We discuss the limitations of pain models when research findings fail to be translated from animal models to human clinics. But we also point to some recent successes in analgesic drug development that highlight strategies for improving the predictive validity of animal models of pain. Finally, we emphasize the importance of using assortments of preclinical pain models to identify pain subtype mechanisms, and to foster the development of better analgesics.In plants, hypoxia (low-oxygen stress) is induced by soil waterlogging or submergence and this major abiotic stress has detrimental effects on plant growth, development, distribution, and productivity. To survive low-oxygen stress, plants have evolved a set of morphological, physiological, and biochemical adaptations. These adaptations integrate metabolic acclimation and signaling networks allowing plants to endure or escape from low-oxygen environments by altering their metabolism and growth. Lipids are ubiquitously involved in regulating plant responses to hypoxia and post-hypoxic reoxygenation. In particular, the polyunsaturation of long-chain acyl-CoAs regulates hypoxia sensing in plants by modulating acyl-CoA-binding protein-Group VII ethylene response factor dynamics. Moreover, unsaturated very-long-chain ceramide species protect plants from hypoxia-induced cellular damage by regulating the kinase activity of CONSTITUTIVE TRIPLE RESPONSE1 in the ethylene signaling pathway. Finally, the oxylipin jasmonate specifically regulates plant responses to reoxygenation stress by transcriptionally modulating antioxidant biosynthesis. Here we provide an overview of the roles of lipid remodeling and signaling in plant responses to hypoxia/reoxygenation and their effects on the downstream events affecting plant survival. In addition, we highlight the key remaining challenges in this important field.Given the dual life cycle of arboviruses in insect and animal hosts and the importance of serum factors as a first line antiviral defense, we have examined the outcome of interactions between the arbovirus La Crosse Virus (LACV) and human serum. To mimic the life cycle between species, we used LACV derived from insect (I-LACV) and human keratinocyte (HaCaT) cells. Incubation of I-LACV with normal human serum did not result in neutralization, but instead stabilized I-LACV virions and enhanced the amount of infectious virus. Enhanced infectivity was also seen with heat-inactivated serum devoid of complement activity and with serum from a range of animals including mouse, ferret, and non-human primates. selleck chemicals llc Depletion of antibodies from serum resulted in loss of enhancement of infectivity and sucrose gradient sedimentation assays showed IgG co-sedimenting with I-LACV particles. In agreement with our results with I-LACV, HaCaT-derived LACV was not neutralized by complement or antibodies in normal human serum. However, in contrast to I-LACV, HaCaT-derived LACV infectivity was stable when incubated alone and treatment with serum did not enhance infectivity. Our results indicate that LACV derived from insect cells differs substantially from virus derived from human cells, with I-LACV being dependent on serum factors to enhance infectivity. These findings suggest that understanding differential composition of insect versus animal cell-derived LACV may form the foundation for potential new antiviral approaches. Diagnosis of atrial fibrillation (AF) based on electrocardiogram (ECG) with sinus rhythm remains a major challenge. Obtaining a panoramic view with hundreds of automatically measured ECG parameters at sinus rhythm on the predictive capability for AF would be informative. We used a single-center database of a specialist cardiovascular hospital (Shinken Database 2010-2017; n=19,170). We analyzed 12,863 index ECGs with sinus rhythm after excluding those showing AF rhythm, other atrial tachyarrhythmia, pacing beat, or indeterminate axis, and those of patients with structural heart diseases. We used 438 automatically measured ECG parameters in the MUSE data management system. The predictive models were developed using random forest algorithm with the 10-fold cross-validation method. In 12,863 index ECGs with sinus rhythm, a predictive capability for current paroxysmal AF (n=1131) by c-statistics was 0.99981±0.00037 for training dataset and 0.91337±0.00087 for testing dataset, respectively. Excluding AF at baseline (n=11,732), a predictive capability for newly developed AF (n=98) by c-statistics was 0.99973±0.00086 for training dataset and 0.99160±0.00038 for testing dataset, respectively. The distribution of parameter importance was mostly similar among P, QRS, and ST-T segment for both current and newly developed AF. This study intended to provide panoramic information in relation between ECG parameters and AF. The parameter importance of ECG parameters for predicting AF was mostly similar in P, QRS, and ST-T segment in models for both current and future AF.This study intended to provide panoramic information in relation between ECG parameters and AF. The parameter importance of ECG parameters for predicting AF was mostly similar in P, QRS, and ST-T segment in models for both current and future AF.Eimeria ninakohlyakimovae represents a highly pathogenic coccidian parasite causing severe haemorrhagic typhlocolitis in goat kids worldwide. NETosis was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites in vitro and in vivo. In vitro interactions of caprine PMN with parasitic stages of E. ninakohlyakimovae (i. e. oocysts and sporozoites) as well as soluble oocyst antigens (SOA) were analyzed at different ratios, concentrations and time spans. Extracellular DNA staining was used to illustrate classical molecules induced during caprine NETosis [i. e. histones (H3) and neutrophil elastase (NE)] via antibody-based immunofluorescence analyses. Functional inhibitor treatments with DPI and DNase I were applied to unveil role of NADPH oxidase (NOX) and characterize DNA-backbone composition of E. ninakohlyakimovae-triggered caprine NETosis. Scanning electron microscopy (SEM)- and immunofluorescence-analyses demonstrated that caprine PMN underwent NETosis upon contact with sporozoites and oocysts of E.