Love at First Sight: The Interplay Between Privacy Dispositions and Privacy Calculus in Online Social Connectivity Management

Privacy has become the key concern of many users when they are confronted with friend requests on online social networking websites. Nonetheless, users’ responses to friend requests seem at times inconsistent with their concerns about potential privacy implications. They accept friend requests and expose their personal profiles to largely unfamiliar others even though they are aware of the risks involved. Drawing on impression formation theory and the privacy calculus perspective, this paper elucidates the intriguing roles of privacy risks and expected social capital gains in social connectivity management by examining the key types of social information that users consider and their behavioral responses to online friend requests. We conducted a scenario-based experiment with 141 subjects. Our results indicate that individuals utilize two key types of social information; namely, network mutuality and profile diagnosticity in evaluating privacy risks and expected social capital gains. In addition, we find that privacy risks and expected social capital gains powerfully predict the likelihood of no-action and the likelihood of accepting friend requests on online social networking websites. In sum, this study contributes to the information systems literature by integrating impression formation theory and the privacy calculus perspective to identify the key types of social information that influence privacy tradeoff and predict individuals’ behavioral responses toward establishing new online social connections

Versioning data is about more than revisions : A conceptual framework and proposed principles

A dataset, small or big, is often changed to correct errors, apply new algorithms, or add new data (e.g., as part of a time series), etc. In addition, datasets might be bundled into collections, distributed in different encodings or mirrored onto different platforms. All these differences between versions of datasets need to be understood by researchers who want to cite the exact version of the dataset that was used to underpin their research. Failing to do so reduces the reproducibility of research results. Ambiguous identification of datasets also impacts researchers and data centres who are unable to gain recognition and credit for their contributions to the collection, creation, curation and publication of individual datasets. Although the means to identify datasets using persistent identifiers have been in place for more than a decade, systematic data versioning practices are currently not available. In this work, we analysed 39 use cases and current practices of data versioning across 33 organisations. We noticed that the term ‘version’ was used in a very general sense, extending beyond the more common understanding of ‘version’ to refer primarily to revisions and replacements. Using concepts developed in software versioning and the Functional Requirements for Bibliographic Records (FRBR) as a conceptual framework, we developed six foundational principles for versioning of datasets: Revision, Release, Granularity, Manifestation, Provenance and Citation. These six principles provide a high-level framework for guiding the consistent practice of data versioning and can also serve as guidance for data centres or data providers when setting up their own data revision and version protocols and procedures.Peer reviewe

Binding of Hyaluronan to the Native Lymphatic Vessel Endothelial Receptor LYVE-1 Is Critically Dependent on Receptor Clustering and Hyaluronan Organization

The lymphatic endothelial receptor LYVE-1 has been implicated in both uptake of hyaluronan (HA) from tissue matrix and in facilitating transit of leukocytes and tumor cells through lymphatic vessels based largely on in vitro studies with recombinant receptor in transfected fibroblasts. Curiously, however, LYVE-1 in lymphatic endothelium displays little if any binding to HA in vitro, and this has led to the conclusion that the native receptor is functionally silenced, a feature that is difficult to reconcile with its proposed in vivo functions. Nonetheless, as we reported recently, LYVE-1 can function as a receptor for HA-encapsulated Group A streptococci and mediate lymphatic dissemination in mice. Here we resolve these paradoxical findings and show that the capacity of LYVE-1 to bind HA is strictly dependent on avidity, demanding appropriate receptor self-association and/or HA multimerization. In particular, we demonstrate the prerequisite of a critical LYVE-1 threshold density and show that HA binding may be elicited in lymphatic endothelium by surface clustering with divalent LYVE-1 mAbs. In addition, we show that cross-linking of biotinylated HA in streptavidin multimers or supramolecular complexes with the inflammation-induced protein TSG-6 enables binding even in the absence of LYVE-1 cross-linking. Finally, we show that endogenous HA on the surface of macrophages can engage LYVE-1, facilitating their adhesion and transit across lymphatic endothelium. These results reveal LYVE-1 as a low affinity receptor tuned to discriminate between different HA configurations through avidity and establish a new mechanistic basis for the functions ascribed to LYVE-1 in matrix HA binding and leukocyte trafficking in vivo

Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis

Transferrin, an iron-transporting serum glycoprotein, is efficiently taken up into cells by the process of receptor-mediated endocytosis. Transferrin receptors are found on the surface of most proliferating cells, in elevated numbers on erythroblasts and on many kinds of tumors. The efficient cellular mechanism for uptake of transferrin has been subverted for the delivery of low-molecular-weight drugs, protein toxins, and liposomes by linkage of these agents to transferrin or to anti-transferrin receptor antibodies. Linkage may be via chemical conjugation procedures or by the generation of chimeric fusion proteins. Transferrin conjugated to DNA-binding compounds (e.g. polycations or intercalating agents) has been successfully used for the import of DNA molecules into cells. High-level gene expression is obtained only if endosome-disruptive agents such as influenza hemagglutinin peptides or adenovirus particles are included which release the DNA complex from intracellular vesicles into the cytoplasm

Btk inhibition treats TLR7/IFN driven murine lupus.

ABSTRACTBruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling

Genome-wide Analysis of Motor Progression in Parkinson Disease

BACKGROUND AND OBJECTIVES: The genetic basis of Parkinson disease (PD) motor progression is largely unknown. Previous studies of the genetics of PD progression have included small cohorts and shown a limited overlap with genetic PD risk factors from case-control studies. Here, we have studied genomic variation associated with PD motor severity and early-stage progression in large longitudinal cohorts to help to define the biology of PD progression and potential new drug targets. METHODS: We performed a GWAS meta-analysis of early PD motor severity and progression up to 3 years from study entry. We used linear mixed-effect models with additive effects, corrected for age at diagnosis, sex, and the first 5 genetic principal components to assess variability in axial, limb, and total Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores. RESULTS: We included 3,572 unrelated European ancestry patients with PD from 5 observational cohorts and 1 drug trial. The average AAO was 62.6 years (SD = 9.83), and 63% of participants were male. We found an average increase in the total MDS-UPDRS III score of 2.3 points/year. We identified an association between PD axial motor progression and variation at the GJA5 locus at 1q12 (β = -0.25, SE = 0.04, p = 3.4e-10). Exploration of the regulation of gene expression in the region (cis-expression quantitative trait loci [eQTL] analysis) showed that the lead variant was associated with expression of ACP6, a lysophosphatidic acid phosphatase that regulates mitochondrial lipid biosynthesis (cis-eQTL p-values in blood and brain RNA expression data sets: <10-14 in eQTLGen and 10-7 in PsychEncode). DISCUSSION: Our study highlights the potential role of mitochondrial lipid homeostasis in the progression of PD, which may be important in establishing new drug targets that might modify disease progression