Green algae (Viridiplantae) in sediments from three lakes on Vega Island,Antarctica, assessed using DNA metabarcoding

Molecular Biology Reports - Vega Island is located off the eastern tip of the Antarctic Peninsula (Maritime Antarctica), in the Weddell Sea. In this study, we used metabarcoding to investigate...     

Discovery of Power-Law Growth in the Self-Renewal of Heterogeneous Glioma Stem Cell Populations

Background

Accumulating evidence indicates that cancer stem cells (CSCs) drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS) forming model, to generate a population in which glioma stem cells (GSCs) become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability.

Methodology/Principal Findings

To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres). Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone). Log-log plots of distributions of clone sizes yielded a good fit (r>0.90) to a straight line (log(% total clones) = k*log(#cells/clone)) indicating that the system follows a power-law (y = x^k) with a specific degree exponent (k = −1.42). Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = −1.01 to −1.17). Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law-dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM), suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population.

Conclusions/Significance

Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous glioma stem cell populations. That the data always fit a power-law suggests that: (i) clone sizes follow continuous, non-random, and scale-free hierarchy; (ii) precise biologic rules that reflect self-organizing emergent behaviors govern the generation of neurospheres. That the power-law behavior and the original GS heterogeneity are maintained over multiple passages indicates that these rules are invariant. These self-organizing mechanisms very likely underlie tumor heterogeneity during tumor growth. Discovery of this power-law behavior provides a mechanism that could be targeted in the development of new, more effective, anti-cancer agents.     

Factors Associated with Untreated Diabetes: Analysis of Data from 20,496 Participants in the Japanese National Health and Nutrition Survey

Objective

We aimed to examine factors associated with untreated diabetes in a nationally representative sample of the Japanese population.

Research Design and Methods

We pooled data from the Japanese National Health and Nutrition Survey from 2005 to 2009 (n = 20,496). Individuals aged 20 years and older were included in the analysis. We classified participants as having diabetes if they had HbA1c levels ≥6.5% (≥48 mmol/mol). People with diabetes who self-reported that they were not currently receiving diabetic treatment were considered to be untreated. We conducted a multinomial logistic regression analysis to determine factors associated with untreated diabetes relative to non-diabetic individuals.

Results

Of 20,496 participants who were included in the analysis, untreated diabetes was present in 748 (3.6%). Among participants with untreated diabetes, 48.3% were previously diagnosed with diabetes, and 46.5% had HbA1c levels ≥7.0% (≥53 mmol/mol). Participants with untreated diabetes were significantly more likely than non-diabetic participants to be male, older, and currently smoking, have lower HDL cholesterol levels and higher BMI, non-HDL cholesterol levels, and systolic blood pressure.

Conclusions

A substantial proportion of people in Japan with untreated diabetes have poor glycemic control. Targeting relevant factors for untreated diabetes in screening programs may be effective to enhance the treatment and control of diabetes.     

Phenolase of spinach roots

Phenolase activity is not found in germinating spinach embryos, but it appears in the radicles when the vascular tissues have developed, and then increases progressively. Unlike the two phenolases detected earlier in the chloroplasts, the root enzyme is a single protein with higher MW occurring both in 3000 g precipitate and 28 000 g supernatant fractions. The phenolase in 3000 g fraction is not activated by treatment with detergents and trypsin. The enzyme is contained mainly in xylem parenchymatous cells adjacent to primary vessels. It also occurs to a lesser degree in the dermal parts, including epidermis and cortex. Similar tissue-level distribution patterns of this enzyme are also observed in the roots of other angiosperms, especially in Compositae.     

Cultivable fungi present in deep-sea sediments of Antarctica: taxonomy,diversity, and bioprospecting of bioactive compounds

Extremophiles - We accessed the culturable mycobiota present in marine sediments at different depths in Antarctica Ocean. Acremonium fusidioides, Penicillium allii-sativi, Penicillium chrysogenum,...     

Dimethylfumarate inhibits tumor cell invasion and metastasis by suppressing the expression and activities of matrix metalloproteinases in melanoma cells

NF-κB acts as a signal transducer during tumor progression, cell invasion, and metastasis. Dimethylfumarate (DMF) is reported to inhibit tumor necrosis factor-α-induced nuclear entry of NF-κB/p65. However, only a few reports suggest that DMF inhibits tumor metastasis; also the molecular mechanisms underlying the inhibition of metastasis are poorly understood. We investigated the inhibition of tumor invasion and metastasis by DMF in a melanoma cell line, B16BL6. DMF inhibited B16BL6 cell invasion and metastasis by suppressing the expression and activities of MMPs. DMF also inhibited the nuclear entry of NF-κB/p65, thus inhibiting B16BL6 cell invasion and metastasis. These results suggest that DMF is potentially useful as an anti-metastatic agent for the treatment of malignant melanoma.     

A conserved nuclear receptor, Tailless, is required for efficient proliferation and prolonged maintenance of mushroom body progenitors in the Drosophila brain

The intrinsic neurons of mushroom bodies (MBs), centers of olfactory learning in the Drosophila brain, are generated by a specific set of neuroblasts (Nbs) that are born in the embryonic stage and exhibit uninterrupted proliferation till the end of the pupal stage. Whereas MB provides a unique model to study proliferation of neural progenitors, the underlying mechanism that controls persistent activity of MB-Nbs is poorly understood. Here we show that Tailless (TLL), a conserved orphan nuclear receptor, is required for optimum proliferation activity and prolonged maintenance of MB-Nbs and ganglion mother cells (GMCs). Mutations of tll progressively impair cell cycle in MB-Nbs and cause premature loss of MB-Nbs in the early pupal stage. TLL is also expressed in MB-GMCs to prevent apoptosis and promote cell cycling. In addition, we show that ectopic expression of tll leads to brain tumors, in which Prospero, a key regulator of progenitor proliferation and differentiation, is suppressed whereas localization of molecular components involved in asymmetric Nb division is unaffected. These results as a whole uncover a distinct regulatory mechanism of self-renewal and differentiation of the MB progenitors that is different from the mechanisms found in other progenitors.     

Inhibition by oxalates of spinach chloroplast phenolase in unfrozen and frozen states

Spinach chloroplast phenolase was inhibited by oxalic acid and its salts. Complete inhibitions were induced instantly in the acidic region (e.g. by 1 and 5 mM oxalate at pH 5 and 5.5, respectively), and in the neutral region pre-incubation of the enzyme with oxalates could also lead to complete loss of activity. The inhibition mode was non-competitive for phenol substrate with K_i of 0.9 mM pH 6.8. Reduction of enzyme activity in a crude extract of chloroplasts induced by freezing at neutral pH was due to the presence of ammonium oxalate. With 0.5 mM oxalate, the inhibition attained 75% under frozen conditions, whilst no inhibition could be detected in the enzyme which had not been frozen. Free oxalic acid and K⁺ and Na⁺ salts also caused freezing inhibition. Glyoxylic and oxamic acids acted as inhibitors with less efficiency. With a pure mushroom tyrosinase (phenolase), essentially the identical results were obtained using the same conditions.     

Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies

Objective

Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence.

Data sources

MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included.

Review methods

Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting.

Results

We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07–1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98–1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results.

Conclusion

Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.