Multipotent Cancer Stem Cells Derived from Human Malignant Peritoneal Mesothelioma Promote Tumorigenesis

During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized a CSC model for MPeM using stably expandable tumorigenic stem cells derived from patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction and the differentiating cells express lineage-specific markers such as TUBB3, an early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARγ and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression.     

An eight-nucleotide sequence in the potato virus X 3' untranslated region is required for both host protein binding and viral multiplication.

Gel retardation and UV-cross-linking techniques were used to demonstrate that two tobacco proteins, with approximate molecular masses of 28 and 32 kDa, bind to a site within the 3' region of potato virus X (PVX) genomic RNA. The protein binding is specific, in that a 50-fold excess of unlabeled probe prevents formation of the complexes but no reduction is observed with a 2,000-fold molar excess of yeast tRNA. Complex formation is inhibited by poly(U) but is relatively unaffected by poly(A), poly(G), or poly(C-I). PVX RNA-host protein complex formation occurs in vitro at salt concentrations up to 400 mM. Deletion mapping indicates that the proteins bind within the 3' untranslated region (UTR) of PVX genomic RNA and that an 8-nucleotide U-rich sequence (5'-UAUUUUCU) is required for the binding. Deletion of the 8-nucleotide U-rich region from the 3' UTR of a sensitive PVX reporter virus that carries the luciferase gene in place of the PVX coat protein gene results in a more than 70,000-fold reduction in luciferase expression in tobacco protoplasts. RNA probes carrying the sequence GCGC in place of the central four contiguous uridines of the 8-nucleotide U-rich motif fail to bind host protein at detectable levels, and the same mutation, when introduced into the PVX reporter virus, eliminates viral multiplication. Mutations of 1 or 2 nucleotides within the same four uridines reduced both binding of host proteins and replication of reporter virus. These results indicate that the 8-nucleotide U-rich motif within the PVX 3' UTR is important for some aspect of viral multiplication and suggest that host protein binding plays a role in the process.     

Moving forward with the primate microbiome: Introduction to a special issue of the American Journal of Primatology

Primate microbiome research is a quickly growing field with exciting potential for informing our understanding of primate biology, ecology, and evolution as well as host‐microbe interactions more broadly. This introductory essay to a special section of the American Journal of Primatology provides a cross‐sectional snapshot of current activity in these areas by briefly summarizing the diversity of contributed papers and their relationships to key themes in host‐associated microbiome research. It then uses this survey as a foundation for consolidating a set of key research questions to broadly guide future research. It also argues for the importance of methods standardization to facilitate comparative analyses and the identification of generalizable patterns and relationships. While primatology will benefit greatly from the integration of microbial datasets, it is uniquely positioned to address important questions regarding microbiology and macro‐ecology and evolution more generally. We are eager to see where the primate microbiome leads us.     

Energy from vascular plant wastewater treatment systems

Water hyacinth (Eichhornia crassipes), duckweed (Spirodela sp. andLemna sp.), water pennywort (Hydrocotyle ranunculoides), and kudzu (Pueraria lobata) were anaerobically fermented using an anaerobic filter technique that reduced the total digestion time from 90 d to an average of 23 d and produced 0.14-0.22 m³ CH₄/kg (dry weight) (2.3-3.6 ft³/lb) from mature filters for the 3 aquatic species. Kudzu required an average digestion time of 33 d and produced an average of 0.21 m³ CH₄/kg (dry weight) (3.4 ft³/lb). The anaerobic filter provided a large surface area for the anaerobic bacteria to establish and maintain an optimal balance of facultative, acid-forming, and methane-producing bacteria. Consequently the efficiency of the process was greatly improved over prior batch fermentations.     

Ferritin in normal human peripheral blood T-lymphocyte subpopulations

Six peripheral blood lymphoid fractions (total lymphocytes, non-T, T, Tar (autologous rosette-forming T cells/precursor), T mu (helper), and T gamma (suppressor) lymphocytes) isolated through rosetting procedures were examined for the presence of ferritin by a direct immunofluorescence technique. Although ferritin was present in all lymphoid fractions studied, a significantly higher proportion of ferritin-containing cells were detected in the T-cell fraction than in the non-T-cell fraction, (mean +/- SD = 7.9 +/- 1.6% and 5.0 +/- 1.2%, respectively). T mu- and T gamma-cell fractions showed a twofold increase in the number of ferritin-positive cells (14.1 +/- 1.4% and 15.4 +/- 2.6%, respectively), as compared with Tar (7.0 +/- 0.9%)-and total lymphocyte (6.9 +/- 1.3%)-cell fractions. These results indicate that ferritin is preferentially distributed in T mu and T gamma lymphocytes and may constitute the basis for explaining some of the roles exercised by these cells in the control of other biological systems.     

Climatic forcing and larval dispersal capabilities shape the replenishment of fishes and their habitat‐forming biota on a tropical coral reef

Fluctuations in marine populations often relate to the supply of recruits by oceanic currents. Variation in these currents is typically driven by large‐scale changes in climate, in particular ENSO (El Nino Southern Oscillation). The dependence on large‐scale climatic changes may, however, be modified by early life history traits of marine taxa. Based on eight years of annual surveys, along 150 km of coastline, we examined how ENSO influenced abundance of juvenile fish, coral spat, and canopy‐forming macroalgae. We then investigated what traits make populations of some fish families more reliant on the ENSO relationship than others. Abundance of juvenile fish and coral recruits was generally positively correlated with the Southern Oscillation Index (SOI), higher densities recorded during La Niña years, when the ENSO‐influenced Leeuwin Current is stronger and sea surface temperature higher. The relationship is typically positive and stronger among fish families with shorter pelagic larval durations and stronger swimming abilities. The relationship is also stronger at sites on the coral back reef, although the strongest of all relationships were among the lethrinids (r = .9), siganids (r = .9), and mullids (r = .8), which recruit to macroalgal meadows in the lagoon. ENSO effects on habitat seem to moderate SOI–juvenile abundance relationship. Macroalgal canopies are higher during La Niña years, providing more favorable habitat for juvenile fish and strengthening the SOI effect on juvenile abundance. Conversely, loss of coral following a La Niña‐related heat wave may have compromised postsettlement survival of coral dependent species, weakening the influence of SOI on their abundance. This assessment of ENSO effects on tropical fish and habitat‐forming biota and how it is mediated by functional ecology improves our ability to predict and manage changes in the replenishment of marine populations.