Newly Discovered Bright z~9-10 Galaxies and Improved Constraints on Their Prevalence Using the Full CANDELS Area

We report the results of an expanded search for z~9-10 candidates over the ~883 arcmin^2 CANDELS+ERS fields. This study adds 147 arcmin^2 to the search area we consider over the CANDELS COSMOS, UDS, and EGS fields, while expanding our selection to include sources with bluer J_{125}-H_{160} colors than our previous J_{125}-H_{160}>0.5 mag selection. In searching for new z~9-10 candidates, we make full use of all available HST, Spitzer/IRAC, and ground-based imaging data. As a result of our expanded search and use of broader color criteria, 3 new candidate z~9-10 galaxies are identified. We also find again the z=8.683 source previously confirmed by Zitrin+2015. This brings our sample of probable z~9-11 galaxy candidates over the CANDELS+ERS fields to 19 sources in total, equivalent to 1 candidate per 47 arcmin^2 (1 per 10 WFC3/IR fields). To be comprehensive, we also discuss 28 mostly lower likelihood z~9-10 candidates, including some sources that seem to be reliably at z>8 using the HST+IRAC data alone, but which the ground-based data show are much more likely at z<4. One case example is a bright z~9.4 candidate COS910-8 which seems instead to be at z~2. Based on this expanded sample, we obtain a more robust LF at z~9 and improved constraints on the volume density of bright z~9 and z~10 galaxies. Our improved z~9-10 results again reinforce previous findings for strong evolution in the UV LF at z>8, with a factor of ~10 evolution seen in the luminosity density from z~10 to z~8.Comment: 22 pages, 12 figures, 6 tables, accepted for publication in the Astrophysical Journa

A Spectroscopic Redshift Measurement for a Luminous Lyman Break Galaxy at z=7.730 using Keck/MOSFIRE

We present a spectroscopic redshift measurement of a very bright Lyman break galaxy at z=7.7302+-0.0006 using Keck/MOSFIRE. The source was pre-selected photometrically in the EGS field as a robust z~8 candidate with H=25.0 mag based on optical non-detections and a very red Spitzer/IRAC [3.6]-[4.5] broad-band color driven by high equivalent width [OIII]+Hbeta line emission. The Lyalpha line is reliably detected at 6.1 sigma and shows an asymmetric profile as expected for a galaxy embedded in a relatively neutral inter-galactic medium near the Planck peak of cosmic reionization. The line has a rest-frame equivalent width of EW0=21+-4 A and is extended with V_FWHM=360+90-70 km/s. The source is perhaps the brightest and most massive z~8 Lyman break galaxy in the full CANDELS and BoRG/HIPPIES surveys, having assembled already 10^(9.9+-0.2) M_sol of stars at only 650 Myr after the Big Bang. The spectroscopic redshift measurement sets a new redshift record for galaxies. This enables reliable constraints on the stellar mass, star-formation rate, formation epoch, as well as combined [OIII]+Hbeta line equivalent widths. The redshift confirms that the IRAC [4.5] photometry is very likely dominated by line emission with EW0(OIII+Hbeta)= 720-150+180 A. This detection thus adds to the evidence that extreme rest-frame optical emission lines are a ubiquitous feature of early galaxies promising very efficient spectroscopic follow-up in the future with infrared spectroscopy using JWST and, later, ELTs.Comment: 6 pages, 4 figures, small updates to match ApJL accepted versio

In silico identification of new putative pathogenic variants in the NEU1 sialidase gene affecting enzyme function and subcellular localization

The NEU1 gene is the first identified member of the human sialidases, glycohydrolitic enzymes that remove the terminal sialic acid from oligosaccharide chains. Mutations in NEU1 gene are causative of sialidosis (MIM 256550), a severe lysosomal storage disorder showing autosomal recessive mode of inheritance. Sialidosis has been classified into two subtypes: sialidosis type I, a normomorphic, late-onset form, and sialidosis type II, a more severe neonatal or early-onset form. A total of 50 causative mutations are reported in HGMD database, most of which are missense variants. To further characterize the NEU1 gene and identify new functionally relevant protein isoforms, we decided to study its genetic variability in the human population using the data generated by two large sequencing projects: the 1000 Genomes Project (1000G) and the NHLBI GO Exome Sequencing Project (ESP). Together these two datasets comprise a cohort of 7595 sequenced individuals, making it possible to identify rare variants and dissect population specific ones. By integrating this approach with biochemical and cellular studies, we were able to identify new rare missense and frameshift alleles in NEU1 gene. Among the 9 candidate variants tested, only two resulted in significantly lower levels of sialidase activity (pC and c.700G>A. These two mutations give rise to the amino acid substitutions p.V217A and p.D234N, respectively. NEU1 variants including either of these two amino acid changes have 44% and 25% residual sialidase activity when compared to the wild-type enzyme, reduced protein levels and altered subcellular localization. Thus they may represent new, putative pathological mutations resulting in sialidosis type I. The in silico approach used in this study has enabled the identification of previously unknown NEU1 functional alleles that are widespread in the population and could be tested in future functional studies

Prokineticin 2 upregulation in the peripheral nervous system has a major role in triggering and maintaining neuropathic pain in the chronic constriction injury model

The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI) of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7) reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi) and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease

Nutrition in Pediatric Inflammatory Bowel Disease: From Etiology to Treatment : A Systematic Review

Nutrition is involved in several aspects of pediatric inflammatory bowel disease (IBD), ranging from disease etiology to induction and maintenance of disease. With regards to etiology, there are pediatric data, mainly from case-control studies, which suggest that some dietary habits (for example consumption of animal protein, fatty foods, high sugar intake) may predispose patients to IBD onset. As for disease treatment, exclusive enteral nutrition (EEN) is an extensively studied, well established, and valid approach to the remission of pediatric Crohn's disease (CD). Apart from EEN, several new nutritional approaches are emerging and have proved to be successful (specific carbohydrate diet and CD exclusion diet) but the available evidence is not strong enough to recommend this kind of intervention in clinical practice and new large experimental controlled studies are needed, especially in the pediatric population. Moreover, efforts are being made to identify foods with anti-inflammatory properties such as curcumin and long-chain polyunsaturated fatty acids n-3, which can possibly be effective in maintenance of disease. The present systematic review aims at reviewing the scientific literature on all aspects of nutrition in pediatric IBD, including the most recent advances on nutritional therapy

Chronic periodontitis and immunity, towards the implementation of a personalized medicine: A translational research on gene single nucleotide polymorphisms (SNPs) linked to chronic oral dysbiosis in 96 caucasian patients

Chronic periodontitis (CP) is a complex pathology with a significant impact worldwide causing bone loss. Oral dysbiosis is a highly inflammatory condition associated to a long-term insulting infection and represents an underestimated CP key factor associated with an imbalance of pro-inflammatory and anti-inflammatory gene responses. The presence of a single nucleotide polymorphisms (SNPs) in the promoter region of interleukin 10 (IL-10) gene-1082,-819, and-592 was a possible determinant cause. This translational research aimed to provide outcomes on the role of IL-10 gene expression in bone loss diseases in patients affected by CP. Caucasian patients (n = 96) affected by CP were recruited from the Italian population. The subgingival samples were collected using the Bacterial Periodontal Assessment by Biomolecular Diagnostic® and the characterization of a set of 15 bacterial DNA responsible of periodontitis was performed by real-time multiplex PCR. In addition, two viruses, Epstein-Barr Virus (EBV) and Herpes Simplex Virus 1 (HSV-1), and a pathogenic fungi (Candida albicans) were included as a part of our panel. Our results confirmed an existing association between IL-10 gene polymorphisms and polymorphism of tumor necrosis factor alpha (TNFff), interleukin 1α-β-RN (IL-1α-β-RN), collagen type-l alpha (COLIA1), and vitamin D receptor (VDRs) genes in CP. Further studies are needed to improve diagnosis and endorse more effective therapeutic procedures for periodontal disease

The Super Eight Galaxies: Properties of a Sample of Very Bright Galaxies at 7 \u3c z \u3c 8

We present the Super Eight galaxies - a set of very luminous, high-redshift (7.1 \u3c z \u3c 8.0) galaxy candidates found in the Brightest of Reionizing Galaxies (BoRG) Survey fields. The original sample includes eight galaxies that are Y-band dropout objects with H-band magnitudes of m H \u3c 25.5. Four of these objects were originally reported in Calvi et al. Combining new Hubble Space Telescope (HST) WFC3/F814W imaging and Spitzer IRAC data with archival imaging from BoRG and other surveys, we explore the properties of these galaxies. Photometric redshift fitting places six of these galaxies in the redshift range of 7.1 \u3c z \u3c 8.0, resulting in three new high-redshift galaxies and confirming three of the four high-redshift galaxy candidates from Calvi et al. We calculate the half-light radii of the Super Eight galaxies using the HST F160W filter and find that the Super Eight sizes are in line with the typical evolution of size with redshift. The Super Eights have a mean mass of log (M ∗/M o) ∼10, which is typical for sources in this luminosity range. Finally, we place our sample on the UV z ∼ 8 luminosity function and find that the Super Eight number density is consistent with other surveys in this magnitude and redshift range