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Physics of Infrared Radiation, Natural and Artificial Sources, Experimental Infrared A Irradiation Doses Solar radiation is filtered by the atmosphere and when it finally hits human skin, it includes photons of 290-4,000 nm in wavelength. This portion of the electromagnetic spectrum is divided into three major bands: ultraviolet (UV) radiation (290-400 nm), visible light (400-760 nm) and infrared (IR) radiation (760-4,000 nm), with IR radiation being further divided into IRA (760-1,440 nm), IRB (1,440-3,000 nm) and IRC (3,000-1 mm). Concerning the impact of the three major bands, approximately 54% of the solar energy reaching the human skin is IR radiation, while UV radiation only accounts for 7% of the energy Most of the IRA radiation load of human skin is of solar origin, but in recent years artificial IRA sources are used increasingly. Besides therapeutic approaches the use of IRA for nontherapeutic, i.e., wellness and lifestyle, purposes is steadily rising The question which IRA doses are of physiological relevance has been addressed in a recent discussion Human dermal fibroblasts withstand IRA doses up to at least 1,200 J/cm 2 [4] ; the gene-regulatory effects can Key Words Solar radiation ؒ Infrared A radiation ؒ Skin ageing ؒ Photoageing Abstract Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage

The Increased Activity of TRPV4 Channel in the Astrocytes of the Adult Rat Hippocampus after Cerebral Hypoxia/Ischemia

The polymodal transient receptor potential vanilloid 4 (TRPV4) channel, a member of the TRP channel family, is a calcium-permeable cationic channel that is gated by various stimuli such as cell swelling, low pH and high temperature. Therefore, TRPV4-mediated calcium entry may be involved in neuronal and glia pathophysiology associated with various disorders of the central nervous system, such as ischemia. The TRPV4 channel has been recently found in adult rat cortical and hippocampal astrocytes; however, its role in astrocyte pathophysiology is still not defined. In the present study, we examined the impact of cerebral hypoxia/ischemia (H/I) on the functional expression of astrocytic TRPV4 channels in the adult rat hippocampal CA1 region employing immunohistochemical analyses, the patch-clamp technique and microfluorimetric intracellular calcium imaging on astrocytes in slices as well as on those isolated from sham-operated or ischemic hippocampi. Hypoxia/ischemia was induced by a bilateral 15-minute occlusion of the common carotids combined with hypoxic conditions. Our immunohistochemical analyses revealed that 7 days after H/I, the expression of TRPV4 is markedly enhanced in hippocampal astrocytes of the CA1 region and that the increasing TRPV4 expression coincides with the development of astrogliosis. Additionally, adult hippocampal astrocytes in slices or cultured hippocampal astrocytes respond to the TRPV4 activator 4-alpha-phorbol-12,-13-didecanoate (4αPDD) by an increase in intracellular calcium and the activation of a cationic current, both of which are abolished by the removal of extracellular calcium or exposure to TRP antagonists, such as Ruthenium Red or RN1734. Following hypoxic/ischemic injury, the responses of astrocytes to 4αPDD are significantly augmented. Collectively, we show that TRPV4 channels are involved in ischemia-induced calcium entry in reactive astrocytes and thus, might participate in the pathogenic mechanisms of astroglial reactivity following ischemic insult

The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review

Background: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. Methods: The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were reviewed to determine whether validation data were reported, and then examined in full. Publications concentrating on monitoring of disease burden or mutations were excluded. Results: The search identified 94 ctDNA studies meeting the criteria for review. All but 5 studies examined one cancer type, with breast, colorectal and lung cancers representing 60% of studies. The size and design of the studies varied widely. Controls were included in 77% of publications. The largest study included 640 patients, but the median study size was 65 cases and 35 controls, and the bulk of studies (71%) included less than 100 patients. Studies either estimated cfDNA levels non-specifically or tested for cancer-specific mutations or methylation changes (the majority using PCR-based methods). Conclusion: We have systematically reviewed ctDNA blood biomarkers for the early detection of cancer. Pre-analytical, analytical, and post-analytical considerations were identified which need to be addressed before such biomarkers enter clinical practice. The value of small studies with no comparison between methods, or even the inclusion of controls is highly questionable, and larger validation studies will be required before such methods can be considered for early cancer detection

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Flora of toxic depots in selected industrial zones

Floristic composition in three industrial areas with soils contaminated by heavy metals (As, Cd, Cu, Hg, Pb, Zn) and organic pollutants (polychlorinated biphenyls) was studied. The content of Pb was only significantly correlated with the floristic composition and explained 13.8% of its variability considering spatial dependency of the sites. No correlation was found for PCBs. Altogether, 237 plant vascular species were found at three study sites (117, 133 and 105, respectively). The three study areas differed in their species composition represented by their own characteristic species. The gradient in the content of natives/non-natives, species number, prevailing life forms and indicator values for plant species investigated was revealed. Based on our results, for phytoremediation purposes we can select productive plant species with high biomass and ability to accumulate large amounts of heavy metals or organic compounds and surviving on soils with low mineral content

The first structure function study of GH151 alpha l fucosidase uncovers new oligomerization pattern, active site complementation, and selective substrate specificity

Fucosylated compounds are abundantly present in nature and are associated with many biological processes, therefore carrying great potential for use in medicine and biotechnology. Efficient ways to modify fucosylated compounds are still being developed. Promising results are provided by glycosyl hydrolases with transglycosylating activities, such as amp; 945; l fucosidase isoenzyme 2 from Paenibacillus amp; 8201;thiaminolyticus family GH151 of Carbohydrate Active enZYmes . Currently, there is no 3D structure representing this glycoside hydrolase family and only a few members have been investigated. Here, we present the first structure function study of a GH151 member, providing the key insights into its specific oligomerization and active site properties. According to the crystal structure, small angle X ray scattering data and catalytic investigation, this enzyme functions as a tetramer of a new type and represents the second known case of active site complementation among all amp; 945; l fucosidases. Mutation of the active site complementing residue histidine 503 to alanine confirmed its influence on amp; 945; l fucosidase activity and, specifically, on substrate binding. Several unique features of GH151 family amp; 945; l fucosidases were revealed, including the oligomerization pattern, active site accessibility and complementation, and substrate selectivity. Some common properties of GH151 glycosyl hydrolases then would be the overall three domain structure and conservation of the central domain loop 2 function, including its complementation role and the formation of the carbohydrate binding platform in the active site vicinit