Gender Gaps in the Measurement of Public Opinion About Homosexuality in Cross-national Surveys: A Question-Wording Experiment

Measures of attitudes towards homosexuality in cross-national studies have received criticism for not being ‘gender-sensitive’. The current study used a split-ballot design allowing for separate analyses of the attitudes towards ‘gay men and lesbian women’, ‘gay men’, and ‘lesbian women’ in a pooled sample of 3,381 participants from Great Britain, Hungary, and Portugal. Analyses controlling for sociodemographics showed that differences in attitudes towards male and female targets were generally small and did not interact with the gender of the rater. In addition, results showed that men’s attitudes towards homosexuality were more strongly related to their gender ideology than women’s attitudes. Implications of these findings for cross-national studies measuring attitudes towards homosexuality are discussed

Additional file 1: Figure S1. of DectICO: an alignment-free supervised metagenomic classification method based on feature extraction and dynamic selection

Comparisons of classification performance between DectICO and the unsupervised alignment-free metagenomic clustering methods. Table S2. The information of the three collections of metagenomes. Table S3. The sizes of the training and testing sets for three collections of metagenomes used in our stability test and generality test. Figure S2. Comparisons of classification performances between DectICO and the non-dynamic feature-selection-based method on the T2D dataset. Figure S3. Comparisons of classification performances between DectICO and RSVM that based on the ICO on the asthma and T2D datasets. Table S4. Comparisons of the stability (from stability test) and generality (from generality test) between DectICO and the RSVM that with the ICO on asthma dataset. Table S5. Comparisons of the stability (from stability test) and generality (from generality test) between DectICO and the RSVM that with the ICO on T2D dataset. Table S6. The runtime of calculation for the feature vectors of ICO based on three kinds of metagenomic samples and 1 Mbp contig. Table S7. The consumed RAM of calculation for the feature vectors of ICO based on three kinds of metagenomic samples. Table S8. The runtime of classification process with varying rounds of feature selection and different numbers of samples in training set on the T2D metagenomes. Table S9. The consumed RAM of classification process with varying rounds of feature selection and different numbers of samples in training set on the T2D metagenomes. Table S10. The ICO vector dimension for different length oligonucleotides. (DOCX 76 kb

Additional file 2: Table S1. of DectICO: an alignment-free supervised metagenomic classification method based on feature extraction and dynamic selection

The difference of the LOOCV accuracy between DectICO and the-sequence-composition-based method for each classifier. (XLSX 13 kb

Ormosianines A–P, Structurally Diverse Quinolizidine Alkaloids with AChE Inhibitory Effects from <i>Ormosia yunnanensis</i>

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A–P (1–16), and 18 known congeners (17–34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27–29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 μM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480

Discovery of Novel and Potent Prolyl Hydroxylase Domain-Containing Protein (PHD) Inhibitors for The Treatment of Anemia

Stabilization of hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase domain enzymes (PHDs) represents a breakthrough in treating anemia associated with chronic kidney disease. Here, we identified a novel scaffold for noncarboxylic PHD inhibitors by utilizing structure-based drug design (SBDD) and generative models. Iterative optimization of potency and solubility resulted in compound 15 which potently inhibits PHD thus stabilizing HIF-α in vitro. X-ray cocrystal structure confirmed the binding model was distinct from previously reported carboxylic acid PHD inhibitors by pushing away the R383 and Y303 residues resulting in a larger inner subpocket. Furthermore, compound 15 demonstrated a favorable in vitro/in vivo absorption, distribution, metabolism, and excretion (ADME) profile, low drug–drug interaction risk, and clean early safety profiling. Functionally, oral administration of compound 15 at 10 mg/kg every day (QD) mitigated anemia in a 5/6 nephrectomy rat disease model

Discovery of Novel and Potent Prolyl Hydroxylase Domain-Containing Protein (PHD) Inhibitors for The Treatment of Anemia

Stabilization of hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase domain enzymes (PHDs) represents a breakthrough in treating anemia associated with chronic kidney disease. Here, we identified a novel scaffold for noncarboxylic PHD inhibitors by utilizing structure-based drug design (SBDD) and generative models. Iterative optimization of potency and solubility resulted in compound 15 which potently inhibits PHD thus stabilizing HIF-α in vitro. X-ray cocrystal structure confirmed the binding model was distinct from previously reported carboxylic acid PHD inhibitors by pushing away the R383 and Y303 residues resulting in a larger inner subpocket. Furthermore, compound 15 demonstrated a favorable in vitro/in vivo absorption, distribution, metabolism, and excretion (ADME) profile, low drug–drug interaction risk, and clean early safety profiling. Functionally, oral administration of compound 15 at 10 mg/kg every day (QD) mitigated anemia in a 5/6 nephrectomy rat disease model

Transcriptomic Characterization of Hepatocellular Carcinoma with <i>CTNNB1</i> Mutation

<div><p>Purpose</p><p>Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. HCC is a particularly serious threat to the Chinese population. Although many molecular alterations are known to be involved in the tumorigenesis of hepatocytes, no systemic survey has examined the somatic mutations in HCC samples from Chinese patients. Our goal was to elucidate somatic mutations in Chinese HCC patients and investigate the possible molecular mechanisms involved in tumorigenesis.</p><p>Experimental Design</p><p>A total of 110 hepatitis B virus (HBV)-positive HCC samples and 46 HBV-negative HCC samples were genotyped for hot-spot mutations in the <i>CSF1R</i>, <i>CTNNB1</i>, <i>KRAS</i>, <i>BRAF</i>, <i>NRAS</i>, <i>ERBB2</i>, <i>MET</i>, <i>PIK3CA</i>, <i>JAK1</i>, and <i>SMO</i> genes. The transcriptomes of the <i><u>C</u>TNNB1</i> mutation-positive HCC samples from the H<u>B</u>V-positive patients (CB+ HCC) were compared to adjacent non-cancerous livers, and significantly altered genes were functionally validated <i>in vitro</i>.</p><p>Results</p><p><i>CTNNB1</i> mutations accounted for the majority of the mutations detected in our study. A slightly higher mutation rate was found in the HBV-positive patients than in their negative counterparts. A distinct pattern of <i>CTNNB1</i> mutation was detected in these two populations, and drastic changes at the transcriptomic level were detected in the CB+ tumors compared to adjacent non-cancerous livers. Potential tumor suppressors (FoxA3 and Onecut1) and oncogenes (MAFG and SSX1) were functionally validated.</p><p>Conclusions</p><p>Our work is the first systemic characterization of oncogenic mutations in HCC samples from Chinese patients. Targeting the Wnt-β-catenin pathway may represent a valid treatment option for Chinese HCC patients. Our work also suggests that targeting ONECUT1, FOXA3, SSX1, and MAFG may be a valid treatment option for CTNNB1 mutation positive HCC patients.</p></div

Statistical analysis of mutational information in the Chinese HCC patients.

<p>A: <i>CTNNB1</i> mutation is the predominant mutagenic event. Of the 156 samples assessed, 15 cases (9.6%) were found to have <i>CTNNB1</i> mutations. 14 cases (8.97%) had CTNNB1 mutation only, one case (0.64%) harbored CTNNB1 mutation and SMO (K575M) mutation, and one case (0.64%) had a KRAS (G12D) mutation. B: All of the mutations in CTNNB1 were clustered within the N-terminal region; five cases exhibited the T41A mutation, whereas three cases had the S37C mutation. The G34E and S45P mutations were found in two cases each, and the G34V, D32Y and D32G mutations were detected in only one case each in this study.</p

Characteristics of HCC patients.

<p>Characteristics of HCC patients.</p

<i>CTNNB1</i> mutation-positive patients have a better prognosis.

<p>Statistical analysis of 110 HBV-positive patients and 46 HBV-negative HCC patients showed that the <i>CTNNB1</i> mutation-positive patients have a longer survival time; Difference was not significant.</p