Chromosome X-encoded Cancer/Testis antigens are less frequently expressed in non-seminomatous germ cell tumors than in seminomas

Cancer/Testis (CT) antigens are normally only expressed in germ cells and yet are aberrantly activated in a wide variety of human cancers. Most chromosome X-encoded CT antigens (CT-X) show restricted expression in pre-meiotic germ cells in adult testis, except for the expression of SPANX in post-meiotic germ cells. In the present study, the expression of eight CT-X antigens (MAGE-A, NY-ESO-1, GAGE, MAGE-C1/CT7, MAGE-C2/CT10, CT45, SAGE1, and SPANX) in non-seminomatous germ cell tumors was evaluated immunohistochemically, including 24 embryonal carcinomas, 20 yolk sac tumors, 9 teratomas, and 3 choriocarcinomas, and the results were compared to our previous study of 77 classic seminomas and 2 spermatocytic seminomas. SPANX was not detected in any germ cell tumors tested. Spermatocytic seminoma showed strong expression of all CT-X antigens tested (except SPANX), reflecting their origin from adult CT-Xpositive pre-meiotic germ cells. Classic seminomas, originating from prenatal gonocytes, showed widely variable frequency of CT-X antigen expression, ranging from > 80% (CT7, CT10, CT45, and GAGE), 63% (MAGE-A), 18% (NY-ESO-1) to only 4% (SAGE1). In comparison, non-seminomatous germ cell tumors expressed CT-X antigens much less frequently and usually only in small subsets of tumor cells. Intratubular germ cell neoplasia (ITGCN) were mostly CT-X-negative, even in CT-X positive classic seminomas. These findings indicate that CT-X antigens are not expressed in the fetal precursor cells for germ cell tumors, and their expression likely reflects germ cell differentiation of the neoplastic cells (in seminomas) or aberrant gene activation as cancer antigens (in non-seminomatous tumors)

Synthetic anthocyanidins and their antioxidant properties

Anthocyanidins were synthesized to study the effect of methoxy substitution on the B ring to their antioxidant property. Comparative FRAP studies show 2′- and 4′-methoxy substituents have higher antioxidant activities, which may be attributed to both resonance and inductive effects.Graphical abstract:Anthocyanidins as reducing agents Electronic supplementary material The online version of this article (doi:10.1186/s40064-015-1250-x) contains supplementary material, which is available to authorized users

The Effect of Altruistic Tendency on Fairness in Third-Party Punishment

Third-party punishment, as an altruistic behavior, was found to relate to inequity aversion in previous research. Previous researchers have found that altruistic tendencies, as an individual difference, can affect resource division. Here, using the event-related potential (ERP) technique and a third-party punishment of dictator game paradigm, we explored third-party punishments in high and low altruists and recorded their EEG data. Behavioral results showed high altruists (vs. low altruists) were more likely to punish the dictators in unfair offers. ERP results revealed that patterns of medial frontal negativity (MFN) were modulated by unfairness. For high altruists, high unfair offers (90:10) elicited a larger MFN than medium unfair offers (70:30) and fair offers (50:50). By contrast, for low altruists, fair offers elicited larger MFN while high unfair offers caused the minimal MFN. It is suggested that the altruistic tendency effect influences fairness consideration in the early stage of evaluation. Moreover, the results provide further neuroscience evidence for inequity aversion

The Effect of Altruistic Tendency on Fairness in Third-Party Punishment

Third-party punishment, as an altruistic behavior, was found to relate to inequity aversion in previous research. Previous researchers have found that altruistic tendencies, as an individual difference, can affect resource division. Here, using the event-related potential (ERP) technique and a third-party punishment of dictator game paradigm, we explored third-party punishments in high and low altruists and recorded their EEG data. Behavioral results showed high altruists (vs. low altruists) were more likely to punish the dictators in unfair offers. ERP results revealed that patterns of medial frontal negativity (MFN) were modulated by unfairness. For high altruists, high unfair offers (90:10) elicited a larger MFN than medium unfair offers (70:30) and fair offers (50:50). By contrast, for low altruists, fair offers elicited larger MFN while high unfair offers caused the minimal MFN. It is suggested that the altruistic tendency effect influences fairness consideration in the early stage of evaluation. Moreover, the results provide further neuroscience evidence for inequity aversion

Multiple Cancer/Testis Antigens Are Preferentially Expressed in Hormone-Receptor Negative and High-Grade Breast Cancers

BACKGROUND: Cancer/testis (CT) antigens are protein antigens normally expressed only in germ cells of testis, and yet are expressed in a proportion of a wide variety of human cancers. CT antigens can elicit spontaneous immune responses in cancer patients with CT-positive cancers, and CT antigen-based therapeutic cancer vaccine trials are ongoing for "CT-rich" tumors. Although some previous studies found breast cancer to be "CT-poor", our recent analysis identified increased CT mRNA transcripts in the ER-negative subset of breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed a comprehensive immunohistochemical study to investigate the protein expression of eight CT genes in 454 invasive ductal carcinomas, including 225 ER/PR/HER2-negative (triple-negative) carcinomas. We found significantly more frequent expression of all eight CT antigens in ER-negative cancers, and five of them--MAGEA, CT7, NY-ESO-1, CT10 and CT45, were expressed in 12-24% of ER-negative cancers, versus 2-6% of ER-positive cancers (p<0.001 to 0.003). In comparison, GAGE, SAGE1 and NXF2 were only expressed in 3-5% of ER-negative and 0-2% of ER-positive cancers. ER-negative cancers were also more likely to simultaneously co-express multiple CT antigens, with 27% (34/125) of ER-negative, CT-positive tumors expressing three or more CT antigens. HER2 status had no consistent effect on CT expression, and triple-negative carcinomas showed similar frequencies of MAGEA and NY-ESO-1 expression as ER-negative/HER2-positive carcinomas. More frequent CT expression was also found in tumors with higher nuclear grade (p<0.001 to p = 0.01) and larger in size (>2 cm). CONCLUSIONS/SIGNIFICANCE: CT antigens are preferentially expressed in hormone receptor-negative and high-grade breast cancer. Considering the limited treatment options for ER/PR/HER2 triple-negative breast cancer, the potential of CT-based immunotherapy should be explored

Analysis of Major Aroma Compounds in Fermented and Prepared Hawthorn Wine

In this study, liquid-liquid extraction-solvent assisted flavor evaporation (LLE-SAFE), headspace solid phase microextraction extraction (HS-SPME), gas chromatography-quadrupole-mass spectrometry (GC-Quadrupole-MS), gas chromatography-orbitrap-mass spectrometry (GC-Orbitrap-MS) and gas chromatography-olfactometry (GC-O) were used in combination to identify the volatile components in a fermented hawthorn wine (SBL-J) and a prepared hawthorn wine (FS), and the results of sensory analysis, modified frequency (MF) and odor activity value (OAV) were used to determine the key aroma compounds. Totally 89 aroma compounds were identified by LLE-SAFE/GC-O-MS. In addition, 29 and 38 aroma compounds with MF values of more than 20% were found in SBL-J and FS, respectively. A total of 123 volatile components were detected by HS-SPME/GC-Quadrupole-MS and HS-SPME/GC-Orbitrap-MS and there were 29 and 33 aroma compounds with OAV of greater than 1 (0.1 for esters) identified in SBL-J and FS, respectively. 2-Methybutyl acetate, ethyl hexanoate, ethyl octanoate and phenylethyl alcohol were the key aroma compounds in the two samples. To our knowledge, 2-methybutyl acetate, ethyl isovalerate, (E,E)-2,4-hexadienoic acid ethyl ester and ethyl butyrate, were identified for the first time as the key aroma components of hawthorn wine

Comparative genomic analyses of Cutibacterium granulosum provide insights into genomic diversity

Cutibacterium granulosum, a commensal bacterium found on human skin, formerly known as Propionibacterium granulosum, rarely causes infections and is generally considered non-pathogenic. Recent research has revealed the transferability of the multidrug-resistant plasmid pTZC1 between C. granulosum and Cutibacterium acnes, the latter being an opportunistic pathogen in surgical site infections. However, there is a noticeable lack of research on the genome of C. granulosum, and the genetic landscape of this species remains largely uncharted. We investigated the genomic features and evolutionary structure of C. granulosum by analyzing a total of 30 Metagenome-Assembled Genomes (MAGs) and isolate genomes retrieved from public databases, as well as those generated in this study. A pan-genome of 6,077 genes was identified for C. granulosum. Remarkably, the ‘cloud genes’ constituted 62.38% of the pan-genome. Genes associated with mobilome: prophages, transposons [X], defense mechanisms [V] and replication, recombination and repair [L] were enriched in the cloud genome. Phylogenomic analysis revealed two distinct mono-clades, highlighting the genomic diversity of C. granulosum. The genomic diversity was further confirmed by the distribution of Average Nucleotide Identity (ANI) values. The functional profiles analysis of C. granulosum unveiled a wide range of potential Antibiotic Resistance Genes (ARGs) and virulence factors, suggesting its potential tolerance to various environmental challenges. Subtype I-E of the CRISPR-Cas system was the most abundant in these genomes, a feature also detected in C. acnes genomes. Given the widespread distribution of C. granulosum strains within skin microbiome, our findings make a substantial contribution to our broader understanding of the genetic diversity, which may open new avenues for investigating the mechanisms and treatment of conditions such as acne vulgaris

Claudin-2 enhances human antibody-mediated complement-dependent cytotoxicity of porcine endothelial cells by modulating antibody binding and complement activation

BackgroundImmune rejection represents a significant barrier to transplantation, especially in the context of xenotransplantation. Endothelial cells (ECs) derived from pigs serve as the initial barrier against the human immune system in xenotransplantation. Tight junction proteins are essential components of endothelial cell tight junctions; however, their role in xenotransplantation has been less thoroughly investigated. Claudin-2, a key tight junction protein, was investigated here for its role in human antibody-mediated complement-dependent cytotoxicity (CDC).MethodsUsing an in vitro model of human antibody-mediated CDC, we assessed the effect of Claudin-2 on porcine aortic endothelial cells (PAECs) and porcine iliac endothelial cells (PIECs). Claudin-2 expression was either knocked down or overexpressed in these cells. A flow cytometry assay was used to evaluate C3c, C9, and the C5b-9 deposition, as well as the extent of human IgM and IgG binding to PIECs. The mRNA levels of complement regulators (CD46, CD55, CD59, Factor H, Factor I) were quantified by real-time PCR.ResultsThe loss of Claudin-2 protected PAECs and PIECs from human antibody-mediated CDC, while the overexpression of Claudin-2 enhanced the cytotoxicity in PAECs and PIECs within the same model. Unexpectedly, the loss or overexpression of Claudin-2 did not influence the mRNA expression levels of complement regulators (CD46, CD55, CD59, Factor H, and Factor I). Importantly, the loss of Claudin-2 significantly decreased the deposition of the C5b-9 complex, commonly referred to as the membrane attack complex (MAC), whereas the overexpression of Claudin-2 enhanced the deposition of the C5b-9 complex, indicating that Claudin-2 facilitates complement activation. Furthermore, the loss of Claudin-2 resulted in a decrease in the deposition of C3c and C9 on PIECs. Moreover, Claudin-2 enhanced human antibody binding to porcine ECs, as evidenced by increased IgG and IgM binding.ConclusionOur findings indicate that Claudin-2 enhances the cytotoxicity of porcine ECs through modulating antibody binding and complement activation. The deficient of Claudin-2 in genetically modified pigs is likely to protect porcine ECs and enhance xenograft survival in pig-to-human organ or tissue xenotransplantation

Expression and characterization of SARS-CoV-2 spike protein in Thermothelomyces heterothallica C1

The COVID-19 pandemic demonstrated a pressing need for rapid, adaptive, and scalable manufacturing of vaccines and reagents. With the transition into an endemic disease and rising threats of other emerging pandemics, production of these biologicals requires a stable and sustainable supply chain and accessible distribution methods. In this study, we demonstrate the strength of an engineered filamentous fungal platform, Thermothelomyces heterothallica C1, for high volumetric productivity of the full-length spike glycoprotein. Spike protein produced in this system is highly thermostable and immunization of mice with spike made in C1 or mammalian platforms resulted in a similar humoral response. Additionally, it was shown that the native N-glycan profile can be redecorated with complex sialylated structures, if necessary, resulting in a more human-like glycan profile, without impacting binding characteristics as shown experimentally and in simulations. Through extensive physicochemical analysis, the C1-produced spike performs similarly to spike proteins produced in other commercially available systems. The data presented is evidence that C1 can be a strong platform for production of complex glycosylated recombinant proteins such as subunit antigen vaccines