Most tissues are populated by tissue-resident memory T cells (T
cells), which are adapted to their niche and appear to be indispensable for local protection against pathogens. Here we show that human ...white matter-derived brain CD8
T cells can be subsetted into CD103
CD69
and CD103
CD69
T cells both with a phenotypic and transcription factor profile consistent with T
cells. Specifically, CD103 expression in brain CD8
T cells correlates with reduced expression of differentiation markers, increased expression of tissue-homing chemokine receptors, intermediate and low expression of the transcription factors T-bet and eomes, increased expression of PD-1 and CTLA-4, and low expression of cytolytic enzymes with preserved polyfunctionality upon activation. Brain CD4
T cells also display T
cell-associated markers but have low CD103 expression. We conclude that the human brain is surveilled by T
cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate ...CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.
The world is combating an ongoing COVID-19 pandemic with health-care systems, society and economies impacted in an unprecedented way. It is unclear how many people have contracted the causative ...coronavirus (SARS-CoV-2) unknowingly and are asymptomatic. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of the Netherlands, which is a highly affected country, using a high-performance immunoassay. Our results indicate that one month into the outbreak (i) the seroprevalence in the Netherlands was 2.7% with substantial regional variation, (ii) the hardest-hit areas showed a seroprevalence of up to 9.5%, (iii) the seroprevalence was sex-independent throughout age groups (18-72 years), and (iv) antibodies were significantly more often present in younger people (18-30 years). Our study provides vital information on the extent of exposure to SARS-CoV-2 in a country where social distancing is in place.
Purpose
A vast amount of studies suggest that internalizing or externalizing problems are related to individual functioning, and often co-occur. Yet, a focus on their additive and interactive effects ...is scarce. Furthermore, most research has focused on a limited number of developmental domains and mostly on maladaptive functioning. Therefore, the current prospective study examined whether early childhood (ages 4–8) internalizing and externalizing problems and their interaction were related to a broad range of (mal)adaptive functioning outcomes in emerging adulthood (ages 20–24).
Methods
Data from the Flemish Study on Parenting, Personality and Development were used. At Time 1 (1999) mothers of 374 children (45% boys) and fathers of 357 children (46% boys) rated internalizing and externalizing problems through the Child Behavior Checklist. Outcomes in emerging adulthood were measured through self-reports 16 years later across the following domains: psychological functioning, social functioning, work, physical health, and self-concept.
Results
Early externalizing problems were related to maladaptive outcomes on the psychological and social domains. With regard to adaptive functioning, externalizing problems were associated with lower satisfaction regarding general health on the physical domain. Early internalizing problems were not associated with any emerging adulthood outcomes. The interaction of (father reported) internalizing and externalizing problems was related to aggressive behavior.
Conclusion
Early childhood externalizing problems were associated with maladaptive and adaptive functioning over a time span of 16 years. The results add to studies on the implementation of prevention and intervention programs in early childhood and to the value for developing personalized interventions.
This study aimed to understand how relationships with peers and teachers contribute to the development of internalizing problems via children's social self-concept. The sample included 570 children ...aged 7 years 5 months (SD = 4.6 months). Peer nominations of peer rejection, child-reported social self-concept, and teacher-reported internalizing problems were assessed longitudinally in the fall and spring of Grades 2 and 3. Teacher reports of support to the child were assessed in Grade 2. Results showed that peer rejection impeded children's social self-concept, which in turn affected the development of internalizing problems. Partial support was found for individual (but not classroom-level) teacher support to buffer the adverse effects of peer problems on children's self-concept, thereby mitigating its indirect effects on internalizing problems.
This study explored the development of mood variability in 474 Dutch adolescents (56.8% male, 90.1% medium to high socioeconomic status) from a community sample, followed from ages 13 to 18 years. ...Three times per year, adolescents reported on daily happiness, anger, sadness, and anxiety for 5 days using Internet diaries (15 assessment weeks; from 2006 to 2010). Mood variability scores were calculated as means of absolute differences between consecutive days. Results showed that happiness, anger, and sadness variability continuously declined across adolescence, while anxiety variability increased initially, then decreased, and then increased toward late adolescence. Despite females experiencing higher happiness and sadness variability, the rate of change across adolescence was similar for both sexes. Implications for normative emotional development and future studies are discussed.
This 4-year, multi-informant longitudinal study (N = 480, initial age: 15) investigated the interplay between parental support, behavioral and psychological control, and adolescents' emotion ...regulation development. We examined reciprocal effects between parents and children, mothers' versus fathers' unique roles in emotion regulation development, and sex differences. Multi-informant data allowed us to compare effects of adolescent-perceived and parent-reported parenting. Finally, innovative analyses allowed us to disentangle between-family differences from within-family predictive processes. Parenting and emotion regulation were associated at the between-family and within-family levels, especially according to adolescent reports. Support primarily played a role between mothers and adolescents, and perceived behavioral control between fathers and adolescents. Sex moderation revealed that support played a more prominent role in mother-daughter than mother-son relationships, and that daughters experienced greater behavioral control. Child effects outnumbered parent effects, which might reflect the increasing equality of adolescent-parent relationships. Finally, adolescent-perceived parenting was a stronger correlate of emotion regulation than parent-reports, suggesting that adolescents' perceptions are a relevant source of information for research and practice. Consistent with the self-determination theory perspective on parenting, emotion regulation flourished when adolescents felt like mothers provided support, and fathers loosened behavioral control. These results are in line with the notion that mother-child relationships are supportive attachment relationships, whereas fathers provide "activation" relationships, challenging adolescents to regulate emotions autonomously by providing less explicit structure.
Tissue-resident memory CD8
T cells (T
cells) are crucial in protecting against reinvading pathogens, but the impact of reinfection on their tissue confinement and contribution to recall responses is ...unclear. We developed a unique lineage tracer mouse model exploiting the T
-defining transcription factor homolog of Blimp-1 in T cells (Hobit) to fate map the T
progeny in secondary responses. After reinfection, a sizeable fraction of secondary memory T cells in the circulation developed downstream of T
cells. These tissue-experienced ex-T
cells shared phenotypic properties with the effector memory T cell population but were transcriptionally and functionally distinct from other secondary effector memory T cell cells. Adoptive transfer experiments of T
cells corroborated their potential to form circulating effector and memory cells during recall responses. Moreover, specific ablation of primary T
cell populations substantially impaired the secondary T cell response, both locally and systemically. Thus, T
cells retain developmental plasticity and shape both local and systemic T cell responses on reinfection.
To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT.
Five low ...and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom.
Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The translation 95% confidence intervals are within clinically applied margins of 5 mm, and plan adaption for intrafraction motion was required in only 4 out of 100 fractions.
This is the first study to investigate prostate intrafraction motions during entire MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and prostate tracking during RT is feasible with beam-on. The clinically applied margins of 5 mm have proven to be sufficient for these treatments and may potentially be further reduced using intrafraction plan adaptation guided by cine-MR imaging.
This study explored whether early elementary school aged children's externalizing problems impede academic functioning and foster negative social experiences such as peer victimization, thereby ...making these children vulnerable for developing internalizing problems and possibly increasing their externalizing problems. It also explored whether early internalizing problems contributed to an increase in externalizing problems. The study examined 1,558 Canadian children from ages 6 to 8 years. Externalizing and internalizing problems, peer victimization, and school achievement were assessed annually. Externalizing problems lead to academic underachievement and experiences of peer victimization. Academic underachievement and peer victimization, in turn, predicted increases in internalizing problems and in externalizing problems. These pathways applied equally to boys and girls. No links from internalizing to externalizing problems were found.
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