bluuebunny/crossref_metadata_2025 huggingface dataset:
Eating Away from Home: A Parent's Perspective
Authors: Looney Shannon , Crosby Lori , Stark Lori
Published: June 2021

Eating away from home (EAFH) promotes consumption of energy‐dense, nutrient‐poor foods and large portion sizes; both antecedents to an increased energy intake, and poor diet quality in children. There has been a shift toward EAFH, but little is known about the barriers to a child eating at home from a parent's perspective. Twenty‐seven parents (37.6 ± 6.5 years, 85.2% female, 63% white) with a child 4‐10 years‐old who reported EAFH for dinner 蠅3 days per week participated in one of four focus groups. Questions focused on reasons for EAFH and cooking at home. Each focus group was audio‐taped and transcribed. Responses were independently coded for themes by two primary coders and one reliability coder. As anticipated time and convenience were major themes. In addition, parents reported early school lunches lead to children being hungry upon school dismissal, so the family would buy food on the way home or the child would eat convenience food and not be hungry at dinner. After school activities also lead to children eating “on the go” and at non‐traditional dinner times. In both scenarios the whole family is not home or hungry at dinner time to warrant the parent making a home prepared meal and the parent did not want to make dinner in the later evening, perpetuating consumption of convenience foods or EAFH. Parents reported EAFH was more relaxing than cooking dinner and they ate out to gain better quality time as a family. EAFH was reported to be more rewarding than cooking because all family members could get what they wanted and no one complained about what was served or rejected food because of picky eating, a common phenomenon reported. This study provides insight into the barriers to preparing dinner at home for parents of young children. Results may guide development of interventions to promote family meals at home.
Vision Issues and Space Flight: Evaluation of One‐Carbon Metabolism Polymorphisms
Authors: Smith Scott , Gregory Jesse , Zeisel Steven , Ueland Per , Gibson C , Mader Thomas , Kinchen Jason , Ploutz‐Snyder Robert , Zwart Sara
Published: June 2021

Intermediates of the one‐carbon metabolic pathway are altered in astronauts who experience vision‐related issues during and after space flight. Serum concentrations of homocysteine, cystathionine, 2‐methylcitric acid, and methylmalonic acid were higher in astronauts with ophthalmic changes than in those without (Zwart et al., J Nutr, 142:427‐31, 2012). These differences existed before, during, and after flight. Potential confounding factors did not explain the differences. Genetic polymorphisms could contribute to these differences, and could help explain why crewmembers on the same mission do not all have ophthalmic issues, despite the same environmental factors (e.g., microgravity, exercise, diet). A follow‐up study was conducted to evaluate 5 polymorphisms of enzymes in the one‐carbon pathway, and to evaluate how these relate to vision and other ophthalmic changes after flight. Preliminary evaluations of the genetic data indicate that all of the crewmembers with the MTRR GG genotype had vision issues to one degree or another. However, not everyone who had vision issues had this genetic polymorphism, so the situation is more complex than the involvement of this single polymorphism. Metabolomic and further data analyses are underway to clarify these findings, but the preliminary assessments are promising. This study was funded by the Human Health Countermeasures Element of the NASA Human Research Program.
Effect of Vitamin B6‐antagonist from Flaxseed on Amino Acid Metabolism in Moderately Vitamin B6‐deficient Rats
Authors: Mayengbam Shyamchand , Raposo Sara , House James
Published: June 2021

Pyridoxal 5‐phosphate (PLP) plays a crucial role as a cofactor in amino acid metabolism. There is a prevalence of moderate vitamin B6 deficiency in the population that may be exacerbated through the ingestion of 1‐amino D‐proline (1ADP), a B6‐antagonist found in flaxseed. We investigated the nutritional co‐insult induced by 1ADP intake (flax‐derived vs. synthetic) and moderate B6 deficiency in a rodent model. Male weanling rats (n=8/treatment) consumed a semi‐purified diet containing either 7 (adequate) or 0.7 mg/kg diet (moderately deficient) pyridoxine(PN)•HCl, each with 0 or 10mg/kg diet of 1ADP from synthetic or flaxseed‐derived sources, for 5 weeks. Plasma B6 vitamers were significantly decreased (P蠄0.001) due to 1ADP ingestion, irrespective of source, in moderately B6‐deficient rats. Moderate B6‐deficient rats consuming 1ADP as a flaxseed extract exhibited, relative to controls, a significant increase in plasma cystathionine (P=0.007), and decreases in plasma α‐aminobutyric acid (P=0.002) and glutamic acid (P=0.01) concentrations. However, the synthetic 1ADP elicited greater perturbations in plasma amino acids, compared to the 1ADP extracted from flaxseed. Both 1ADP sources inhibited the activities of the PLP‐dependent cystathionine β‐synthase and cystathionine γ‐lyase (P<0.001). The metabolic perturbations of 1ADP exposure were not evident in rats consuming adequate B6. The current data provide evidence that an anti‐pyridoxine agent now prevalent in the human food supply may pose challenges to those individuals presenting with marginal B6 status. Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC).
The consumption of a grape and blueberry polyphenol‐rich mixture is safe in dogs
Authors: Martineau Anne‐Sophie , Leray Véronique , Gaudout David , Lepoudère Anne , Ouguerram Khadija , Nguyen Patrick
Published: June 2021

Grape polyphenols have beneficial health effects, but grape ingestion has been associated with acute renal failure leading most often to fatal issue in dogs. The responsible factors are unknown.

Our aim was to check the safety of a supplement of polyphenol‐rich mixture (grape and blueberry extracts (specific pet Neurophenols® blend)) in dogs.

Seventeen dogs were given, for 12 wks, capsules containing 4 (n=5) or 20 (n=6) or 40 (n=6) mg/kg/d of the polyphenol mixture. Five control dogs were given maltodextrin capsules. Blood and 24‐h urine were taken before the beginning of the study (W0), then after 4 wks and 12 wks of supplementation. Plasma standard analysis (creatinine (Creat), urea, minerals (Na, K, Ca, P), total protein, hepatic biomarkers (ALT, ALP)) were assayed. New biomarkers that reveal early renal damage were measured : plasma and urinary cystatin C (CysC), clusterin (Clu), neutrophil gelatinase‐associated lipocalin (NGAL). Urinary biomarkers/Creat ratios were calculated. Data were compared with limits of reference intervals or with the highest values from our control dogs and experimental dogs at W0.

Whatever the week, plasma standard analysis were below high limits of reference intervals. Plasma CysC concentration was below our own high limit. Plasma Clu and NGAL concentrations were below limits of reference intervals. Urinary CysC/Creat, Clu/Creat, NGAL/Creat ratios were below our own limit.

Grape extract and blueberry extract (specific pet Neurophenols® blend) consumption was not associated with any sign of renal failure and can be consumed safely in dogs.
WNT1‐inducible protein 1 functions as a pro‐repair molecule in the intestine
Authors: Quiros Miguel , Nishio Hikaru , Neumann Philipp , Leoni Giovanna , Bernal Gabriela , Feng Mingli , Keshavarzian Ali , Mutlu Ece , Parkos Charles , Nusrat Asma
Published: June 2021

In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces. The epithelial reparative response is influenced by inflammation at sites of injury. Wnt‐b catenin signaling plays an important role in controlling intestinal epithelial homeostasis. We identified increased expression of a WNT1‐inducible signaling protein 1 (WISP1) in biopsy‐induced resealing intestinal mucosal wounds. WISP1 treatment of model intestinal epithelial cell (IEC) lines in vitro promotes wound repair by increasing epithelial cell proliferation. WISP1 associates with LRP6 and b1 integrin that are cell surface transmembrane proteins. Analysis of the signaling pathways revealed activation of src and Akt that promote epithelial cell proliferation and ultimately wound repair. In vivo analysis of healing intestinal mucosal wounds in response to biopsy‐induced injury demonstrated upregulation of WISP1 mRNA and protein in resealing intestinal mucosal wounds. Increased secretion of WISP1 in response to the anti‐inflammatory cytokine IL‐10 was observed in healing murine intestinal mucosal wounds. Lastly, WISP1 mRNA and protein was upregulated in human biopsies from patients with active inflammatory bowel disease. In summary, the above findings demonstrate an important role of WISP1 in promoting intestinal mucosal wound repair.
Desmoglein 3 Inhibits Keratinocyte Migration by Suppressing p38MAPK Activity
Authors: Spindler Volker , Hartlieb Eva , Rötzer Vera , Waschke Jens
Published: June 2021

The desmosomal transmembrane adhesion molecule desmoglein 3 (Dsg3) is required for strong keratinocyte cohesion. Recently, we have shown that Dsg3 loss of function, either by siRNA silencing or by peptides interfering with Dsg3 binding, increases the activity of p38MAPK. In this study, we aim to investigate the physiological role of Dsg3‐dependent p38MAPK suppression. Dsg3‐deficient mice display repetitive skin erosions most of which rapidly heal spontaneously. In lysates from wound biopsies but also from perilesional areas, p38MAPK activation was detectable compared to control animals. Similarly, in skin biopsies of pemphigus patients which suffer from impaired cell cohesion due to autoantibodies targeting Dsg3, p38MAPK activity was increased in areas of epidermal blistering. This led us to speculate that Dsg3 regulates wound repair in a p38MAPK‐dependent manner. Indeed, silencing of Dsg3 resulted in increased p38MAPK activity which was paralleled by enhanced migration speed. In line with this, scratch wounded keratinocyte monolayers exhibited p38MAPK activation in cells lining the wound edge. Importantly, migration was efficiently blocked by inhibition of p38MAPK both in control and Dsg3 knockdown keratinocytes. These data indicate that Dsg3 via p38MAPK inhibition prevents a switch from an adhesive to a migratory keratinocyte phenotype. Upon wounding, impaired Dsg3 adhesion may thus favor wound closure by facilitating p38MAPK‐dependent migration.
Epigenetic Modification of Von Willebrand Factor (VWF) Leads to its Expression in Cancer Cells with Increased Metastatic Activity
Authors: Mojiri Anahita , eisenstat David , Lewis John , Stoletov Konstantin , Simmen Katia , Jahroudi Nadia
Published: June 2021

VWF is an adhesive procoagulant protein that is exclusively expressed in endothelial cell (EC) and megakaryocytes. It is key initiator of blood clotting cascade. Increased plasma levels of VWF and alterations in coagulation system in patients with metastasis and cancer progression are reported. We hypothesised that a subpopulation of some cancer cells of non‐endothelial origin may acquire VWF expression and as a result develop enhanced metastatic potential.

RT‐PCR, western blot and Immunoflourescent (IF) analyses showed significant levels of VWF expression in an osteosarcoma (Saos2) and glioma (U251, M016, M049) cell lines. Chromatin IP assays demonstrated a similar pattern of transcription factors binding as is observed for VWF gene in EC. The epigenetic modification analysis showed that histone modification of the VWF promoter in glioma (U251, M016, M049) and Saos2 is consistent with transcriptionally active VWF promoter. In vitro cell‐cell interaction analyses showed that cancer cell lines expressing VWF, exhibited increased affinity to adhere to the platelets and an EC monolayer under sheer stress. IF analyses of human glioma tumor samples, demonstrated VWF expression in some cells of non‐endothelial origin in the tumor region, highly suggestive of VWF expression in a subset of glioma cancer cells. Chick Chorioallantoic Membrane assay showed increased extravasation and metastatic lesions for cancer cells expressing VWF.

A subpopulation of cancer cells of non‐endothelial origin acquires denovo expression of VWF as a result of epigenetic modification of the VWF promoter. Acquired VWF expressions by cancer cells increase their adhesive properties and may contribute to their metastatic potential.
A High Fat Diet Supplemented with Soy Prevents Diet Induced Promotion of Liver Tumors in DEN‐Treated Male Mice
Authors: Mercer Kelly , Hennings Leah , Lai Keith , Jones Ellen , Drake Richard , Ronis Martin
Published: June 2021

In the United States, the increase in hepatocellular cancer incidence rates can be partially attributed to increased prevalence of risk factors associated with obesity and metabolic syndrome. Previously we have shown high fat feeding increases tumor progression in DEN‐treated male mice, which was related to hepatic TNFa signaling and macrophage recruitment. In the present study, saline treated and DEN‐treated male mice were fed a 35% high fat liquid diet containing either casein (HF/cas) or soy (HF/soy) as the sole protein source for 16 wks. High fat feeding increased tumor incidence and multiplicity in the HF/cas group compared to the DEN‐treated chow fed group, p<0.05. Soy protein substitution decreased total tumor number which corresponded to reductions in serum ALT concentrations, hepatic steatosis and immune cell infiltration, and nuclear accumulation of NFkB protein in the HF/soy group compared to HF/cas mice , p<0.05. Detection of sphingolipids using high resolution MALDI‐FTICR Imaging mass spectrometry revealed an increase in C18 ceramide and sphingosine 1‐P accumulation in the HF/cas group compared to the HF/soy group. Further analysis demonstrated a significant increase in mRNA expression of ceramide synthase 1 and 4, and in the translocation sphingosine kinase 1 to hepatic microsomal fractions, all of which were ameliorated by soy supplementation. We conclude that soy prevents tumorigenesis in part by reducing the pro‐inflammatory environment by reducing sphingosine 1‐P /NFkB signaling. Supported in part by NCI R21 CA169389 (MJR).
From GWAS to Therapy: Fatty Acid Synthase in Uterine Leiomyomata
Authors: Ordulu Zehra , Hayden Mark , Eggert Stacey , Shinohara Masakazu , Serhan Charles , Quade Bradley , Morton Cynthia
Published: June 2021

Uterine leiomyomata (UL) pose apublic health problem given high prevalence (>70%) in women of reproductive age and being a major indication for hysterectomies. Genome‐wide association studies for UL predisposition identified a candidate SNP (rs4247357) under a linkage peak in 17q25.3 that spans the gene fatty acid synthase (FASN). By immunohistochemistry we found elevated FAS protein levels (3‐fold) in UL in comparison to matched myometrial tissue. FAS isreported to be upregulated in various neoplasms and implicated in tumor cell survival. We assessed effects of FAS inhibitors Orlistat and C75 in primary cell cultures of 20 matched myometrium and UL by cell proliferation assays. Cell counts are reduced in a dose‐dependent manner with a half maximal inhibitory concentration ranging between 50‐75 uM (Orlistat) and 30‐45 uM (C75) (similar dosage with previously published cancer types treated with FAS inhibitors). Further, Orlistat treatment reduced free fatty acids and increased fatty acid CoA‐esters by Gas chromatography–mass spectrometry (GC‐MS) analysis, supporting its role through inhibition of the thioesterase domain of FAS. FASN represents the first potential UL predisposition gene identified in white women. Responsiveness of UL to inhibition of FAS is a potential model for targeted therapy to mitigate risks of surgical management.
Autophagy triggered by p14.3.3z induces Akt full activation in intestinal epithelial cells.
Authors: Gómez‐Suárez Mauricio , Hernandez Marcela , Candelario Aurora , Schnoor Michael , Ortiz‐Navarrete Vianney , Villegas‐Sepulveda Nicolás , Nava Porfirio
Published: June 2021

Akt activation has been associated with proliferation, differentiation and survival in epithelial cells. Phosphorylation of Thr308 of Akt by PDK1 is critical for optimal activation of its kinase activity. Despite the relevance of the phosphorylation of Akt at Threonine 308, the mechanism(s) regulating this process remain unclear. Here, we report that 14.3.3 proteins control Akt Thr308 phosphorylation during intestinal inflammation. Mechanistically we found that proinflammatory cytokines fully activate Akt by inducing degradation of the PDK1 inhibitor, 14.3.3η via autophagy. Interestingly we also observed that exposure of intestinal epithelial cells to proinflammatory cytokines reduces autophagy, suggesting that during inflammation full Akt activation is prevented. Notably, inhibition of 14.3.3 function by the chemical inhibitor BV02 results in uncontrolled Akt activation and increased cell death. Taken togetherour results show that 14.3.3 proteins tamper Akt activation to regulate its physiological functions, thereby providing a new mechanistic link between cell survival and apoptosis phenotype on intestinal epithelial cells during inflammation.
mRNA‐binding protein IMP1 is a novel regulator of autophagy following intestinal irradiation injury
Authors: Hamilton Kathryn , Chatterji Priya , Andres Sarah , Lundsmith Emma , Whelan Kelly , Giroux Veronique , Mah Amanda , Van Landeghem Laurianne , Lund Pauline , Rustgi Anil
Published: June 2021

Background

Post‐transcriptional regulation of intestinal homeostasis via mRNA‐binding proteins, including Igf2 mRNA‐binding protein 1 (IMP1), is an area of emerging interest. Imp1‐null mice exhibit severe intestinal growth defects, yet Imp1 deletion in intestinal epithelium (Imp1ΔIEC) reveals minimal phenotype. Imp1 expression is significantly increased in intestinal stem/progenitor cells post‐irradiation, and new data indicate that Imp1ΔIEC mice exhibit increased baseline autophagy. We hypothesized that Imp1 is essential for intestinal response to irradiation, possibly via modulation of autophagy.

Methods

We treated Imp1ΔIEC and control mice with 12Gy irradiation and evaluated small intestine 96 hours later. Epithelia were evaluated for changes in autophagy via western blot and FACS. Enteroids plated from crypts of Imp1ΔIEC and control mice evaluated stem cell growth.

Results

Autophagy is up‐regulated in control mice following irradiation; however, Imp1ΔIEC mice exhibit repressed autophagy. In control mice, irradiation increases the proportion of spheres (non‐differentiated) to budding enteroids (differentiated), reflecting stem cell expansion. Intriguingly, irradiated Imp1ΔIEC mice show a further increase in sphere‐like enteroids, indicating that Imp1 may function to modulate stemness/differentiation following injury.

Conclusions

Our data suggest that Imp1 may regulate autophagy in response to irradiation in the intestine, representing a novel paradigm by which autophagy may influence stemness in intestinal homeostasis.
Muscle‐Specific Ubiquitin Ligase MuRF1 Regulates Myocardial Autophagic Flux in vivo
Authors: Parry Traci , Quintana Megan , Hill Joseph , Willis Monte
Published: June 2021

The ubiquitin‐proteasome and autophagy systems are complementary protein degradation pathways that play a critical role in protein quality control and protein turnover in cardiomyocytes. The specificity of the UPS is carried out by ubiquitin ligases (E3), including the muscle‐specific Muscle Ring Finger‐1 (MuRF1). Mounting evidence suggests that there is interplay between the UPS and autophagic pathways; however they are not yet well understood in the heart. To identify MuRF1′s regulation of autophagic flux, MuRF1‐/‐ and sibling MuRF1+/+ controls were treated with Bafilomycin A1 and hearts harvested for western analysis of LC3BI/II expression. MuRF1‐/‐ animals showed significantly less autophagic flux (72% reduction vs. MuRF1+/+, P<0.01). The p62/SWSQSTM1 ubiquitin‐binding scaffold that colocalized with ubiquitinated protein aggregates were decreased in the absence of MuRF1 and significantly increased when MuRF1 expression increased in vivo (MuRF1 Tg+ hearts) by western analysis. Taken together, these findings suggest MuRF1 expression regulates myocardial autophagy in vivo and may link convergence of the UPS and autophagy system. Since increasing cardiomyocyte autophagic flux can support the heart's resiliency (ischemia reperfusion injury) or impair its ability to maintain function (pressure overload induced‐cardiac hypertrophy), its regulation can be finely tuned in a disease‐specific manner. Understanding MuRF1′s regulation of autophagy provides useful insight for the development of therapies targeting autophagy in heart disease.
Is Accreditation Driving Our Teaching in The Right Direction?
Authors: Lufler Rebecca
Published: June 2021

There are many approaches to teaching and learning in higher education settings, including traditional lecture, flipped classroom, and a hybrid of these learning models. Accrediting bodies are beginning to mandate active learning over passive learning environments, causing institutions to change from traditional lectures, yet there is limited evidence to support such changes. The objective of this study is to compare the effectiveness of a flipped classroom and a hybrid learning model used within a two semester Physician Assistant (PA) gross anatomy course.

30 PA students (group A) experienced a flipped classroom model (students learn content on their own before class and utilize class time to apply content) and 40 PA students (group B) experienced a hybrid model (both lecture and flipped classroom techniques are used to learn content) during gross anatomy in 2013 and 2014 respectively. Quantitative data (mean exam scores, final grades, performance on exam questions) and qualitative data (course evaluations) were gathered for both models.

70 students completed the course, 30 students in group A and 40 students in group B. Group B performed significantly higher than group A in the course during semester 1 (mean 94.89 and 91.27, p<0.001) and semester 2 (mean 95.08 and 90.93, p<0.001). Qualitative data showed that students prefered the hybrid learning model.

Based on these preliminary results, 1st year PA students earned a higher final grade in a gross anatomy course under the hybrid learning model. Students' course evaluation comments also favored the hybrid learning over the flipped classroom model. These results will help improve and inform teaching approaches to be used in the course and help other courses adjust to accreditation standards.
Microbiome/Metabolic Syndrome/Diabetes and CVD
Authors: Lusis Aldons J , Org Elin , Emert Benjamin , Joo Jong Wha , Mehrabian Margarete , Schwartzman William , Parks Brian , Davis Richard , Blum Yuna , Furuta John , Navab Mohamad , Fogelman Alan , Drake Thomas , Knight Rob , Gunsalus Robert , Hazen Stanley , Eskin Eleazar
Published: June 2021

We have carried out taxonomic profiling of gut microbiota in a population of about 100 commercially available inbred strains of mice termed the Hybrid Mouse Diversity Panel (HMDP). This panel has been developed as a systems genetics resource and can be used for high resolution association mapping of complex traits. When maintained under controlled environmental conditions, the gut microbiota composition exhibits high heritability in the HMDP as calculated using a linear mixed model assuming additive genetic effects. Genome‐wide association analysis with informative SNPs identified significant loci in the mouse genome associated with relative abundances of specific taxa. The HMDP mice have been typed for a number of cardiovascular, metabolic, and other clinical traits, allowing correlation analysis of gut microbiota composition with clinical traits. Some of these associations, such as the association between Akkermansia muciniphila levels and high fat diet response, have subsequently been confirmed in published experimental studies. A number of novel associations are presently being tested using co‐fostering of different inbred strains or experimental introduction of cultured bacterial species. A variety of diets have been studied across the HMDP. In conclusion, studies of natural variations in gut microbiota composition in mice may help identify regulatory host factors as well as providing a global view of the relationships between microbiota and clinically relevant traits.
A Holistic Approach to Training the next Generation of Diverse Biomedical Researchers
Authors: Barbour Suzanne , Lloyd Joyce , Wu‐Pong Susanna
Published: June 2021

The Virginia Commonwealth University (VCU) Initiative for Maximizing Student Diversity (IMSD) program was prompted by a self‐study that indicated underrepresented minority (URM) PhD students were under‐performing in their programs. Seventy five percent of supported VCU‐IMSD PhD students are making good progress towards their degrees and the first of these individuals completed the PhD in 2013. Two of the eight supported students have secured independent support for their training and the most senior trainees have published papers. Some IMSD PhD trainees achieved these successes despite modest performance on the GRE and in first year course work. We attribute success of these individuals to several factors. First, the IMSD program has embraced a “coaching” model for student training. The Program Director coaches students, without the evaluative role of a traditional PhD mentor. Second, IMSD PhD students participate in a professional‐development program (VCU‐BEST) designed to help them identify their career paths. The students tend to be more productive and successful once they have identified their career paths. Third, the IMSD program is a mechanism to bring URM PhD students together and provides a sense of “cohort”. IMSD PhD students also benefit from shared experiences with their majority peers that reduce social barriers, thereby making it easier for them to collaborate and support each other in laboratory and academic settings. Finally, IMSD PhD students are role models and coaches for underrepresented undergraduates and postbaccalaureates. This leadership opportunity enhances self‐efficacy, further increasing productivity and success. Although the IMSD PhD program was designed to support URM students, we argue that these activities are potentially beneficial for all PhD students.
Building Better Career Development Programs
Authors: Micoli Keith
Published: June 2021

Recent reports and recommendations have drawn increasing attention to the difficulties of the job market for PhD scientists, particularly in the biomedical disciplines. Clearly, the current model fails to prepare trainees for the careers they will most likely pursue, whether or not the number of trainees is sustainable.

A growing number of institutions now provide diverse training opportunities, bolstered by the NIH's establishment of the Broadening Experiences in Scientific Training (BEST) Program. Now supporting 17 institutions, this program intends to change the culture of academic scientific training, and embraces the fact that most PhDs will not pursue faculty positions.

This talk focuses on the program at New York University, which provides an enriched training environment aiming to expand the breadth of career development opportunities for trainees without lengthening the time spent in training. Our hypothesis is that trainees with a defined career plan will be more focused in their efforts, more satisfied with their experience, and ultimately find rewarding careers more quickly.

Our program begins with career planning and exploration, develops broad professional skills, and culminates in career‐specific training and experience. We have established a rigorous evaluation model and tracking system that will determine what resources are most effective, where our trainees go after leaving NYU, and provide a deeper understanding of the needs of trainees and their ultimate employers.
Circadian Regulation of Intestinal Host‐Microbe Interactions
Authors: Hooper Lora , Yu Xiaofei , Ruhn Kelly , Stubblefield Jeremy , Green Carla , Kashiwada Masaki , Rothman Paul , Takahashi Joseph
Published: June 2021

Twenty‐four hour cycles of day and night are a fundamental feature of life on earth. Virtually all life forms undergo physiological and behavioral changes on a ~24 hour cycle (known as a “circadian” cycle), in synchrony with the changes in natural light. Such processes are controlled by a network of transcription factors, collectively termed the “circadian clock”, which function together in individual cells, capturing light cues from the visual and nervous systems and using these cues to regulate gene expression. Despite the importance of circadian regulation for many aspects of physiology, little is known about how the circadian clock regulates immunity.

We have unveiled a molecular link between the circadian clock circuitry and T cells that impacts immune interactions with the intestinal microbiota. Interleukin‐17‐producing T helper (Th17) cells are proinflammatory immune cells that regulate interactions with intestinal bacteria. We have found that the lineage specification of these cells varies diurnally and have unraveled a molecular mechanism that links Th17 cell lineage commitment to the circadian clock. We have further found that light cycle disruption elevates intestinal Th17 cell frequencies and increases susceptibility to intestinal inflammation. Our findings reveal direct circadian control of a key intestinal immune cell and show that this pathway is essential for homeostasis with the intestinal microbiota.
Genome‐Wide Association Studies (GWAS) of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue: Relationships with Insulin Sensitivity
Authors: Marklund Matti , Gustafsson Stefan , Keildson Sarah , Morris Andrew , Ingelsson Erik , Lindgren Cecilia , Risérus Ulf
Published: June 2021

Fatty acid desaturases (FADS) catalyze formation of mono‐ and polyunsaturated fatty acids (FA) and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may affect the link to IS.

The study aimed at identifying genetic variants influencing estimated FADS activity in serum cholesterol esters (CE) and adipose tissue (AT); and to evaluate if identified loci affect IS.

GWAS of Δ9‐ (D9D), Δ6‐ (D6D), and Δ5‐desaturase (D5D) activities (estimated by product‐to‐precursor FA ratios analyzed by gas chromatography) in CE (n=1,453, 70% men) and AT (n=783, all men) were performed in two Swedish population‐based cohorts. Associated loci (P <5.0E‐8) were evaluated for associations with IS measured by hyperinsulinemic euglycemic clamp (n=554).

Variants in one locus (FADS1) were strongly associated with D5D in CE (P=1.9E‐70) and AT (P=1.1E‐27). Variants in three loci were associated at a genome wide‐significant level with CE D6D (FADS2, P=3.0E‐67; PDXDCI, P= 4.8E‐8; and near MC4R, P=3.7E‐8) and one with AT D9D (PKDL1, P=2.2E‐19). After Bonferroni correction, one locus was significantly associated with IS (PDXDCI, P=0.030).

FADS genes determined estimated FADS activity, although FA ratios in AT and CE represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential effects on IS.

The Wellcome Trust funded the study.
Acute Peanut Consumption Benefits Postprandial Endothelial Function in Overweight Healthy Males
Authors: Liu Xiaoran , Hill Alison , West Sheila , Gabauer Rachel , McCrea Cindy , Fleming Jennifer , Kris‐Etherton Penny
Published: June 2021

Endothelial dysfunction is important in the onset and progression of atherosclerosis. Postprandial hyperlipidemia is associated with an impairment (i.e. reduction) of endothelial function. We evaluated the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow‐mediated dilatation (FMD) of the brachial artery in fifteen overweight males (BMI 31.4±0.8). Participants were randomized to either a peanut meal contain 3 oz. of ground peanuts (1198 kcal, 40.0% CHO, 47.7% FAT: 19.4% SFA, 13.2% PRO) or a control meal with matched energy and macronutrients, followed by the alternative meal scheduled at least one week apart. The meals were delivered as shakes. The lipid profile, glucose and insulin were measured postprandially at baseline, 0.5, 1, 2, and 4h. FMD was measured at baseline and at 4h. Acute peanut consumption resulted in a blunted triglyceride response 2h after consumption compared with the control meal (94.5±13.4 mg/dL vs. 117.1±13.4 mg/dL, p=0.034). The change in total cholesterol, LDL‐cholesterol, HDL‐cholesterol, glucose and insulin was similar between the test meals. Compared to baseline, the control meal decreased FMD at 4h (‐1.2%±0.5, p=0.03), whereas no significant difference was observed after consumption of the peanut meal (‐0.6%±0.5, p=0.3). The present study demonstrated that the inclusion of peanuts (3 oz.) as part of a high fat meal improved the postprandial triglyceride response and preserved endothelial function. Support: the Peanut Institute; Clinicaltrials.gov identifier NCT01405300
The Effects of Orange Polyphenols on Vascular and Cognitive Function
Authors: Saunders Caroline , Harkness Laura , Spencer Jeremy
Published: June 2021

Introduction

Evidence suggests that polyphenols may beneficially influence vascular function and neurocognition. The aims of the current research was to determine the pharmacokinetics of the major polyphenols in oranges and to determine whether orange beverages, with different levels of polyphenols, can modulate vascular and cognitive function.

Methods

In men (n=6) we measured the maximum plasma concentration (Cmax) and time to reach maximum concentration (Tmax) of hesperetin and naringenin following consumption of 3 different orange beverages. Subsequently we assessed flow mediated dilatation (FMD) at baseline and at 2, 5 and 7 hours in a randomized, double blind, cross over study in males with moderately raised lipids or BMI (n=37) following one of 4 treatments; water with sugar control (WSC), orange juice without pulp (OJWP), processed whole orange (PWO) or whole orange (WO). We also assessed cognitive performance at baseline and 2 and 5 hours following consumption of either the WSC or PWO.

Results

The Cmax of hesperetin and naringenin were 0.25µm and 0.09µm respectively and the Tmax 6.8h and 6.7h. Compared to the control OJWP, PWO and WO attenuated a meal induced decrease in FMD (fig. 1). PWO attenuated a decline in subjective alertness, improved speed of processing and overall cognitive performance.

image

Conclusion

The effects on vascular and cognitive function correlated with the peak plasma concentration of flavonoid metabolites. The effects on cognition are likely due to changes in blood flow and improved delivery of metabolic substrates to neural tissue.

These results suggest that polyphenol rich orange products can modify a biomarker associated with a reduced risk of cardiovascular disease and beneficially influence neurocognition.
The Association between Insomnia Symptoms and Diet Quality and Energy Intake
Authors: Cheng Feon , Li Yanping , Winkelman John , Hu Frank , Rimm Eric , Gao Xiang
Published: June 2021

Insomnia, characterized by difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early‐morning awakenings (EMA), or nonrestorative sleep (NRS), is the most common sleep disorder. While some small clinical studies have shown potential impact of sleep on eating habits, the relationship between insomnia and diet remains unclear. We thus conducted a longitudinal analysis to examine whether men with insomnia symptoms had a lower diet quality and greater energy intake 2 years later. Analysis included 15,005 US men (mean age 67.3 ± 8 y) participating in the Health Professionals Follow‐up Study and free of cancer, diabetes, and cardiovascular diseases. Insomnia was assessed in 2004 via questionnaires by asking participants how often (rarely/never, sometimes, or most of the time) they experienced insomnia symptoms. Dietary intake was assessed by a validated food frequency questionnaire in 2002 and 2006; the Alternative Healthy Eating Index (AHEI) was utilized as the measure of diet quality. Analyses adjusted for age, smoking, body mass index, AHEI and total energy intake in 2002, and other potential confounders. Men with DIS in 2004 tended to have a lower diet quality score (P‐trend<0.0001) and higher energy intake (P‐trend=0.07) in 2006, in a dose‐dependent manner. Reporting DMS and NRS were associated with higher energy intake (P‐trend<0.01 for both). In contrast, we did not observe significant associations between other insomnia symptoms and diet quality or energy intake. In conclusion, certain insomnia symptoms could have potential unfavorable impact on diet.
INTACT β,β‐CAROTENE ‐9′,10′‐OXYGENASE 2 (BCO2) IS ESSENTIAL TO INTEGRITY OF HEPATIC MITOCHONDRIAL FUNCTION IN MICE
Authors: Wu Lei , Guo Xin , Hartson Steve , Clarke Stephen , Lucas Edralin , Smith Brenda , Lin Dingbo
Published: June 2021

Objective

β,β‐carotene‐9′, 10′‐dioxygenase 2 (BCO2) is a carotenoid cleavage enzyme in the inner membrane of mitochondria. However, BCO2 is inactivated in human macula where xanthophylls are preferentially accumulated. The purpose of this study is to determine whether intact BCO2 protein impacts integrity of hepatic mitochondrial function in mice.

Methods

Male BCO2 knockout (KO) and the genetic background wild type (WT) mice, at 6 weeks of age, were used. Isolated hepatic mitochondria with and/or without zeaxanthin treatments were subjected to mitochondrial proteome profiling (by LC‐MS/MS) and functional integrity assay (by the assay of coupling and electron flow). Liver tissue metabolomics was also explored.

Results

The basal respiratory rate and the proton leak were both significantly elevated in the BCO2 KO liver, though the maximum respiratory capacity remained similar between both WT and KO mice. The oxygen consumption rate of the electron transport chain (ETC) complex IV was significantly greater in KO mice than that in the WT. The alteration was more deleterious by application of zeaxanthin in KO but not WT. Mitochondrial proteomic profiling results indicated alterations of enzymes and proteins involved in fatty acid β–oxidation, the tricarboxylic acid cycle, ETC/oxidative phosphorylation, and the metabolism of carotenoids. The global metabolic profiles of BCO2 KO liver confirmed oxidative stress and mitochondrial stress resulting from the loss of BCO2.

Conclusions

The functional and ‐omics data suggest that BCO2 contributes to normal mitochondrial function in the liver of mice.
F‐actin Binding Protein, Anillin, Regulates Integrity of Intercellular Junctions in Human Epithelial Cells
Authors: Wang Dongdong , Chadha Gibran , Feygin Alex , Ivanov Andrei
Published: June 2021

Tight junctions (TJ) and adherens junctions (AJ) are key morphological features of differentiated epithelial cells that regulate the integrity and permeability of tissue barriers. Structure and remodeling of epithelial junctions depends on their interactions with the underlying actomyosin cytoskeleton. Anillin is a unique scaffolding protein interacting with different cytoskeletal components, including actin filaments and myosin motors. Its role in the regulation of mammalian epithelial junctions remains unexplored. Downregulation of anillin expression in human prostate and lung epithelial cells triggered disassembly of AJ and TJ without altering the expression of junctional proteins. This junctional disassembly was accompanied by dramatic disorganization of the perijunctional actomyosin belt; while the general architecture of the actin cytoskeleton and activation of non‐muscle myosin II remained unchanged. Furthermore, loss of anillin disrupted the adducin‐spectrin membrane skeleton at the areas of cell‐cell contact, selectively decreased γ‐adducin mRNA and protein expression, and induced cytoplasmic aggregation of αII‐spectrin. Down‐regulation of γ‐adducin mimicked the effects of anillin knockdown on epithelial junction integrity. These findings suggest a novel role for anillin in regulating TJ and AJ in human epithelia by controlling assembly of the perijunctional actomyosin cytoskeleton and the membrane skeleton. This work was supported by NIH grants DK083968 and DK084953 to A.I.I.
Towards a whole animal, whole lineage perspective on the evolution of tetrapod locomotion
Authors: Pierce Stephanie , Hutchinson John
Published: June 2021

One of the great mysteries regarding the evolution of animals is how and when tetrapods achieved the ability to stand and move on solid ground. Old perceptions that our fish ancestors gradually evolved limbs with digits on terra firma have been discarded in light of new evidence favouring a wholly aquatic origin. But which pioneering tetrapod species could move on land and how well‾ This question must be resolved in order to piece together how “modern” walking evolved. Our recent work has shown that the morphology of known stem tetrapods could not have supported walking in a typical salamander‐like fashion and that a mudskipper‐like crutching gait was more likely to be employed. Such a hypothesis means we still know very little about the evolution of modern walking behaviours. To further our investigation, we are forging work that links three‐dimensional whole animal morphology, empirically tested biomechanical performance indices, and whole lineage character changes. Our goal is to create validated, dynamic simulations of locomotion in extinct tetrapods bridging the water‐land transition.
Genetic and Environmental Control on Mandibular Form and Function in Mice
Authors: Rayfield Emily
Published: June 2021

Bone modelling and remodelling is a means by which organisms may be able to plastically modify the external morphology and internal structure of their skeletal tissues. We have shown previously that lab mice of the C56BL/6 strain that were fed either hard or soft foodstuffs with the same nutritional value have significantly different shaped jaws. The shape differences manifest as difference in function, with the mandibles of hard food eaters possessing a higher mechanical advantage (MA) of the temporalis and masseter adductor musculature than the soft food eaters. Here we compare the magnitude of difference in MA between the C56BL/6 hard and soft food eaters to the difference in MA between C56BL/6 hard food eaters and BALB/c hard food eaters. We also compare the difference between strains and between plastically generated morphotypes in resistance to bending and torsion from second moment of area measurements from CT scans and in simulated functional bony stress and strain deduced from finite element models. Hard food eaters have increased resistance to bending, torsion (n=39) and loading induced stress and strain (n=4) compared to soft food eaters. C56BL/6 and BALB/c mice have significantly different shaped jaws with BALB/c mice having more gracile jaws with a less developed masseteric ridge (n = 20). Comparative finite element (FE) models show that BABL/c mice also experience consistently greater deformation when subject to functional feeding‐induced loads (n=4). Environmentally driven plasticity leads to functional differences that favour the efficiency of food processing in the hard food eaters. Difference in performance between hard and soft food eaters exceed the difference in performance between lab strains, suggesting plasticity as a mechanism to provide morphological variation on which natural selection may act.
Changes in Vertebral Morphology with Increasing Aquatic Adaptation in Crocodylomorphs
Authors: Molnar Julia , Pierce Stephanie , Hutchinson John
Published: June 2021

The lineage leading to modern crocodylians has undergone dramatic evolutionary changes in both morphology and locomotion over the past 200 million years. Our objective was to estimate changes in osteological range of motion (RoM) and intervertebral joint (IVJ) compliance of thoracic and lumbar vertebrae with increasing aquatic adaptation in crocodylomorphs. Using 3D virtual models and morphometrics, we compared the modern crocodile Crocodylus to four extinct crocodylomorphs, Terrestrisuchus, Protosuchus, Pelagosaurus, and Metriorhynchus, which span the spectrum from fully terrestrial to fully aquatic. In Crocodylus, we also experimentally measured changes in trunk flexibility with sequential removal of osteoderms and soft tissues.
Our results showed that both IVJ compliance and RoM increased with adaptation to aquatic locomotion, as expected, but this trend seems to have reversed somewhat in aquatic specialists. The IVJs of modern crocodylians had the greatest osteological RoM, but their morphometrics suggested reduced IVJ compliance, lending support to the idea that the trunks of early crocodylomorphs primarily were stabilized by their extensive osteodermal shields rather than IVJs. The most important structures for determining RoM and compliance of the trunk in Crocodylus were different in dorsoventral versus mediolateral bending, suggesting that changes in osteoderm and rib morphology over crocodylomorph evolution would have affected movements in some directions more than others.
Cephalic Muscle Evolution in Chordates
Authors: Ziermann Janine , Diogo Rui
Published: June 2021

The origin and early evolution of the vertebrate head has fascinated scientists for centuries. However, many studies still do not include an extensive analysis of soft tissues, such as muscles. Urochordates are the closest sister‐group of vertebrates and the recent finding that urochordates have a cardiopharyngeal field has a great impact in our understanding of the origin and evolution of vertebrates. We provide and updated overview of the cephalic muscles in cyclostomes and chondrichthyans and present and extensive comparative analyses that infers the plesiomorphic conditions for vertebrates and gnathostomes. Based on this homologies and important evolutionary patterns of the cephalic muscles in vertebrates will be presented. The last common ancestor of extant vertebrates probably had one intermandibularis and other mandibular muscles (labial muscles), some constrictores branchiales and hyoidei, and epibranchial and hypobranchial muscle sheets. The division of the cucullaris into levatores arcuum branchialium and protractor pectoralis is an osteichthyan synapomorphy and reflects an evolutionary trend towards a greater separation between the head and pectoral girdle that culminated in the formation of the tetrapod neck. Those results provide a basis for future evolutionary and developmental studies of vertebrates and their subgroups.
Spatial ability and learning anatomy
Authors: Smith Claire
Published: June 2021

Understanding how spatial ability relates to learning anatomy is important in developing safe doctors and health care professionals. This study brings together three separate projects. Project 1 involved a series of spatial ability experiments on medical students (n=30) and doctors (n=20) at the University of Southampton, UK. It aimed to explore if spatial ability could be trained for. The results indicated that metric (depth) perception increased with training (p=0.007). Project 2 conducted at the University of Brighton and Sussex Medical School aimed to see if medical students (n= 105) previous experience of learning made a difference. The results indicated that students who had studied physics had an improved spatial ability (p=0.022). Project 3 measured the use of touch mediated perception during examination on a cadaver removing the heart/lungs using motion tracking devices. The results indicated that the total distance of flexion and extension was 8765 degrees with radial and ulna deviation of 5475 degrees. In conclusion these 3 projects inform us that spatial ability has an element of being a learned and trained ability and this is reflected by those who had studied a visual subject. Educational theory recommends an active learning approach as being an effective study method and using human cadavers has been proposed as a method that reflects active learning, the final experiment reflects how active examination of a specimen is!