Exosomes regulate cell behavior by binding to and delivering their cargo to target cells; however, the mechanisms mediating exosome-cell interactions are poorly understood. Heparan sulfates on target ...cell surfaces can act as receptors for exosome uptake, but the ligand for heparan sulfate on exosomes has not been identified. Using exosomes isolated from myeloma cell lines and from myeloma patients, we identify exosomal fibronectin as a key heparan sulfate-binding ligand and mediator of exosome-cell interactions. We discovered that heparan sulfate plays a dual role in exosome-cell interaction; heparan sulfate on exosomes captures fibronectin, and on target cells it acts as a receptor for fibronectin. Removal of heparan sulfate from the exosome surface releases fibronectin and dramatically inhibits exosome-target cell interaction. Antibody specific for the Hep-II heparin-binding domain of fibronectin blocks exosome interaction with tumor cells or with marrow stromal cells. Regarding exosome function, fibronectin-mediated binding of exosomes to myeloma cells activated p38 and pERK signaling and expression of downstream target genes DKK1 and MMP-9, two molecules that promote myeloma progression. Antibody against fibronectin inhibited the ability of myeloma-derived exosomes to stimulate endothelial cell invasion. Heparin or heparin mimetics including Roneparstat, a modified heparin in phase I trials in myeloma patients, significantly inhibited exosome-cell interactions. These studies provide the first evidence that fibronectin binding to heparan sulfate mediates exosome-cell interactions, revealing a fundamental mechanism important for exosome-mediated cross-talk within tumor microenvironments. Moreover, these results imply that therapeutic disruption of fibronectin-heparan sulfate interactions will negatively impact myeloma tumor growth and progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vaccines, when available, will likely become our best tool to control the COVID-19 pandemic. Even in the most optimistic scenarios, vaccine shortages will likely occur. Using an age-stratified ...mathematical model paired with optimization algorithms, we determined optimal vaccine allocation for four different metrics (deaths, symptomatic infections, and maximum non-ICU and ICU hospitalizations) under many scenarios. We find that a vaccine with effectiveness ≥50% would be enough to substantially mitigate the ongoing pandemic, provided that a high percentage of the population is optimally vaccinated. When minimizing deaths, we find that for low vaccine effectiveness, irrespective of vaccination coverage, it is optimal to allocate vaccine to high-risk (older) age groups first. In contrast, for higher vaccine effectiveness, there is a switch to allocate vaccine to high-transmission (younger) age groups first for high vaccination coverage. While there are other societal and ethical considerations, this work can provide an evidence-based rationale for vaccine prioritization.
The goal congruity perspective provides a theoretical framework to understand how motivational processes influence and are influenced by social roles. In particular, we invoke this framework to ...understand communal goal processes as proximal motivators of decisions to engage in science, technology, engineering, and mathematics (STEM). STEM fields are not perceived as affording communal opportunities to work with or help others, and understanding these perceived goal affordances can inform knowledge about differences between (a) STEM and other career pathways and (b) women’s and men’s choices. We review the patterning of gender disparities in STEM that leads to a focus on communal goal congruity (Part I), provide evidence for the foundational logic of the perspective (Part II), and explore the implications for research and policy (Part III). Understanding and transmitting the opportunities for communal goal pursuit within STEM can reap widespread benefits for broadening and deepening participation.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Homologous and Heterologous Covid-19 Booster Vaccinations Atmar, Robert L; Lyke, Kirsten E; Deming, Meagan E ...
New England journal of medicine/The New England journal of medicine,
03/2022, Volume:
386, Issue:
11
Journal Article
Peer reviewed
Open access
Participants who had been fully vaccinated with current Covid-19 vaccines received homologous or heterologous boosters, and their immune response was measured on days 15 and 29. Homologous boosters ...increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73.
Scientists are trained to evaluate and interpret evidence without bias or subjectivity. Thus, growing evidence revealing a gender bias against women—or favoring men—within science, technology, ...engineering, and mathematics (STEM) settings is provocative and raises questions about the extent to which gender bias may contribute to women’s underrepresentation within STEM fields. To the extent that research illustrating gender bias in STEM is viewed as convincing, the culture of science can begin to address the bias. However, are men and women equally receptive to this type of experimental evidence? This question was tested with three randomized, double-blind experiments—two involving samples from the general public (n= 205 and 303, respectively) and one involving a sample of university STEM and non-STEM faculty (n= 205). In all experiments, participants read an actual journal abstract reporting gender bias in a STEM context (or an altered abstract reporting no gender bias in experiment 3) and evaluated the overall quality of the research. Results across experiments showed that men evaluate the gender-bias research less favorably than women, and, of concern, this gender difference was especially prominent among STEM faculty (experiment 2). These results suggest a relative reluctance among men, especially faculty men within STEM, to accept evidence of gender biases in STEM. This finding is problematic because broadening the participation of underrepresented people in STEM, including women, necessarily requires a widespread willingness (particularly by those in the majority) to acknowledge that bias exists before transformation is possible.
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Although women have nearly attained equality with men in several formerly male-dominated fields, they remain underrepresented in the fields of science, technology, engineering, and mathematics ...(STEM). We argue that one important reason for this discrepancy is that STEM careers are perceived as less likely than careers in other fields to fulfill communal goals (e.g., working with or helping other people). Such perceptions might disproportionately affect women's career decisions, because women tend to endorse communal goals more than men. As predicted, we found that STEM careers, relative to other careers, were perceived to impede communal goals. Moreover, communal-goal endorsement negatively predicted interest in STEM careers, even when controlling for past experience and self-efficacy in science and mathematics. Understanding how communal goals influence people's interest in STEM fields thus provides a new perspective on the issue of women's representation in STEM careers.
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BFBNIB, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK
The interfacial spreading and exfoliation of graphene was used to create low-density, hollow microspheres defined by a thin shell of graphene. The spheres were templated by a thermodynamically driven ...self-assembly process in which graphite spontaneously exfoliated and spread at the high-energy interfaces of a water-in-oil emulsion. Graphene thus acted as a 2D surfactant to stabilize the dispersed water droplets utilized as polymerization templates. Using a mixture of organic solvent and monomer as the emulsion oil phase, polystyrene-coated hollow graphene microspheres were created. These spheres were characterized by optical and electron microscopy, thermo-gravimetric analysis, nanoindentation, and particle sizing. The mechanism leading to the microsphere surface morphology and shape is discussed, with the oil phase composition shown to play a critical role.
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IJS, KILJ, NUK, PNG, UL, UM
Prolific use of crime mapping has led to critical inquiry as to the power and impact of mapping on criminology, public policy, and understandings of crime and violence more generally. Despite the ...proliferation of maps, few critical inquiries into the power of crime maps exist. Drawing on the historical emergence of crime mapping in one urban juvenile court, this article shows how maps hid and obscured existing power relations based on race and class. Instead of undoing the power of scientific racism in the juvenile court, the emergence of mapping rationalized and normalized the imagined geography of delinquency contained within eugenic philosophies of delinquency. These two eras are joined by a single epistemological cartography of delinquency that continues to pervade the court.
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BFBNIB, NMLJ, NUK, PNG, PRFLJ, UL, UM, UPUK
Sleep is a nearly universal behavior that is regulated by diverse environmental stimuli and physiological states. A defining feature of sleep is a homeostatic rebound following deprivation, where ...animals compensate for lost sleep by increasing sleep duration and/or sleep depth. The fruit fly, Drosophila melanogaster, exhibits robust recovery sleep following deprivation and represents a powerful model to study neural circuits regulating sleep homeostasis. Numerous neuronal populations have been identified in modulating sleep homeostasis as well as depth, raising the possibility that the duration and quality of recovery sleep is dependent on the environmental or physiological processes that induce sleep deprivation. Here, we find that unlike most pharmacological and environmental manipulations commonly used to restrict sleep, starvation potently induces sleep loss without a subsequent rebound in sleep duration or depth. Both starvation and a sucrose-only diet result in increased sleep depth, suggesting that dietary protein is essential for normal sleep depth and homeostasis. Finally, we find that Drosophila insulin like peptide 2 (Dilp2) is acutely required for starvation-induced changes in sleep depth without regulating the duration of sleep. Flies lacking Dilp2 exhibit a compensatory sleep rebound following starvation-induced sleep deprivation, suggesting Dilp2 promotes resiliency to sleep loss. Together, these findings reveal innate resilience to starvation-induced sleep loss and identify distinct mechanisms that underlie starvation-induced changes in sleep duration and depth.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Development of HIV-1 prevention methods is a global priority. In this randomized, controlled trial in sub-Saharan Africa, a vaginal ring containing the antiretroviral dapivirine was 27% effective in ...protecting against HIV-1 acquisition.
More than half of the 35 million persons currently living with human immunodeficiency virus type 1 (HIV-1) infection are women. A majority of these women reside in sub-Saharan Africa,
1
a region that has some of the highest incidences of HIV-1 infection in any population worldwide.
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The use of antiretroviral medications as pre-exposure prophylaxis is a promising approach to the prevention of HIV-1 acquisition.
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Several clinical trials of the antiretroviral tenofovir showed such protection against HIV-1.
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,
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However, in three trials involving African women, adherence to tenofovir-containing pills and vaginal gels was low, and HIV-1 protection was not shown. . . .
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