Poynting effect of brain matter in torsion

We investigate experimentally and model theoretically the mechanical behaviour of brain matter in torsion. Using a strain-controlled rheometer we perform torsion tests on fresh porcine brain samples. We quantify the torque and the normal force required to twist a cylindrical sample at constant twist rate. Data fitting gives a mean value for the shear modulus {\mu} = 900 $\pm$ 312 Pa and for the second Mooney-Rivlin parameter $c_2$ = 297 $\pm$ 189 Pa, indicative of extreme softness. Our results show that brain always displays a positive Poynting effect; in other words, it expands in the direction perpendicular to the plane of twisting. We validate the experiments with Finite Element simulations and show that when a human head experiences a twisting motion in the horizontal plane, the brain can experience large forces in the axial direction.Comment: 6 pages, 6 figures, 2 table

Morpho-elasticity of intestinal villi

In the context of morphogenetic processes in animal biology, in particular for those related to soft tissues, a morpho-elastic model for the embryonal development of intestinal villi, is presented. Villi originate from the embryonic development of the epithelial layer in the intestinal mucosa. Since the first stages of development, a bi-dimensional pattern starts to affect the intestinal epithelium, as a consequence of growth and residual stresses inside the tissue. It's from this undulated pattern, that villi will start to elongate. The embryonic mucosa is modeled as a growing thick-walled cylinder, and its mechanical behavior is described using an hyperelastic constitutive model, which also accounts for the anisotropic characteristics of the reinforcing fibers at the micro-structural level. The occurrence of surface undulations is investigated using a linear stability analysis based on the theory of incremental deformations superimposed on a finite deformation. The Stroh formulation of the incremental boundary value problem is derived and a numerical solution procedure is implemented for calculating the growth thresholds of instability. The numerical results, obtained from different growth scenarios are finally compared with the existing experimental results, showing that the geometrical and mechanical properties of the tissue and the differential growth between epithelium and mesenchyma, can drive the formation of intestinal villi in embryos

Photocatalytic Fe-doped n-TiO2: From synthesis to utilization of in vitro cell models for screening human and environmental nanosafety

The utilization of different types nanomaterials (NMs) in environmental remediation and wastewater treatment requires information on the potential harmful effects on human and environmental health. In this light, the utilization of human cell models together with cells from lower organisms, representative of different environmental compartments, could represent a valuable tool for the in vitro screening of the potential toxicity of different NMs used in nanoremediation. Among NMs, n-TiO2, because of its peculiar optical and chemical properties, is widely applied for photosensitized UV oxidation of organic pollutants. Moreover, development in design of metal- and non metal- doped TiO2 with extended photocatalytic activity in the visible region represents the subject of ongoing research. In this work, the cytotoxic effects of three different types of recently synthetized Fe-doped n-TiO2 were compared in two cell models widely utilized for screening cellular toxicity of NMs in humans and aquatic organisms, human vascular endothelial cells (HECV) and immune cells (hemocytes) of the marine invertebrate, the mussel Mytilus spp, respectively. Parallel studies were carried out using N-doped n-TiO2. The results indicate both distinct and common behavior (agglomeration state) in different media (human cell culture medium and mussel hemolymph serum) and biological effects (cytotoxicity, nitric oxide production) of different types of doped- n-TiO2 in different cell models. Although in vitro studies represent a first step in the toxicological assessment of NMs, studies comparing their effects on human and aquatic invertebrate cells that take into account the effects of different exposure media represent an useful tool for evaluating potential cytotoxicity of those NMs, like TiO2-based photocatalytic NMs, widely applied in environmental remediation, and whose potential risks are poorly understood

Canceling the elastic Poynting effect with geometry

The Poynting effect is a paragon of nonlinear soft matter mechanics. It is the tendency (found in all incompressible, isotropic, hyperelastic solids) exhibited by a soft block to expand vertically when sheared horizontally. It can be observed whenever the length of the cuboid is at least four times its thickness. Here we show that the Poynting effect can be easily reversed and the cuboid can shrink vertically, simply by reducing this aspect ratio. In principle, this discovery means that for a given solid, say one used as a seismic wave absorber under a building, an optimal ratio exists where vertical displacements and vibrations can be completely eliminated. Here we first recall the classical theoretical treatment of the positive Poynting effect, and then show experimentally how it can be reversed. Using finite-element simulations, we then investigate how the effect can be suppressed. We find that cubes always provide a reverse Poynting effect, irrespective of their material properties (in the third-order theory of weakly nonlinear elasticity)

Interactions of cationic polystyrene nanoparticles with marine bivalve hemocytes in a physiological environment: Role of soluble hemolymph proteins

none12The bivalve Mytilus galloprovincialis has proven as a suitable model invertebrate for evaluating the potential impact of nanoparticles (NPs) in the marine environment. In particular, in mussels, the immune system represents a sensitive target for different types of NPs. In environmental conditions, both NP intrinsic properties and those of the receiving medium will affect particle behavior and consequent bioavailability/uptake/toxicity. However, the evaluation of the biological effects of NPs requires additional understanding of how, once within the organism, NPs interact at the molecular level with cells in a physiological environment. In mammalian systems, different NPs associate with serum soluble components, organized into a "protein corona", which affects particle interactions with target cells. However, no information is available so far on the interactions of NPs with biological fluids of aquatic organisms. In this work, the influence of hemolymph serum (HS) on the in vitro effects of amino modified polystyrene NPs (PS-NH2) on Mytilus hemocytes was investigated. Hemocytes were incubated with PS-NH2 suspensions in HS (1, 5 and 50µg/mL) and the results were compared with those obtained in ASW medium. Cell functional parameters (lysosomal membrane stability, oxyradical production, phagocytosis) were evaluated, and morphological changes were investigated by TEM. The activation state of the signalling components involved in Mytilus immune response (p38 MAPK and PKC) was determined. The results show that in the presence of HS, PS-NH2 increased cellular damage and ROS production with respect to ASW medium. The effects were apparently mediated by disregulation of p38 MAPK signalling. The formation of a PS-NH2-protein corona in HS was investigated by centrifugation, and 1D- gel electrophoresis and nano-HPLC-ESI-MS/MS. The results identified the Putative C1q domain containing protein (MgC1q6) as the only component of the PS-NH2 hard protein corona in Mytilus hemolymph. These data represent the first evidence for the formation of a NP bio-corona in aquatic organisms and underline the importance of the recognizable biological identity of NPs in physiological exposure medium when testing their potential impact environmental model organisms. Although the results obtained in vitro do not entirely reflect a realistic exposure scenario and the more complex formation of a bio-corona that is likely to occur in vivo, these data will contribute to a better understanding of the effects of NPs in marine invertebrates.openCanesi, Laura; Ciacci, Caterina; Fabbri, Rita; Balbi, Teresa; Salis, Annalisa; Damonte, Gianluca; Cortese, Katia; Caratto, Valentina; Monopoli, Marco P; Dawson, Kenneth; Bergami, Elisa; Corsi, IlariaCanesi, Laura; Ciacci, Caterina; Fabbri, Rita; Balbi, Teresa; Salis, Annalisa; Damonte, Gianluca; Cortese, Katia; Caratto, Valentina; Monopoli, Marco P; Dawson, Kenneth; Bergami, Elisa; Corsi, Ilari

Evidence for sub-haplogroup h5 of mitochondrial DNA as a risk factor for late onset Alzheimer's disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy

Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection

Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

Morphogenèse, croissance et remodelage des tissus biologiques

Among the fundamental processes involved in the development of an organism, morphogenesis is one of the most complex. During the past centuries, an amount of experimental studies have improved our actual knowledge of the mechanisms which drive many morphogenetic processes in living organisms. Only recently, experiments have been complemented with mathematical modeling as a tool for proving novel insights on morphogenesis in soft tissues. In this context, this thesis aims at developing new mathematical models for the formation of patterns and forms in soft tubular organs. A macroscopic approach is adopted, where the tissue is considered as a continuum body undergoing growth and remodeling. The main idea behind the proposed models is that during growth and remodeling, residual stresses can arise and once they exceed a critical value, an elastic instability can occur in the tissue and lead to a morphological change. Therefore, the morphoelastic models are developed integrating the modern theories of growth and remodeling within the framework of the thermo-mechanics of open systems. The occurrence of the elastic instability is investigated using the method of incremental deformations superposed on finite deformations. The critical thresholds for the onset of the instability are determined together with the modes of the associated instability pattern. The morphoelastic theory is applied to the modeling of different morphogenetic processes occurring in soft tubular organs and gives useful insights in two interesting problems: the formation of the wide range of patterns in the gastro-intestinal system and the occurrence of torsional instabilities in pre-stressed tubular organs.Parmi les processus fondamentaux qui ont lieu pendant le développement d'un organisme, la morphogenèse est un des plus complexes. De nombreuses études expérimentales ont contribué à mieux comprendre les mécanismes morphogénétiques dans les organismes vivants. Cependant peu de modèles mathématiques ont été proposés afin d'étudier la morphogenèse dans les tissus vivants. Dans ce contexte, la thèse se propose de développer de nouveaux modèles mathématiques pour étudier les changements de forme dans les tissus mous tubulaires. L'approche adoptée est macroscopique où le tissu biologique est considéré comme un milieu continu déformable. L'hypothèse principale sur laquelle se basent les modèles proposés est la suivante: pendant les processus de croissance et remodelage, des contraintes résiduelles peuvent s'accumuler dans le tissu et, une fois une valeur critique dépassée, le mener à un changement morphologique sous la forme d'une instabilité élastique. Pour cela, les modèles développés intègrent les théories modernes de croissance et remodelage, dans le cadre de la thermomécanique des systèmes ouverts. Ensuite, l'analyse de stabilité linéaire permet de calculer les seuils et modes de l'instabilité élastique en utilisant la méthode des déformations incrémentales superposées aux déformations finies. L'ensemble de ces techniques (théorie morpho-élastique) est utilisé dans cette thèse afin de modéliser deux différents processus morphogénétiques ayant lieu dans les tissus mous tubulaires : la formation d'une variété des formes dans le système gastro-intestinal et le flambage hélicoïdal dans les organes tubulaires avec précontraintes