TMEM100 Modulates TGF-β Signaling Pathway to Inhibit Colorectal Cancer Progression

Objectives. This study investigated the functional mechanism of transmembrane protein 100 (TMEM100) as a tumor inhibitor gene in CRC cells and offered a reference for the treatment of CRC. Methods. The mRNA expression data of CRC were acquired from the TCGA database to mine differentially expressed mRNAs. The role of TMEM100 in the progression of CRC cells was evaluated by MTT, colony formation, scratch healing, and Transwell assays. The influence of TMEM100 on the TGF-β signaling pathway was detected by western blot. Results. TMEM100 was markedly lowly expressed in CRC. CRC cell growth was significantly suppressed by overexpressing TMEM100 but noticeably facilitated by silencing TMEM100. Overexpression of TMEM100 inhibited the activation of the TGF-β signaling pathway, thus inhibiting malignant progression of CRC. Conclusion. TMEM100 is lowly expressed in CRC, which can suppress CRC cell growth by regulating the TGF-β signaling pathway.

Longer or shorter spines: Reciprocal trait evolution in stickleback via triallelic regulatory changes in Stanniocalcin2a

Vertebrates have repeatedly modified skeletal structures to adapt to their environments. The threespine stickleback is an excellent system for studying skeletal modifications, as different wild populations have either increased or decreased the lengths of their prominent dorsal and pelvic spines in different freshwater environments. Here we identify a regulatory locus that has a major morphological effect on the length of stickleback dorsal and pelvic spines, which we term Maser (major spine enhancer). Maser maps in a closely linked supergene complex that controls multiple armor, feeding, and behavioral traits on chromosome IV. Natural alleles in Maser are differentiated between marine and freshwater sticklebacks; however, alleles found among freshwater populations are also differentiated, with distinct alleles found in short- and long-spined freshwater populations. The distinct freshwater alleles either increase or decrease expression of the bone growth inhibitor gene Stanniocalcin2a in developing spines, providing a simple genetic mechanism for either increasing or decreasing spine lengths in natural populations. Genomic surveys suggest many recurrently differentiated loci in sticklebacks are similarly specialized into three or more distinct alleles, providing multiple ancient standing variants in particular genes that may contribute to a range of phenotypes in different environments.

Influence of Activating and Inhibitory Killer Immunoglobulin-Like Receptors (KIR) genes on the recurrence rate of ocular toxoplasmosis in Brazil

BackgroundRecurrence is a hallmark of ocular toxoplasmosis (OT), and conditions that influence its occurrence remain a challenge. Natural killer cells (NK) are effectors cells whose primary function is the cytotoxic activity against many parasites, including Toxoplasma gondii. Among the NK cell receptors, immunoglobulin-like receptors (KIR) deserve attention due to their high polymorphism. This study aimed to analyze the influence of KIR gene polymorphism in the course of OT infection and its association with recurrences after an active episode.MethodsNinety-six patients from the Ophthalmologic Clinic of the National Institute of Infectology Evandro Chagas (INI/Fiocruz/RJ, Brazil) were followed for up to five years. After DNA extraction, genotyping of the patients was performed by PCR-SSO utilizing Luminex equipment for reading. During follow-up, 57.4% had a recurrence.ResultsWe identified 25 KIR genotypes and found a higher frequency of genotypes 1 (31.7%) with worldwide distribution. We note that the KIR2DL2 inhibitor gene and the gene activator KIR2DS2 were more frequent in patients without recurrence (P = 0.03 and P = 0.02, respectively). Additionally, we observed one activating gene, KIR2DS1, associated with more than four times faster progression to the development of recurrent ocular toxoplasmosis than individuals without this gene (aRR = 4.6, P = 0.04).ConclusionThe KIR2DL2 and KIR2DS2 are associated as possible protection markers and the KIR2DS1 acting as a possible susceptibility marker. Additionally, the lower proportion of activating genes observed in individuals with recurrence corroborating with the hypothesis that these individuals are more susceptible to ocular toxoplasmosis recurrence (OTR).

Cyclin-Dependent Kinase Inhibitor Gene TaICK1 acts as a Potential Contributor to Wheat Male Sterility induced by a Chemical Hybridizing Agent

Heterosis has been widely accepted as an effective strategy to increase yields in plant breeding. Notably, the chemical hybridization agent SQ-1 induces male sterility in wheat, representing a critical potential tool in hybrid seed production. However, the mechanisms underlying the male sterility induced by SQ-1 still remain poorly understood. In this study, a cyclin-dependent kinase inhibitor gene, TaICK1, which encodes a 229 amino acid protein, was identified as a potential contributor to male sterility in common wheat. The expression of TaICK1 was upregulated during the development of anthers in Xinong1376 wheat treated with SQ-1. Meanwhile, the seed setting rate was found to be significantly decreased in TaICK1 transgenic rice. Furthermore, we identified two cyclin proteins, TaCYCD2;1 and TaCYCD6;1, as interactors through yeast two-hybrid screening using TaICK1 as the bait, which were validated using bimolecular fluorescence complementation. Subcellular localization revealed that the proteins encoded by TaICK1, TaCYCD2;1, and TaCYCD6;1 were localized in the cell nucleus. The expression levels of TaCYCD2;1 and TaCYCD6;1 were lower in Xinong1376 treated with SQ-1. A further analysis demonstrated that the expression levels of OsCYCD2;1 and OsCYCD6;1 were lower in transgenic TaICK1 rice lines as well. Taken together, these results suggest that the upregulation of TaICK1, induced by SQ-1, may subsequently suppress the expression of TaCYCD2;1 and TaCYCD6;1 in anthers, resulting in male sterility. This study provides new insights into the understanding of SQ-1-induced wheat male sterility, as well as the developmental mechanisms of anthers.