Limited Effects of Precipitation Manipulation on Soil Respiration and Inorganic N Concentrations Across Soil Drainage Classes in Northern Minnesota Aspen Forests

It is critical to gain insight into the responses of forest soils to the changing climate. We simulated future climate conditions with growing season throughfall reduction (by 50%) and winter snow removal using a paired-plot design across a soil drainage class gradient at three upland, Populus-dominated forests in northern Minnesota, USA. In situ bulk soil respiration and concentrations of extractable soil N were measured during the summers of 2020–2021. Soil respiration and N concentrations were not affected by throughfall reduction and snow removal, which was largely attributed to the limited treatment effects on soil moisture content and soil temperature. Drainage class was only a significant factor during the spring thaw period in 2021. During this period, the poorly drained plots had lower respiration rates compared to the well-drained plots, which was associated with the drainage class effects on soil temperature. The results of the companion laboratory incubation with varying levels of soil moisture also indicated no effect of the treatment on soil respiration, but effects of drainage class and moisture content on respiration were observed. Our results indicate that the combined effects of reduced summer and winter precipitation on soil respiration and N dynamics may be limited across the range of conditions that occurred in our study

The Effects of Combined Throughfall Reduction and Snow Removal on Soil Physical Properties Across a Drainage Gradient in Aspen Forests of Northern Minnesota, USA

Climate change is projected to alter precipitation patterns across northern latitudes, with decreased snow accumulation and summer rainfall predicted. These changes may alter soil physical properties such as soil strength, which would have implications for the feasibility of forest management activities. Reductions in summer and winter precipitation were simulated using a paired-plot design with throughfall reduction and snow removal as treatments across four soil drainage classes (well, moderately well, somewhat poor, and poorly drained) at each of three locations in northern Minnesota, USA. Snow removal caused large reductions in soil temperature and significantly deeper penetration of frost that varied by drainage class, where frost depth decreased with decreasing (wetter) drainage. There was a positive relationship between air freezing index and frost depth, where the rate of frost development was much higher in the snow removal treatment compared to the control (r2 of treatment = 0.8, slope = 0.093, p \u3c 0.001; r2 of control = 0.18, slope = 0.012, p \u3c 0.001). Throughfall reduction had limited effects on soil water content (SWC) and inconsistent effects on soil strength; relationships between SWC and strength were positive, negative, or non-existent. Based on these findings, changes in soil physical properties with altered precipitation are likely to manifest primarily in winter. Drainage class and air freezing index may be used to predict when sufficient soil frost is present for forest management activities to occur without detrimental effects to soil functions

Limited Effects of Precipitation Manipulation on Soil Respiration and Inorganic N Concentrations across Soil Drainage Classes in Northern Minnesota Aspen Forests

It is critical to gain insight into the responses of forest soils to the changing climate. We simulated future climate conditions with growing season throughfall reduction (by 50%) and winter snow removal using a paired-plot design across a soil drainage class gradient at three upland, Populus-dominated forests in northern Minnesota, USA. In situ bulk soil respiration and concentrations of extractable soil N were measured during the summers of 2020–2021. Soil respiration and N concentrations were not affected by throughfall reduction and snow removal, which was largely attributed to the limited treatment effects on soil moisture content and soil temperature. Drainage class was only a significant factor during the spring thaw period in 2021. During this period, the poorly drained plots had lower respiration rates compared to the well-drained plots, which was associated with the drainage class effects on soil temperature. The results of the companion laboratory incubation with varying levels of soil moisture also indicated no effect of the treatment on soil respiration, but effects of drainage class and moisture content on respiration were observed. Our results indicate that the combined effects of reduced summer and winter precipitation on soil respiration and N dynamics may be limited across the range of conditions that occurred in our study

Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, which is mainly due to late diagnosis and profound resistance to treatment. The latter is to a large extent attributed to the tumor stroma that is exceedingly prominent in PDAC and engages in complex interactions with the cancer cells. Hence, relevant preclinical models of PDAC should also include the tumor stroma. We herein describe the establishment and functional validation of an ex vivo organotypic culture of human PDAC that is based on precision-cut tissue slices from surgical specimens and reproducibly recapitulates the complex cellular and acellular composition of PDAC, including its microenvironment. The cancer cells, tumor microenvironment and interspersed remnants of nonneoplastic pancreas contained in these 350 µm thick slices maintained their structural integrity, phenotypic characteristics and functional activity when in culture for at least 4 days. In particular, tumor cell proliferation persisted and the grade of differentiation and morphological phenotype remained unaltered. Cultured tissue slices were metabolically active and responsive to rapamycin, an mTOR inhibitor. This culture system is to date the closest surrogate to the parent carcinoma and harbors great potential as a drug sensitivity testing system for the personalized treatment of PDAC

The Role of γδ T Cells as a Line of Defense in Viral Infections after Allogeneic Stem Cell Transplantation: Opportunities and Challenges

In the complex interplay between inflammation and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-HSCT), viral reactivations are often observed and cause substantial morbidity and mortality. As toxicity after allo-HSCT within the context of viral reactivations is mainly driven by αβ T cells, we describe that by delaying αβ T cell reconstitution through defined transplantation techniques, we can harvest the full potential of early reconstituting γδ T cells to control viral reactivations. We summarize evidence of how the γδ T cell repertoire is shaped by CMV and EBV reactivations after allo-HSCT, and their potential role in controlling the most important, but not all, viral reactivations. As most γδ T cells recognize their targets in an MHC-independent manner, γδ T cells not only have the potential to control viral reactivations but also to impact the underlying hematological malignancies. We also highlight the recently re-discovered ability to recognize classical HLA-molecules through a γδ T cell receptor, which also surprisingly do not associate with GVHD. Finally, we discuss the therapeutic potential of γδ T cells and their receptors within and outside the context of allo-HSCT, as well as the opportunities and challenges for developers and for payers

Cellular immunotherapy on primary multiple myeloma expanded in a 3D bone marrow niche model

Bone marrow niches support multiple myeloma, providing signals and cell-cell interactions essential for disease progression. A 3D bone marrow niche model was developed, in which supportive multipotent mesenchymal stromal cells and their osteogenic derivatives were co-cultured with endothelial progenitor cells. These co-cultured cells formed networks within the 3D culture, facilitating the survival and proliferation of primary CD138+ myeloma cells for up to 28 days. During this culture, no genetic drift was observed within the genomic profile of the primary myeloma cells, indicating a stable outgrowth of the cultured CD138+ population. The 3D bone marrow niche model enabled testing of a novel class of engineered immune cells, so called TEGs (αβT cells engineered to express a defined γδTCR) on primary myeloma cells. TEGs were engineered and tested from both healthy donors and myeloma patients. The added TEGs were capable of migrating through the 3D culture, exerting a killing response towards the primary myeloma cells in 6 out of 8 donor samples after both 24 and 48 hours. Such a killing response was not observed when adding mock transduced T cells. No differences were observed comparing allogeneic and autologous therapy. The supporting stromal microenvironment was unaffected in all conditions after 48 hours. When adding TEG therapy, the 3D model surpassed 2D models in many aspects by enabling analyses of specific homing, and both on- and off-target effects, preparing the ground for the clinical testing of TEGs. The model allows studying novel immunotherapies, therapy resistance mechanisms and possible side-effects for this incurable disease

Cellular immunotherapy on primary multiple myeloma expanded in a 3D bone marrow niche model

Bone marrow niches support multiple myeloma, providing signals and cell-cell interactions essential for disease progression. A 3D bone marrow niche model was developed, in which supportive multipotent mesenchymal stromal cells and their osteogenic derivatives were co-cultured with endothelial progenitor cells. These co-cultured cells formed networks within the 3D culture, facilitating the survival and proliferation of primary CD138+ myeloma cells for up to 28 days. During this culture, no genetic drift was observed within the genomic profile of the primary myeloma cells, indicating a stable outgrowth of the cultured CD138+ population. The 3D bone marrow niche model enabled testing of a novel class of engineered immune cells, so called TEGs (αβT cells engineered to express a defined γδTCR) on primary myeloma cells. TEGs were engineered and tested from both healthy donors and myeloma patients. The added TEGs were capable of migrating through the 3D culture, exerting a killing response towards the primary myeloma cells in 6 out of 8 donor samples after both 24 and 48 hours. Such a killing response was not observed when adding mock transduced T cells. No differences were observed comparing allogeneic and autologous therapy. The supporting stromal microenvironment was unaffected in all conditions after 48 hours. When adding TEG therapy, the 3D model surpassed 2D models in many aspects by enabling analyses of specific homing, and both on- and off-target effects, preparing the ground for the clinical testing of TEGs. The model allows studying novel immunotherapies, therapy resistance mechanisms and possible side-effects for this incurable disease

TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product

Straetemans and colleagues characterized αβT cells engineered to express a defined γδT cell receptor (TEG001) used in a first-in-human clinical study, with TLA in combination with NGS and qPCR. They provide a rapid strategy to evaluate the presence, integrity, and persistence of genetic information along the production chain of any GTMP

Gender specific trends in alcohol use: cross-cultural comparisons from 1998 to 2006 in 24 countries and regions

Contains fulltext : 77252.pdf (author's version ) (Open Access)Objective: To examine trends in the prevalence of monthly alcohol use and lifetime drunkenness among 15 year olds in 20 European countries, the Russian Federation, Israel, the United States of America, and Canada. Methods: Alcohol use prevalence and drunkenness were assessed in the Health Behavior in School-aged Children Survey conducted in each country in 1998, 2002, and 2006. Trends were determined using the Cochran-Mantel-Haenszel test for trends. Results: Average monthly alcohol use across all countries declined from 45.3 % to 43.6 % and drunkenness declined from 37.2% to 34.8. There was substantial variability across countries, with decreases in some countries and increases or no change in use or drunkenness in others. The overall decline was greater among boys, from 41.2 % to 36.7 % than among girls, 33.3 % to 31.9 %. In most of the countries where drinking or drunkenness increased, it was due mainly to increases among girls. Conclusions: Trends in alcohol use and drunkenness varied by country. Drinking and drunkenness remained higher among boys than girls, but the gap between boys and girls declined and girls appear to be catching up with boys in some countries