Photobiomodulation prevents PTSD-like memory impairments in rats

Abstract: A precise fear memory encoding a traumatic event enables an individual to avoid danger and identify safety. An impaired fear memory (contextual amnesia), however, puts the individual at risk of developing posttraumatic stress disorder (PTSD) due to the inability to identify a safe context when encountering trauma-associated cues later in life. Although it is gaining attention that contextual amnesia is a critical etiologic factor for PTSD, there is no treatment currently available that can reverse contextual amnesia, and whether such treatment can prevent the development of PTSD is unknown. Here, we report that (I) a single dose of transcranial photobiomodulation (PBM) applied immediately after tone fear conditioning can reverse contextual amnesia. PBM treatment preserved an appropriately high level of contextual fear memory in rats revisiting the “dangerous” context, while control rats displayed memory impairment. (II) A single dose of PBM applied after memory recall can reduce contextual fear during both contextual and cued memory testing. (III) In a model of complex PTSD with repeated trauma, rats given early PBM interventions efficiently discriminated safety from danger during cued memory testing and, importantly, these rats did not develop PTSD-like symptoms and comorbidities. (IV) Finally, we report that fear extinction was facilitated when PBM was applied in the early intervention window of memory consolidation. Our results demonstrate that PBM treatment applied immediately after a traumatic event or its memory recall can protect contextual fear memory and prevent the development of PTSD-like psychopathological fear in rats

Identification of Susceptibility Pathways for the Role of Chromosome 15q25.1 in Modifying Lung Cancer Risk

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer

Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26), a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv) antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID) syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action.Conclusions: Although further studies will be necessary to validate the effect of the antibody in vivo, the methodology described here can be extended to select antibodies against hemichannels composed by other connexin isoforms and, consequently, to target other pathologies associated with hyperactive hemichannels. Our study highlights the potential of this approach and identifies connexins as therapeutic targets addressable by screening phage display libraries expressing human randomized antibodies

Use of nanomaterials in the pretreatment of water samples for environmental analysis

The challenge of providing clean drinking water is of enormous relevance in today’s human civilization, being essential for human consumption, but also for agriculture, livestock and several industrial applications. In addition to remediation strategies, the accurate monitoring of pollutants in water sup-plies, which most of the times are present at low concentrations, is a critical challenge. The usual low concentration of target analytes, the presence of in-terferents and the incompatibility of the sample matrix with instrumental techniques and detectors are the main reasons that renders sample preparation a relevant part of environmental monitoring strategies. The discovery and ap-plication of new nanomaterials allowed improvements on the pretreatment of water samples, with benefits in terms of speed, reliability and sensitivity in analysis. In this chapter, the use of nanomaterials in solid-phase extraction (SPE) protocols for water samples pretreatment for environmental monitoring is addressed. The most used nanomaterials, including metallic nanoparticles, metal organic frameworks, molecularly imprinted polymers, carbon-based nanomaterials, silica-based nanoparticles and nanocomposites are described, and their applications and advantages overviewed. Main gaps are identified and new directions on the field are suggested.publishe

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

An alternate learning approach for destructive testing in civil engineering - Benefits from remote laboratory experimentation

An alternative learning approach for destructive testing of structural specimens in civil engineering is explored by using a remote laboratory experimentation method. The remote laboratory approach focuses on overcoming the constraints in the hands-on experimentation without compromising the understanding of the students on the concepts and mechanics of reinforced concrete structures. The goal of this study is to evaluate whether or not the remote laboratory experimentation approach can become a standard in civil engineering teaching. The teaching activity using remote-laboratory experimentation is presented here and the outcomes of this activity are outlined. The experience and feedback gathered from this study are used to improve the remote-laboratory experimentation approach in future years to other aspects of civil engineering where destructive testing is essential

Long-Term Variations of Global Solar Radiation and Atmospheric Constituents at Sodankylä in the Arctic

An empirical model of global solar irradiance (EMGSI) under all sky conditions was developed by using solar radiation and meteorological parameters at Sodankylä. The calculated hourly global solar irradiance is in agreement with that observed at the ground during 2008–2011 and at the top of the atmosphere (TOA). This model is used to calculate the global solar irradiance at the ground and its attenuation in the atmosphere due to absorbing and scattering substances in 2000–2018. The sensitivity test indicates that the responses of global solar irradiance to changes in water vapor and scattering factors are nonlinear and negative, and global solar irradiance is more sensitive to changes in scattering (expressed by the scattering factor S/G, S and G are diffuse and global solar radiation, respectively) than to changes in water vapor. Using this empirical model, we calculated the albedos at the TOA and the surface, which are in agreement with the satellite-retrieved values. A good relationship between S/G and aerosol optical depth (AOD) was determined and used to estimate AOD in 2000–2018. An empirical model for estimation of tropospheric NO2 vertical column density (VCD) was also developed and used to calculate tropospheric NO2 VCD in 2000–2018. During 2000–2018, the estimated global solar irradiance decreased by 0.92%, and diffuse irradiance increased by 1.28% per year, which is ascribed to the increases of S/G (1.73%) and water vapor (0.43%). Annual surface air temperature increases by 0.07 °C per year. Annual mean loss of global solar irradiance caused by absorbing and scattering substances and total loss are 1.94, 1.17 and 3.11 MJ m−2, respectively. Annual mean losses of absorbing and scattering global solar irradiance show negative and positive trends, respectively, and the annual total loss increases by 0.24% per year. Annual mean losses due to absorption were much larger than those due to scattering. The calculated albedos at the TOA are smaller than at the surface. The calculated and satellite-retrieved annual albedos decrease at the TOA and increase at the surface. During 2000–2018, annual means of the AOD and the tropospheric NO2 VCD increased by 8.23% and 0.03% per year, respectively

Heavy vehicle over bridges on the route to transport coal in Shaanxi, Northwest China

Paper presented at the 23rd Annual Southern African Transport Conference 12 - 15 July 2004 "Getting recognition for the importance of transport", CSIR International Convention Centre, Pretoria, South Africa. This paper describes numerous overweight and overloaded vehicles on the Fu-Dian Highway, Shaanxi, China. On the base of investigation, 9 types of load models are sorted. Taking gross weight and axle–load as abscissa, and proportion of corresponding load range vehicles to total vehicles as ordinate, gross weight and axle-load histograms are drawn out. According to the above results, various assessment load models are carried out. The bearing capacity of reinforced bridges and load effect of overweight vehicles are calculated. The paper also raises suggestions for the road management authority. * This paper is part of the results from the China-South Africa S&T Co-operative project: 'Innovation and Promotion on Infrastructure Information Management Systems for Highway Authorities in South Africa and the Great Western Area of China'.This paper was transferred from the original CD ROM created for this conference. The material on the CD ROM was published using Adobe Acrobat technology. The original CD ROM was produced by Document Transformation Technologies Postal Address: PO Box 560 Irene 0062 South Africa. Tel.: +27 12 667 2074 Fax: +27 12 667 2766 E-mail: [email protected] URL: http://www.doctech.co.z