Hafida Hamdache, Alexia Gazeu, Marion Gambart
et al.
Neuroblastoma, is a highly heterogeneous pediatric tumour and is responsible for 15% of pediatric cancer-related deaths. The clinical outcomes can vary from spontaneous regression to high metastatic disease. This extracranial tumour arises from a neural crest-derived cell and can harbor different phenotypes. Its heterogeneity may result from variations in differentiation states influenced by genetic and epigenetic factors and individual patient characteristics. This leads downstream to disruption of homeostasis and a metabolic shift in response to the tumour needs. Nutrition can play a key role in influencing various aspects of a tumour behaviour. This review provides an in-depth exploration of the aetiology of neuroblastoma and the different avenues of disease progression, which can be targeted with individualized nutrition intervention strategies to improve the well-being of children and optimize clinical outcomes.
Yuqi Xiao, Leah Edelstein-Keshet, Alain Goriely
et al.
Capsular contracture is a pathological response to implant-based reconstructive breast surgery, where the ``capsule'' (tissue surrounding an implant) painfully thickens, contracts and deforms. It is known to affect breast-cancer survivors at higher rates than healthy women opting for cosmetic cosmetic breast augmentation with implants. We model the early stages of capsular contracture based on stress-dependent recruitment of contractile and mechanosensitive cells to the implant site. We derive a one-dimensional continuum spatial model for the spatio-temporal evolution of cells and collagen densities away from the implant surface. Various mechanistic assumptions are investigated for linear versus saturating mechanical cell responses and cell traction forces. Our results point to specific risk factors for capsular contracture, and indicate how physiological parameters, as well as initial states (such as inflammation after surgery) contribute to patient susceptibility.
Marta Gonzalez-Sanz, Clara Crespillo-Andújar, Sandra Chamorro-Tojeiro
et al.
Chagas disease is currently present in many non-endemic countries and remains a neglected tropical disease globally. A review of the literature identified significant gaps and scarcity of updated information from European countries, with most studies reporting data from Spain and Italy. The index of underdiagnosis may be as high as 70%, affecting mainly females of child-bearing age. Standardized screening of fertile, non-pregnant, women from endemic countries and subsequent treatment is considered an essential strategy to control transmission and prevent new cases, yet no uniform legislation for screening risk groups exists. There is heterogeneity in Europe in terms of preventive strategies to avoid transfusion-related transmission of Chagas disease, not necessarily in line with the European directives, with some countries conducting systematic screening for T. cruzi infection in blood donors, whilst others rely on pre-transfusion questionnaires. The growing burden of the infection in resource-rich areas may provide an opportunity for progress in certain aspects of control and prevention. Options for improving screening strategies, management and linkage to care are reviewed.
Fabiola V. Borbolla-Jiménez, Ian A. García-Aguirre, María Luisa Del Prado-Audelo
et al.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant inherited disease characterized by progressive ataxia and retinal degeneration. SCA7 belongs to a group of neurodegenerative diseases caused by an expanded CAG repeat in the disease-causing gene, resulting in aberrant polyglutamine (polyQ) protein synthesis. PolyQ ataxin-7 is prone to aggregate in intracellular inclusions, perturbing cellular processes leading to neuronal death in specific regions of the central nervous system (CNS). Currently, there is no treatment for SCA7; however, a promising approach successfully applied to other polyQ diseases involves the clearance of polyQ protein aggregates through pharmacological activation of autophagy. Nonetheless, the blood–brain barrier (BBB) poses a challenge for delivering drugs to the CNS, limiting treatment effectiveness. This study aimed to develop a polymeric nanocarrier system to deliver therapeutic agents across the BBB into the CNS. We prepared poly(lactic-co-glycolic acid) nanoparticles (NPs) modified with Poloxamer188 and loaded with rapamycin to enable NPs to activate autophagy. We demonstrated that these rapamycin-loaded NPs were successfully taken up by neuronal and glial cells, demonstrating high biocompatibility without adverse effects. Remarkably, rapamycin-loaded NPs effectively cleared mutant ataxin-7 aggregates in a SCA7 glial cell model, highlighting their potential as a therapeutic approach to fight SCA7 and other polyQ diseases.
Stefan Landmann, Caroline M. Holmes, Mikhail Tikhonov
Bacteria live in environments that are continuously fluctuating and changing. Exploiting any predictability of such fluctuations can lead to an increased fitness. On longer timescales bacteria can "learn" the structure of these fluctuations through evolution. However, on shorter timescales, inferring the statistics of the environment and acting upon this information would need to be accomplished by physiological mechanisms. Here, we use a model of metabolism to show that a simple generalization of a common regulatory motif (end-product inhibition) is sufficient both for learning continuous-valued features of the statistical structure of the environment and for translating this information into predictive behavior; moreover, it accomplishes these tasks near-optimally. We discuss plausible genetic circuits that could instantiate the mechanism we describe, including one similar to the architecture of two-component signaling, and argue that the key ingredients required for such predictive behavior are readily accessible to bacteria.
Daniele Proverbio, Luca Gallo, Barbara Passalacqua
et al.
Using a Multi-agent systems paradigm, the present project develops, validates and exploits a computational $\textit{testbed}$ that simulates micro-biological complex systems, namely the aggregation patterns of the social amoeba $\textit{Dyctiostelium discoideum}$. We propose a new design and implementation for managing discrete simulations with autonomous agents on a microscopic scale, thus focusing on their social behavior and mutual interactions. Then, the dependence on the main physical variables is tested, namely density and number of amoebas; in addition, we analyze the robustness of the dynamics against various noise sources. Along with these results, we suggest a methodology for further studies that make use of our validated model.
PurposeThis study aims to provide an extensive overview of OA journals’ status and quality in 27 research areas based on all Scopus-indexed journals. It shows the volume of OA journals, proportion of publications in OA journals and the quality of these journals in comparison with subscription-based counterparts.Design/methodology/approachThis research investigated 22,256 active peer-reviewed journals indexed by Scopus in 2015. Data were gathered using the Journal Metrics website. The current research adopted four indicators to compare the quality of OA and non-OA journals indexed in Scopus under each subject area, namely citedness rate, CiteScore, SNIP and SJR.FindingsOA journals comprised approximately 17 per cent out of the total journals indexed by Scopus in 2015. The results revealed an uneven spread of OA journals across disciplines, ranged from 5.5 to 28.7 per cent. Studying the quality of journals as measured by CiteScore, SJR SNIP leads us to the finding that, in all research areas, except for health profession and nursing, non-OA journals attain statistically significant higher average quality than do OA journals.Originality/valueAlthough OA publishing improves the visibility of scholarly journals, this increase is not always coupled with increase in journals’ impact and quality.
Purpose The purpose of this paper is to examine usage trends during the first four years of the implementation of the Springer Book Archives (SBA) at the University of Melbourne. The paper assesses the benefits of the SBA against perceptions at the time of purchase and seeks to evaluate the long-term value of the purchase. Design/methodology/approach The methodology included a literature search to identify issues in the adoption of large backlists of ebooks, examination of detailed usage data supplied in COUNTER complaint spreadsheets and tables by Springer, validating findings with librarians and academics and positing next steps. Findings Usage of ebooks, like other electronic resources, is difficult to predict. Resources expected to be used, may not be and vice versa. Access to large aggregations of electronic content creates new opportunities for teaching and research, additional economies and benefits, as well as unexpected outcomes. Research limitations/implications Detailed data on user profiles were not available and an evaluation of user perceptions was not possible at this time. Originality/value The literature review suggests that this is the only published study of institutional usage of the SBA at this time.
Purpose The purpose of this annotated bibliography is to show perspectives on intellectual freedom from literature that provides approaches for librarians in faith-based institutions. The articles reviewed in this annotated bibliography will assist both Christian and secular librarians in selecting library materials. Design/methodology/approach The author identified sources using LISTA, ATLA and other common library databases. Sources were selected from 1993 to the present, focusing on sources that are on the application of intellectual freedom in the Christian academic library and/or librarian. Findings Best (2010) discusses censorship in academic libraries based on the top ten most-challenged books in 2007 which have research implications for Christian institutions. Johnson (2002), Davis (2002) and Smith (2004) offer library recommendations based on the review of the literature and their own practice. Hippenhammer (1993/1994) presents survey data and findings on collection development policies and intellectual freedom from Christian libraries. Matacio (2003) shares quantitative research from Seventh-Day Adventist (SDA) libraries applicable to other Christian institutions. Research limitations/implications The majority of the research on intellectual freedom and Christian librarianship is from 10 or more years ago. Originality/value This annotated bibliography is a starting point for research that could be conducted to help in the evaluation of Christian academic library’s collection development policy.
Serge Moulin, Nicolas Seux, Stéphane Chrétien
et al.
Motivation: LTR retrotransposons are mobile elements that are able, like retroviruses, to copy and move inside eukaryotic genomes. In the present work, we propose a branching model for studying the propagation of LTR retrotransposons in these genomes. This model allows to take into account both positions and degradations of LTR retrotransposons copies. In our model, the duplication rate is also allowed to vary with the degradation level. Results: Various functions have been implemented in order to simulate their spread and visualization tools are proposed. Based on these simulation tools, we show that an accurate estimation of the parameters of this propagation model can be performed. We applied this method to the study of the spread of the transposable elements ROO, GYPSY, and DM412 on a chromosome of \textit{Drosophila melanogaster}. Availability: Our proposal has been implemented using Python software. Source code is freely available on the web at https://github.com/SergeMOULIN/retrotransposons-spread.
Some cells have to take decision based on the quality of surroundings ligands, almost irrespective of their quantity, a problem we name "absolute discrimination". An example of absolute discrimination is recognition of not-self by immune T Cells. We show how the problem of absolute discrimination can be solved by a process called "adaptive sorting". We review several implementations of adaptive sorting, as well as its generic properties such as antagonism. We show how kinetic proofreading with negative feedback implements an approximate version of adaptive sorting in the immune context. Finally, we revisit the decision problem at the cell population level, showing how phenotypic variability and feedbacks between population and single cells are crucial for proper decision.
Catherine E. Patterson, Bruce P. Ayati, Sarah A. Holstein
Multiple myeloma is a plasma cell cancer that leads to a dysregulated bone remodeling process. We present a partial differential equation model describing the dynamics of bone remodeling with the presence of myeloma tumor cells. The model explicitly takes into account the roles of osteoclasts, osteoblasts, precursor cells, stromal cells, osteocytes, and tumor cells. Previous models based on ordinary differential equations make the simplifying assumption that the bone and tumor cells are adjacent to each other. However, in actuality, these cell populations are separated by the bone marrow. Our model takes this separation into account by including the diffusion of chemical factors across the marrow, which can be viewed as communication between the tumor and bone. Additionally, this model incorporates the growth of the tumor and the diminishing bone mass by utilizing a ``moving boundary.'' We present numerical simulations that qualitatively validate our model's description of the cell population dynamics.
Caspases are a family of cysteine proteases that play essential roles during apoptosis, and we presume some of them may also protect the cell from oxidative stress. We found that the absence of yeast caspase 1(Yca1)in Saccharomyces cerevisiae leads to a more intense burst of mitochondrial reactive oxygen species (ROS) In addition, compared to wild type yeast cells, the ability of yca1 mutant cells to maintain mitochondrial activity is significantly reduced after either oxidative stress treatment or aging. During mitochondrial ROS burst, deletion of the yca1 gene delayed structural damage of a green fluorescent protein (GFP) reporter bound in the inner mitochondrial membrane. This work implies that yeast caspase 1 is closely connected to the oxidative stress response. We speculate that Yca1 can discriminate proteins damaged by oxidation and accelerate their hydrolysis to attenuate the ROS burst.
Epigenetic Tracking is a mathematical model of biological cells, originally conceived to study embryonic development. Computer simulations proved the capacity of the model to generate complex 3-dimensional cellular structures, and the potential to reproduce the complexity typical of living beings. The most distinctive feature of this model is the presence in the body of a homogeneous distribution of stem cells, which are dinamically and continuously created during development from non-stem cells and reside in niches. Embryonic stem cells orchestrate early developmental events, adult stem cells direct late developmental and regeneration events, ageing stem cells cause ageing and cancer stem cells are responsible for cancer growth. The conceptual backbone provided by Epigenetic Tracking brings together a wide range of biological phenomena: for this reason, we think it can be proposed as a general model for multicellular biology. Despite, or perhaps due to its theoretical origin, the model allowed us to make predictions relevant to very diverse fields of biology, such as transposable elements, and cancer-related patterns of gene mutations. This paper contains a summary of the model and its implications.
Most sensory cells use cross-membrane chemoreceptors to detect chemical signals in the environment. The biochemical properties and spatial organization of chemoreceptors play important roles in achieving and maintaining sensitivity and accuracy of chemical sensing. Here we investigate the effects of receptor cooperativity and adaptation on the limits of gradient sensing. We study a single cell with aggregated chemoreceptor arrays on the cell surface and derive general formula to the limits for gradient sensing from the uncertainty of instantaneous receptor activity. In comparison to independent receptors, we find that cooperativity by non-adaptative receptors could significantly lower the sensing limit in a chemical concentration range determined by the biochemical properties of ligand-receptor binding and ligand-induced receptor activity. Cooperativity by adaptative receptors are beneficial to gradient sensing within a broad range of background concentrations. Our results also show that isotropic receptor aggregate layout on the cell surface represents an optimal configuration to gradient sensing.
All cells must keep time to consistently perform vital biological functions. To that end, the coupling and interrelatedness of diverse subsecond events in the complex cellular environment, such as protein folding or translation rates, cannot simply result from the chance convergence of the inherent chemical properties of these phenomena, but may instead be synchronized through a cell-wide pacemaking mechanism. Picosecond vibrations of lipid membranes may play a role in such a mechanism.
This paper proposes an original theory of aging of multicellular organisms. The cells of multicellular organisms, in contrast to unicellular organisms, are burdened with a two- part genome: housekeeping and specialized (multicellular), responsible for ontogenesis and terminal differentiation. The two parts of the genome compete for limited adaptive resources thereby interfering with the ability of the house-keeping part of the genome to adequately perform reparative and adaptive functions in post mitotic cells. The necessity to complete the ontgenesis program, leads to increased activity of the multicellular components of the genome. As a result, the allocation of cellular resources to specialized genome con-tinuously increases with time. This leads to a deficit of reparative and adaptive capacity in post mitotic cells. Suggestions for future research focus on identifying groups of genes responsible for regulation of growth rate of specialized genome and suppressing ability of the cell division. A better understanding of the relationship between the two parts of the genome will not only help us to manipulate ontogenesis and aging, but will also improve our understanding of cancer development and ontogenesis.
S. López-Cuenca, L. A. Pérez Carrillo, M. Rabelero Velasco
et al.
The high-yield synthesis of zinc oxide (ZnO) primary nanoparticles with high purity and with diameters between 6 and 22 nm using bicontinuous microemulsions is reported in this work. The ZnO nanoparticles were made by hydrolysis of Zn(NO3)2with NaOH aqueous solution and precipitation, followed by calcination of the precipitate. Higher yields and productivities of ZnO nanoparticles were obtained compared to values produced with w/o micremulsions reported in the literature. Particles were characterized by transmission electronic microscopy (TEM), X-ray diffraction, and atomic absorption spectroscopy.