Resident Corneal Cells Communicate with Neutrophils Leading to the Production of IP-10 during the Primary Inflammatory Response to HSV-1 Infection

In this study we show that murine and human neutrophils are capable of secreting IP-10 in response to communication from the HSV-1 infected cornea and that they do so in a time frame associated with the recruitment of CD8+ T cells and CXCR3-expressing cells. Cellular markers were used to establish that neutrophil influx corresponded in time to peak IP-10 production, and cellular depletion confirmed neutrophils to be a significant source of IP-10 during HSV-1 corneal infection in mice. A novel ex vivo model for human corneal tissue infection with HSV-1 was used to confirm that cells resident in the cornea are also capable of stimulating neutrophils to secrete IP-10. Our results support the hypothesis that neutrophils play a key role in T-cell recruitment and control of viral replication during HSV-1 corneal infection through the production of the T-cell recruiting chemokine IP-10

A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies.

Jeune asphyxiating thoracic dystrophy (JATD) is a skeletal dysplasia characterized by a small thoracic cage and a range of skeletal and extra-skeletal anomalies. JATD is genetically heterogeneous with at least nine genes identified, all encoding ciliary proteins, hence the classification of JATD as a skeletal ciliopathy. Consistent with the observation that the heterogeneous molecular basis of JATD has not been fully determined yet, we have identified two consanguineous Saudi families segregating JATD who share a single identical ancestral homozygous haplotype among the affected members. Whole-exome sequencing revealed a single novel variant within the disease haplotype in CEP120, which encodes a core centriolar protein. Subsequent targeted sequencing of CEP120 in Saudi and European JATD cohorts identified two additional families with the same missense mutation. Combining the four families in linkage analysis confirmed a significant genome-wide linkage signal at the CEP120 locus. This missense change alters a highly conserved amino acid within CEP120 (p.Ala199Pro). In addition, we show marked reduction of cilia and abnormal number of centrioles in fibroblasts from one affected individual. Inhibition of the CEP120 ortholog in zebrafish produced pleiotropic phenotypes characteristic of cilia defects including abnormal body curvature, hydrocephalus, otolith defects and abnormal renal, head and craniofacial development. We also demonstrate that in CEP120 morphants, cilia are shortened in the neural tube and disorganized in the pronephros. These results are consistent with aberrant CEP120 being implicated in the pathogenesis of JATD and expand the role of centriolar proteins in skeletal ciliopathies

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

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

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

Evaluation of potential habitat with an integrated analysis of a spatial conservation strategy for David’s deer, Elaphurus davidians

How to assess the potential habitat integrating landscape dynamics and population research, and how to reintroduce animals to potential habitats in environments highly human disturbed are still questions to be answered in conservation biology. According to behavioral research on Elaphurus davidians, we have developed a suitability index and a risk index to evaluate the potential habitats for the deer. With these indices, we conducted two transect assessments to evaluate the gradient change of the target region. Then, taking rivers as border lines, we tabulated the forest areas, high grassland area and total area and then compared the forest and high grassland area in each subregion. Furthermore, we computed the land use transfer matrix for the whole Yancheng coast during 1987–2000. We also computed human modified index (HMI) in six subregions. Lastly with a geographical information system support we obtained the spatial distribution of the indices and evaluation of the whole potential habitats from a neighborhood analysis. The transect assessment showed that the suitability of the coastal area was higher than that of the inland area for the deer, while the southern area was higher than the northern. Landscape metrics and HMI analysis showed that different landscape patterns and different anthropogenic disturbance existed within the region, and the increasing human disturbance was the key factor causing the pattern dynamics. The evaluation of potential habitats showed that there was an estimated carrying capacity of no more than 10,000 for David’s deer reintroduction into the natural area. Also the reintroduction strategy was discussed. This integrated approach linked the population research and the landscape metrics, and the dataset with different scale; thus, it is an approach likely to be useful for the protection of other large animal in a landscape highly disturbed by humans

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

Analysis of action oriented effects on perceptual process of object recognition using physiological responses

Action on any objects provides perceptual information about the environment. There is a significant evidence that human visual system responds to action possibilities in an image as perceiving any ones action stimulates human motor system. However very limited studies have been done to analyze the effect of object affordance during action perception and execution. To study the effect of object affordance on human perception, in this paper we have analyzed the human brain signals using EEG based oscillatory activity of brain. EEG responses corresponding to images of objects shown with correct, incorrect and without grips are examined. Exploration of different gripping effects has been done by extracting Alpha and Beta frequency bands using Discrete Wavelet Transform based band extraction method, then baseline normalized power of Alpha and Beta frequency bands at 24 positions of motor area of left and right side of brain are examined. The result shows that 12 pooled electrodes at central and central parietal region provides a clear discrimination among the three gripping cases in terms of calculated power. The presented research explores new applicabilities of object affordance to develop a variety of Brain Computer Interface (BCI) based devices and to improve motor imagery ability among motor disorder related patients