Sudden Shifts in Ecological Systems: Intermittency and Transients in the Coupled Ricker Population Model

Many real ecological systems show sudden changes in behavior, phenomena sometimes categorized as regime shifts in the literature. The relative importance of exogenous versus endogenous forces producing regime shifts is an important question. These forces’ role in generating variability over time in ecological systems has been explored using tools from dynamical systems. We use similar ideas to look at transients in simple ecological models as a way of understanding regime shifts. Based in part on the theory of crises, we carefully analyze a simple two patch spatial model and begin to understand from a mathematical point of view what produces transient behavior in ecological systems. In particular, since the tools are essentially qualitative, we are able to suggest that transient behavior should be ubiquitous in systems with overcompensatory local dynamics, and thus should be typical of many ecological systems. This work has been supported by NSF Grant EF-0434266.     

Dynamic Ligand Discrimination in the Notch Signaling Pathway

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Cell‐specific responses to the cytokine TGFβ are determined by variability in protein levels

The cytokine TGFβ provides important information during embryonic development, adult tissue homeostasis, and regeneration. Alterations in the cellular response to TGFβ are involved in severe human diseases. To understand how cells encode the extracellular input and transmit its information to elicit appropriate responses, we acquired quantitative time‐resolved measurements of pathway activation at the single‐cell level. We established dynamic time warping to quantitatively compare signaling dynamics of thousands of individual cells and described heterogeneous single‐cell responses by mathematical modeling. Our combined experimental and theoretical study revealed that the response to a given dose of TGFβ is determined cell specifically by the levels of defined signaling proteins. This heterogeneity in signaling protein expression leads to decomposition of cells into classes with qualitatively distinct signaling dynamics and phenotypic outcome. Negative feedback regulators promote heterogeneous signaling, as a SMAD7 knock‐out specifically affected the signal duration in a subpopulation of cells. Taken together, we propose a quantitative framework that allows predicting and testing sources of cellular signaling heterogeneity.     

地理信息系统及其在动物空间行为研究中的应用

空间属性是动物行为的重要特征,也是行为生态学研究中必须要面对的难题之一。地理信息系统(Geographic Information System,GIS)具有强大的空间分析功能,它在动物行为生态学研究中得到了越来越广泛的应用,如生境选择、领域分析、迁徙路线、活动节律等。本文较系统地阐述了GIS的原理以及在行为生态学研究中所涉及的基本概念和原理,对近年来利用GIS进行的行为生态学研究做了回顾和总结,并对其未来的发展进行了展望。     

The diverse origins of circulating cell‐free DNA in the human body: a critical re‐evaluation of the literature

Since the detection of cell‐free DNA (cfDNA) in human plasma in 1948, it has been investigated as a non‐invasive screening tool for many diseases, especially solid tumours and foetal genetic abnormalities. However, to date our lack of knowledge regarding the origin and purpose of cfDNA in a physiological environment has limited its use to more obvious diagnostics, neglecting, for example, its potential utility in the identification of predisposition to disease, earlier detection of cancers, and lifestyle‐induced epigenetic changes. Moreover, the concept or mechanism of cfDNA could also have potential therapeutic uses such as in immuno‐ or gene therapy. This review presents an extensive compilation of the putative origins of cfDNA and then contrasts the contributions of cellular breakdown processes with active mechanisms for the release of cfDNA into the extracellular environment. The involvement of cfDNA derived from both cellular breakdown and active release in lateral information transfer is also discussed. We hope to encourage researchers to adopt a more holistic view of cfDNA research, taking into account all the biological pathways in which cfDNA is involved, and to give serious consideration to the integration of in vitro and in vivo research. We also wish to encourage researchers not to limit their focus to the apoptotic or necrotic fraction of cfDNA, but to investigate the intercellular messaging capabilities of the actively released fraction of cfDNA and to study the role of cfDNA in pathogenesis.     

Dynamic Behavior of an Intrinsically Unstructured Linker Domain Is Conserved in the Face of Negligible Amino Acid Sequence Conservation

Proteins or regions of proteins that do not form compact globular structures are classified as intrinsically unstructured proteins (IUPs). IUPs are common in nature and have essential molecular functions, but even a limited understanding of the evolution of their dynamic behavior is lacking. The primary objective of this work was to test the evolutionary conservation of dynamic behavior for a particular class of IUPs that form intrinsically unstructured linker domains (IULD) that tether flanking folded domains. This objective was accomplished by measuring the backbone flexibility of several IULD homologues using nuclear magnetic resonance (NMR) spectroscopy. The backbone flexibility of five IULDs, representing three kingdoms, was measured and analyzed. Two IULDs from animals, one IULD from fungi, and two IULDs from plants showed similar levels of backbone flexibility that were consistent with the absence of a compact globular structure. In contrast, the amino acid sequences of the IULDs from these three taxa showed no significant similarity. To investigate how the dynamic behavior of the IULDs could be conserved in the absence of detectable sequence conservation, evolutionary rate studies were performed on a set of nine mammalian IULDs. The results of this analysis showed that many sites in the IULD are evolving neutrally, suggesting that dynamic behavior can be maintained in the absence of natural selection. This work represents the first experimental test of the evolutionary conservation of dynamic behavior and demonstrates that amino acid sequence conservation is not required for the conservation of dynamic behavior and presumably molecular function.     

Single‐cell sequencing unveils the lifestyle and CRISPR‐based population history of Hydrotalea sp. in acid mine drainage

Acid mine drainage (AMD) is characterized by an acid and metal‐rich run‐off that originates from mining systems. Despite having been studied for many decades, much remains unknown about the microbial community dynamics in AMD sites, especially during their early development, when the acidity is moderate. Here, we describe draft genome assemblies from single cells retrieved from an early‐stage AMD sample. These cells belong to the genus Hydrotalea and are closely related to Hydrotalea flava. The phylogeny and average nucleotide identity analysis suggest that all single amplified genomes (SAGs) form two clades that may represent different strains. These cells have the genomic potential for denitrification, copper and other metal resistance. Two coexisting CRISPR‐Cas loci were recovered across SAGs, and we observed heterogeneity in the population with regard to the spacer sequences, together with the loss of trailer‐end spacers. Our results suggest that the genomes of Hydrotalea sp. strains studied here are adjusting to a quickly changing selective pressure at the microhabitat scale, and an important form of this selective pressure is infection by foreign DNA.     

An approximate line attractor in the hypothalamus encodes an aggressive state

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Conformational changes induced by ATP-hydrolysis in an ABC transporter: a molecular dynamics study of the Sav1866 exporter

ATP-Binding Cassette (ABC) transporters are ubiquitous membrane proteins that use energy from ATP binding or/and hydrolysis to actively transport allocrites across membranes. In this study, we identify ATP-hydrolysis induced conformational changes in a complete ABC exporter (Sav1866) from Staphylococcus aureaus, using molecular dynamics (MD) simulations. By performing MD simulations on the ATP and ADP+IP bound states, we identify the conformational consequences of hydrolysis, showing that the major rearrangements are not restricted to the NBDs, but extend to the transmembrane domains (TMDs) external regions. For the first time, to our knowledge, we see, within the context of a complete transporter, NBD dimer opening in the ADP+IP state in contrast with all ATP-bound states. This opening results from the dissociation of the ABC signature motif from the nucleotide. In addition, in both states, we observe the opening of a gate entrance in the intracellular loop region leading to the exposure of the TMDs internal cavity to the cytoplasm. To see if this opening was large enough to allow allocrite transport, the adiabatic energy profile for doxorubicin passage was determined. For both states, this profile, although an approximation, is overall downhill from the cytoplasmatic to the extracellular side, and the local energy barriers along the TMDs are relatively small, evidencing the exporter nature of Sav1866. The major difference between states is an energy barrier located in the cytoplasmic gate region, which becomes reduced upon hydrolysis, suggesting that allocrite passage is facilitated, and evidencing a possible molecular mechanism for the active transport in these proteins.     

Inferring and quantifying the role of an intrinsic current in a mechanism for a half-center bursting oscillation

This paper illustrates an informatic technique for inferring and quantifying the dynamic role of a single intrinsic current in a mechanism of neural bursting activity. We analyze the patterns of the most dominant currents in a model of half-center oscillation in the leech heartbeat central pattern generator. We find that the patterns of dominance change substantially over a cycle, allowing different local reductions to be applied to the model. The result is a hybrid dynamical systems model, which is a piecewise representation of the mechanism combining multiple vector fields and discrete state changes. The simulation of such a model tests explicit hypotheses about the mechanism and is a novel way to retain both mathematical clarity and scientific detail in answering mechanistic questions about a complex model. Several insights into the central mechanism of “escape-release” in the model are elucidated by this analysis and compared with previous studies. The broader application and extension of this technique is also discussed.     

Negative allosteric modulation of the glucagon receptor by RAMP2

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Dynamic response of UV-absorbing compounds, quantum yield and the xanthophyll cycle to diel changes in UV-B and photosynthetic radiations in an aquatic liverwort

We studied the diel responses of the liverwort Jungermannia exsertifolia subsp. cordifolia to radiation changes under laboratory conditions. The samples were exposed to three radiation regimes: P (only PAR), PA (PAR + UV-A), and PAB (PAR + UV-A + UV-B). The day was divided in four periods: darkness, a first low-PAR period, the high-PAR plus UV period, and a second low-PAR period. After 15 days of culture, we measured photosynthetic pigments, chlorophyll fluorescence and UV-absorbing compounds in the four periods of the day on two consecutive days. With respect to UV-absorbing compounds, we analyzed their global amount (as the bulk UV absorbance of methanolic extracts) and the concentration of seven hydroxycinnamic acid derivatives, both in the soluble (mainly vacuolar) and insoluble (cell wall-bound) fractions of the plant extracts. PAB samples increased the bulk UV absorbance of the soluble and insoluble fractions, and the concentrations of p-coumaroylmalic acid in the soluble fraction and p-coumaric acid in the cell wall. Most of these variables showed significant diel changes and responded within a few hours to radiation changes (more strongly to UV-B), increasing at the end of the period of high-PAR plus UV. F_v/F_m, Φ_PSII, NPQ and the components of the xanthophyll cycle showed significant and quick diel changes in response to high PAR, UV-A and UV-B radiation, indicating dynamic photoinhibition and protection of PSII from excess radiation through the xanthophyll cycle. Thus, the liverwort showed a dynamic protection and acclimation capacity to the irradiance level and spectral characteristics of the radiation received.     

Conformational analysis by NMR and molecular dynamics of adamantane-doxorubicin prodrugs and their assemblies with β-cyclodextrin: A focus on the design of platforms for controlled drug delivery

Nanoscale design and construction of affinity-based drug delivery systems (ADDS) is an active research area with enormous potential for the improvement of cancer treatment. For the therapeutic load of these ADDS, a promising strategy is the design of pH-sensitive prodrugs based on the construction of conjugates between adamantane and doxorubicin (Ad-Dox), which stands out as an excellent model system to obtain novel supramolecular materials. Construction of these prodrugs involves a modification of three zones of doxorubicin which in principle does not affect the action mechanism: the carbonyl group C13 (hydrazone linker), the primary alcohol neighboring the carbonyl (ester linker) and the 3′ amino group of daunosamine sugar (amide linker). These modifications are aimed to improve the efficacy and reduce the systemic toxicity of the drug chemotherapy by controlling its release in cancer cells. In this work, we performed 2D NMR experiments and molecular dynamics simulations to characterize the conformational changes of three constructed prodrugs. Our results demonstrated that ring A and the daunsamine sugar of the hydrazone and amide linkers conserve the half-chair state ⁹H₈, while the ester linker disrupts this conformation. Our study also showed that the hydrazone-linked compound (Ad-h-Dox) does not modify the conformation of the original drug and maintains cytotoxic activity. Moreover, the inclusion complex (IC) of Ad-h-Dox with β-cyclodextrin (βCD) generated a highly soluble platform in water, whereas the ester-linked compound (Ad-e-Dox) causes the loss of biological activity. This study proves that Ad-h-Dox prodrug can be an optimum prodrug and act as a building block for a more complex drug transport system.