Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gerbich, T. M., McLaughlin, G. A., Cassidy, K., Gerber, S., Adalsteinsson, D., & Gladfelter, A. S. Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity. Journal of Cell Biology, 219(7), (2020): e201910021, doi:10.1083/jcb.201910021.Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity through forming macromolecular structures that behave like condensates. Whi3 has distinct spatial localizations and mRNA targets, making it a powerful model for how, when, and where specific identities are established for condensates. We identified residues on Whi3 that are differentially phosphorylated under specific conditions and generated mutants that ablate this regulation. This yielded separation of function alleles that were functional for either cell polarity or nuclear cycling but not both. This study shows that phosphorylation of individual residues on molecules in biomolecular condensates can provide specificity that gives rise to distinct functional identities in the same cell.The work was supported by National Institutes of Health grant R01-GM-081506

Experiences of Microaggressions, Attributions, and Impact Among US Young Adults: An Intersectional Perspective Regarding Sexual/Gender and Racial/Ethnic Minorities

BACKGROUND: Understanding discrimination (e.g., microaggressions) toward sexual/gender minorities (SGM) and racial/ethnic minorities (REM) from an intersectional perspective is critical in informing interventions to reduce such experiences and their impacts. PURPOSE: This study examined US young adults identifying as SGM, REM, both, or neither in relation to microaggression experiences, and these factors in relation to mental health. METHODS: Using 2022 data from 932 US adults (M = 27.61) in an online survey study, we compared subgroups (SGM-only, REM-only, both, neither) in relation to microaggression experiences and mental health symptoms, stratified by sex (male, female). Multivariable linear regression examined: 1) sex and intersectional subgroup in relation to number of microaggressions experienced; and 2) sex, subgroup, and number of microaggression experiences in relation to mental health symptoms. RESULTS: Among females (n = 612), 42.0% were SGM-only, 17.3% REM-only, 15.2% both, and 25.5% neither. Among males (n = 320), 25.0% were SGM-only, 25.0% REM-only, 8.4% both, and 41.6% neither. Females (vs. males) reported more microaggressions (M = 5.67, SD = 3.00 vs. M = 3.95, SD = 3.46, p \u3c .001). Those with intersecting minority identities experienced the most microagressions (females: M = 6.98, SD = 2.64; males: M = 6.44, SD = 2.95, respectively). In multivariable analyses, females and those in any of the 3 minority-identifying subgroups experienced more microaggressions; those with intersecting minority identities experienced more microaggressions than SGM-only and REM-only. Identifying as SGM-only or both SGM and REM, as well as experiencing more microaggressions, was associated with greater mental health symptoms. CONCLUSIONS: Intersecting minority identities increase risk for microaggressions and mental health consequences. Multilevel interventions must reduce minority subgroups\u27 experiences of microaggressions and their impacts

UBC Science Writing Resources for Learning (www.ScWRL.ubc.ca)

We believe science students are more motivated to practice communication skills in the context of science. Additionally, colleagues told us they would prefer using science-specific instructional materials for teaching writing. Thus, faculty, staff, and students from the Faculty of Science and the Writing Centre at the University of British Columbia collaborated to create science-specific writing learning resources for students and educators. The resources are available on our website www.scwrl.ubc.ca. We focused on issues specific to communicating scientific information. Student resources include advice about communicating science; learning strategies for communicating science; finding, identifying, and citing sources; grammar and style; and developing an effective writing process. Resources include short YouTube videos, worksheets, background readings, and assessments. Educators are able to use our site to learn more about strategies for teaching writing and grading techniques. Included are eleven class-tested lessons with pre-class, in-class, and post-class activities, grading keys, and rubrics that educators can adopt or modify. Lesson topics (e.g. active and passive voice and communicating uncertainty) span writing style and grammar to audiences for scientific communication. The resources can be used individually or as part of a learning sequence. Our preliminary testing and our efforts to disseminate these resources initially locally encouraged us to share them with the broader science education community. Please visit our poster to learn more about our site and exchange ideas on science writing. We would also love to hear from you about additional resources you would find useful as we plan to expand our offerings

Resident Memory T Cells and Their Effect on Cancer

Resident memory T (TRM) cells are a unique subset of CD8+ T cells that are present within certain tissues and do not recirculate through the blood. Long term memory establishment and maintenance are dependent on tissue population of memory T cells. They are characterized by dual CD69/CD103 positivity, and play a role in both response to viral infection and local cancer immunosurveillance. Human TRM cells demonstrate the increased expression of adhesion molecules to facilitate tissue retention, have reduced proliferation and produce both regulatory and immune responsive cytokines. TRM cell phenotype is often characterized by a distinct expression profile driven by Runx3, Blimp1, and Hobit transcription factors. The accumulation of TRM cells in tumors is associated with increased survival and response to immunotherapies, including anti-PD-1 and anti-CTLA-4. In this review, we explore potential mechanisms of TRM cell transformation and maintenance, as well as potential applications for the use of TRM cells in both the development of supportive therapies and establishing more accurate prognoses

A review of social media platform policies that address cannabis promotion, marketing and sales

Abstract Background Cannabis marketing exposure via social media may impact use in youth and young adults. Most states with recreational cannabis lack policies regarding social media-based marketing. Thus, we examined such policies among prominent platforms, particularly those popular among youth and young adults. Methods In September-October 2022, 3 research team members extracted policies applying to the general community, advertising, and any specific content regarding drug-related content for 11 social media sites: Discord, Facebook, Instagram, Pinterest, Reddit, Snapchat, TikTok, Tumblr, Twitch, Twitter, and YouTube. Using inductive thematic analysis, they then dual-coded restrictions on cannabis-related content (e.g., paid advertising, unpaid promotion, sales). Descriptive analyses were conducted. Results Ten (all except TikTok) referenced cannabis/marijuana, 7 (all except Discord, Instagram, TikTok, and YouTube) distinguished different cannabis-derived products, and 5 (Reddit, Snapchat, TikTok, Tumblr, Twitter) noted jurisdictional differences in cannabis regulations/legality. All prohibited sales, 9 (all except Snapchat and Tumblr) prohibited paid advertising, and 4 (Discord, Reddit, Snapchat, TikTok) prohibited unpaid promotion (e.g., user-generated content). All restricted underage access to cannabis-related content. However, policies varied and were ambiguous regarding how “promotion” was defined, whether/how jurisdictional differences in legality were addressed, how businesses may interact on social media, barriers implemented to inhibit the facilitation of sales, and enforcement protocols. Conclusions Social media policies regarding cannabis marketing are ambiguous and may facilitate cannabis marketing, promotion, sales, and underage exposure, thus compounding concerns regarding insufficient governmental regulations. Greater specificity in social media cannabis-related policies and enforcement is needed

A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma

Metastatic renal cell carcinoma (RCC) is a molecularly heterogeneous disease that is intrinsically resistant to chemotherapy and radiotherapy. Although therapies targeted to the molecules vascular endothelial growth factor and mammalian target of rapamycin have shown clinical effectiveness, their effects are variable and short-lived, underscoring the need for improved treatment strategies for RCC. Here, we used quantitative phosphoproteomics and immunohistochemical profiling of 346 RCC specimens and determined that Src kinase signaling is elevated in RCC cells that retain wild-type von Hippel-Lindau (VHL) protein expression. RCC cell lines and xenografts with wild-type VHL exhibited sensitivity to the Src inhibitor dasatinib, in contrast to cell lines that lacked the VHL protein, which were resistant. Forced expression of hypoxia-inducible factor (HIF) in RCC cells with wild-type VHL diminished Src signaling output by repressing transcription of the Src activator protein tyrosine phosphatase 1B (PTP1B), conferring resistance to dasatinib. Our results suggest that a HIF-regulated VHL-PTP1B-Src signaling pathway determines the sensitivity of RCC to Src inhibitors and that stratification of RCC patients with antibody-based profiling may identify patients likely to respond to Src inhibitors in RCC clinical trials

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020