Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

Structure–property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure–property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the ‘more accurate’ beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body

Online Training of an Opto-Electronic Reservoir Computer

Reservoir Computing is a bio-inspired computing paradigm for processing time dependent signals. Its analog implementations equal and sometimes outperform other digital algorithms on a series of benchmark tasks. Their performance can be increased by switching from offline to online training method. Here we present the first online trained opto-electronic reservoir computer. The system is tested on a channel equalisation task and the algorithm is executed by an FPGA chip. We report performances close to previous implementations and demonstrate the benefits of online training on a non-stationary task that could not be easily solved using offline methods.info:eu-repo/semantics/publishe

Auditory Selective Attention to Speech Modulates Activity in the Visual Word Form Area

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level–dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers

Nanomechanical investigation of soft biological cell adhesion using atomic force microscopy

Mechanical coupling between living cells is a complex process that is important for a variety of biological processes. In this study the effects of specific biochemical treatment on cell-to-cell adhesion and single cell mechanics were systematically investigated using atomic force microscopy (AFM) single cell force spectroscopy. Functionalised AFM tipless cantilevers were used for attaching single suspended cells that were brought in contact with substrate cells. Cell-to-cell adhesion parameters, such as maximum unbinding force (F max) and work or energy of detachment (W D), were extracted from the retraction force–displacement (F–d) curves. AFM indentation experiments were performed by indenting single cells with a spherical microbead attached to the cantilever. Hertzian contact model was applied to determine the elastic modulus (E) of single cells. Following treatment of the cells with neutralising antibody for epithelial (E)-cadherin, F max was increased by 25%, whereas W D decreased by 11% in response to a 43% increase in E. The results suggest that although the adhesion force between cells was increased after treatment, the energy of adhesion was decreased due to the reduced displacement separation as manifested by the loss of elastic deformation. Conclusively, changes in single cell mechanics are important underlying factors contributing to cell-to-cell adhesion and hence cytomechanical characterization is critical for cell adhesion measurements

Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing.</p> <p>Methods/Design</p> <p>A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use.</p> <p>Discussion</p> <p>This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws.</p