Harnessing the power of cell transplantation to target respiratory dysfunction following spinal cord injury.

The therapeutic benefit of cell transplantation has been assessed in a host of central nervous system (CNS) diseases, including disorders of the spinal cord such as traumatic spinal cord injury (SCI). The promise of cell transplantation to preserve and/or restore normal function can be aimed at a variety of therapeutic mechanisms, including replacement of lost or damaged CNS cell types, promotion of axonal regeneration or sprouting, neuroprotection, immune response modulation, and delivery of gene products such as neurotrophic factors, amongst other possibilities. Despite significant work in the field of transplantation in models of SCI, limited attention has been directed at harnessing the therapeutic potential of cell grafting for preserving respiratory function after SCI, despite the critical role pulmonary compromise plays in patient outcome in this devastating disease. Here, we will review the limited number of studies that have demonstrated the therapeutic potential of intraspinal transplantation of a variety of cell types for addressing respiratory dysfunction in SCI

Polar features in the flagellar propulsion of E. coli bacteria

E. coli bacteria swim following a run and tumble pattern. In the run state all flagella join in a single helical bundle that propels the cell body along approximately straight paths. When one or more flagellar motors reverse direction the bundle unwinds and the cell randomizes its orientation. This basic picture represents an idealization of a much more complex dynamical problem. Although it has been shown that bundle formation can occur at either pole of the cell, it is still unclear whether this two run states correspond to asymmetric propulsion features. Using holographic microscopy we record the 3D motions of individual bacteria swimming in optical traps. We find that most cells possess two run states characterised by different propulsion forces, total torque and bundle conformations. We analyse the statistical properties of bundle reversal and compare the hydrodynamic features of forward and backward running states. Our method is naturally multi-particle and opens up the way towards controlled hydrodynamic studies of interacting swimming cells

Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.

BACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins. METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1. RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins. CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed

Metamodeling and metaquerying in OWL 2 QL

OWL 2 QL is a standard profile of the OWL 2 ontology language, specifically tailored to Ontology-Based Data Management. Inspired by recent work on higher-order Description Logics, in this paper we present a new semantics for OWL 2 QL ontologies, called Metamodeling Semantics (MS), and show that, in contrast to the official Direct Semantics (DS) for OWL 2, it allows exploiting the metamodeling capabilities natively offered by the OWL 2 punning. We then extend unions of conjunctive queries with both metavariables, and the possibility of using TBox atoms, with the purpose of expressing meaningful metalevel queries. We first show that under MS both satisfiability checking and answering queries including only ABox atoms, have the same complexity as under DS. Second, we investigate the problem of answering general metaqueries, and single out a new source of complexity coming from the combined presence of a specific type of incompleteness in the ontology, and of TBox axioms among the query atoms. Then we focus on a specific class of ontologies, called TBox-complete, where there is no incompleteness in the TBox axioms, and show that general metaquery answering in this case has again the same complexity as under DS. Finally, we move to general ontologies and show that answering general metaqueries is coNP-complete with respect to ontology complexity, Π2p-complete with respect to combined complexity, and remains AC0 with respect to ABox complexity

Radon concentration in self-bottled mineral spring waters as a possible public health issue

Since 2013, the Council Directive 2013/51/Euratom has been regulating the content of radioactive substances in water intended for human consumption. However, mineral waters are exempted from this regulation, including self-bottled springs waters, where higher radon concentration are expected. Therefore, a systematic survey has been conducted on all the 33 mineral spring waters of Lazio (a region of Central Italy) in order to assess if such waters, when self-bottled, may be of concern for public health. Waters have been sampled in two different ways to evaluate the impact of bottling on radon concentration. Water sampling was possible for 20 different spring waters, with 6 samples for each one. The results show that 2 (10%) of measured mineral spring waters returned radon concentrations higher than 100 Bq L−1, i.e., the parametric value established by the Council Directive. These results, if confirmed by other surveys involving a higher number of mineral spring waters, would suggest regulating also these waters, especially in countries like Italy for which: (i) mineral water consumption is significant; (ii) mineral concession owners generally allow the consumers to fill bottles and containers, intended for transport and subsequent consumption, directly from public fountains or from fountains within the plant; (iii) the consumers’ habit of drinking self-bottled mineral water is widespread

A Formal Model of Algorand Smart Contracts

We develop a formal model of Algorand stateless smart contracts (stateless ASC1). We exploit our model to prove fundamental properties of the Algorand blockchain, and to establish the security of some archetypal smart contracts. While doing this, we highlight various design patterns supported by Algorand. We perform experiments to validate the coherence of our formal model w.r.t. the actual implementation

Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs

The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the beta-CoV spike protein family, using sequence information alone, can provide valuable insights on the molecular basis of the specificity of beta-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptor adaptation of circulating and future novel b-CoVs. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology

Local BDNF Delivery to the Injured Cervical Spinal Cord using an Engineered Hydrogel Enhances Diaphragmatic Respiratory Function.

We developed an innovative biomaterial-based approach to repair the critical neural circuitry that controls diaphragm activation by locally delivering brain-derived neurotrophic factor (BDNF) to injured cervical spinal cord. BDNF can be used to restore respiratory function via a number of potential repair mechanisms; however, widespread BDNF biodistribution resulting from delivery methods such as systemic injection or lumbar puncture can lead to inefficient drug delivery and adverse side effects. As a viable alternative, we developed a novel hydrogel-based system loaded with polysaccharide-BDNF particles self-assembled by electrostatic interactions that can be safely implanted in the intrathecal space for achieving local BDNF delivery with controlled dosing and duration. Implantation of BDNF hydrogel after C4/C5 contusion-type spinal cord injury (SCI) in female rats robustly preserved diaphragm function, as assessed b

FEM simulation of a crack propagation in a round bar under combined tension and torsion fatigue loading

An edge crack propagation in a steel bar of circular cross-section undergoing multiaxial fatigue loads is simulated by Finite Element Method (FEM). The variation of crack growth behaviour is studied under axial and combined in phase axial+torsional fatigue loading. Results show that the cyclic Mode III loading superimposed on the cyclic Mode I leads to a fatigue life reduction. Numerical calculations are performed using the FEM software ZENCRACK to determine the crack path and fatigue life. The FEM numerical predictions have been compared against corresponding experimental and numerical data, available from literature, getting satisfactory consistencyN/