bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights into membrane dynamics in autophagy
Authors: Yoshimori Tamotsu 
Published: June 2021

In autophagy, the unique double membrane‐bound autophagosomes transiently emerge in the cytoplasm, sequester portion of cytosol and organelles, and eventually fuse with lysosomes to degrade the contents. The longstanding question in the filed is where autophagosome membrane comes from. We found that one of autophagy‐related (Atg) proteins, Atg14L localizes to the endoplasmic reticulum (ER) as well as autophagosome and the cytosol and its localization to the ER is essential to autophagosome formation. Meanwhile, electron tomography revealed that a subdomain of the ER forms a cradle encircling an immature autophagosome and the membranes were interconnected. Taken together, we suggest that the ER is a platform of autophagosome biogenesis. Furthermore, we revealed that autophagosome formation involves the linkage between the ER and mitochondria, which is also suggested as the autophagosome generator by another group.In addition, through investigation of autophagy against invading Salmonella, we showed that the LC3 (Atg8) system is recruited through a mechanism that is independent of the autophagosome membrane generation machinery, providing new insights into the mechanisms and the widely accepted model for selective autophagy.
Alteration of Metabolic Program by whiB6 Enhances Tuberculosis Persistence
Authors: Jacobs William , Weinrick Brian 
Published: June 2021

Persisters, drug sensitive survivors of drug treatment, may be the basis of the need for lengthy treatment regimens to cure tuberculosis and could also contribute to the ability of the bacteria to establish a latent infection.We established a basic model of persistence by treating M. tuberculosis cells with isoniazid, an antibiotic that induces lytic cell death. After four days exposure 99.9% of the initial inoculum is killed and the remaining population is significantly enriched in persisters. The transcriptional profile of these persister cells was compared to untreated cells. The most differentially expressed gene not also affected by short‐term isoniazid treatment was a putative transcription factor, whiB6.We created whiB6 knock out and complemented strains and identified the whiB6 regulon by transcriptional profiling. The whiB6 regulon is composed of genes involved in lipid anabolism, energy metabolism, and adaptation to hypoxia, heat shock, and oxidative stresses. The whiB6 mutant displayed drug tolerance alterations only under conditions simulating in vivo growth. We investigated the behavior of the whiB6 mutant in a mouse model of drug treatment, latency, and reactivation. The mutant was more effectively killed by drug treatment and may be less likely to enter a latent state.
Opportunities in the Private Sector
Authors: Rosenberg Martin 
Published: June 2021

The number of life science graduates (BS, MS, PhD and post doc) entering the job market continues to significantly outpace the career opportunities available for academic research faculty positions. This trend has been ongoing for decades but has certainly become more pronounced in recent years. During the 1980s and ‘90s the growth in private sector jobs for life scientists (e.g., the Biotech industry, R&D expansion in Pharma, etc.), in addition to increased hiring in the public sector (e.g., government) provided alternative careers for the ever‐increasing numbers of graduates. Many of the jobs in the non‐academic sectors did not require bench skills but did require strong scientific acumen.In the past decade however, a variety of factors (e.g., economic) have resulted in major shifts in the availability of non‐academic bench and non‐bench opportunities for life scientists. Jobs in academia remain stagnant and the training period for PhDs and post docs has expanded, in part, due to the slow down in employment opportunities.We will discuss the impact of these various changes on the current and future trends in the life sciences job markets. Are there bright spots? What skill sets are needed to be competitive? Are the current training systems adequate and appropriate for meeting the needs? My hope is to stimulate your thinking about how to maximize your marketability and competitiveness in these challenging times.
Using Small Molecules to Engineer and Explore Human Immunity
Authors: Spiegel David A 
Published: June 2021

Antibody‐based therapeutics have become critical instruments in treating diseases ranging from rheumatoid arthritis to cancer. However, antibodies and other therapeutic proteins are limited by their peptide‐based chemical nature: they require intravenous administration, are often highly immunogenic or allergenic, and treatment regimens are often very costly.This talk describes recent research efforts in our laboratories toward the design, synthesis, and biological characterization of antibody‐recruiting small molecules against prostate cancer, Staphylococcus aureus, and HIV. These are bifunctional molecules designed to redirect antibodies already present in the human bloodstream to the surfaces of pathogenic cells, forming a ternary complex that will lead to immune‐mediated pathogen destruction. In theory, this strategy would exploit many advantages of biologics, while circumventing the disadvantages, by capitalizing on the chemical properties of small molecules (high oral bioavailability, facile synthesis, and low cost).We hope that this small molecule‐based strategy will serve as a starting point toward entirely novel therapeutic approaches to a wide range of disease states.
Control of expression of cell wall stress‐induced yeast genes by transcriptional attenuation
Authors: Levin David E , Kim Ki-Young 
Published: June 2021

The MAPK Mpk1 of the Cell Wall Integrity signaling pathway uses a non‐catalytic mechanism to activate transcription of cell wall stress‐induced genes by acting as a co‐transcription factor. Mpk1 serves an additional function in transcription elongation that is also independent of its catalytic activity. This function is mediated by an interaction between Mpk1 and the Paf1 subunit of the Paf1C elongation complex associated with RNA Pol II. The Mpk1‐Paf1 interaction blocks recruitment of the Sen1 termination complex to the elongating RNA Pol II, thereby preventing transcriptional attenuation shortly after initiation. Attenuation under non‐inducing conditions appears to be a mechanism to minimize basal expression of stress‐induced genes. However, under inducing conditions, attenuation must be disabled to allow gene expression. Therefore, Mpk1 serves as an attenuation‐relief factor for cell wall stress‐induced genes.We found additionally that 10% of yeast protein coding genes are subject to Sen1‐mediated attenuation control that is independent of Mpk1 and cell wall stress. This subset is highly enriched for genes induced under various stress conditions, suggesting that transcriptional attenuation is a widespread phenomenon that extends to genes induced in response to a diverse array of stress conditions.
Identifying non‐vitamin & mineral bioactive (non‐VM) ingredients for inclusion in Dietary Supplement (DS) Composition Databases
Authors: Saldanha Leila G , Dwyer Johanna T , Holden Joanne M , Andrews Karen W , Bailey Regan L , Betz Joseph M , Gahche Jaime J , Hardy Constance J , Milner John , Roseland Janet M 
Published: June 2021

DSHEA defined DS and permitted addition of non‐VM ingredients if they meet the Act's requirements. Dietary Supplement Ingredient Database (DSID) is a federally funded database that contains analytically derived information on the composition of DS. DSID contains estimates of adult & child multi‐VM supplements (MVMs). Addition of over‐the‐counter (OTC) prenatal MVMs & omega‐3 fatty acid supplements to the database is in‐progress.ObjectiveDevelop a plan for including non‐VM ingredients in DSID.MethodThe DSID working group identified 41 non‐VM ingredients of interest. The criteria to rank and prioritize the 41 bioactives were existence of studies or safety concerns, public exposure, federal research priorities, and availability of validated analytical methods and analytical reference materials. Public health significance, previously used to rank VM ingredients, was not scored due to lack of data. The top 11 ingredients were: CoQ10, garlic, saw palmetto, ginkgo biloba, glucosamine, ginseng, green tea catechins (EGCG and other catechins), milk thistle, echinacea, flaxseed, and turmeric (curcumin).ConclusionObtaining input from the research community on which of these non‐VM ingredients should be incorporated into DSID and deciding on whether and how to report data for constituent levels not declared on the product label, i.e., proprietary formulas. (Funding Office of Dietary Supplements, NIH)
Dietary intake of overweight and obese children attending a weight‐loss program
Authors: Kranz Sibylle , Brauchla Mary , Garant Amanda , Gupta Sandeep 
Published: June 2021

Low diet quality is associated with the risk of overweight/obesity in adults but limited data is available on the effects in children. To improve the understanding of the role of diet on childhood obesity, we conducted a cross‐sectional observational pilot study in 5–11 year oldsattending the the Pediatric Overweight Education and Research Program (POWER) at Riley Hospital for Children, Indiana University, Indianapolis IN. Dietary intake was assessed using two 24‐hour recalls and mean intake of total energy, foodgroups, fiber, macro‐; and selected micronutrients was estimated. Results showed a mean daily intake of 1,503 kcals; 1.8, 1.6, 5.4, 0.9, 2.5 and 1.3 servings of fruits, vegetables, grains, whole grains, dairy, and meat, respectively. Thus, the diets of the children in this study were still deficient in fruits, vegetables, and whole grains, which led to fiber consumption levels below the recommendations. The foods consumed that contributed most of the fiber intake in this population were sweetened ready‐to‐eat cereals, fruits (apples, pears, pineapple, banana), fast‐food pizza, and meat sandwhiches. In conclusion, improving diet quality by increasing intake of fiber‐rich foods could possibly help support the establishing of healthy weight in this population.Grant Funding Source : Purdue University PDT grant
Paradigm Shift in Graduate Education: A Transdisciplinary Approach to Childhood Obesity Prevention
Authors: Kemmer Teresa M. , Koszewski Wanda M. , Meendering Jessica , Jensen Becky , Fischer Jean Ann 
Published: June 2021

The Transdisciplinary Childhood Obesity Prevention Graduate Program (T.O.P.) is designed to avoid the failed silo approach to obesity prevention and advance toward a team‐based participatory approach. The program combines expertise from South Dakota State University (SDSU) and the University of Nebraska‐Lincoln (UNL) in the areas of nutrition, early childhood education, family and consumer sciences, child development, exercise science, nutrigenomics and biostatistics.Students from a variety of disciplines implement and manage programs and research. The synergistic multidisciplinary team‐based learning approach enables students to foster working relationships and impact children, families, schools and communities. The program prepares students to 1) conduct research on the behavioral, social, biological, and environmental causes of childhood obesity, 2) implement evidence‐based transdisciplinary approaches to prevention, 3) expand understanding of the complex influences associated with excess weight gain and 4) develop and evaluate programs intended to prevent childhood obesity. To address health disparities, students participate in experiential learning opportunities in minority, underserved populations. Students graduate with a Master's or Doctoral degree from their respective college and obtain a T.O.P certificate. Funding: USDA NIFA Competitive Grants 2011□67002□30202.
Biomarkers of Nutrition for Development (BOND): An Overview
Authors: Raghavan Ramkripa , Darnton-Hill Ian , Raiten Daniel J 
Published: June 2021

ObjectiveThe aim of the BOND program is to harmonize the decision making process about what biomarkers are best for use in support of research, program development and evaluation, and generation of evidence‐based policy.MethodsTargeted workshops were held to discuss the growing need for nutrient biomarkers. Funding proposal was submitted to support the BOND program and a framework was developed to include a complementary translational and research tracks to further develop specific program activities.ResultsThe initial focus of BOND is on 6 case study nutrients: iodine, vitamin A, iron, folate, vitamin B12 and zinc, chosen for their public health importance and unique challenges related to the biomarker agenda. A Query Based System (QBS), which is a renewable and interactive IT resource, was developed to provide customized evidence‐based advice to users with regard to appropriate biomarker(s) for a given use. Nutrient specific expert panels were constituted to review and assess the extant literature and the evidence generated is being applied to the QBS and used to identify research gaps.ConclusionA system has been created whereby customized biomarker advice will be available via the QBS. The BOND project will inform the research agenda and lead to new technologies and approaches for biomarker discovery and development.Support: Bill & Melinda Gates Foundation; PepsiCo; NIH (ODS, DNRC, NICHD)
Dietary Milk Polar Lipids Benefit Gut Barrier Integrity And Lipid Metabolism In C57BL/6J Mice During Systemic Inflammation Induced By Escherichia Coli Lipopolysaccharide
Authors: Zhou Albert Lihong , Ward Robert E. , Hintze Korry J. 
Published: June 2021

To explore dynamic interactions among dietary fat, gut permeability and lipid metabolism in the context of systemic inflammation, 3 groups of C57BL/6J mice were fed for 8 weeks: (1) modified AIN‐93G diet (CO); (2) CO with milk gangliosides (GG); (3) CO with milk phospholipids (PL). After 2 weeks’ feeding, animals were injected subcutaneously with Escherichia coli lipopolysaccharide (LPS) endotoxin to induce acute inflammation. Animals were fed for 6 more weeks to observe recovery. Gut permeability was assessed by differential sugar tests at baseline and 24h, 2 week plus 4 week after LPS stress. GG protected intestinal integrity against LPS stress while PL facilitated the recovery of small intestine barrier function. Both GG and PL suppressed colon permeability increase against LPS stress and facilitated barrier integrity recovery while PL had a bigger effect for prevention and GG had a stronger effect for recovery. GG or PL did not affect food intake, weight gain or fasting plasma levels of glucose, cholesterol and triglycerides. Expressions of 13 genes on liver lipid metabolism were assessed by RT‐qPCR. GG increased beta‐oxidation gene ACAA compared with CO & PL. PL suppressed fatty acid synthesis gene ACC and cholesterol synthesis gene HMGCR compared with CO & GG. In general, dietary milk polar lipids may have beneficial effects on gut permeability and lipid metabolism in the context of systemic inflammation.Grant Funding Source: Western Dairy Center
Using Program Impact Pathways to Improve Anemia Reduction Programs
Authors: Phillips Erica Lyn , Pelletier David , Gervais Suzanne , Stoltzfus Rebecca , Young Sera , Michaud Lesly 
Published: June 2021

Recent evidence of the benefits of iron supplementation during pregnancy to reduce low birth weight and maternal mortality highlights the need for iron supplementation in pregnancy, an intervention known to be efficacious. Despite implementation of anemia reduction programs in many developing countries, the worldwide prevalence of maternal anemia in pregnancy remains over 40%. This suggests limitations in program delivery.To improve the delivery of a large‐scale anemia reduction program delivered through a mobile clinic program in rural Haiti, we designed a “Program Impact Pathway” (PIP) to delineate the mechanisms by which program activities resulted in desired outcomes. Survey data (n=663) from program beneficiaries were used to asses each essential component of the PIP, including consistent distribution of iron folic acid (IFA) at monthly clinics, women's understanding of how and why to IFA and barriers to adherence. Although knowledge about IFA benefits was high, irregular clinic attendance and inconsistent delivery of IFA resulted in a low median number of times women received IFA during pregnancy.Iron supplementation programs will be successful only if all essential elements linking program efforts to desired outcomes are identified and understood. The PIP provides such a method, and the lessons from its use in Haiti can be applied to other such programs.Research support: USAID, NIH/NIDDK
Plant cell culture strategies to increase 13C‐enrichment of lycopene for human metabolic tracing studies
Authors: Moran Nancy Engelmann , Conlon Lauren E. , Rogers Randy B. , Lila Mary Ann , Erdman John W. , Clinton Steven K. 
Published: June 2021

The red tomato carotenoid lycopene (LYC) and/or its metabolites may contribute to anti‐cancer bioactivity. However, little is known regarding LYC metabolites that are endogenously‐produced or absorbed from foods. To better understand LYC metabolism, tracer LYC was 13C‐biolabeled using tomato cell cultures grown in 13C‐glucose‐ containing media. Biolabeling produces a mixture of 13C‐mass isotopomers. The goal of this work was to shift the enrichment of LYC (C40H56) toward the uniformly labeled ([U]‐13C‐LYC) isotopomer, in order to provide a strong signal for metabolite detection. ‘Ailsa Craig’ hp‐1 cell cultures were grown in 13C‐glucose‐containing media for 1, 2, or 3 serial growth cycles and mass isotopomeric distribution was quantitated by tandem high pressure liquid chromatography (HPLC)‐mass spectrometry. Serially culturing cells for 1, 2, or 3 growth cycles led to [U]‐13CLYC yields of 10, 38, 46 %, respectively, with no deleterious effect on total LYC yield (~5 mg LYC/L culture for each cycle). To optimize harvest timing, HPLC evaluation of media glucose utilization during the labeling cycle indicated 99% of media glucose was incorporated by day 12 of the growth period. These approaches greatly enhance production efficiency of highly enriched a 13C‐LYC tracer for human carotenoid metabolism research.Grant Funding Source : Pelotonia Postdoctoral Fellowship at OSU and NIH/NCCAM 5R21AT005166‐02
Children's Very Low Food Security is Associated with Increased Dietary Intakes in Energy, Fat, and Added Sugar among Mexican‐origin Children (6–11 y) in Texas Border Colonias
Authors: Sharkey Joseph R. , Nalty Courtney , Johnson Cassandra , Dean Wesley R. 
Published: June 2021

BackgroundFood insecurity among Mexican‐origin and Hispanic households is a critical nutritional health issue of national importance. This study assessed the relationship between children's experience of food insecurity and nutrient intake from food and beverages among Mexican‐origin children (age 6–11 y) who resided in Texas border colonias.MethodsBaseline data from 50 Mexican‐origin children were collected in the home by trained promotora‐researchers. All survey (demographics and nine‐item child food security measure) and 24‐hour dietary recall data were collected in Spanish. Separate multiple regression models were individually fitted for specific nutrients.ResultsThirty‐two children (64%) reported low or very low food security. Very low food security was associated with greater intakes of total energy and percentage of calories from fat and added sugar.ConclusionsSuch findings have implications at a regional and national level, as the Mexican‐origin population continues to grow along the border and in new destination communities. Child‐reported food insecurity situations could serve as a screen for nutrition problems in children. Further, the National School Lunch and School Breakfast Programs, which play a major beneficial role in children's weekday intakes, may not be enough to keep pace with the nutritional needs of low and very low food secure Mexican‐origin children.
A Role for microRNAs in Axenfeld Rieger Syndrome and Craniofacial/Tooth Anomalies
Authors: Amendt Brad A. , Cao Huojun , Wang Jianbo , Li Xiao , Gutierrez Diana 
Published: June 2021

Mutations in the PITX2 homeobox gene are associated with Axenfeld Rieger syndrome (ARS) and defective PITX2 transcriptional activity affects microRNA expression.MethodsConditional knockout and transgenic mice, molecular and biochemical assays reveal molecular mechanisms of specific microRNAs and a regulated network for their expression.ResultsWe have identified discrete sets of mircoRNAs expressed at various stages of craniofacial development. Conditional knockout (cKO) of Dicer1 (mature microRNAs) in the dental and oral epithelium using the Pitx2 Cre mice results in multiple and branched enamel‐free incisors, cusp‐less molars and cleft palate. The cervical loop (stem cell niche) is expanded in Dicer1 cKO and epithelial cell differentiation is repressed. PITX2 regulates the expression of microRNAs that target Noggin, a potent BMP inhibitor, Lef‐1/Wnt‐β‐catenin signaling and HMGN2 a chromatin‐associated remodeling factor. PITX2 positively and negatively regulates a novel microRNA‐gene expression network involved in progenitor cell (stem cell) proliferation and differentiation.ConclusionsPITX2 regulates microRNA expression and microRNAs feedback to regulate PITX2 expression through several novel molecular mechanisms. Support for this research was provided from grants DE13941 and DE18885 from the National Institute of Dental and Craniofacial Research.
Muse cells: a novel type of adult human pluripotent stem cells in mesenchymal tissues and their contribution to tissue repair
Authors: Dezawa Mari 
Published: June 2021

We newly found a unique type of stem cells which we named Multilineage differentiating Stress Enduring (Muse) cells (PNAS, 2010). They can be isolated as cells double positive for mesenchymal marker CD105 and human ES cell marker SSEA‐3 from bone marrow, skin, fat tissues and human cultured mesenchymal cells. They express pluripotent stem cell markers, self‐renew and generate cells representative of all three germ layers. Most importantly, they do not show tumorigenic proliferation. When human Muse cells are infused into tail vein of Nog‐mouse suffering from fulminant hepatitis, human Muse cells integrated into mouse liver and differentiated into hepatocyte having an ability to release human albumin into blood stream.Recently, we found that Muse cells are a primary source of iPS cells in human fibroblasts (PNAS, 2011). When human fibroblasts were separated into Muse and non‐Muse cells and transduced with Yamanaka four factors, iPS cells were generated exclusively from Muse cells, but never from non‐Muse cells. Epigenetic alterations were not seen in non‐Muse cells and some of the major pluripotency markers were not expressed for the entire period of generation.Thus, Muse cells will be beneficial for cell‐based therapy and biomedical research.