How the soul slips in: Virginia Woolf\u27s (un)natural history of dogs

Dogs have a crucial place in articulating ideas about class and sexuality in Woolf and her milieu. Her works move from considering dogs as representative instruments of class and gender in Mrs. Dalloway, to thinking more complexly about the dog/human boundary in Orlando. Human-to-animal ontologies are an evaluation of human biopolitical affiliations, where human social categories and function are embedded and reflected in canine behavior. The “anthropological machine” and the fabulated nature of the human world is exposed in contact zones associated with problems of sexuality, class, and gender, as these internal and external distinctions are able to evade human social typologies, especially in relation to the political and cultural metamorphosis of the interwar period. By identifying how canine signifiers operate, human-making ontologies are better understood. Animality is not an earmark of the “other,” rather it is more often revealed when compulsions of the State are at work on unstable human categories. Woolf uses animals (specifically dogs) because they are a natural proxy to human social structural functionalism. Dogs are fundamentally expressive despite their willingness to please a master; moreover, dogs do not control their desires or physicality as that is generally imposed upon them. Animal selfhood is not easily discoverable or evident, and is thus punished or ignored; they are queered by the perpetually human-driven insistence that they unnaturally accommodate a world exploited by human interest. In Mrs. Dalloway and Orlando, animality is foregrounded where the boundaries between human and animal collapse, and it is under this weight of censorship-by-way-of-animal where nonhuman taxonomies interpolate and correspond with human social hierarchies

Development and Application of an Interdisciplinary Rapid Message Testing Model for COVID-19 in North Carolina

Introduction From the onset of the COVID-19 pandemic, public health officials have sought to develop evidence-based messages to reduce COVID-19 transmission by communicating key information to media outlets and the public. We describe the development of an interdisciplinary rapid message testing model to quickly create, test, and share messages with public health officials for use in health campaigns and policy briefings. Methods An interdisciplinary research team from the University of North Carolina at Chapel Hill assembled in March 2020 to assist the state health department in developing evidence-based messages to influence social distancing behaviors in the state. We developed and iteratively executed a rapid message testing model; the components of the 4-step model were message creation, survey development, survey administration, and analysis and presentation to health department officials. The model was executed 4 times, each during a 7-day period in April and May, and each subsequent survey included new phrasing and/or messaging informed by the previous week’s survey. A total of 917 adults from North Carolina participated in the 4 surveys. Results Survey participants rated messages focused on protecting oneself and others higher than messages focused on norms and fear-based approaches. Pairing behaviors with motivations increased participants’ desire to social distance across all themes and subgroups. For example, adding “Protect your grandmother, your neighbor with cancer, and your best friend with asthma,” to messaging received a 0.9-point higher score than the base message, “Stay 6 feet apart from others when out in public.” Practice Implications Our model to promote social distancing in North Carolina during the COVID-19 pandemic can be used for rapid, iterative message testing during public health emergencies

Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival: Alloimmunization in SCD

Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD

Cellular localization of a Hsp90 homologue in Porphyromonas gingivalis

We previously reported an association between elevated serum antibody titers to the 90-kDa human heat shock protein (Hsp90), periodontal health and colonization by Porphyromonas gingivalis . In this study, we examined the cellular localization of the Hsp90 homologue of P. gingivalis . Cultures of P. gingivalis were heat-stressed (45°C) and examined for localization of the Hsp90 homologue. Heat stress induced a 4–5-fold increase in anti-Hsp90 antibody reactivity over that of the unstressed controls. Western blot analysis revealed two bands (44 and 68 kDa) that reacted with anti-Hsp90 antibodies. The 68-kDa band was heat-inducible, while the 44-kDa band was not. Immunogold staining revealed that the Hsp90 homologue localized principally to the membrane and extracellular vesicles. Subcellular fractionation confirmed that the Hsp90 homologue was primarily membrane-associated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72856/1/j.1574-6968.1999.tb08820.x.pd

Social stigma and executive compensation

We document that executives working at firms perceived negatively in light of social norms, such as tobacco, gambling and alcohol, earn a significant compensation premium. The premium compensates for personal costs executives bear due to their employer’s negative public perception and include: (i) a reduced likelihood these CEOs will serve as directors on other firms’ boards, which associates with lower executives’ social status, and (ii) impaired job mobility as employers shun stigmatized executives. The compensation premium is not explained by higher managerial skill required in firms we investigate, higher employment contract risk, political capital, litigation risk, or differences in corporate governance quality, and robust to endogeneity concerns. Our results highlight the significant impact job-related social stigma has on executive compensation

Nostalgia and style in retro America: moods, modes and media recycling

This paper considers nostalgia as a cultural mode in contemporary America

Unlike for Human Monocytes after LPS Activation, Release of TNF-α by THP-1 Cells Is Produced by a TACE Catalytically Different from Constitutive TACE

Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-α, initially synthesized as a membrane-anchored precursor (pro-TNF-α), is processed by proteolytic cleavage to generate the secreted mature form. TNF-α converting enzyme (TACE) is currently the first and single protease described as responsible for the inducible release of soluble TNF-α.Here, we demonstrated the presence on THP-1 cells as on human monocytes of a constitutive proteolytical activity able to cleave pro-TNF-α. Revelation of the cell surface TACE protein expression confirmed that the observed catalytic activity is due to TACE. However, further studies using effective and innovative TNF-α inhibitors, as well as a highly selective TACE inhibitor, support the presence of a catalytically different sheddase activity on LPS activated THP-1 cells. It appears that this catalytically different TACE protease activity might have a significant contribution to TNF-α release in LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity remains catalytically unchanged even after LPS activation.On the surface of LPS activated THP-1 cells we identified a releasing TNF-α activity, catalytically different from the sheddase activity observed on human monocytes from healthy donors. This catalytically-modified TACE activity is different from the constitutive shedding activity and appears only upon stimulation by LPS

PDE 7 Inhibitors: New Potential Drugs for the Therapy of Spinal Cord Injury

BACKGROUND: Primary traumatic mechanical injury to the spinal cord (SCI) causes the death of a number of neurons that to date can neither be recovered nor regenerated. During the last years our group has been involved in the design, synthesis and evaluation of PDE7 inhibitors as new innovative drugs for several neurological disorders. Our working hypothesis is based on two different facts. Firstly, neuroinflammation is modulated by cAMP levels, thus the key role for phosphodiesterases (PDEs), which hydrolyze cAMP, is undoubtedly demonstrated. On the other hand, PDE7 is expressed simultaneously on leukocytes and on the brain, highlighting the potential crucial role of PDE7 as drug target for neuroinflammation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present two chemically diverse families of PDE7 inhibitors, designed using computational techniques such as virtual screening and neuronal networks. We report their biological profile and their efficacy in an experimental SCI model induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. We have selected two candidates, namely S14 and VP1.15, as PDE7 inhibitors. These compounds increase cAMP production both in macrophage and neuronal cell lines. Regarding drug-like properties, compounds were able to cross the blood brain barrier using parallel artificial membranes (PAMPA) methodology. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with S14 and VP1.15, two PDE7 inhibitors, significantly reduced the degree of spinal cord inflammation, tissue injury (histological score), and TNF-α, IL-6, COX-2 and iNOS expression. CONCLUSIONS/SIGNIFICANCE: All these data together led us to propose PDE7 inhibitors, and specifically S14 and VP1.15, as potential drug candidates to be further studied for the treatment of SCI