Systems biology and synthetic biology: A new epoch for toxicology research

Copyright © 2015 Mark T. Mc Auley et al. This is an open access article distributed under the Creative Commons Attribution License 3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditional computational approaches to toxicology and epidemiology research, using polycyclic aromatic hydrocarbons (PAHs) and their effects on adverse birth outcomes as an illustrative example. We introduce how systems toxicology (and their subdisciplines, genomic, proteomic, and metabolomic toxicology) will help to overcome such limitations. In particular, we discuss the advantages and disadvantages of mathematical frameworks that computationally represent biological systems. Finally, we discuss the nascent discipline of synthetic biology and highlight relevant toxicological centred applications of this technique, including improvements in personalised medicine. We conclude this review by presenting a number of opportunities and challenges that could shape the future of these rapidly evolving disciplines.Veronica M. Miller would like to acknowledge funding from Alexander and Bo McInnis and the Autism Research Institute for her toxicological studies and support

Preliminary Efficacy of Group Medical Nutrition Therapy and Motivational Interviewing among Obese African American Women with Type 2 Diabetes: A Pilot Study

Objective. To assess the efficacy and acceptability of a group medical nutritional therapy (MNT) intervention, using motivational interviewing (MI). Research Design & Method. African American (AA) women with type 2 diabetes (T2D) participated in five, certified diabetes educator/dietitian-facilitated intervention sessions targeting carbohydrate, fat, and fruit/vegetable intake and management. Motivation-based activities centered on exploration of dietary ambivalence and the relationships between diet and personal strengths. Repeated pre- and post-intervention, psychosocial, dietary self-care, and clinical outcomes were collected and analyzed using generalized least squares regression. An acceptability assessment was administered after intervention. Results. Participants (n = 24) were mostly of middle age (mean age 50.8 ± 6.3) with an average BMI of 39 ± 6.5. Compared to a gradual pre-intervention loss of HbA1c control and confidence in choosing restaurant foods, a significant post-intervention improvement in HbA1c (P = 0.03) and a near significant (P = 0.06) increase in confidence in choosing restaurant foods were observed with both returning to pre-intervention levels. 100% reported that they would recommend the study to other AA women with type 2 diabetes. Conclusion. The results support the potential efficacy of a group MNT/MI intervention in improving glycemic control and dietary self-care-related confidence in overweight/obese AA women with type 2 diabetes

Levels of autotrophy and heterotrophy in mesophotic corals near the end photic zone

Mesophotic corals live at ~30-150 m depth and can sustain metabolic processes under light-limited conditions by enhancing autotrophy through specialized photoadaptations or increasing heterotrophic nutrient acquisition. These acclimatory processes are often species-specific, however mesophotic ecosystems are largely unexplored and acclimation limits for most species are unknown. This study examined mesophotic coral ecosystems using a remotely operated vehicle (Ashmore Reef, Western Australia at 40 – 75m depth) to investigate the trophic ecology of five species of scleractinian coral (from genera Leptoseris, Pachyseris, and Craterastrea) using stable isotope analyses (δ13C and δ15N) of host and symbiont tissues and protein concentration. Trophic strategies were analyzed between species and between overall corals sampled above and below the end-photic point, where light is only 1% of surface irradiance. Results showed species-specific differences in resource use. Leptoseris hawaiiensis, L. scabra, and P. speciosa had similar Δ13C values (δ13C host - δ13C symbiont) approaching zero ( \u3c 0.5 ‰) which indicated greater dependence on symbiont autotrophy. In contrast, Leptoseris glabra and Craterastrea levis had higher Δ13C values (1.4 to 3.5 ‰) which indicated a greater reliance on external carbon sources. The latter two species also demonstrated tight nitrogen recycling within the holobiont, exhibiting low Δ15N values (host δ15N - symbiont δ15N = \u3c 0.5 ‰), compared to more autotrophic species (Δ15N = \u3e 1.2 ‰). Some species demonstrated the ability to maintain metabolic processes despite substantially reduced light availability (0.5 – 2% of surface irradiance). This research challenges our knowledge of acclimation limits for many scleractinian corals and contributes novel information for Ashmore Reef, the Western Australia region and mesophotic ecosystems in general, and critically examines common methods used to interpretate trophic ecology with bulk stable isotopes δ13C and δ15N

Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein

Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms, including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single mRNA transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work, we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during its biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamics simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results indicate that cotranslational folding of this viral protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent polypeptide chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding or binding events may also stimulate PRF

Preliminary Efficacy of Group Medical Nutrition Therapy and Motivational Interviewing among Obese African American Women with Type 2 Diabetes: A Pilot Study

Objective. To assess the efficacy and acceptability of a group medical nutritional therapy (MNT) intervention, using motivational interviewing (MI). Research Design & Method. African American (AA) women with type 2 diabetes (T2D) participated in five, certified diabetes educator/dietitian-facilitated intervention sessions targeting carbohydrate, fat, and fruit/vegetable intake and management. Motivation-based activities centered on exploration of dietary ambivalence and the relationships between diet and personal strengths. Repeated pre-and post-intervention, psychosocial, dietary self-care, and clinical outcomes were collected and analyzed using generalized least squares regression. An acceptability assessment was administered after intervention. Results. Participants (n = 24) were mostly of middle age (mean age 50.8 ± 6.3) with an average BMI of 39 ± 6.5. Compared to a gradual pre-intervention loss of HbA1c control and confidence in choosing restaurant foods, a significant post-intervention improvement in HbA1c (P = 0.03) and a near significant (P = 0.06) increase in confidence in choosing restaurant foods were observed with both returning to pre-intervention levels. 100% reported that they would recommend the study to other AA women with type 2 diabetes. Conclusion. The results support the potential efficacy of a group MNT/MI intervention in improving glycemic control and dietary self-care-related confidence in overweight/obese AA women with type 2 diabetes

HIV-1 viral load assays for resource-limited settings: Authors' reply [5]

The authors discuss studies on the low-cost viral load assays that are currently available and their potential for use in resource-limited settings

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines

The Grizzly, April 7, 1989

History in Making: Middle States Arrive Sunday • APO Holds Local Fraternity Chapter Conference • Letters: Normal Pledging O.K.; Booby not Prize • DeLeon Woos Wismer • Hundreds to Storm Campus • Friday\u27s Fun, But Not Food Fantasy • Men\u27s Lacrosse Begins with a Bang! • Bowers Leads U.C. to Win • Driscoll, Ursinus Set High Goals • Tough Schedule to Benefit U.C. Lax • Two Week Pledging Proposed by Subcommittee on Greeks • Boston: Seats Going Fast • It\u27s Tenure Time Once Again! • U.S.G.A Update • Cinders to Rock U.C. • U.S.G.A. Needs You! • Rumors a Real Bomb • Take a Bite! • College Displays Crime Statshttps://digitalcommons.ursinus.edu/grizzlynews/1234/thumbnail.jp

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

Chronic Hepatitis B Finite Treatment: similar and different concerns with new drug classes

Chronic hepatitis B, a major cause of liver disease and cancer, affects over 250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative HBV therapies are underway, consisting of combinations of multiple novel agents +/- nucleos(t)ide reverse transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, and subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives and regulatory agencies. This Viewpoint outlines areas of consensus within our multi-stakeholder group for stopping finite therapies in chronic Hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, pre-defined stopping criteria, pre-defined retreatment criteria, duration of investigational therapies, and follow up after stopping therapy. Future research of unmet needs are discussed