Background: The Arctic and Antarctic are the two most geographically distant bioregions on earth. Recent sampling efforts and following metagenomics have shed light on the global ocean microbial diversity and function, yet the microbiota of polar regions has not been included in such global analyses.Results: Here a metagenomic study of seawater samples (n= 60) collected from different depths at 28 locations in the Arctic and Antarctic zones was performed, together with metagenomes from theTaraOceans. More than 7500 (19%) polar seawater-derived operational taxonomic units could not be identified in theTaraOceans datasets, and more than 3,900,000 protein-coding gene orthologs had no hits in the Ocean Microbial Reference Gene Catalog. Analysis of 214 metagenome assembled genomes (MAGs) recovered from the polar seawater microbiomes, revealed strains that are prevalent in the polar regions while nearly undetectable in temperate seawater. Metabolic pathway reconstruction for these microbes suggested versatility for saccharide and lipids biosynthesis, nitrate and sulfate reduction, and CO₂fixation. Comparison between the Arctic and Antarctic microbiomes revealed that antibiotic resistance genes were enriched in the Arctic while functions like DNA recombination were enriched in the Antarctic.Conclusions: Our data highlight the occurrence of dominant and locally enriched microbes in the Arctic and Antarctic seawater with unique functional traits for environmental adaption, and provide a foundation for analyzing the global ocean microbiome in a more complete perspective.

Cervical cancer is a common and fatal malignancy of the female reproductive system. Human papillomavirus (HPV) is the primary causal agent for cervical cancer, but HPV infection alone is insufficient to cause the disease. Actually, most HPV infections are sub-clinical and cleared spontaneously by the host immune system; very few persist and eventually develop into cervical cancer. Therefore, other host or environmental alterations could also contribute to the malignant phenotype. One of the candidate co-factors is the β-catenin protein, a pivotal component of the Wnt/β-catenin signaling pathway. β-Catenin mainly implicates two major cellular activities: cell–cell adhesion and signal transduction. Recent studies have indicated that an imbalance in the structural and signaling properties of β-catenin leads to various cancers, such as cervical cancer. In this review, we will systematically summarize the role of β-catenin in cervical cancer and provide new insights into therapeutic strategies.

We have previously shown that ASK1 undergoes ubiquitination and degradation in resting endothelial cells (EC) and that proinflammatory cytokine tumor necrosis factor (TNF) induces deubiquitination and stabilization, leading to ASK1 activation. However, the mechanism for the regulation of ASK1 stability is not known. In the present study, we have shown that SOCS1, a member of suppressor of cytokine signaling, induces ASK1 degradation. SOCS1 was constitutively expressed in EC and formed a labile complex with ASK1 that can be stabilized by proteasomal inhibitors. The phosphotyrosine-binding SH2 domain of SOCS1 was critical for its association with ASK1. Thus a SOCS1 mutant defective in phosphotyrosine binding failed to bind to and induce ASK1 degradation. Phosphotyrosine of ASK1 was induced in response to growth factors, and TNF induced dephosphorylation and dissociation of ASK1 from SOCS1. ASK1 with a mutation at Tyr-718 diminished the binding to SOCS1, suggesting that the phosphotyrosine-718 of ASK1 is critical for SOCS1 binding. Moreover, ASK1 expression and activity were up-regulated in SOCS1-deficient mice and derived EC, resulting in enhanced TNF-induced activation of JNK, expression of proinflammatory molecules, and apoptotic responses. We concluded that SOCS1 functions as a negative regulator in TNF-induced inflammation in EC, in part, by inducing ASK1 degradation.

Organelles form tight connections through membrane contact sites, thereby cooperating to regulate homeostasis and cell function. Among them, the contact between endoplasmic reticulum (ER), the main intracellular calcium storage organelles, and mitochondria has been recognized for decades, and its main roles in the ion and lipid transport, ROS signaling, membrane dynamic changes and cellular metabolism are basically determined. At present, many tumor chemotherapeutic drugs rely on ER-mitochondrial calcium signal to function, but the mechanism of targeting resident molecules at the mitochondria-associated endoplasmic reticulum membranes (MAM) to sensitize traditional chemotherapy and the new tumor therapeutic targets identified based on the signal pathways on the MAM have not been thoroughly discussed. In this review, we highlight the key roles of various signaling pathways at the ER-mitochondria contact site in tumorigenesis and focus on novel anticancer therapy strategies targeting potential targets at this contact site.

Cervical cancer (CC) is the second most common malignant cancer in women. CC is difficult to diagnose, has a high recurrence rate, and is resistant to systemic therapies; as a result, CC patients have a relatively poor prognosis. One potential link to CC is the Wnt signaling pathway and its downstream effectors, which regulate cell differentiation, proliferation, migration, and fate. The aberrant activation of Wnt signaling is associated with various cancers, including CC. Recent studies have shown that activating or inhibiting the intracellular signal transduction in this pathway can regulate cancer cell growth and viability. This review will summarize the experimental evidence supporting the significance of the Wnt signaling pathway in CC, and will also discuss the current clinical role of Wnt signaling in CC diagnosis, therapy, and prognosis.

Marine microbial eukaryotes are ubiquitous, comprised of phylogenetically diverse groups and play key roles in microbial food webs and global biogeochemical cycling. However, their vertical distribution in the deep sea has received little attention. In this study, we investigated the composition and diversity of the eukaryotes of both 0.2–3 μm and >3 μm size fractions from the surface to the hadal zone (8727 m) of the Mariana Trench using Illumina MiSeq sequencing for the 18S rDNA. The microbial eukaryotic community structure differed substantially across size fractions and depths. Operational taxonomic unit (OTU) richness in the >3 μm fraction was higher than that in the 0.2–3 μm fraction at the same depth. For the 0.2–3 μm fraction, sequences of Retaria (Rhizaria) were most abundant in the surface water (53.5%). Chrysophyceae (Stramenopiles) sequences dominated mostly in the samples from water depths below 1795 m. For the >3 μm fraction, sequences of Dinophyceae (Alveolata) were most abundant in surface waters (49.3%) and remained a significant proportion of total sequences at greater depths (9.8%, on average). Retaria sequences were abundant in samples of depths ≥1000 m. Amoebozoa and Apusozoa sequences were enriched in the hadal sample, comprising 38 and 20.4% of total sequences, respectively. Fungi (Opisthokonta) sequences were most abundant at 1759 m in both size fractions. Strong positive associations were found between Syndiniales (mainly MALV-I and MALV-II) and Retaria while negative associations were shown between MALV-II and Fungi in a co-occurrence analysis. This study compared the community structure of microbial eukaryotes in different zones in the deep sea and identified a distinct hadal community in the larger size fraction, suggesting the uniqueness of the eukaryotes in the biosphere in the Mariana Trench.