Spontaneous Patchiness in a Host-Parasitoid Integrodifference Model

Observations of a host-parasitoid interaction in which victims are significantly less motile than their exploiters suggest the possibility of stable spatial pattern in a fairly homogeneous environment. Findings of pattern formation in continuous-time models are not fully able to account for this behavior. Those findings often rely on questionable biological conditions, and more fundamentally, the continuous nature of time in such models does not reflect the reality of the observed interaction. In this paper, we introduce a discrete-time spatial model of the interaction. The final state of our model is often a striking spatial pattern, similar to those observed. We analyze the model, describe its transient behavior, and find the conditions under which these spatial patterns occur, as well as an estimate of maximum possible patch size under those conditions. We also discuss the existence of such conditions in the natural system.     

Insights into the structural perturbations of spliced variants of CD44: a modeling and simulation approach

Transient interactions between cancer stem cells and components of the tumor microenvironment initiate various signaling pathways crucial for carcinogenesis. Predominant hyaluronan (HA) receptor, CD44 is structurally and functionally one of the most variable cell surface receptors having the potential to generate a diverse repertory of CD44 isoforms by alternative splicing of variant exons and post-translational modifications. A structurally distinctive variant of CD44, CD44v10, has an inevitable role in malignant progression, invasion, and metastasis. This can be attributed to the binding of HA with CD44v10, which demonstrates a completely different behavioral pattern as compared to the other spliced variants of CD44 molecule. Absence of a comprehensively predicted crystal structure of human CD44s and CD44v10 is an impediment in understanding the resultant structural alterations caused by the binding of HA. Thus, in this study, we aim to predict the CD44s and CD44v10 structures to their closest native confirmation and study the HA binding-induced structural perturbations using homology modeling, molecular docking, and MD simulation approach. The results depicted that modeled 3D structures of CD44s and CD44v10 isoforms were found to be stable throughout MD simulations; however, a substantial decrease was observed in the binding affinity of HA with CD44v10 (?5.355 kcal/mol) as compared to CD44s. Furthermore, loss and gain of several H-bonds and hydrophobic interactions in CD44v10–HA complex during the simulation process not only elucidated the reason for decreased binding affinity for HA but also prompted toward the plausible role of HA-induced structural perturbations in occurrence and progression of carcinogenesis.     

A UV resonance Raman investigation of poly(rI): Evidence for cation-dependent structural perturbations

Poly(rI) stabilized by either Na⁺ or K⁺ was investigated using uv resonance Raman (UVRR) spectroscopy. Raman excitation profiles of inosine 5′-monophosphate demonstrated the 250 nm excitation selectively enhances base stacking interactions, while ribose and carbonyl stretching vibrations are preferentially enhanced with 210 nm excitation. These wavelengths were used to examine the structure of poly(rI) in the presence of either K⁺ or Na⁺ as a function of temperature. UVRR studies revealed that the K⁺ stabilized form is more thermally stable, yielding a T_m of ∼ 47°C compared to a T_m of ∼ 30°C for the Na⁺ stabilized form. We observed that both the ribosyl conformation and the coordination of the carbonyl groups depend on the nature of the cation. The C₆O stretching frequency indicates that Na⁺ coordinates much more strongly to the carbonyl groups than K⁺ (1672 cm⁻¹ Na⁺ vs 1684 cm⁻¹ K⁺ at 4°C). Conformationally sensitive modes of the phosphate backbone and the ribosyl ring indicate that Na⁺ stabilized poly(rI) predominantly exists in a C_3′-endo ribose conformation, whereas K⁺ stabilized poly(rI) adopts a C_2′-endo conformation possibly as a consequence of the larger ionic radius of the K⁺ ion. © 1998 John Wiley & Sons, Inc. Biopoly 46: 475–487, 1998     

Chromatin perturbations during the DNA damage response in higher eukaryotes

The DNA damage response is a widely used term that encompasses all signaling initiated at DNA lesions and damaged replication forks as it extends to orchestrate DNA repair, cell cycle checkpoints, cell death and senescence. ATM, an apical DNA damage signaling kinase, is virtually instantaneously activated following the introduction of DNA double-strand breaks (DSBs). The MRE11-RAD50-NBS1 (MRN) complex, which has a catalytic role in DNA repair, and the KAT5 (Tip60) acetyltransferase are required for maximal ATM kinase activation in cells exposed to low doses of ionizing radiation. The sensing of DNA lesions occurs within a highly complex and heterogeneous chromatin environment. Chromatin decondensation and histone eviction at DSBs may be permissive for KAT5 binding to H3K9me3 and H3K36me3, ATM kinase acetylation and activation. Furthermore, chromatin perturbation may be a prerequisite for most DNA repair. Nucleosome disassembly during DNA repair was first reported in the 1970s by Smerdon and colleagues when nucleosome rearrangement was noted during the process of nucleotide excision repair of UV-induced DNA damage in human cells. Recently, the multi-functional protein nucleolin was identified as the relevant histone chaperone required for partial nucleosome disruption at DBSs, the recruitment of repair enzymes and for DNA repair. Notably, ATM kinase is activated by chromatin perturbations induced by a variety of treatments that do not directly cause DSBs, including treatment with histone deacetylase inhibitors. Central to the mechanisms that activate ATR, the second apical DNA damage signaling kinase, outside of a stalled and collapsed replication fork in S-phase, is chromatin decondensation and histone eviction associated with DNA end resection at DSBs. Thus, a stress that is common to both ATM and ATR kinase activation is chromatin perturbations, and we argue that chromatin perturbations are both sufficient and required for induction of the DNA damage response.     

Establishment and characterization of stable,diverse, fecal-derived in vitro microbial communities that model the intestinal microbiota

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Nonlinear control of HIV-1 infection with a singular perturbation model

Using a singular perturbation approximation, a nonlinear state-space model of HIV-1 infection, having as state variables the number of healthy and infected CD4+T cells and the number of virion particles, is simplified and used to design a control law. The control law comprises an inner block that performs feedback linearizing of the virus dynamics and an outer block implementing an LQ regulator that drives the number of virion particles to a number below the specification. A sensitivity analysis of the resulting law is performed with respect to the model parameter to the infection rate, showing that the controlled system remains stable in the presence of significant changes of this parameter with respect to the nominal value.     

Evolution of the coccolith genus Lotharingius during the Late Pliensbachian-Early Toarcian interval in Asturias (N Spain). Consequences of the Early Toarcian environmental perturbations

The evolution of the coccolith genus Lotharingius was investigated in 18 samples from the West Rodiles section (Asturias, Northern Spain), Upper Pliensbachian-Lower Toarcian in age. In each sample, the length and width of the coccolith and of its central area were measured on 150 specimens of Lotharingius. A total of 2700 specimens were measured, and 10,800 measurements were obtained. Based on the results of the morphometric analysis, the stratigraphic ranges, the abundance patterns and the light microscope observations, the aims of this work are to determine whether the specimens analysed correspond to different species, to distinct ecophenotypes or to an anagenetic lineage of morphotypes of a single species with overlapping stratigraphic ranges, and to test the influence of the paleoenvironmental perturbations during the Early Toarcian on the studied genus. Three species of Lotharingius were distinguished: L. hauffii, L. sigillatus and L. crucicentralis. Based on central area size and structure, two morphotypes (A and B) of L. hauffii were differentiated. All the parameters measured show a great overlap between the morphotypes and species. An increase in both coccolith and central area size and a development of more complex central area structures were observed through the studied section. L. hauffii is the smallest form, followed by L. sigillatus, and finally L. crucicentralis is the largest species and has the most complex central area structure. A clear decrease in size or “dwarfing” of the species was observed in the samples corresponding to the Early Toarcian environmental perturbations. L. crucicentralis was not identified in these samples. We hypothesize that the changes in size and abundance of the Lotharingius species could be related to the unfavourable palaeoenvironmental conditions for the biomineralization of their coccoliths.