Impact of microbiota in colorectal carcinogenesis: lessons from experimental models

A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC

ER stress response plays an important role in aggregation of α-synuclein

<p>Abstract</p> <p>Background</p> <p>Accumulation of filamentous α-synuclein as Lewy bodies is a hallmark of Parkinson's disease. To identify the mechanisms involved in α-synuclein assembly and determine whether the assemblies are cytotoxic, we developed a cell model (3D5) that inducibly expresses wild-type human α-synuclein and forms inclusions that reproduce many morphological and biochemical characteristics of Lewy bodies. In the present study, we evaluated the effects of several histone deacetylase inhibitors on α-synuclein aggregation in 3D5 cells and primary neuronal cultures. These drugs have been demonstrated to protect cells transiently overexpressing α-synuclein from its toxicity.</p> <p>Results</p> <p>Contrary to transient transfectants, the drug treatment did not benefit 3D5 cells and primary cultures. The treated were less viable and contained more α-synuclein oligomers, active caspases 3 and 9, as well as ER stress markers than non-treated counterparts. The drug-treated, induced-3D5 cells, or primary cultures from transgenic mice overexpressing (<2 fold) α-synuclein, displayed more α-synuclein oligomers and ER stress markers than non-induced or non-transgenic counterparts. Similar effects were demonstrated in cultures treated with tunicamycin, an ER stressor. These effects were blocked by co-treatment with salubrinal, an ER stress inhibitor. In comparison, co-treatment with a pan caspase inhibitor protected cells from demise but did not reduce α-synuclein oligomer accumulation.</p> <p>Conclusions</p> <p>Our results indicate that an increase of wild-type α-synuclein can elicit ER stress response and sensitize cells to further insults. Most importantly, an increase of ER stress response can promote the aggregation of wild type α-synuclein.</p

Turbidity Currents, Submarine Landslides and the 2006 Pingtung Earthquake off SW Taiwan

Submarine landslides or slumps may generate turbidity currents consisting of mixture of sediment and water. Large and fast-moving turbidity currents can incise and erode continental margins and cause damage to artificial structures such as telecommunication cables on the seafloor. In this study, we report that eleven submarine cables across the Kaoping canyon and Manila trench were broken in sequence from 1500 to 4000 m deep, as a consequence of submarine landslides and turbidity currents associated with the 2006 Pingtung earthquakes offshore SW Taiwan. We have established a full-scale scenario and calculation of the turbidity currents along the Kaoping canyon channel from the middle continental slope to the adjacent deep ocean. Our results show that turbidity current velocities vary downstream ranging from 20 to 3.7 and 5.7 m/s, which demonstrates a positive relationship between turbidity current velocity and bathymetric slope. The violent cable failures happened in this case evidenced the destructive power of the turbidity current to seafloor or underwater facilities that should not be underestimated

Therapeutic Effect of Repurposed Temsirolimus in Lung Adenocarcinoma Model

Lung cancer is one of the major cause of cancer-related deaths worldwide. The poor prognosis and resistance to both radiation and chemotherapy urged the development of potential targets for lung cancer treatment. In this study, using a network-based cellular signature bioinformatics approach, we repurposed a clinically approved mTOR inhibitor for renal cell carcinomans, temsirolimus, as the potential therapeutic candidate for lung adenocarcinoma. The PI3K-AKT-mTOR pathway is known as one of the most frequently dysregulated pathway in cancers, including non-small-cell lung cancer. By using a well-documented lung adenocarcinoma mouse model of human pathophysiology, we examined the effect of temsirolimus on the growth of lung adenocarcinoma in vitro and in vivo. In addition, temsirolimus combined with reduced doses of cisplatin and gemcitabine significantly inhibited the lung tumor growth in the lung adenocarcinoma mouse model compared with the temsirolimus alone or the conventional cisplatin–gemcitabine combination. Functional imaging techniques and microscopic analyses were used to reveal the response mechanisms. Extensive immunohistochemical analyses were used to demonstrate the apparent effects of combined treatments on tumor architecture, vasculature, apoptosis, and the mTOR-pathway. The present findings urge the further exploration of temsirolimus in combination with chemotherapy for treating lung adenocarcinoma

Photothermal responsivity of van der Waals material-based nanomechanical resonators

Nanomechanical resonators made from van der Waals materials (vdW NMRs) provide a new tool for sensing absorbed laser power. The photothermal response of vdW NMRs, quantified from the resonant frequency shifts induced by optical absorption, is enhanced when incorporated in a Fabry-Perot (FP) interferometer. Along with the enhancement comes the dependence of the photothermal response on NMR displacement, which lacks investigation. Here, we address the knowledge gap by studying electromotively driven niobium diselenide drumheads fabricated on highly reflective substrates. We use a FP-mediated absorptive heating model to explain the measured variations of the photothermal response. The model predicts a higher magnitude and tuning range of photothermal responses on few-layer and monolayer NbSe$_{2}$ drumheads, which outperform other clamped vdW drum-type NMRs at a laser wavelength of $532\,$nm. Further analysis of the model shows that both the magnitude and tuning range of NbSe$_{2}$ drumheads scale with thickness, establishing a displacement-based framework for building bolometers using FP-mediated vdW NMRs.Comment: 7 pages, 4 figure

Identification of single nucleotide polymorphism markers associated with resistance to bruchids (Callosobruchus spp.) in wild mungbean (Vigna radiata var. sublobata) and cultivated V. radiata through genotyping by sequencing and quantitative trait locus analysis

Interval mapping of bruchid resistance on physical maps of populations TC1966 x NM94 and V2802. (DOCX 14 kb

Developing a lifestyle intervention program for overweight or obese preconception, pregnant and postpartum women using qualitative methods.

The time period before, during and after pregnancy represents a unique opportunity for interventions to cultivate sustained healthy lifestyle behaviors to improve the metabolic health of mothers and their offspring. However, the success of a lifestyle intervention is dependent on uptake and continued compliance. To identify enablers and barriers towards engagement with a lifestyle intervention, thematic analysis of 15 in-depth interviews with overweight or obese women in the preconception, pregnancy or postpartum periods was undertaken, using the integrated-Promoting Action on Research Implementation in Health Services framework as a guide to systematically chart factors influencing adoption of a novel lifestyle intervention. Barrier factors include time constraints, poor baseline knowledge, family culture, food accessibility, and lack of relevant data sources. Enabling factors were motivation to be healthy for themselves and their offspring, family and social support, a holistic delivery platform providing desired information delivered at appropriate times, regular feedback, goal setting, and nudges. From the findings of this study, we propose components of an idealized lifestyle intervention including (i) taking a holistic life-course approach to education, (ii) using mobile health platforms to reduce barriers, provide personalized feedback and promote goal-setting, and (iii) health nudges to cultivate sustained lifestyle habits

Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients

Background The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family, ABCA1 was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that ABCA1 may be involved in ovarian cancer and its initiation. Results We first compared the expression level of ABCA1 in IOSE cells and a panel of ovarian cancer cell lines and found that ABCA1 was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of ABCA1 in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of ABCA1 increased the cholesterol level and promoted cell growth in vitro and in vivo. Further analysis of ABCA1 methylation in 76 ovarian cancer patient samples demonstrated that patients with higher ABCA1 methylation are associated with high stage (P = 0.0131) and grade (P = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of ABCA1 have shorter overall survival (P = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival (P = 0.038). Conclusions ABCA1 may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients

Optoelectrical nanomechanical resonators made from multilayered 2D materials

Studies involving nanomechanical motion have evolved from its detection and understanding of its fundamental aspects to its promising practical utility as an integral component of hybrid systems. Nanomechanical resonators' indispensable role as transducers between optical and microwave fields in hybrid systems, such as quantum communications interface, have elevated their importance in recent years. It is therefore crucial to determine which among the family of nanomechanical resonators is more suitable for this role. Most of the studies revolve around nanomechanical resonators of ultrathin structures because of their inherently large mechanical amplitude due to their very low mass. Here, we argue that the underutilized nanomechanical resonators made from multilayered two-dimensional (2D) materials are the better fit for this role because of their comparable electrostatic tunability and larger optomechanical responsivity. To show this, we first demonstrate the electrostatic tunability of mechanical modes of a multilayered nanomechanical resonator made from graphite. We also show that the optomechanical responsivity of multilayered devices will always be superior as compared to the few-layer devices. Finally, by using the multilayered model and comparing this device with the reported ones, we find that the electrostatic tunability of devices of intermediate thickness is not significantly lower than that of ultrathin ones. Together with the practicality in terms of fabrication ease and design predictability, we contend that multilayered 2D nanomechanical resonators are the optimal choice for the electromagnetic interface in integrated quantum systems