Herbivore Effects on Ecosystem Process Rates in a Low-Productive System

Mammalian herbivores shape the structure and function of many nutrient-limited or low-productive terrestrial ecosystems through modification of plant communities and plant–soil feedbacks. In the tundra biome, mammalian herbivores may both accelerate and decelerate plant biomass growth, microbial activity and nutrient cycling, that is, ecosystem process rates. Selective foraging and associated declines of palatable species are known to be major drivers of plant–soil feedbacks. However, declines in dominant plants of low palatability often linked with high herbivore densities may also modify ecosystem process rates, yet have received little attention. We present data from an island experiment with a 10-year vole density manipulation, to test the hypothesis that herbivores accelerate process rates by decreasing the relative abundance of poorly palatable plants to palatable ones. We measured plant species abundances and community composition, nitrogen contents of green plant tissues and multiple soil and litter variables under high and low vole density. Corroborating our hypothesis, periodic high vole density increased ecosystem process rates in low-productive tundra. High vole density was associated with both increasing relative abundance of palatable forbs over unpalatable evergreen dwarf shrubs and higher plant N content both at species and at community level. Changes in plant community composition, in turn, explained variation in microbial activity in litter and soil inorganic nutrient availability. We propose a new conceptual model with two distinct vole–plant–soil feedback pathways. Voles may drive local plant–soil feedbacks that either increase or decrease ecosystem process rates, in turn promoting heterogeneity in vegetation and soils across tundra landscapes.</p

Definition and Characteristics of Behavioral Medicine, and Main Tasks and Goals of the International Society of Behavioral Medicine—an International Delphi Study

© 2020, The Author(s). Background: In the past decades, behavioral medicine has attained global recognition. Due to its global reach, a critical need has emerged to consider whether the original definition of behavioral medicine is still valid, comprehensive, and inclusive, and to reconsider the main tasks and goals of the International Society of Behavioral Medicine (ISBM), as the umbrella organization in the field. The purpose of the present study was to (i) update the definition and scope of behavioral medicine and its defining characteristics; and (ii) develop a proposal on ISBM’s main tasks and goals. Method: Our study used the Delphi method. A core group prepared a discussion paper. An international Delphi panel rated questions and provided comments. The panel intended to reach an a priori defined level of consensus (i.e., 70%). Results: The international panel reached consensus on an updated definition and scope of behavioral medicine as a field of research and practice that builds on collaboration among multiple disciplines. These disciplines are concerned with development and application of behavioral and biomedical evidence across the disease continuum in clinical and public health domains. Consensus was reached on a proposal for ISBM’s main tasks and goals focused on supporting communication and collaboration across disciplines and participating organizations; stimulating research, education, and practice; and supporting individuals and organizations in the field. Conclusion: The consensus on definition and scope of behavioral medicine and ISBM’s tasks and goals provides a foundational step toward achieving these goals

Understanding similarities and differences in land use visions for Scotland

The successful transition towards a global society that can live within planetary boundaries is one of the greatest challenges for the twenty-first century. Sustainable land use and land management will be essential to ensure the continued delivery of the ecosystem goods and services needed to support a rapidly growing global population. To support the transition towards sustainable development, decision-makers need to better understand how land use change affects people and the environment. However, these insights are of limited use without societal agreement on future land uses. Understanding synergies and differences between land use visions forms a first step in assessing and comparing alternative pathways towards a sustainable future. This thesis uses a range of methods to understand visions of future land use amongst professional land use stakeholders, society at large, and young people in Scotland. Twenty semi-structured interviews were held with policy experts from the Scottish land use sectors. A nationwide statistically representative web-based survey provided insight into the visions of the Scottish population. And finally, a novel visual interview methodology was used to interview 26 pupils from two high schools in Perthshire. Inductive content analysis and descriptive statistics were used to analyse the results and understand and compare the land use visions of these different groups. As expected, different groups had different visions of future land use. There was, however, general agreement on certain themes, in particular the desire for a more sustainable lifestyle and the importance of a healthy environment. The sectoral stakeholders would like to see more partnerships, dialogue and collaboration; a society that is more engaged and aware about land use; resilient local economies; and short-, medium-, and long-term policies that help to achieve these goals. One of the key challenges for these groups will be how to translate abstract concepts such as ‘healthy ecosystem’ and ‘dialogue and partnerships’ into practice. This clearly requires a shared understanding of what a ‘healthy ecosystem’ means to different stakeholders, as well as appreciation of what true dialogue means and how this can be used to co-create solutions – potentially a radical change from the traditional top-down approaches. The research also identified divisions in Scottish society between those who want to continue a ‘status quo’ lifestyle, and those – in particular younger people (who spent time in the natural environment, through either school or home life) and those from a higher socio-economic background – who want a more sustainable lifestyle and to be more connected with the natural environment. These results are important, as policy makers need to be able to identify the factors that have successfully engaged certain groups and to promote these factors. Programmes that provide access to the natural environment (such as the Duke of Edinburgh’s Award) need to ensure equal opportunities by targeting disadvantaged groups. Simultaneously, it needs to be explored how to encourage those who would like to continue a ‘status quo’ lifestyle into a more sustainable one. Past research has shown how preferences can be influenced and how changes can be initiated by incentives and restrictions in order to promote desired behaviours. The power of the media should be leveraged: programmes such as BBC’s ‘Blue Planet’ highlight how our lifestyle choices impact on the natural environment and can provide the motivation for change. The current issues surrounding Brexit and Climate Change require a national conversation; using methods such as those presented in the thesis to elicit land use visions can help identify the commonalties and differences between stakeholders’ views. This can provide a starting point for dialogue and critical reflection on current instruments and objectives, and how they might be adapted to better reflect Scottish preferences and conditions

The role of collagen XIII in B-cell lymphoma development, and characterization of its biosynthesis and tissue distribution

Abstract Collagen XIII belongs to the subgroup of collagenous transmembrane proteins. It has a wide tissue distribution and has been localized to many sites of cell-matrix and cell-cell interaction in tissues. Biochemical and in silico analyses of collagen XIII and other collagenous transmembrane proteins revealed that the biosynthesis of this structurally varied group is characterized by a coiled-coil motif following the transmembrane domain, and these trimerization domains appear to be associated with each of the collagenous domains. The collagen XIII trimer was shown to have an interchain disulfide bond at the junction of the NC1 and COL1 domains, and several other collagenous transmembrane proteins have a pair of cysteines in the same location. Furthermore, furin cleavage at the NC1 domain can be expected in most of the proteins. Mice heterozygous for the Col13a1del transgene, encoding a mutant collagen XIII, developed clonal mature B-cell lineage lymphomas originating in the mesenteric lymph node (MLN). The incidence of disease in conventionally reared mice was 2-fold higher than for mice raised in a specific pathogen-free facility. The lymphomas often associated with large populations of macrophages and T cells. Lymphomas expressed little if any collagen XIII, suggesting that the effect of the mutation was B-cell extrinsic and likely to be associated with collagen XIII-positive tissues drained by the MLN. Studies of the small intestines of transgenic mice showed highly abnormal subepithelial basement membranes (BM), associated with heightened expression of genes involved in immune responses. These findings suggest that collagen XIII-dependent maintenance of the intestinal BM is a critical determinant of cancer susceptibility. Collagen XIII exhibited a wide tissue distribution at the protein level, and the most intense expression was found in lung. Tissues contained 1-4 collagen XIII polypeptides, their size ranging between 78 and 102 kDa. Collagen XIII staining was detected in a restricted set of blood vessels in the liver, pancreas, adrenal gland, epididymis and brain. Moreover, Col13a1del transgene expression in the absence of endogenous collagen XIII proved to be deleterious for mouse embryonal development, leading to early fetal mortality

Systemic inflammation in colorectal cancer:underlying factors, effects, and prognostic significance

Abstract Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40% of colorectal cancer patients. The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation. While the low-level systemic inflammation is often clinically silent, its consequences are many and may ultimately lead to chronic cancer-associated wasting, cachexia. In this review, we discuss the pathogenesis of cancer-related systemic inflammation, explore the role of systemic inflammation in promoting cancer growth, escaping antitumor defense, and shifting metabolic pathways, and how these changes are related to less favorable outcome

KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells

Abstract In a number of types of cancer, anoikis, a form of apoptosis induced by loss of extracellular matrix (ECM) attachment, is disturbed. Anoikis resistance is essential in the formation of metastases. A recent study identified carcinoma cell subpopulations surviving without ECM contact in pathological specimens of colorectal cancer. The occurrence of these subpopulations indicated anoikis resistance. In the present study, it is demonstrated that KRAS and BRAF mutations induce anoikis resistance in colon cancer (Caco‑2) cells. In 3D cultures, Caco‑2 cells transfected with mutated KRAS or BRAF formed multicellular structures analogous to anoikis‑resistant subpopulations in actual carcinomas, and serve as an in vitro model for anoikis resistance. Caco‑2 cell lines were constructed, with KRAS or BRAF mutations, using retroviral delivery. The current study investigated anoikis resistance using an Annexin V apoptosis test from suspension cultures. 3D in vitro cultures, which were generated in collagen‑matrigel mixtures, were assessed using confocal microscopy. 3D cultures embedded in paraffin were analyzed using conventional histopathology. In suspension cultures, Caco‑2 cells with KRAS or BRAF mutations indicated a significantly lower proportion of Annexin positivity than the native Caco‑2 cells, indicating that these mutations induce anoikis resistance in Caco‑2 cells. 3D cultures displayed native Caco‑2 cells forming polarized cysts with a single layer thick epithelium, whereas Caco‑2 cells with KRAS or BRAF mutations formed partially filled cystic structures or solid round structures where only the outermost layer was in contact with the ECM. Additionally, KRAS mutations induced reversed polarity to Caco‑2 cells along with the emergence of solid growth. The present study demonstrated that KRAS and BRAF mutations induce anoikis resistance in Caco‑2 colorectal cancer cells. The growth patterns generated from the KRAS and BRAF mutated cells in 3D cultures revealed a resemblance to the putative anoikis‑resistant subpopulations in actual carcinomas, including micropapillary structures and solid tumor cell islands. Additionally, KRAS mutation induced the emergence of inverted polarity. In conclusion, 3D cultures with modified Caco‑2 cells serve as a valid in vitro model for anoikis resistance and inverted polarity

A prognostic score based on B cell and plasma cell densities compared to T cell densities in colorectal cancer

Abstract Purpose: The purpose of this study was to compare a B cell/plasma cell–based scoring system to T cell score and evaluate their prognostic value in colorectal cancer. Methods: We used immunohistochemistry to analyze the expression of CD20, CD138, CD3, and CD8 in 221 colorectal cancer patients. CD20+ B cell and CD138+ plasma cell densities in the tumor center and invasive margin were calculated and converted into a B cell/plasma cell score. T cell score was defined similarly, using CD3+ and CD8+ T cell densities. Their associations with tumor and patient characteristics and survival were analyzed. Results: Kaplan–Meier analysis showed a high B cell/plasma cell score was associated with a tendency towards longer survival (p = 0.089), but no statistically significant association was found. High T cell score associated with longer cancer-specific survival in Kaplan–Meier analysis and multivariable Cox regression analysis (p &lt; 0.001). Additionally, high T cell score associated with lower disease stage (p &lt; 0.001) and lesser lymphovascular invasion (p = 0.020). Conclusions: High T cell score is associated with longer survival and clinicopathological factors typical to less aggressive tumors. This study did not support the additional prognostic value of B cell/plasma cell quantification

SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes

Abstract Proper functioning of each secretory and endocytic compartment relies on its unique pH micro-environment that is known to be dictated by the rates of V-ATPase-mediated H+ pumping and its leakage back to the cytoplasm via an elusive “H+ leak” pathway. Here, we show that this proton leak across Golgi membranes is mediated by the AE2a (SLC4A2a)-mediated bicarbonate-chloride exchange, as it is strictly dependent on bicarbonate import (in exchange for chloride export) and the expression level of the Golgi-localized AE2a anion exchanger. In the acidic Golgi lumen, imported bicarbonate anions and protons then facilitate a common buffering reaction that yields carbon dioxide and water before their egress back to the cytoplasm via diffusion or water channels. The flattened morphology of the Golgi cisternae helps this process, as their high surface-volume ratio is optimal for water and gas exchange. Interestingly, this net acid efflux pathway is often upregulated in cancers and established cancer cell lines, and responsible for their markedly elevated Golgi resting pH and attenuated glycosylation potential. Accordingly, AE2 knockdown in SW-48 colorectal cancer cells was able to restore these two phenomena, and at the same time, reverse their invasive and anchorage-independent growth phenotype. These findings suggest a possibility to return malignant cells to a benign state by restoring Golgi resting pH

Herbivore effects on ecosystem process rates in a low-productive system

Abstract Mammalian herbivores shape the structure and function of many nutrient-limited or low-productive terrestrial ecosystems through modification of plant communities and plant–soil feedbacks. In the tundra biome, mammalian herbivores may both accelerate and decelerate plant biomass growth, microbial activity and nutrient cycling, that is, ecosystem process rates. Selective foraging and associated declines of palatable species are known to be major drivers of plant–soil feedbacks. However, declines in dominant plants of low palatability often linked with high herbivore densities may also modify ecosystem process rates, yet have received little attention. We present data from an island experiment with a 10-year vole density manipulation, to test the hypothesis that herbivores accelerate process rates by decreasing the relative abundance of poorly palatable plants to palatable ones. We measured plant species abundances and community composition, nitrogen contents of green plant tissues and multiple soil and litter variables under high and low vole density. Corroborating our hypothesis, periodic high vole density increased ecosystem process rates in low-productive tundra. High vole density was associated with both increasing relative abundance of palatable forbs over unpalatable evergreen dwarf shrubs and higher plant N content both at species and at community level. Changes in plant community composition, in turn, explained variation in microbial activity in litter and soil inorganic nutrient availability. We propose a new conceptual model with two distinct vole–plant–soil feedback pathways. Voles may drive local plant–soil feedbacks that either increase or decrease ecosystem process rates, in turn promoting heterogeneity in vegetation and soils across tundra landscapes