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Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system (CNS). CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory responses. Here, we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS diseases. Further, we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders. [ABSTRACT FROM AUTHOR]

The activation of microglia and the various substances they produce have been linked to the pathologic development of Parkinson's disease (PD), but the precise role of microglia in PD remains to be defined. The survival of microglia depends on colony-stimulating factor 1 receptor (CSF1R) signaling, and CSF1R inhibition results in rapid elimination of microglia in the central nervous system. Using a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, we showed that the depletion of microglia via the CSF1R inhibitor PLX3397 exacerbated the impairment of locomotor activities and the loss of dopaminergic neurons. Further, depletion of microglia augmented the production of inflammatory mediators and infiltration of leukocytes in the brain after MPTP exposure. Microglia depletion-induced aggravation of MPTP neurotoxicity was also seen in lymphocyte-deficient mice. In addition, the depletion of microglia did not affect the production of brain-derived neurotrophic factor, but it dramatically augmented the production of inflammatory mediators by astrocytes after MPTP treatment. Our findings suggest microglia play a protective role against MPTP-induced neuroinflammation and dopaminergic neurotoxicity. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. After ICH, the immediate infiltration of leukocytes and activation of microglia are accompanied by a rapid up-regulation of the 18-kDa translocator protein (TSPO). TSPO ligands have shown anti-inflammatory and neuroprotective properties in models of CNS injury. In this study, we determined the impact of a TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of ICH. TSPO was up-regulated in Iba1+ cells from brains of patients with ICH and in CD11b+CD45int cells from mice subjected to collagenase-induced ICH. Etifoxine significantly reduced neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In collagenase-induced ICH mice, the protection of etifoxine was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6 and TNF-α. Etifoxine improved blood-brain barrier integrity and diminished cell death. Notably, the protective effect of etifoxine was abolished in mice depleted of microglia by using a colony-stimulating factor 1 receptor inhibitor. These results indicate that the TSPO ligand etifoxine attenuates brain injury and inflammation after ICH. TSPO may be a viable therapeutic target that requires further investigations in ICH. [ABSTRACT FROM AUTHOR]

A biparental soybean population of 364 recombinant inbred lines (RILs) derived from Zhongdou 41 ( ZYD 02.878 was used to identify quantitative trait loci (QTL) associated with hundred-seed weight (100-SW), pod length (PL), and pod width (PW). 100-SW, PL, and PW showed moderate correlations among one another, and 100-SW was correlated most strongly with PW (0.64–0.74). Respectively 74, 70, 75 and 19 QTL accounting for 38.7%–78.8% of total phenotypic variance were identified by inclusive composite interval mapping, restricted two-stage multi-locus genome-wide association analysis, 3 variancecomponent multi-locus random-SNP-effect mixed linear model analysis, and conditional genome-wide association analysis. Of these QTL, 189 were novel, and 24 were detected by multiple methods. Six loci were associated with 100-SW, PL, and PW and may be pleiotropic loci. A total of 284 candidate genes were identified in colocalizing QTL regions, including the verified gene Seed thickness 1 (ST1). Eleven genes with functions involved in pectin biosynthesis, phytohormone, ubiquitin-protein, and photosynthesis pathways were prioritized by examining single nucleotide polymorphism (SNP) variation, calculating genetic differentiation index, and inquiring gene expression. The prediction accuracies of genomic selection (GS) for 100-SW, PL, and PW based on single trait-associated markers reached 0.82, 0.76, and 0.86 respectively, but selection index (SI)-assisted GS strategy did not increase GS efficiency and inclusion of trait-associated markers as fixed effects reduced prediction accuracy. These results shed light on the genetic basis of 100-SW, PL, and PW and provide GS models for these traits with potential application in breeding programs. [ABSTRACT FROM AUTHOR]

Microglia are the first responders to intracerebral hemorrhage, but their precise role in intracerebral hemorrhage remains to be defined. Microglia are the only type of brain cells expressing the colony-stimulating factor 1 receptor, a key regulator for myeloid lineage cells. Here, we determined the effects of a colony-stimulating factor 1 receptor inhibitor (PLX3397) on microglia and the outcome in the context of experimental mouse intracerebral hemorrhage. We show that PLX3397 effectively depleted microglia, and the depletion of microglia was sustained after intracerebral hemorrhage. Importantly, colony-stimulating factor 1 receptor inhibition attenuated neurodeficits and brain edema in two experimental models of intracerebral hemorrhage induced by injection of collagenase or autologous blood. The benefit of colony-stimulating factor 1 receptor inhibition was associated with reduced leukocyte infiltration in the brain and improved blood-brain barrier integrity after intracerebral hemorrhage, and each observation was independent of lesion size or hematoma volume. These results demonstrate that suppression of colony-stimulating factor 1 receptor signaling ablates microglia and confers protection after intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Drought is one of the primary abiotic stress factors affecting the yield, growth, and development of soybeans. In extreme cases, drought can reduce yield by more than 50%. The seedling stage is an important determinant of soybean growth: the number and vigor of seedlings will affect growth and yield at harvest. Therefore, it is important to study the drought resistance of soybean seedlings. In this study, a recombinant inbred line (RIL) population comprising 234 F6:10 lines (derived from Zhonghuang 35 - Jindou 21) and a panel of 259 soybean accessions was subjected to drought conditions to identify the effects on phenotypic traits under these conditions. Using a genetic map constructed by single nucleotide polymorphism (SNPs) markers, 18 quantitative trait loci (QTL) on 7 soybean chromosomes were identified in two environments. This included 9 QTL clusters identified in the RIL population. Fifty-three QTL were identified in 19 soybean chromosomes by genome-wide association analysis (GWAS) in the panel of accessions, including 69 significant SNPs (-log10 (P) - 3.97). A combination of the two populations revealed that two SNPs (-log10 (P) - 3.0) fell within two of the QTL (qPH7-4 and qPH7-6) confidence intervals. We not only re-located several previously reported drought-resistance genes in soybean and other crops but also identified several non-synonymous stress-related mutation site differences between the two parents, involving Glyma.07g093000, Glyma.07g093200, Glyma.07g094100 and Glyma.07g094200. One previously unreported new gene related to drought stress, Glyma.07g094200, was found by regional association analysis. The significant SNP CHR7-17619 (G/T) was within an exon of the Glyma.07g094200 gene. In the RIL population, the DSP value of the "T" allele of CHR7-17619 was significantly (P < 0.05) larger than the "G" allele in different environments. The results of our study lay the groundwork for cloning and molecular marker-assisted selection of droughtresistance genes in soybeans at the seedling stage. [ABSTRACT FROM AUTHOR]

Thiamphenicol and florfenicol are two phenicol antibiotics widely used in aquaculture and are ubiquitous as micropollutants in surface waters. The present study investigated their photodegradation kinetics, hydroxyl-radical (radical dotOH) oxidation reactivities and products. Firstly, the photolytic kinetics of the phenicols in pure water was studied as a function of initial concentrations (C0) under UV–vis irradiation (λ > 200 nm). It was found that the kinetics was influenced by C0. A linear plot of the pseudo-first-order rate constant vs C0 was observed with a negative slope. Secondly, the reaction between the phenicol antibiotics and radical dotOH was examined with a competition kinetic method under simulated solar irradiation (λ > 290 nm), which quantified their bimolecular reaction rate constants of (2.13 ± 0.02) × 109 M-1 s-1 and (1.82 ± 0.10) × 109 M-1 s-1 for thiamphenicol and florfenicol, respectively. Then the corresponding radical dotOH oxidated half-lives in sunlit surface waters were calculated to be 90.5–106.1 h. Some main intermediates were formed from the reaction, which suggested that the two phenicols underwent hydroxylation, oxygenation and dehydrogenation when radical dotOH existed. These results are of importance to assess the phenicol persistence in wastewater treatment and sunlit surface waters. [ABSTRACT FROM AUTHOR]