Differential Subcellular Localization of the Splice Variants of the Zinc Transporter ZnT5 Is Dictated by the Different C-Terminal Regions

Zinc is emerging as an important intracellular signaling molecule, as well as fulfilling essential structural and catalytic functions through incorporation in a myriad of zinc metalloproteins so it is important to elucidate the molecular mechanisms of zinc homeostasis, including the subcellular localizations of zinc transporters.Two splice variants of the human SLC30A5 Zn transporter gene (ZnT5) have been reported in the literature. These variants differ at their N- and C-terminal regions, corresponding with the use of different 5' and 3' exons. We demonstrate that full length human ZnT5 variant B is a genuine transcript in human intestinal cells and confirm expression of both variant A and variant B in a range of untreated human tissues by splice variant-specific RT-PCR. Using N- or C-terminal GFP or FLAG fusions of both isoforms of ZnT5 we identify that the differential subcellular localization to the Golgi apparatus and ER respectively is a function of their alternative C-terminal sequences. These different C-terminal regions result from the incorporation into the mature transcript of either the whole of exon 14 (variant B) or only the 5' region of exon 14 plus exons 15-17 (variant A).We thus propose that exons 15 to 17 include a signal that results in trafficking of ZnT5 to the Golgi apparatus and that the 3' end of exon 14 includes a signal that leads to retention in the ER

The Nonlinear Stability of the Trivial Solution to the Maxwell-Born-Infeld System

In this article, we use an electromagnetic gauge-free framework to establish the existence of small-data global solutions to the Maxwell-Born-Infeld (MBI) system on the Minkowski space background in 1 + 3 dimensions. Because the nonlinearities in the system satisfy a version of the null condition, we are also able to show that these solutions decay at exactly the same rates as solutions to the linear Maxwell-Maxwell system. In addition, we show that on any Lorentzian manifold, the MBI system is hyperbolic in the interior of the field-strength regime in which its Lagrangian is real-valued.Comment: A few additional comments and some references were added. Some typos were corrected. 73 page

Manual / Issue 9 / Out of Line

Manual, a journal about art and its making. Out of Line. The nineth issue. This issue of *Manual*—themed Out of Line—is a collection about the way that lines disrupt, point outward. In poetry, the attention to detail one takes in crafting a line is all about making the line disappear, making something it holds to take front stage. . . . The space between the lines creating the image . . . the space around that argues for the importance of all that the lines hold. Manual 9 (Out of Line) complemented Lines of Thought: Drawing from Michelangelo to Now, presented in collaboration with the British Museum, on view at the RISD Museum October 6, 2017 to January 7, 2018. Softcover, 76 pages. Published 2017 by the RISD Museum. Manual 9 (Out of Line) contributors include Fida Adely, Reginald Dwayne Betts, Stefano Bloch, Mimi Cabell, Namita Vijay Dharia, Douglas W. Doe, Jared A. Goldstein, Lucinda Hitchcock, Jan Howard, Kate Irvin, Douglas Kearney, Amber Lopez, Jeffrey Moser, Sheida Soleimani, and Craig Taylor.https://digitalcommons.risd.edu/risdmuseum_journals/1035/thumbnail.jp

Immune responses to influenza D virus in calves previously infected with bovine viral diarrhea virus 2

Bovine viral diarrhea virus (BVDV) induces immunosuppression and thymus depletion in calves. This study explores the impact of prior BVDV-2 exposure on the subsequent immune response to influenza D virus (IDV). Twenty 3-week-old calves were divided into four groups. Calves in G1 and G3 were mock-treated on day 0, while calves in G2 and G4 received BVDV. Calves in G1 (mock) and G2 (BVDV) were necropsied on day 13 post-infection. IDV was inoculated on day 21 in G3 calves (mock + IDV) and G4 (BVDV + IDV) and necropsy was conducted on day 42. Pre-exposed BVDV calves exhibited prolonged and increased IDV shedding in nasal secretions. An approximate 50% reduction in the thymus was observed in acutely infected BVDV calves (G2) compared to controls (G1). On day 42, thymus depletion was observed in two calves in G4, while three had normal weight. BVDV-2-exposed calves had impaired CD8 T cell proliferation after IDV recall stimulation, and the α/β T cell impairment was particularly evident in those with persistent thymic atrophy. Conversely, no difference in antibody levels against IDV was noted. BVDV-induced thymus depletion varied from transient to persistent. Persistent thymus atrophy was correlated with weaker T cell proliferation, suggesting correlation between persistent thymus atrophy and impaired T cell immune response to subsequent infections.Veterinary PathobiologyDean of Veterinary Medicin

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

The Great Mortgaging: Housing Finance, Crises, and Business Cycles

This paper unveils a new resource for macroeconomic research: a long-run dataset covering disaggregated bank credit for 17 advanced economies since 1870. The new data show that the share of mortgages on banks' balance sheets doubled in the course of the 20th century, driven by a sharp rise of mortgage lending to households. Household debt to asset ratios have risen substantially in many countries. Financial stability risks have been increasingly linked to real estate lending booms which are typically followed by deeper recessions and slower recoveries. Housing finance has come to play a central role in the modern macroeconomy

Novel analytical method, Birth Date Selection Mapping, detects response of the Angus (Bos taurus) genome to selection on complex traits

Background: Several methods have recently been developed to identify regions of the genome that have been exposed to strong selection. However, recent theoretical and empirical work suggests that polygenic models are required to identify the genomic regions that are more moderately responding to ongoing selection on complex traits. We examine the effects of multi-trait selection on the genome of a population of US registered Angus beef cattle born over a 50-year period representing approximately 10 generations of selection. We present results from the application of a quantitative genetic model, called Birth Date Selection Mapping, to identify signatures of recent ongoing selection.Results: We show that US Angus cattle have been systematically selected to alter their mean additive genetic merit for most of the 16 production traits routinely recorded by breeders. Using Birth Date Selection Mapping, we estimate the time-dependency of allele frequency for 44,817 SNP loci using genomic best linear unbiased prediction, generalized least squares, and BayesCpi analyses. Finally, we reconstruct the primary phenotypes that have historically been exposed to selection from a genome-wide analysis of the 16 production traits and gene ontology enrichment analysis.Conclusions: We demonstrate that Birth Date Selection Mapping utilizing mixed models corrects for time-dependent pedigree sampling effects that lead to spurious SNP associations and reveals genomic signatures of ongoing selection on complex traits. Because multiple traits have historically been selected in concert and most quantitative trait loci have small effects, selection has incrementally altered allele frequencies throughout the genome. Two quantitative trait loci of large effect were not the most strongly selected of the loci due to their antagonistic pleiotropic effects on strongly selected phenotypes. Birth Date Selection Mapping may readily be extended to temporally-stratified human or model organism populations.Peer reviewedAnimal Scienc

Parental investment by skin feeding in a caecilian amphibian

Although the initial growth and development of most multicellular animals depends on the provision of yolk, there are many varied contrivances by which animals provide additional or alternative investment in their offspring(1). Providing offspring with additional nutrition should be favoured by natural selection when the consequent increased fitness of the young offsets any corresponding reduction in fecundity(2). Alternative forms of nutrition may allow parents to delay and potentially redirect their investment. Here we report a remarkable form of parental care and mechanism of parent-offspring nutrient transfer in a caecilian amphibian. Boulengerula taitanus is a direct-developing, oviparous caecilian(3), the skin of which is transformed in brooding females to provide a rich supply of nutrients for the developing offspring. Young animals are equipped with a specialized dentition, which they use to peel and eat the outer layer of their mother's modified skin. This new form of parental care provides a plausible intermediate stage in the evolution of viviparity in caecilians. At independence, offspring of viviparous and of oviparous dermatotrophic caecilians are relatively large despite being provided with relatively little yolk. The specialized dentition of skin-feeding (dermatophagous) caecilians may constitute a pre-adaptation to the fetal feeding on the oviduct lining of viviparous caecilians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62957/1/nature04403.pd

Retrieving the C and O Abundances of HR 7672~AB: a Solar-Type Primary Star with a Benchmark Brown Dwarf

A benchmark brown dwarf (BD) is a BD whose properties (e.g., mass and chemical composition) are precisely and independently measured. Benchmark BDs are valuable in testing theoretical evolutionary tracks, spectral synthesis, and atmospheric retrievals for sub-stellar objects. Here, we report results of atmospheric retrieval on a synthetic spectrum and a benchmark BD -- HR 7672~B -- with \petit. First, we test the retrieval framework on a synthetic PHOENIX BT-Settl spectrum with a solar composition. We show that the retrieved C and O abundances are consistent with solar values, but the retrieved C/O is overestimated by 0.13-0.18, which is $\sim$4 times higher than the formal error bar. Second, we perform retrieval on HR 7672~B using high spectral resolution data (R=35,000) from the Keck Planet Imager and Characterizer (KPIC) and near infrared photometry. We retrieve [C/H], [O/H], and C/O to be $-0.24\pm0.05$, $-0.19\pm0.04$, and $0.52\pm0.02$. These values are consistent with those of HR 7672~A within 1.5-$\sigma$. As such, HR 7672~B is among only a few benchmark BDs (along with Gl 570~D and HD 3651~B) that have been demonstrated to have consistent elemental abundances with their primary stars. Our work provides a practical procedure of testing and performing atmospheric retrieval, and sheds light on potential systematics of future retrievals using high- and low-resolution data.Comment: 29 pages, 17 figures, 5 tables, resubmitted to AAS journals after first revisio

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN