30,375 research outputs found
Complexity in cancer stem cells and tumor evolution: towards precision medicine
In this review, we discuss recent advances on the plasticity of cancer stem
cells and highlight their relevance to understand the metastatic process and to
guide therapeutic interventions. Recent results suggest that the strict
hierarchical structure of cancer cell populations advocated by the cancer stem
cell model must be reconsidered since the depletion of cancer stem cells leads
the other tumor cells to switch back into the cancer stem cell phenotype. This
plasticity has important implications for metastasis since migrating cells do
not need to be cancer stem cells in order to seed a metastasis. We also discuss
the important role of the immune system and the microenvironment in modulating
phenotypic switching and suggest possible avenues to exploit our understanding
of this process to develop an effective strategy for precision medicine.Comment: 2 Figures, to appear in Seminars in Cancer Biology, Available online
23 February 201
The multiple faces of leukocyte interstitial migration
Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cellâcell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments
A new paradigm for SpeckNets:inspiration from fungal colonies
In this position paper, we propose the development of a new biologically inspired paradigm based on fungal colonies, for the application to pervasive adaptive systems. Fungal colonies have a number of properties that make them an excellent candidate for inspiration for engineered systems. Here we propose the application of such inspiration to a speckled computing platform. We argue that properties from fungal colonies map well to properties and requirements for controlling SpeckNets and suggest that an existing mathematical model of a fungal colony can developed into a new computational paradigm
The effects of symmetry on the dynamics of antigenic variation
In the studies of dynamics of pathogens and their interactions with a host
immune system, an important role is played by the structure of antigenic
variants associated with a pathogen. Using the example of a model of antigenic
variation in malaria, we show how many of the observed dynamical regimes can be
explained in terms of the symmetry of interactions between different antigenic
variants. The results of this analysis are quite generic, and have wider
implications for understanding the dynamics of immune escape of other
parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs
African Trypanosomes undermine humoral responses and vaccine development : link with inflammatory responses?
African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i) early parasite diagnosis, (ii) anti-trypanosome (drugs) treatment, and (iii) anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
There is an ongoing debate on the therapeutic potential of vaso-modulatory
interventions against glioma invasion. Prominent vasculature-targeting
therapies involve functional tumour-associated blood vessel deterioration and
normalisation. The former aims at tumour infarction and nutrient deprivation
medi- ated by vascular targeting agents that induce occlusion/collapse of
tumour blood vessels. In contrast, the therapeutic intention of normalising the
abnormal structure and function of tumour vascular net- works, e.g. via
alleviating stress-induced vaso-occlusion, is to improve chemo-, immuno- and
radiation therapy efficacy. Although both strategies have shown therapeutic
potential, it remains unclear why they often fail to control glioma invasion
into the surrounding healthy brain tissue. To shed light on this issue, we
propose a mathematical model of glioma invasion focusing on the interplay
between the mi- gration/proliferation dichotomy (Go-or-Grow) of glioma cells
and modulations of the functional tumour vasculature. Vaso-modulatory
interventions are modelled by varying the degree of vaso-occlusion. We
discovered the existence of a critical cell proliferation/diffusion ratio that
separates glioma invasion re- sponses to vaso-modulatory interventions into two
distinct regimes. While for tumours, belonging to one regime, vascular
modulations reduce the tumour front speed and increase the infiltration width,
for those in the other regime the invasion speed increases and infiltration
width decreases. We show how these in silico findings can be used to guide
individualised approaches of vaso-modulatory treatment strategies and thereby
improve success rates
Spiking Neural Networks for Inference and Learning: A Memristor-based Design Perspective
On metrics of density and power efficiency, neuromorphic technologies have
the potential to surpass mainstream computing technologies in tasks where
real-time functionality, adaptability, and autonomy are essential. While
algorithmic advances in neuromorphic computing are proceeding successfully, the
potential of memristors to improve neuromorphic computing have not yet born
fruit, primarily because they are often used as a drop-in replacement to
conventional memory. However, interdisciplinary approaches anchored in machine
learning theory suggest that multifactor plasticity rules matching neural and
synaptic dynamics to the device capabilities can take better advantage of
memristor dynamics and its stochasticity. Furthermore, such plasticity rules
generally show much higher performance than that of classical Spike Time
Dependent Plasticity (STDP) rules. This chapter reviews the recent development
in learning with spiking neural network models and their possible
implementation with memristor-based hardware
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