Creating semiclassical black holes in collider experiments and keeping them on a string

We argue that a simple modification of the TeV scale quantum gravity scenario allows production of semiclassical black holes in particle collisions at the LHC. The key idea is that in models with large extra dimensions the strength of gravity in the bulk can be higher than on the brane where we live. A well-known example of this situation is the case of warped extra dimensions. Even if the energy of the collision is not sufficient to create a black hole on the brane, it may be enough to produce a particle which accelerates into the bulk up to trans-Planckian energy and creates a large black hole there. In a concrete model we consider, the black hole is formed in a collision of the particle with its own image at an orbifold plane. When the particle in question carries some Standard Model gauge charges the created black hole gets attached to our brane by a string of the gauge flux. For a 4-dimensional observer such system looks as a long-lived charged state with the mass continuously decreasing due to Hawking evaporation of the black hole. This provides a distinctive signature of black hole formation in our scenario.Comment: Journal version, a misprint correcte

Synthesis and Characterization of a Model Nickel Superoxide Dismutase Metallopeptide Functionalized for Hydrogen Production

Hydrogenases (H2ase) are naturally occuring enzymes that reversibly catalyze the oxidation and production of H2 from protons at low overpotential with very high catalytic activity. As a result these enzymes have gained increased attention over recent years as potential models for technological materials in the industrial production of hydrogen as a stock fuel. Despite the many attempts to replicate the properties of these enzymes synthetically, very few synthetic models have shown catalytic activity comparable to that of the native enzyme. This project seeks to utilize key features from the coordination environment selected by nature for the seemingly unrelated NiSOD (nickel-superoxide dismutase) metalloenzyme to produce a biological mimic of [NiFe]H2ase. A metallopeptide consisting of the 12 N-terminal residues from the NiSOD primary sequence, which has been extensively studied by the Shearer group, was used as the basis for constructing this mimic because it is a structurally and mechanistically welldefined system. Careful consideration of the requirements necessary for nickel coordination to the NiSOD apopeptide and the influence of structure on the reactivity of the nickel containing metallopeptide provided a guide for its modification resulting in properties that may be useful in the construction of an H2ase active metallopeptide. Substitution of the N-terminal histidine residue with the phosphine PTA (1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) is proposed to optimize the active site of this enzyme toward H2 production while maintaining redox activity and stability. The synthesis and characterization by nuclear magnetic resonance, electronic absorption and X-ray absorption spectroscopy of this modified maquette are reported herein. It will be shown that this novel metallopeptide [Ni(H2aseM1)] contains NiII in square pyramidal environment with ligands derived from the PTA (P atom), Cys(2) and Cys(6) (S atoms), the Cys(2) amidate (N atom) and water (H2O). Further studies of this system will be aimed at understanding the functional properties of the metallopeptide as a hydrogenase

A FAMILY OF CATION ATPASE-LIKE MOLECULES FROM PLASMODIUM-FALCIPARUM

Abstract. We report the nucleotide and derived amino acid sequence of the ATPase 1 gene from Plasmodium falciparum. The amino acid sequence shares homology with the family of "P-type cation transloeating ATPases in conserved regions important for nucleotide binding, conformational change, or phosphorylation. The gene, which is present on chromosome 5, has a product longer than any other reported for a P-type ATPase. Interstrain analysis from 12 parasite isolates by the polymerase chain reaction reveals that a 330-bp nucleotide sequence encoding three cytoplasmic regions conserved in cation ATPases (regions a-c) is of constant length. By contrast, another 360-bp sequence which is one of four regions we refer to as

Letter, George G. Meade to A. M. Gayley, December 12, 1865

This handwritten letter, dated December 12, 1865, is written from George G. Meade, a United States Army officer and civil engineer best known for decisively defeating Confederate General Robert E. Lee at the Battle of Gettysburg in the American Civil War, to A. M. Gayley. The letter is a thank you note for some items that were sent to him. There is some staining in the center of the page. This letter was found tipped into volume seven, between pages 262-263 of Abraham Lincoln : A History by John G. Nicolay and John Hay.https://scholarsjunction.msstate.edu/fvw-manuscripts-nicolay-and-hay-documents/1041/thumbnail.jp

β-Defensins: Farming the Microbiome for Homeostasis and Health

peer-reviewedDiverse commensal populations are now regarded as key to physiological homeostasis and protection against disease. Although bacteria are the most abundant component of microbiomes, and the most intensively studied, the microbiome also consists of viral, fungal, archael, and protozoan communities, about which comparatively little is known. Host-defense peptides (HDPs), originally described as antimicrobial, now have renewed significance as curators of the pervasive microbial loads required to maintain homeostasis and manage microbiome diversity. Harnessing HDP biology to transition away from non-selective, antibiotic-mediated treatments for clearance of microbes is a new paradigm, particularly in veterinary medicine. One family of evolutionarily conserved HDPs, β-defensins which are produced in diverse combinations by epithelial and immune cell populations, are multifunctional cationic peptides which manage the cross-talk between host and microbes and maintain a healthy yet dynamic equilibrium across mucosal systems. They are therefore key gatekeepers to the oral, respiratory, reproductive and enteric tissues, preventing pathogen-associated inflammation and disease and maintaining physiological normality. Expansions in the number of genes encoding these natural antibiotics have been described in the genomes of some species, the functional significance of which has only recently being appreciated. β-defensin expression has been documented pre-birth and disruptions in their regulation may play a role in maladaptive neonatal immune programming, thereby contributing to subsequent disease susceptibility. Here we review recent evidence supporting a critical role for β-defensins as farmers of the pervasive and complex prokaryotic ecosystems that occupy all body surfaces and cavities. We also share some new perspectives on the role of β-defensins as sensors of homeostasis and the immune vanguard particularly at sites of immunological privilege where inflammation is attenuated

Avian Resistance to Campylobacter jejuni Colonization Is Associated with an Intestinal Immunogene Expression Signature Identified by mRNA Sequencing

peer-reviewedThis research was funded by the The Irish Department of Agriculture and Food’s Food Institutional Research Measure (http://www.agriculture.gov.ie/ research/foodinstitutionalresearchmeasurefirm) – Grant No: 06_RDD_486.Campylobacter jejuni is the most common cause of human bacterial gastroenteritis and is associated with several post-infectious manifestations, including onset of the autoimmune neuropathy Guillain-Barré syndrome, causing significant morbidity and mortality. Poorly-cooked chicken meat is the most frequent source of infection as C. jejuni colonizes the avian intestine in a commensal relationship. However, not all chickens are equally colonized and resistance seems to be genetically determined. We hypothesize that differences in immune response may contribute to variation in colonization levels between susceptible and resistant birds. Using high-throughput sequencing in an avian infection model, we investigate gene expression associated with resistance or susceptibility to colonization of the gastrointestinal tract with C. jejuni and find that gut related immune mechanisms are critical for regulating colonization. Amongst a single population of 300 4-week old chickens, there was clear segregation in levels of C. jejuni colonization 48 hours post-exposure. RNAseq analysis of caecal tissue from 14 C. jejuni-susceptible and 14 C. jejuni-resistant birds generated over 363 million short mRNA sequences which were investigated to identify 219 differentially expressed genes. Significantly higher expression of genes involved in the innate immune response, cytokine signaling, B cell and T cell activation and immunoglobulin production, as well as the renin-angiotensin system was observed in resistant birds, suggesting an early active immune response to C. jejuni. Lower expression of these genes in colonized birds suggests suppression or inhibition of a clearing immune response thus facilitating commensal colonization and generating vectors for zoonotic transmission. This study describes biological processes regulating C. jejuni colonization of the avian intestine and gives insight into the differential immune mechanisms incited in response to commensal bacteria in general within vertebrate populations. The results reported here illustrate how an exaggerated immune response may be elicited in a subset of the population, which alters host-microbe interactions and inhibits the commensal state, therefore having wider relevance with regard to inflammatory and autoimmune disease

Non-canonical Inflammasome-Mediated IL-1β Production by Primary Endometrial Epithelial and Stromal Fibroblast Cells Is NLRP3 and Caspase-4 Dependent

peer-reviewedInflammation of the post-partum uterus is a normal physiological event, crucial for tissue involution and repair. However, in the bovine, some cows fail to resolve this inflammation, resulting in endometritis, which compromises fertility. Earlier work has identified upregulated expression of the potent inflammatory cytokine IL-1β early post-partum, in cows which subsequently develop endometritis. As a result, targeting IL-1β expression holds potential as a novel treatment for this disease, yet the regulatory mechanisms contributing to IL-1β expression in the bovine endometrium remain unknown. To investigate this, endometrial tissue samples were obtained 7 and 21 days post-partum (DPP) from cows that were diagnosed with endometritis at 21 DPP and cows that experienced a physiological level of inflammation throughout involution. IL-1β was measured by qPCR, ELISA, and immunohistochemistry. Seven DPP, endometrial IL-1β protein levels were significantly higher in animals that proceeded to develop endometritis at 21 DPP. IL-1β production could be detected in luminal and glandular epithelium, in underlying stromal fibroblasts as well as infiltrating immune cells. To investigate the mechanisms regulating IL-1β expression, primary endometrial epithelial cells, stromal fibroblasts and PBMCs were stimulated with LPS and the inflammasome activator nigericin. Stromal fibroblast cells were particularly potent producers of IL-1β. Basolateral LPS stimulation of polarized epithelial cells induced IL1B mRNA and a previously undescribed IL-1β protein isoform, with preferential protein secretion into the apical compartment. Key inflammasome components [nod-like receptor protein 3 (NLRP3), nima-related kinase-7 (NEK7), apoptosis speck like protein containing a CARD (ASC), and gasdermin-D] were expressed by endometrial cells following stimulation. Endometrial cell stimulation in the presence of NLRP3 receptor (MCC950) and pan-caspase (Z-VAD-FMK) inhibitors blocked IL-1β production, demonstrating its dependence on the NLRP3 inflammasome and on caspase activity. Furthermore, caspase-4 specific siRNA prevented IL-1β production, confirming that inflammasome activation in endometrial cells is caspase-4 but not caspase-1 dependent, as shown in other species. Identifying the tissue- and species-specificity of inflammasome assembly and activation has critical relevance for our understanding of inflammation and suggests new therapeutic targets to enhance the resolution of inflammatory pathologies including endometritis in cattle

The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

peer-reviewedWe hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle

Cervico-vaginal mucus (CVM) – an accessible source of immunologically informative biomolecules

peer-reviewedCervico-vaginal mucus (CVM), the product of epithelial cells lining the uterus, cervix and vagina, is secreted to facilitate uterine lubrication and microbial clearance. Predominantly composed of water and mucins, CVM also contains high levels of immuno-active proteins such as immunoglobulin A (IgA), lactoferrin and lysozyme which protect against infection by blocking adhesion and mediating microbial killing. The repertoire of cytokines, chemokines and antimicrobial peptides is predominantly generated by the secretions of endometrial epithelial cells into the uterine lumen and concentrated in the CVM. The quantity and relative proportions of these inflammatory biomarkers are affected by diverse factors including the estrus cycle and health status of the animal and therefore potentially provide important diagnostic and prognostic indicators. We propose that measuring molecular signatures in bovine CVM could be a useful approach to identifying and monitoring genital tract pathologies in beef and dairy cows

Spectacle lens fabrication in an optometric practice

Recently many of our classmates have asked questions concerning the actual set-up of an ophthalmic lens fabrication lab in an optometric practice. Our colleagues and peers not only want to know about feasibility, investment, space, equipment, and prices, but also how to perform the actual process of spectacle making. As graduating optometrists some of our classmates will enter into an association with an older established optometrist and some will go into solo practice. In either case one of their duties may be doing the actual lab work in spectacle fabrication. This is very common practice in the current optometric community. As more and more optometrists become involved with lab work, the need for a manual of this type is obvious. A literature search proved fruitless in obtaining any source that covers the breadth and scope of the edging process in its entirety. Optometric and optician\u27s publications sometimes deal with various aspects of the spectacle fabrication process, but we have found these to be too general and in the style of an overview or snapshot . We were unable to find any source containing the actual mechanisms involved. A previous research project involved a video tape of the edging process from a local laboratory, and was aimed toward explaining how the edging process is accomplished. We feel that the tape was good in that it oriented the viewer as to how this is done . However, the thrust of our project is to explain, step-by-step, how to edge lenses in an optometric office. The manual will be written from the perspective of How to do it , rather than how it is done . To our knowledge, this work will be the first of its kind, and will represent a compilation of technical information obtained from manufacturers of laboratory equipment, combined with textbook information, and original writings based on our training and experience as laboratory 1 opticians. The authors do not intend this manual to be a statement saying that professional optometrists should spend their time edging lenses. To the contrary, we feel that the optometrist should spend his/her time doing what he/she was trained to do, that is, providing vision care. If however, a spectacle fabrication lab is to be incorporated into an optometric practice, two things are necessary. First, the optometrist needs to know the processes involved as well as the equipment required in order to set up the lab. Second, he/she needs a working knowledge of the basic mechanics and procedures involved, in order to train personnel if necessary