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Computational Structure-Activity Relationship (SAR) of Berberine Analogs in Double-Stranded and G-Quadruplex DNA Binding Reveals Both Position and Target Dependence

Sun et al. | Dec 18, 2020

Computational Structure-Activity Relationship (SAR) of Berberine Analogs in Double-Stranded and G-Quadruplex DNA Binding Reveals Both Position and Target Dependence

Berberine, a natural product alkaloid, and its analogs have a wide range of medicinal properties, including antibacterial and anticancer effects. Here, the authors explored a library of alkyl or aryl berberine analogs to probe binding to double-stranded and G-quadruplex DNA. They determined that the nature of the substituent, the position of the substituent, and the nucleic acid target affect the free energy of binding of berberine analogs to DNA and G-quadruplex DNA, however berberine analogs did not result in net stabilization of G-quadruplex DNA.

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The non-nutritive sweeteners acesulfame potassium and neotame slow the regeneration rate of planaria

Russo et al. | Nov 29, 2023

The non-nutritive sweeteners acesulfame potassium and neotame slow the regeneration rate of planaria
Image credit: Russo et al. 2023

The consumption of sugar substitute non-nutritive sweeteners (NNS) has dramatically increased in recent years. Despite being advertised as a healthy alternative, NNS have been linked to adverse effects on the body, such as neurodegenerative diseases (NDs). In NDs, neural stem cell function is impaired, which inhibits neuron regeneration. The purpose of this study was to determine if the NNS acesulfame potassium (Ace-K) and neotame affect planaria neuron regeneration rates. Since human neurons may regenerate, planaria, organisms with extensive regenerative capabilities due to stem cells called neoblasts, were used as the model organism. The heads of planaria exposed to either a control or non-toxic concentrations of NNS were amputated. The posterior regions of the planaria were observed every 24 hours to see the following regeneration stages: (1) wound healing, (2) blastema development, (3) growth, and (4) differentiation. The authors hypothesized that exposure to the NNS would slow planaria regeneration rates. The time it took for the planaria in the Ace-K group and the neotame group to reach the second, third, and fourth regeneration stage was significantly greater than that of the control. The results of this study indicated that exposure to the NNS significantly slowed regeneration rates in planaria. This suggests that the NNS may adversely impact neoblast proliferation rates in planaria, implying that it could impair neural stem cell proliferation in humans, which plays a role in NDs. This study may provide insight into the connection between NNS, human neuron regeneration, and NDs.

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Contrasting role of ASCC3 and ALKBH3 in determining genomic alterations in Glioblastoma Multiforme

Sriram et al. | Sep 27, 2022

Contrasting role of <i>ASCC3</i> and <i>ALKBH3</i> in determining genomic alterations in Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is the most malignant brain tumor with the highest fraction of genome alterations (FGA), manifesting poor disease-free status (DFS) and overall survival (OS). We explored The Cancer Genome Atlas (TCGA) and cBioportal public dataset- Firehose legacy GBM to study DNA repair genes Activating Signal Cointegrator 1 Complex Subunit 3 (ASCC3) and Alpha-Ketoglutarate-Dependent Dioxygenase AlkB Homolog 3 (ALKBH3). To test our hypothesis that these genes have correlations with FGA and can better determine prognosis and survival, we sorted the dataset to arrive at 254 patients. Analyzing using RStudio, both ASCC3 and ALKBH3 demonstrated hypomethylation in 82.3% and 61.8% of patients, respectively. Interestingly, low mRNA expression was observed in both these genes. We further conducted correlation tests between both methylation and mRNA expression of these genes with FGA. ASCC3 was found to be negatively correlated, while ALKBH3 was found to be positively correlated, potentially indicating contrasting dysregulation of these two genes. Prognostic analysis showed the following: ASCC3 hypomethylation is significant with DFS and high ASCC3 mRNA expression to be significant with OS, demonstrating ASCC3’s potential as disease prediction marker.

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The effects of stress on the bacterial community associated with the sea anemone Diadumene lineata

Cahill et al. | Feb 15, 2021

The effects of stress on the bacterial community associated with the sea anemone Diadumene lineata

In healthy ecosystems, organisms interact in a relationship that helps maintain one another's existence. Stress can disrupt this interaction, compromising the survival of some of the members of such relationships. Here, the authors investigate the effect of stress on the interaction between anemones and their microbiome. Their study suggests that stress changes the composition of the surface microbiome of the anemone D. lineata, which is accompanied by an increase in mucus secretion. Future research into the composition of this stress-induced mucus might reveal useful antimicrobial properties.

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Male Feminization of the Common Pillbug Armadillidium vulgare by Wolbachia bacteria

Ramanan et al. | Jun 30, 2024

Male Feminization of the Common Pillbug <i>Armadillidium vulgare</i> by <i>Wolbachia</i> bacteria
Image credit: Ramanan et al. 2024

Wolbachia pipientis (Wolbachia) is a maternally inherited endosymbiotic bacterium that infects over 50% of arthropods, including pillbugs, and acts as a reproductive parasite in the host. In the common terrestrial pillbug Armadillidium vulgare (A. vulgare), Wolbachia alters the sex ratio of offspring through a phenomenon called feminization, where genetic males develop into reproductive females. Previous studies have focused on the presence or absence of Wolbachia as a sex ratio distorter in laboratory cultured and natural populations mainly from sites in Europe and Japan. Our three-year study is the first to evaluate the effects of the Wolbachia sex ratio distorter in cultured A. vulgare offspring in North America. We asked whether Wolbachia bacteria feminize A. vulgare isopod male offspring from infected mothers and if this effect can be detected in F1 offspring by comparing the male/female offspring ratios. If so, the F1 offspring ratio should show a higher number of females than males compared to the offspring of uninfected mothers. Over three years, pillbug offspring were cultured from pregnant A. vulgare females and developed into adults. We determined the Wolbachia status of mothers and counted the ratios of male and female F1 progeny to determine feminization effects. In each year sampled, significantly more female offspring were born to Wolbachia-infected mothers than those from uninfected mothers. These ratio differences suggest that the Wolbachia infection status of mothers directly impacts the A. vulgare population through the production of reproductive feminized males, which in turn provides an advantage for further Wolbachia transmission.

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The effect of Omega-3 on bovine blood cells as a potential remedy for Cerebral Cavernous Malformations

Pulluru et al. | Sep 22, 2023

The effect of Omega-3 on bovine blood cells as a potential remedy for Cerebral Cavernous Malformations
Image credit: Carolien van Oijen

Here, the authors investigated if dietary Omega-3 fatty acids could reduce the potential for cerebral cavernous malformations, which are brain lesions that occur due to a genetic mutation where high membrane permeability occurs between endothelial cell junctions. In a bovine-based study where some cows were fed an Omega-3 diet, the authors found the membranes of bovine blood cells increased in thickness with Omega-3 supplementation. As a result, they suggest that dietary Omega-3 could be considered as a possible preventative measure for cerebral cavernous malformations.

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Application of gene therapy for reversing T-cell dysfunction in cancer

Hyun Lee et al. | Aug 25, 2022

Application of gene therapy for reversing T-cell dysfunction in cancer

Since cancer cells inhibit T-cell activity, the authors investigated a method to reverse T-cell disfunction with gene therapy, so that the T-cells would become effective once again in fighting cancer cells. They used the inhibition of proprotein convertases (PCSK1) in T cells and programmed death-ligand 1 (CD274) in cancer cells. They observed the recovery of IL-2 expression in Jurkat cells, with increased recovery noted in a co-culture sample. This study suggests a novel strategy to reactivate T cells.

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Contribution of environmental factors to genetic variation in the Pacific white-sided dolphin

Talwar et al. | Jan 23, 2024

Contribution of environmental factors to genetic variation in the Pacific white-sided dolphin
Image credit: Flavio

Here the authors sought to understand the effects of different variables that may be tied to pollution and climate change on genetic variation of Pacific white-sided dolphins, a species that is currently threatened by water pollution. Based on environmental data collected alongside a genetic distance matrix, they found that ocean currents had the most significant impact on the genetic diversity of Pacific white-sided dolphins along the Japanese coast.

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