Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (i.r.) SIVmac239, intravenous (i.v.) SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL) peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.)-infected than in SIVmac251 (i.v.)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.)-infected than in SIVmac251 (i.v.)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v.) than in those infected with SIVmac251 (i.v.), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies

Photoluminescence Sensing of Chloride Ions in Sea Sand Using Alcohol-Dispersed CsPbBr3@SiO2 Perovskite Nanocrystal Composites

In this study, CsPbBr3@SiO2 perovskite nanocrystal composites (CsPbBr3@SiO2 PNCCs) were synthesized by a benzyl bromide nucleophilic substitution strategy. Homogeneous halide exchange between CsPbBr3@SiO2 PNCCs and Cl− solution (aqueous phase) was applied to the determination of Cl− in sea sand samples. Fast halide exchange with Cl− in the aqueous phase without any magnetic stirring or pH regulation resulted in the blue shift of the photoluminescence (PL) wavelength and vivid PL color changes from green to blue. The results show that the PL sensing of Cl− in aqueous samples could be implemented by using the halide exchange of CsPbBr3@SiO2 PNCCs. A linear relationship between the PL wavelength shift and the Cl− concentration in the range of 0 to 3.0% was found, which was applied to the determination of Cl− concentration in sea sand samples. This method greatly simplifies the detection process and provides a new idea for further broadening PL sensing using the CsPbBr3 PNC halide

Photoluminescence Sensing of Chloride Ions in Sea Sand Using Alcohol-Dispersed CsPbBr₃@SiO₂ Perovskite Nanocrystal Composites

In this study, CsPbBr3@SiO2 perovskite nanocrystal composites (CsPbBr3@SiO2 PNCCs) were synthesized by a benzyl bromide nucleophilic substitution strategy. Homogeneous halide exchange between CsPbBr3@SiO2 PNCCs and Cl− solution (aqueous phase) was applied to the determination of Cl− in sea sand samples. Fast halide exchange with Cl− in the aqueous phase without any magnetic stirring or pH regulation resulted in the blue shift of the photoluminescence (PL) wavelength and vivid PL color changes from green to blue. The results show that the PL sensing of Cl− in aqueous samples could be implemented by using the halide exchange of CsPbBr3@SiO2 PNCCs. A linear relationship between the PL wavelength shift and the Cl− concentration in the range of 0 to 3.0% was found, which was applied to the determination of Cl− concentration in sea sand samples. This method greatly simplifies the detection process and provides a new idea for further broadening PL sensing using the CsPbBr3 PNC halide

The complete chloroplast genome and phylogenetic analysis of Bupleurum yinchowense Shan & Yin Li

Bupleurum yinchowense Shan & Yin Li was first described as a new Bupleurum species in 1974, but its classification status has always been disputed. Here, its complete chloroplast genome was provided to resolve this issue. The length of the B. yinchowense chloroplast genome is 155,851 bp and composed of two inverted repeats (IR: 26,307 bp), a large single-copy region (LSC: 85,625 bp), and a small single-copy region (SSC: 17,612 bp). The overall GC content is 37.6%. The chloroplast genome consists of 113 genes, including 79 protein-coding genes, four rRNA genes, and 30 tRNA genes. Phylogenetic analysis suggested that Bupleurum yinchowense holds a distinct phylogenetic position and can be considered as an accepted species

The IDH1 Mutation-Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA Methylation and Expression of PD-L1 in Gliomas

Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas.Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed.Results: The results demonstrate that when compared with IDH1-mutant tumors, IDH1 wildtype tumors represent an immunosuppression landscape and elevated levels of PD-L1 expression. DNA hypo-methylation of the PD-L1 gene, as well as high gene and protein expressions, were observed in the wildtype tumors. We also found that quantitative levels of IDH1 mutant proteins were positively associated with recurrence-free survival (RFS). A key product of the IDH1 mutation (2-hydroxyglutarate) was found to transiently increase DNA methylation and suppress PD-L1 expression.Conclusions: IDH1 mutations impact the immune landscape of gliomas by affecting immune infiltrations and manipulating checkpoint ligand PD-L1 expression. Applications of immune checkpoint inhibitors may be beneficial for chemoradiation-insensitive IDH1-wildtype gliomas

Division of developmental phases of freshwater leech Whitmania pigra and key genes related to neurogenesis revealed by whole genome and transcriptome analysis

Abstract The freshwater leech Whitmania pigra (W. pigra) Whitman (Annelida phylum) is a model organism for neurodevelopmental studies. However, molecular biology research on its embryonic development is still scarce. Here, we described a series of developmental stages of the W. pigra embryos and defined five broad stages of embryogenesis: cleavage stages, blastocyst stage, gastrula stage, organogenesis and refinement, juvenile. We obtained a total of 239.64 Gb transcriptome data of eight representative developmental phases of embryos (from blastocyst stage to maturity), which was then assembled into 21,482 unigenes according to our reference genome sequenced by single-molecule real-time (SMRT) long-read sequencing. We found 3114 genes differentially expressed during the eight phases with phase-specific expression pattern. Using a comprehensive transcriptome dataset, we demonstrated that 57, 49 and 77 DEGs were respectively related to morphogenesis, signal pathways and neurogenesis. 49 DEGs related to signal pathways included 30 wnt genes, 14 notch genes, and 5 hedgehog genes. In particular, we found a cluster consisting of 7 genes related to signal pathways as well as synapses, which were essential for regulating embryonic development. Eight genes cooperatively participated in regulating neurogenesis. Our results reveal the whole picture of W. pigra development mechanism from the perspective of transcriptome and provide new clues for organogenesis and neurodevelopmental studies of Annelida species

CD4+ and Perivascular Foxp3+ T Cells in Glioma Correlate with Angiogenesis and Tumor Progression

BackgroundAngiogenesis and immune cell infiltration are key features of gliomas and their manipulation of the microenvironment, but their prognostic significance remains indeterminate. We evaluate the interconnection between tumor-infiltrating lymphocyte (TIL) and tumor blood-vasculatures in the context of glioma progression.MethodsPaired tumor tissues of 44 patients from three tumor-recurrent groups: diffuse astrocytomas (DA) recurred as DA, DA recurred as glioblastomas (GBM), and GBM recurred as GBM were evaluated by genetic analysis, immunohistochemistry for tumor blood vessel density, TIL subsets, and clinical outcomes. These cells were geographically divided into perivascular and intratumoral TILs. Associations were examined between these TILs, CD34+ tumor blood vessels, and clinical outcomes. To determine key changes in TIL subsets, microarray data of 15-paired tumors from patients who failed antiangiogenic therapy- bevacizumab, and 16-paired tumors from chemo-naïve recurrent GBM were also evaluated and compared.ResultsUpon recurrence in primary gliomas, similar kinetic changes were found between tumor blood vessels and each TIL subset in all groups, but only CD4+ including Foxp3+ TILs, positively correlated with the density of tumor blood vessels. CD4 was the predominant T cell population based on the expression of gene-transcripts in primary GBMs, and increased activated CD4+ T cells were revealed in Bevacizumab-resistant recurrent tumors (not in chemo-naïve recurrent tumors). Among these TILs, 2/3 of them were found in the perivascular niche; Foxp3+ T cells in these niches not only correlated with the tumor vessels but were also an independent predictor of shortened recurrence-free survival (RFS) (HR = 4.199, 95% CI 1.522–11.584, p = 0.006).ConclusionThe minimal intratumoral T cell infiltration and low detection of CD8 transcripts expression in primary GBMs can potentially limit antitumor response. CD4+ and perivascular Foxp3+ TILs associate with tumor angiogenesis and tumor progression in glioma patients. Our results suggest that combining antiangiogenic agents with immunotherapeutic approaches may help improve the antitumor efficacy for patients with malignant gliomas

Additional file 7 of Division of developmental phases of freshwater leech Whitmania pigra and key genes related to neurogenesis revealed by whole genome and transcriptome analysis

Additional file 7: Table S5. List of non coding RNA (miRNA, tRNA, rRNA, snRNA)

Additional file 10 of Division of developmental phases of freshwater leech Whitmania pigra and key genes related to neurogenesis revealed by whole genome and transcriptome analysis

Additional file 10: Table S8. RNA-Seq results of eight phases