Transcriptome profiling of colorectal tumors from patients with sepsis reveals an ethnic basis for viral infection risk and sepsis progression.

Mortality from cancer-associated sepsis varies by cancer site and host responses to sepsis are heterogenous. Native Hawaiians have the highest mortality risk from cancer-associated sepsis and colorectal cancer (CRC), even though they demonstrate lower CRC incidence compared to other ethnicities. We conducted a retrospective transcriptomic analysis of CRC tumors and adjacent non-tumor tissue from adult patients of Native Hawaiian and Japanese ethnicity who died from cancer-associated sepsis.

Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study.

Background: Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA).

Methods: Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60-65.

Serum micro-RNA Identifies Early Stage Colorectal Cancer in a Multi-Ethnic Population.

Objective: Certain microRNAs (miR) have been previously described to be dysregulated in cancers and can be detected in blood samples. Studies examining the utility of miRs for colon cancer screening have primarily been performed in ethnically homogeneous groups of patients, thus the performance of miRs in multiethnic populations is unknown.

Methods: Four miRs were selected that were shown to be aberrantly expressed in the blood or stool of patients with colorectal cancer (CRC) of various ethnicities.

Phospho-regulation of the Shugoshin - Condensin interaction at the centromere in budding yeast.

Correct bioriented attachment of sister chromatids to the mitotic spindle is essential for chromosome segregation. In budding yeast, the conserved protein shugoshin (Sgo1) contributes to biorientation by recruiting the protein phosphatase PP2A-Rts1 and the condensin complex to centromeres. Using peptide prints, we identified a Serine-Rich Motif (SRM) of Sgo1 that mediates the interaction with condensin and is essential for centromeric condensin recruitment and the establishment of biorientation.

Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice.

Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene () in mice ( or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes.

miR-192-5p Silencing by Genetic Aberrations Is a Key Event in Hepatocellular Carcinomas with Cancer Stem Cell Features.

Various cancer stem cell (CSC) biomarkers have been identified for hepatocellular carcinoma (HCC), but little is known about the implications of heterogeneity and shared molecular networks within the CSC population. Through miRNA profile analysis in an HCC cohort ( = 241) for five groups of CSC HCC tissues, i.e.

RNA sequencing-based analysis of the laying hen uterus revealed the novel genes and biological pathways involved in the eggshell biomineralization.

Eggshell is the outermost calcified covering of an egg that protects it from microbial invasion and physical damage, and is critical for egg quality. However, understanding of the genes/proteins and the biological pathways regulating the eggshell formation is still obscure. We hypothesized that the transcriptomic analysis of the chicken uteri using RNA-sequencing may reveal novel genes and biological pathways involved in the eggshell biomineralization.

Time Series miRNA-mRNA integrated analysis reveals critical miRNAs and targets in macrophage polarization.

Polarization of macrophages is regulated through complex signaling networks. Correlating miRNA and mRNA expression over time after macrophage polarization has not yet been investigated. We used paired RNA-Seq and miRNA-Seq experiments to measure the mRNA and miRNA expression in bone marrow-derived macrophages over a time-series of 8 hours.

Pan-Cancer Analyses Reveal Long Intergenic Non-Coding RNAs Relevant to Tumor Diagnosis, Subtyping and Prognosis.

Long intergenic noncoding RNAs (lincRNAs) are a relatively new class of non-coding RNAs that have the potential as cancer biomarkers. To seek a panel of lincRNAs as pan-cancer biomarkers, we have analyzed transcriptomes from over 3300 cancer samples with clinical information. Compared to mRNA, lincRNAs exhibit significantly higher tissue specificities that are then diminished in cancer tissues.

Sgo1 regulates both condensin and Ipl1/Aurora B to promote chromosome biorientation.

Correct chromosome segregation is essential in order to prevent aneuploidy. To segregate sister chromatids equally to daughter cells, the sisters must attach to microtubules emanating from opposite spindle poles. This so-called biorientation manifests itself by increased tension and conformational changes across kinetochores and pericentric chromatin.

Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells.

Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid counterparts. We found that whereas transcription levels reflect the chromosome copy number changes, the abundance of some proteins, such as subunits of protein complexes and protein kinases, is reduced toward diploid levels.

Defined subunit arrangement and rab interactions are required for functionality of the HOPS tethering complex.

Within the endomembrane system of eukaryotic cells, multisubunit tethering complexes together with their corresponding Rab-GTPases coordinate vesicle tethering and fusion. Here, we present evidence that two homologous hexameric tethering complexes, the endosomal CORVET (Class C core vacuole/endosome transport) and the vacuolar HOPS (homotypic vacuole fusion and protein sorting) complex, have similar subunit topologies. Both complexes contain two Rab-binding proteins at one end, and the Sec1/Munc18-like Vps33 at the opposite side, suggesting a model on membrane bridging via Rab-GTP and SNARE binding.

The CORVET subunit Vps8 cooperates with the Rab5 homolog Vps21 to induce clustering of late endosomal compartments.

Membrane tethering, the process of mediating the first contact between membranes destined for fusion, requires specialized multisubunit protein complexes and Rab GTPases. In the yeast endolysosomal system, the hexameric HOPS tethering complex cooperates with the Rab7 homolog Ypt7 to promote homotypic fusion at the vacuole, whereas the recently identified homologous CORVET complex acts at the level of late endosomes. Here, we have further functionally characterized the CORVET-specific subunit Vps8 and its relationship to the remaining subunits using an in vivo approach that allows the monitoring of late endosome biogenesis.

UVRAG reveals its second nature.

UVRAG, a known regulator of autophagosome formation, also promotes autophagosome maturation by recruiting the fusion machinery of the late endosome.

The CORVET tethering complex interacts with the yeast Rab5 homolog Vps21 and is involved in endo-lysosomal biogenesis.

The dynamic equilibrium between vesicle fission and fusion at Golgi, endosome, and vacuole/lysosome is critical for the maintenance of organelle identity. It depends, among others, on Rab GTPases and tethering factors, whose function and regulation are still unclear. We now show that transport among Golgi, endosome, and vacuole is controlled by two homologous tethering complexes, the previously identified HOPS complex at the vacuole and a novel endosomal tethering (CORVET) complex, which interacts with the Rab GTPase Vps21.

Rab cascades and tethering factors in the endomembrane system.

Rab GTPases are key proteins that determine organelle identity and operate at the center of fusion reactions. Like Ras, they act as switches that are connected to a diverse network of tethering factors, exchange factors and GTPase activating proteins. Recent studies suggest that Rabs are linked to each other via their effectors, thus coordinating protein transport in the endomembrane system.

Self-interaction of a SNARE transmembrane domain promotes the hemifusion-to-fusion transition.

SNARE proteins mediate intracellular fusion of eukaryotic membranes. Some SNAREs have previously been shown to dimerise via interaction of their transmembrane domains. However, the functional significance of these interactions had remained unclear.

The SNARE Ykt6 is released from yeast vacuoles during an early stage of fusion.

The farnesylated SNARE (N-ethylmaleimide-sensitive factor attachment protein receptor) Ykt6 mediates protein palmitoylation at the yeast vacuole by means of its amino-terminal longin domain. Ykt6 is localized equally to membranes and the cytosol, although it is unclear how this distribution is mediated. We now show that Ykt6 is released efficiently from vacuoles during an early stage of yeast vacuole fusion.