| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Cai, Huan, et al.
(författare)
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Critical role of Lama4 for hematopoiesis regeneration and acute myeloid leukemia progression
- 2022
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 139:20, s. 3040-3057
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Tidskriftsartikel (refereegranskat)abstract
- Impairment of normal hematopoiesis and leukemia progression are 2 well-linked processes during leukemia development and are controlled by the bone marrow (BM) niche. Extracellular matrix proteins, including laminin, are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied by altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4−/− mice. Upon AML exposure, Lama4−/− mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations, including upregulation of inflammatory cytokines that favor AML growth. Lama4−/− MSCs displayed increased antioxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4−/− mice post–cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates the critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.
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| 5. |
- Dolinska, Monika, et al.
(författare)
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Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 6. |
- Dolinska, Monika, et al.
(författare)
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Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 7. |
- Guo, Feilong, et al.
(författare)
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How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease?
- 2021
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory condition of the intestine without any efficient therapeutic regimens. Gut microbiota, which plays an instrumental role in the development and maturation of the immune system, has been implicated in the pathogenesis of IBD. Emerging evidence has established that early-life events particularly maternal influences and antibiotic treatment are strongly correlated with the health or susceptibility to disease of an individual in later life. Thus, it is proposed that there is a critical period in infancy, during which the environmental exposures bestow a long-term pathophysiological imprint. This notion sheds new light on the development of novel approaches for the treatment, i.e., early interventions, more precisely, the prevention of many uncurable chronic inflammatory diseases like IBD. In this review, we have integrated current evidence to describe the feasibility of the "able-to-be-regulated microbiota," summarized the underlying mechanisms of the "microbiota-driven immune system education," explored the optimal intervention time window, and discussed the potential of designing early-probiotic treatment as a new prevention strategy for IBD.
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| 8. |
- Jin, Yi, et al.
(författare)
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Self-aware distributed deep learning framework for heterogeneous IoT edge devices
- 2021
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Ingår i: Future generations computer systems. - : Elsevier BV. - 0167-739X .- 1872-7115. ; 125, s. 908-920
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Tidskriftsartikel (refereegranskat)abstract
- Implementing artificial intelligence (AI) in the Internet of Things (IoT) involves a move from the cloud to the heterogeneous and low-power edge, following an urgent demand for deploying complex training tasks in a distributed and reliable manner. This work proposes a self-aware distributed deep learning (DDL) framework for IoT applications, which is applicable to heterogeneous edge devices aiming to improve adaptivity and amortize the training cost. The self-aware design including the dynamic self-organizing approach and the self-healing method enhances the system reliability and resilience. Three typical edge devices are adopted with cross-platform Docker deployment: Personal Computers (PC) for general computing devices, Raspberry Pi 4Bs (Rpi) for resource-constrained edge devices, and Jetson Nanos (Jts) for AI-enabled edge devices. Benchmarked with ResNet-32 on CIFAR-10, the training efficiency of tested distributed clusters is increased by 8.44x compared to the standalone Rpi. The cluster with 11 heterogeneous edge devices achieves a training efficiency of 200.4 images/s and an accuracy of 92.45%. Results prove that the self-organizing approach functions well with dynamic changes like devices being removed or added. The self-healing method is evaluated with various stabilities, cluster scales, and breakdown cases, testifying that the reliability can be largely enhanced for extensively distributed deployments. The proposed DDL framework shows excellent performance for training implementation with heterogeneous edge devices in IoT applications with high-degree scalability and reliability.
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| 9. |
- Li, Sirui, et al.
(författare)
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Glioma grading, molecular feature classification, and microstructural characterization using MR diffusional variance decomposition (DIVIDE) imaging
- 2021
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31:11, s. 8197-8207
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the potential of diffusional variance decomposition (DIVIDE) for grading, molecular feature classification, and microstructural characterization of gliomas. Materials and methods: Participants with suspected gliomas underwent DIVIDE imaging, yielding parameter maps of fractional anisotropy (FA), mean diffusivity (MD), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), total mean kurtosis (MKT), MKA/MKT, and microscopic fractional anisotropy (μFA). Tumor type and grade, isocitrate dehydrogenase (IDH) 1/2 mutant status, and the Ki-67 labeling index (Ki-67 LI) were determined after surgery. Statistical analysis included 33 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG). Tumor diffusion metrics were compared between HGG and LGG, among grades, and between wild and mutated IDH types using appropriate tests according to normality assessment results. Receiver operating characteristic and Spearman correlation analysis were also used for statistical evaluations. Results: FA, MD, MKA, MKI, MKT, μFA, and MKA/MKT differed between HGG and LGG (FA: p = 0.047; MD: p = 0.037, others p < 0.001), and among glioma grade II, III, and IV (FA: p = 0.048; MD: p = 0.038, others p < 0.001). All diffusion metrics differed between wild-type and mutated IDH tumors (MKI: p = 0.003; others: p < 0.001). The metrics that best discriminated between HGG and LGGs and between wild-type and mutated IDH tumors were MKT and FA respectively (area under the curve 0.866 and 0.881). All diffusion metrics except FA showed significant correlation with Ki-67 LI, and MKI had the highest correlation coefficient (rs = 0.618). Conclusion: DIVIDE is a promising technique for glioma characterization and diagnosis. Key Points: • DIVIDE metrics MKIis related to cell density heterogeneity while MKAand μFA are related to cell eccentricity. • DIVIDE metrics can effectively differentiate LGG from HGG and IDH mutation from wild-type tumor, and showed significant correlation with the Ki-67 labeling index. • MKIwas larger than MKAwhich indicates predominant cell density heterogeneity in gliomas. • MKAand MKIincreased with grade or degree of malignancy, however with a relatively larger increase in the cell eccentricity metric MKAin relation to the cell density heterogeneity metric MKI.
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| 10. |
- Liu, Wei, et al.
(författare)
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Pickering multiphase materials using plant-based cellulosic micro/nanoparticles
- 2024
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Ingår i: Aggregate. - 2692-4560.
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Forskningsöversikt (refereegranskat)abstract
- Pickering multiphase systems stabilized by solid particles have recently attracted increasing attention due to their excellent stability. Among various solid stabilizers, natural and renewable cellulosic micro/nanoparticles that are derived from agricultural and forestry sources have become promising candidates for Pickering stabilization due to their unique morphological features and tunable surface properties. In this review, recent progress on forming and stabilizing Pickering multiphase systems using cellulosic colloidal particles is summarized, including the physicochemical factors affecting their assembly at the interfaces and the preparation methods suitable for producing Pickering emulsions. In addition, relevant application prospects of corresponding Pickering multiphase materials are outlined. Finally, current challenges and future perspectives of such renewable Pickering multiphase systems are presented. This review aims to encourage the utilization of cellulosic micro/nanoparticles as key components in the development of Pickering systems, leading to enhanced performance and unique functionalities. image
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| 11. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 12. |
- Sandhow, Lakshmi, et al.
(författare)
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Skin mesenchymal niches maintain and protect AML-initiating stem cells
- 2023
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Ingår i: Journal of Experimental Medicine. - 0022-1007 .- 1540-9538. ; 220:10
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Tidskriftsartikel (refereegranskat)abstract
- Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantation. Prospective niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs protected AML-initiating stem cells (LSCs) from chemotherapy in vitro partially via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs appeared to be retained in Lama4−/− mouse skin after cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining and protecting AML LSCs during chemotherapy, meriting future exploration of their impact on AML relapse.
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| 13. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 14. |
- Xu, Jun, et al.
(författare)
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Optimal response to habitat linkage of local fish diversity and mean trophic level
- 2016
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Ingår i: Limnology and Oceanography. - : Wiley. - 1939-5590 .- 0024-3590. ; 61:4, s. 1438-1448
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Tidskriftsartikel (refereegranskat)abstract
- Spatially segregated ecosystems are frequently subsidized by cross-habitat linkages, but the extent to which the functional links between habitats influence local community attributes, such as consumer and food web structure is still poorly understood. Using the bidirectional linkage between benthic and pelagic habitats in floodplain lakes, we address this important question by looking for evidence of an optimal extent of habitat linkage supporting maximum taxonomic richness and mean trophic level. We then ask if there are significant changes in these local community attributes between historical and current communities, and if these reflect the history of species loss resulting from the intense human alteration of these lakes. We found a strong optimal response of maximum richness and mean trophic level along the pelagic-benthic gradient, both across and within individual lakes. This is consistent with the expectation of optimal resource availability along the habitat linkage gradient supporting more and taxonomically richer communities. Comparison between historical and current assemblages revealed a significant decrease in the optimal linkage for maximum richness in response to the history of species loss, but not for maximum mean trophic level, probably a response to the increased habitat homogenization and enhanced productivity caused by the recent history of nutrient-enrichment and habitat alteration. Our study provides strong evidence of high diversity and trophic level occurring at intermediate levels of coupling between pelagic and benthic resources, suggesting assemblage reliance on multiple production sources, and offers novel insight into the responses of this relationship to species loss due to human activities.
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