related to synaptic transmission, cognition, and memory. OB PITHD1 expression increases with age in wild-type (WT) mice and decreases in Tg2576 AD mice at late stages. The analysis across 6 neurological disorders reveals that olfactory tract (OT) PITHD1 is specifically upregulated in human AD. Stimulation of olfactory neuroepithelial (ON) cells with PITHD1 alters the ON phosphoproteome, modifies the proliferation rate, and induces a pro-inflammatory phenotype. This workflow applied by the Spanish C-HPP and Human Brain Proteome Project (HBPP) teams across the ON-OB-OT axis can be adapted as a guidance to decipher functional features of dark proteins. Data are available via ProteomeXchange with identifiers PXD018784 and PXD021634. ; This work was funded by grants from the Spanish Ministry of Science Innovation and Universities (ref. PID2019-110356RB-I00 to JFI and ES) and Department of Economic and Business Development from Government of Navarra (ref. 0011-1411-2020-000028) to ES and from MEXT-JSPS 17K08884 and Takeda Science Foundation to IO. The Proteomics Unit of Navarrabiomed is a member of Proteored (PRB3-ISCIII) and is supported by grant PT17/0019/009 to JFI, of the PE I+D+I 2013–2016 funded by ISCIII and FEDER. MLM was supported by a postdoctoral fellowship from the Public University of Navarra (UPNA).