Deciphering the regulatory landscapte of fetal and adult γδ T-cell development at single-cell resolution

γδ T cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases, and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of γδ T cells in the thymus is incompletely understood. Here, we establish a high‐resolution map of γδ T‐cell differentiation from the fetal and adult thymus using single‐cell RNA sequencing. We reveal novel sub‐types of immature and mature γδ T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult γδ T‐cell differentiation. By performing a combined single‐cell analysis of Sox13, Maf, and Rorc knockout mice, we demonstrate sequential activation of these factors during IL ‐17‐producing γδ T‐cell (γδT17) differentiation. These findings substantially expand our understanding of γδ T‐cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages

Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor

We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms' tumor in a familial setting, which give insight into the complex controls of imprinting and gene expression in the chromosome 11p15 region. We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor. Maternal inheritance of the deletion is associated with IGF2 loss of imprinting and up-regulation of IGF2 mRNA. However, in at least one affected family member a second genetic lesion (a duplication of maternal 11p15) was identified and accompanied by a further increase in IGF2 rnRNA levels 35-fold higher than control values. Our results suggest that the combined effects of the H19//GF2-imprinting center microdeletion and 11p15 chromosome duplication were necessary for manifestation of BWS

Remineralization of demineralized dentin using a dual analog system.

ObjectiveImproved methods are needed to remineralize dentin caries in order to promote conservation of dentin tissue and minimize the surgical interventions that are currently required for clinical treatment. Here, we test the hypothesis that bulk substrates can be effectively mineralized via a dual analog system proposed by others, using a tripolyphosphate (TPP) "templating analog" and a poly(acrylic acid) (PAA) or poly(aspartic acid) (pAsp) "sequestration analog," the latter of which generates the polymer-induced liquid-precursor (PILP) mineralization process studied in our laboratory.Material & methodsDemineralized human dentin slices were remineralized with and without pre-treatment with TPP, using either PAA or pAsp as the PILP process-directing agent. A control experiment with no polymer present was used for comparison.ResultsNo mineralization was observed in any of the PAA groups. In both the pAsp and no polymer groups, TPP inhibited mineralization on the surfaces of the specimens but promoted mineralization within the interiors. Pre-treatment with TPP enhanced overall mineralization of the pAsp group. However, when analysed via TEM, regions with little mineral were still present.ConclusionPoly(acrylic acid) was unable to remineralize demineralized dentin slices under the conditions employed, even when pre-treated with TPP. However, pre-treatment with TPP enhanced overall mineralization of specimens that were PILP-remineralized using pAsp

Understanding forest health with Remote sensing-Part II-A review of approaches and data models

Stress in forest ecosystems (FES) occurs as a result of land-use intensification, disturbances, resource limitations or unsustainable management, causing changes in forest health (FH) at various scales from the local to the global scale. Reactions to such stress depend on the phylogeny of forest species or communities and the characteristics of their impacting drivers and processes. There are many approaches to monitor indicators of FH using in-situ forest inventory and experimental studies, but they are generally limited to sample points or small areas, as well as being time- and labour-inte

Reanalysis in Earth System Science: Towards Terrestrial Ecosystem Reanalysis

A reanalysis is a physically consistent set of optimally merged simulated model states and historical observational data, using data assimilation. High computational costs for modelled processes and assimilation algorithms has led to Earth system specific reanalysis products for the atmosphere, the ocean and the land separately. Recent developments include the advanced uncertainty quantification and the generation of biogeochemical reanalysis for land and ocean. Here, we review atmospheric and oceanic reanalyses, and more in detail biogeochemical ocean and terrestrial reanalyses. In particular, we identify land surface, hydrologic and carbon cycle reanalyses which are nowadays produced in targeted projects for very specific purposes. Although a future joint reanalysis of land surface, hydrologic and carbon processes represents an analysis of important ecosystem variables, biotic ecosystem variables are assimilated only to a very limited extent. Continuous data sets of ecosystem variables are needed to explore biotic-abiotic interactions and the response of ecosystems to global change. Based on the review of existing achievements, we identify five major steps required to develop terrestrial ecosystem reanalysis to deliver continuous data streams on ecosystem dynamics

Absence of Macrophage Inflammatory Protein-1α Prevents the Development of Blinding Herpes Stromal Keratitis

Prior studies in our laboratory have suggested that the CC chemokine macrophage inflammatory protein-1α (MIP-1α) may be an important mediator in the blinding ocular inflammation which develops following herpes simplex virus type 1 (HSV-1) infection of the murine cornea. To directly test this hypothesis, MIP-1α-deficient (−/−) mice and their wild-type (+/+) counterparts were infected topically on the scarified cornea with 2.5 × 105 PFU of HSV-1 strain RE and subsequently graded for corneal opacity. Four weeks postinfection (p.i.), the mean corneal opacity score of −/− mice was 1.1 ± 0.3 while that of the +/+ mice was 3.7 ± 0.5. No detectable infiltrating CD4+ T cells were seen histologically at 14 or 21 days p.i. in −/− animals, whereas the mean CD4+ T-cell count per field (36 fields counted) in +/+ hosts was 26 ± 2 (P 80% in comparison to the wild-type controls. At 2 weeks p.i., no interleukin-2 or gamma interferon could be detected in six of seven −/− mice, whereas both T-cell cytokines were readily demonstrable in +/+ mouse corneas. Also, MIP-2 and monocyte chemoattractant protein-1 protein levels were significantly lower in MIP-1α −/− mouse corneas than in +/+ host corneas, suggesting that MIP-1α directly, or more likely indirectly, influences the expression of other chemokines. Interestingly, despite the paucity of infiltrating cells, HSV-1 clearance from the eyes of −/− mice was not significantly different from that observed in +/+ hosts. We conclude that MIP-1α is not needed to control virus growth in the cornea but is essential for the development of severe stromal keratitis

Framing the concept of satellite remote sensing essential biodiversity variables: challenges and future directions

Although satellite-based variables have for long been expected to be key components to a unified and global biodiversity monitoring strategy, a definitive and agreed list of these variables still remains elusive. The growth of interest in biodiversity variables observable from space has been partly underpinned by the development of the essential biodiversity variable (EBV) framework by the Group on Earth Observations – Biodiversity Observation Network, which itself was guided by the process of identifying essential climate variables. This contribution aims to advance the development of a global biodiversity monitoring strategy by updating the previously published definition of EBV, providing a definition of satellite remote sensing (SRS) EBVs and introducing a set of principles that are believed to be necessary if ecologists and space agencies are to agree on a list of EBVs that can be routinely monitored from space. Progress toward the identification of SRS-EBVs will require a clear understanding of what makes a biodiversity variable essential, as well as agreement on who the users of the SRS-EBVs are. Technological and algorithmic developments are rapidly expanding the set of opportunities for SRS in monitoring biodiversity, and so the list of SRS-EBVs is likely to evolve over time. This means that a clear and common platform for data providers, ecologists, environmental managers, policy makers and remote sensing experts to interact and share ideas needs to be identified to support long-term coordinated actions

A genome-wide association study identifies multiple loci for variation in human ear morphology

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1