bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of iodine contents in breast milk and dairy products by inductively coupled plasma mass spectrometry (250.8)
Authors: Liu Liping , Li Xiaowei , Li Yiwei , Du Shufa
Published: June 2021

China is one of the countries most severely affected by iodine deficiency disorders (IDD) with 375 million of population affected. Both overconsumption and underconsumption of iodine are detrimental to children’s body and brain development. Breast milk and dairy products are essential iodine sources for infants while few iodine contents in breast milk or dairy products available in China. We collected breast milk samples from 12 provinces in China and dairy products from supermarkets in Beijing. We extracted iodine from samples by using tetramethylammonium hydroxide and hydrogen peroxide. Using Te128 as the internal standard, we determined iodine contents in breast milk and dairy products with inductively coupled plasma mass spectrometry (ICP‐MS). Detection limit of the method was 0.09 ng/mL; the linear range was between 0‐400 ng/mL; and the linear coefficient(r) was better than 0.9995. The precision of the method (RSD%) were all less than 5%. Precision and accuracy were evaluated by analysis of certified reference materials NIST 1549 non‐fat milk powder. The recoveries for real samples were from 83.3% to 116.5%. The iodine contents were around 0.15 mg/kg in fresh milk and yogurt. The iodine contents in breast milk were 0.41‐0.47 mg/kg in urban areas, significantly higher than that in rural areas, 0.16‐0.35 mg/kg. Infants in rural areas are more vulnerable to IDD.
The anti‐inflammatory effects of manniflavanone extracted from Garcinia buchananii bark in obesity‐induced mice model (259.3)
Authors: Bibi Shima , Balemba Onesmo , Carrion‐Rabanal Rocio , Nyavor Yvonne , Noratto Giuliana
Published: June 2021

The stem bark of Garcinia buchananii trees is used traditionally to treat diarrhea, dysentery, weight control, and diabetes in Africa. We investigated the anti‐inflammatory and antioxidant activity of the stem bark extracts and identified manniflavanone (Mf) as the most active antioxidant and anti‐inflammatory phenolic compound among the isolated bark phenolics. Seven‐week‐old C57Bl/6 J mice (4 groups) were fed a standard chow (SC) diet and high fat (HF) diet with Mf (SCMf, HFMf) extract (0.164 mg/day) for 3 weeks. Mice were terminated after 8 weeks, fecal and colon tissue was collected for analysis of inflammatory markers and microbiota. Results showed that body mass index (BMI) of mice on SCMf was lower (3.3 Kg/m2) than mice on SC (3.75 Kg/m2). Colon IL‐8, NF‐ĸB and TNF‐α mRNA levels were downregulated in SCMf to 0.69‐, 0.68‐ and 0.49‐fold of SC control, respectively, while IL‐8 and NF‐ĸB were downregulated in the HFMf to 0.27‐ and 0.53‐fold of HF control, respectively. These results indicate that the underlying anti‐inflammatory effects of Mf are related to inhibition of NF‐ĸB and NF‐ĸB‐target genes and we are currently investigating the link with changes in fecal microbiota.

Grant Funding Source: wheat project
Consumption of vegetable oils with different unsaturated fatty acid profiles increases cholesterol efflux from THP‐1 macrophages (269.4)
Authors: Liu Xiaoran , Kris‐Etherton Penny , West Sheila , Lamarche Benoît , Couture Patrick , Jenkins David , Fleming Jennifer , Vanden Heuvel Jack , Jones Peter
Published: June 2021

Cholesterol efflux (CEx) from peripheral tissues is thought to be cardioprotective. Vegetable oils with different unsaturated fatty acid (UFA) profiles and low in saturated fatty acids (SFA) (<10g /100g) may enhance CEx from lipid laden macrophages. The Canola Oil Multicentre Intervention Trial was a double‐blind, randomized, 5‐period crossover, controlled feeding (weight maintenance) study designed to evaluate the efficacy of five vegetable oil treatments on CEx in individuals at risk for Mets with central obesity. These treatment oils were canola oil (62.8% MUFA, 29.3% PUFA: 19.5% LA, 10% ALA), high oleic canola oil (72% MUFA, 17% PUFA: 15% LA, 2% ALA), high oleic canola oil with DHA (63.8% MUFA, 13% LA, 6% DHA), corn/safflower oil (69.3% LA, 17.6% MUFA), and flax/safflower oil (69.4% PUFA: 37.5% LA, 32% ALA, 17.9% MUFA). Subjects (n=100: 51 women, 49 men) were fed isocaloric, heart healthy diet (50% CHO, 15% PRO, 35% FAT, SFA < 7%) containing one of the five treatment oils incorporated in a smoothie for 4 weeks followed by a 2‐4 week break between diets. CEx was measured via a high‐throughput assay using THP‐1 macrophages incubated with human sera from baseline or post diet treatment. At the end of each treatment, canola oil, high oleic canola oil with DHA, corn/safflower oil and flax/safflower oil increased CEx by 28.5%, 31.6%, 20.7%, 20.1% respectively, compared to baseline values (p<0.05). The increase in CEx following high oleic canola oil consumption was 8% (NS). Predictors of CEx capacity in subjects at risk for MetS with central obesity include gender, weight status and baseline CEx. In summary, vegetable oils high in UFA and low in SFA increase CEx from macrophages.

Grant Funding Source: Supported by: Canola Council of Canada
Biochemical studies on replication of the genome in eukaryotes (27.1)
Authors: Stillman Bruce , Speck Christian , Li Huilin
Published: June 2021

Our primary goal has been to understand how chromosomes are duplicated during the cell division cycle to ensure faithful inheritance of genetic information in eukaryotes. By initially investigating SV40 DNA replication, we reconstituted the entire process of DNA replication from the SV40 origin and in so doing discovered how the replication fork is assembled. Later, from studies on replication of DNA from chromosomal origins of DNA replication in eukaryotic cells, we discovered an ATP‐dependent protein machine, the Origin Recognition Complex (ORC) that is required to form a pre‐Replicative Complex (pre‐RC) at all origins of DNA replication prior to S phase. The process of pre‐RC assembly at origins of DNA replication licenses chromosomes for subsequent DNA replication during the S phase of the cell cycle. Pre‐RC assembly has been reconstituted in vitro with purified proteins and structural studies have revealed a conserved mechanism of protein assembly on origin DNA. Activation of DNA replication requires multiple protein kinase signaling systems, including the Cyclin‐Dependent Protein Kinase (CDK), the Cdc7‐Dbf4 Protein Kinase (DDK) and the Mec1 (ATM/ATR) checkpoint kinase. The presentation will focus on both the mechanism and regulation of the initiation of DNA replication.
Site‐and promoter‐specific epigenetic alterations by a common dietary compound (271.5)
Authors: Dey Moul , Liu Yi
Published: June 2021

Effects of dietary compounds on site‐specific histone modifications, which are key epigenetic regulators of gene expression impacting cancer etiology, remain relatively unexplored. Phenethylisothiocyanate (PEITC) is a common dietary compound derived from cruciferous vegetables. Our previous research have shown promising anti‐inflammatory and chemo preventive properties of PEITC. The present study reports novel, dynamic, site‐specific chemical changes to histone H3 in a gene‐promoter‐specific manner, associated with PEITC exposure in human colon tumor‐derived epithelial cells. The time‐and concentration‐dependent effects of PEITC on histone modifications (di‐and tri‐methylations of lysine‐9 and lysine‐27 and acetylation) and gene expression changes were achieved at low, non‐cytotoxic concentrations, in contrast to the higher concentrations necessary to halt cancer cell proliferation likely mediated by caspase‐dependent apoptotic signaling. Increased understanding of specific epigenetic alterations by dietary compounds may provide molecular predictors for improved preventive strategies for reducing the healthcare burden of cancer and other human diseases.

Grant Funding Source: The work is supported by the National Institutes of Health grant R00AT4245 and SDAES grant 328100/31
Comparative bioavailability of omega‐3 fatty acids from four different omega‐3 supplements (272.6)
Authors: Laidlaw Maggie , Cockerline Carla , Rowe William
Published: June 2021

This was an open‐label cross‐over study. Thirty‐five healthy subjects were randomized to consume one of four products for four weeks, followed by a four‐week washout. The four products and daily doses (as recommended on the product labels) were: Nordic Naturals ProOmega® Concentrated Triglyceride fish oil: EPA of 650 mg, DHA of 450 mg Minami MorEPA® Platinum Ethyl Ester fish oil: EPA of 756 mg, DHA of 228 mg Source Naturals ArcticPure® Phospholipid krill oil: EPA of 150 mg, DHA of 90 mg New Chapter Wholemega® Triglyceride (TG) salmon oil: EPA of 180 mg, DHA of 220 mg This schedule continued until participants had consumed each product for four weeks, in random order. Blood samples before and after supplementation were quantified for whole blood fatty acids by gas chromatography flame ionization, followed by statistical analyses using ANOVA for repeated measures.

At the prescribed daily dose, concentrated TG fish oil was statistically superior to all of its comparators in the bioavailability of EPA+DHA, and of DHA alone. Its EPA percentage increase was more than four times that of krill oil and TG salmon oil. At an extrapolated dose of 1,000 mg/day of omega‐3 fatty acid of interest, concentrated TG fish oil maintained its superiority over all three comparators for the whole blood EPA, DHA and EPA+DHA increases over 28 days of supplementation. For patients, type and dose of omega‐3 supplementation may be clinically important.
Chewing gum influences grocery shopping behavior (273.4)
Authors: Wansink Brian , Tal Aner , Miquel‐Kergoat Sophie
Published: June 2021

The studies aimed to examine whether chewing gum during grocery shopping can increase lower calorie food purchases. Participants (N = 59) in a lab study were asked to shop at a simulated online grocery store while chewing gum or not (determined by random assignment). Participants chewing gum selected 21.25% fewer bags of chips and Doritos and 17.89% more fruits and vegetables compared to those who were not chewing gum. The overall ratio of less caloric foods to more caloric foods in their total grocery choices increased by 14.69% from 62% to 77% (p = 0.03). In a pilot field study designed to examine the mechanisms behind this phenomenon, shoppers (N = 289) were randomly assigned to gum‐chewing or no gum‐chewing conditions, and asked to report on their level of hunger and cravings at the end of their shopping trip. There was a significant reduction in self‐reported hunger for those chewing (p = .03), as well as directional reductions in self‐reported cravings. Chewing gum while shopping appears to lead consumers to select healthier food, possibly due to reduced hunger and cravings.

Grant Funding Source: Wrigley’s Science Institute
Visiting Scholars and BlastOff! Flow from BECUR (29.3)
Authors: Cai Wesley , Cheah Cheryl , Phan Andy , Seto Nicki , Taniguchi Sho , Figueroa Eric , Hazzard James
Published: June 2021

The University of Arizona UAN Chapter engages middle school, high school, and undergraduate students through research‐oriented outreach. Our fifth annual BECUR Conference held in February 2014 featured posters and talks by undergraduate and high school students with Professor Roy Parker as the keynote speaker. Building upon the success of BECUR, our chapter is organizing two more outreach activities: the Visiting Scholars program and BlastOff! summer camp. Visiting Scholars sends undergraduates into high school classrooms to present research, provide information on opportunities in science, and share their college experiences. The program is now a formal department course. BlastOff! is a five‐day biology‐oriented summer camp that recruits middle school students from underrepresented populations in the sciences. Campers are exposed to “wet lab” techniques, scientific theories, and hands‐on projects, while field trips and presentations by guest speakers complement lab activities.
Visualizing molecular biology through animation and installation art (29.6)
Authors: Peterson Celeste , Murthy Anastasia , Swerdlow Kyle , French Lisa , Berkmen Melanie
Published: June 2021

To promote molecular biology education to elementary school children and the general public, we have initiated a number of projects that bring the arts into traditional STEM outreach programs. Here we present two case projects of our UAN (Undergraduate Affiliate Network) chapter work in Boston and Cambridge, i) The “What is a Germ Contest?” movie and animation project and ii) Central Elements installation art project. The “What is a Germ?” contest, created and organized by ASBMB, challenges students to create a piece of art that best explains the question of what a germ is, as judged by elementary school children. We designed our script so that each UAN college student chose a germ and wrote the dialog for their part and then the whole group worked together to create a stop‐motion clay animation short. The animation approach for explaining molecular processes has received positive feedback from students. This following year, the UAN students are mentoring an inner city youth group as they develop their own video entry. The Central Elements Project, organized by the Cambridge Science Festival, pairs groups of scientists with artists to represent a chemical element in a shop front window. Students working on this project explain the science to the artist and work with them to emphasize the underlying concepts. Both of the projects described here enable students to dive deep into specific molecular biology topics and also creatively think about visually compelling ways to educate different audiences.
From mental health to the host microbiome: Looking at the forest not just the trees in wound healing (337.1)
Authors: Shupp Jeffrey , Moffatt Lauren
Published: June 2021

The pathophysiology of acute and chronic wounds continues to be an area of active investigation. However, little is known about the interplay between transcript and epigenomic alterations and augmentations in wound healing. Further, research is lacking in identification of genotypic signatures that may lead to customized approaches to treatment. Additionally the interplay between the endogenous and the acquired microbiome may have great impacts on wound phenotype, healing, and scarring. The prokaryotic‐host interaction may play a substantial role in determining the quality and speed of wound repair. Studies examining 57 patients after burn injury show that stress system activation contributes to burn‐related pain, itch and healing. Identification of patient specific transcript signatures may lead to early identification of problematic wounds and customizable treatment. Similarly in animals and patients exposed to stress and subsequently exhibiting symptoms of PTSD immunosuppression and perturbations in pathways relating to wound healing are consistent and persist over time. Understanding the influence of these multi‐system changes could lead to the early identification of patients that need more aggressive care in order to prevent chronic non‐healing wounds that have poor healing quality. Host prokaryotic bio‐burden is being examined to determine the cutaneous microbiome and how it is altered by traumatic wounds. Experiments in burn patients and animals examining phenotypic alterations of benign microbes after injury show that virulence factor production is altered. The resulting PAMPs and DAMPs interact directly with cutaneous cells causing an innate immune response that not only leads to augmentation in inflammatory response but induces differential regulation of multiple pathways responsible for wound healing and scar.
An anatomy ontology for oro‐pharyngeal muscles and the logical underpinnings of comparative anatomy (338.4)
Authors: Druzinsky Robert
Published: June 2021

The FEED ontology is an ontology for oro‐pharyngeal muscles and behaviors (http://code.google.com/p/feedontology/). The FEED ontology is an outgrowth of the Feeding Experiments End‐User Database (FEED, http://www.feedexp.org), a multi‐species mammalian database that includes EMG, bone strain, bite force, sonomicrometry, and kinematic data collected during feeding behaviors. FEED utilizes a controlled vocabulary of terms for mammalian feeding muscles and feeding behaviors. The FEED ontology contains classes that refer to anatomical structures, behaviors, and other entities involved in feeding, each of which is given a unique identifier and an explicit definition that is interconnected to other entities by logically defined relationships. These logical definitions make explicit the semantic underpinnings of comparative anatomy. Many of the classes have been merged directly into Uberon (Mungall et al., 2012. Genome Biology, 13(1), R5), a large, multi‐species anatomy ontology. The structure enables connections and queries across the FEED and other ontologies with which it is integrated, such as GO (Gene Ontology), and MA (Mouse Anatomy), as well as to the FEED database itself, and it contributes to the growing framework of ontologies and databases for organizing and analyzing biological data across disciplines and domains.
Getting a head: changing perspectives on craniofacial development (340.1)
Authors: Noden Drew
Published: June 2021

This occasion prompts reflection on questions raised related to craniofacial development. Lineage tracing methods have clarified movements and fates of paraxial and lateral mesoderms and neural crest cells in several model species. These approaches have delineated shared, conserved from specialized, derived patterns of tissue dispersal. For example, laryngeal cartilages, which traditionally were homologized with pharyngeal arch elements, receive substantial contributions from lateral mesoderm.

“Migratory” is an attribute frequently applied to crest cells. However, underlying locomotory mechanisms are varied and both active locomotion and passive displacement contribute. Paraxial mesodermal cells display a panoply of behaviors, from stationary pre‐chondroblasts to directed pre‐osteoblasts to undirected, invasive movements of angioblasts. These bring mesodermal populations to the interface with crest cells, but crossing is selectively controlled.

Musculoskeletal assembly is hierarchical, with crest‐derived connective tissue progenitors at the top. Executing these assemblies requires progressive interactions that bring redundancy to the process. Some of these interactions are similar to those operating in other body regions, whilst others are unique to each niche. These features of craniofacial development will be discussed in the context of questions yet unanswered.
Introduction of an anatomy multi‐station integrated table conference (343.1)
Authors: Morton David , Hutcheson David
Published: June 2021

Assessment is the culmination for any educational activity. Anatomy assessments in medical school traditionally consist of multiple choice and cadaver practical exams. When the University of Utah School of Medicine adopted an integrated curriculum the mode of assessments also changed including the addition of Objective Structured Clinical Exams (OSCEs) as the summative form of clinical assessment. An OSCE is a one‐on‐one exam with multiple stations testing communication, physical exam, clinical knowledge, and radiographic interpretation among other skills. We asked the question, “How can we as anatomy professors create an assessment similar to the OSCE?” We implemented an anatomy multi‐station, integrated table conference into the dissection schedule. Three times throughout the Foundations of Medicine Unit medical and dental students were tested one‐on‐one regarding their knowledge of anatomy. The anatomy questions were standardized and had correlations to clinical medicine, histology, embryology and radiology. The students rotated from station to station using a combination of cadavers, skeletons, and images (either on iPads or printed and placed on the wall) to answer the questions. As a result, students were graded not only on their knowledge of anatomy but also their verbalization of this knowledge within an integrated context of medicine and clinical sciences.

Grant Funding Source: Supported by the Department of Neurobiology and Anatomy
RAP Sessions ‐ interdisciplinary delivery of anatomy, radiology, and procedural skills (343.2)
Authors: Lee‐Poy Michael , Abrams Mitch , Green Lawrence , Morris Cathy , Bridgewater Darren
Published: June 2021

The McMaster University Michael G. DeGroote School of Medicine’s undergraduate medicine curriculum is a concepts‐based curriculum with anatomy sessions, lectures and small group tutorials. Curriculum review revealed a paucity of radiology and procedural skills in the pre‐clerkship training. An interdisciplinary program of anatomy, radiology, and procedural skills was developed. Method: A 3‐hour curriculum was developed that integrated chest anatomy taught by an anatomist, radiology related to the chest taught by a radiologist, and the procedural skill of placing a chest tube by a general surgeon. The session revolved around a case that was part of their regular small group tutorials. Students rated their knowledge of chest anatomy, knowledge of placing a chest tube and their comfort with placing a chest tube pre and post session using a 10‐point Likert rating scale. Students were also asked to rate the experience on a number of dimensions. Results: 23 students participated in this workshop. All completed the pre and post questionnaires. Students reported an increase in self‐rated knowledge of chest anatomy (4.3 vs 6.4), knowledge in placing a chest tube (1.8 vs 7.7), and in comfort with placing a chest tube (1.4 vs 6.3 post. These results were analyzed using Wilcoxon Signed‐Rank Test and the differences were all statistically significant (p<0.001). The sessions were highly rated, with the mean value for organization/venue scale being 9.4 out of 10 (SD=0.6) and educational value scale (effective, appropriate) being 9.3 out of 10 (SD=0.07). Conclusion: RAP sessions are an innovative interdisciplinary curriculum integrating radiology, anatomy and procedural skills within the context of a concept based medical curriculum. Students reported an increase in knowledge and skills and highly rated the experience as a valuable teaching session for concept integration.
The influence of spatial ability on high and low order anatomy examination questions in a first year integrated medical curriculum (343.4)
Authors: Martin Charys , Edmondson Anna , Nguyen Ngan
Published: June 2021

Students with high spatial visualization ability (Vz) achieve higher grades in anatomy than students with low Vz; however, the influence of Vz on different Bloom’s Taxonomy levels of exam questions has not been established. This study examines the effect of Vz on different Bloom’s Taxonomy levels of anatomy questions. It is hypothesized that students with high Vz will outperform students with low Vz on higher order questions. Participants completed the Mental Rotations Test (MRT) to establish Vz. The mean Vz was 11.5±4.7, which divided participants into high Vz (n=30; mean MRT=15.4±2.7) & low Vz (n=29; mean MRT=7.5±2.5) groups. Exam questions were categorized into 4 Bloom’s levels: knowledge, comprehension, application & analysis. Preliminary data indicate students with high Vz (Vz=90.67±6.91) outperform students with low Vz (Vz=84.55±12.86; p<0.05). Students with high Vz performed better on comprehension level questions (p<0.05) whereas, there was no difference when assessing other exam question levels. This suggests that while high Vz students perform better overall & on comprehension questions, there may not be significant differences on knowledge, application & analysis questions. However, this sample only included 5 knowledge, 8 application & 2 analysis questions indicating that the inclusion of future exam questions may be required to establish significance within the other question levels.
Anatomy integration blueprint: a 4th year musculoskeletal anatomy elective model (343.5)
Authors: Lazarus Michelle , Kauffman Gordon , Kothari Milind , Silvis Matthew , Wawrzyniak John , Anderson Daniel , Black Kevin
Published: June 2021

Medical school curricular trends focus on an increase in basic science education in clinical years. This vertical integration is difficult and poorly reported in the literature. We have outlined a course wherein the primary learning objective is to integrate anatomy knowledge with clinical education. This course has a foundation in adult learning theories and was developed through collaboration by a multi‐specialist course development team, composed of both basic scientists and physicians. The course developers utilized current published reports regarding the areas of clinical care relying heavily on anatomy knowledge. The course focuses on the role of anatomy in the diagnosis and treatment of musculoskeletal conditions. This iterative implementation and research approach to course development has yielded a curricular template for anatomy integration into clinical years. Positive findings included: Clinical anatomy curriculum can be developed which is applicable to multiple future specialties, faculty enthusiasm and investment in course objectives impacts course effectiveness, providing multiple learning approaches enhances the educational experience, communication between specialists is an important course component and that having the student perform as the teacher enhances learning and student enjoyment. This work serves to enhance current methods of anatomy integration.
A gift in disguise: teaching opportunities that are overlooked in the gross anatomy laboratory (343.7)
Authors: Rae Guenevere , McGoey Robin , Newman William , Del Valle Luis , Swartz William
Published: June 2021

The Anatomy faculty worked in collaboration with the Department of Pathology to enhance the first year medical student’s gross anatomy laboratory experience. Pathology faculty visited the laboratory three times during the gross anatomy course to identify pathology encountered in the cadavers and to discuss these clinico‐pathologic incidences with the medical students. Pathologists took tissue samples from the cadaveric specimens and presented a 45‐minute PowerPoint slide show at the end of the course. This collaboration enabled the pathology and anatomy faculty to incorporate both vertical and horizontal integration of disciplines taught within the undergraduate medical curriculum. As a result of this interdepartmental collaboration, there were several learning opportunities that were captured by the pathology faculty that would have been overlooked by the anatomy faculty. As an assessment of this interdepartmental collaboration on first year medical students, the students were asked questions on their course evaluation about the impact of the clinico‐pathologic course material on their learning. In addition, the student’s end of the year reports on their cadaver were qualitatively analyzed for clinico‐pathologic references and compared to those of previous years. In conclusion, the addition of pathology into the anatomy course can be beneficial to both students and faculty.

Grant Funding Source: Academy for the Advancement of Educational Scholarship LSUHSC
Cell intercalation and migration mediated by actin contractility are key cellular behaviors in fusion of the mammalian secondary palate (344.2)
Authors: Bush Jeffrey , Kim Seungil
Published: June 2021

Fusion of two distinct embryonic prominences is a process common to numerous developmental contexts and often requires the removal of an intervening epithelium. Upon fusion of the mammalian secondary palatal shelves, the resulting medial epithelial seam (MES) must be removed to allow formation of a continuous secondary palate. This problem has been studied at great length, leading to three main cellular explanations. Whereas considerable investigation has been made into epithelial to mesenchymal transition (EMT) and programmed cell death of the intervening epithelium as the definitive cellular mechanisms, the contribution of cell migration of the intervening epithelium in this process is not clear. By combining confocal live imaging in explant culture with functional molecular genetics in mice, we now provide direct evidence that cell migration is a key component of removal of the MES. Further, we find that integration of a disorganized multi‐layered epithelium into a shared single layer epithelium is an essential early step in secondary palate fusion. Both integration and migration of the MES requires an actin contractility pathway involving Rho Kinase (ROCK), Myosin light chain kinase (MLCK) and culminating with activation of Non‐muscle myosin IIA (NMIIA). Together, these data provide direct support for cell migration in removal of the MES, and allow us to begin to assemble a molecular pathway controlling this action.

Grant Funding Source: Supported by R03 DE022818 from NIH/NIDCR
A nucleolar role for FGFR2 in bent bone dysplasia syndrome (344.5)
Authors: Neben Cynthia , Idoni Brian , Salva Joanna , Tuzon Creighton , Rice Judd , Krakow Deborah , Merrill Amy
Published: June 2021

Fibroblast Growth Factor Receptor 2 (FGFR2) promotes osteoprogenitor cell proliferation and differentiation during bone development, yet it remains unclear how the receptor couples these distinct cellular processes. Analysis of the new FGFR2‐skeletal disorder Bent Bone Dysplasia Syndrome (BBDS) suggests that the receptor, in addition to its canonical activities, regulates bone formation within the nucleolus. We previously showed that the FGFR2 mutations in BBDS reduce receptor levels at the plasma membrane and markedly diminish responsiveness to extracellular FGF2. Despite decreased canonical FGF signaling, cells with mutant FGFR2 show enhanced nucleolar localization with intracellular FGF2. The nucleolus is the site of ribosome biogenesis, and ribosome dysfunction is linked to skeletal birth defects. By employing the BBDS mutations in cultured preosteoblasts, we found that nucleolar FGFR2, along with FGF2 and the rDNA transcription factor UBF1, interacts at the rDNA promoter to promote transcription and subsequently cell proliferation. Our studies also show that nucleolar FGFR2 blocks the transcriptional repressor activities of RUNX2, the master regulator of osteoblast differentiation, at rDNA. Together this data suggest that nucleolar FGFR2 links proliferation and differentiation in preosteoblasts by regulating rRNA transcription, the rate‐limiting step in ribosome production.

Grant Funding Source: Supported by NIH/NIDCR #T90DE021982 to C.L.N., MOD #5‐FY12‐166 to A.E.M., NIDCR 5 P30 DE020750‐02
Synthetically rerouting phagocytosis by rapidly turning inert cells into “eat you” mode (345.1)
Authors: Inoue Takanari
Published: June 2021

Through ceaseless communications with the environment, cellular surface represents an origin of information flow that determines diverse cellular processes. Techniques to rapidly engineer the surface property of living cells should thus offer a power to harness the cellular functions. In this study, we developed and implemented a technique to induce presentation of a molecule of interest at the cell surface on a timescale of minutes. While the molecular mechanism of phagocytosis is well characterized, minimal molecular events that are sufficient to trigger this elaborate process remain elusive. With an induced surface display of a C2 domain of MFG‐E8 protein as well as Rac small GTPase activation inside cells, we rapidly turned inert human HeLa cells into “eat you” mode and made them bind and engulf apoptotic human Jurkat T cells. Actuation of neither signal was sufficient on its own to trigger phagocytosis, indicating target cell attachment and actin reorganization constitute minimal molecular events for fulfillment of phagocytosis. The present surface display technique may be used as a targeted cell‐based therapy where unwanted cells with characteristic surface molecules will be rapidly eliminated by engineered cells.
Mitochondria play a central role in NLRP3 inflammasome activation (349.1)
Authors: Subramanian Naeha , Natarajan Kannan , Clatworthy Menna , Wang Ze , Germain Ronald
Published: June 2021

NLRP3 is a key component of the macromolecular signaling complex called the inflammasome that promotes caspase 1‐dependent production of IL‐1β. The adapter ASC is necessary for NLRP3‐dependent inflammasome function, but it is not known if ASC is a sufficient partner, and whether inflammasome formation occurs in the cytosol or in association with mitochondria is controversial. Here we show that the mitochondria‐associated adapter molecule, MAVS, is required for optimal NLRP3 inflammasome activity. MAVS mediates recruitment of NLRP3 to mitochondria, promoting production of IL‐1β and the pathophysiologic activity of the NLRP3 inflammasome in vivo. Our data support a more complex model of NLRP3 inflammasome activation than previously appreciated, with at least two adapters required for maximal function. Since MAVS is a mitochondria‐associated molecule previously considered to be uniquely involved in type 1 interferon production, these findings also reveal unexpected polygamous involvement of PYD/CARD domain‐containing adapters in innate immune signaling events.
The role of glycans in platelet birth and death (359.2)
Authors: Hoffmeister Karin , Jurak Begonja Antonjia , Giannini Silvia
Published: June 2021

Delayed platelet recovery and bleeding complications are major determinants of morbidity and mortality following cancer treatment. Platelets are produced by megakaryocytes (MKs), which normally reside in the vascular bone marrow (BM) niche and interact with sinusoidal BM endothelial cells to release platelets into the bloodstream. Following release, platelets circulate for 5 days in mice and 10 days in humans. The regulatory mechanisms of platelet death and birth remain unclear. In recent years it has become increasingly apparent that platelet life‐span is regulated by glycan‐lectin clearance mechanisms. We have now obtained direct evidence that lactosaminyl glycans (LacNAc) synthesized by the β4galatosyltransferase 1 (β4GalT1) not only regulate platelet life span, but are key regulators of thrombopoiesis. β4GalT1‐/‐ mice exhibit severe macro‐thrombocytopenia because megakaryocytes lacking functional β4GalT1 fail to produce circulating platelets, although they mature and differentiate normally. Expression of lactosaminyl glycans within hematopoietic marrow cells occurs in a stage‐specific and lineage‐specific fashion. Our data show that LacNAc synthesis mediated by β4GalT1 is crucial for platelet genesis but not for megakaryocyte maturation, pointing to a very specific role for LacNAc sythesis in the last step of megakaryocyte differentiation, i.e platelet production, and in the interaction with the components of the vascular BM niche.
Exploring Lebanese children’s experiences of food insecurity (378.2)
Authors: Ghattas Hala , Aqeel Marah , Sassine AnnieBelle , Hwalla Nahla , Sahyoun Nadine
Published: June 2021

Recent studies from the USA show that child‐specific instruments to assess food insecurity describe childhood food insecurity more accurately than parent reports, and that this experience is unique in terms of content and context. Whether this is true in cultural contexts outside of the USA is unknown. We conducted semi‐structured interviews with 37 mother‐child (aged 8‐12 years) dyads living in food insecure families in Lebanon, and explored children’s experiences and perceptions of food insecurity. We found that children were able to rationalize economic aspects of food insecurity including the value of money, the importance of salary as household income and the unaffordable nature of specific foods. Children expressed emotions such as worry and empathy related to food insecurity, particularly for their siblings and parents. Children were physically aware of hunger and participated in various coping strategies, including decreasing the amount of food they consumed, prioritizing younger siblings, saving money, working and managing with whatever was available. These data can be used to better understand and assess childhood food insecurity and to develop child‐specific insights to inform interventions to alleviate food insecurity in Lebanese children.

Grant Funding Source: Supported by University Research Board, American University of Beirut and Nestle Middle East
Household food insecurity associated with child cognitive development in a rural Kenyan community on Lake Victoria (378.6)
Authors: Milner Erin , Fiorella Kathryn , Hickey Matthew , Salmen Charles , Omollo Dan , Mattah Brian , Magerenge Richard , Brashares Justin , Fernald Lia
Published: June 2021

Household food insecurity around Kenya’s Lake Victoria is widespread. The goal of this study was to examine the associations between food insecurity, child anthropometry and child development in 300 children 0‐2 years old living in a rural lakeside community in Kenya. Outcome measures obtained included anthropometric measurements (length and weight) and the Ages and Stages Questionnaire [ASQ] (Gross Motor, Personal‐Social, and Communication sub‐scales). Household food insecurity was assessed using the Household Food Insecurity Access Scale [HFIAS], and a scale of household food security was created using standard techniques. Results indicate that household food insecurity was associated with scores on the ASQ. In sub‐scale analyses, performance on the Gross Motor sub‐scale was most strongly associated with food insecurity (p=0.008). Stunting is significantly associated with gross motor scores (β=‐0.012, 95%CI:‐0.022 to ‐0.0029, p=0.01) and personal‐social scores (β=‐0.021, 95%CI:‐0.042 to ‐0.00079, p=0.04). Mediation analyses suggest that some of the association between household food security and child development is explained by child anthropometry (length‐for‐age). The associations between food insecurity and child development have potential policy and program implications. Understanding these findings may also inform future interventions designed to improve child cognitive development.

Grant Funding Source: NSF‐GEO grant #115057, NAS Partnerships for Enhanced Engagement in Research
Dietary n‐3 fatty acids differentially modulate cecal bacterial populations and intestinal inflammation in colitis‐prone mice (382.4)
Authors: Comstock Sarah , Auchtung Jennifer , Gurzell Eric , Langohr Ingeborg , Britton Robert , Fenton Jenifer
Published: June 2021

30% of adults in the United States take n‐3 supplements. Dietary lipids, including n‐3 fatty acids, alter an individual’s risk for developing inflammatory bowel disease. However, the effect of dietary n‐3 on gut bacterial populations is poorly described. To determine if dietary fish oil alters gut‐associated bacterial populations, colitis‐prone mice were fed diets containing soybean oil (CON), menhaden fish oil (MO), docosahexaenoic acid‐rich fish oil (DFO) or eicosapentaenoic acid‐rich fish oil (EFO) for five weeks. Cecal and colon inflammation and dysplasia were scored. To identify bacteria, the V3‐V5 variable regions in the 16S rRNA gene were amplified from cecal content DNA. Amplicons were sequenced by 454 and data was processed with mothur. DFO mice had similar amounts of Firmicutes and tended to have more Bacteroidetes than CON or MO mice. The increased abundance of Bacteroidetes in DFO mice was driven by the family Porphyromonadaceae. Porphyromonadaceae abundance was highest in DFO mice with intestinal inflammation and lowest in CON mice with little intestinal inflammation. This difference was due to increased abundance of members of the genus Parabacteroides in DFO mice with intestinal inflammation. Diet‐induced changes in cecal bacteria prior to bacterial infection may explain the exacerbation of bacterially‐induced inflammatory colitis in mice fed DFO.
Bioenergetic characterization of macrophage inflammatory responses attenuated by anthocyanins (383.2)
Authors: Komarnytsky Slavko , Chen Amelia , Thor Yiwen , Palatini Kimberly , Wilson Mickey , Esposito Debora
Published: June 2021

Anthocyanins present strong anti‐inflammatory properties, thus leading to the potential use as functional food ingredients for the prevention and treatment of chronic inflammatory diseases and increased intestinal permeability to endotoxins, notably LPS. However, the differences between individual anthocyanins and their effects on cellular signaling and metabolism need to be further elucidated. In this study, we evaluated the protection afforded by anthocyanins against LPS‐induced inflammatory response in RAW 264.7 macrophages and determined changes in oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) during the macrophage activation. Basal OCR and ECAR increased as the macrophages underwent LPS stimulation from 283.3±38.4 to 361.7±47.9 pmol/min, and from 9.7±2.4 to 27.6±3.8 mpH/min, respectively, suggesting that energy required for activation is rapidly provided by changes in glycolytic pathways. When tested in physiological concentrations (0.1‐3 uM), malvidin and, to a certain degree, delphinidin, were more effective than cyaniding or pelargonidin in the reduction of mRNA and protein biomarkers of inflammation. Different effects exerted by individual anthocyanins suggested that the presence of the methylated hydroxyls on the B ring may be critical for their greater biological activity. Anthocyanin‐treated macrophages developed a distinct metabolic profile with respect to glycolysis versus oxidative phosphorylation, in part by increasing spare respiratory capacity and therefore shifting to mitochondria as their main source of ATP.

Grant Funding Source: Supported by NCSU faculty start up funds to SK.
Low‐grade inflammation and weight gain in reproductive‐aged women (391.4)
Authors: Perng Wei , Rich‐Edwards Janet , Stuebe Allison , Oken Emily
Published: June 2021

Objective To investigate whether low‐grade inflammation is related to weight gain in reproductive‐aged women.

Methods We quantified C‐reactive protein (CRP) and interleukin‐6 (IL‐6) in plasma of 440 Project Viva mothers at 3 y postpartum, and obtained research measures of weight and waist circumference (WC) at 3 and 7 y postpartum. There were no intervening pregnancies during the study period. Using multivariable linear regression, we examined the relation of CRP and IL‐6 quartiles with weight and WC change over 4 y of follow‐up.

Results At 3 y postpartum, median age was 37 y (range: 20 ‐ 48). Mean ± SD BMI was 26.3 ± 6.4 kg/m2, waist circumference 87.5 ± 12.8 cm, CRP 2.02 ± 3.74 mg/L, and IL‐6 1.57 ± 2.94 pg/mL; 73.6% were white. Weight (2.6 ± 5.8 kg) and WC (2.4 ± 6.5 cm) increased during follow‐up. After adjustment for age, parity, race, education level, delivery method, anthropometry at 3 y postpartum, and time lag between the 3 and 7 y anthropometric assessments, there were no associations of CRP or IL‐6 with weight or WC change.

Conclusions Inflammation was not related to weight gain in this sample of reproductive‐aged women. Future studies with a longer duration of follow‐up are warranted.

Grant Funding Source: Supported by the National Institutes of Health
Essential role for Notch1 mediated myofibroblast differentiation in the pathogenesis of pulmonary fibrosis (406.5)
Authors: Hu Biao , Liu Tianju , Wu Zhe , Liu Jianhua , Ullenbruch Matthew , Phan Sem
Published: June 2021

Notch signaling pathway is involved in the regulation of cell fate, differentiation, proliferation and apoptosis. Previous studies indicate that Notch1 activates myofibroblast differentiation, a key feature of lung fibrosis. However, the in vivo importance of Notch1 mediated myofibroblast differentiation is not clear. In this study, the effects of mesenchymal‐specific deletion of Notch1 on pulmonary fibrosis were examined. Crossing of mice with the floxed notch1 gene with α2(I) collagen enhancer‐CreER(T)‐bearing mice successfully generated progeny with a conditional knockout (CKO) of notch1 in collagen I‐expressing (“mesenchymal”) cells only upon treatment with tamoxifen (notch1 CKO). When treated with endotracheal bleomycin injection, Notch1 CKO mice showed significant attenuation of pulmonary fibrosis relative to control mice as examined by collagen deposition, myofibroblast differentiation and histopathological analyses. No significant differences in inflammatory/immune cell influx were observed in the mutant mice relative to the control mice as showed by flow cytometry analysis. These findings confirmed an essential role for Notch1 mediated myofibroblast differentiation in the pathogenesis of pulmonary fibrosis.

Grant Funding Source: Supported by National Institute of Health grants (HL52285, HL91775, HL112880 and DK020572)
miR‐223 a new signaling hub accounting for DNA damage signaling and STAT3 activation in pulmonary arterial hypertension (406.6)
Authors: Vinck Jerome , Ruffenach Gregoire , Potus François , Sandra Breuils‐Bonnet , Provencher Steeve , Bonnet Sebastien
Published: June 2021

Background: We reported that pulmonary arterial hypertension (PAH) is associated with an increased activation of Poly(ADP‐ribose) polymerase‐1 (PARP‐1) and the transcription factor STAT3 within the pulmonary arterial smooth muscle cells (PASMC). PARP‐1/STAT3 are common denominators to numerous pathways implicated in PAH including inflammation, Warburg effect; DNA repair; proliferation and apoptosis; thus PARP‐1/STAT3 activation can eventually leads to PAH. Despite extensive research PARP‐1/STAT3 activation mechanism remains elusive. Micro‐RNAs are non‐coding small RNA implicated in PAH etiology, in sillico analysis revealed that an interaction between the transcription factor CEBPα and miR‐233 is likely implicated in PARP‐1/STAT3 activation. We hypothesized that miR‐223 is downregulated in PAH contributing to PARP‐1/STAT3 activation.

Methods and results: Using qRT‐PCR, we demonstrated that miR‐223 is significantly downregulated in Human PAH lungs, distal pulmonary arteries (<800μm) and cultured PAH‐PASMCs compare to control donors (n=3 to 5 patients). Downregulation of miR‐223 was associated with a significant downregulation at both mRNA (qRT‐PCR) and protein levels (immunoblot and immunofluorescence) of CEBPα, a transcription factor known to regulate miR‐223. Interestingly, the CEBPα‐dependent downregulation of miR‐223 was associated with PARP‐1 and STAT3 activation in PAH‐PASMC contributing to their prolifération.

Conclusion: We provide preliminary evidences of the implication of a CEBPα/miR‐223 axis in the etiology of PAH, and its likely implication in the activation of PARP‐1/STAT3 signaling known to regulates PASMC proliferation and resistance to apoptosis. Therefore, CEBPα/miR‐223 represents a new avenue of investigation and a putative new therapeutic target for PAH.