Biological Situations Research Articles

Action of the multifunctional peptide BP100 on native biomembranes examined by solid-state NMR.

Membrane composition is a key factor that regulates the destructive activity of antimicrobial peptides and the non-leaky permeation of cell penetrating peptides in vivo. Hence, the choice of model membrane is a crucial aspect in NMR studies and should reflect the biological situation as closely as possible. Here, we explore the structure and dynamics of the short multifunctional peptide BP100 using a multinuclear solid-state NMR approach. The membrane alignment and mobility of this 11 amino acid peptide was studied in various synthetic lipid bilayers with different net charge, fluidity, and thickness, as well as in native biomembranes harvested from prokaryotic and eukaryotic cells. (19)F-NMR provided the high sensitivity and lack of natural abundance background that are necessary to observe a labelled peptide even in protoplast membranes from Micrococcus luteus and in erythrocyte ghosts. Six selectively (19)F-labeled BP100 analogues gave remarkably similar spectra in all of the macroscopically oriented membrane systems, which were studied under quasi-native conditions of ambient temperature and full hydration. This similarity suggests that BP100 has the same surface-bound helical structure and high mobility in the different biomembranes and model membranes alike, independent of charge, thickness or cholesterol content of the system. (31)P-NMR spectra of the phospholipid components did not indicate any bilayer perturbation, so the formation of toroidal wormholes or micellarization can be excluded as a mechanism of its antimicrobial or cell penetrating action. However, (2)H-NMR analysis of the acyl chain order parameter profiles showed that BP100 leads to considerable membrane thinning and thereby local destabilization.

Noise-induced Canard and Mixed-Mode Oscillations in Large-Scale Stochastic Networks

Slow-fast dynamical systems, such as those describing the excitable dynamics of nerve cells, can present a variety of very delicate phenomena, such as canard explosions or mixed-mode oscillations (MMOs), in which dramatic transitions occur upon very small variation of the parameters. In biological situations, these excitable systems are coupled and subject to intense noise, which may have the effect of destroying these phenomena. While this is true for single cells or small networks, we show that large-scale networks do display reliable canard explosions and MMOs in the presence of noise, and these transitions can even occur upon variation of the noise standard deviation. We show that this phenomenon can be related to averaging effects occurring in large populations by investigating a network of interconnected Wilson--Cowan rate neurons which converges to a stochastic process whose mean satisfies a slow-fast dynamical system in which noise is a parameter. In this system, we show using a combination of analytic and numerical arguments that generic canard explosions and MMOs occur as noise is varied. This result sheds new light on the qualitative effects of noise and sensitivity to precise noise values in large stochastic networks. We further investigate finite-sized networks and show that systematic differences with the mean-field limits arise in bistable regimes (where random switches between different attractors occur) or in MMOs, where the finite-sized effects induce early jumps due to the sensitivity of the attractor.

Marcadores biomoleculares en la tromboembolia asociada al cáncer

Patients with cancer have an increased risk of developing thromboembolism, which is associated with increased morbidity and mortality and hinders its clinical management. Cancer generates a hypercoagulable state that increases the generation of thrombin. This coagulation activation, along with the inflammatory changes fostered by the neoplastic cells, favors tumor progression at the local and distal level. In this review, we present the most salient aspects of the pathophysiology of hypercoagulability in cancer and list the hemostatic biomarkers that reflect this biological situation of hypercoagulability. These parameters can be used as risk factors to predict the probability of developing thrombosis, which help identify patients who can benefit from antithrombotic prophylaxis.

Propuesta de prevención primaria del maltrato infantil: modelo teórico explicativo para identificar factores histórico-bio-psico-socio-culturales

The child maltreatment is a social and public health problem of multifactorial character that, in major or minor measure, include a wide range of cultural, historical, social, juridical, economic, political, psychological and biological situations that understand a intrincate framework of violence, addictions, diseases, abandon, disinterest, abuses, negligence and poverty. In this situation, the present work tries to serve as theoretical contribution in the field of the psychology for the unification of criteria in the field of the primary prevention of the infantile mistreatment. As a hypothetical approach, we affirm which the theoretical analysis of the historical, biological, psychological, social and cultural factors that are involved in the phenomenon of the child mistreatment will allow to establish an integral definition that contemplates the totality of the problem and that facilitates the production of effective programs of primary prevention. General objective is to describe and analyze theoretically which are the historical, biological, psychological, social and cultural factors involved in child maltreatment and to describe the interaction between them, also, to generate a comprehensive definition in order to establish the structure that should have all the primary prevention programs of child maltreatment and in turn, to develop a way to proposed a theoretical model of a program for the primary prevention of child maltreatment. On the other hand, this work is a documentary study because it seeks to develop a theoretical conceptual frame to form a body of ideas on a subject of study (Galan, 2011). Among other things it is concluded that the elements traditionally used as the traditional aggressor-victim model with which to has been addressed child abuse and the fact consider the cases of abuse as emerging only in the family environment represent a limited perspective that does not allow effective interventions and programs in terms of primary prevention.

On global minimizers of repulsive-attractive power-law interaction energies.

We consider the minimization of the repulsive–attractive power-law interaction energies that occur in many biological and physical situations. We show the existence of global minimizers in the discrete setting and obtain bounds for their supports independently of the number of Dirac deltas in a certain range of exponents. These global discrete minimizers correspond to the stable spatial profiles of flock patterns in swarming models. Global minimizers of the continuum problem are obtained by compactness. We also illustrate our results through numerical simulations.

Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study.

The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols. Test #1 examined urine samples from adult volunteers either spiked or not spiked with 32 metabolite standards. Test #2 involved a low biological contrast situation comparing the plasma of rats fed a diet either supplemented or not with vitamin D. The spectral information from each instrument was assembled into separate statistical blocks. Correlations between blocks (e.g., instruments) were examined (RV coefficients) along with the structure of the common spectral information (common components and specific weights analysis). In addition, in Test #1, an outlier individual was blindly introduced, and its identification by the various platforms was evaluated. Despite large differences in the number of spectral features produced after post-processing and the heterogeneity of the analytical conditions and the data treatment, the spectral information both within (NMR and LCMS) and across methods (NMR vs. LCMS) was highly convergent (from 64 to 91 % on average). No effect of the LCMS instrumentation (TOF, QTOF, LTQ-Orbitrap) was noted. The outlier individual was best detected and characterised by LCMS instruments. In conclusion, untargeted metabolomics analyses report consistent information within and across instruments of various technologies, even without prior standardisation.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0740-0) contains supplementary material, which is available to authorized users.

An eco-epidemiological model of competitive interacting species with Allee effect

An attempt has been made in the present investigation to extend and modify the study of the model representing competition of the species introduced by Gause (Science 79:16, 1934). His interesting piece of work has been updated here with the introduction of Allee effect in one species and the disease in another species keeping the realistic biological situation in mind. The diseased population is classified into the susceptible and the infected categories. The equilibria of the model system under consideration has been analysed systematically in terms of the admittance of persistency, global stability together with the existence of Hopf bifurcation, bistability and the multiple limit cycles as well. Here center manifold theorem and normal form method are also used to find the nature of the bifurcating limit cycle. Numerical illustration has been finally carried out through graphical representations of those results towards the end in order to validate the applicability of the present model.

Using Vignette Testing to Measure Student Science Teachers’ Professional Competencies

Instruments to measure teachers’ professional competencies with good context validity have been discussed before. We propose a measuring instrument based on vignette testing that analyzes professional competencies for science education using extended teaching contexts. It assesses pedagogical content knowledge (PCK) and compares it to pedagogical knowledge (PK). The test consists of text vignettes that describe authentically complex teaching situations in biology, chemistry and physics and then asks open-ended questions. It is analyzed by means of content analysis, thereby integrating quantitative and qualitative methods. The evaluation of the instrument is indicative of a valid measurement instrument and has shown promising potential for assessing competencies. We used the vignette test to compare the competencies of students in different training programs and with different educational backgrounds with the objective of improving science teacher education. The testing format developed in this study proved to be able to assess teachers’ professional competencies validly in their situational context of teaching. Results show a significant increase in competencies among science teacher students in the course of their training. The results of the control group (science students not pursuing a career in teaching) are remarkably poorer. Moreover, differences were identified when comparing the vignette based competency profiles of science teacher students and teacher students of other subjects, the latter scoring significantly lower in PCK. In addition, we compared competencies of students from different teacher training programs and found differences for students trained in interdisciplinary approaches (combining the disciplines biology, chemistry and physics) and students in separate-discipline approaches.

Precarious Present, Fragile Futures: Literature and Uncertainty in the Early Twenty-First Century

Fragility describes the condition of a world subject to flux, and in which order is only ever contingent. So pervasive is fragility to existence that it arguably constitutes an existential modality. Fragility is both promising and threatening: it indicates the possibility for change, yet this possibility also places the prevailing order at risk. To come to grips with fragility it becomes necessary to move from an abstract account of the dialectic of order and disorder to its concrete manifestation. Literature, it is argued, constitutes a powerful medium through which to investigate fragility and, particularly, the fragile future: not only is it able to stage sophisticated explorations of biological, social, economic, political and aesthetic situations of fragility, but its codes, media and genres are themselves subject to the fragilities they seek to represent. Addressing a range of themes, the articles gathered here collectively attest to the power of literature to bear witness to the fragile future. Beginning with the precarity of the present, they proceed to examine transitional sequences, and to investigate the way in which literature often adopts the tactic of looking back in order to look forward. A number of articles are concerned with ecological fragility, or with apocalyptic and post-apocalyptic themes, exposing the fragile relation between human knowledge, technology and the physical world.The fragile future is also a reality with which the literary humanities must grapple in its disciplinary dimension, staging a difficult negotiation between the antifragility and expansive logic of neoliberalism, and the fragility and critical facility of what remains of humanistic discourse.

ChemInform Abstract: Back to the Future — The Value of Single Protein Species Investigations

AbstractReview: 21 refs.

Os espaços livres e edificados e a forma urbana no vetor norte da região metropolitana de Belo Horizonte

As formas urbanas são decorrentes das alterações ambientais do lugar, ou seja, das suas condições físicas, biológicas e antrópicas, sendo a última a principal indutora de transformações. As cidades e suas paisagens alteram-se quando mudam as condições socioeconômicas e culturais, como ocorre em Belo Horizonte, capital de Minas Gerais, que se expande além de seus limites físicos e políticos, conurbando-se com os demais municípios da Região Metropolitana. As ocupações ocorrem desordenadamente, ocasionando problemas de gestão pública, saneamento, mobilidade, além de problemas de ordem ambiental. O presente trabalho aborda a área conurbada da Região Norte da Região Metropolitana de Belo Horizonte (RMBH), chamada de “Vetor Norte”, e sua relação com os espaços livres públicos existentes, através de análises qualitativas e quantitativas. Ainda que os espaços livres públicos sejam considerados como permanências no tecido urbano, os espaços edificados ampliam-se, respeitando ou não as legislações vigentes. A ocorrência maior deste conflito está localizada, principalmente, na área abordada, impulsionada pela construção da Linha Verde e de outros equipamentos, razão da sua escolha para o estudo. Através do conhecimento destes espaços, com base nas variáveis históricas e contemporâneas, será possível construir um referencial metodológico das relações entre os espaços livres públicos, os espaços edificados e a forma urbana. Os espaços livres podem ser considerados elementos estruturantes da forma da cidade, e de legítima importância para a qualidade de vida urbana.

Complex role of space in the crossing of fitness valleys by asexual populations

The evolution of complex traits requires the accumulation of multiple mutations, which can be disadvantageous, neutral or advantageous relative to the wild-type. We study two spatial (two-dimensional) models of fitness valley crossing (the constant-population Moran process and the non-constant-population contact process), varying the number of loci involved and the degree of mixing. We find that spatial interactions accelerate the crossing of fitness valleys in the Moran process in the context of neutral and disadvantageous intermediate mutants because of the formation of mutant islands that increase the lifespan of mutant lineages. By contrast, in the contact process, spatial structure can accelerate or delay the emergence of the complex trait, and there can even be an optimal degree of mixing that maximizes the rate of evolution. For advantageous intermediate mutants, spatial interactions always delay the evolution of complex traits, in both the Moran and contact processes. The role of the mutant islands here is the opposite: instead of protecting, they constrict the growth of mutants. We conclude that the laws of population growth can be crucial for the effect of spatial interactions on the rate of evolution, and we relate the two processes explored here to different biological situations.

Regulation of the human endogenous retrovirus K (HML-2) transcriptome by the HIV-1 Tat protein.

Approximately 8% of the human genome is made up of endogenous retroviral sequences. As the HIV-1 Tat protein activates the overall expression of the human endogenous retrovirus type K (HERV-K) (HML-2), we used next-generation sequencing to determine which of the 91 currently annotated HERV-K (HML-2) proviruses are regulated by Tat. Transcriptome sequencing of total RNA isolated from Tat- and vehicle-treated peripheral blood lymphocytes from a healthy donor showed that Tat significantly activates expression of 26 unique HERV-K (HML-2) proviruses, silences 12, and does not significantly alter the expression of the remaining proviruses. Quantitative reverse transcription-PCR validation of the sequencing data was performed on Tat-treated PBLs of seven donors using provirus-specific primers and corroborated the results with a substantial degree of quantitative similarity. The expression of HERV-K (HML-2) is tightly regulated but becomes markedly increased following infection with HIV-1, in part due to the HIV-1 Tat protein. The findings reported here demonstrate the complexity of the genome-wide regulation of HERV-K (HML-2) expression by Tat. This work also demonstrates that although HERV-K (HML-2) proviruses in the human genome are highly similar in terms of DNA sequence, modulation of the expression of specific proviruses in a given biological situation can be ascertained using next-generation sequencing and bioinformatics analysis.

A generic anisotropic continuum damage model integration scheme adaptable to both ductile damage and biological damage-like situations

This paper aims at presenting a general versatile time integration scheme applicable to anisotropic damage coupled to elastoplasticity, considering any damage rate and isotropic hardening formulations. For this purpose a staggered time integration scheme in a finite strain framework is presented, together with an analytical consistent tangent operator. The only restrictive hypothesis is to work with an undamaged isotropic material, assumed here to follow a J2 plasticity model. The only anisotropy considered is thus a damage-induced anisotropy. The possibility to couple any damage rate law with the present algorithm is illustrated with a classical ductile damage model for aluminium, and a biological damage-like application. The later proposes an original bone remodelling law coupled to trabecular bone plasticity for the simulation of orthodontic tooth movements. All the developments have been considered in the framework of the implicit non-linear finite element code Metafor (developed at the LTAS/MN2L, University of Liège, Belgium – www.metafor.ltas.ulg.ac.be).

Same universality class for the critical behavior in and out of equilibrium in a quenched random field

The random-field Ising model (RFIM) is one of the simplest statistical-mechanical models that captures the anomalous irreversible collective response seen in a wide range of physical, biological, or socio-economic situations in the presence of interactions and intrinsic heterogeneity or disorder. When slowly driven at zero temperature it can display an out-of-equilibrium phase transition associated with critical scaling ("crackling noise"), while it undergoes at equilibrium, under either temperature or disorder-strength changes, a thermodynamic phase transition. We show that the out-of-equilibrium and equilibrium critical behaviors are in the same universality class: they are controlled, in the renormalization-group (RG) sense, by the same zero-temperature fixed point. We do so by combining a field-theoretical formalism that accounts for the multiple metastable states and the exact (functional) RG. As a spin-off, we also demonstrate that critical fluids in disordered porous media are in the same universality class as the RFIM, thereby unifying a broad spectrum of equilibrium and out-of-equilibrium phenomena.

Meta-Analysis and Gene Set Analysis of Archived Microarrays Suggest Implication of the Spliceosome in Metastatic and Hypoxic Phenotypes

We propose to make use of the wealth of underused DNA chip data available in public repositories to study the molecular mechanisms behind the adaptation of cancer cells to hypoxic conditions leading to the metastatic phenotype. We have developed new bioinformatics tools and adapted others to identify with maximum sensitivity those genes which are expressed differentially across several experiments. The comparison of two analytical approaches, based on either Over Representation Analysis or Functional Class Scoring, by a meta-analysis-based approach, led to the retrieval of known information about the biological situation – thus validating the model – but also more importantly to the discovery of the previously unknown implication of the spliceosome, the cellular machinery responsible for mRNA splicing, in the development of metastasis.

Chapter Fifteen - Phospholipid Scrambling on the Plasma Membrane

Phospholipids are asymmetrically distributed at plasma membrane in normal cells, and scrambled in various biological situations such as blood clotting and apoptotic cell death. Recent studies revealed that phospholipid scrambling is mediated by at least two independent mechanisms. An eight transmembrane-containing protein TMEM16F Ca(2+)-dependently promotes the phospholipid scrambling, which is required for the PS exposure in activated platelets during blood clotting. On the other hand, a six transmembrane-containing protein Xk-related family protein 8 is activated by caspases during apoptosis and promotes the phospholipid scrambling, thus exposing PS as an "eat-me-signal." In this chapter, we describe procedures for assaying phospholipid scrambling.

Back to the future-The value of single protein species investigations

In proteomics, in the past years, there was a focus on high throughput and reaching of large numbers of identified proteins with the basic discourse of protein expression. To avoid the impression of producing pure lists attempts are usually made to correlate proteins changed in amount between two biological situations to different pathways or protein interactions. This discourse is based on two simplifications, which limit the applicability of proteomics drastically: (i) it is sufficient to quantify a protein from several enzymatic digestion products; (ii) a biological situation is sufficiently described, if a peptide with its PTM is identified, resulting in long lists of modified peptides with data amounts, which are not anymore made accessible for the reader of a publication. The elucidation of N-terminal methylation of proteasome subunit Rpt1 in yeast by Kimura et al. (Proteomics 2013, 13, 3167-3174), which represents the focus on one protein, shows the value of solid chemical analysis with a complete data documentation and paves the way to proteomics based on the protein speciation discourse.

Research prioritization through prediction of future impact on biomedical science: a position paper on inference-analytics

BackgroundAdvances in biotechnology have created “big-data” situations in molecular and cellular biology. Several sophisticated algorithms have been developed that process big data to generate hundreds of biomedical hypotheses (or predictions). The bottleneck to translating this large number of biological hypotheses is that each of them needs to be studied by experimentation for interpreting its functional significance. Even when the predictions are estimated to be very accurate, from a biologist’s perspective, the choice of which of these predictions is to be studied further is made based on factors like availability of reagents and resources and the possibility of formulating some reasonable hypothesis about its biological relevance. When viewed from a global perspective, say from that of a federal funding agency, ideally the choice of which prediction should be studied would be made based on which of them can make the most translational impact.ResultsWe propose that algorithms be developed to identify which of the computationally generated hypotheses have potential for high translational impact; this way, funding agencies and scientific community can invest resources and drive the research based on a global view of biomedical impact without being deterred by local view of feasibility. In short, data-analytic algorithms analyze big-data and generate hypotheses; in contrast, the proposed inference-analytic algorithms analyze these hypotheses and rank them by predicted biological impact. We demonstrate this through the development of an algorithm to predict biomedical impact of protein-protein interactions (PPIs) which is estimated by the number of future publications that cite the paper which originally reported the PPI.ConclusionsThis position paper describes a new computational problem that is relevant in the era of big-data and discusses the challenges that exist in studying this problem, highlighting the need for the scientific community to engage in this line of research. The proposed class of algorithms, namely inference-analytic algorithms, is necessary to ensure that resources are invested in translating those computational outcomes that promise maximum biological impact. Application of this concept to predict biomedical impact of PPIs illustrates not only the concept, but also the challenges in designing these algorithms.

A novel method to assess collagen architecture in skin

BackgroundTexture within biological specimens may reveal critical insights, while being very difficult to quantify. This is a particular problem in histological analysis. For example, cross-polar images of picrosirius stained skin reveal exquisite structure, allowing changes in the basketweave conformation of healthy collagen to be assessed. Existing techniques measure gross pathological changes, such as fibrosis, but are not sufficiently sensitive to detect more subtle and progressive pathological changes in the dermis, such as those seen in ageing. Moreover, screening methods for cutaneous therapeutics require accurate, unsupervised and high-throughput image analysis techniques.ResultsBy analyzing spectra of images post Gabor filtering and Fast Fourier Transform, we were able to measure subtle changes in collagen fibre orientation intractable to existing techniques. We detected the progressive loss of collagen basketweave structure in a series of chronologically aged skin samples, as well as in skin derived from a model of type 2 diabetes mellitus.ConclusionsWe describe a novel bioimaging approach with implications for the evaluation of pathology in a broader range of biological situations.