Mouse models for pseudoxanthoma elasticum: Genetic and dietary modulation of the ectopic mineralization phenotypes

Pseudoxanthoma elasticum (PXE), a heritable ectopic mineralization disorder, is caused by mutations in the ABCC6 gene. Null mice ( Abcc6 -/-) recapitulate the genetic, histopathologic and ultrastructural features of PXE, and they demonstrate early and progressive mineralization of vibrissae dermal sheath, which serves as a biomarker of the overall mineralization process. Recently, as part of a mouse aging study at The Jackson Laboratory, 31 inbred mouse strains were necropsied, and two of them, KK/HlJ and 129S1/SvImJ, were noted to have vibrissae dermal mineralization similar to Abcc6-/- mice. These two strains were shown to harbor a single nucleotide polymorphism (rs32756904) in the Abcc6 gene, which resulted in out-of-frame splicing and marked reduction in ABCC6 protein expression in the liver of these mice. The same polymorphism is present in two additional mouse strains, DBA/2J and C3H/HeJ, with similar reduction in Abcc6 protein levels, yet these mice did not demonstrate tissue mineralization when kept on standard rodent diet. However, all four mouse strains, when placed on experimental diet enriched in phosphate and low in magnesium, developed extensive ectopic mineralization. These results indicate that the genetic background of mice and the mineral composition of their diet can profoundly modulate the ectopic mineralization process predicated on mutations in the Abcc6 gene. These mice provide novel model systems to study the pathomechanisms and the reasons for strain background on phenotypic variability of PXE. © 2014 Li et al

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Specifying and Operationalizing an Organizational Theory of Crowdsourcing

Introduction: Despite rapid developments across multiple areas of research and practice, an organizational-level theory of Crowdsourcing has yet to emerge. Objectives: Therefore, this thesis has two major objectives; 1) specify the boundaries, constructs, and relationships of an organizational-level theory of Crowdsourcing, and 2) begin the theoretical validation process by operationalizing the theory for new exploratory, explanatory, and conceptual research. Methods: In respect to the first objective, an organizational-level theory of Crowdsourcing is created through inductive processes based upon observations of the real-world, and the extant organizational literature. In respect to the second objective, a mixed-methods research design is implemented to present three separate studies that use the theoretical perspective as a lens to operationalize new exploratory, explanatory, and conceptual Crowdsourcing research. Results: The Crowd Capital perspective is introduced, and defines three new constructs for the Crowdsourcing research; Dispersed Knowledge, Crowd Capability, and Crowd Capital. Crowd Capital theory is shown to be a valid theoretical contribution in the management research by illustrating the perspective’s incremental originality and scientific utility. Conclusion: The thesis develops and validates an organizational-level theory explaining how and why organizations implement Crowdsourcing, and through the exploratory and explanatory operationalizations of the Crowd Capital perspective, this work contributes to the empirical knowledge-base in the Crowdsourcing research. Further, this thesis contributes methodologically by illustrating and implementing a mixed-methods research design for theory validation in the Crowdsourcing research, while also supplying managers and executives with detailed guidance on the trade-offs inherent to the different modalities of Crowdsourcing. Thesis Organization: This thesis is organized in a monograph format comprised of eight chapters; 1) Introduction, 2) Literature review, 3) Theoretical model, 4) Methodology, 5) Exploratory research, 6) Explanatory research, 7) Conceptual research, and 8) Conclusion. As an outcome of this thesis, three journal articles and five conference proceedings have been accepted in peer-reviewed outlets1, and the author has been awarded a mini-track about Crowdsourcing at one of the most prestigious conferences in the field. The articles and the conference mini-track details are listed in Appendix A &amp; B at the end of the dissertation

Next Generation Crowdsourcing for Collective Intelligence

New techniques leveraging IT-mediated crowds such as Crowdsensing, Situated Crowdsourcing, Spatial Crowdsourcing, and Wearables Crowdsourcing have now materially emerged. These techniques, here termed next generation Crowdsourcing, serve to extend Crowdsourcing efforts beyond the heretofore dominant desktop computing paradigm. Employing new configurations of hardware, software, and people, these techniques represent new forms of organization for IT-mediated crowds. However, it is not known how these new techniques change the processes and outcomes of IT-mediated crowds for Collective Intelligence purposes? The aim of this exploratory work is to begin to answer this question. The work ensues by outlining the relevant findings of the first generation Crowdsourcing paradigm, before reviewing the emerging literature pertaining to the new generation of Crowdsourcing techniques. Premised on this review, a collectively exhaustive and mutually exclusive typology is formed, organizing the next generation Crowdsourcing techniques along two salient dimensions common to all first generation Crowdsourcing techniques. As a result, this work situates the next generation Crowdsourcing techniques within the extant Crowdsourcing literature, and identifies new research avenues stemming directly from the analysis