Subcortical control of precision grip after human spinal cord injury.

The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1-3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip

On The Symplectic Two-Form of Gravity in Terms of Dirac Eigenvalues

The Dirac eigenvalues form a subset of observables of the Euclidean gravity. The symplectic two-form in the covariant phase space could be expressed, in principle, in terms of the Dirac eigenvalues. We discuss the existence of the formal solution of the equations defining the components of the symplectic form in this framework.Comment: misprints corrected, final interpretation of results give

Some evolutionary patterns of palaeokarst developed in Pleistocene deposits (Ebro Basin, NE Spain): Improving geohazard awareness in present-day karst

Pleistocene detrital deposits in the central Ebro Basin frequently show deformation features due mainly to karstification in the underlying Neogene evaporites. In 123 cases, estimation of parameters of shape and minimum volume of materials involved was accomplished. Six of them were analysed in more detail to establish the main processes involved in their genesis and the succession of events. All the deformation features in the selected sites are synsedimentary. To achieve the objectives, intense fieldwork was made applying methods of sedimentology and structural geology. Usually, a complex evolutionary pattern was observed, with evidences of dissolution, sagging, collapse, gravity flow, suffosion, and plastic flow. In a schematic way, three main situations, independent of the age of the analysed deposits, can be distinguished: (a) slow subsidence, (b) collapse, and (c) temporal overlapping of both processes. In the first 2 scenarios, basins with smooth or abrupt borders, respectively, were generated on the land surface. In the third one, slow subsidence was followed by a collapse, located in the area of maximum flexure. These patterns are also observed in present-day dolines. Comparison of direct and indirect parameters between paleodolines and present-day dolines indicates a bigger size of the latter, probably caused by the different conditions of observation. This study helps to know the possibilities in the evolution of mantled karst features, to estimate the volume of material affected by karstification and to improve the knowledge of present-day dolines behaviour. Consequently, study of paleodolines must be considered to achieve a better urban planning in active karstic areas

Comparing climatic suitability and niche distances to explain populations responses to extreme climatic events

Habitat suitability calculated from Species Distribution Models (SDMs) has been used to assess population performance, but empirical studies have provided weak or inconclusive support to this approach. Novel approaches measuring population distances to niche centroid and margin in environmental space have been recently proposed to explain population performance, particularly when populations experience exceptional environmental conditions that may place them outside of the species niche. Here, we use data of co-occurring species’ decay, gathered after an extreme drought event occurring in the SE of the Iberian Peninsula which highly affected rich semiarid shrubland communities, to compare the relationship between population decay (mortality and remaining green canopy) and (1) distances between populations’ location and species niche margin and centroid in the environmental space, and (2) climatic suitability estimated from frequently used SDMs (here MaxEnt) considering both the extreme climatic episode and the average reference climatic period before this. We found that both SDMs-derived suitability and distances to species niche properly predict populations performance when considering the reference climatic period; but climatic suitability failed to predict performance considering the extreme climate period. In addition, while distance to niche margins accurately predict both mortality and remaining green canopy responses, centroid distances failed to explain mortality, suggesting that indexes containing information about the position to niche margin (inside or outside) are better to predict binary responses. We conclude that the location of populations in the environmental space is consistent with performance responses to extreme drought. Niche distances appear to be a more efficient approach than the use of climate suitability indices derived from more frequently used SDMs to explain population performance when dealing with environmental conditions that are located outside the species environmental niche. The use of this alternative metrics may be particularly useful when designing conservation measures to mitigate impacts of shifting environmental conditions

Bifurcations and Slow-Fast Analysis in a Cardiac Cell Model for Investigation of Early Afterdepolarizations

In this study, we teased out the dynamical mechanisms underlying the generation of arrhythmogenic early afterdepolarizations (EADs) in a three-variable model of a mammalian ventricular cell. Based on recently published studies, we consider a 1-fast, 2-slow variable decomposition of the system describing the cellular action potential. We use sweeping techniques, such as the spike-counting method, and bifurcation and continuation methods to identify parametric regions with EADs. We show the existence of isolas of periodic orbits organizing the different EAD patterns and we provide a preliminary classification of our fast-slow decomposition according to the involved dynamical phenomena. This investigation represents a basis for further studies into the organization of EAD patterns in the parameter space and the involved bifurcations

Update of the G2D tool for prioritization of gene candidates to inherited diseases

G2D (genes to diseases) is a web resource for prioritizing genes as candidates for inherited diseases. It uses three algorithms based on different prioritization strategies. The input to the server is the genomic region where the user is looking for the disease-causing mutation, plus an additional piece of information depending on the algorithm used. This information can either be the disease phenotype (described as an online Mendelian inheritance in man (OMIM) identifier), one or several genes known or suspected to be associated with the disease (defined by their Entrez Gene identifiers), or a second genomic region that has been linked as well to the disease. In the latter case, the tool uses known or predicted interactions between genes in the two regions extracted from the STRING database. The output in every case is an ordered list of candidate genes in the region of interest. For the first two of the three methods, the candidate genes are first retrieved through sequence homology search, then scored accordingly to the corresponding method. This means that some of them will correspond to well-known characterized genes, and others will overlap with predicted genes, thus providing a wider analysis. G2D is publicly available at http://www.ogic.ca/projects/g2d_2

Outer membrane pore protein prediction in mycobacteria using genomic comparison

Proteins responsible for outer membrane transport across the unique membrane structure of Mycobacterium spp. are attractive drug targets in the treatment of human diseases caused by the mycobacterial pathogens, M. tuberculosis, M. bovis, M. leprae and M. ulcerans. In contrast to E. coli, relatively few outer membrane proteins (OMPs) have been identified in Mycobacterium spp., largely due to the difficulties in isolating mycobacterial membrane proteins and our incomplete understanding of secretion mechanisms and cell wall structure in these organisms. To further expand our knowledge of these elusive proteins in Mycobacterium, we have improved upon our previous method of OMP prediction in mycobacteria by taking advantage of genomic data from seven mycobacteria species. Our improved algorithm suggests 4333 sequences as putative OMPs in these seven species with varying degrees of confidence. The most virulent pathogenic mycobacterial species are slightly enriched in these selected sequences. We present examples of predicted OMPs involved in horizontal transfer and paralogy expansion. Analysis of local secondary structure content allowed identifying small domains predicted to perform as OMPs; some examples show their involvement in events of tandem duplication and domain rearrangements. We discuss the taxonomic distribution of these discovered families and architectures, often specific to mycobacteria or the wider taxonomic class of Actinobacteria. Our results suggest that OMP functionality in mycobacteria is richer than expected and provide a resource to guide future research of these understudied proteins

Automatic muscle elongation measurement during shoulder arthroplasty planning

Adequate deltoid and rotator cuff lengthening in total shoulder arthroplasty (TSA) is crucial to maximize the postoperative functional outcome and to avoid complications (La¨dermann et al., 2014). Hence surgeons and patients could benefit from including muscle length information in preoperative planning software. Although different methods have been introduced to automatically indicate patient-specific muscle attachment and wrapping points (Kaptein & van der Helm, 2004; Marra et al., 2015), the definition of a fast and accurate workflow is still a challenge, due to the large variability in bone shapes. Statistical shape modelling (SSM) has recently been used to automatically indicate landmark on target bones (Plessers et al., 2018). This method is less dependent on shape variability and could overcome the aforementioned limitation in accuracy. Therefore, the goal of this study is to develop and evaluate the accuracy of a novel automatic method for measuring deltoid and rotator cuff elongation during preoperative planning of shoulder arthroplasty, based on a statistical shape modelling approach

Cooperative Fabrication Methodology for Embedding Wireon Corved Surfaces

In conventional additive manufacturing (AM), an object is fabricated by depositing material in a layer by layer fashion. Typically, this process is retained so that deposition can occur on flat surfaces and motion can be constrained to requiring only three degrees of freedom (DOF) in a Cartesian coordinate system. When incorporating wire in three-dimensional (3D) objects, there is sometimes a need for placement along curved surfaces on which positions are defined not only by 3D Cartesian coordinates but also angular ones. Therefore, a minimum of two additional DOFs are required allowing movement to be generated at the build platform as well as of the extrusion head. This paper addresses a method for trajectory planning of both systems, that is, the extrusion head and the movable build platform, allowing for cooperative and harmonic motion between the two.Mechanical Engineerin

A method for cell type marker discovery by high-throughput gene expression analysis of mixed cell populations

BACKGROUND: Gene transcripts specifically expressed in a particular cell type (cell-type specific gene markers) are useful for its detection and isolation from a tissue or other cell mixtures. However, finding informative marker genes can be problematic when working with a poorly characterized cell type, as markers can only be unequivocally determined once the cell type has been isolated. We propose a method that could identify marker genes of an uncharacterized cell type within a mixed cell population, provided that the proportion of the cell type of interest in the mixture can be estimated by some indirect method, such as a functional assay. RESULTS: We show that cell-type specific gene markers can be identified from the global gene expression of several cell mixtures that contain the cell type of interest in a known proportion by their high correlation to the concentration of the corresponding cell type across the mixtures. CONCLUSIONS: Genes detected using this high-throughput strategy would be candidate markers that may be useful in detecting or purifying a cell type from a particular biological context. We present an experimental proof-of-concept of this method using cell mixtures of various well-characterized hematopoietic cell types, and we evaluate the performance of the method in a benchmark that explores the requirements and range of validity of the approach