RESUMO
Virtual interviewing has become ubiquitous with the academic job market. Here, we highlight the best practices for candidates and departments to consider when using virtual interviewing. We propose how virtual interviews can be leveraged and adapted for hybrid academic job searches combining virtual and in-person activities in a post-pandemic world.
Assuntos
Emprego , Entrevistas como Assunto , Universidades , COVID-19/epidemiologia , Escolha da Profissão , Docentes , HumanosRESUMO
We identify problematic areas throughout the Science, Technology, Engineering and Mathematics (STEM) pipeline that perpetuate racial disparities in academia. Distinct ways to curtail these disparities include early exposure and access to resources, supportive mentoring networks and comprehensive training programs specifically for racially minoritized students and trainees at each career stage. These actions will revitalize the STEM pipeline.
Assuntos
Engenharia/educação , Matemática/educação , Ciência/educação , Tecnologia/educação , Educação de Pós-Graduação , Humanos , UniversidadesRESUMO
The process of evaluating and negotiating a tenure-track job offer is unstructured and highly variable, making it susceptible to bias and inequitable outcomes. We outline common aspects of and recommendations for negotiating an academic job offer in the life sciences to support equitable recruitment of diverse faculty.
Assuntos
Escolha da Profissão , Emprego , Docentes , NegociaçãoRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented obstacles for new investigators to traverse. The pandemic's impact exacerbates inequities for groups historically excluded from science. We provide recommendations to support junior faculty, including women and faculty from groups historically excluded from science, in establishing laboratories during the pandemic and foreseeable future.
Assuntos
COVID-19 , Pandemias , Feminino , Humanos , LaboratóriosRESUMO
The process of starting a laboratory varies between institutions. However, there are universal tasks all investigators will need to address when launching their laboratories. In this piece, we provide a brief summary of considerations for incoming group leaders to centralize this information for the scientific community.
Assuntos
Laboratórios , Pesquisadores , HumanosRESUMO
Scientific success is mainly supported by mentoring, which often occurs through face-to-face interactions. Changes to the research environment incurred by the Coronavirus 2019 (COVID-19) pandemic have necessitated mentorship adaptations. Here, we describe how mentors can broaden their mentorship to support trainee growth and provide reassurance about trainee development amid uncertain circumstances.
Assuntos
COVID-19/epidemiologia , Tutoria , Pandemias , Pesquisadores/educação , SARS-CoV-2 , HumanosRESUMO
The interplay between academics and society within the environment of the COVID-19 pandemic has impacted on scientists across the world, prompting reevaluation of how virtual toolboxes can be used to support responsible collaborative research practices. We provide awareness of virtual resources and activities that enable scientific discovery using safe and efficient practices.
Assuntos
Pesquisa Biomédica/organização & administração , COVID-19/epidemiologia , COVID-19/psicologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Práticas Interdisciplinares/organização & administração , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Interface Usuário-Computador , Betacoronavirus/patogenicidade , COVID-19/transmissão , COVID-19/virologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Disseminação de Informação , Distanciamento Físico , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Saúde Pública , SARS-CoV-2 , Mídias SociaisRESUMO
Heparan sulfate proteoglycans are a family of glycoproteins that modulate cell signaling by binding growth factors and changing their bioavailability. Syndecans are a specific family of transmembrane heparan sulfate proteoglycans that regulate cell adhesion, migration, and signaling. In this review, we will summarize emerging evidence for the functions of syndecans in the normal and malignant blood systems and their microenvironments. More specifically, we detail the known functions of syndecans within normal hematopoietic stem cells. Furthermore, we discuss the functions of syndecans in hematological malignancies, including myeloid malignancies, lymphomas, and bleeding disorders. As normal and malignant hematopoietic cells require cues from their microenvironments to function, we also summarize the roles of syndecans in cells of the stromal, endothelial, and osteolineage compartments. Syndecan biology is a rapidly evolving field; a comprehensive understanding of these molecules and their place in the hematopoietic system promises to improve our grasp on disease processes and better predict the efficacies of growth factor-targeting therapies.
Assuntos
Células-Tronco Hematopoéticas , Nicho de Células-Tronco , Sindecanas , Humanos , Células-Tronco Hematopoéticas/metabolismo , Animais , Sindecanas/metabolismo , Sindecanas/genética , Transdução de Sinais , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Hematopoese/fisiologiaRESUMO
The discovery of novel hematopoietic stem cell (HSC) surface markers can enhance understanding of HSC identity and function. We have discovered a population of primitive bone marrow (BM) HSCs distinguished by their expression of the heparan sulfate proteoglycan Syndecan-2, which serves as both a marker and a regulator of HSC function. Syndecan-2 expression was increased 10-fold in CD150+CD48-CD34-c-Kit+Sca-1+Lineage- cells (long-term HSCs [LT-HSCs]) compared with differentiated hematopoietic cells. Isolation of BM cells based solely on syndecan-2 surface expression produced a 24-fold enrichment for LT-HSCs and sixfold enrichment for α-catulin+c-kit+ HSCs, and yielded HSCs with superior in vivo repopulating capacity compared with CD150+ cells. Competitive repopulation assays revealed the HSC frequency to be 17-fold higher in syndecan-2+CD34-KSL cells compared with syndecan-2-CD34-KSL cells and indistinguishable from CD150+CD34-KSL cells. Syndecan-2 expression also identified nearly all repopulating HSCs within the CD150+CD34-KSL population. Mechanistically, syndecan-2 regulates HSC repopulating capacity through control of expression of Cdkn1c (p57) and HSC quiescence. Loss of syndecan-2 expression caused increased HSC cell cycle entry, downregulation of Cdkn1c, and loss of HSC long-term repopulating capacity. Syndecan-2 is a novel marker of HSCs that regulates HSC repopulating capacity via control of HSC quiescence.
Assuntos
Células-Tronco Hematopoéticas/citologia , Sindecana-2/metabolismo , Animais , Ciclo Celular , Diferenciação Celular , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Masculino , Camundongos , Sindecana-2/genéticaRESUMO
Chemotherapy and irradiation cause DNA damage to hematopoietic stem cells (HSCs), leading to HSC depletion and dysfunction and the risk of malignant transformation over time. Extrinsic regulation of HSC DNA repair is not well understood, and therapies to augment HSC DNA repair following myelosuppression remain undeveloped. We report that epidermal growth factor receptor (EGFR) regulates DNA repair in HSCs following irradiation via activation of the DNA-dependent protein kinase-catalytic subunit (DNA-PKcs) and nonhomologous end joining (NHEJ). We show that hematopoietic regeneration in vivo following total body irradiation is dependent upon EGFR-mediated repair of DNA damage via activation of DNA-PKcs. Conditional deletion of EGFR in hematopoietic stem and progenitor cells (HSPCs) significantly decreased DNA-PKcs activity following irradiation, causing increased HSC DNA damage and depressed HSC recovery over time. Systemic administration of epidermal growth factor (EGF) promoted HSC DNA repair and rapid hematologic recovery in chemotherapy-treated mice and had no effect on acute myeloid leukemia growth in vivo. Further, EGF treatment drove the recovery of human HSCs capable of multilineage in vivo repopulation following radiation injury. Whole-genome sequencing analysis revealed no increase in coding region mutations in HSPCs from EGF-treated mice, but increased intergenic copy number variant mutations were detected. These studies demonstrate that EGF promotes HSC DNA repair and hematopoietic regeneration in vivo via augmentation of NHEJ. EGF has therapeutic potential to promote human hematopoietic regeneration, and further studies are warranted to assess long-term hematopoietic effects.
Assuntos
Reparo do DNA por Junção de Extremidades , Receptores ErbB/metabolismo , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/metabolismo , Regeneração , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Dano ao DNA , Proteína Quinase Ativada por DNA/genética , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/genética , Células-Tronco Hematopoéticas/citologia , Humanos , CamundongosRESUMO
A toolkit for mentoring minority students and trainees in science.
Assuntos
Tutoria , Mentores , Humanos , Grupos Minoritários , EstudantesRESUMO
Many students and early-career scientists too often agree to new tasks and chores and end up overworked. Learning how and when to say "no" is therefore an important part of career development.
Assuntos
Escolha da Profissão , Estudantes , Humanos , AprendizagemAssuntos
Pesquisa Biomédica/tendências , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , COVID-19 , Escolha da Profissão , Humanos , Mentores , National Institutes of Health (U.S.) , Inovação Organizacional , Isolamento de Pacientes , Editoração , Quarentena , Pesquisadores , Apoio à Pesquisa como Assunto , Viagem , Estados UnidosRESUMO
The word minority, when used incorrectly, is a condescending term that segregates, inaccurately represents groups as being smaller or less important, and fuels microaggressions. Scientific societies and other institutions have normalized using the word minority, or the "M word," to refer to members of underrepresented groups in Science, Technology, Engineering, and Mathematics (STEM). The message put forth using the term minority often directly conflicts with the inclusive agenda these societies seek to enact. More inclusive acronyms such as PEER (Persons Excluded because of their Ethnicity or Race) have been created to more accurately reflect the active process of exclusion by institutions. Here, we detail the rationale behind the decision to eradicate the word minority from the name of a prominent committee within the American Society for Cell Biology (ASCB). The ASCB Minority Affairs Committee changed its name to the Maximizing Access to Cell Biology for PEERS Committee. Herein, we emphasize the basis for the name change and highlight the contradictions intrinsic to the word minority in this context. We highlight why swift action is required for this rewording within the context of a committee dedicated to supporting the inclusion of PEERs in the scientific community.
Assuntos
Biologia Celular , Grupos Minoritários , Humanos , Sociedades Científicas , Estados Unidos , Grupo Associado , Terminologia como AssuntoRESUMO
Neuropilin-1 acts as a coreceptor with vascular endothelial growth factor receptors to facilitate binding of its ligand, vascular endothelial growth factor. Neuropilin-1 also binds to heparan sulfate, but the functional significance of this interaction has not been established. A combinatorial library screening using heparin oligosaccharides followed by molecular dynamics simulations of a heparin tetradecasaccharide suggested a highly conserved binding site composed of amino acid residues extending across the b1 and b2 domains of murine neuropilin-1. Mutagenesis studies established the importance of arginine513 and lysine514 for binding of heparin to a recombinant form of Nrp1 composed of the a1, a2, b1, and b2 domains. Recombinant Nrp1 protein bearing R513A,K514A mutations showed a significant loss of heparin-binding, heparin-induced dimerization, and heparin-dependent thermal stabilization. Isothermal calorimetry experiments suggested a 1:2 complex of heparin tetradecasaccharide:Nrp1. To study the impact of altered heparin binding in vivo, a mutant allele of Nrp1 bearing the R513A,K514A mutations was created in mice (Nrp1D) and crossbred to Nrp1+/- mice to examine the impact of altered heparan sulfate binding. Analysis of tumor formation showed variable effects on tumor growth in Nrp1D/D mice, resulting in a frank reduction in tumor growth in Nrp1D/- mice. Expression of mutant Nrp1D protein was normal in tissues, suggesting that the reduction in tumor growth was due to the altered binding of heparin/heparan sulfate to neuropilin-1. These findings suggest that the interaction of neuropilin-1 with heparan sulfate modulates its stability and its role in tumor formation and growth.
Assuntos
Heparitina Sulfato , Neuropilina-1 , Neuropilina-1/metabolismo , Neuropilina-1/genética , Neuropilina-1/química , Animais , Heparitina Sulfato/metabolismo , Camundongos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Ligação Proteica , Sítios de Ligação , Camundongos Endogâmicos C57BL , Heparina/metabolismo , Heparina/química , Simulação de Dinâmica Molecular , MutaçãoRESUMO
Informal mentoring affects the development of cell biologists by providing essential career, scientific, and educational guidance to mentees. In this piece, we discuss the importance of formally recognizing casual mentorship to encourage this crucial form of mentorship that contributes to the advancement of an inclusive cell biology community.
Assuntos
Tutoria , Humanos , MentoresRESUMO
Diversity, equity, and inclusion (DEI) efforts have increased drastically as companies and institutions recognize their value in fostering innovative ideas for success. Individuals trained in these efforts can impart their knowledge and expertise in consultation, but this transaction should be mutually beneficial. Here, we provide recommendations to maximize consulting opportunities.
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Encaminhamento e Consulta , HumanosRESUMO
Shadow mentoring relationships are those outside of traditional mentoring roles and are an unseen yet critical component of trainee retention that is rarely acknowledged. In this paper, we detail the costs and benefits of shadow mentoring and propose mechanisms to ensure that shadow mentoring is acknowledged as a vital contribution to scientific communities.
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Tutoria , Análise Custo-Benefício , Humanos , MentoresRESUMO
Protein tyrosine phosphatase receptor σ (PTPσ) is highly expressed by murine and human hematopoietic stem cells (HSCs) and negatively regulates HSC self-renewal and regeneration. Previous studies of the nervous system suggest that heparan sulfate proteoglycans can inactivate PTPσ by clustering PTPσ receptors on neurons, but this finding has yet to be visually verified with adequate resolution. Here, we sought to visualize and quantify how heparan sulfate proteoglycans regulate the organization and activation of PTPσ in hematopoietic stem/progenitor cells (HSPCs). Our study illustrates that syndecan-2 promotes PTPσ clustering, which sustains phospho-tyrosine and phospho-ezrin levels in association with augmentation of hematopoietic colony formation. Strategies that promote clustering of PTPσ on HSPCs may serve to powerfully augment hematopoietic function.