Heterogeneity

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Martin Ackermann - One of the best experts on this subject based on the ideXlab platform.

  • Substrate and electron donor limitation induce phenotypic Heterogeneity in different metabolic activities in a green sulphur bacterium
    Environmental Microbiology Reports, 2018
    Co-Authors: Matthias Zimmermann, Stephane Escrig, Martin Ackermann, Anders Meibom, Gaute Lavik, Marcel M. M. Kuypers, Frank Schreiber
    Abstract:

    Populations of genetically identical cells can display marked variation in phenotypic traits; such variation is termed phenotypic Heterogeneity. Here, we investigate the effect of substrate and electron donor limitation on phenotypic Heterogeneity in N2 and CO2 fixation in the green sulphur bacterium Chlorobium phaeobacteroides. We grew populations in chemostats and batch cultures and used stable isotope labelling combined with nanometer‐scale secondary ion mass spectrometry (NanoSIMS) to quantify phenotypic Heterogeneity. Experiments in H2S (i.e. electron donor) limited chemostats show that varying levels of NH4+ limitation induce Heterogeneity in N2 fixation. Comparison of phenotypic Heterogeneity between chemostats and batch (unlimited for H2S) populations indicates that electron donor limitation drives Heterogeneity in N2 and CO2 fixation. Our results demonstrate that phenotypic Heterogeneity in a certain metabolic activity can be driven by different modes of limitation and that Heterogeneity can emerge in different metabolic processes upon the same mode of limitation. In conclusion, our data suggest that limitation is a general driver of phenotypic Heterogeneity in microbial populations.

  • phenotypic Heterogeneity driven by nutrient limitation promotes growth in fluctuating environments
    Nature microbiology, 2016
    Co-Authors: Sten Littmann, Stephane Escrig, Martin Ackermann, Anders Meibom, Gaute Lavik, Marcel M. M. Kuypers, Frank Schreiber
    Abstract:

    Most microorganisms live in environments where nutrients are limited and fluctuate over time. Cells respond to nutrient fluctuations by sensing and adapting their physiological state. Recent studies suggest phenotypic Heterogeneity1 in isogenic populations as an alternative strategy in fluctuating environments, where a subpopulation of cells express a function that allows growth under conditions that might arise in the future2–9. It is unknown how environmental factors such as nutrient limitation shape phenotypic Heterogeneity in metabolism and whether this allows cells to respond to nutrient fluctuations. Here, we show that substrate limitation increases phenotypic Heterogeneity in metabolism, and this Heterogeneity allows cells to cope with substrate fluctuations. We subjected the N2-fixing bacterium Klebsiella oxytoca to different levels of substrate limitation and substrate shifts, and obtained time-resolved single-cell measurements of metabolic activities using nanometre-scale secondary ion mass spectrometry (NanoSIMS). We found that the level of NH4+ limitation shapes phenotypic Heterogeneity in N2 fixation. In turn, the N2 fixation rate of single cells during NH4+ limitation correlates positively with their growth rate after a shift to NH4+ depletion, experimentally demonstrating the benefit of Heterogeneity. The results indicate that phenotypic Heterogeneity is a general solution to two important ecological challenges—nutrient limitation and fluctuations—that many microorganisms face. Single-cell measurements of metabolic activities using NanoSIMS reveals that substrate limitation increases phenotypic Heterogeneity in Klebsiella oxytoca metabolism, which allows cells to cope with nutrient fluctuations.

Masaaki Inaba - One of the best experts on this subject based on the ideXlab platform.

  • Thyroid Heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid peroxidase antibodies in euthyroid Hashimoto's thyroiditis.
    Thyroid Research, 2013
    Co-Authors: Yosuke Wakita, Toshiki Nagasaki, Yuki Nagata, Yasuo Imanishi, Shinsuke Yamada, Koichiro Yoda, Masanori Emoto, Eiji Ishimura, Masaaki Inaba
    Abstract:

    Objective: To prospectively evaluate the heterogeneous appearance of the thyroid gland, reflecting inflammation and destruction in euthyroid Hashimoto’s thyroiditis (HT), we investigated the clinical utilities of the Heterogeneity index (HI) [the coefficient of variance (CV) of the ultrasonographic (US) intensities], focusing on anti-thyroid peroxidase antibodies (TPO-Ab), which represent not only disease activity but also subsequent thyroid destruction of HT. Methods: Forty-four consecutive patients with euthyroid HT [60.5± 2.7 years old (mean ± SE)] and 30 age-matched normal controls were studied. HI was calculated as the CV (SD/mean) of US intensities of either four points per lobe of the thyroid gland along a horizontal line at the depth of the right common carotid artery. Evaluation included serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), thyroglobulin and thyroid volume. Results: While no differences were observed for TSH, FT4 and FT3, thyroglobulin and thyroid volume between the two groups, HI exhibited a tendency towards a significant difference (3.59±0.20% in HT patients vs 3.23±0.19% in normal group, p =0.089). In HT patients, there was a significant and positive correlation of HI with TPO-Ab (r=0.396, p =0.034), whereas such a correlation was absent in normal controls. In both groups, there were no significant correlations of HI with Tg-Ab, FT3 ,F T4 or TSH. Conclusions: This is the first report of the close relation between Heterogeneity of US of the thyroid gland and TPO-Ab in euthyroid HT patients before the Heterogeneity becomes distinguishable from normal thyroid glands. Furthermore, at this stage, subsequent thyroid destruction in HT might be already be predicted through the heterogeniety of the thyroid tissue.

  • Thyroid Heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid peroxidase antibodies in euthyroid Hashimoto’s thyroiditis
    Thyroid Research, 2013
    Co-Authors: Yosuke Wakita, Toshiki Nagasaki, Yuki Nagata, Yasuo Imanishi, Shinsuke Yamada, Koichiro Yoda, Masanori Emoto, Eiji Ishimura, Masaaki Inaba
    Abstract:

    Objective To prospectively evaluate the heterogeneous appearance of the thyroid gland, reflecting inflammation and destruction in euthyroid Hashimoto’s thyroiditis (HT), we investigated the clinical utilities of the Heterogeneity index (HI) [the coefficient of variance (CV) of the ultrasonographic (US) intensities], focusing on anti-thyroid peroxidase antibodies (TPO-Ab), which represent not only disease activity but also subsequent thyroid destruction of HT. Methods Forty-four consecutive patients with euthyroid HT [60.5 ± 2.7 years old (mean ± SE)] and 30 age-matched normal controls were studied. HI was calculated as the CV (SD/mean) of US intensities of either four points per lobe of the thyroid gland along a horizontal line at the depth of the right common carotid artery. Evaluation included serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), thyroglobulin and thyroid volume. Results While no differences were observed for TSH, FT_4 and FT_3, thyroglobulin and thyroid volume between the two groups, HI exhibited a tendency towards a significant difference (3.59 ± 0.20% in HT patients vs 3.23 ± 0.19% in normal group, p = 0.089). In HT patients, there was a significant and positive correlation of HI with TPO-Ab (r = 0.396, p = 0.034), whereas such a correlation was absent in normal controls. In both groups, there were no significant correlations of HI with Tg-Ab, FT_3, FT_4 or TSH. Conclusions This is the first report of the close relation between Heterogeneity of US of the thyroid gland and TPO-Ab in euthyroid HT patients before the Heterogeneity becomes distinguishable from normal thyroid glands. Furthermore, at this stage, subsequent thyroid destruction in HT might be already be predicted through the heterogeniety of the thyroid tissue.

Frank Schreiber - One of the best experts on this subject based on the ideXlab platform.

  • Substrate and electron donor limitation induce phenotypic Heterogeneity in different metabolic activities in a green sulphur bacterium
    Environmental Microbiology Reports, 2018
    Co-Authors: Matthias Zimmermann, Stephane Escrig, Martin Ackermann, Anders Meibom, Gaute Lavik, Marcel M. M. Kuypers, Frank Schreiber
    Abstract:

    Populations of genetically identical cells can display marked variation in phenotypic traits; such variation is termed phenotypic Heterogeneity. Here, we investigate the effect of substrate and electron donor limitation on phenotypic Heterogeneity in N2 and CO2 fixation in the green sulphur bacterium Chlorobium phaeobacteroides. We grew populations in chemostats and batch cultures and used stable isotope labelling combined with nanometer‐scale secondary ion mass spectrometry (NanoSIMS) to quantify phenotypic Heterogeneity. Experiments in H2S (i.e. electron donor) limited chemostats show that varying levels of NH4+ limitation induce Heterogeneity in N2 fixation. Comparison of phenotypic Heterogeneity between chemostats and batch (unlimited for H2S) populations indicates that electron donor limitation drives Heterogeneity in N2 and CO2 fixation. Our results demonstrate that phenotypic Heterogeneity in a certain metabolic activity can be driven by different modes of limitation and that Heterogeneity can emerge in different metabolic processes upon the same mode of limitation. In conclusion, our data suggest that limitation is a general driver of phenotypic Heterogeneity in microbial populations.

  • phenotypic Heterogeneity driven by nutrient limitation promotes growth in fluctuating environments
    Nature microbiology, 2016
    Co-Authors: Sten Littmann, Stephane Escrig, Martin Ackermann, Anders Meibom, Gaute Lavik, Marcel M. M. Kuypers, Frank Schreiber
    Abstract:

    Most microorganisms live in environments where nutrients are limited and fluctuate over time. Cells respond to nutrient fluctuations by sensing and adapting their physiological state. Recent studies suggest phenotypic Heterogeneity1 in isogenic populations as an alternative strategy in fluctuating environments, where a subpopulation of cells express a function that allows growth under conditions that might arise in the future2–9. It is unknown how environmental factors such as nutrient limitation shape phenotypic Heterogeneity in metabolism and whether this allows cells to respond to nutrient fluctuations. Here, we show that substrate limitation increases phenotypic Heterogeneity in metabolism, and this Heterogeneity allows cells to cope with substrate fluctuations. We subjected the N2-fixing bacterium Klebsiella oxytoca to different levels of substrate limitation and substrate shifts, and obtained time-resolved single-cell measurements of metabolic activities using nanometre-scale secondary ion mass spectrometry (NanoSIMS). We found that the level of NH4+ limitation shapes phenotypic Heterogeneity in N2 fixation. In turn, the N2 fixation rate of single cells during NH4+ limitation correlates positively with their growth rate after a shift to NH4+ depletion, experimentally demonstrating the benefit of Heterogeneity. The results indicate that phenotypic Heterogeneity is a general solution to two important ecological challenges—nutrient limitation and fluctuations—that many microorganisms face. Single-cell measurements of metabolic activities using NanoSIMS reveals that substrate limitation increases phenotypic Heterogeneity in Klebsiella oxytoca metabolism, which allows cells to cope with nutrient fluctuations.

Andrés Hidalgo - One of the best experts on this subject based on the ideXlab platform.

  • Heterogeneity of neutrophils
    Nature Reviews Immunology, 2019
    Co-Authors: Renato Ostuni, Andrés Hidalgo
    Abstract:

    Structured models of ontogenic, phenotypic and functional diversity have been instrumental for a renewed understanding of the biology of immune cells, such as macrophages and lymphoid cells. However, there are no established models that can be used to define the diversity of neutrophils, the most abundant myeloid cells. This lack of an established model is largely due to the uniquely short lives of neutrophils, a consequence of their inability to divide once terminally differentiated, which has been perceived as a roadblock to functional diversity. This perception is rapidly evolving as multiple phenotypic and functional variants of neutrophils have been found, both in homeostatic and disease conditions. In this Opinion article, we present an overview of neutrophil Heterogeneity and discuss possible mechanisms of diversification, including genomic regulation. We suggest that neutrophil Heterogeneity is an important feature of immune pathophysiology, such that co-option of the mechanisms of diversification by cancer or other disorders contributes to disease progression. Emerging data indicate that neutrophils exist in several different ‘flavours’. Here, the authors outline potential underlying mechanisms for the presence of distinct neutrophil subsets in health and disease.

  • Heterogeneity of neutrophils.
    Nature Reviews Immunology, 2019
    Co-Authors: Renato Ostuni, Andrés Hidalgo
    Abstract:

    Structured models of ontogenic, phenotypic and functional diversity have been instrumental for a renewed understanding of the biology of immune cells, such as macrophages and lymphoid cells. However, there are no established models that can be used to define the diversity of neutrophils, the most abundant myeloid cells. This lack of an established model is largely due to the uniquely short lives of neutrophils, a consequence of their inability to divide once terminally differentiated, which has been perceived as a roadblock to functional diversity. This perception is rapidly evolving as multiple phenotypic and functional variants of neutrophils have been found, both in homeostatic and disease conditions. In this Opinion article, we present an overview of neutrophil Heterogeneity and discuss possible mechanisms of diversification, including genomic regulation. We suggest that neutrophil Heterogeneity is an important feature of immune pathophysiology, such that co-option of the mechanisms of diversification by cancer or other disorders contributes to disease progression.

Ernesto Estrada - One of the best experts on this subject based on the ideXlab platform.

  • Quantifying network Heterogeneity.
    Physical review. E Statistical nonlinear and soft matter physics, 2010
    Co-Authors: Ernesto Estrada
    Abstract:

    Despite degree distributions give some insights about how heterogeneous a network is, they fail in giving a unique quantitative characterization of network Heterogeneity. This is particularly the case when several different distributions fit for the same network, when the number of data points is very scarce due to network size, or when we have to compare two networks with completely different degree distributions. Here we propose a unique characterization of network Heterogeneity based on the difference of functions of node degrees for all pairs of linked nodes. We show that this Heterogeneity index can be expressed as a quadratic form of the Laplacian matrix of the network, which allows a spectral representation of network Heterogeneity. We give bounds for this index, which is equal to zero for any regular network and equal to one only for star graphs. Using it we study random networks showing that those generated by the Erdös-Rényi algorithm have zero Heterogeneity, and those generated by the preferential attachment method of Barabási and Albert display only 11% of the Heterogeneity of a star graph. We finally study 52 real-world networks and we found that they display a large variety of heterogeneities. We also show that a classification system based on degree distributions does not reflect the Heterogeneity properties of real-world networks.

  • Quantifying network Heterogeneity.
    Physical Review E, 2010
    Co-Authors: Ernesto Estrada
    Abstract:

    Despite degree distributions give some insights about how heterogeneous a network is, they fail in giving a unique quantitative characterization of network Heterogeneity. This is particularly the case when several different distributions fit for the same network, when the number of data points is very scarce due to network size, or when we have to compare two networks with completely different degree distributions. Here we propose a unique characterization of network Heterogeneity based on the difference of functions of node degrees for all pairs of linked nodes. We show that this Heterogeneity index can be expressed as a quadratic form of the Laplacian matrix of the network, which allows a spectral representation of network Heterogeneity. We give bounds for this index, which is equal to zero for any regular network and equal to one only for star graphs. Using it we study random networks showing that those generated by the Erdos-Renyi algorithm have zero Heterogeneity, and those generated by the preferential attachment method of Barabasi and Albert display only 11% of the Heterogeneity of a star graph. We finally study 52 real-world networks and we found that they display a large variety of heterogeneities. We also show that a classification system based on degree distributions does not reflect the Heterogeneity properties of real-world networks.