bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of neuropeptide Y and aquaporin 4 in the pathogenesis of intestinal dysfunction caused by traumatic brain injury
Authors: Duan Hubin , Hao Chunyan , Li Shuzhen , Fan Yimin , Wang Hongqin , Hao Jiehe , Liu Yueting , Liu Xiaodong
Published: June 2021

Backgroud and purpose

To study the role of neuropeptide Y(NPY) and aquaporin 4 (AQP4) in the pathogenesis of intestinal dysfunction caused by traumatic brain injury£TBI£©.

Methods

40 Wistar rats were randomly divided into control group, mild trauma group, moderate trauma group and severe trauma group. All the rats were sacrificed at 24 hours after the operation. The contents of NPY and AQP4 in the rats blood and jejunum were detected by ELISA, PCR, western blot and immunohistochemical staining. The pathological changes of intestinal cells structure and ultrastructure were observed by light microscopy and transmission electron microscopy.

Results

The more severe the grade of trauma, the more serious the degree of intestinal mucosal injury, the higher the content of NPY and AQP4 in the plasma and jejunum of rats(P<0.05). Moreover, there are positive correlation between NPY and AQP4(P<0.05).

Conclusion

AQP4 and NPY may be involved in the pathogenesis of intestinal dysfunction after TBI. Increased NPY level might be responsible for the Intestinal ischemia and hypoxia, AQP4 might play an important role in intestinal edema. In addition, the increase of NPY content might be one of the main reasons that lead to the increased of AQP4 content after TBI.
Regulation of mRNA export by the PI3 kinase/AKT signaling pathway
Authors: Vancor Emily Anne , Quaresma Alexandre Jose Christino , Nickerson Jeffrey A.
Published: June 2021

mRNA export from the nucleus is critical for gene expression, but its regulation is not well understood. We studied the regulation of mRNA export by the PI3Kinase/AKT pathway, a controller of proliferation and survival often deregulated in cancer. UAP56, ALY/REF, and NXF1 are mRNA export factors that sequentially bind at the TRanscription/EXport (TREX) complex at the 5′ end of nuclear mRNA. NXF1 subsequently binds at nuclear pores for mRNP export. We used Fluorescence Recovery after Photobleaching (FRAP) to measure binding of these export factors in complexes at an integrated array of actively transcribed β‐globin genes and at RNA splicing speckled domains. Inhibition of the PI3 kinase/AKT pathway decreased the fraction of UAP56 and ALY/REF in complexes at β‐globin transcription sites. Pathway inhibition did not significantly affect localization of export factors at the β‐globin genes, but did affect localization of the splicing factor SRm300. qRT‐PCR results showed pathway inhibition did not affect turnover rates for selected mRNAs but may affect exon inclusion for β‐globin. These data clarify the regulation of mRNA metabolism by PI3 kinase/AKT signaling. This work was supported by NCI (PO1CA82834).
Production and characterization of oxidation‐resistant variants of the human ribonuclease inhibitor
Authors: Uebersohn Alec W , Dickson Kimberly A.
Published: June 2021

Repeat proteins are widely used in nature to modulate protein activity. New protein engineering technologies have exploited the scaffolds of repeat proteins to construct novel protein‐binding surfaces that rival the specificity and robustness of antibodies. The human ribonuclease inhibitor (RI) is a horseshoe‐shaped leucine‐rich repeat (LRR) protein that binds to pancreatic‐type ribonucleases with extraordinary affinity (KD ≈ fM). Its conserved modular frameworks and extensive surface area renders it an alluring scaffold for protein engineering. Unfortunately, RI is extremely sensitive to oxidation due to the high number of cysteines (32 residues, 7 % of total amino acids). Oxidation of only a few cysteines results in a collapse of the tertiary structure and complete inactivation. We have constructed oxidation‐resistant variants of RI in which some or all of its 32 cysteine residues have been replaced. Six variants of RI have been produced in which groups of 5–7 cysteines (at conserved positions within the LRR motif) have been mutated. Preliminary results indicate that the RI variants maintain affinity for ribonucleases, but possess decreased oxidation sensitivity. These data contribute to our understanding of the structural stability of LRR proteins and suggest that RI and other LRR proteins are practical scaffolds for the design of novel binding surfaces.

This work was supported by a Lawrence University Excellence in Science Grant and a Mellon Foundation Grant for Senior Experience to A.W.U and Lawrence University start‐up funds to K.A.D.
Development of Effective Learning Modules to Integrate the Anatomy and Clinical Skill of Musculoskeletal System
Authors: Doroudi Majid
Published: June 2021

Development of Effective Learning Modules to Integrate the Anatomy and Clinical Skill of Musculoskeletal System

Many students find memorizing MSK materials difficult and daunting, and often find themselves feeling overwhelmed by the number of muscles, bones, innervations, vessels and special tests that they must commit to memory. The overall objective of this study was to encourage students to adopt a more anatomical approach to clinical skills and also to show explicitly the relevance of musculoskeletal anatomy, thus moving away from rote memorization of physical exam skills and anatomical knowledge. The focus of this project was to develop effective learning modules that will help students learn musculoskeletal materials and enhance their education environment. In order to accomplish the goal of interactive modules we used the Medicine and Dentistry Integrated Curriculum Online (MEDICOL) Vista to create two modules that integrated the anatomy and clinical skill of musculoskeletal system. Using the MEDICOL we were able to add interactive labeled diagrams to review MSK anatomy and pictures to study clinical skills and integrated quizzes to test student knowledge. The MSK modules were evaluated objectively from the survey questionnaire results and subjectively from the comments from the results. Before the modules 55% of students felt they knew the MSK materials well or very well. After the modules 83% of students felt they knew the MSK materials well or very well.
Phenotype and genotype comparison of C57BL/6N substrains contributing to the International Mouse Phenotyping Consortium (IMPC)
Authors: Elder Bruce , Engelhard Eric , Flenniken Ann , Herault Yann , McKerlie Colin , Nutter Lauryl , Sorg‐Guss Tania
Published: June 2021

The International Mouse Phenotyping Consortium (IMPC) is a 10‐ year program to produce a null mutant mouse line for every gene in the mouse genome, generate comprehensive phenotype data for each, and provide all the resources to the scientific community. The chosen mouse strain is the C57BL/6N, however there are several substrains of this mouse including C57BL/6NCrl (NCrl), C57BL/6NTac (NTac), and C57BL/6NJ (NJ). A C57BL/6Nderived embryonic stem (ES) cell line (JM8) was used to create the gene‐targeted clones. Given the scope of the IMPC project, it is important to catalog phenotype and genotype similarities or differences between the C57BL/6N substrains and ES cells used by the various IMPC centers. Here we describe results from genotype analyses using the Affymetrix Mouse Diversity Genotyping array to compare single‐nucleotide polymorphisms (SNP) between NCrl and NTac mice, and JM8 and C2 ES cell lines. In addition, whole genome sequencing (WGS) was carried out on NCrl, NTac, NJ, and JM8 genomic DNA. Phenotype analyses using the IMPC pipeline was conducted on NCrl and NTac mice at two separate locations; The Toronto Centre for Phenogenomics (TCP) and the Institut Clinique de la Souris (ICS). Substrain differences in certain traits were detected and the number of differences was strongly influenced by the rearing environment of the cohort, with fewer differences between NCrl and NTac cohorts derived from animals born and raised within the same institution.
Beta Interferon Protein Therapy for Multiple Sclerosis
Authors: Farooque Alma , Huettl Maggie , Kaiser Jennifer , Shukla Neehal , Van Oudenhoven Quinn , Dopp Amy , Rolak Loren
Published: June 2021

Multiple sclerosis (MS) is an autoimmune disorder in cause the demyelination of neurons, resulting in degenerative symptoms. MS activates inert autoreactive myelin T‐cells, lymphocytes specific to the destruction of central nervous system myelin, to cross the blood brain barrier and secrete inflammatory cytokines, recruiting other leukocytes and macrophages that demyelinate axons primarily through the release of myelinotoxic substances. The most effective treatment for MS is administration of β interferon, which reduces relapse rate of nervous tissue attacks. The Marshfield SMART Team (Students Modeling A Research Topic) designed a model of β interferon using 3D printing technology to understand its interaction with T‐cells to treat MS. β interferon is an endogenous polypeptide that regulates T‐cells and are hypothesized to convert autoreactive myelin T‐cells into suppressor cells that can deactivate other myelin targeting lymphocytes. β interferon may also lead to the inhibition of cytokines, preventing activation of the autoreactive T cells. Interferons may inhibit the leukocyte migration across the blood‐brain barrier to prevent access to myelin. Understanding the structure and function of β interferon could lead to more precise and effective drugs to treat MS. Supported by grants from the Marshfield Clinic Research Foundation and NIH‐SEPA.
Astrocytes expressing Nef promote apoptosis and SMAD signaling in Neurons
Authors: Manoharan‐Valerio Michael Anand , Colon Janet , Martinez Neysha , Quiroz Elisa , Noel Richard
Published: June 2021

HIV is known to infect cells in the brain causing neurological impairments. Damage ranges from mild (HAND) to severe (HAD). We found learning impairment in rats infused with astrocytes expressing Nef. Histological studies performed on the brain tissues showed loss of neurons near the infusion site as well as evidence for TGFB signaling. We set up in vitro experiments to test for relationships between astrocytic Nef, TGFB signaling and neuron loss. We propose this loss is due to an apoptotic response of the neurons to the astrocytes expressing Nef. We exposed neuronal cells to astrocytes expressing Nef or GFP. Annexin V staining was used to measure apoptosis and a reporter assay measured SMAD activity by TGFB signaling. Results suggest that astrocytic Nef expression causes neuronal apoptosis. These neurons also show an increase in SMAD reporter activity. These studies suggest that loss of neurons may have been due to apoptosis caused by astrocytic Nef expression. These studies are relevant to understanding the high prevalence of HAND among patients receiving antiretroviral treatment.

Supported by STEP‐UP Program, DA026722, RR003050/MD007579, GM09695 and 5G12RR003050/8G12MD007579.
Regulation of hemoglobin gene expression in the clam Lucina pectinata
Authors: Montes Ingrid , Cadilla Carmen , Lopez‐Garriga Juan
Published: June 2021

The clam Lucina pectinata has three different hemoglobins (Hbs): hemoglobin I (HbI), a sulfide‐reactive protein and two oxygen‐reactive proteins, hemoglobin II (HbII) and hemoglobin III (HbIII). In order to better understand the physiological roles of these hemoproteins we evaluated their gene expression at the mRNA level by RT‐qPCR. We compared two groups of clams, one group was harvested from their natural environment and the other group of clams was phytoplankton fed in a fish tank. The Hb mRNAs expression levels were normalized to that of the 18S rRNA (18S). We also evaluated histone H3 gene expression. We found that expression of the three Hb mRNAs was highest in ctenidia tissue for both conditions, while in mantle, muscle, and visceral mass, the Hbs were expressed at much lower levels for both conditions. The expression of the Hbs decreased significantly in the clams kept in a fish tank, while the expression of the housekeeping gene, 18S, and histone H3 gene, were similar in both groups, except for the visceral mass tissue where the expression of histone H3 decreased 20‐fold. These suggests that hemoglobin gene expression may be subject to environmental control, which may include response to changes in hydrogen sulfide (H2S) and oxygen (O2) concentration as well as other factors in the conditions we tested. This research was supported by NIH grants 8G12‐MD007600 and 5R25GM088023.
Change in Sialic Acid in Pulmonary Arterial Hypertension
Authors: Morrow Rebekah , Cioffi Eugene , Cioffi Donna
Published: June 2021

Sialic acid (SA) is a vital component of the cellular glycocalyx. Increased serum levels of SA are found in cancers and cardiovascular disease. The levels of free and total SA in pulmonary arterial hypertension (PAH) are unknown. PAH is often undiagnosed until the patient is near or in heart failure, and right heart catheterization is required for diagnosis. Knowing that serum SA is increased in other diseases, we asked whether it was also increased in PAH. Levels of free and total SA were measured in the serum of three groups: healthy volunteers (HV), idiopathic PAH (IPAH), and connective tissue disease‐associated PAH (CTD). While total SA does not change significantly between groups, free SA in IPAH and CTD serum is increased compared to HV serum. In addition, PAH patients have anti‐endothelial cell antibodies. Antibodies are highly glycosylated proteins whose function may be altered by changes in sialylation. We asked whether IgG from PAH patients contains increased SA as compared to IgG from healthy volunteers. IgG was purified from serum by affinity chromatography. Samples were hydrolyzed and total SA was measured. IPAH IgG shows an increased percentage of SA as compared to HV or CTD IgG. Collectively, these results suggest that PAH changes the sialylation patterns of immunoglobulins and possibly their antigenic targets. SA levels may also be a useful biomarker for diagnosing PAH. Supported by R00HL089361.
Anti‐inflammatory effects of lysine‐galactose Maillard reaction products in Caco‐2 and RAW264.7 co‐culture systems
Authors: Oh Jun‐Gu , Hong Chung‐Oui , Nam Mi‐Hyun , Seol Hae Min , Lee Kwang‐won
Published: June 2021

Maillard reaction is a nonenzymatic reaction between an amino acid and a reducing sugar that usually occurs upon heating. This reaction occurs routinely in cooking and its products are considered as safe materials. In this study, various MRPs samples were prepared from three different amino acids (lysine, arginine and glycine) and sugars (glucose, fructose and galactose) for 1 h heating at 121¡É. Treatments with the MRPs samples on RAW264.7 cells stimulated with lipopolysaccharide (LPS) decrease nitric oxide (NO) expression compared to control. Moreover, a MRPs sample derived from lysine and galactose most significantly inhibited NO expression. We also evaluated antiinflammatory effect of MRPs with a co‐culture system consisting of Caco‐2 intestinal epithelial cell line (apical side) and RAW264.7 macrophage cell line (basolateral side) to investigate the gut inflammation reaction. In this system, RAW264.7 cells stimulated with LPS decreased transepithelial electrical resistance (TEER), which is a marker of the integrity of cells, and increased TNF‐α productions and gene expressions of IL‐8 and IL‐1¥â in Caco‐2 cells. In this system, ultrafiltration fractions with high molecular weight suppressed IL‐8 gene expression as well as reduction of TNF‐α production from RAW264.7 cells stimulated with LPS.
GENE EXPRESSION IN FOLIC ACID FORTIFICATION AND RISK OF COLORECTAL CARCINOGENESIS IN RATS
Authors: Cohen Celia , Cardoso João Felipe Rito , Garcia Sergio Britto , Vannucchi Helio
Published: June 2021

This study aimed to evaluate the effects of folic acid deprivation, fortification and supplementation followed by fortification in gene expression in colorectal carcinogenesis in rats.Wistar rats received either Standard AIN‐93M diet during all experiment (G1), diet without folic acid during all experiment (G2), diet with 3.25mg of folic acid during all experiment (G3) or diet with 5mg of folic acid before carcinogenesis induction followed by a diet with 3.25mg of folic acid through the experimental period (G4). Colorectal carcinogenesis was induced by 4 doses of MNNG (5mg/mL) twice a week during 2 weeks. Analysis: colonic S‐adenosylmetionine (SAM) and S‐adenosylhomocysteine (SAH) ratio; gene expression of Bax, CDKN1A, Bcl2. Statistical analysis: ANOVA, p<0.05. G3 had higher SAM than the other groups (p<0.05). G2 showed an increased SAH when compared to the other groups (p<0.001) and G3 had lower SAH than G4 (p<0.01). G3 presented elevated colonic SAM/SAH ratio in comparison to the other groups (p<0.05). G3 had increased Bax gene expression when compared to the other groups (p<0.05) and higher CDKN1A expression when compared to G1 and G4 (p<0.05). Bcl‐2 showed no difference among the groups studied (p>;0.05). Folic acid fortification (G3) seemed to improve the colorectal carcinogenesis biomarkers studied and modulate cell cycle and apoptosis gene expression. Financial Support: FAPESP
Vitamin D supplementation for four months causes cardiac hypertrophy and diastolic dysfunction in normal rats
Authors: Santos Priscila Portugal , Rafacho Bruna , Gonçalves Andréa , Cândido Renata , Ferreira Vanessa , Roscani Meliza , Minicucci Marcos , Campana Alvaro , Zornoff Leonardo , Gaiolla Paula , Paiva Sergio
Published: June 2021

The aim of the study was to evaluate different vitamin D supplementation doses in the cardiac structure and function in normal rats.

Methods

46 male rats allocated into 3 groups: control (C, n=14) received standard chow; D3 (n=16) and D10 (n=16) received 3,000 and 10,000 IU of cholecalciferol/kg chow for 4 months, after was performed echocardiography evaluation and morphometry.

Results

The posterior wall thickness (C=1.3(1.3–1.5); D3=1.8(1.8–2.0); D10=1.8(1.7–1.8) mm; p<0.001), relative wall thickness (C=0.39±0.04; D3=0.52±0.09; D10=0.50±0.06; p<0.001) and left ventricle mass/weight body (WB)(C=1.6±0.2; D3=2.0±0.3; D10=2.0±0.4 mg/g; p<0.001) were higher in supplemented groups compared to C. The supplemented animals presented higher left atrial diameter/aortic diameter (C=1.1±0.1; D3=1.4±0.2; D10=1.3±0.2; p<0,001). The worst diastolic dysfunction was in D10, which led to lower values of tricuspid E/A‐wave ratio (C=0.66(0.57–1.28); D3=0.58(0.52–0.71); D10=0.53(0.47–0.60); p=0.04) and higher values of right ventricle weight/WB(C=0.46±0.03; D3=0.46±0.03; D10=0.50±0.05 mg/g; p=0.014) compared to C.

Conclusion

Normal rats supplemented with vitamin D showed concentric cardiac hypertrophy and diastolic dysfunction with impaired right side heart in animals supplemented with the highest dose.
Preventing iron deficiency: Results of a randomized controlled trial of double‐fortified salt in female Indian tea pluckers
Authors: Hammons Julie , Venkatramanan Sudha , Mehta Saurabh , Haas Jere
Published: June 2021

Previous research has shown that consuming iron‐fortified salt improves iron status. The present analyses examined predictors of the prevention of iron deficiency (ID) during a randomized, double‐blinded, placebo controlled intervention of double‐fortified salt (DFS). Participants were 217 female tea pluckers, aged 19–55 years, from West Bengal, India. Mixed models were used to assess the effect of DFS on the change in baseline iron status and other micronutrient indicators (iodine, folate, vitamin B12). Predictors of ID incidence were identified using logistic regression models. DFS significantly decreased the odds that women who had normal iron status at baseline would develop moderate or clinical ID (ferritin <20 or 12 μg/mL, respectively). Higher hemoglobin and lower transferrin receptor concentrations at baseline also predicted lower odds of developing ID or moderate ID. The results are discussed in the context of designing interventions in multiple‐micronutrient‐deficient settings and may help identify populations likely to benefit from future efficacy and effectiveness trials of dietary iron interventions. Supported by the Mathile Institute and the Micronutrient Initiative.
Sorghum extract lowers blood and hepatic lipids in rats fed a high fat diet
Authors: Kim Juyeon , Noh Sang K.
Published: June 2021

Recently, we have shown that sorghum extract (SE) lowers the intestinal absorption of lipids and also increases their biliary secretion in rats. Further study was conducted to examine if SE would affect blood and hepatic lipids in rats fed a high fat diet for 6 wk. One group of five rats (control) were fed an AIN‐93G diet mixed with 3% (w/v) lard and 0.2% cholesterol (C) and the other with the same control diet but containing SE at 7.5 g/kg diet. Rats had free access to their respective diets over 6 wk. At 0, 3, and 6 wk, serum triglycerides, total C, HDL‐C, and non‐HDL‐C were determined. No difference in bodyweight changes was noted between the groups throughout 6 wk. However, the concentrations of serum triglycerides, total C, HDL‐C, and non‐HDL‐C were significantly lowered in rats given SE. Also, total lipids in the liver of SE rats were significantly lower than control rats. Taken together, these results indicate that SE has a profound inhibitory effect on serum and hepatic lipids by lowering the intestinal absorption of lipids and also enhancing their biliary secretion.
Beneficial effect of blueberry wine on alcoholic fatty liver in rats
Authors: Choi Hansol , Kim Juyeon , Park Joonghyeap , Noh Sang K.
Published: June 2021

Evidence indicates that wines made from berry fruits are beneficial for health. This study was conducted to investigate whether blueberry wine would ameliorate the accumulation of serum and hepatic lipids in ethanol‐induced fatty liver rats. Adult male rats were fed either an ethanol Lieber‐DeCarli liquid diet or an isocaloric control diet or the ethanol diet with blueberry wine. Rats were fed equally their respective diets for 6 wk. Serum triglycerides, total cholesterol (C), HDL‐C, and non‐HDL‐C were determined at 0, 3, and 6 wk. The liver was removed for histology at 6 wk. Blueberry wine administration significantly lowered liver weight, compared to ethanol‐fed rats. Also, blueberry wine significnatly decreased hepatic lipids to the levels of control. These data indicate that blueberry wine protects the liver from fat accumulation induced by ethanol comsumption.

This work (Grants No. C0035781) was supported by Business for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Small and Medium Business Administration in 2012.
An inverse Association of Vitamin D Serum Concentration with Inflammatory markers among older Puerto Ricans
Authors: Jamal‐Allial Aziza , Tucker Katherine L.
Published: June 2021

Vitamin D deficiency has been linked to obesity, metabolic syndrome and autoimmune diseases.

Several reports suggest an association between serum 25‐hydroxy vitamin D concentration (25(OH)D) and inflammation. We examined, cross‐sectionally, the relation between serum 25(OH)D concentration and serum inflammatory markers in 963 Puerto Rican adults, 268 men and 695 women, aged 45–75 years. After adjusting for age, sex and seasonality, serum 25(OH)D was significantly negatively associated with tumor necrosis factor‐alpha (TNF‐α) and interleukin 6 (IL‐6) (P<0.01 and P<0.04 respectively), but not with insulin‐like growth factor‐1 (IGF‐1) or high‐sensitivity C‐reactive protein (hs‐CRP). The associations remained significant with further adjustment for waist circumference (WC), total body fat, abdominal fat mass, smoking status, alcohol intake, vitamin D supplement use and physical activity score. In conclusion, lower serum 25(OH)D concentration was significantly associated with higher concentrations of inflammatory markers in this population of older Puerto Rican adults living in the Boston area. This is important, as this population has high prevalence of vitamin D deficiency and of chronic conditions. Longitudinal studies are needed to clarify causal pathways.
Increased waist circumference is associated with increased malondialdehyde and decrease of adiponectin in women with Metabolic Syndrome
Authors: Talon Lidiana Camargo , Oliveira Claudia Diniz Lopes , Pierine Damiana Tortolero , Nunes Vania Santos , Okoshi Marina Politi , Correa Camila Renata
Published: June 2021

The aim of the study was to correlate waist circumference (WC) with oxidative stress (OS) and production of adiponectin. We included 15 healthy women (HW) and 15 women with MS, aged between 18 and 50 years old. To confirm the diagnosis of MS the following parameters were determined: WC, HDL, triglycerides (TG), blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP). We also performed a body mass index (BMI), leptin, adiponectin and malondialdehyde (MDA). Statistical analyzes were performed by Student's t test and Pearson's correlation. The MS group presented increased BMI, WC, TG, blood, leptin, DBP, MDA and lower values for HDL and adiponectin. There was negative correlation between WC and adiponectin (r = −0.56156, p = 0.0012) and positive correlation between MDA and WC (r = 0.45913 and p = 0.0107) and leptin and glucose (r = 0.52735, p = 0.0027). We can conclude that abdominal obesity leads to increased OS and a decrease in adiponectin and this can lead to cardiovascular disease. Financial Support: CNPq, FAPESP 2011/08373–5
Effect of social mobility on body mass index from birth to adolescence: a cohort study
Authors: Muraro Ana Paula , Gonçalves‐Silva Regina Maria Veras , Ferreira Márcia Gonçalves , Sichieri Rosely
Published: June 2021

It was evaluated the effect of family socioeconomic status (SES) and social mobility on the trajectory of Body Mass Index (BMI) from birth to adolescence. A population based sample of 2405 children aged 0 to 5 years, living in the city of Cuiabá‐MT, Brazil in 1999, was followed. Socioeconomic Status was classified by an asset‐based wealth index called in: low, middle and high classes. Anthropometric data were measured at childhood and adolescence. Weight and length at birth were those from hospital records. Linear mixed effect models were used (using SAS Proc MIXED). A total of 1716 adolescents were followed to adolescence (71.4% of baseline) and 51.2% were male. The prevalence of overweight/obesity was 20.4% in childhood and 27.7% in adolescence. At adolescence, higher family SES was associated with higher prevalence of overweight/obesity. Expressive social mobility occurred, mainly among lowest SES group. There was a greater rate of change of BMI from birth to adolescence among those who were from higher SES in childhood and those who remained in the higher SES from childhood to adolescence. In conclusion, tracking a high BMI from childhood to adolescence occurred in the families of high SES at childhood, with no effect of social mobility.

Financial support:

CNPq and FAPEMAT.
Plasma Total Antioxidant Capacity (TAC), Alcohol Dependence and HIV Disease Progression in HIV‐Infected Adults
Authors: Martinez Janet Diaz , Campa Adriana , Parsons Mary , Martinez Sabrina Sales , Williams Shawn , Barr Shakira , Greer Pedro , Baum Marianna K
Published: June 2021

Objective

Chronic alcohol consumption is associated with increased oxidative stress (OS) resulting in alcohol‐induced liver injury. Since plasma TAC may be an early marker of OS, we examined the relationship between plasma TAC levels and HIV disease progression in HIV+ adults with alcohol dependence as compared to those who were not alcohol dependent.

Methods

After consenting, TAC was determined using a copper‐reducing antioxidant power assay in 34 alcohol dependent and 34 not dependent HIV infected participants. Alcohol Use Disorders Identification Test (AUDIT) scores ≥13 for women and ≥15 for men were categorized as alcohol dependence. CD4 cell and viral load were obtained from medical records.

Results

Participants were 67.6% male, 67.2% African American; mean age was 44.9±7.2 years. The mean TAC in HIV‐1 alcohol dependent participants was 0.038±0.026 μM copper reducing equivalents, and was significantly lower than the TAC mean of the group not alcohol dependent (0.069±0.071 μM copper reducing equivalents, [p<0.01]). TAC was positively associated with viral load in HIV+ alcohol dependent participants (β=5.78, SE=2.56, p=0.032), after controlling for age.

Conclusion

Our results show that alcohol dependence has a detrimental effect on plasma TAC in HIV+ adults. TAC can be used as an early marker of OS and may help to optimize and monitor antioxidant therapy in this population.

Supported by NIAAA
A human, left temporal bone: a complex anatomical model of the middle stage of the basis of the cranium with aperture of the middle ear cavity and vascular representations
Authors: LE FLOCH‐PRIGENT Patrice Pierre , GILLOT Jean‐Bernard
Published: June 2021

A left temporal bone with somme elements of the adjacent sphenoid and occipital bones, exponed the exo and endo‐cranial aspects of the middle floor of the basis of the cranium. It was mounted on a wooden basis (9 × 9× 1,8 cm) by a metallic stem; a label « CLAY ADAMS CO SKELETONS. ANATOMICAL AND BIOLOGICAL MODELS 25 EAST 26th NEW YORK » was sticked on its superior face. Its maximal dimensions were 10 cm long, 9 cm high and 6 cm wide. It belonged to the scientific, Alain Brieux Library in Paris. Several (arteries and veins) vascular representations were figured. The bone had been sawed along its longitudinal axis in order to expone the middle ear. A window had been hollowed on the superior face of the temporal bone to expone the semi‐circular canals; another one had been removed from the external face of the mastoid process showing its cavities. The simplicity of the mounting of this model made from real bones was only apparent and the manufacture could have been delicate. This model had been probably produced in the years 1940 (Carline Zanon). We thanks Mr Alexandre Piffault.
PEPTIDE VACCINE TO RECOVERY THE SALIVARY GLANDS OF DIABETIC MICE
Authors: Caldeira Eduardo José , da Silva Rodrigo Eduardo , Dias Marco Antônio , Mancio Rafael Dias , Netto Raphael Oliveira , Rojas Fernanda , Peroni Luis , Júnior Rui Seabra Ferreira
Published: June 2021

Current treatments for diabetes, such as insulin, are ineffective to recovery of organs and tissues. Thus, the aim of this study was to evaluate the effects of peptides P217 and P290 in the recovery of salivary glands of diabetic mice. Animals were divided into 3 groups; Group I (7 Balb/C mice), Group II (7 NOD mice), and Group III (7 NOD mice/treated). Group III received the peptides during a total period of 21 days. Groups I and II received saline solution to simulate the experimental treatment. After treatment tissue samples were analyzed by light and fluorescence microscopy. Treated animals consumed less liquid and solid. Reduction of body weight was observed in untreated animals. High levels of glucose were observed in animals of group II, while in treated diabetic animals, a reduction was observed in these levels. Inflammatory process was not observed in group I. Intense inflammatory process was observed in untreated diabetic animals. Reduction of inflammatory process was observed in treated animals. In these animals were observed decrease of lymphocytes and increase of neutrophils. Tissue restructuration was observed after the immunization, as well as was observed the recovery of insulin receptor expression. This treatment was effective in the recovery of salivary cells, contributed to homeostasis of body metabolism and reduction of inflammatory process, that suggest an attempt of tissue reorganization. This immunomodulation promoted a beneficial effect on the recovery of these tissues.
Fish oil disrupts B cell MHC class II lateral organization in the murine immunological synapse
Authors: Rockett Benjamin Drew , Melton Mark , Teague Heather , Harris Mitchel , Bridges Lance , Shaikh Saame Raza
Published: June 2021

Fish oil enriched long chain n‐3 polyunsaturated fatty acids disrupts the lateral organization of proteins on the T cell side of the immunological synapse. However, the impact of fish oil on the antigen presenting cell side of the immunological synapse is unclear. We previously demonstrated that B cells isolated from mice fed fish oil suppressed B cell microdomain clustering as well as the ability to activate naïve CD4+ T cells through antigen presentation. In this study, using a combination of quantitative imaging methods, we tested the effect of fish oil on the lateral organization of B cell major histocompatibility complex (MHC) class II molecules involved in forming the immunological synapse. Fish oil had no impact on pre‐synaptic B cell MHC II clustering. However, fish oil did suppress the recruitment of MHC class II to the synapse. As a consequence, T cell PKCθ recruitment to the synapse was also diminished. The effects were independent of changes in B‐T cell adhesion. Finally, we compared the impact from fish oil to cholesterol depletion using methyl‐β‐cyclodextrin treatment and found similar results. Overall, the results reveal commonality in the mechanism by which fish oil manipulates protein lateral organization of B cells compared to T cells. Furthermore, the data establish MHC class II lateral organization on the B cell side of the immunological synapse as a novel molecular target of fish oil.

NIH R15AT006122
Investigating the Effects of 12 Week Almond Consumption in Type 2 Diabetes.
Authors: Ricklefs Kristin , Petersen Katherine , Alanbagy Sameer , Johnston Carol S , Sweazea Karen L
Published: June 2021

The national cost of diabetes exceeds $174 billion each year. Heart disease and stroke are the primary causes of death and disability among people with type 2 diabetes (T2D). The objective of this ongoing 12‐week randomized, parallel‐arm controlled feeding trial is to determine if the addition of almonds (1.5 oz/d) to a normal diet will result in significant improvements in diabetic and cardiovascular risk markers in subjects with T2D who are not currently taking insulin compared to matched controls who were instructed to maintain their normal eating patterns. To date, twelve participants have completed the trial (5 almond and 7 controls). Although the change in biomarkers are not significantly different between groups at this point in the trial, change in biomarkers were favorable for the almond vs. controls for hemoglobin A1c (−2% vs. +1%), diastolic blood pressure (−6% vs. 0), and waist circumference (−3% vs. +1%). Enrollment continues in the trial through March 2013. Previous studies from our labs have shown almonds to promote a significant reduction in hemoglobin A1c and improvements in anthropometric indices in individuals with T2D. This trial will provide further evidence regarding the efficacy of daily almond ingestion for managing the diabetic condition. This study was funded by The Almond Board of California.
Resistance of guinea pig cardiac cytochrome c oxidase (complex IV) to extended ischemic time during global ischemia and reperfusion
Authors: Wuenstel Andrew M , Camara Amadou KS , Heisner James S , Aldakkak Mohammed , Stowe David F
Published: June 2021

Reactive oxygen species (ROS) produced from cardiac mitochondria during ischemia and reperfusion (IR) injury can damage respiratory complexes I–V. We reported that complexes I and III, but not IV, were damaged after 30 min global ischemia. Here we examined for damaging effects of extended ischemic time on complex IV. Guinea pig heart mitochondria were isolated after 30 min reperfusion in four groups: time control (TC), 35 min ischemia alone, 45 min ischemia alone, and 45 min ischemia plus a cocktail of ROS scavengers (MnTBAP, catalase, glutathione, resveratrol) given 10 min before ischemia and throughout reperfusion. Complex IV enzyme activity was assessed by the conversion of reduced cytochrome c to oxidized cytochrome c in a spectrophotometer at 550 nm. Phasic (systolic – diastolic) left ventricular pressures (LVP) were 92±1 (SEM), 47±7, 17±5, 23±3 mmHg, and diastolic LVPs were 0, 9±4, 41±5, 22±2 mmHg, for TC and ischemia lasting 35, 45, and 45 min + ROS scavengers, respectively. Despite differences in cardiac function, complex IV activity was not different among groups including TC. Respiratory complexes that are most susceptible to ischemic damage are important for developing targeted strategies to protect them. Understanding why and how complex IV is resistant to oxidative stress could provide insight into better strategies to protect the more susceptible complexes against IR injury. (supported by NIH HL89514)
Histopathologic changes in S‐adenosyl‐L‐methionine treated patients with alcoholic liver disease: an in‐depth look at data from a double‐blinded, randomized, placebo controlled trial
Authors: Le Mary D , Enbom Elena , Traum Peter K , Medici Valentina , Halsted Charles H , French Samuel W
Published: June 2021

Objective

The objective of this study is to assess if there were any changes in liver biopsies after treatment with S‐adenosyl‐L‐methionine (SAMe) in alcoholic liver disease patients.

Design

Liver biopsies of 14 patients were randomized for SAMe treatment at week 0 (biopsy #1) and at 24 weeks (biopsy #2). Patients received 1.2 g of SAMe or placebo by mouth daily and stopped alcohol intake. Biopsies were semi‐quantitatively scored for: necrosis, tunnel formation, smooth muscle actin, kupffer cells, polymorphonuclear leukocytes, lipogranules, lymphocytes, balloon cell formation, and duct metaplasia.

Results

Comparing treatment arm to placebo arm, no significant difference was found between biopsy #1 and biopsy #2. However, when both study arms were grouped together, there was decrease in smooth muscle actin stain, where the p‐value=0.027.

Conclusion

Treatment with SAMe did not show a statistically significant difference in the characteristics studied. However, when both the treatment and placebo arm data were grouped together to increase the n and power, there was a decrease in the smooth muscle actin stain, reflecting a decrease in stellate cells activation, likely due to the alcohol abstinence. This study shows that it may not be beneficial to wait for more definitive treatment, like liver transplant, because the liver tissue will remain with the same degree of pathology six months out, regardless.
Angiotensin II and its role in fat embolism‐induced lung pathology
Authors: Abbas Fizza , Herndon Betty , Quinn Tim , Likhitsup Alisa , Salzman Gary , Molteni Agostino
Published: June 2021

Fat embolism (FE) after bone fractures increases pulmonary pathology. Our data suggests that lung damage in rats is less severe when angiotensin blocking drugs including captopril or losartan are given. Preliminary to my study, fat embolism was induced by i.v. injection of 0.2 ml triolein into 60 rats. Some animals received 50 mg/kg captopril i.p. or 10 mg/kg losartan i.p. one hour after triolein. Lungs were fixed for histology, or frozen for later study at 24–96 hr. Angiotensin peptides, detected by histochemistry, were increased by triolein‐induced FE compared to saline controls, and both captopril and losartan reduced the histochemical inflammation and fibrosis. Angiotensin II (A II) appeared to be mediating FE ‐induced pathology. To determine relationship of histology to tissue AII, lungs of 60 rats were homogenized into 500 μL protein buffer with protease inhibitor. Peptides were purified on micro C‐18 columns then tested by ELISA for AII.

The angiotensin peptide present in lungs of rats with fat embolism syndrome increased from 24 (0.049) to 96 hr (0.062). The drugs produced significant increases in AII in the lungs (0.14 – 0.17 at 48 hr; p=0.001). Both ACE inhibitor captopril and AT1 blocker losartan partly improved pulmonary histology in animals given fat embolism in vivo. Comparison of pulmonary histology and A II peptide levels in the lungs continues with more mechanistic study. Funding: Gelmacher Foundation
Gastrin‐Releasing Peptide (GRP) Mediates Early Radiation‐Induced Airway Responses Predictive of Later Lung Injury
Authors: Sunday Mary E , Zhou Shutang , Kant Erin Potts , Jackson Isabel L , Vujaskovic Zelcko , Foster W. Michael
Published: June 2021

Ionizing radiation (RT) induces lung injury, with pneumonitis 1–4 months later and fibrosis 4–6 months later, but early detection of RT lung injury is elusive. We recently showed GRP mediates RT‐induced pulmonary fibrosis in mice. GRP also mediates asthmatic responses in mice. We tested whether RT triggers airway responses via GRP. C57BL/6 (pneumonitis‐resistant) and C57L/J (pneumonitis‐sensitive) mice were exposed to thoracic RT (5,10, or 15Gy), followed by GRP blockade (small molecule 77427 or mAb 2A11) one‐hour later. We tested pulmonary function 6–72h post‐RT with bronchoalveolar lavage (BAL) for cells, cytokines, and albumin. RT‐dose‐dependent airway hyperreactivity (AHR) was increased 6–72h post‐RT, C57L/J>;C57BL/6, abrogated by GRP blockade. Only C57L/J responded to low‐dose RT. GRPR‐null mice had no AHR. C57L/J had elevated IL‐6 and γIFN in BAL, but C57BL/6 did not. GRP mRNA was highest in lungs of C57L/J. RT also increased vascular permeability via GRP, measured by BAL albumin levels 6–24h post‐RT, C57L/J>;C57BL/6. Thus, early pulmonary function testing could identify individuals most susceptible to developing fibrosis following radiation exposure.
Assessment of a novel compressed sensing algorithm for reconstructing phase contrast CT images of the canine prostate
Authors: Montgomery James , Zhu Zangen , Wahid Khan
Published: June 2021

Phase contrast computed tomography (PC CT) represents a generational advance in medical and anatomical imaging with greatly improved spatial and soft tissue contrast resolution. Achieving good image quality with PC CT can require up to 4000 image projections leading to a high radiation dose and long image acquisition time. New image reconstruction methods would greatly reduce the number of projections without substantially sacrificing image quality. In sparse‐view imaging, strong streak artifacts may appear in conventionally reconstructed images, compromising image quality. Compressed sensing algorithm has shown potential to accurately recover images from highly incomplete data. The main feature of our algorithm is the use of two sparsity transforms: discrete wavelet transform and discrete gradient transform, both of which are proven to be powerful sparsity transforms. We reconstructed canine prostate images with filtered back projection and our compressed sensing algorithm using 50, 100, 120, 150, and 180 projections. Our results demonstrate that our proposed method can produce satisfactory images from only 150 projections. Research funding was provided by the Saskatchewan Health Research Fund.
Different effects of aerobic and anaerobic exercise on the capillary in the extensor digitorum longus: PGC‐1a, VEGF, Flk‐1 and Capillary Architecture.
Authors: Murakami Shinichiro , Fujita Naoto , Morifuji Takeshi , Kanasasi Miho , Sakita Masahiro , Kondo Hiroyo , Momota Ryusuke , Ohtsuka Aiji , Fujino Hidemi
Published: June 2021

The rat extensor digitorum longus (EDL) muscles that performed to the different intensities of exercise were used as representatives of fast muscles. Kind of the intensity of exercise to rats was chosen by aerobic low‐intensity (LO) or anaerobic high‐intensity (HI) either. And they were compared with the rat did not do exercise (Cont). Fiber cross‐sectional area and capillary density were not different. Mitochondrial oxidative capacity from SDH of performed LO or HI was higher than that of Cont. And these increased mitochondrial oxidative capacity had different pattern according with muscle fiber type respectively. Moreover level of PGC‐1a was high in order of Cont, LO and HI. Capillary volume and capillary diameter were different, LO was higher than Cont. Moreover HI was higher than Cont and LO. The expression level of VEGF f was not different. However level of vascular endothelial growth factor receptor 2 (Flk‐1) was high in order of Cont, LO and HI. It may be that the effect of the capillary in fast muscle performed exercise is based on the increase in Flk‐1 instead of the increase in VEGF.
Rufy1 or Hnrnph1 is a likely quantitative trait gene for methamphetamine sensitivity
Authors: Bryant Camron D , Parker Clarissa C , Guido Michael A , Kole Loren A , Goldberg Lisa R , Kirkpatrick Stacey L , Sokoloff Greta , Lim Jackie , Cheng Riyan , Palmer Abraham A
Published: June 2021

Sensitivity to the locomotor stimulant properties of drugs of abuse is a heritable trait and its genetic basis may be shared with alleles that modulate activation of the mesolimbic reward pathway. We previously used mouse lines derived from C57BL/6J and DBA/2J alleles that were selected for high and low methamphetamine (MA) sensitivity and identified a genome‐wide significant quantitative trait locus (QTL) on chromosome 11. In order to further pursue this QTL, we utilized the power of an F2 cross and the iterative nature of interval‐specific congenic lines in an effort to identify the causal gene(s) underlying this QTL. The results of F2 mice and the larger congenic lines revealed two large‐effect QTLs for MA‐induced locomotor activity; however, the phenotypic results of the smaller subcongenic lines revealed additional smaller effect QTLs with different modes of inheritance. One subcongenic locus converged remarkably well with the QTL peak in the F2 cross and altered methamphetamine sensitivity in a time‐dependent manner. We generated eight sub‐subcongenic lines derived from this subcongenic line (17 congenic lines total). Owing to a fortuitous recombination event, we identified and replicated a 0.23 Mb region spanning 50.17–50.40 Mb that was critical for MA sensitivity. This region contains only three genes (Rufy1, Hnrnph1, and Cby3) and only two of these genes are expressed in the brain (Rufy1 and Hnrnph1). This study exemplifies how a careful and detailed use of congenic lines can yield narrow QTL intervals and a tractable number of genes for quantitative trait gene identification.
Moderate intensity exercise does not modulate myostatin and follistatin gene expression in the gastrocnemius muscle of spontaneously hypertensive rats with heart failure
Authors: Damatto Ricardo Luiz , Pagan Luana , Lima Aline , Cezar Marcelo , Martinez Paula , Bonomo Camila , Guizoni Daniele , Gomes Mariana , Okoshi Katashi , Okoshi Marina
Published: June 2021

The myostatin/follistatin pathway modulates skeletal muscle trophism. Physical exercise has an important role in the heart failure treatment. In this study we evaluated the effects of moderate aerobic physical training on myostatin and follistatin gene expression and trophism in the gastrocnemius of spontaneously hypertensive rats with heart failure. Sixteen‐month‐old SHRs and normotensive Wistar‐Kyoto (WKY) rats were assigned to sedentary or trained groups. Exercise was performed on treadmill, 30 min/day, 5 days/week, 12 m/min for 4 months. Transthoracic echocardiogram was performed at the end of experiment. Gene expression was evaluated by real time RT‐PCR. Fiber cross‐sectional area was measured in HE‐stained histological sections.

Statistical analysis

two‐way ANOVA and Tukey.

Results

Echocardiography showed left cardiac chambers dilation and left ventricular systolic and diastolic dysfunction in both SHR groups compared to the WKY groups. Gene expression of myostatin and follistatin did not differ between groups. Cross‐sectional area was reduced in both SHR groups compared to WKY and was not changed by exercise.

Conclusion

Physical exercise does not modulate skeletal muscle trophism and myostatin and follistatin gene expression in spontaneously hypertensive rats with heart failure.