Pharmaceutically active compounds have increasingly been detected in groundwater worldwide. Despite constituting a risk for human health and ecosystems, their fate in the environment has still not been exhaustively investigated. This study characterizes the transport behavior of five selected pharmaceutically active compounds (antipyrine, atenolol, caffeine, carbamazepine and sulfamethoxazole) in two sediments (coarse quartz sand and sandy loam) using column experiments with long-term injection of spiked groundwater. Transport parameters were estimated using an analytical reactive transport model. When five selected compounds were injected simultaneously, transport behavior of antipyrine, carbamazepine and the antibiotic sulfamethoxazole were similar to the conservative tracer in both sediments and under varying redox conditions. Atenolol and caffeine were retarded significantly stronger in the sandy loam sediment than in the coarse quartz sand. Biodegradation of caffeine was observed in both sediments after an adaption period and depended on dissolved oxygen. The identification of biodegradation processes was supported by monitoring of intracellular adenosine triphosphate (ATPitc) as a measure for microbial activity. ATPitc was present in varying concentrations in all sediments and was highest when biodegradation of pharmaceuticals, especially caffeine, was observed. When only caffeine and sulfamethoxazole were injected simultaneously, sulfamethoxazole was degraded while caffeine degradation was reduced. The latter seemed to be influenced by low concentrations in dissolved oxygen rather than the presence of the antibiotic sulfamethoxazole. Results of these experiments emphasize the impact on pharmaceutical sorption and (bio)degradation of sediment type and redox conditions, as well as available time for microbial adaption and the combination of pharmaceuticals that are released together into groundwater.Antisense oligonucleotides (ASOs) are a promising clinical tool that could be applied for unmet medical needs, but there are several limitations for their therapeutic application. Here, we designed and synthesized (S)-5'-C-aminopropyl-2'-O-methylcytidine, and oligonucleotides containing (S)-5'-C-aminopropyl-2'-O-methyluridine and -methylcytidine. We then investigated the properties of ASOs containing these nucleoside analogs. (S)-5'-C-Aminopropyl modifications enhanced the thermal stability of DNA/RNA duplexes when compared to other commercially available 2'-O-methyl modifications. This suggested that the terminal ammonium cation on the alkyl side chains neutralized the negative charge of the phosphates in the duplex. Additionally, the overall conformation of ASO/RNA duplexes was retained with the modified ASOs. Thus, these duplexes exhibited the ability to elicit RNase H activity. Furthermore, we found that ASOs containing the (S)-5'-C-aminopropyl modification exhibited higher antisense potency than those containing the 2'-O-methyl modification in cultured cells. Therefore, the (S)-5'-C-aminopropyl-2'-O-methyl nucleosides synthesized in this study are promising candidates for developing antisense therapeutics.The neurophysiology of face processing has been studied extensively in the context of social impairments associated with autism spectrum disorder (ASD), but the existing studies have concentrated mainly on univariate analyses of responses to upright faces, and, less frequently, inverted faces. The small number of existing studies on neurophysiological responses to inverted face in ASD have used univariate approaches, with divergent results. Here, we used a data-driven, classification-based, multivariate machine learning decoding approach to investigate the temporal and spatial properties of the neurophysiological evoked response for upright and inverted faces, relative to the neurophysiological evoked response for houses, a neutral stimulus. 21 (2 females) ASD and 29 (4 females) TD participants ages 7 to 19 took part in this study. Group level classification accuracies were obtained for each condition, using first the temporal domain of the evoked responses, and then the spatial distribution of the evoked responses on the cortical surface, each separately. We found that classification of responses to inverted neutral faces vs.  https://www.selleckchem.com/products/liraglutide.html  houses was less accurate in ASD compared to TD, in both the temporal and spatial domains. In contrast, there were no group differences in the classification of evoked responses to upright neutral faces relative to houses. Using the classification in the temporal domain, lower decoding accuracies in ASD were found around 120 ms and 170 ms, corresponding the known components of the evoked responses to faces. Using the classification in the spatial domain, lower decoding accuracies in ASD were found in the right superior marginal gyrus (SMG), intra-parietal sulcus (IPS) and posterior superior temporal sulcus (pSTS), but not in core face processing areas. Importantly, individual classification accuracies from both the temporal and spatial classifiers correlated with ASD severity, confirming the relevance of the results to the ASD phenotype.
  Modulation of sympathetic activity during acute sleep deprivation can produce various effects on body functions. We studied the effects of acute sleep deprivation before ischemia/reperfusion on myocardial injury in isolated rat hearts, and the role of sympathetic nervous system that may mediate these sleep deprivation induced effects.
 
  The animals were randomized into four groups (n=11 per group) Ischemia- Reperfusion group (IR), Acute sleep deprivation group (SD), Control group for sleep deprivation (CON-SD) and Sympathectomy+ASD group (SYM-SD). In SD group, sleep deprivation paradigm was used 24h prior to induction of ischemia/reperfusion. In SYM-SD group, the animals were chemically sympathectomized using 6-hydroxydopamine, 24h before sleep deprivation. Then, the hearts of animals were perfused using Langendorff setup and were subjected to 30min regional ischemia followed by 60min of reperfusion. Throughout the experiment, the hearts were allowed to beat spontaneously and left ventricular developed pressure (LVDP) and rate pressure product (RPP) were recorded.