bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Analysis of Prenatal Cocaine Exposure on Maternal and Pup Related Developmental Variables
Authors: Johnson Marquita , Jackson Tanise , Womble Tracy , Goodman Carl
Published: June 2021

Cocaine is a potent psychostimulant whose use gained popularity within the United States in the late 1970′s and extends well into today. The high abuse rate and addictive nature of cocaine has led to an increase in the amount of infants born to cocaine abusing mothers. However, the full extent of its effects on the development of offspring exposed during gestation has yet to be elucidated. The purpose of this experiment is to evaluate maternal weight, litter size, pup weight, and pup brain weight in Sprague‐Dawley rat pups following prenatal cocaine exposure. Maternal and pup total body weight were significantly decreased following prenatal cocaine exposure. However, differences in litter size and pup brain weights were not observed. Data obtained from this study will lay the foundation for determining cocaine's deleterious effects in offspring as well as facilitate cross‐species comparisons of prenatal cocaine exposure.
Prions causing Alzheimer's and Parkinson's‐Quest for Effective Therapeutics
Authors: Prusiner Stanley
Published: June 2021

Mounting evidence argues that prions feature in the pathogenesis of many, if not all, neurodegenerative diseases. Such disorders include Alzheimer's, Parkinson's, Lou Gehrig's and Creutzfeldt‐Jakob diseases as well as the fronto‐temporal dementias. In each of these illnesses, aberrant forms of a particular protein accumulate as pathological deposits referred to as amyloid plaques, neurofibrillary tangles, Lewy bodies, as well as glial cytoplasmic and/or nuclear inclusions. The heritable forms of the neurodegenerative diseases are often caused by mutations in the genes encoding the mutant, prion proteins that accumulate in the CNS of patients with these fatal disorders. The late onset of the inherited neurodegenerative diseases seems likely to be explained by the protein quality control systems being less efficient in older neurons and thus, more permissive for prion accumulation. To date, there is not a single drug that halts or even slows one neurodegenerative disease. Using high content analysis (HCA) we are screening chemical libraries for compounds that lower the levels of prions in cultured cells. Hits from such studies are being turned into leads through iterative chemistry that will be tested for drug efficacy in animal models.
Impact of Different Small Student Group Learning Approaches to Compressed Medical Anatomy Education
Authors: Ramnanan Christopher , Whelan Alexander , Leddy John
Published: June 2021

The University of Ottawa utilizes two approaches to small group laboratory learning in its compressed (46.5 hrs) medical anatomy program. The Facilitated Active Learning (FAL) approach is driven by Faculty who promote student progression through learning objectives. In the Emphasized Independent Learning (EIL) approach, independent pre‐lab preparation is stressed, with limited Faculty involvement, based on 'flipped classroom' principles. This study characterized student perceptions and academic performance related to these approaches. Perceptions were surveyed using both Likert‐style items and open‐ended items. Open‐ended items were analyzed for consensus, emerging themes. Student performance was compared on overall practical examinations, anatomy‐related items, and discriminating anatomy items (testing knowledge application). While the survey analysis revealed perceived strengths attributed to both EIL (collaboration, communication skills) and FAL (appropriate direction and enhanced learning of objectives) methods, the EIL method was noted for lack of direction and inefficient student learning. Active learning in FAL classes was variable and sometimes limited by Faculty teaching style. While FAL students only scored 4% higher than EIL students on practical exams (P<0.05), FAL students scored 6% and 8% higher on anatomy‐related MCQs and discriminating anatomy‐related MCQs, respectively, indicating a significant (P<0.01) impact of teaching style on learning. Despite some perceived benefits, emphasizing independent student learning had a negative impact on student performance (particularly on discriminating items), relative to Faculty‐facilitated learning, in a compressed anatomy program.
Mechanisms and Adult Treatments for Cognitive Deficits Associated with Neurodevelopmental Disorders
Authors: Silva Alcino
Published: June 2021

Mouse model studies in our laboratory have uncovered mechanisms and treatments for learning and memory disorders, including those associated with Neurofibromatosis type I, Tuberous Sclerosis, Noonan Syndrome and DISC1 mutations. These and other related findings illustrate how insights into the biology of molecular, cellular and system processes in the brain are changing the way we understand and envision treating cognitive disorders. They demonstrate that adult treatments one day will help many of the millions of people affected with cognitive problems caused by neurodevelopmental disorders.
Facebook in Anatomy Education: Why and How?
Authors: Jaffar Akram
Published: June 2021

With the rapid development in information technologies various changes have been made in terms of the methods in the teaching and learning process. The popularity of social networking sites (SNSs) provided a newly emerging tool of e‐learning. Facebook is currently the leading SNS on which students spend a considerable time every day; therefore, it is the logical place to start when integrating SNSs into education.

A faculty administered Facebook platform was used to supplement anatomy education of medical students for three academic years. A vivid model of this use is provided here. The aim is to establish Facebook penetration among students, justify its educational use, highlight its potentials, validate its capabilities, recognize its limitations, support its effectiveness in contributing to learning, and describe patterns of students' engagement with educational posts.

Facebook can deliver more media richness which students expect in their anatomy learning. A wider educational use of Facebook should be adopted not only because students are embracing its use, but for its effectiveness in boosting learning. Facebook is no more a site merely for social activities; it offers the opportunity for the students to be highly engaged with educational content outside the classroom boundaries. Our students are willing and prepared to embrace the new technology. Are we, as their teachers, equally ready?
Technology and Innovation in Histology: Adapting to a Changing Landscape of Teaching in Medical Microanatomy
Authors: Goldman Haviva , Churchill Judy , Hanau Cheryl
Published: June 2021

The teaching of medical microanatomy has shifted in recent years, with virtual microscopy now regularly utilized to supplement or replace microscope‐based laboratories. This, combined with increasing pressure to integrate curricula, reduce course hours, and enhance student self‐directed and active learning, introduces new opportunities and challenges for histology teaching. Here we describe how we have utilized technology to deliver histology content to students and facilitate active learning sessions within a Problem Based Learning curriculum (‘PIL’) at Drexel University College of Medicine.

Microanatomy in the PIL curriculum is a stand‐alone course, integrated with Gross Anatomy, Physiology and Neuroscience in a Block format. While students are introduced to some topics through lecture, particularly early on in the year, much of the course content is delivered online through web‐based tutorials packaged as interactive presentations or as recorded powerpoint lectures. Students also access web‐based laboratory assignments with annotated virtual slides and a guide to EM images. Students then meet in groups for laboratory sessions that consist of scavenger hunt exercises and faculty led, interactive review. Application exercises with pathological images are incorporated into these sessions once students begin to study organ systems. Support for struggling students is provided through live Histohelp sessions and guidance to all students is accomplished through an online course blog. Analysis of student feedback demonstrates more student participation relative to previous formats, and a more positive perception of microanatomy.
Degeneration and repair after spinal cord injury (SCI) in the non‐human primate (NHP)
Authors: Bresnahan Jacqueline
Published: June 2021

We will discuss the establishment of a new NHP model of contusion SCI using an electronically controlled impactor with feedback to produce a unilateral cervical contusion at the C5 vertebral level similar to our rat model. Pre‐op and post‐injury MRIs were taken. Recovery of over‐ground locomotion, climbing and object manipulation were scored in an open‐field; forelimb and sensory function were assessed in a primate chair. EMG activity patterns in forelimb muscles were assessed in one subject. Three subjects had BDA labeling of the cortico‐spinal tract (CST) at 4‐5 months. Peak force during impact was a good predictor of behavioral outcome at 2 weeks (r=0.88; p<0.004). Histological analysis showed that the lesion can be graded, and the injury produces a consistent pattern of degeneration in the gray and white matter, with a central contusion region (that formed a cystic cavity in some animals), with a peripheral rim of spared fibers. At the rim of the contusion, demyelinated axons, remyelinated axons, and macrophages are present. CST tracing shows that this rim can contain spared CST fibers at the lesion epicenter that provide dense innervation of the gray matter below the injury. Microglial activation away from the lesion is prominent in the degenerating tracts. Principle components analysis of the relationships of all injury parameters, behavioral outcomes and histological measures were performed and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also characterized an integrated metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of hind‐limb, fore‐limb and hand function, while lower energy impacts produced early paralysis followed by substantial recovery with enduring deficits in fine digital control (e.g., pincer grasp). (Supported by the VA, CH Neilsen Foundation, and NIH)
Mechanisms underlying macrophage polarization in spinal cord injury ‐ detrimental and beneficial influences on recovery
Authors: David Samuel
Published: June 2021

Activated macrophages in the injured CNS can have detrimental and beneficial effects, which may be due to their polarization state. Macrophages can be polarized along a continuum to M1 cells which are pro‐inflammatory and cytotoxic, and M2 cells which are anti‐inflammatory and pro‐repair. Myelin phagocytosis in vitro can induce M1 polarized cells to shift to a M2 phenotype. However, although myelin phagocytosis occurs after spinal cord injury (SCI), macrophages remain predominantly M1 polarized. Our work shows that this failure to switch to a M2 phenotype in vivo after SCI despite on‐going phagocytosis is due in part to TNF. TNF which is upregulated after SCI prevents the myelin phagocytosis induced switch from M1 to M2 polarization. Our work also shows that iron loading of macrophages induces M2 polarized cells to switch to M1 cells and produce TNF. This is important because hemorrhage and cell death after SCI lead to the release of iron. These data indicate that TNF can prevent phagocytosis induced shift of M1 to M2, and increased intracellular iron can promote shift of M2 to M1 phenotype. The combined effect of these influences is detrimental to recovery after SCI.
Zygomatic Arch Development in Mammals: Phenotypic Plasticity and Osteoblast Behavior
Authors: Ravosa Matthew
Published: June 2021

In vivo and ex vivo analyses facilitate a direct knowledge of how anatomical structures and their cellular constituents respond to external stimuli, information critical for documenting the mechanobiology of connective tissues. In the mammalian skull, diet‐related variation in loading patterns induces a cascade of changes at the gross, tissue, cellular, protein and genetic levels, with such tissue modeling and remodeling maintaining the integrity of bony elements. Research using a rabbit model of long‐term dietary plasticity provides novel insight into site‐specific variation in reaction norms between the zygomatic arch and other masticatory elements, as well as between masticatory and non‐masticatory regions of the skull. These data are integrated with ongoing work on the intrinsic activity and osteogenic responses of osteoblasts from the mouse cranial vault, cranial base and jaws. In highlighting the potential cellular bases of relative growth in the skull, our research suggests that cranial osteoblasts are not a homogeneous group of cells, but rather exhibit distinct behaviors depending on their anatomical location and embryological origin. Such novel findings are important for highlighting why bone should not be viewed as similar across skeletal regions with respect to its intrinsic growth potential or vis‐a‐vis loading stimuli, an assumption inherent to most comparative and experimental studies.
Developmental and evolutionary significance of the zygomatic bone
Authors: Richtsmeier Joan
Published: June 2021

The evolution of vertebrate groups, including Homo, is marked by repeated instances of extension and retrusion of the facial skeleton. The exact processes by which these changes occur are unknown but require marked cooperation among developing hard and soft tissues, the cooperation likely driven by genes. Several different mutations in fibroblast growth factor receptors (FGFRs) cause craniosynostosis syndromes, human diseases marked by facial retrusion. 3D morphometric analysis of humans carrying FGFR mutations confirms a correspondence between facial retrusion and causative mutations but the zygoma is relatively less affected than other facial bones depending on the specific mutation. We analyze variation in facial morphology in humans and mice carrying orthologous FGFR mutations, in dogs selected for unusually flat faces, and in a managed colony of captive baboons showing pronounced variation in facial prognathism. Regardless of the source of variation (mutation, selection, normal variation), zygoma morphology remains relatively stable while other bones of the midface change drastically. Whether zygoma morphology represents an adjustment that resists the effects of changes in midfacial architecture while ensuring proper hafting of the facial skeleton onto the neurocranium, and how this adjustment might be accomplished developmentally remain open questions.
Development and Applications of CRISPR‐Cas9 for Genome Manipulations
Authors: Zhang Feng
Published: June 2021

The Cas9 endonuclease from the microbial adaptive immune system CRISPR can be easily programmed to bind or cleave specific DNA sequence using a short RNA guide. Cas9 is enabling the generation of more realistic disease models and is broadening the number of genetically‐tractable organisms that can be used to study a variety of biological processes. Previously we have demonstrated that the Cas9 nuclease can be successfully engineered to facilitated genome editing by targeting DNA double strand breaks or single strand nicking in mammalian cells. The Cas9 nuclease can also be modified to modulate transcription, and alter epigenetic states in living cells. In this presentation we will look at the latest developments including structure‐function analysis of Cas9, unbiased characterization of targeting specificity, applications to study gene functions in vivo, as well as high‐throughput screening assays.
New Approaches to Finding Next‐Generation Treatments for Malaria
Authors: Winzeler Elizabeth
Published: June 2021

Malaria still kills up to 1 million people annually. While malaria can be treated using different drug combinations, the constant emergence of resistant parasites means there is a continued need to place new compounds in the drug development pipeline. In addition to providing symptomatic relief, new drugs should have novel mechanisms of action to combat pre‐existing resistance. They should also prevent further malaria transmission, and eliminate latent‐stage parasites. Given that there are no known malaria drug targets that could yield a compound with this profile, we have been using cellular screening methods to find drug development leads that could eventually yield such medicines. These include screens designed to detect molecules active against malaria hepatic stages, the symptomatic blood stages and the parasite forms transmitted from humans to mosquitoes. We are using chemical genetics to work backwards to discover the targets of both promising leads for drug development, and tool compounds. Our unbiased efforts have resulted in the discovery of two completely novel small molecules that are currently in clinical trials for the treatment of malaria. In addition, the work is revealing a variety of novel parasite vulnerabilities.
Use of Mass Spectrometry‐Based Phosphoproteomics to Characterize a Receptor Protein Kinase‐Mediated Signaling Pathway that Negatively Regulates Plant Cell Growth.
Authors: Sussman Michael , Haruta Miyoshi , Minkoff Benjamin , Sabat Grzegorz , Stecker Kelly
Published: June 2021

Plant cells are immobile and thus, cell expansion plays a critical role in the shape, growth and development of plants. The precise molecular mechanism by which the plasma membrane initiates changes in the cellular growth rate remains elusive. Using metabolic labeling with the stable isotope, 15N, in Arabidopsis seedlings we performed isotope‐assisted quantitative mass spectrometric measurements of the plasma membrane phosphoproteome following brief treatments with a secreted 49 amino acid long peptide known as RALF (for Rapid Alkalinization Factor). This hormone causes alkalinization of the extracellular medium and suppresses cell elongation. Out of ~500‐600 phosphopeptides in the plasma membrane fraction quantified, we found a handful of proteins in which at least one phosphosite was altered. The largest change was observed in phosphosites at the carboxy terminus of the cell surface receptor kinase known as FERONIA and we hypothesized that this was due to autophosphorylation induced by RALF binding to the receptor. A direct peptide‐receptor interaction was supported by specific binding of RALF to the extracellular domain of FERONIA and reduced binding and insensitivity to RALF‐induced growth inhibition in feronia mutants. Phosphoproteome measurements also demonstrated that the RALF‐FERONIA interaction caused phosphorylation of a plasma membrane proton pump at Ser899, mediating the inhibition of proton transport. These results, together with additional reverse genetic analysis of the phosphorylated proteins, reveal a molecular mechanism for RALF‐induced extracellular alkalinization and a signaling pathway that regulates cell expansion.
Using Lipidomics to Probe Lipid Metabolism
Authors: Welti Ruth , Shiva Sunitha , Vu Hieu , Roth Mary , Tamura Pamela , Samarakoon Thilani , Colter Madeline , Sarowar Sujon , Li Maoyin , Gadbury Gary , Wang Xuemin , Shah Jyoti
Published: June 2021

Direct‐infusion electrospray ionization triple quadrupole mass spectrometry method with multiple reaction monitoring (MRM) has been employed to measure Arabidopsis thaliana galactolipids and phospholipids (including monoacyl molecular species, molecular species with oxidized acyl chains, phosphatidic acids (PAs), tri‐and tetra‐galactosyldiacylglycerols (TrGDGs and TeGDGs), head‐group‐acylated galactolipids, and head‐group‐acylated phosphatidylglycerol (acPG)), sulfoquinovosyldiacylglycerols (SQDGs), sphingolipids, di‐ and tri‐acylglycerols (DAGs and TAGs), and sterol derivatives following wounding, cold, and freezing stresses. Changes observed are consistent with activation of lipid oxidizing, hydrolyzing, glycosylating, and acylating activities. Analysis of the lipid changes, their inter‐relationships, and their genetic underpinnings will be discussed.
Role of Exosomic MicroRNAs in Cancer Cell Cross‐Talk within the Tumor Microenvironment
Authors: Fabbri Muller , Wise Petra , Murtadha Mariam , Neviani Paolo , Challagundla Kishore
Published: June 2021

MicroRNAs (miRNAs) regulate gene expression in cells and are frequently dys‐regulated in human cancers. Recent evidence indicates that miRNAs are released by normal and cancer cells within microvesicles called exosomes and can be functionally transferred to surrounding cells. We showed that cancer cell secreted exosomic miRNAs can function as agonists of Toll‐like receptor 8 (TLR8) in tumor‐associated macrophages (TAMs), favoring a pro‐tumoral and pro‐metastatic tumor microenvironment. These effects are mediated by the activation of the NF‐kB pathway and increased secretion of interleukin‐6 and tumor necrosis factor alpha by TAMs. We also report that the cross‐talk elicited by exosomic miRNAs is responsible for increased drug resistance in neuroblastoma cells, through exchange of exosomic miRNAs by cancer‐cell “educated” TAMs. This newly identified mechanism harbors promising potentials to prevent and/or overcome the development of resistance to drugs by cancer cells, which still represents the most prominent cause of cancer‐related deaths.
The Non‐Coding Transcriptome as a Dynamic Regulator of Prostate Cancer Metastasis
Authors: Helgason Cheryl , Parolia Abhijit , Liu Rebecca , Xu Hui , Wang Yuzhuo , Crea Francesco
Published: June 2021

While localized prostate cancer (PCa) is readily treated using surgery or radiotherapy, there are no curative therapeutic options available for metastatic PCa. Long non‐coding RNAs (lncRNAs) play critical roles in cancer, either as oncogenes or tumor suppressors, although the mechanisms by which they regulate tumor development and progression are still poorly understood. We utilized our unique collection of patient‐derived prostate tumor tissue xenograft models to identify lncRNAs differentially expressed in metastatic versus non‐metastatic xenografts. PCAT18 is a previously uncharacterized lncRNA specifically expressed in the prostate compared to 11 other normal tissues and up‐regulated in PCa compared to 15 other neoplasms. PCAT18 silencing significantly inhibited PCa cell proliferation, migration and invasion, and also triggered caspase 3/7 activation, with no effect on non‐neoplastic BPH1 cells. Among the lncRNAs down‐regulated in the metastatic xenograft, we focused on LOC153684, which is classified as an uncharacterized lncRNA. Higher expression of this transcript is associated with longer progression‐free survival after prostatectomy (p=0.03). In keeping with its putative onco‐suppressive role, LOC153684 is significantly down‐regulated in prostate cancer specimens, compared to normal prostatic tissue (p=0.04, average fold change ‐1.99). In addition, expression of this transcript is higher in BPH1 cells (non‐neoplastic) compared to all PCa cell lines tested. Understanding the molecular mechanisms by which these lncRNAs regulate PCa progression may facilitate the development of novel therapeutics.
Diet, the Gut Microbiome and Cardio‐Metabolic Risk
Authors: Lovegrove Julie
Published: June 2021

The gut microbiome has been implicated as a potential mediator of diet‐related effects on cardio‐metabolic risk. There is evidence to suggest that diet can alter human physiology and disease risk by influencing the composition and activity of the gut microbiota, via mechanisms that may include the production of short chain fatty acids, bile acid deconjugation and polyphenol metabolism. There is substantial variation in the microbiota, with greater variation in fecal bacterial composition between individuals than within an individual, a finding that might underlie variance in the expression of risk factors for chronic diseases.

This presentation will examine evidence that dietary modification of cardio‐metabolic risk is mediated, in part, through the gut microbiome. It will address the impact of dietary fatty acids, carbohydrates, prebiotics in novel functional foods, and increased consumption of fruits and vegetables on the gut microbiome and metabolic risk in randomized controlled trials (RCT).

The ‘RISCK’ study was a multi‐centred RCT which was designed to evaluated the impact of the amount and quality of dietary fat and carbohydrate on cardio‐metabolic risk in a population at risk of metabolic syndrome. Low fat, high carbohydrate diets increased fecal Bifidobacterium, and reduce fasting glucose and cholesterol. Diets containing high glycaemic index carbohydrates also increased fecal Bacteroides, while high carbohydrate low glycaemic index diets increased Faecalibacterium prausnitzii. In other studies, a high intake of fermentable fibre and plant polyphenols were shown to regulate microbial activities within the gut. In conclusion, these findings provide further evidence for the impact of diet on the gut microbiome, the significance of these effects on cardio‐metabolic risk remain to be confirmed.
A Tale of Two Proteins
Authors: Matthews Kathleen , Bondos Sarah , Swint‐Kruse Liskin
Published: June 2021

Genetic regulatory proteins sense input signals to modulate transcription. In these proteins, intrinsic disorder (ID) is emerging as a common theme. Prokaryotic regulators have short ID segments, whereas eukaryotic regulators have extended regions that lack predicted 2° structure. Two examples illustrate the impact of ID on gene regulation: Lac repressor (LacI) in E. coli and the Hox protein Ultrabithorax (Ubx) in D. melanogaster. ID in the LacI hinge was first indicated by proteolytic susceptibility and later confirmed by physical studies. This short hinge region in free LacI is unfolded, but forms a folded dimeric structure that inserts into the minor groove and bends DNA to facilitate helix‐turn‐helix (HTH) domain contacts critical for high affinity binding. Restriction of hinge motions by a disulfide bond limits response to inducer, indicating the key role of the hinge in DNA binding and induction. Similarly, DNA binding by the structured Ubx HTH is augmented by an adjacent, disordered sequence, and Ubx‐DNA binding is also regulated by extensively disordered regions found well outside the HTH. These ID regions enable Ubx to interact with itself and a wide range of partners to further influence DNA binding. ID‐HTH interactions also mediate the non‐natural assembly of Ubx into strong, flexible fibers with intriguing materials properties. The importance of intrinsic disorder in genetic regulatory proteins appears widespread and may derive from the need to be flexible both in response and, particularly in eukaryotes, in partner selection.
Wnt Modification by Tiki Proteins
Authors: He Xi
Published: June 2021

We focus on understanding the molecular mechanism of Wnt signaling in vertebrate development, stem cell regulation, and human cancer and diseases. We are interested in canonical Wnt/b‐catenin signaling and noncanonical Wnt signaling pathways. We employ molecular, structural, cellular, and developmental approaches in Xenopus, mice, and human cell culture.

Using functional cDNA expression screening, we identified Tiki1, a transmembrane protein that is expressed specifically in the Spemann‐Mangold Organizer in Xenopus embryos and is required for anterior development. Tiki1 antagonizes Wnt function by acting as a metalloprotease to cleave a few amino terminal residues of a Wnt protein, resulting in oxidized Wnt oligomers that exhibit normal secretion but minimized receptor‐binding capability. Tiki1 is the first known Wnt inactivating enzyme, and is conserved from invertebrates to vertebrates including humans. I will discuss our ongoing study of the function, Wnt cleavage specificity and regulation of Tiki proteins.
The Discovery of New Enzymes in the Human Gut Microbiome
Authors: Raushel Frank , Hobbs Merlin
Published: June 2021

A previously unknown metabolic pathway for the utilization of L‐galactose was discovered in a prevalent human gut bacterium, Bacteroides vulgatus. The new pathway consists of three previously uncharacterized enzymes that were found to be responsible for the conversion of L‐galactose to D‐tagaturonate. Bvu0219 oxidizes L‐galactose to L‐galactono‐1,5‐lactone. However, the kinetic product of the reaction catalyzed by Bvu0219 is converted nonenzymatically to the thermodynamically more stable product, L‐galactono‐1,4‐lactone. The second enzyme, Bvu0220, hydrolyzes both the kinetic and thermodynamic products of the reaction catalyzed by Bvu0219 to L‐galactonate. However, L‐galactono‐1,5‐lactone is estimated to be hydrolyzed 300 fold faster than its thermodynamically more stable counterpart, L‐galactono‐1,4‐lactone. The final enzyme in this pathway, Bvu0222, converts L‐galactonate to D‐tagaturonate. D‐Tagaturonate is subsequently converted to D‐glyceraldehyde and pyruvate through enzymes encoded within the degradation pathway for D‐glucuronate and D‐galacturonate.
DHA‐enriched high oleic canola oil diet may accelerate the cholesterol synthesis in humans.
Authors: Jones Peter , Pu Shuaihua , Rodríguez‐Pérez Celia , Ramprasath Vanu , Khaloufi Khatima , Sabra Ali , Segura‐Carretero Antonio
Published: June 2021

Circulating plant sterols are commonly used as surrogate biomarkers of cholesterol absorption, while desmosterol and lathosterol levels indicate cholesterol synthesis. To investigate the health benefits of various dietary oils varying n‐9/n‐6 fatty acid profiles on cholesterol trafficking using markers of cholesterol absorption and synthesis, a double‐blinded randomized crossover clinical trial consisting of five 30‐d periods was conducted. Diets included 60 g/d of canola oil (Canola, 59% OA, 20% LA, 10% ALA), high oleic canola oil (CanoalOleic, 72% OA, 15% LA), high oleic canola/DHA oil (CanolaDHA, 63% OA, 13% LA, 6% DHA), corn/safflower oil (CornSaff, 18% OA, 69% LA) and flax/safflower oil (FlaxSaff, 18% OA, 38% LA, 32% ALA). Total cholesterol and other sterol measures were determined using GC‐FID at endpoints. Results (n=54) showed that CanolaDHA feeding produced the highest serum total cholesterol levels (p<0.05) compared to other four treatments. No differences were observed in desmosterol levels across all diets. CanolaDHA also produced the highest lathosterol (p<0.0001) among all treatments with 27% more than the n‐6 control CornSaff. The sum of sitosterol and campesterol levels within three n‐9 rich diets, Canola, CanolaDHA, and CanolaOleic were higher (p<0.001) than two n‐6 rich diets by 27%, 34% and 20%, respectively. The data suggest that dietary DHA oil may accelerate cholesterol synthesis, resulting in high circulating cholesterol levels while n‐9 rich diets can elevate cholesterol absorption compared to n‐6 rich diets.
Correspondence between effects of dietary cholesterol versus plant sterols on plasma cholesterol responsiveness and cholesterol trafficking in healthy humans
Authors: Alphonse Peter AS , Ramprasath Vanu , Jones Peter
Published: June 2021

The objective was to determine the degree of correspondence in plasma cholesterol concentration changes caused by dietary cholesterol (DC) versus plant sterols (PS) and their effects on cholesterol trafficking. A randomized, cross‐over, placebo controlled free‐living clinical trial (n=51) with 3 treatment phases of 4 week duration each separated by a 4 week washout was conducted. During each phase, participants consumed one of the three treatments containing 0.6 g DC, 2 g PS/day or a placebo after breakfast meal. Plasma lipid profile was determined and cholesterol absorption (CA) was measured by using a stable isotope [3, 4‐13C]‐labeled cholesterol administered orally. Cholesterol synthesis (CS) was assessed using plasma lathosterol as a surrogate marker. DC intake increased total cholesterol (TC) compared to placebo (0.16 mmol/L; P = 0.037) and PS (0.25 mmol/L; P = 0.005). PS intake reduced (0.20 mmol/L; P = 0.042) LDL‐C only compared to DC. Cholesterol absorption was inhibited (P = 0.0001) by PS consumption compared to placebo. Results showed that the degree of cholesterol lowering with PS intake was not in concordance with the cholesterol elevating offset caused by DC intake with respect to TC and LDL‐C. The offsets in CA and CS caused by DC and PS did not align with those of LDL‐C and TC. The large inter‐individual variability in the plasma lipid responsiveness to PS and DC intake in the population could be ascribed to the above results.
Effect of High Linoleic Acid Diet on Carbohydrate‐stimulated Expression of Lipogenic Genes
Authors: Axen Kathleen , Harper Marianna , Edupghanti Tushara , Brown JoAnn , Thomas Kadeem , Axen Kenneth
Published: June 2021

Linoleic acid, an ω‐6 PUFA, has been proposed to inhibit de novo lipogenesis (DNL) by decreasing expression of SREBP‐1c, a major regulator of DNL. To investigate whether previous intake of a high linoleic acid diet inhibits carbohydrate‐stimulated SREBP‐1c expression and DNL in vivo, we compared the expression of SREBP‐1c and its lipogenic targets in the fasted and post‐meal states in male Sprague‐Dawley rats fed: 1) a 55% fat (78% linoleic acid) diet (n=15, P); 2) a 55% fat (linoleic acid‐free) diet (n=15, S); or 3) a no‐fat diet (n=15, N) for 1 wk. All rats were fasted for 24 h; liver samples were obtained at fasting, 16h after refeeding on a 74% carbohydrate, fat‐free meal, or 45 min after injection with insulin + glucose.
Body weights and liver lipid levels were greater in P and S than N rats (P=S>N; p< .01) but % body fat was higher in P than S rats (P>S=N, p< .01). Refeeding increased mRNA for SREBP‐1c and the lipogenic enzymes Acetyl CoA Carboxylase, Steroyl CoA Desaturase 1, and Pyruvate Kinase compared with fasting in all groups similarly, but expression of Fatty Acid Synthase was lower in the P vs. S group (p< .02). In all groups, refeeding or insulin decreased Phosphoenolpyruvate Carboxykinase mRNA and increased Glucokinase mRNA, indicating normal insulin sensitivity. Refeeding decreased expression of INSIG2, a protein which inhibits maturation of SREBP‐1c, in the S and N groups (p< .002), but not the P group.

The minimal reduction in the stimulation of lipogenic gene expression seen in the high‐linoleic acid group was not associated with decreased expression SREBP‐1c, but was associated with lack of suppression of INSIG2 expression, suggesting that ω‐6 PUFA may impair processing rather than expression of SREBP‐1c.
Food Metabolome in Clinical Nutrition Research: from Dietary Patterns to Discovering Disease Risk Biomarkers. Evidence from PREDIMED Study
Authors: Andres‐Lacueva C , Llorach R , Urpi‐Sardà M , Tulipani S , Vazquez‐Fresno R , Khymenets O , Lupianez‐Barbero A , Garcia‐Aloy M
Published: June 2021

Diet plays an important role in the prevention and development of chronic diseases. Interventional and observational studies have provided evidence of the health benefits of dietary bioactive compounds. The assessment of dietary intake has been estimated using self‐reported questionnaires, which provide less reliable data than nutritional biomarkers. Nutrimetabolomics has been proposed as a tool for discovering new biomarkers of exposure.

Different clinical studies provides complementary information about dietary exposure, and thus in the discovery of new biomarkers. In the current study we applied an HPLC‐Q‐ToF‐MS untargeted metabolomics strategy followed by multivariate analysis (OSC‐PLS‐DA) to characterize the urinary metabolome of subjects who followed an acute or chronic intervention of the food item or dietary pattern, as well as in a free‐living population from the PREDIMED cohort (www.predimed.org). Discriminating metabolites were associated with complex metabolic pattern linked to fatty acids, microbial metabolites, compounds from tryptophan & serotonin pathway, phytochemicals, processing‐derived compounds and endogenous metabolites. Diet‐related differences in urinary metabolome were associated with food digestion, microbiota metabolism and endogenous metabolism.

Nutrimetabolomics has the potential to unveil the metabolic signature that differentiates healthy from metabolically perturbed subjects, access unexplored metabolic pathways impacted by diet, and elucidate the inter‐individual differences in the effects of dietary interventions.
Eating Fried Foods: Negotiating health, taste and tradition in the Spanish Caribbean
Authors: Fuster Melissa
Published: June 2021

This paper explores food preferences and perceptions around fried foods in the Spanish Caribbean (SC) community in New York City, as part of traditional diets. The consumption of fried food has been linked with adverse health effects such as Type 2 diabetes (T2D) and heart disease, conditions that disproportionately affect Hispanic populations. Using unstructured interviews (N=25), this study assessed the perceived level of importance of fried foods, as part of traditional diets (as defined by respondents). The relative importance of fried foods was analyzed using Atlas.ti and compared by country of background (Cuba, Dominican Republic, and Puerto Rico), gender and time spent in the United States. The comparative analysis revealed that, despite the similarities in traditional diets and food culture, there were differences in the level of importance given to fried foods across the different SC backgrounds. Fried foods were more salient in how Puerto Ricans spoke about their food preferences and traditional diets, and this increased among respondents born and/or raised in the US. The conversations revealed how knowledge of the potential health effects of these foods is negotiated against taste and emotive values, which was especially difficult for respondents suffering from diet‐related conditions, mostly T2D. The result of this qualitative study provide a greater understanding of the cultural values attached to traditional fried foods and important difference across Hispanic populations. The study can be best applied to improve nutrition education initiatives targeting health disparities among Hispanic populations, as well as the growing rate of obesity and diet‐related diseases in the SC region.
Exploring Fruit and Vegetable Intake of American Indian Children Using a Mixed Methods Approach
Authors: Sinley Rachel , Albrecht Julie
Published: June 2021

American Indian (AI) children experience disproportionate rates of obesity compared to counterparts in other ethnic groups. Contributing to this issue may be inadequate consumption of fruits and vegetables (f/v). Little research exists on factors that contribute to f/v intake of American Indian children. The objective of this on‐going study is to assess how perceptions of f/v impact the f/v intake of AI children. During the initial qualitative phase, caregivers (n=45) and community stakeholders (n=10) participated in focus groups and individual interviews, respectively. The questions asked during these sessions focused on understanding what perceptions caregivers and community stakeholders have in regards to children's f/v intake. Data was analyzed using qualitative content analysis strategies, with each focus group and interview analyzed separately and then combined and assessed for concordance and discordance. Codes and categories were assessed for applicability to and grouped into the three constructs of the Information‐Motivation‐Behavioral Skills (IMB) Model of health behavior. Key quotes from each construct have been used in the development of a quantitative assessment tool.

Construct/Theme
Sub‐Theme
Qualitative Quote
Quantitative Item

Information
Food Safety
"Some vegetables are worse than others. You always hear about tomatoes and spinach, so I don't even buy them."
"Some fruits and vegetables will give you food poisoning."

Motivation
Social Support
"I am the only one in my family that cares about fruits or vegetables at all."
"I am the only one in my family that cares about eating healthy."

Behavioral Skills
Role Modeling
"My daughter, she'll be like, mom is doing it so let me try it."
"When it comes to eating vegetables, I feel I am a good role model for my child."

This tool will be administrated with a f/v food frequency questionnaire to empirically test and validate these qualitative findings. Findings from this mixed methods study will aid public health and nutrition professionals working with caregivers of AI children to develop effective nutrition messaging.
Human milk oligosaccharides and galactosyloligosaccharides attenuate inflammation in human intestine
Authors: Newburg David , Ko Jae , Leone Serena , Nanthakumar N Nanda
Published: June 2021

The immature intestinal mucosa is hyperresponsive to exogenous and endogenous inflammatory insults. Human milk provides immune protection to infants, and its oligosaccharides (HMOS) are putative immunomodulators. Of these, galactosyloligosaccharides (GOS) are high in colostrum, but not mature milk. The objective is to determine the ability of GOS to directly attenuate inflammation, and potential mechanisms investigated. Human models of immature and mature intestine were used to investigate the ability of a mixture of HMOS or synthetic GOS to attenuate inflammation induced by proinflammatory stimuli and enteric pathogens. These results were confirmed in the ex vivo immature human intestinal organ cultures. The ability of TNFα and of pathogens to elicit pro‐inflammatory neutrophil chemoattractants IL‐8, MIP‐3α and MCP1 and their mRNA levels was significantly attenuated by HMOS and GOS. TNFα‐induced nuclear translocation of NF‐κB was mitigated by HMOS and GOS. Consistent with previous indications of bioactivity of galactosyllactose from human colostrum, trimeric galactosyloligosaccharides interact with cell receptors to inhibit inflammatory response. HMOS and GOS suppress NF‐κB activation, thereby directly attenuating TNFα‐ and pathogen‐induced inflammation in human intestine. This provides a novel mechanism whereby specific galactosyloligosaccharides found in human milk may prove a novel therapeutic agent against gut inflammation.
Citrobacter rodentium Infection Alters Murine Colonic microRNA Signature
Authors: Wen Bijun , Chen Jianmin , Taibi Amel , Comelli Elena
Published: June 2021

MicroRNAs (miRs) have been suggested to play a part in the interaction between pathogenic bacteria and host cells. Citrobacter rodentium is a murine pathogen causing transmissible colonic hyperplasia and colitis with similar pathogenicity as the foodborne enterohaemorrhagic Escherichia coli O157:H7 in humans. This study aimed to examine if colonic microRNA signature is altered during C. rodentium infection. C57Bl6/J male mice were randomized to C. rodentium‐infected or control group, and sacrificed at the peak of infection (10 days post‐infection). Crypt hyperplasia and intestinal inflammation were confirmed by histology and in vivo permeability test. Colonic RNA was used to profile 578 miRs by NanoString technology. Statistics and hierarchical clustering were performed in R. Gene targets of the differentially expressed miRs were identified in silico by prediction algorithms and cross‐matching with experimentally verified targets databases. Ninety‐four miRs were differentially expressed (p<0.05), with 42 downregulated and 52 upregulated vs control (0.2‐8.6 fold), and infected samples clustered together and separately from the controls based on their expression profile. Many of these miRs, including miR‐21, miR‐148a, and miR‐152, are known to regulate barrier function, cell proliferation and inflammatory pathways. Moreover, prediction analysis revealed that globally gene targets are mainly involved in cell cycle and immune response. This study shows that C. rodentium infection alters the colonic microRNA signature; differentially expressed miRs may be involved in the pathogenicity mechanism and serve as targets of nutritional or therapeutic interventions.

Funding: NSERC, JP Bickell Foundation, and NSERC Alexander Graham Bell Canada Graduate Scholarship
Leptin Receptor (OBR) Resistance On Immune Cells From People With Obesity
Authors: Funes Salome , Santander Stephanie , Grijalva Marcelo , Fornasini Marco , Baldeon Manuel
Published: June 2021

Leptin hormone controls food intake and has important immune functions. People with obesity show hypothalamic OBR resistance leading to high serum leptin levels. The increased risk to infections in people with obesity could be related to OBR resistance on immune cells. Few studies have compared the immune response between people with obesity matched with normal controls. This study compared the expression and response of the OBR on peripheral blood mononuclear cells (PBMCs) isolated from people with obesity and healthy controls. Fifteen subjects with obesity and age and sex matched normal weight controls participated in the study. Peripheral blood mononuclear cells were isolated from control and people with obesity after overnight fasting and were cultured with or without leptin or LPS for 24 hours. At the end of the treatment period, IL‐1β, IL‐6, and TNF‐α were measured by ELISA from culture supernatants. Also the expression of OBR on the surface of freshly isolated PBMCs was measured by flow cytometry. Data indicate that there was lower expression of OBR on PBMCs from subjects with obesity than from normal controls. Down‐regulation on the expression of OBR could indicate resistance to leptin stimulation. Also, there was lower production of IL‐1β, IL‐6, and TNF‐α in the supernatants of cultured PBMCs from subjects with obesity after leptin and LPS treatment than from normal controls. A lower cytokine production after leptin stimulation could also indicate OBR resistance due to lower expression and faulty activity of the receptor. Together these data are consistent with partial resistance of OBR on PBMCs from patients with obesity.
Vitamin K Status Associated with MRI Measures of Memory‐Related Brain Activity : A Pilot Study
Authors: Ferland Guylaine , Mellah Samira , Roy Sylvie , Ouliass Bouchra , Belleville Sylvie
Published: June 2021

Discovered for its role in blood coagulation, vitamin K (VK) is emerging as an important nutrient for brain function and cognition. In brain, VK participates in sphingolipid metabolism and activates proteins with cell sigaling actions (Gas6 and protein S) and involved in vascular function (proteins C and S). Recent reports also point to beneficial effects of VK in cognition, notably during aging. To extend our understanding of the action of VK in brain, we investigated, using functional magnetic resonance imaging, the relationship between VK status and brain activity in healthy older adults. Brain activity was investigated in nine healthy older adults using an episodic memory paradigm that involves memorizing pairs of semantically unrelated concrete words (encoding) and indicating in a following block (retrieval) whether words had been presented during encoding (item memory) and whether they were presented as a pair (associative memory).VK status was based on fasting phylloquione concentration (by HPLC). Mean VK concentration for the group was 1.22 nmol/L [range 0.49 ‐ 2.22 nmolL], values in line with previous studies. Brain activity during the encoding phase was not associated with VK status. However, negative correlations (p<0.005) were observed between VK status and brain activity during both item (parietal lobe) and associative (frontal and temporal lobes) retrieval, suggesting that subjects with lower VK status had to recruit more brain tissue to accomplish the memory task. This study confirms the role of VK status in cognition, notably in episodic memory. Financial suport for this study was from CRIUGM.