Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations

Epstein-Barr virus (EBV) is a highly successful herpesvirus, colonizing more than 90% of the adult human population worldwide, although it is also associated with various malignant diseases. Primary infection is usually clinically silent, and subsequent establishment of latency in the memory B lymphocyte compartment allows persistence of the virus in the infected host for life. EBV is so markedly B-lymphotropic when exposed to human lymphocytes in vitro that the association of EBV with rare but distinct types of T and NK cell lymphoproliferations was quite unexpected. Whilst relatively rare, these EBV-associated T and NK lymphoproliferations can be therapeutically challenging and prognosis for the majority of patients is dismal. In this review, we summarize the current knowledge on the role of EBV in the pathogenesis of these tumours, and the implications for treatment. \ud \u

“Design of Molecular Mechanics Modeling Techniques For Exploring Molecular Recognition Using Cyclodextrins.

Molecular mechanics modeling techniques have been developed to study the behavior of cyclodextrins (CDs) in capillary electrophoresis (CE) separations. Using the commercial computational package, Sybyl, the mechanisms of molecular recognition between organic analytes and CDs are investigated. Cyclodextrin-modified capillary electrochromatography (CDCE) experiments were conducted to separate neutral derivitized naphthalene solutes using carboxymethyl-beta-cyclodextrin (CM-b-CD). Grid conformation-searching programs were developed to explore the interaction space between CD and solute and to calculate their interaction energies using molecular mechanics. The interaction energies correlated remarkably well with the separation behavior. It was found that extensive minimization (more than 3000 iterations) was required at each of the docking positions to achieve the best agreement between computational and experimental distribution coefficients (Kd). Molecular modeling techniques were also used to guide the development of a new charged cyclodextrin resolving agent, heptakis (6-O-carboxymethyl-2,3-dimethyl)-b-cyclodextrin (HDMCM-b-CD). Molecular computer aided design (MolCAD) analysis and docking techniques revealed that HDMCM-b-CD would be superior to commercially available CDs for forming inclusion complexes with the target naphthalene derivative analytes. Molecular modeling studies also showed that significant intermolecular CD-CD interactions can occur under certain conditions, explaining some anomalous experimental findings. Additionally, the grid conformation-searching modeling technique was applied to chiral CDCE separations of dansyl amino acids (AAs) to explain separation behavior and to investigate different CD-CD interactions

Reverse genetic screening of innexin gap junction proteins in drosophila neurons

The reflexive response and perception of pain (nociception) is an evolutionarily conserved process in animals. Pain can be a major health concern and current treatments often prove insufficient, especially in regards to chronic pain. Greater understanding of the molecular processes underlying pain sensation could lead to new and more effective treatments. The aim of this study is to investigate the molecular mechanisms of cold nociception in Drosophila melanogaster. A specific subset of peripheral sensory neurons (Class III dendritic arborization (da) neurons), are implicated in Drosophila larvae’s response to noxious cold. Previous literature has associated a family of gap junction protein, termed Innexins, to be responsible for various roles in the structure of the central nervous system and the giant fiber system in Drosophila. It is unknown if the Innexin family also functions in the Peripheral Nervous System (PNS). This study focused on Innexin family members as potential mediators of noxious cold-evoked sensory behavior within multidendritic neurons of the PNS. A cold behavioral assay was used to investigate the role of two innexin family member genes: ogre and shaking-B. The analyses revealed that Shaking-B may be required for nociceptors to react properly to a cold stimulus. Ogre was revealed to have an apparent inverse effect, in which Drosophila larvae responded more strongly to a cold stimulus when lacking the gene producct. These studies indicate that Innexins probably do play a role in the peripheral nervous system and in reacting to noxious cold stimuli

Transient Large-Scale Chlorine Releases in the Jack Rabbit II Field Tests: Rainout Source Data Analysis from Video Records

PresentationSponsored by the Chemical Security Analysis Center (CSAC) of the U.S. Department of Homeland Security, the Defense Threat Reduction Agency (DTRA) of the U.S. Department of Defense, Transport Canada, and Defence Research and Development Canada (DRDC), the Jack Rabbit II tests were designed to release liquid chlorine at ambient temperature in quantities of 5 to 20 T for the purpose of quantifying the behavior and hazards of catastrophic chlorine releases at scales represented by rail and truck transport vessels. In 2015, five successful field trials were conducted in which chlorine was released in quantities of 5 to 10 tons through a 6-inch circular breach in the tank and directed vertically downward at 1 m elevation over a concrete pad. In 2016, three additional trials were conducted with releases of 10 tons also through 6-inch circular breaches at different release orientations. A final 20 ton test was conducted in 2016. Data from the test program is being made available. This paper summarizes an analysis of the available data from the concrete pad including analysis of the temperature measurements below and above grade in the concrete pad. Assessment of the chlorine rainout is estimated based on temperature measurements and available video data analysis

Isolation and Biochemical Characterization of Rubelase, a Non-Hemorrhagic Elastase from Crotalus ruber ruber (Red Rattlesnake) Venom

A novel non-hemorrhagic basic metalloprotease, rubelase, was isolated from the venom of Crotalus ruber ruber. Rubelase hydrolyzes succinyl-L-alanyl-L-alanyl-L-alanyl p-nitroanilide (STANA), a specific substrate for elastase, and the hydrolytic activity was inhibited by chelating agents. It also hydrolyzes collagen and fibrinogen. However, hemorrhagic activity was not observed. By ESI/Q-TOF and MALDI/TOF mass spectrometry combined with Edman sequencing procedure, the molecular mass of rubelase was determined to be 23,266 Da. Although its primary structure was similar to rubelysin (HT-2), a hemorrhagic metalloprotease isolated from the same snake venom, the circumstances surrounding putative zinc binding domain HEXXHXXGXXH were found to be different when the three-dimensional computer models of both metalloproteases were compared. The cytotoxic effects of rubelase and rubelysin on cultured endothelial and smooth muscle cells were also different, indicating that the substitution of several amino acid residues causes the changes of active-site conformation and cell preference

Discover EDS: Tales of Implementation and Use

This paper supplements the panel, which was delivered in a “Lively Lunch” format and included presentations by librarians who have employed EBSCO’s Discovery System (EDS) in their academic institutions. The panelists addressed several important aspects of launching a discovery system in an academic library, such as Implementation; Information Literacy; and Assessment, Usability and Customization. The implementation component included technical aspects, business requirements, enhancing the operability of link resolvers, launch preparation, and implementation success. The information literacy portion addressed how academic reference services and library instruction have been transformed because of EDS. Assessment, Usability and Customization focused on customizing the search box and assessing EDS using statistics and usability testing. Michael Gorrell, Executive Vice President of Technology and Chief Information Officer of EBSCO Publishing, was present, and a Q&A time was scheduled at the end of each session for audience members to ask questions, comment, and share experiences. The implementation process of a Discovery Service involves many different aspects and is a large undertaking for any library. Depending on the size of the library, its technology infrastructure, and the number of staff involved, the implementation time can vary greatly. In addition, the planning processes and the considerations made prior to implementation are also affected by the nature and needs of end-users in these institutions. Selecting the resources to include in the discovery service, resolving technical issues, developing a strategy to publicize and market to end-users, and assessing and customizing the product are all part of a continuous course of implementing Discovery Services—a process that begins long before implementation and has no fixed completion. This process involves a collaborative and consorted effort from all areas of librarian expertise, from technical services to public services. The simplicity and comprehensiveness of discovery tools redefine how libraries deliver services across the board, changing the expectations users have of the experience of searching library resources and challenging librarians to redesign instruction and teach information literacy in new ways. These considerations and our own experience with implementing EBSCO’s Discovery System (EDS) at the University of South Florida prompted us to open up a discussion across university and college libraries in the U.S. and across librarian functions, technical, and public services, in order to share, discuss, and learn from each other the lessons of Discovery Service implementation and use. We wanted to focus on the continuous nature of this process, involving the user perspective, as well as the perspective of the vendor, EBSCO. We believe that talking with our colleagues and collaborating with publishers makes us much better positioned to anticipate the changing needs of users and enhance the experience, accessibility, and discoverability of library content

Obesity accelerates Helicobacter felis-induced gastric carcinogenesis by enhancing immature myeloid cell trafficking and TH17 response

Objective: To investigate the role of obesity-associated inflammation and immune modulation in gastric carcinogenesis during Helicobacter-induced chronic gastric inflammation. Design: C57BL/6 male mice were infected with H felis and placed on a high-fat diet (45% calories from fat). Study animals were analysed for gastric and adipose pathology, inflammatory markers in serum, stomach and adipose tissue, and immune responses in blood, spleen, stomach and adipose tissue. Results: H felis-induced gastric carcinogenesis was accelerated in diet-induced obese mice compared with lean controls. Obesity increased bone marrow-derived immature myeloid cells in blood and gastric tissue of H felis-infected mice. Obesity also led to elevations in CD4 T cells, IL-17A, granulocyte macrophage colony-stimulating factor, phosphorylated STAT3 and prosurvival gene expression in gastric tissue of H felis-infected mice. Conversely, in adipose tissue of obese mice, H felis infection increased macrophage accumulation and expression of IL-6, C-C motif ligand 7 (CCL7) and leptin. Finally, the combination of obesity and gastric inflammation synergistically increased serum proinflammatory cytokines, including IL-6. Conclusions: Here, we have established a model to study the molecular mechanism by which obesity predisposes individuals to gastric cancer. In H felis-infected mice, obesity increased proinflammatory immune responses and accelerated gastric carcinogenesis. Interestingly, gastric inflammation augmented obesity-induced adipose inflammation and production of adipose-derived factors in obese, but not lean, mice. Our findings suggest that obesity accelerates Helicobacter-associated gastric cancer through cytokine-mediated cross-talk between inflamed gastric and adipose tissues, augmenting immune responses at both tissue sites, and thereby contributing to a protumorigenic gastric microenvironment.National Institutes of Health (U.S.) (grant 5R01CA093405-11)Columbia University Medical Center (Naomi Berrie Diabetes Center, grant P30DK063608

A comparison of facial expression properties in five hylobatid species

Little is known about facial communication of lesser apes (family Hylobatidae) and how their facial expressions (and use of) relate to social organization. We investigated facial expressions (defined as combinations of facial movements) in social interactions of mated pairs in five different hylobatid species belonging to three different genera using a recently developed objective coding system, the Facial Action Coding System for hylobatid species (GibbonFACS). We described three important properties of their facial expressions and compared them between genera. First, we compared the rate of facial expressions, which was defined as the number of facial expressions per units of time. Second, we compared their repertoire size, defined as the number of different types of facial expressions used, independent of their frequency. Third, we compared the diversity of expression, defined as the repertoire weighted by the rate of use for each type of facial expression. We observed a higher rate and diversity of facial expression, but no larger repertoire, in Symphalangus (siamangs) compared to Hylobates and Nomascus species. In line with previous research, these results suggest siamangs differ from other hylobatids in certain aspects of their social behavior. To investigate whether differences in facial expressions are linked to hylobatid socio-ecology, we used a Phylogenetic General Least Square (PGLS) regression analysis to correlate those properties with two social factors: group-size and level of monogamy. No relationship between the properties of facial expressions and these socio-ecological factors was found. One explanation could be that facial expressions in hylobatid species are subject to phylogenetic inertia and do not differ sufficiently between species to reveal correlations with factors such as group size and monogamy level. Am. J. Primatol. 76:618-628, 2014