bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down‐regulation of desmoglein‐2 in colonic epithelial cells suppresses proliferation and reduces tumor growth via a desmocollin‐2‐dependent mechanism
Authors: Kolegraff Keli , Kamekura Ryuta , Hilgarth Roland , Nava Porfirio , Parkos Charles , Nusrat Asma 
Published: June 2021

Expression of the desmosomal cadherins desmoglein‐2 (Dsg2) and desmocollin‐2 (Dsc2) is altered in epithelial cancers, and we have shown that loss of Dsc2 in colonic epithelial cell lines enhances proliferation and tumor formation, thus providing evidence of a tumor suppressor function for Dsc2. To determine if loss of Dsg2 has similar effects, we used shRNA to down‐regulate Dsg2 expression in colonic epithelial cell lines. Interestingly, loss of Dsg2 decreased cell proliferation and inhibited xenograft tumor formation in mice. Furthermore, down‐regulation of Dsg2 in a Dsc2‐negative epithelial cell line had no effect on proliferation or tumor growth, indicating that Dsc2 may promote growth suppression following loss of Dsg2. To examine whether Dsc2 contributes to growth suppression in Dsg2‐deficient cells, we assessed the effect of Dsg2 loss on Dsc2 expression. Our results show that Dsg2‐deficient cells have increased Dsc2 protein levels compared to controls, suggesting that compensatory Dsc2 up‐regulation may mediate growth suppression. Consistent with this notion, siRNA knockdown of Dsc2 restored proliferation in Dsg2‐deficient colonic epithelial cell lines. Taken together, our data demonstrate that, unlike Dsc2, loss of Dsg2 reduces cell growth and inhibits tumor formation in vivo. Thus, anti‐Dsg2‐targeted therapies may be useful for inhibiting growth of tumors expressing both Dsc2 and Dsg2.This work was supported by CCFA Fellowship and AGA Research Scholar Awards (PN) and NIH grants DK61379 (CP), DK55679 and DK59888 (AN).
Mechanisms of transcriptional regulation in the p53 network
Authors: Espinosa Joaquin 
Published: June 2021

The tumor suppressor p53 is transcription factor that orchestrates diverse responses to cellular stress via regulation of target genes involved in cell cycle arrest, senescence, autophagy and apoptosis. The p53 transcriptional program varies greatly in a cell type‐ and stimulus‐specific manner, but the mechanisms generating this regulatory diversity are poorly defined.We have recently performed several genomics studies that revealed novel mechanisms conferring regulatory diversity to the p53 network. These experiments include shRNA screens for gene‐specific p53 cofactors and identification of novel p53‐regulated RNAs via global run‐on deep sequencing. We will present the results of these experiments and discuss new strategies to manipulate the p53 response for therapeutic purposes.
Replication Forks Restarted by Homologous Recombination Display a High Frequency of Errors at Inverted Repeats
Authors: Carr Antony Michael , Murray Johanne Milne 
Published: June 2021

Replication restart by HR at the sites of a collapsed replication fork promotes cell survival, but at the expense of increasing the potential for genome rearrangement. We have previously shown that, when a replication fork collapses within a small (~900bp) inverted repeat, homologous recombination is required to restart the collapsed fork. In the majority of cases, the restart event is effective and promotes cell survival. However, the presence of a nearby repeat (homologous sequence) results in an inappropriate template exchange in a few percent of events, producing dicentric and acentric giant palindromic chromosomes.We also studied the consequence of restarted replication fork progression through a small palindrome. We observed that restarted forks are prone to generate errors when they replicate through small inverted repeats. Thus, two distinct mechanisms can result in gross chromosomal rearrangements: 1. When replication forks collapse within a repeated sequence, incorrect homologous recombination can occur that results in repeat fusion. 2. The restarted replication fork is itself error prone, and is particularly sensitive to making errors when replicating closely spaced inverted repeats.
Effects of prebiotic inclusion and chain length on intestinal barrier, histomorphology, and mRNA abundance in obese C57BL/6J mice
Authors: Cephas Kimberly D. , Mangian Heather F. , Tappenden Kelly A. , Swanson Kelly S. 
Published: June 2021

Obesity is linked with increased intestinal permeability, which may contribute to low grade inflammation. The objective of this study was to test the effects of prebiotics on intestinal permeability, morphology and gene expression in an obese mouse model. Obese 18‐week old, C57 mice (n=6) were randomized to high‐fat diets containing 5% cellulose, 10% cellulose, 10% scFOS or 10% inulin and fed for 28 d. Distal ileum, cecum and colon samples were collected for Ussing chamber, histomorphology, and RT‐qPCR analyses. Cecal epithelial resistance was greater (p<0.05) in mice fed inulin vs. mice fed cellulose or scFOS. Distal colon epithelial resistance tended to increase (p=0.08) in mice fed scFOS vs. mice fed cellulose or inulin. Ileal and cecal crypt depth was greater (p<0.05) in mice fed scFOS or inulin vs. mice fed cellulose. Ileal MUC2 expression was greater (p<0.05) in mice fed 10% cellulose vs. mice fed 5% cellulose, inulin or scFOS. Distal colon AMPK and ZO‐1 expression was greater (p<0.05) in mice fed scFOS vs. mice fed cellulose or inulin. Ileal and cecal occludin expression was lower (p<0.05) in mice fed inulin or scFOS vs. mice fed 5% cellulose. Colon occludin expression was lower (p<0.05) in mice fed inulin or scFOS vs. mice fed 10% cellulose. These data suggest prebiotics improve intestinal permeability in the obese and involve tight junction proteins, but the effects vary regionally depending on prebiotic properties.Grant Funding Source: Internal funding
Determinants of breastfeeding modes in the prevention of mother‐to‐child HIV transmission (PMTCT) Kesho Bora study
Authors: Bork Kirsten , Cames Cecile , Cournil Amandine 
Published: June 2021

Breastfeeding (BF) determinants were investigated in 1028 HIV‐infected African women participating in a 5 site PMTCT study, which provided antiretroviral prevention during pregnancy and postpartum (PP) (a triple antiretroviral prophylaxis up to 6 mo PP or the standard ZDV‐based regimen until 7 d PP). Women were counselled to either breastfeed exclusively up to 6 mo or formula‐feed exclusively for 6 mo. Some 76% ever breastfed, among whom 73% still breastfed at 3 mo (40% exclusively and 24% predominantly). In multiple logistic regression analysis, significant determinants of formula‐feeding were study site, CD4 <200mm3, secondary schooling and emergency C‐section. BF at 3 mo (if breastfed at 1 mo) was independently associated with study site (P<0.001) and neonatal morbidity reported by the mother (OR: 0.60 (0.37–0.985)) but not with report of maternal morbidity (fever or fatigue) during the first mo PP (0.57 (0.31–1.02)), CD4 cell count or schooling (P>0.20 for both). By 3 mo, boys tended to be less breastfed (0.70 (0.46–1.05)) and were less often exclusively breastfed than girls (0.52 (0.34–0.78)). This study suggests that exclusive breastfeeding is shorter among boys of HIV‐positive African women. The importance of neonatal morbidity for breastfeeding duration requires further investigation.Funding: ANRS, DFID, EDCTP, Trasher Research Fund, GlaxoSmithKline Fund, CDC, NIH, WHO
Television viewing and intake of added sugars related to increased central adiposity in prepubertal children
Authors: Khan Naiman A , Raine Lauren B , Drollette Eric , Scudder Mark , Pontifex Matthew , Castelli Darla M , Hillman Charles H , Donovan Sharon M , Evans Ellen M 
Published: June 2021

Central adiposity is related to insulin resistance and may be the most clinically relevant body fat in children as is the case in adults. This study aimed to determine relationships between child's television viewing (TV), aerobic fitness, diet and central adiposity in 172 prepubertal children (8–9 years). Parents reported child's weekday and weekend TV viewing. Maximal oxygen consumption (VO2max) and one 24‐hour recall assessed fitness and diet, respectively. Dual energy X‐ray absorptiometry was used to measure percent fat mass (%Fat) and central adiposity (FM‐abd). Waist circumference to height ratio (WHtR) was also measured. Aerobic fitness was not related to TV, however, it was negatively related to %FM (r=−0.49, p < 0.01) and FM‐abd (r=−0.41, p < 0.01). Weekday and weekend TV was positively related to FM‐abd (r=0.18, p=0.02 and r=0.20, p=0.01). After adjusting for VO2max and total diet energy density (kcals/g), added sugars (g) positively related to FM‐abd (r=0.18, p=0.03). To further assess central adiposity, children were classified as normal (n=129) or obese (n=43) based on the 0.5 cut off for WHtR. Obese children had significantly higher weekday TV (p=0.03) and consumed higher amounts of added sugars (p=0.02). Our findings suggest that central adiposity is related to increased intake of added sugars independent of aerobic fitness and energy density in prepubertal children. (Funding source: NIH HD055352)Grant Funding Source: NIH HD055352
The gut microbiome of kittens is affected by dietary protein: carbohydrate ratio and correlated with blood metabolite and hormone concentrations
Authors: Hooda Seema , Boler Brittany M Vester , Dowd Scot E , Swanson Kelly S 
Published: June 2021

This study was conducted to test the effects of dietary protein: carbohydrate ratio on the composition of the gut microbiota using 454 pyrosequencing and identify associations with blood metabolites of growing kittens. Male domestic shorthair kittens were raised by mothers fed moderate‐protein, moderate‐carbohydrate (MPMC; n=7) or high‐protein, low‐carbohydrate (HPLC; n=7) diets. Fasted blood samples were collected and analyzed for blood metabolites and hormones. Pyrosequencing resulted in a total of 384,588 sequences, with an average of 9,374 sequences per sample. A dual hierarchical clustering dendogram of the most abundant bacterial genera indicated distinct clustering of samples based on protein:carbohydrate ratio. The principal component analysis of fecal bacterial families, blood metabolites, and hormones resulted in 4 distinct clusters. One cluster included blood triglycerides and fecal Clostridiaceae, Eubacteriaceae, Ruminococcaceae, Fusobacteriaceae, and Lachnospiraceae. A second cluster consisted of blood ghrelin and fecal Coriobacteriaceae, Bifidobacteriaceae, and Veillonellaceae. A third cluster consisted of blood glucose, cholesterol, and leptin and fecal Lactobacillaceae. The strong correlations between blood hormones and metabolites and well‐known probiotic bacterial families indicate potential significance as it pertains to satiety and host metabolism.Grant Funding Source : United States Department of Agriculture‐Cooperative State Research, Education and Extension Service (project ILLU‐538‐396)
School childrenˈs consumption of fat‐free, low added sugar flavored milk
Authors: Yon Bethany A , Johnson Rachel K 
Published: June 2021

USDA's proposed rule for school meals requires flavored milk (FM) to be fat‐free. The IOM report on competitive foods limits added sugar in FM to 10 gm/8 oz. Milk is an important source of shortfall nutrients. As most elementary children choose FM, it is important to know how well children consume FM meeting these standards. Plate waste studies were conducted in May 2010 and 2011 in 2 southern schools (grades 3–5) using FM meeting both standards. In 2010, FM was USDA compliant (fat‐free). In 2011, added sugar was lowered to meet IOM guidance. FM consumption was highly skewed, thus categorized as a binary variable (0–7oz, >7oz). Excluding unopened cartons (27% in 2010, 20% in 2011), 37% of children in school A (Urban; 97% Hispanic; 88% eligible for free/reduced meals) consumed >7 oz of milk in 2010 compared to 44% in 2011 (p=0.19). School B (Rural; 52% White, 41% Hispanic; 61% eligible for free/reduced meals) changed from plastic bottles to paper cartons in 2011. The number of unopened FM containers increased in 2011 (3% to 16%, p=0.001). Excluding unopened containers, 68% of children consumed >7 oz of milk in 2010 compared to 46% in 2011 (p=0.03). Consistent with earlier research, children drink more milk from plastic bottles. When packaging was consistent, children consumed similar amounts of fat‐free FMs with higher vs lower added sugar.Grant Funding Source: USDA Hatch and the Dairy Research Institute
Pyruvate protects the HT22 neuronal cells treated with rtPA against hypoxia‐reoxygenation damage
Authors: Ryou Myoung-Gwi , Liu Ran , Mallet Robert T , Yang Shao-Hua 
Published: June 2021

Recombinant tissue plasminogen activator (rtPA) is the only FDA approved treatment for ischemic stroke, but delayed rtPA treatment may be neurotoxic. Pyruvate has proven neuroprotective in animal models of stroke. We examined pyruvate + rtPA cotreatment of neuronal cells subjected to an in vitro stroke model.MethodsHT22 cells were exposed to 2 or 6 h hypoxia (0.5% O2) + glucose deprivation (OGD), followed by 24 h reoxygenation. Pyruvate (8 mM) and/or rtPA (10 μg/ml) were applied upon reoxygenation. Cell viability was assessed with Calcein AM. DCF‐DA and mitosox staining detected reactive oxygen species (ROS). Matrix metalloproteinase (MMP) activities were measured by gelzymography; MMP, tissue inhibitor of metalloproteinase 2, HIF‐1α, EPO and actin contents were determined by immunoblot.ResultsOGD lowered cell viability by 50% vs. normoxic control (P <0.05). Although rtPA treatment did not increase post‐OGD cell death, it intensified ROS production and activated MMP. Pyruvate‐induced cytoprotection was not compromised by rtPA cotreatment, and pyruvate dampened rtPA‐induced ROS and MMP. Delayed rtPA treatment intensified cell death 2 h after OGD, but pyruvate salvaged 50% of these cells.ConclusionPyruvate attenuates rtPA‐induced MMP activation and ROS formation, thereby protecting reoxygenated HT22 cells. Pyruvate could be a useful cotreatment with rtPA for ischemic stroke. NIH support: R01NS054687, R01NS054651, R01NS076975, T32AG020494
TRANSCRIPTIONAL REGULATION OF THE METHIONINE ADENOSYLTRANSFERASE 2A GENE DURING HEPATIC STELLATE CELL QUIESCENCE AND ACTIVATION
Authors: Ramani Komal , Tomasi Maria Lauda 
Published: June 2021

ObjectiveMethionine adenosyltransferases (MAT) catalyze the formation of the methyl donor, S‐adenosylmethionine (SAMe). The MAT2A gene encoding the catalytic subunit α2, is induced in de‐differentiated liver particularly in activated hepatic stellate cells (HSCs). MAT2A silencing reduces HSC activation. Our aim is to understand how MAT2A is regulated during HSC quiescence and activation.MethodsRosiglitazone (RSG)‐treated HSC cells or bile ducted ligation (BDL)‐activated primary rat HSCs were assayed for MAT2A expression, promoter activity and transcription factor binding.ResultsWe identified peroxisome proliferator‐activated receptor (PPAR) response elements (PPREs) in the MAT2A promoter. The PPARγ agonist, RSG, promoted quiescence in HSCs, decreased the expression and promoter activity of MAT2A and enhanced PPARγ binding to MAT2A PPREs. BDL‐mediated liver injury lowered PPARγ interaction with MAT2A PPREs in activated HSCs. Silencing PPARγ increased MAT2A transcription and over‐expressing it had the opposite effect showing that PPARγ negatively controls this gene. Mutation analysis showed that PPREs are required for PPARγ to repress MAT2A in normal HSCs and the loss of PPARγ during HSC activation allows positive regulators like PPARβ to bind to the same PPREs and activate MAT2A transcription.ConclusionPPARγ is a negative regulator of MAT2A in normal HSCs. A switch from quiescence to activation abolishes this control and allows PPARβ to up‐regulate MAT2A transcription.Research support: NIH grants 5K99AA017774‐02 (Komal Ramani), F32AA201502 (Maria Lauda Tomasi).
Endoscopic investigation of the palatopharyngeal muscular anatomy of the great apes: Anatomic models for the study of obstructive sleep apnea etiology
Authors: adar tony , Papaxanthos Michael , Lawson William , Pagano Anthony S , Petit Thierry 
Published: June 2021

Laryngeal descent and external basicranial flexion create an upper respiratory tract ideal for spoken language, but predispose humans to obstructive sleep apnea (OSA). OSA may be related to soft palate flaccidity and length, as well as a failure of its paramedian resorption, causing airway collapse. To this end, non‐human hominoids (great apes) were used as anatomic models for a structural configuration divergent from humans. There exist no documented cases of OSA among great apes, likely a result of their upper respiratory tract anatomy. Endoscopic examination was performed on a sample of adult Pan troglodytes (n=1), Pongo pygmaeus (n=1), Gorilla gorilla (n=1), neonate Gorilla gorilla (n=1) and Hylobates sp. (n=1) from La Palmyre Zoo in Les Mathes, France. Great apes exhibited marked soft palate length, which expanded posteriorly in a nearly horizontal orientation—as opposed to the comparatively vertical orientation of humans—to cover a relatively deep nasopharynx. Uvular projection from the palatopharyngeal arch was short compared to humans. The neonates, however, displayed more shallow nasopharynges and vertical soft palate and palatopharyngeal arch orientations, similar to humans. Future studies should investigate whether OSA related to airway constriction at the fauces is prevented in great apes by a greater nasopharyngeal depth and reduced palatopharyngeal and surrounding soft tissue flaccidity.Grant Funding Source : alumni association
Modulation of secretion in Drosophila by amino‐acid starvation
Authors: Rabouille Catherine 
Published: June 2021

Secretion is mediated by the secretory pathway that have a basic functional organisation very similar in Drosophila as in mammalian cells.Here, I will discuss evidence showing that secretion is be modulated by physiological conditions. Using Drosophila S2 cells, we have shown that amino‐acid starvation stimulates a pathway that inhibits secretion. This pathway relies on the atypical MAP Kinase ERK7 that we found is stabilised by amino acid starvation, leading in turn to the modification of Sec16, a key protein required for the functional organisation of the ER exit sites that are critical for secretion. Once modified, Sec16 no longer associates to ER membrane, ER exit site biogenesis is inhibited, and so is secretion as a whole. Furthermore, this pathway is independent of the TOR complex 1.These results indicate that secretion inhibition under amino‐acid starvation is an active mechanism requiring ERK7, not only a passive response to the absence of growth factors. Furthermore, they show that in the absence of nutrient, cytoplasm growth is inhibited via TORC1 inhibition whereas plasma membrane growth via secretion is inhibited independently.
The novel ‘syncretion’ approach to learning gross anatomy with clay models: Is it a plausible alternative for learning the muscles in the anterior forearm?
Authors: Kim Hanna , Johnson Marjorie , Wilson Timothy 
Published: June 2021

Traditionally, dissection has been the method of choice for learning gross anatomy at the undergraduate level. However, rising problems in medical curriculums, such as reduced hours dedicated to anatomy education, has yielded a plethora of research in alternatives. A novel approach to learning gross anatomy, called ‘syncretion,’ has yet to be proven efficacious. The purpose of the current study is to evaluate student performance on a “bell‐ringer” examination following exposure to a syncretic or dissection model of the anterior forearm. Students will be randomly assigned into three test groups: the syncretion group will reconstruct, or build up, the anterior forearm using pre‐formed clay representations of the 8 muscles; the dissection group will “dissect” through a fully‐assembled clay model of the anterior forearm with a scalpel to visualize deeper muscles; and, the control group will learn the 8 muscles without a model. All groups will complete pre‐ and post‐tests to evaluate spatial identification, spatial reasoning and comprehension of function of musculature and osteology. It is hypothesized that the change in scores from pre‐test to post‐test in the syncretion group will mirror those exhibited by the dissection group. Following this, it is also thought that the change in scores in the two treatment groups will be greater than that of the control group, due to the added benefit of a tactile model.Grant Funding Source: Western Graduate Scholarship
A digital atlas for ultrasound guided nerve blocks of the upper limb
Authors: Rawski Ryan James , Brookes Jon , Johnson Marjorie , Ganapathy Sugantha 
Published: June 2021

Ultrasound guidance (UG) ameliorates the dependency on surface landmarks to perform nerve blocks by providing real‐time imaging of subcutaneous tissues, allowing for purposeful needle movements to accurately deliver anesthetic. UG has been associated with improvements in the quality of sensory blocks, the onset time, and the success rate. The objective of this project is to create a digital atlas (DA) to aid trainees with their interpretation of ultrasound (U) anatomy, so that benefits of UG are actualized. Surface anatomy, serial cadaver dissections, U, and Visible Human Project images have been integrated into the DA to illustrate relationships between surface landmarks, physical anatomical relationships, and the planar U image. Each block and its indications are described in text and subsequently demonstrated in narrated videos. The DA includes an introductory module on mechanics and operation of the U device. Feedback solicited at monthly anesthesiology resident training will guide the design of the DA as content for trunk and lower limb blocks is developed. We anticipate that having online access to the DA will allow residents to acquire the requisite foundation of knowledge to interpret U anatomy. This would allow training programs to efficaciously use limited lab time to reinforce key concepts and develop students procedural skills (needle/ultrasound probe manipulation) through kinesthetic learning.Grant Funding Source: Ontario Graduate Scholarship
Restoration and Preservation of Pathological Surgical Specimens
Authors: Zekhtser Mitchell , Tugbenyoh Mawuli , Nusse Gloria 
Published: June 2021

San Francisco State University received a historically significant pathology specimen collection from Stanford University in the 1970s. Originally, the specimens had been preserved in formaldehyde and water, but as the years went by the formaldehyde degenerated, causing decomposition of the tissues. As a result, the anatomy lab had stopped using them as teaching tools because they had become cloudy and dark.Ethanol has become the widely accepted professional method of liquid preservation partly because it is a less toxic and more environmentally friendly solution for long‐term storage and display. However, not much has been written about its use for human tissue revitalization in collections such as this.We found that the tissues dried out significantly when we changed solvents immediately from formaldehyde and water to an ethanol solution. After researching the problem, we decided to use sequential positive step‐gradient incubation in alcohol. First, the specimens were drained of the formaldehyde and water. Then, the ethanol was introduced in 20% increments. The slow steps of the ethanol incubation prevented the tissue from drying. Four months after this revitalization, the results show that the tissues have not shrunk and have sustained their integrity.By restoring these rare specimens to prime condition, we are once again able to use them as invaluable learning tools in the anatomy lab.Grant Funding Source : San Francisco State University Biology Department