359,926 research outputs found
High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils
Background Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. ABPP utilizes cell/tissue proteomes and features the FP-warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Existing ABPP approaches characterize global SH activity based on mobility in gel or MS-based target identification and cannot reveal the identity of the cell-type responsible for an individual SH activity originating from complex proteomes. Results Here, by using an activity probe with broad reactivity towards the SH family, we advance the ABPP methodology to glioma brain cryosections, enabling for the first time high-resolution confocal fluorescence imaging of global SH activity in the tumor microenvironment. Tumor-associated cell types were identified by extensive immunohistochemistry on activity probe-labeled sections. Tissue-ABPP indicated heightened SH activity in glioma vs. normal brain and unveiled activity hotspots originating from tumor-associated neutrophils (TANs), rather than tumor-associated macrophages (TAMs). Thorough optimization and validation was provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Conclusions Our study advances the ABPP methodology to tissue sections, enabling high-resolution confocal fluorescence imaging of global SH activity in anatomically preserved complex native cellular environment. To achieve global portrait of SH activity throughout the section, a probe with broad reactivity towards the SH family members was employed. As ABPP requires no a priori knowledge of the identity of the target, we envisage no imaginable reason why the presently described approach would not work for sections regardless of species and tissue source.Peer reviewe
High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils
Background Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. ABPP utilizes cell/tissue proteomes and features the FP-warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Existing ABPP approaches characterize global SH activity based on mobility in gel or MS-based target identification and cannot reveal the identity of the cell-type responsible for an individual SH activity originating from complex proteomes. Results Here, by using an activity probe with broad reactivity towards the SH family, we advance the ABPP methodology to glioma brain cryosections, enabling for the first time high-resolution confocal fluorescence imaging of global SH activity in the tumor microenvironment. Tumor-associated cell types were identified by extensive immunohistochemistry on activity probe-labeled sections. Tissue-ABPP indicated heightened SH activity in glioma vs. normal brain and unveiled activity hotspots originating from tumor-associated neutrophils (TANs), rather than tumor-associated macrophages (TAMs). Thorough optimization and validation was provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Conclusions Our study advances the ABPP methodology to tissue sections, enabling high-resolution confocal fluorescence imaging of global SH activity in anatomically preserved complex native cellular environment. To achieve global portrait of SH activity throughout the section, a probe with broad reactivity towards the SH family members was employed. As ABPP requires no a priori knowledge of the identity of the target, we envisage no imaginable reason why the presently described approach would not work for sections regardless of species and tissue source.Peer reviewe
Emerging Adults and Identity Development in the Time of COVID-19
The COVID-19 pandemic severely altered the lives of people across the world. Although the social isolation and disruption wrought by the pandemic have been universal experiences, emerging adults are at a pivotal moment and are potentially uniquely affected. Emerging adulthood is a critical time for identity development and the college setting fosters an environment for identity exploration. Studies show that in emerging adulthood, turning point events (e.g., global or national tragedies, personal challenges, transitions, or any form of upheaval, such as a pandemic) that are resolved positively are connected more closely with progress in identity formation, and the importance of positive resolution of negative events appears to be unique to emerging adults. This study explored how emerging adults in college (N = 231) were processing the COVID-19 pandemic and whether identity was a factor that affected an individualâs perception of the pandemic. The results of the present study support the hypotheses that an emerging adultâs identity does affect their pandemic processing, as does a personâs political identity, and self-reported mental health. The study revealed that pandemic processing was significantly related to studentsâ identity, mental well-being, and political beliefs. This study informs practitioners of education, families, and students themselves about how identity affects reactions to adversity and how turning negative experiences into positive experiences can have long-term benefits on a personâs sense of self well-being beyond emerging adulthood
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TripL - Living, Learning, Leading: A Program for Ongoing Cultural Training for House Leaders at Mossgate Preparatory School
This paper is a program proposal for an ongoing intercultural training program for boarding house leaders at Mossgate Preparatory School (MPS). High turnover rates for house leaders at MPS have been linked to conflict and frustration related to living and working in a multicultural environment. A Multicultural Competency questionnaire was distributed to 2014-15 MPS house leaders, and the results showed that approximately half of all house leaders had never received any sort of intercultural training. In order to address this need, the TripL Program was conceived.
Through initial and ongoing trainings conducted for all house leaders at MPS, the TripL Program will promote cross-cultural communication, cultural awareness information for living in a multi-cultural community, acculturation stress, effective conflict-resolution techniques, team building and community development. House leaders will also gain insight into the teenage brain and ethnic identity development. TripL will strengthen the house leader community, and in turn the individual boarding house communities they live and serve. Finally, house leaders will be able to build stronger, healthier relationships with and between students in their houses. MPS students, in turn, will benefit from being supported in learning how to successfully and harmoniously live in a multicultural environment, making them better global citizens
The role of climate and plant functional trade-offs in shaping global biome and biodiversity patterns
Aim: Two of the oldest observations in plant geography are the increase in plant diversity from the poles towards the tropics and the global geographic distribution of vegetation physiognomy (biomes). The objective of this paper is to use a process-based vegetation model to evaluate the relationship between modelled and observed global patterns of plant diversity and the geographic distribution of biomes.Location: The global terrestrial biosphere.Methods: We implemented and tested a novel vegetation model aimed at identifying strategies that enable plants to grow and reproduce within particular climatic conditions across the globe. Our model simulates plant survival according to the fundamental ecophysiological processes of water uptake, photosynthesis, reproduction and phenology. We evaluated the survival of an ensemble of 10,000 plant growth strategies across the range of global climatic conditions. For the simulated regional plant assemblages we quantified functional richness, functional diversity and functional identity.Results: A strong relationship was found (correlation coefficient of 0.75) between the modelled and the observed plant diversity. Our approach demonstrates that plant functional dissimilarity increases and then saturates with increasing plant diversity. Six of the major Earth biomes were reproduced by clustering grid cells according to their functional identity (mean functional traits of a regional plant assemblage). These biome clusters were in fair agreement with two other global vegetation schemes: a satellite image classification and a biogeography model (kappa statistics around 0.4).Main conclusions: Our model reproduces the observed global patterns of plant diversity and vegetation physiognomy from the number and identity of simulated plant growth strategies. These plant growth strategies emerge from the first principles of climatic constraints and plant functional trade-offs. Our study makes important contributions to furthering the understanding of how climate affects patterns of plant diversity and vegetation physiognomy from a process-based rather than a phenomenological perspective
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