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PLOS Biology: New Articles

  • Queer- and trans-inclusive faculty hiring—A call for change

    by J. L. Weissman, Callie R. Chappell, Bruno Francesco Rodrigues de Oliveira, Natalya Evans, Anna C. Fagre, Desiree Forsythe, Steven A. Frese, Rachel Gregor, Suzanne L. Ishaq, Juliet Johnston, Bittu K. R., Shayle B. Matsuda, Sam McCarren, Melanie Ortiz Alvarez de la Campa, Troy A. Roepke, Nasa. Sinnott-Armstrong, Cora S. Stobie, Lauren Talluto, José M. Vargas-Muñiz, The Advancing Queer and Trans Equity in Science (AQTES) Consortium

    As queer and trans scientists, we face varied and systemic barriers to our professional success, resulting in our relative absence from faculty ranks at many institutions. In this Perspective, we call for a change in faculty hiring practices and present concrete guidance to make it a more inclusive process. Queer and trans scientists face varied and systemic barriers to their professional success, resulting in a relative absence from faculty ranks at many institutions. This Perspective calls for a change in faculty hiring practices and present concrete guidance to make it a more inclusive process.

  • CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells

    by Bianca Pellegrino, Keren David, Stav Rabani, Bar Lampert, Thuy Tran, Edward Doherty, Marta Piecychna, Roberto Meza-Romero, Lin Leng, Dov Hershkovitz, Arthur A. Vandenbark, Richard Bucala, Shirly Becker-Herman, Idit Shachar

    CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD), which regulates transcription in naïve B and chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the role of CD74 in the regulation of the immunosuppressive tumor microenvironment (TME) in triple-negative breast cancer (TNBC). TNBC is the most aggressive breast cancer subtype and is characterized by massive infiltration of immune cells to the tumor microenvironment, making this tumor a good candidate for immunotherapy. The tumor and immune cells in TNBC express high levels of CD74; however, the function of this receptor in the tumor environment has not been extensively characterized. Regulatory B cells (Bregs) and tolerogenic dendritic cells) tol-DCs (were previously shown to attenuate the antitumor immune response in TNBC. Here, we demonstrate that CD74 enhances tumor growth by inducing the expansion of tumor-infiltrating tol-DCs and Bregs. Utilizing CD74-KO mice, Cre-flox mice lacking CD74 in CD23+ mature B cells, mice lacking CD74 in the CD11c+ population, and a CD74 inhibitor (DRQ), we elucidate the mechanism by which CD74 inhibits antitumor immunity. MIF secreted from the tumor cells activates CD74 expressed on DCs. This activation induces the binding of CD74-ICD to the SP1 promotor, resulting in the up-regulation of SP1 expression. SP1 binds the IL-1β promotor, leading to the down-regulation of its transcription. The reduced levels of IL-1β lead to decreased antitumor activity by allowing expansion of the tol-DC, which induces the expansion of the Breg population, supporting the cross-talk between these 2 populations. Taken together, these results suggest that CD74+ CD11c+ DCs are the dominant cell type involved in the regulation of TNBC progression. These findings indicate that CD74 might serve as a novel therapeutic target in TNBC.

  • A call for research to address the threat of paper mills

    by Jennifer A. Byrne, Anna Abalkina, Olufolake Akinduro-Aje, Jana Christopher, Sarah E. Eaton, Nitin Joshi, Ulf Scheffler, Nick H. Wise, Jennifer Wright

    Research paper mills are covert organizations that provide low-quality or fabricated manuscripts to paying clients. As members of the United2Act Research Working Group, we propose 5 key research questions on paper mills that require resourcing and support. Research paper mills are covert organizations that provide low quality or fabricated manuscripts to paying clients. This Perspective, written by members of the United2Act Research Working Group, proposes five key research questions on paper mills that require resourcing and support.

  • Turnover of retroelements and satellite DNA drives centromere reorganization over short evolutionary timescales in <i>Drosophila</i>

    by Cécile Courret, Lucas W. Hemmer, Xiaolu Wei, Prachi D. Patel, Bryce J. Chabot, Nicholas J. Fuda, Xuewen Geng, Ching-Ho Chang, Barbara G. Mellone, Amanda M. Larracuente

    Centromeres reside in rapidly evolving, repeat-rich genomic regions, despite their essential function in chromosome segregation. Across organisms, centromeres are rich in selfish genetic elements such as transposable elements and satellite DNAs that can bias their transmission through meiosis. However, these elements still need to cooperate at some level and contribute to, or avoid interfering with, centromere function. To gain insight into the balance between conflict and cooperation at centromeric DNA, we take advantage of the close evolutionary relationships within the Drosophila simulans clade—D. simulans, D. sechellia, and D. mauritiana—and their relative, D. melanogaster. Using chromatin profiling combined with high-resolution fluorescence in situ hybridization on stretched chromatin fibers, we characterize all centromeres across these species. We discovered dramatic centromere reorganization involving recurrent shifts between retroelements and satellite DNAs over short evolutionary timescales. We also reveal the recent origin (<240 Kya) of telocentric chromosomes in D. sechellia, where the X and fourth centromeres now sit on telomere-specific retroelements. Finally, the Y chromosome centromeres, which are the only chromosomes that do not experience female meiosis, do not show dynamic cycling between satDNA and TEs. The patterns of rapid centromere turnover in these species are consistent with genetic conflicts in the female germline and have implications for centromeric DNA function and karyotype evolution. Regardless of the evolutionary forces driving this turnover, the rapid reorganization of centromeric sequences over short evolutionary timescales highlights their potential as hotspots for evolutionary innovation.

  • The human posterior parietal cortices orthogonalize the representation of different streams of information concurrently coded in visual working memory

    by Yaoda Xu

    The key to adaptive visual processing lies in the ability to maintain goal-directed visual representation in the face of distraction. In visual working memory (VWM), distraction may come from the coding of distractors or other concurrently retained targets. This fMRI study reveals a common representational geometry that our brain uses to combat both types of distractions in VWM. Specifically, using fMRI pattern decoding, the human posterior parietal cortex is shown to orthogonalize the representations of different streams of information concurrently coded in VWM, whether they are targets and distractors, or different targets concurrently held in VWM. The latter is also seen in the human occipitotemporal cortex. Such a representational geometry provides an elegant and simple solution to enable independent information readout, effectively combating distraction from the different streams of information, while accommodating their concurrent representations. This representational scheme differs from mechanisms that actively suppress or block the encoding of distractors to reduce interference. It is likely a general neural representational principle that supports our ability to represent information beyond VWM in other situations where multiple streams of visual information are tracked and processed simultaneously.