Using Gut Microbiome as A Tool in Dietary Intervention for Prevention and Management of Obesity

The gut microbiome has trillions of bacteria which play an important role in human health and disease. Several animal and human studies have shown that dysbiosis, microbial imbalance as the causative factor in obesity and metabolic syndrome. Significant research evidence demonstrates that changes in the proportion of Bacteroidetes and Firmicutes has been associated with obesity, but this has been recently challenged. Similar studies were carried out in several populations, however, there are no such studies, to date, among Asian Indians. We aimed to examine the usefulness of gut microbiome testing in developing personalized diet for managing obesity. In this study, we selected individuals, generally healthy, free- living adults, both men and women with BMI 25- 40 kg/m2 and with previous history of failures at weight loss who visited a Weight Loss Clinic, based in Coimbatore, India & were offered a gut microbiome test. We included 54 individuals in the intervention group who received personalized dietary advice for weight loss based on the gut microbiome test and another set of 52 individuals visiting the same clinic were included in the comparison group based on their age, height, weight and BMI who received generic diet. A statistically significant increase in the Bacteroidetes genus was observed in the personalized nutrition group (p = .04). The change (delta) values in gut microbiome composition in personalized nutrition group were significantly higher at the end of 120 days. Gut microbiome-based personalized microbiome modulation through diet significantly improves gut microbiome profiles among obese individuals.  We would further need studies with larger sample size to validate these study findings and long-term follow-up are needed

In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate

Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (Kd) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future.Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (Kd) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future

Investigating undergraduate mathematics learners’ cognitive engagement with recorded lecture videos

The use of recorded lecture videos (RLVs) in mathematics instruction continues to advance. Prior research at the post-secondary level has indicated a tendency for RLV use in mathematics to be negatively correlated with academic performance, though it is unclear whether this is because regular users are generally weaker mathematics students or because RLV use is somehow depressing student learning. Through the lens of cognitive engagement, a quasi-experimental pre- and post-test design study was conducted to investigate the latter possibility. Cognitive engagement was operationalised using the Revised Two-Factor Study Process Questionnaire (R-SPQ-2F), which measures learning approaches on two major scales: surface and deep. In two mathematics courses at two universities, in Australia and the UK, participants were administered the questionnaire near the course start and finish. Overall findings were similar in both contexts: a reduction in live lecture attendance coupled with a dependence on RLVs was associated with an increase in surface approaches to learning. This study has important implications for future pedagogical development and adds to the sense of urgency regarding research into best practices using RLVs in mathematics

Flexible free-standing Ni-Mn oxide antenna decorated CNT/nanofiber membrane for high-volumetric capacitance supercapacitors

There is growing demand for lightweight flexible supercapacitors with high electrochemical performance for wearable and portable electronics. Here, we spun nanoparticles of nickel-manganese oxides along with carbon nanotubes into carbon nanofibers and engineered a 3D networked Ni-Mn oxides/CNT@CNF free-standing membrane for flexible supercapacitor applications. The electrospinning process controlled the nanoparticle aggregation while subsequent heat treatment generates nanochannels in the fibres, resulting in a very porous tubular nanocomposite structure. The preparation process also enabled good interfacial contact between the nanoparticles and the conductive carbon network. The resulting Ni-Mn oxides/CNT@CNF membrane displays high mass loading (Ni-Mn oxides) of 855 mg cm-3 and low CNT incorporation of ∼0.4%. The outstanding porous structure, synergy of the carbon with Ni-Mn oxides, and fast and facile faradaic reactions on the electrode were responsible for the superior volumetric capacitance of 250 F cm-3 at 1 A cm-3, energy density as high as 22 mW h cm-3 and an excellent power density of 12 W cm-3. Despite the low CNT loading, the hybrid electrode exhibits excellent cycling performance with capacitance retention of 96.4% after 10 000 cycles evidencing a well-preserved Ni-manganese oxide nanostructure throughout the cycling. The resulting outstanding electrochemical performances of the Ni-Mn oxides/CNT@CNF synergic system offer new insights into effective utilization of transition metal oxides for establishing high-performance flexible supercapacitors within a confined volume

Investigating the efficacy of functionalized graphene oxide with polyhedral oligomeric silsesquioxane as an effective additive in sustainable ionic liquid-based electrolytes for dye-sensitized solar cells through experimental and DFT studies

The focus of the study has been on the first-ever use of functionalized graphene oxide with polyhedral oligomeric silsesquioxane (FGO-POSS) as an effective additive to ionic liquid-based electrolytes in dye-sensitized solar cells (DSSCs). The electrolytes consisted of binary ionic liquids (ILs), 1-ethyl-3-methylimidazolium iodide (EMII), and 1-butyl-3-methylimidazolium iodide (BMII). Different concentrations of the efficient additive FGO-POSS, ranging from 0% to 1%, were incorporated into the electrolytes. Under highly controlled conditions, a series of reactions was conducted to synthesize FGO-POSS. By reacting graphene oxide (GO) with L-phenylalanine, initially, GO-L-phenylalanine was obtained. In the next phase, GO-L-Phenylalanine reacted with SSQ-[3-(2-Aminoethyl) amino] propyl-Heptaisobutyl substituted to modify its structure with polyhedral oligomeric silsesquioxane (POSS). The ILs, namely EMII, and BMII, were synthesized using the scientific methodologies detailed in the referenced articles. Furthermore, BMII was functionalized with CuI (BMICuI-2) through a specific procedure. Five types of electrolytes were prepared to be employed in DSSCs using prepared ILs and FGO-POSS, and their results were reported to show the electrical and gelatin features of these types of electrolytes. According to this study's findings, using FGO-POSS as an innovative and efficient additive in ILs-based environmentally sustainable nanocomposite electrolytes in an amount of 0.75 wt% increased the value of the short circuit current density (JSC) from 9.433 mA.cm−2 to 15.592 mA.cm−2, the open circuit voltage (VOC) from 0.738 V to 0.762 V, and the overall efficiency (η) increased from 4.965 to 8.303 %. The FGO-POSS and ILs, EMII, and BMICuI-2 boost electron transport and electrolyte conductivity, resulting in increased JSC, VOC, and η. Results of the density functional theory (DFT) calculation indicated that the adsorption of the FGO-POSS electrolyte additives on the TiO2 electrode surface produces midgap states in the band gap of TiO2, resulting in the reduction of the total bandgap and less barrier electron transfer and a redshift in the adsorption edge and enhancement of DSSCs' efficiency

A DSMC-CFD coupling method using surrogate modelling for low-speed rarefied gas flows

A new Micro-Macro-Surrogate (MMS) hybrid method is presented that couples the Direct Simulation Monte Carlo (DSMC) method with Computational Fluid Dynamics (CFD) to simulate low-speed rarefied gas flows. The proposed MMS method incorporates surrogate modelling instead of direct coupling of DSMC data with the CFD, addressing the limitations CFD has in accurately modelling rarefied gas flows, the computational cost of DSMC for low-speed and multiscale flows, as well as the pitfalls of noise in conventional direct coupling approaches. The surrogate models, trained on the DSMC data using Bayesian inference, provide noise-free and accurate corrections to the CFD simulation enabling it to capture the non-continuum physics. The MMS hybrid approach is validated by simulating low-speed, steady-state, force-driven rarefied gas flows in a canonical 1D parallel-plate system, where corrections to the boundary conditions and stress tensor are considered and shows excellent agreement with DSMC benchmark results. A comparison with the typical domain decomposition DSMC-CFD hybrid method is also presented, to demonstrate the advantages of noise-avoidance in the proposed approach. The method also inherently captures the uncertainty arising from micro-model fluctuations, allowing for the quantification of noise-related uncertainty in the predictions. The proposed MMS method demonstrates the potential to enable multiscale simulations where CFD is inaccurate and DSMC is prohibitively expensive

Folding of the lysine riboswitch: importance of peripheral elements for transcriptional regulation

The Bacillus subtilis lysC lysine riboswitch modulates its own gene expression upon lysine binding through a transcription attenuation mechanism. The riboswitch aptamer is organized around a single five-way junction that provides the scaffold for two long-range tertiary interactions (loop L2–loop L3 and helix P2–loop L4)—all of this for the creation of a specific lysine binding site. We have determined that the interaction P2–L4 is particularly important for the organization of the ligand-binding site and for the riboswitch transcription attenuation control. Moreover, we have observed that a folding synergy between L2–L3 and P2–L4 allows both interactions to fold at lower magnesium ion concentrations. The P2–L4 interaction is also critical for the close juxtaposition involving stems P1 and P5. This is facilitated by the presence of lysine, suggesting an active role of the ligand in the folding transition. We also show that a previously uncharacterized stem–loop located in the expression platform is highly important for the riboswitch activity. Thus, folding elements located in the aptamer and the expression platform both influence the lysine riboswitch gene regulation

The Transcription Factor YY1 Is a Substrate for Polo-Like Kinase 1 at the G2/M Transition of the Cell Cycle

Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate