In vivo assessment of the mechanical properties of the child cortical bone using quantitative computed tomography

The mechanical properties of the rib cortical bone are extremely rare on children due to difficulties to obtain specimens to perform conventional tests. Some recent studies used cadaveric bones or bone tissues collected during surgery but are limited by the number of samples that could be collected. A non-invasive technique could be extremely valuable to overcome this limitation. It has been shown that a relationship exists between the mechanical properties (apparent Young’s modulus and ultimate strength) and the bone mineral density (assessed using Quantitative Computed Tomography, QCT), for the femur and recently by our group for the adult ribs ex vivo. Thus the aim of this study was to assess the mechanical properties of the child rib cortical bone using both QCT images in vivo and the previous relationship between bone mineral density and mechanical properties of the rib cortical bone. Twenty-eight children were included in this study. Seven age-groups have been considered (1, 1.5, 3, 6, 10, 15, 18 years old). The QCT images were prescribed for various thoracic pathologies at the pediatric hospital in Lyon. A calibration phantom was added to the clinical protocol without any modifications for the patient. The protocol was approved by the ethical committee. A 3D reconstruction of each thorax was performed using the QCT images. A custom software was then used to obtain cross-sections to the rib midline. The mean bone mineral density was then computed by averaging the Hounsfield Units in a specific cross-section and by converting the mean value (Hounsfield Units) in bone mineral density using the calibration phantom. This bone mineral density was assessed for the 6th rib of each subject. Our relationship between the bone mineral density and the mechanical properties of the rib cortical bone was used to derive the mechanical properties of the child ribs in vivo. The results give values for the apparent Young’s modulus and the ultimate strength. The mechanical properties increase along growth. As an example the apparent Young’s modulus in the lateral region ranges from 7 GPa +/-3 at 1 year old up to 13 GPa +/- 2 at 18 years old. These data are in agreement with the few previous values obtained from child tissues. This methodology opens the way to in vivo measurement of the mechanical properties of the child cortical bone based on calibrated QCT images

A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding

The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan-derived fluorophore into the pharmacophore of an ATP-competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two-photon cross section of the inhibitor is amenable for excitation at 700 nm

Chestnut wood in compression perpendicular to the grain : non-destructive correlations for test results in new and old wood

This paper addresses the evaluation of the compressive properties of chestnut wood under compression perpendicular to the grain, using destructive and non-destructive methods. Three non-destructive methods (ultrasonic testing, Resistograph and Pilodyn) are proposed and the possibility of their application is discussed based on the application of simple linear regression models. Timber specimens were tested up to failure, divided in two different groups for assessing a possible load history related degradation, namely New Chestnut Wood (NCW), never been used structurally, and Old Chestnut Wood (OCW), obtained from structural elements belonging to ancient buildings. The specimens were also divided into four groups according to the orientation of annual growth rings towards load and wave propagation direction. The results show, in general, good correlations between compression strength and stiffness with non-destructive techniques via ultrasonic testing, Resistograph and Pilodyn. However, the orientation of the loading direction with respect to the annual growth rings must be taken into account. This conclusion, and the observation that NCW and OCW shows correlations and regression models usually different, add additional complexity to the quantitative use of non-destructive evaluation techniques for the assessment of the mechanical behaviour of timber elements.Fundação para a Ciência e Tecnologia (FCT) - SFRH/BD/ 5002/200

A Bio-Based Pro-Antimicrobial Polymer Network Via Degradable Acetal Linkages

The synthesis of a fully degradable, bio-based, sustained release, pro-antimicrobial polymer network comprised of degradable acetals (PANDA) is reported. The active antimicrobial agent – p-anisaldehyde (pA) (an extract from star anise) – was converted into a UV curable acetal containing pro-antimicrobial monomer and subsequently photopolymerized into a homogenous thiol-ene network. Under neutral to acidic conditions (pH \u3c 8), the PANDAs undergo surface erosion and exhibit sustained release of pA over 38 days. The release of pA from PANDAs was shown to be effective against both bacterial and fungal pathogens. From a combination of confocal microscopy and transmission electron microscopy, we observed that the released pA disrupts the cell membrane. Additionally, we demonstrated that PANDAs have minimal cytotoxicity towards both epithelial cells and macrophages. Although a model platform, these results point to promising pathways for the design of fully degradable sustained-release antimicrobial systems with potential applications in agriculture, pharmaceuticals, cosmetics, household/personal care, and food industries

From Antenna to Antenna: Lateral Shift of Olfactory Memory Recall by Honeybees

Honeybees, Apis mellifera, readily learn to associate odours with sugar rewards and we show here that recall of the olfactory memory, as demonstrated by the bee extending its proboscis when presented with the trained odour, involves first the right and then the left antenna. At 1–2 hour after training using both antennae, recall is possible mainly when the bee uses its right antenna but by 6 hours after training a lateral shift has occurred and the memory can now be recalled mainly when the left antenna is in use. Long-term memory one day after training is also accessed mainly via the left antenna. This time-dependent shift from right to left antenna is also seen as side biases in responding to odour presented to the bee's left or right side. Hence, not only are the cellular events of memory formation similar in bees and vertebrate species but also the lateralized networks involved may be similar. These findings therefore seem to call for remarkable parallel evolution and suggest that the proper functioning of memory formation in a bilateral animal, either vertebrate or invertebrate, requires lateralization of processing

Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone