Hypoxic regulation of RIOK3 is a major mechanism for cancer cell invasion and metastasis.

Hypoxia is a common feature of locally advanced breast cancers that is associated with increased metastasis and poorer survival. Stabilisation of hypoxia-inducible factor-1α (HIF1α) in tumours causes transcriptional changes in numerous genes that function at distinct stages of the metastatic cascade. We demonstrate that expression of RIOK3 (RIght Open reading frame kinase 3) was increased during hypoxic exposure in an HIF1α-dependent manner. RIOK3 was localised to distinct cytoplasmic aggregates in normoxic cells and underwent redistribution to the leading edge of the cell in hypoxia with a corresponding change in the organisation of the actin cytoskeleton. Depletion of RIOK3 expression caused MDA-MB-231 to become elongated and this morphological change was due to a loss of protraction at the trailing edge of the cell. This phenotypic change resulted in reduced cell migration in two-dimensional cultures and inhibition of cell invasion through three-dimensional extracellular matrix. Proteomic analysis identified interactions of RIOK3 with actin and several actin-binding factors including tropomyosins (TPM3 and TPM4) and tropomodulin 3. Depletion of RIOK3 in cells resulted in fewer and less organised actin filaments. Analysis of these filaments showed reduced association of TPM3, particularly during hypoxia, suggesting that RIOK3 regulates actin filament specialisation. RIOK3 depletion reduced the dissemination of MDA-MB-231 cells in both a zebrafish model of systemic metastasis and a mouse model of pulmonary metastasis. These findings demonstrate that RIOK3 is necessary for maintaining actin cytoskeletal organisation required for migration and invasion, biological processes that are necessary for hypoxia-driven metastasis

Bioinformatics and molecular modeling in glycobiology

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed

Factors that shape pregnant women's perceptions regarding the safety of cannabis use during pregnancy.

BACKGROUND: Cannabis use among pregnant women has increased. We surveyed pregnant women in rural Pennsylvania to examine cannabis use and opinions regarding its safety during pregnancy. We examined associations between challenges of pregnancy (e.g., exhaustion, pain, nausea) and cannabis use. METHODS: A cross-sectional survey was administered to a convenience sample of English-speaking pregnant women receiving prenatal care at Geisinger, May-June 2019. Principal component analysis (PCA) was used to construct three scores (overwhelmed/exhausted, happy/optimistic, and health worries) based on 10 questions regarding common experiences during pregnancy (e.g., nausea/vomiting, pain, exhaustion, mood). A score based on four questions regarding cannabis safety during pregnancy was also constructed. RESULTS: From a maximum of 300 surveys distributed, 284 were completed (95%). Most participants were white (87%), married (49%) or living with a partner (38%), and had private health insurance (62%). Most women indicated it was unsafe to use alcohol and tobacco products during pregnancy (> 90%), but that proportion dropped to 82% and 63% regarding recreational cannabis and medical cannabis, respectively. Only women with prior cannabis use (23% of sample) continued to do so during pregnancy: 57% of women reporting daily cannabis use prior to pregnancy continued to use cannabis during pregnancy with 33% reporting daily use. Two thirds of users during pregnancy indicated they were self-medicating for: nausea (90%), anxiety (70%), insomnia (30%), and pain management (30%). Many (56%) of the women who used cannabis during pregnancy believed it is safe. Younger women and women who were overwhelmed/exhausted or less happy/optimistic were more likely to believe cannabis use is safe. Women valued healthcare provider advice more than advice from family and friends. Study strengths include a high response rate. Weaknesses include self-report and that is was a convenience sample; however, the demographics of the sample were similar to past studies. CONCLUSION: Women with a history of cannabis use, especially daily use, are at risk of continuing during pregnancy and should receive counseling. Younger women and women with greater stressors during pregnancy also are at greater risk. Screening for prior use and for stressors may identify patients that would benefit from enhanced counseling