Two divergent haplogroups of a sacsin-like gene in Acropora corals

Reef-building corals are declining due to environmental changes. Sacsin is a member of the heat shock proteins and has been reported as a candidate protein associated with the stress response in Acropora corals. Recently, high nucleotide diversity and the persistence of two divergent haplogroups of sacsin-like genes in Acropora millepora have been reported. While it was not clear when the two haplogroups have split and whether the haplogroups have persisted in only A. millepora or the other lineages in the genus Acropora. In this study, we analyzed a genomic region containing a sacsin-like gene from Acropora and Montipora species. Higher nucleotide diversity in the sacsin-like gene compared with that of surrounding regions was also observed in A. digitifera. This nucleotide diversity is derived from two divergent haplogroups of a sacsin-like gene, which are present in at least three Acropora species. The origin of these two haplogroups can be traced back before the divergence of Acropora and Montipora (119 Ma). Although the link between exceptionally high genetic variation in sacsin-like genes and functional differences in sacsin-like proteins is not clear, the divergent haplogroups may respond differently to envionmental stressors and serve in the adaptive phsiological ecology of these keystone species.

Chromatin-Associated Protein Sugp2 Involved in mRNA Alternative Splicing During Mouse Spermatogenesis

Mammalian spermatogenesis is a highly ordered process that is determined by chromatin-associated moderators which still remain poorly understood. Through a multi-control group proteomics strategy, we confirmed that Sugp2 was a chromatin-associated candidate protein, and its signal arose along spermatogenesis. The expression results showed that Sugp2, which is mainly expressed in the testis, had two transcripts, encoding one protein. During spermatogenesis, Sugp2 was enriched in the nucleus of male germ cells. With the depletion of Sugp2 by CRISPER-Cas9 technology, we found that Sugp2 controlled a network of genes on metal ion and ATP binding, suggesting that alternative splicing regulation by Sugp2 is involved in cellular ion and energy metabolism during spermatogenesis, while it had a little effect on meiotic progression and male fertility. Collectively, these data demonstrated that, as a chromatin-associated protein, Sugp2 mediated the alternative splicing regulatory network during spermatogenesis.

Longitudinal association of the anti-inflammatory serum marker GDF-15 with serum IgA and IgG in apparently healthy children

Both the innate and adaptive immune responses are deregulated in individuals with obesity and are key drivers of its associated metabolic alterations. Although the anti-inflammatory growth differentiation factor 15 (GDF-15) is a candidate protein against obesity, its mechanisms regulating the immune responses are not fully cleared. We examined whether GDF-15 was related to serum immunoglobulins in a children’s cohort assessed longitudinally during childhood. Results showed that circulating GDF-15 positively associated with IgA (p < 0.002) and IgG (p < 0.001) levels and the IgA*IgG product (p < 0.001) in apparently healthy children at both baseline (age 9) and follow-up (age 13). The associations were readily observed in heavier children (those with BMI-SDS above the median) as well as in children with higher renal fat accumulation (those with renal fat-to-height ratio above the median) and remained significant after correcting for possible confounding variables. Serum GDF-15 levels accounted for up to 16% of the variance of follow-up IgG levels and up to 14% of the variance of follow-up IgA*IgG product. The longitudinal associations of the anti-inflammatory GDF-15 with IgA, IgG and the IgA*IgG product in children with higher BMI or higher renal fat accumulation suggest a role of GDF-15 in human obesity through the regulation of the immune adaptive system.

Transferrin Receptor (TFRC): A Potential Biomarker for The Diagnosis and Prognosis of Sepsis

Objective This study applies the data independent acquisition (DIA) technique combined with bioinformatics to identify differential proteins in sepsis patients and performed ELISA method to validate the candidate protein of clinical value, in an attempt to find new biomarkers for the diagnosis and prognosis of sepsis. Methods Blood samples from sepsis patients (Sepsis group, n = 50) and healthy individuals (NC group, n = 10) were collected from Affiliated Hospital of Southwest Medical University. Mass spectrometry analysis was designed for 22 sepsis samples (randomly selected) and 10 healthy controls by DIA method, and the obtained differential proteins were subjected to GO annotation, meta-analysis and survival analysis to identify the candidate biomarker protein. ELISA was applied to validate the protein expression in original cohorts. ROC curves based on ELISA data were plotted to discuss the diagnostic and prognostic performance of the candidate protein and several clinical indexes, including C-reactive protein (CRP), procalcitonin (PCT) and lactate (Lac). Results DIA data showed that there were 142 differential proteins in the Sepsis group versus the NC group, comprising 36 down-regulated and 106 up-regulated. GO annotation revealed that the differential proteins were significantly enriched in the biological functions involved in immune response, response to stress, inflammatory response, and cell activation. The top 11 proteins with the greatest difference were found according to the p-values in DIA (FUCO2, MGAT1, OAF, AACT, TFRC, CCL14, EXTL2, KLKB1, TETN,CRP,SAA1). Meta-analysis identified significant differential expression of TFRC in the NC versus Sepsis and in the Survival versus Non-survival groups based on GEO database. Survival analysis revealed that the low expression of TFRC indicated a higher survival rate in sepsis patients. ELISA found TFRC concentration in collected clinical samples were significant differential in the NC versus Sepsis and in the Survival versus Nonsurvival groups (p < 0.05). ROC curves gave an AUC of 0.790 for TFRC in distinguishing the normal individuals and sepsis patients, showing good diagnostic performance. Besides, the AUC for TFRC in distinguishing the survivors and deaths was 0.744, indicating good prognostic performance, which was superior to PCT, CRP and Lac. Conclusion This study identified TFRC through DIA, bioinformatics and ELISA analyses, which showed differential expression in sepsis patients as well as good diagnostic and prognostic value. TFRC is expected to be a potential biomarker for sepsis.

Plasma checkpoint protein 1 (Chk1) as a potential diagnostic biomarker for opisthorchiasis and cholangiocarcinoma

BACKGROUND: Patients infected with a parasite often develop opisthorchiasis viverrini, which often progresses into cholangiocarcinoma (CCA) due to the asymptomatic nature of the infection. Currently, there are no effective diagnostic methods for opisthorchiasis or cholangiocarcinoma. OBJECTIVE: The aim of this study was to identify the host-responsive protein that can be developed as a diagnostic biomarker of opisthorchiasis and cholangiocarcinoma. METHODS: Plasma samples were collected from non-OVCCA, OV, and CCA subjects, and the proteomes were investigated by LC-MS/MS. Venn diagrams and protein network prediction by STITCH were used to identify the potential biomarkers. The level of candidate protein, the plasma checkpoint protein 1 (Chk1), was measured by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: Chk1 was present in the center of the protein network analysis in both the OV and CCA groups. In addition, the plasma Chk1 levels were significantly increased in both groups (P< 0.05). The sensitivity of the opisthorchiasis viverrini and cholangiocarcinoma was 59.38% and 65.62%, respectively, while the specificity of both was 85.71%. CONCLUSION: Chk1 was identified by differential plasma proteomes and was increased in O. viverrini-infected and cholangiocarcinoma-derived plasma samples. Higher levels of plasma Chk1 levels may serve as a potential diagnostic biomarker for opisthorchiasis and cholangiocarcinoma.

The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis

Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.