Authors: Marieke de Regt , Rogier Ooijevaar , Marcel Jonges , Matthijs R A Welkers , Alex Wagemakers

In Life Sciences

By NCBI Pubmed

A 26-year-old man reporting a 6-day history of fever, malaise, and a swollen cheek, was referred to our emergency room. The day before his attendance, he had been seen by his general practitioner and started on oral amoxicillin and clavulanic acid. However, his cheek continued to swell, and he developed a temperature of 39·4oC, prompting the referral.

Authors: Andrew G. Soerens , Marco Künzli , Clare F. Quarnstrom , Milcah C. Scott , Lee Swanson , JJ. Locquiao , Hazem E. Ghoneim , Dietmar Zehn , Benjamin Youngblood , Vaiva Vezys , David Masopust

In Life Sciences, Nature

By NCBI Pubmed

Differentiated somatic mammalian cells putatively exhibit species-specific division limits that impede cancer but may constrain lifespans1,2,3. To provide immunity, transiently stimulated CD8+ T cells undergo unusually rapid bursts of numerous cell divisions, and then form quiescent long-lived memory cells that remain poised to reproliferate following subsequent immunological challenges. Here we addressed whether T cells are intrinsically constrained by chronological or cell-division limits. We activated mouse T cells in vivo using acute heterologous prime–boost–boost vaccinations4, transferred expanded cells to new mice, and then repeated this process iteratively. Over 10 years (greatly exceeding the mouse lifespan)5 and 51 successive immunizations, T cells remained competent to respond to vaccination. Cells required sufficient rest between stimulation events. Despite demonstrating the potential to expand the starting population at least 1040-fold, cells did not show loss of proliferation control and results were not due to contamination with young cells. Persistent stimulation by chronic infections or cancer can cause T cell proliferative senescence, functional exhaustion and death6. We found that although iterative acute stimulations also induced sustained expression and epigenetic remodelling of common exhaustion markers (including PD1, which is also known as PDCD1, and TOX) in the cells, they could still proliferate, execute antimicrobial functions and form quiescent memory cells. These observations provide a model to better understand memory cell differentiation, exhaustion, cancer and ageing, and show that functionally competent T cells can retain the potential for extraordinary population expansion and longevity well beyond their organismal lifespan.

Authors: Yingyue Zhou , Mari Tada , Zhangying Cai , Prabhakar S. Andhey , Amanda Swain , Kelly R. Miller , Susan Gilfillan , Maxim N. Artyomov , Masaki Takao , Akiyoshi Kakita , Marco Colonna

In Life Sciences, Nature

By NCBI Pubmed

The TREM2–DAP12 receptor complex sustains microglia functions. Heterozygous hypofunctional TREM2 variants impair microglia, accelerating late-onset Alzheimer’s disease. Homozygous inactivating variants of TREM2 or TYROBP-encoding DAP12 cause Nasu–Hakola disease (NHD), an early-onset dementia characterized by cerebral atrophy, myelin loss and gliosis. Mechanisms underpinning NHD are unknown. Here, single-nucleus RNA-sequencing analysis of brain specimens from DAP12-deficient NHD individuals revealed a unique microglia signature indicating heightened RUNX1, STAT3 and transforming growth factor-β signaling pathways that mediate repair responses to injuries. This profile correlated with a wound healing signature in astrocytes and impaired myelination in oligodendrocytes, while pericyte profiles indicated vascular abnormalities. Conversely, single-nuclei signatures in mice lacking DAP12 signaling reflected very mild microglial defects that did not recapitulate NHD. We envision that DAP12 signaling in microglia attenuates wound healing pathways that, if left unchecked, interfere with microglial physiological functions, causing pathology in human. The identification of a dysregulated NHD microglia signature sparks potential therapeutic strategies aimed at resetting microglia signaling pathways.

Authors: Heidi M. Levitt , Michael Bamberg , John W. Creswell , David M. Frost , Ruthellen Josselson , Carola Suárez-Orozco

In Other

By NCBI Pubmed

The American Psychological Association Publications and Communications Board Working Group on Journal Article Reporting Standards for Qualitative Research (JARS–Qual Working Group) was charged with examining the state of journal article reporting standards as they applied to qualitative research and with generating recommendations for standards that would be appropriate for a wide range of methods within the discipline of psychology. These standards describe what should be included in a research report to enable and facilitate the review process. This publication marks a historical moment—the first inclusion of qualitative research in APA Style, which is the basis of both the Publication Manual of the American Psychological Association (APA, 2010) and APA Style CENTRAL, an online program to support APA Style. In addition to the general JARS–Qual guidelines, the Working Group has developed standards for both qualitative meta-analysis and mixed methods research. The reporting standards were developed for psychological qualitative research but may hold utility for a broad range of social sciences. They honor a range of qualitative traditions, methods, and reporting styles. The Working Group was composed of a group of researchers with backgrounds in varying methods, research topics, and approaches to inquiry. In this article, they present these standards and their rationale, and they detail the ways that the standards differ from the quantitative research reporting standards. They describe how the standards can be used by authors in the process of writing qualitative research for submission as well as by reviewers and editors in the process of reviewing research.

Authors: Linda Darling-Hammond , Lisa Flook , Channa Cook-Harvey , Brigid Barron , David Osher

In Education

By NCBI Pubmed

This article draws out the implications for school and classroom practices of an emerging consensus about the science of learning and development, outlined in a recent synthesis of the research. Situating the review in a developmental systems framework, we synthesize evidence from the learning sciences and several branches of educational research regarding well-vetted strategies that support the kinds of relationships and learning opportunities needed to promote children’s well-being, healthy development, and transferable learning. In addition, we review research regarding practices that can help educators respond to individual variability, address adversity, and support resilience, such that schools can enable all children to find positive pathways to adulthood.