Browningmarcussen7622

Currently, the most potent and specific TRPM7 inhibitor is waixenicin A, a xenicane diterpenoid from the Hawaiian soft coral Sarcothelia edmondsoni. Using waixenicin A as a pharmacological tool, we demonstrated that TRPM7 is involved in promoting neurite outgrowth in vitro. Most recently, we found that waixenicin A reduced hypoxic-ischemic brain injury and preserved long-term behavioral outcomes in mouse neonates. We here suggest that TRPM7 is an emerging drug target for CNS diseases and disorders, and waixenicin A is a viable drug lead for these disorders.RIP1 kinase is proposed to play a critical role in driving necroptosis and inflammation in neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS). Preclinical studies indicated that while pharmacological inhibition of RIP1 kinase can ameliorate axonal pathology and delay disease onset in the mutant SOD1 transgenic (SOD1-Tg) mice, genetic blockade of necroptosis does not provide benefit in this mouse model. To clarify the role of RIP1 kinase activity in driving pathology in SOD1-Tg mice, we crossed SOD1-Tgs to RIP1 kinase-dead knock-in mice, and measured disease progression using functional and histopathological endpoints. Genetic inactivation of the RIP1 kinase activity in the SOD1-Tgs did not benefit the declining muscle strength or nerve function, motor neuron degeneration or neuroinflammation. In addition, we did not find evidence of phosphorylated RIP1 accumulation in the spinal cords of ALS patients. On the other hand, genetic inactivation of RIP1 kinase activity ameliorated the depletion of the neurotransmitter dopamine in a toxin model of dopaminergic neurodegeneration. These findings indicate that RIP1 kinase activity is dispensable for disease pathogenesis in the SOD1-Tg mice while inhibition of kinase activity may provide benefit in acute injury models.An amendment to this paper has been published and can be accessed via a link at the top of the paper.About 70% of all antibiotics produced in the world are used in the farm animal industry. The massive usage of antibiotics during farm animal production has caused rapid development of antibiotic resistance in bacteria, which poses a serious risk to human and livestock health when treating bacterial infections. Protegrin-1 (PG-1) is a potent antimicrobial peptide (AMP). It was initially identified in pig leukocytes with a broad-spectrum antibacterial and antiviral activity, and a low rate of inducing bacterial resistance. To develop a genetic approach for reducing the use of antibiotics in farm animal production, we produced transgenic mice carrying a bovine tracheal AMP gene promoter-controlled PG-1 transgene. The PG-1 transgene was specifically expressed in the respiratory tract of transgenic mice upon induction by bacterial infection. These PG-1 transgenic mice exhibited enhanced resistance to nasal bacterial infection as the transgenic mice showed a higher survival rate (79.17% VS. 34.78%), lower bacterial load and milder histological severity than their wild-type control littermates. The improved resistance to bacterial infection in the PG-1 transgenic mice could be resulted from the direct bacteria-killing activities of PG-1, and the immunomodulatory effects of PG-1 via stimulating interleukin 1 beta secretion. The present study provides a promising genetic strategy to prevent airway bacterial infections in farm animals by bacteria-inducible tissue-specific expression of PG-1 transgene. This approach may also be helpful for decreasing the possibility of inducing bacterial resistance during farm animal production.Although intensively studied, few works had looked into S. pennellii's ability to cope with water-deficit conditions from a breeding point of view. In this study, we assessed potential traits of S. pennellii, that had previously been linked to high yields in other plant species, under long-term water-limited conditions and made a parallel with plant yield. For this purpose, the drought-resistant tomato genotypes IL 3-5 and IL 10-1, and the drought-sensitive IL 2-5 and IL 7-1 at seed level, together with both parents the S. pennellii accession LA 716 and the cultivar M82 were kept at 50 and 100% ASW throughout the growing season. Our findings confirm the superiority of LA 716 under water-limited conditions compared to the other S. lycopersicum genotypes in terms of plant water status maintenance. Percentual reduction on plant yield was higher in IL 3-5 and IL 10-1 than in M82 plants, indicating no correlation between drought resistance on germination and plant productive stages. A strong positive correlation was found between fruit yield and A, gs, and Ψleaf at 50% ASW, suggesting these traits as important selection criteria. LT and gmin, LA 716's most promising traits, did not show a linear correlation with fruit yield under low water regimes. This study unravels traits behind tomato performance under water-limited conditions and should work as guidance for breeders aiming at developing drought-resistant tomato cultivars.Marine oil spills and the resulting environmental contamination is common along coastal areas; however, information is lacking about the safety of impacted beaches for public use, especially for the most vulnerable population children. One route of exposure for children at oil impacted beaches is through contact with sands. selleck products of this study was to evaluate beach sand skin adherence for children under the age of seven. Each of 122 children participated in a hand press trial conducted at one of four different U.S. beaches (two in Miami, FL, and two in Galveston, TX USA). During the hand press trials, hand conditions of the children were randomized (dry, wet, or with sunscreen), and soil adherence (mass of sand per palmar surface area of the hand) and the maximum pressure applied (force applied per area of hand) was measured and calculated. Each child was instructed to press their hands on a soil laden tray for 5 s and pressure of contact was measured using a scale. Results (n = 98) showed that the average soil adherence for both palmar hands across the four beaches ranged from 0.200 to 234 mg/cm2 with an average of 35.7 mg/cm2, with boys (40.4 mg/cm2) showing slightly higher means than girls (31.7 mg/cm2), but these differences were not significant even after adjusting for age. Among the three conditions evaluated, the highest loading was measured for children with wet hands (mean 65.3 mg/cm2), followed by dry hands (mean 24.5 mg/cm2). Sunscreen hands (mean 23.2 mg/cm2) had the lowest loadings. The pressure of contact ranged from 0.180 to 1.69 psi and varied by age groups and by height and weight, where pressure of contact did not have a significant influence on soil adherence. The average adhered sand grain size and average ambient sand grain size both had a statistically significant impact on hand soil adherence. #link# Overall results from this study can be utilized in exposure and risk assessment models to evaluate the possible health impacts from contaminants found in beach sands.Enhancing nitrogen fertilization efficiency for improving yield is a major challenge for smallholder farming systems. Rapid and cost-effective methodologies with the capability to assess the effects of fertilization are required to facilitate smallholder farm management. This study compares maize leaf and canopy-based approaches for assessing N fertilization performance under different tillage, residue coverage and top-dressing conditions in Zimbabwe. Among the measurements made on individual leaves, chlorophyll readings were the best indicators for both N content in leaves (R  less then  0.700) and grain yield (GY) (R  less then  0.800). Canopy indices reported even higher correlation coefficients when assessing GY, especially those based on the measurements of the vegetation density as the green area indices (R  less then  0.850). Canopy measurements from both ground and aerial platforms performed very similar, but indices assessed from the UAV performed best in capturing the most relevant information from the whole plot and correlations with GY and leaf N content were slightly higher. Leaf-based measurements demonstrated utility in monitoring N leaf content, though canopy measurements outperformed the leaf readings in assessing GY parameters, while providing the additional value derived from the affordability and easiness of using a pheno-pole system or the high-throughput capacities of the UAVs.Ancient DNA studies provide genomic information about the origins, population structures, and physical characteristics of ancient humans that cannot be solely examined by archeological studies. The DNAs extracted from ancient human bones, teeth, or tissues are often contaminated with coexisting bacterial and viral genomes that contain DNA from ancient microbes infecting those of ancient humans. Information on ancient viral genomes is useful in making inferences about the viral evolution. Here, we have utilized metagenomic sequencing data from the dental pulp of five Jomon individuals, who lived on the Japanese archipelago more than 3000 years ago; this is to detect ancient viral genomes. We conducted de novo assembly of the non-human reads where we have obtained 277,387 contigs that were longer than 1000 bp. These contigs were subjected to homology searches against a collection of modern viral genome sequences. We were able to detect eleven putative ancient viral genomes. Among them, we reconstructed the complete sequence of the Siphovirus contig89 (CT89) viral genome. The Jomon CT89-like sequence was determined to contain 59 open reading frames, among which five genes known to encode phage proteins were under strong purifying selection. The host of CT89 was predicted to be Schaalia meyeri, a bacterium residing in the human oral cavity. Finally, the CT89 phylogenetic tree showed two clusters, from both of which the Jomon sequence was separated. Our results suggest that metagenomic information from the dental pulp of the Jomon people is essential in retrieving ancient viral genomes used to examine their evolution.The urbanization process systematically leads to the loss of biodiversity. Only certain arthropods are resilient to the urbanization process and can thrive in the novel conditions of urbanized landscapes. However, the degree to which arthropod communities survive in urban habitats depends on landscape and local effects and biological interactions (e.g., trophic interactions). link2 In the present study, we examined the relative importance of various factors at landscape (isolation, edge density and area of surrounding greenery) and local (size of park, canopy cover, understory vegetation cover, defoliation depth, weight of dried leaves, soil temperature, soil moisture, and soil pH) spatial scales on the diversity of ants, beetles and spiders in urban parks. Our results indicated that park edge density was negatively correlated with diversity metrics in ants, beetles, and spiders in urban parks relative to the degree of proximity with the peri-urban forest. In other words, parks that located adjacent to the peri-urban forest may not necessarily have high biodiversity. The results suggested that man-made structures have been effective dispersal barriers that limit the spillover effects of ants and spiders but not the spillover of comparatively strong fliers, such as beetles. However, the area of surrounding greenery may have facilitated the colonization of forest-dependent taxa in distant parks. link3 Large parks with reduced edge density supported a higher arthropod diversity because of the minimal edge effect and increased habitat heterogeneity. Vegetation structure consistently explained the variability of ants, beetles, and spiders, indicating that understory plant litter is crucial for providing shelters and hibernation, oviposition, and foraging sites for the major taxa in urban parks. Therefore, efforts should focus on the local management of ground features to maximize the conservation of biological control in urban landscapes.