Neuroprotective Effects of Sigma 1 Receptor Ligands on Motoneuron Death after Spinal Root Injury in Mice

Loss of motor neurons (MNs) after spinal root injury is a drawback limiting the recovery after palliative surgery by nerve or muscle transfers. Research based on preventing MN death is a hallmark to improve the perspectives of recovery following severe nerve injuries. Sigma-1 receptor (Sig-1R) is a protein highly expressed in MNs, proposed as neuroprotective target for ameliorating MN degenerative conditions. Here, we used a model of L4–L5 rhizotomy in adult mice to induce MN degeneration and to evaluate the neuroprotective role of Sig-1R ligands (PRE-084, SA4503 and BD1063). Lumbar spinal cord was collected at 7, 14, 28 and 42 days post-injury (dpi) for immunohistochemistry, immunofluorescence and Western blot analyses. This proximal axotomy at the immediate postganglionic level resulted in significant death, up to 40% of spinal MNs at 42 days after injury and showed markedly increased glial reactivity. Sig-1R ligands PRE-084, SA4503 and BD1063 reduced MN loss by about 20%, associated to modulation of endoplasmic reticulum stress markers IRE1α and XBP1. These pathways are Sig-1R specific since they were not produced in Sig-1R knockout mice. These findings suggest that Sig-1R is a promising target for the treatment of MN cell death after neural injuries.     

Assessing the performance of methods to detect and quantify African dust in airborne particulates

African dust (AD) contributions to particulate matter (PM) levels may be reported by Member States to the European Commission during justification of exceedances of the daily limit value (DLV). However, the detection and subsequent quantification of the AD contribution to PM levels is complex, and only two measurement-based methods are available in the literature: the Spanish-Portuguese reference method (SPR), and the Tel Aviv University method (TAU). In the present study, both methods were assessed. The SPR method was more conservative in the detection of episodes (71 days identified as AD by SPR, vs 81 by TAU), as it is less affected by interferences with local dust sources. The mean annual contribution of AD was lower with the TAU method than with SPR (2.7 vs 3.5 ± 1.5 μg/m(3)). The SPR and TAU AD time series were correlated with daily aluminum levels (a known tracer of AD), as well as with an AD source identified by the Positive Matrix Factorization (PMF) receptor model. Higher r(2) values were obtained with the SPR method than with TAU in both cases (r(2) = 0.72 vs 0.56, y = 0.05x vs y = 0.06x with aluminum levels; r(2)=0.79 vs 0.43, y = 0.8x vs y = 0.4x with the PMF source). We conclude that the SPR method is more adequate from an EU policy perspective (justification of DLV exceedances) due to the fact that it is more conservative than the TAU method. Based on our results, the TAU method requires adaptation of the thresholds in the algorithm to refine detection of low-impact episodes and avoid misclassification of local events as AD.     

A macroscopic model for high intensity radiofrequency signal detection in swarm robotics systems

In recent years, there has been a growing interest in resource location in unknown environments for robotic systems, which are composed of multiple simple robots rather than one highly capable robot [M. Sempere, F. Aznar, M. Pujol, and R. Rizo, On cooperative swarm foraging for simple, non explicitly connected, agents, 2010]. This tradeoff reduces the design and hardware complexity of the robots and removes single point failures, but adds complexity in algorithm design. The challenge is to programme a swarm of simple robots, with minimal intercommunication and individual capability, to perform a useful task as a group. This paper is focused on finding the highest intensity area of a radiofrequency (RF) signal in urban environments. These signals are usually more intense near the city centre and its proximity, since in these zones the risk of signal saturation is high. RF radiation (RFR) is boosted or blocked mainly depending on orography or building structures. RF providers need to supply enough coverage, setting up different antennas to be able to provide a minimum quality of service. We will define a micro/macroscopic mathematical model to efficiently study a swarm robotic system, predict their long-term behaviour and gain insight into the system design. The macroscopic model will be obtained from Rate Equations, describing the dynamics of the swarm collective behaviour. In our experimental section, the Campus of the University of Alicante will be used to simulate our model. Three RFR antennas will be taken into account, one inside our Campus and the other two in its perimeter. Several tests, that show the convergence of the swarm towards the RFR, will be presented. In addition, the obtained RFR maps and the macroscopic behaviour of the swarm will be discussed.     

EST79232 and EST79376, Two Novel Sigma-1 Receptor Ligands,Exert Neuroprotection on Models of Motoneuron Degeneration

Motor neuron diseases (MNDs) include sporadic and hereditary neurological disorders characterized by progressive degeneration of motor neurons (MNs). Sigma-1 receptor (Sig-1R) is a protein enriched in MNs, and mutations on its gene lead to various types of MND. Previous studies have suggested that Sig-1R is a target to prevent MN degeneration. In this study, two novel synthesized Sig-1R ligands, coded {"type":"entrez-protein","attrs":{"text":"EST79232","term_id":"558729011"}}EST79232 and {"type":"entrez-protein","attrs":{"text":"EST79376","term_id":"558729197"}}EST79376, from the same chemical series, with the same scaffold and similar physicochemical properties but opposite functionality on Sig-1R, were evaluated as neuroprotective compounds to prevent MN degeneration. We used an in vitro model of spinal cord organotypic cultures under chronic excitotoxicity and two in vivo models, the spinal nerve injury and the superoxide dismutase 1 (SOD1)^G93A mice, to characterize the effects of these Sig-1R ligands on MN survival and modulation of glial reactivity. The antagonist {"type":"entrez-protein","attrs":{"text":"EST79376","term_id":"558729197"}}EST79376 preserved MNs in vitro and after spinal nerve injury but was not able to improve MN death in SOD1^G93A mice. In contrast, the agonist {"type":"entrez-protein","attrs":{"text":"EST79232","term_id":"558729011"}}EST79232 significantly increased MN survival in the three models of MN degeneration evaluated and had a mild beneficial effect on motor function in SOD1^G93A mice. In vivo, Sig-1R ligand {"type":"entrez-protein","attrs":{"text":"EST79232","term_id":"558729011"}}EST79232 had a more potent effect on preventing MN degeneration than {"type":"entrez-protein","attrs":{"text":"EST79376","term_id":"558729197"}}EST79376. These data further support the interest in Sig-1R as a therapeutic target for neurodegeneration.     

Superior Thermoelectric Performance of SiGe Nanowires Epitaxially Integrated into Thermal Micro-Harvesters

Semiconductor nanowires have demonstrated fascinating properties with applications in a wide range of fields, including energy and information technologies. Particularly, increasing attention has focused on SiGe nanowires for applications in a thermoelectric generation. In this work, a bottom-up vapour-liquid-solid chemical vapour Deposition methodology is employed to integrate heavily boron-doped SiGe nanowires on thermoelectric generators. Thermoelectrical properties –, i.e., electrical and thermal conductivities and Seebeck coefficient – of grown nanowires are fully characterized at temperatures ranging from 300 to 600 K, allowing the complete determination of the Figure-of-merit, zT, with obtained values of 0.4 at 600 K for optimally doped nanowires. A correlation between doping level, thermoelectric performance, and elemental distribution is established employing advanced elemental mapping (synchrotron-based nano-X-ray fluorescence). Moreover, the operation of p-doped SiGe NWs integrated into silicon micromachined thermoelectrical generators is shown over standalone and series- and parallel-connected arrays. Maximum open circuit voltage of 13.8 mV and power output as high as 15.6 µW cm⁻² are reached in series and parallel configurations, respectively, operating upon thermal gradients generated with hot sources at 200 °C and air flows of 1.5 m s⁻¹. These results pave the way for direct application of SiGe nanowire-based micro-thermoelectric generators in the field of the Internet of Things.     

Chemical Zymogens: Specificity and Steroidal Control of Reactivation

Activating and masking enzymatic activity on demand is of the highest importance in nature. It is achieved by chemical interconversion of enzymes and the corresponding zymogens through, for example, proteolytic processing or reversible phosphorylation, and affords on-demand activation of enzymes, controlled in space and/or time. In stark contrast, examples of chemical zymogens are very few, and in most cases these are based on disulfide chemistry, which is largely indiscriminate as to the nature of the activating thiol. In this work, we address an outstanding challenge of specificity of reactivation of chemical zymogens. We achieve this through engineering affinity between the chemical zymogen and the activator. Additional, higher-level control over zymogen reactivation is installed in a nature-mimicking approach using steroidal hormones. Taken together, the results of this study take a step towards establishing the specificity of reactivation of synthetic, chemical zymogens. We anticipate that the results of this study will contribute significantly to the development of chemical zymogens as tools for diverse use in chemical biology and biotechnology.     

Proteomic Tools for the Quantitative Analysis of Artificial Peptide Libraries: Detection and Characterization of Target-Amplified PD-1 Inhibitors

We report a quantitative proteomics data analysis pipeline, which coupled to protein-directed dynamic combinatorial chemistry (DDC) experiments, enables the rapid discovery and direct characterization of protein-protein interaction (PPI) modulators. A low-affinity PD-1 binder was incubated with a library of >100 D-peptides under thiol-exchange favoring conditions, in the presence of the target protein PD-1, and we determined the S-linked dimeric species that resulted, amplified in the protein samples versus the controls. We chemically synthesized the target dimer candidates and validated them by thermophoresis binding and protein-protein interaction assays. The results provide a proof-of-concept for using this strategy in the high-throughput search of improved drug-like peptide binders that block therapeutically relevant protein-protein interactions.     

Facile preparation of electrodes based on WO3 nanostructures modified with C and S used as anode materials for Li-ion batteries

An appropriate morphological and structure matrix configuration where lithium ions could insert and de-insert is essential for lithium-ion batteries (LiB). Tungsten oxides (WO₃) are especially attractive materials for this aim. In this research, the effects of the morphology and composition of WO₃ nanostructures on the charge/discharge behavior for Li-ion batteries are methodically examined. On the one hand, nanostructured WO₃ thin film was effectively synthesized by an electrochemical procedure. Then, an annealing treatment at 600°C in air environment for 4 h was carried out. In the second electrode synthesized, a carbon layer was uniformly deposited on WO₃ nanostructures to obtain a WO₃/C electrode. Finally, WO₃/WS₂ electrodes were prepared by means of in situ sulfurization of WO₃ one-step solid-state synthesis using tungsten trioxide (WO₃) and thiourea as precursor material. By using X-ray photoelectron spectroscopy, X-ray diffraction analysis, transmission electron microscopy, Raman spectra, and field-emission scanning electron microscopy, the three electrodes have been morphologically characterized. Electrochemical properties were analyzed by cyclic voltammogram, galvanostatic charge/discharge cycling, and electrochemical impedance spectroscopy. Among all the synthesized samples, WO₃/C nanostructures reveal the best performance as they exhibit the greatest discharge capacity and cycle performance (820 mA h g⁻¹).     

Identification of Hypoderma actaeon (Diptera: Oestridae) in red deer (Cervus elaphus) from northern Spain: Microscopy study and molecular analysis

Hypoderma spp. larvae were observed subcutaneously in the dorsal and lumbar regions of red deer (Cervus elaphus) hunted in the province of León (northwestern Spain) causing a myiasis. They were removed and initially classified by their size, shape, color, and location under the skin into the three larval stages that parasitize these animals. The morphological characteristics of the first and second-instar are described and from the features of the third-instar the species was identified as Hypoderma actaeon. To accurately identify this species, five isolates of genomic DNA from the third-instar, two from the second-instar and two from first-instar of H. actaeon were analyzed by PCR analysis of the COI region of mt-DNA. The results confirmed that the examined samples exactly matched with H. actaeon. This study has shown the morphological identification of the three larval stages of H. actaeon and, for the first time, the first and second-instar larvae have been molecularly characterized. Finally, identification of only H. actaeon suggests that this species is the only affecting red deer in the Iberian Peninsula.