bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐fat diet alters serum fatty acid profiles in obesity prone rats: implications for in‐vitro studies
Authors: Liu Tzu‐Wen , Heden Timothy D. , Blandon Abiezer , Morris E. Matthew , Fritsche Kevin L. , Thyfault John P. 
Published: June 2021

High‐fat diet (HFD) feeding is commonly used in animal models to induce obesity and metabolic diseases. However, the effect of HFD on serum fatty acid profiles remains unclear. Changes in serum fatty acid profiles due to HFD may be a factor in lipotoxicity in various organs. Historically, in vitro studies have utilized individual non‐esterified fatty acids (NEFA) to study lipid exposure, potentially ignoring the importance of fatty acid combinations on cellular lipid metabolism.OBJECTIVETo create a physiological relevant fatty acid mixture to investigate lipid exposure in a cell culture system.METHODSObesity prone rats were fed a HFD (60% en fat) or a control diet (10% en fat) for 2 weeks; portal and systemic blood samples were collected. Triglycerides (TG) and NEFA were extracted and analyzed using gas chromatography.RESULTSBoth systemic and portal serum TG were ~40% lower in HFD. In the control, monounsaturated fatty acids (MUFAs) were the predominant fatty acids in serum TG, whereas polyunsaturated fatty acids (PUFAs) were the dominant fatty acids in the HFD group. Serum NEFA levels were not affected by diet.CONCLUSIONHFD alters serum fatty acid composition of TG from one where MUFAs predominant to PUFAs in rats. A more physiologically relevant fatty acid mixture to mimic HFD conditions for in vitro studies may include increased PUFAs relative to saturated fatty acids and MUFAs. Support: R01DK088940 (JPT)
HDAC7 mediated activation of STAT3 in human PTEN deficient glioma cells suppresses angiogenesis and tumor growth in vivo
Authors: Turtoi Andrei , Blomme Arnaud , Castronovo Vincent 
Published: June 2021

Phosphatase and tensin homolog (PTEN) is a key tumor suppressor whose loss is commonly found in glioblastoma multiforme (GBM). In GBM, loss of PTEN leads to inactivation of signal transducer and activator of transcription 3 (STAT3). In contrast to the pro‐oncogenic function of STAT3 in other tumors, STAT3 has emerged as a key tumor suppressor in PTEN−/− GBM.We report for the first time a histone deacetylase 7 (HDAC7) mediated mechanism of STAT3 activation in PTEN−/− GBM. SiRNA induced depletion of HDAC7 in human U87 glioma cells triggered (both in vitro and in vivo) phosphorylation of STAT3 on Y705. In accordance to our previous data, we show that this event is dependent of A‐kinase anchor protein 12 (AKAP12), which is rapidly induced upon HDAC7 silencing. In vivo, siRNA mediated HDAC7 repression abrogated tumor growth in U87‐glioma chick‐chorioallantoic membrane animal model. This effect was reversible when AKAP12 was co‐supressed. Intrigued by the macroscopical appearance of U87 tumors upon HDAC7 silencing, exhibiting small, pale nodules with prominent hemorrhage, we verified if defects in angiogenesis may explain the lack of tumor growth. Indeed, lectin‐based staining of the tumor vasculature revealed a significantly decreased vessel density. We demonstrate that several angiogenesis relevant genes (e.g. angiopoietin 1, angiogenin, interleukin 8) were significantly down‐regulated at transcriptional level.The present study highlights a STAT3 dependent pathway for suppressing the growth PTEN−/− GBM with potential for clinical translation.This work is sponsored by FNRS, Belgium.
Milk 3′ sialyllactose does not increase brain sialic acid concentration in mice
Authors: Autran Chloe , Szyszka Alexandra , Bode Lars 
Published: June 2021

Sialic acid (Sia), a carboxylated 9‐carbon monosaccharide, is a crucial constituent of brain glycoproteins and glycolipids associated with brain development and enhanced cognitive function. Brain Sia concentrations rapidly increase after birth and are significantly higher in breast‐fed than in formula‐fed infants. Compared to formula, human breast milk contains a high amount of sialylated oligosaccharides; yet their direct role in brain Sia accrual is unknown. Our objective was to determine whether sialylated milk oligosaccharides contribute to brain Sia accumulation in mice between birth and weaning. To overcome problems with artificial feeding in newborn pups, we used a cross‐foster approach with pups reared on dams normal or genetically deficient in 3′sialyllactose (3′SL), one of the major sialylated milk oligosaccharides. Urine 3′SL and brain Sia were derivatized and measured by HPLC. While pups reared on dams with normal milk 3′SL had significantly higher urine 3′SL levels than pups fed on 3′SL deficient milk (460 vs. 40 uM at day 7, P<0.001), there was no significant difference in brain Sia one week (6.0±1.1 vs. 6.0±1.2 pmol/ug protein) and three weeks after birth (19.0±9.7 vs. 15.0±4.9 pmol/ug protein). The data indicate that 3′SL, one of the major sialylated milk oligosaccharides, does not contribute to postnatal brain Sia accumulation – at least in mice.Grant Funding Source: NIH
Integrating LGBT Issues into “Clinical Problem Solving (CPS)”, a First Year Medical School PBL Course
Authors: Rogers Ashley N , Rice Ami E , Packer C Subah 
Published: June 2021

In CPS, students learn to work in small groups as they practice methodology necessary to case resolution. In addition to using basic science concepts, CPS students must consider ethical, legal, moral, social and communication issues. Recently, governing bodies (AAMC, LCME) promoted faculty awareness that medical students may be insensitive to LGBT issues. Accordingly, the current project objectives were: 1. assess in‐coming student knowledge of LGBT issues, 2. develop and implement a case in which the patient is a LGBT community member, 3. increase student self‐awareness of their understanding and attitudes of LGBT issues. Self‐awareness and at‐hand knowledge surveys were administered to students before they embarked on resolving the case. The average score on the LGBT basic knowledge questionnaire was 55.5%. Clearly there is a gap in knowledge of LGBT issues for in‐coming students. Project success is being evaluated through after student satisfaction surveys, faculty experience in implementing the new curriculum, and student learning outcomes.(Supported by an IUPUI LGBT Faculty & Staff Council Grant)
Regional variations in cartilage thickness of the radial head; implications for prosthesis design
Authors: Yeung Celine , Deluce Simon , Willing Ryan , Johnson Marjorie , King Graham J.W. , Athwal George S. 
Published: June 2021

BackgroundKnowledge of potential variations in cartilage thickness is important in designing radial head implants.ObjectiveTo characterize the regional variations in radial head cartilage thickness.MethodsTwenty‐seven cadaveric radii were dissected and scanned with computed tomography (CT) in neutral position. Three dimensional models were generated from CT scans and processed through a computer program by two independent observers. Cartilage thickness values were obtained at 41 predetermined landmarks located around the articular dish and side of the radial head.ResultsAt the side of the radial head, cartilage in the posteromedial quadrant (0° to 90°) was significantly thicker than all other quadrants (p < 0.05). Cartilage thickness measurements within the articular dish were similar at a mean of 0.98 ± 0.13mm, but increased towards the rim of the radial head (p < 0.001). Regional variations of cartilage thickness within the rim circumference were also detected, with the thickest region located anteriorly (270°, p < 0.001) and thinnest region laterally (180°, p < 0.05).ConclusionsRegional variations in cartilage thickness exist around the side of the radial head and within the articular dish. Such differences offer insight into the biomechanics of the elbow joint and may also affect overall radius length and dish depth, which may be clinically important for implant design.Funding:DepartmentalGrant Funding Source: Departmental
Foraminal stenosis and anomalous venous drainage in complex craniosynostosis
Authors: Mussell Jason C , St. Hilaire Hugo , Sanchez Ruston 
Published: June 2021

Craniosynostosis, the premature fusion of one or more cranial sutures, is a relatively common congenital defect, affecting ~1/2,500 live births. Craniosynostosis alters skull and brain development and may lead to facial deformities, raised intracranial pressure, cranial venous hypertension, airway obstruction, and exorbitism. Complex craniosynostosis, defined as the fusion of two or more sutures, occurs in 5 to 15% of all cases and is termed syndromic when associated with a pattern of extracranial deformations, typically involving a fibroblast growth factor receptor (FGFR) gene mutation.Craniosynostosis requires operative intervention to remodel the skull and allow adequate brain development. It is vital during preoperative evaluation of children with multiple craniosynostosis to investigate the possibility of anomalous basicranial venous drainage. The detection of abnormally enlarged emissaries serving as major sources of intracranial venous drainage may counter indicate intervention, and it has been reported that disruption of such venous channels during surgery can lead to a fatal rise in intracranial pressure.While venous anomalies are common in children with complex craniosynostosis, there are currently only a limited number of case reports that detail the specific routes of posterior dural sinus drainage in this population
Development of a viewing system for a whole tissue from multiple tissue blocks
Authors: Hashimoto Noriaki , Tanaka Toru , Snuderl Matija , Yagi Yukako 
Published: June 2021

Viewing whole tissue allows us to recognize spatial perspective, which cannot be seen from a single glass slide and could leads to discovery of novel morphologic and growth patterns of human tumors. However, we cannot observe the whole histological image with large tissue organ. Whole Slide Imaging (WSI) can digitize the entire tissue on a glass slide. If we can use the digital images of multiple tissue blocks, it enables to view whole organ. In addition, this method can keep general versatility as conventional WSI scanners are used. Therefore, we propose a system to view a whole large tissue from multiple tissue blocks.First, in this system, whole organ is sectioned into blocks and H&E slides are scanned by WSI scanners. Then, low‐resolution images are used to export location information (Fig. 1). In the viewer, higher magnification images of the region specified by a user are displayed on a monitor using exported information (Fig. 2).To show the validity of the proposed system, we developed the viewer and confirmed that a whole organ can be observed efficiently. This system can makes it easier to compare to other modality images such as gross pictures of a whole organ. Furthermore, if we expand this system to sections in depth, it would allow us to compare with MRI or other medical imaging techniques. This system would be helpful for clinicopathological‐imaging correlations and better understanding of pathological processes.
Ontogeny of sphenoidal, occipital, and temporal bone morphology in humans
Authors: Dalal Deepal , Smith Heather F. 
Published: June 2021

Previous research suggests that the basicranium ossifies early in ontogeny and reflects phylogeny, but the process by which the various basicranial subregions develop is currently unknown. The 3D basicranial landmarks on the sphenoid, temporal, and occipital of 266 subadults and adults in seven populations were collected and compared. The seven populations were found to be significantly different in basicranial morphology in specimens over 5 years old, and those differences significantly reflected their published molecular distances. The differences in morphology significantly reflected genetic distances in childhood, but not adulthood. The occipital bone showed significant differences in morphology in children, and significantly reflected genetic distances; however, this pattern did not continue into adulthood. Temporal bone age categories reflected genetic distances if the Egyptian population was excluded. In sphenoid, the differences among groups were uncorrelated with genetic distances. These results indicate that the morphology of the entire basicranium reflects molecular distances and that this pattern becomes established early in ontogeny. However, the three basicranial regions develop along differing ontogenetic trajectories. Greater landmark density is preferable when using basicranial morphology to reconstruct population history.Grant Funding Source: Midwestern University
Translating Carpal Biomechanics to Triangular Fibrocartilage Complex Injury: Significance of Ulnar Variance in Predicting TFCC Lesions
Authors: Baral Sumit , Adar Tony , Classie Justin Anthony , Marquez Samuel 
Published: June 2021

Ulnar variance (UV) describes the cranio‐caudal position of the distal ulna in relation to the distal radius at the wrist. Neutral ulnar variance (ulna and radius articulating at the carpus at exactly the same level) transmits 20% of the compressive load across the wrist to the distal ulna and 80% to the distal radius. A +2.5mm positive UV has been shown to increase the ulnocarpal load to 40%. The triangular fibrocartilage complex (TFCC) acts as a cushion for the ulnar carpus and transmits axial loads from the wrist to the ulna in a longitudinal direction across the ulnar column of the wrist. Consequently, a positive ulnar variance implicates a greater risk of TFCC injury. This study sought to calculate the prevalence of traumatic TFCC injury in those with a positive UV versus those with a negative UV. 20 cadaveric wrists aged 50 – 90 were assessed for TFCC damage via gross examination and classified according to Palmer's schema. A plain film PA radiograph of each wrist was then taken to measure the degree of UV. Results showed that all wrists had degenerative Class II lesions of the TFCC, while traumatic Class I lesions of the TFCC were found in 69% of wrists with positive UV as compared to 0% of wrists with negative UV (p<0.05). Our investigation prompts further research exploring a “dose‐response” relationship between UV and TFCC damage as well as between the degree of TFCC damage and clinical symptoms or diminished quality of life.Grant Funding Source: SUNY Downstate College of Medicine Alumni Association
Development of an effective in vitro epithelial cell infection model to study Edwardsiella tarda infections
Authors: Tenkink Byron Joel , Siame Bupe Anthony , Leung Ka Yin , Guttman Julian Andrew 
Published: June 2021

Edwardsiella tarda is an enteric pathogen that infects both warm‐water fish and humans. While it is known that E. tarda utilizes syringe‐like secretion systems to deliver bacterially‐derived pathogenic proteins into macrophages during infection, little is known about E. tarda pathogenesis in epithelial cells. To enable the investigation of E. tarda infection mechanisms, we hypothesized that an effective and reliable E. tarda infection model could be developed by utilizing epithelial cells that originate from organs that are targeted during in vivo infections. To develop this in vitro model, isolates of E. tarda from various locations around the world were used to infect 4 different epithelial cell lines derived from fish, using various bacterial loads and durations of the infections. We found that E. tarda infected 10–15% of BF‐2 (Bluegill fry caudal trunk cells) when used at a multiplicity of infection of 10 for three hours at 30°C. The E. tarda infection rate was measured by counting infected cells per slide after fixation and visualization by fluorescence microscopy. Our results constitute the most effective E. tarda infection model ever developed and provides us the foundation to elucidate the strategies E. tarda utilize to cause disease.Grant Funding Source: Natural Sciences and Engineering Research Council
Francisella tularensis does not alter ubiquitylated or SUMOylated proteins profiles during epithelial cell infections
Authors: Chua Michael , Guttman Julian A. 
Published: June 2021

Francisella tularensis are intracellular bacteria that cause tularaemia, an infection that can lead to 60% mortality rates if left untreated. Although these microbes infect both macrophages and epithelial cells, the epithelial cell infections are known to be crucial for the disease process. A variety of bacteria alter the normal processes of post‐translational protein modifications that occur in healthy epithelial cells. These include the processes of ubiquitylation and SUMOylation. To begin to determine the host cell alterations that occur during Francisella‐based epithelial cell infections, we hypothesized that ubiquitylation and/or SUMOylation alterations to host proteins would be altered during the infections. To test this hypothesis, we analyzed protein immunoblots of two cell lines, HeLa and COS‐7, that we infected with Francisella for 24 hours. Comparison of uninfected and infected samples showed no significant differences in ubiquitin, SUMO1 or SUMO2/3 modifications to any host cell proteins. Through our study, we concluded that Francisella does not alter the host ubiquitin or SUMO post‐translational protein modifications as part of their disease mechanism.This study was funded by CIHR.Grant Funding Source: Canadian Institutes of Health Research
Environmental Estrogens Decrease Agrin‐Induced Acetylcholine Receptor Clustering
Authors: Renteria Sarah M , Grow Wade A 
Published: June 2021

In addition to reproductive tissues, estrogen hormones target skeletal muscle. Studies have linked the decline of estrogen during menopause to sarcopenia, a loss in muscle mass and strength with aging. Steroid hormones including estrogens alter gene transcription and affect cell function. Human exposure to environmental estrogens that can mimic endogenous estrogens is increasing. Our lab uses the C2C12 cell culture model to investigate skeletal muscle development, specifically the events of myotube formation and acetylcholine receptor (AChR) clustering. C2C12 myoblasts proliferate and fuse into myotubes in cell culture. Clusters of AChRs form spontaneously on myotubes with motor neuron derived agrin increasing the frequency of AChR clustering. Our objective was to assess if environmental estrogens affect agrin‐induced AChR clustering. We tested four environmental estrogens that represent a range of distributions and toxicities: DDT, methoxychlor, estrone, and 17â‐estradiol. Our results demonstrate that individually and in combination environmental estrogens can decrease agrin‐induced AChR clustering. We conclude that environmental estrogens may interfere with skeletal muscle development.Grant Funding Source: Sarah M. Renteria was supported by the Midwestern University Biomedical Sciences Program. Wade A. Grow was supported by Midwestern University intramural funds.
A Unique Branching Pattern of Celiac Trunk. Its Clinical and Embryological significance
Authors: Valentin Natalia , Veras Wilson R , Duarte Jhonathan , Vilaró José 
Published: June 2021

The celiac trunk is the first ventral branch of the abdominal aorta and is the major blood supply to the supracolic abdominal compartment. Usually, three branches arise from the celiac trunk to supply this region, the splenic, the common hepatic and the left gastric arteries. During a routine dissection in the anatomy laboratory an extraordinary anatomical variation of the celiac trunk and its branches is found. The present case correspond of a celiac trunk, which gave off six branches. It gave off three classical branches, that is left gastric, splenic and common hepatic arteries. Beside these three branches, the right and left inferior phrenic arteries, and the superior posterior pancreaticoduodenal artery arose from the celiac axis. These anatomical variations were accompanied by a right gastric artery arising from the grastroduodenal artery instead of the common hepatic artery as describe in textbooks.During normal development, both dorsal aortas give rise to many ventral segmental (omphalomesenteric) arteries. The ventral segmental arteries regress shortly after fusion of dorsal aortas. The dorsal aorta gives off segmental branches to the digestive tube (ventral splanchnic arteries), the mesonepheric ridge (lateral splanchnic arteries), and intersegmental branches to the body wall (somatic arteries). Anatomical variations of the coeliac trunk are due to developmental changes in the ventral segmental arteries. These ventral segmental arteries supply the yolk sac, allantois and chorion. Three ventral segmental arteries remain as coeliac trunk, superior mesenteric artery and inferior mesenteric artery. Anatomical variations in the branching pattern of the celiac trunk are of considerable importance in liver transplants, laparoscopic surgery, invasive radiological interventions and penetrating injuries to the abdomen. Knowledge of variation found in the present case is very useful to kept in mind to avoid serious vascular complications.
Overexpression of MnSOD provides protection against NRTI‐induced endothelial dysfunction in a drug‐dependent manner
Authors: Glover Mitzi , Hebert Valeria , Xue Stephen , Thibeaux Taylor , Zavecz James H. , Dugas Tammy R 
Published: June 2021

Nucleoside reverse transcriptase inhibitors (NRTI) currently used in HIV therapy have been linked to cardiovascular toxicity. Our prior studies have demonstrated alterations in mitochondrial function and upregulation of mitophagy in endothelial cells after acute treatment, with parameters returning to normal by 24 h. Treatment with coenzyme Q10 prevented this toxicity, suggesting a role for antioxidant supplementation. The current study utilized mice overexpressing MnSOD to determine the protective effects of this mitochondrial antioxidant enzyme. Measurements of plasma vasodilators, vasoconstrictors, and markers of oxidative stress, along with vessel reactivity experiments were used to assess protective effects. Results indicate that although wild‐type mice treated with either AZT or 3TC exhibited reduced vessel reactivity, overexpression of MnSOD only attenuated 3TC‐induced effects. Plasma markers of vascular function either correlated with this finding, or demonstrated MnSOD protection for both NRTI. These findings suggest differential mechanisms of toxicity of the 2 drugs. Supported by R01‐HL08242–0251.Grant Funding Source: R01‐HL08242–0251
Age‐Dependent Myocardial Sheet Dysfunction from 3 to 16 months in Duchenne Muscular Dystrophy Mice (mdx) Defined by Diffusion Tensor Magnetic Resonance Imaging (DTI)
Authors: Cheng Ya‐Jian , Chen Junjie , Caruthers Shelton D. , Wickline Samuel A. 
Published: June 2021

INTROCardiomyocytes are organized in laminar structures (aka, sheets) that contribute to wall thickening/thinning. Diffusion tensor MRI (DTI) measures the sheet reorientation function in intact hearts. We have reported that hearts of 16‐mo old mdx mice exhibit abnormal Ca transients & Ca‐dependent sheet dysfunction at the base but not apex. Because Ca mishandling in isolated mdx cardiomyocytes is age dependent, we hypothesized that sheet dysfunction in intact mdx hearts may also be age dependent.METHODSExcised hearts from 3 & 16 mo old mdx and wildtype were prepared for Langendorff perfusion, and sequentially arrested in diastole then systole for DTI (Varian 11.7 T). The diastolic arrest was achieved with either normal [Ca] (1.2 mM, noted as NC) or low [Ca] (0.078 mM, noted as LC) cardioplegic solution to test the Ca dependency. The systolic arrest was achieved with barium.RESULTSSystolic |β| (defined below) was similar between WT and mdx, whereas diastolic |β| in mdx‐NC was lower for age matched WT‐NC at the base but not apex, indicating a regional failure to fully relax. Low [Ca] (mdx‐LC) perfusion restores the diastolic |β| to normal values at both ages. The Δ|β| (i.e., |β| of each group ‐ |β| of age matched WT‐NC) is 50% larger in 16 mo than for 3 mo old mice, indicating that Ca dependent sheet dysfunction is age dependent and regionally manifest despite the ubiquitous dystrophin deficiency.