bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of pentobarbital anesthesia on “intrinsic” heart rate.
Authors: Billman George Edward , Cagnoli Kristen L.
Published: June 2021

While it is well established that pentobarbital alters cardiac autonomic regulation, the effects of this anesthetic agent on intrinsic heart rate (HRi) remain to be determined. Therefore, HRi, was measured in purpose‐bred mixed breed dogs (n = 11, 22.2 ± 0.9 kg, age 1–3 y) by means of combined adrenergic (propranolol HCl 1.0 mg/kg, i.v.) and muscarinic (atropine sulfate 50 ug/kg iv.) receptor inhibition before (Control, Con) and, at least one week later, during pentobarbital anesthesia (Pen, 30–40 mg/kg, i.v). Pentobarbital significantly (ANOVA, P<0.01) depressed the high frequency component (0.24 – 1.04 Hz, an index of cardiac parasympathetic regulation) of heart rate variability (Con, 7.2 ± 0.4 vs. Pen, 1.0 ± 0.4 ln ms2) and increased baseline heart rate (Con, 105.9 ± 8.7 vs. Pen, 139.1 ± 6.8 beats/min) but decreased HRi (Con, 148.7 ± 6.7 vs. Pen, 128.9 ± 5.3 beats/min). The nonselective adenosine antagonist aminophylline (10 mg/kg, i.v.) did not alter heart rate variability (0.4 ± 0.3 ln ms2) but restored HRi to control (i.e., without pentobarbital) values (141.5 ± 6.7 beats/min). These data suggest that pentobarbital both alters cardiac autonomic regulation and depresses intrinsic heart rate. These data further indicate that the activation of adenosine receptors may play an important role in this apparent depression of cardiac pacemaker rate.
Carboxyl terminus of Hsp70‐interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise
Authors: Willis Monte S , Min Jin‐Na , Wang Shaobin , Wadosky Kristine M. , Patterson Cam
Published: June 2021

The carboxyl terminus of HSP70‐interacting protein (CHIP) is a ubiquitin ligase/co‐chaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP −/−) suffer decreased survival, enhanced myocardial injury, and increased arrhythmias compared to wild type controls following challenge with cardiac ischemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone‐assisted selective autophagy, a process that is associated with exercise‐induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP −/− mice with voluntary exercise. CHIP −/− mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP −/− mice by serial echocardiography over the five weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signaling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in regulating Akt signaling, induced by voluntary running in vivo.
Higher volume of physical activity in the past year is associated with enhanced left ventricular diastolic function and exercise capacity and lower pressure wave reflection in healthy adolescents: no relation with time in sedentary activities
Authors: Pierce Gary L , Pajaniappan Mohanasundari , DiPietro Amy , Darracott Katherine V , Guinter Mark , Kapuku Gaston
Published: June 2021

We hypothesized that higher volume of physical activity (PA) in the past year would be associated with enhanced left ventricular (LV) diastolic function, exercise capacity and lower wave reflection in adolescents independent of time in sedentary activities (e.g., television viewing, etc.). Sixty healthy adolescents (age 16.4 ± 0.2 yrs) were studied. Subjects with higher (HPA, n=30, 25.7 ± 2.3 hrs/week) vs. lower (LPA, n=30, 6.9 ± 0.7 hrs/week) time spent performing PA in the past 12 months (Youth Adolescent Activity Questionnaire) demonstrated greater LV diastolic E/A (echo Pulsed doppler: 2.20 ± 0.07 vs. 1.90 ± 0.06, P<0.01), e′ (echo Tissue doppler: 0.19 ± 0.1 vs. 0.17 ± 0.1 m/s, P=0.03), VO2peak (40 ± 2 vs. 31 ± 2 ml/kg/min, p<0.01), exercise test duration (11.9 ± 0.5 vs.10.1 ± 0.4 min, P<0.01) and lower wave reflection (carotid aug index, −11.83 ± 2.6% vs. −4.77 ± 2.2%, P<0.05) compared with LPA. In the entire cohort, PA was associated with mitral E/A (r=0.31, P<0.02), e′ (r=0.30, P=0.05), carotid AI (r=−0.29, P<0.05), VO2peak (r=0.27, P<0.05) and exercise test duration (r=0.39, P<0.01). All relations except e′ remained significant after adjustment for time spent performing sedentary activities. Higher volume of PA in the past year is associated with enhanced LV diastolic function and exercise tolerance and lower wave reflection in healthy adolescents independent of time performing sedentary activities.
Intramuscular doxorubicin accumulation and skeletal muscle fatigue: effects of prior exercise
Authors: Quinn Colin , Gibson Noah , Bredahl Eric , Schneider Carole , Hayward Reid , Hydock David
Published: June 2021

The anthracycline antibiotic doxorubicin (DOX) has been shown to accumulate in skeletal muscle and result in muscle fatigue, but the role that exercise plays in DOX accumulation and fatigue in skeletal muscle is unclear. The purpose of this study was to examine the effects of exercise prior to DOX administration on intramuscular DOX accumulation and skeletal muscle fatigue. Ten‐week old, male Sprague‐Dawley rats were randomly assigned to an endurance training group (treadmill training), a resistance training group (raised food/water), or a sedentary group for 10 weeks. After the activity treatment period, animals received DOX or saline as a control. One day after injection, the soleus and extensor digitorum longus (EDL) were excised, and fatigue was analyzed ex vivo. DOX levels in the soleus and EDL were then quantified using high performance liquid chromatography. The endurance and resistance training models employed attenuated the increased muscle fatigue associated with DOX treatment, but this reduction in fatigue was not associated with decreased intramuscular DOX levels. This suggests that the beneficial effects of exercise on DOX‐induced skeletal muscle fatigue observed one day following treatment are not necessarily attributed to reduced intramuscular DOX levels.
EFFECTS OF PHYSICAL TRAINING IN CHRONIC LOW BACK PAIN PATIENTS. IMPORTANCE OF VO2max CRITERIA DURING ERGOMETRIC TESTS
Authors: Duque Ivan Leonardo , Duvallet Alain
Published: June 2021

Nowadays physical deconditioning is both a cause and a consequence of chronic low back pain. Health professionals recognize physical exercise as an important compound of chronic low back pain treatment programs; nevertheless published data concerning aerobic capacity in those patients are inconsistent.

An accurate measurement of VO2max is necessary to establish the effect of physical training on aerobic capacity.

101 patients with chronic low back pain underwent a 5week physical restoration program including exercises to improve maximal aerobic capacity.

The use of the primary criterion and secondary criteria (heart rate, respiratory quotient and lactatemy) for obtaining VO2max or VO2peak values during a maximal exercise protocol before and after training led to the establishment of 4 groups of patients. Comparison of VO2 values before and after training was made using a paired t test. VO2max improved significantly only in subjects achieving VO2max values before and after training.

Our study is the first to demonstrate that to determine the evolution of VO2max with training in chronic low back pain patients it is necessary to consider specific metabolic parameters. The inability for all patients to achieve these parameters explains, at least in part, the contradictory results published in the literature.
Whole hydro‐ethanolic Echinacea purpurea (L.) Moench attenuates lipopolysaccharide‐induced inflammation in the uterine cervix of mice via the heme‐oxygenase‐1 pathway
Authors: Coe Ben , Estes Jordan , Nguyen Bao‐Tran , Howington Robert , Ohashi Takako , McCoy JoeAnn , Okunji Chris , Mowa Chishimba
Published: June 2021

Because current treatments for preterm labor are either unsafe or ineffective and bacteria‐induced preterm labor is the leading cause of premature birth, here, we sought to test whether use of a natural product with anti‐bacterial and ‐inflammatory activities and a long history of safe use, namely Echinacea purpurea (L.) Moench (whole hydro‐ethanolic), could be used to attenuate bacteria‐ (lipopolyssacharide, LPS)‐induced inflammation in the mice uterine cervix. We initially optimized routes and dosages of the extract, and then deciphered the likely underlying mechanism by treating animals with either vehicle only, or a combination of whole hydro‐ethanolic root extract, LPS, and/or heme‐oxygenase 1 (HO‐1) inhibitor, dose‐dependently. Tissues were then harvested and evaluated using real time‐PCR, Western blot, histology and confocal immunofluorescence. Our data show that the extract promotes expression of HO‐1 mRNA and HO‐1 inhibitor blocked the protective effects of the extract in animals treated with LPS, dose‐dependently. We conclude from these findings that Echinacea could potentially be used to modulate inflammation‐induced preterm labor and that HO‐1 may mediate the anti‐inflammatory activities of E. purpurea in the uterine cervix. Funding: Office of Students Research, Appalachian State University.
NHE8 plays important roles in male fertility
Authors: Xu Hua , Chen Huacong , Li Jing , Ghishan Fayez K
Published: June 2021

Testes have the dual function of producing sperm and testosterone. Multiple sodium/hydrogen exchanger (NHE) isoforms are expressed in the testes. NHE2 and NHE3 are expressed on the apical membrane of epithelial cells in the efferent and epididymal ducts. The testes of mice lacking NHE3 function have increased fluid volume, which leads to diminished sperm concentration and subfertility. NHE10 is an NHE isoform found in the spermatozoa. Mice lacking of NHE10 are completely infertile due to severely diminished sperm motility. NHE8 is the newest member of the NHE family. Male mice lacking NHE8 are infertile. The overall histological structure in the testes is similar between NHE8KO mice and wild type mice. NHE8KO mice have smaller testis and severely reduced serum testosterone level. NHE8KO male mice have very low number of spermatozoa in the epididymis and virtually none reached the vas deferens. PCR and Western blotting revealed that NHE8 expression is highly abundant in the testes. Immunohistochemistry located NHE8 protein in Leydig cells and in epididymal duct cells. High expression of NHE8 in the Leydig cells and low serum testosterone level in NHE8KO males strongly suggest a critical role for this new NHE isoform in Leydig cell physiology. This study is supported by NIH grant R01DK073638.
DIFFERENTIAL GENE EXPRESSION PROFILES PRODUCED BY A HIGH FAT DIET IN WHITE AND BROWN ADIPOSE
Authors: Faulkner Jessica L , Gomolak Jessica R , Garrett Michael R , Didion Sean P
Published: June 2021

The goal of the present study was to determine gene expression profiles that change in response to a high fat diet (HFD) in white and brown adipose. Male C57Bl/6 mice were fed a control (10% kcal) or a HFD (60% kcal) for 12 wks. Genome‐wide expression profiles were examined in five adipose depots (epididymal (EPAT), perirenal (PRAT), subcutaneous (SCAT), perivascular (PVAT), subscapular (SSAT)) using the Affymetrix platform (GeneChip® Mouse 1.0 ST Array). Expression differences were analyzed using ±2‐fold change (P<0.05) and gene network analysis was performed using Ingenuity Pathway Analysis. In PVAT and SCAT, 21 and 45 genes respectively were found to be differentially expressed. In brown SSAT, 47 genes were differentially expressed; 25 of which were downregulated by 11‐ fold or greater and were classified as muscle‐specific. 130 and 41 genes were found to be differentially expressed in visceral EPAT and PRAT, respectively. In both EPAT and PRAT a number of genes related to inflammation were upregulated. Overall, GPR50 (an orphan receptor implicated in metabolism) had the greatest change in expression (29‐ & 60‐fold increase) in response to a HFD in PRAT and EPAT, respectively. In total, these data demonstrate that in response to a HFD there are gene expression profiles that are shared between adipose depots as well as genes/pathways that differentiate adipose types. Supported by NIH HL‐089884 & HL‐107632.
Fossils, genes, and the origin of organs
Authors: Shubin Neil H
Published: June 2021

Comparative anatomy, fossils, and genetic analyses form complementary approaches in understanding the origin of anatomical novelties. One such novelty, the tetrapod limb, has long been an area of inquiry by paleontologists, anatomists and developmental biologists. Each of these datasets enable us to peer inside the structure and regulatory genome of fins to find antecedents of limb structure and developmental mechanisms in the appendages of basal vertebrates.
Gluteus Maximus Tendon Variability
Authors: Taylor Victor , Wood Addison , Seaman Travis , Crofford Theodore , Guttmann Geoffrey , Reeves Rustin
Published: June 2021

Introduction

As part of a series of dissections geared towards an improved anatomical understanding of Greater Trochanteric Pain Syndrome, it was observed that there were multiple tendons from the gluteus maximus inserting on the femur. In this study, the variability of the gluteus maximus tendon insertion was examined.

Method

The experiment was done on 40 partially dissected, embalmed bodies that were donated through the Willed Body Program at the University of North Texas Health Science Center. The gluteus maximus muscle belly was detached from the iliac crest. In addition, the iliotibial band was cut from the origin (ilium) and reflected to gain access to the gluteus maximus tendon. The fat in the area around the greater trochanter was cleaned until the tendon of the gluteus maximus was revealed.

Results

22 hips had only one tendon from the gluteus maximus inserting on the femur (13 on the right and 9 on the left), 19 hips had 2 tendons inserting (10 on the right and 9 on the left), 7 with 3 insertions (5 on the right and 2 on the left), and 1 with 4 insertions on the left side. When sex was separated, women had more insertions with 2 tendons than insertions with 1 tendon.

Conclusion

It has been shown that there are multiple tendons from the gluteus maximus inserting into the femur.
Lateralization in the vascular supply to the mammary gland
Authors: Bata Barbara , Ubrankovics Anett , Bayadsi Haytham , Molnár Béla Ákos , Székely Andrea Dorottya
Published: June 2021

The aim of the study was to detect the distribution of the medial perforator branches within the 4 quadrants of the mammary gland, based on the fact, that malignomas of the medial quadrants have a worse prognosis than those in the lateral quadrants. The medial side of the mammary region is dominantly supplied by the internal mammary artery (IMA), whereas the lateral quadrants receive their blood supply from the lateral thoracic, thoracoacromial and intercostal perforator arteries.

All interventions were executed according to the Ethical Guidelines of the Semmelweis University and the WMA Declaration of Helsinki ‐ Ethical Principles for Medical Research Involving Human Subjects. Two male and four female formaldehyde fixed hemithoracal specimens were dissected to follow the course of the IMA and the internal mammary vein (IMV) between the 1st and 7th intercostal spaces. The largest perforators were apparent only in the first three intercostal spaces reaching into the lateral quadrants. The arterial perforator branches arose either separate or together with the anterior intercostal branches occasionally encircling the IMV from lateral before emerging through the intercostal space, then piercing the pectoralis muscle. As a next step, the distribution of the medial and lateral perforator branches were observed in coronal and sagittal CT and/or PETCT images to identify their positions relative to tumor location.

Grant Funding Source: N/A
Targeting Lsr2/DNA complexation for dysregulation of gene expression in Mycobacterium Tuberculosis
Authors: Pinault Lucile , Han Jeong‐Sun , Kang Choong‐min , Franco Jimmy , Ronning Donald R.
Published: June 2021

The identification of new drug targets and mechanisms of action against tuberculosis has become urgent, as the emergence of drug‐resistant strains has made many treatments ineffective. Lsr2 is a protein encoded by the Mycobacterium tuberculosis genome that acts as a global repressor of transcription by binding AT‐rich promoter regions of the mycobacterial DNA. Inhibiting this function could potentially dysregulate a wide array of genes, as Lsr2 binds about 20% of the Mycobacterium tuberculosis genome. Described here are experiments demonstrating that Zafirlukast is able to disrupt the Lsr2/DNA complex. This ability was shown in vitro using a fluorescence polarization assay. This compound also exhibits growth inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis on a Kirby Bauer assay but shows no activity against Escherichia coli. Transcription levels of genes shown to be bound by Lsr2 have been monitored in vivo after applying the drug to a culture of Mycobacterium tuberculosis and the results suggest that Zafirlukast promotes dysregulation of mycobacterial transcription. This drug is already commercially available and is commonly used as a treatment for asthma. As its mechanism of action appears to be distinct from current drugs against tuberculosis, it offers a new potential lead for the treatment of this disease.
Influence of education sources on osteoporosis knowledge and calcium intake in adult women
Authors: Enright Amanda , Bai Yeon
Published: June 2021

Osteoporosis prevention among women requires obtaining proper knowledge early in life about the disease, risk factors and treatments. This study's aim was to compare specific education sources to osteoporosis knowledge and calcium intake. Women between ages 18 and 40 completed an online survey that measured osteoporosis knowledge, calcium consumption, and specific education source within categories of age, school classes, television, radio, newspaper, magazine, internet and in‐person. Multiple regression analysis was performed to determine influential education sources for osteoporosis knowledge and calcium intakes. Mean age for participants was 28.7± 4.4 years; mean knowledge score was 13.8 ± 3.3 (score 16 or above is “adequate knowledge”); average daily calcium intake was 1315.1 ± 609.9 mg. Age and newspaper had greatest contribution towards osteoporosis knowledge, while internet, school classes and radio were most influential on calcium intakes. Creating an osteoporosis education initiative utilizing these sources is imperative for increasing disease knowledge and preventive behavior among young women.
Examining the effects of increased vitamin D fortification on dietary inadequacy in Canada
Authors: Shakur Yaseer A , L'Abbe Mary R
Published: June 2021

Despite mandatory fortification of milk and margarine, most Canadians have inadequate vitamin D intake and consequently poor vitamin D status. Inclusion of more foods to be fortified and increasing the levels of fortification are possible strategies to address this inadequacy. We used dietary intakes (24‐h recall) from the 2004 Canadian Community Health Survey 2.2 (n = 34,381) to model the effectiveness of increased vitamin D fortification by determining the prevalence of vitamin D inadequacy and percent of intakes >;Tolerable Upper Intake Level (UL) based on several fortification scenarios. Doubling of milk fortification, and fortification of yogurt and cheese at 6.75 μg/serving led to more than doubling of vitamin D intakes across all sex/age groups and a drop in the prevalence of inadequacy from >;80% to <50% in all groups. Furthermore, no intakes approach the UL under any fortification scenario in any sex/age group. Given the pressing need to improve vitamin D status among Canadians, and the fact that increasing vitamin D in dairy products can lead to increased intake without a risk of excess, increased fortification is a population wide strategy that should be given consideration in Canada. (Funded by the Dairy Farmers of Canada)
The impact of food assistance on nutritional status and disease severity among HIV‐positive, antiretroviral therapy ineligible, individuals in Uganda
Authors: Kadiyala Suneetha , Maluccio John , Faust Elizabeth , Rawat Rahul
Published: June 2021

The complex relationship between food insecurity, undernutrition, and HIV has been well established for over a decade. However, data on the potential benefit of food security and nutrition interventions to people living with HIV (PLHIV) is sparse.

We conducted a quasi‐experimental impact evaluation of World Food Program's food assistance program, provided for 12 months, with a matched control group (matched at district, household and individual levels), among 902 anti‐retroviral therapy (ART) naive PLHIVs (451 per arm) receiving HIV services from The AIDS Support Organization (TASO) in Northern Uganda. The primary impacts of interest were changes in a) nutritional status—body mass index (BMI), mid‐upper arm circumference (MUAC), and hemoglobin (Hb) and b) disease severity (CD4 count).

Utilizing propensity score matching techniques to account for endogeneity, we find significant positive impacts of food assistance on nutritional status, but not CD4 count. Food assistance significantly increased BMI by 0.6 kg/m2 (p< 0.01), and MUAC by 8.3 mm (p< 0.05). These results remained significant, and of similar magnitude when controlling for CD4 trend. Food assistance resulted in an increase of Hb count by approximately 0.5g/dl only among those with CD4>;350 cell/mm3. This study adds to the limited evidence base of the impact of nutrition interventions to PLHIVs, particulary among those not receiving ART.
Proanthocyanidin intake is inversely associated with advanced prostate tumor stages in newly diagnosed prostate cancer patients
Authors: Wang Ying , Vance Terrence M. , Su Joseph , Fontham Elizabeth T.H. , Bensen Jeannette T. , Mohler James L. , Chen Ming‐Hui , Chun Ock K.
Published: June 2021

Data from the North Carolina‐Louisiana Prostate Cancer Project, a population‐based study of incident prostate cancer in African Americans (n=698) and Caucasian Americans (n=904) was used to determine the association between proanthocyanidin (PA) intake and prostate tumor stage at diagnosis. PA intake was calculated from modified NCI DHQ food and nutrient database. Associations between dietary PA and tumor stage were determined by logistic regression analyses. After adjusted for other risk confounders, the odds ratio for advanced tumor stages (T3, T4) was 0.06 (95% CI: 0.01–0.50) for men in the highest quartile of PA intake. Among the sociodemographic characteristics, PSA screening was a strong predictor of advanced tumor stages (p<0.01). PA intake was inversely associated with advanced tumor stages (p<0.01). Mediation analysis revealed that the relationship between PSA screening and tumor stage was attenuated after adding PA intake into the model by changing 19% of beta coefficient. These findings demonstrate that PA intake is a mediator of PSA screening in association with advanced prostate tumor stages.

Grant Funding Source: NIH Cancer Epidemiology Small Grant #1R03CA159421–01A1
Longitudinal changes in body habitus in college freshmen
Authors: Hootman K C , Guertin K A , Cassano P A
Published: June 2021

BACKGROUND

The first year of college is a transition period during which changes in body habitus are common.

METHODS

A large representative sample of freshmen at Cornell University was studied over the first year, with repeated assessments of anthropometry and body composition via dual‐energy x‐ray absorptiometry (DXA).

RESULTS

Among 184 participants with complete data (47% male), 75% gained weight during fall semester, and the mean increase was 1 kg greater in males (p=0.0067). When comparisons were limited to participants who gained weight, the mean change was 3.7 kg (SD 2.2) and 2.6 kg (SD 1.7) in males and females, respectively (p=0.0140). Change in adiposity, estimated by body mass index (BMI), paralleled weight changes, and females increased 0.3 units less compared to males (p=0.0098). The change in DXA body fat percent (BF%), over the academic year, supported anthropometric findings for the first semester. Thus, among those who gained weight in the fall, the increase in BF% was significantly greater in males compared to females, with a change of 1.7% (SD 1.4) and 1.1% (SD 1.9), respectively (p=0.0407).

CONCLUSIONS

Weight gain during freshman year is not universal, primarily indicates adiposity gain, with males gaining more in absolute and relative indicators.

Grant Funding Source: This research was supported by internal funding from Cornell University, and by NRSA Institutional Research Training Grant T32‐DK‐7158–36 (KH)
Dietary factors affecting weight gain in midlife women
Authors: Chopra Vani , Perry Courtney , Reicks Marla
Published: June 2021

Weight gain at midlife increases risk of chronic diseases and physical dysfunction in later life. The purpose of this study was to determine how dietary intake and weight maintenance strategies affected weight gain over 24 months among a sample of midlife women (40–60 years) in the Minneapolis/St. Paul metropolitan area. Baseline and 24‐month weight and 3‐day dietary intake data (Nutrition Data System for Research protocol) were used from women in an untreated control group (n=104) as part of a larger intervention study. Use of weight maintenance strategies was assessed retrospectively at 24 months. Women were divided into 2 groups according to weight change over 24 months (loss/maintain ≤ 0 kg (n=45) and gain >;0 kg) (n=59). Mean baseline BMI was 27.3 ± 5.5 with the gain group having significantly higher BMI at 24 months (p<0.0001). The gain group significantly increased intakes of energy, total fat, saturated and unsaturated fat over 24 months compared to the loss/maintain group. However, no significant differences were observed in change in most other nutrients or food group intakes between groups. Dietary restraint and use of various weight maintenance strategies also did not differ between groups. Differences in energy and fat intakes between groups were not reflected in changes in food group intakes or reported use of weight maintenance strategies. Research support: USDA NRI 2007
Effect of high dietary protein intake on body fat mass and subcutaneous adipose tissue gene expression in humans
Authors: Blokker Britt , Rietman Annemarie , Schwarz Jessica , Siebelink Els , Kok Frans , Müller Michael , Tomé Daniel , Afman Lydia , Mensink Marco
Published: June 2021

Increased protein intake is suggested to prevent adipose tissue mass gain thus being a promising weight management tool. Yet, no mechanistic explanations are available

The objective was to study the effect of increased protein (P) at the expense of carbohydrate (CH) during overeating on body composition and pathways of energy storage in adipose tissue (AT).

A controlled dietary intervention was performed in healthy subjects (male and female, n=27) who were assigned to 1 of 3 intervention groups. One group was given a balanced diet for 4 weeks. In a 2‐weeks cross‐over design 2 groups received a hypercaloric diet of +2 MJ/day extra with either high protein (HP, 40 en% fat; 26 en% P; 34 en% CH) or normal protein (NP, 40 en% fat; 15 en% P; 45 en% CH). Body composition (DEXA) and gene expression in subcutaneous AT biopsies (qPCR) were studied after 2 and 4 weeks of intervention.

Fat mass gain was lower on HP compared to NP (−270g; p=0.02). No changes in expression of a selection of genes involved in fatty acid uptake, de novo lipogenesis, lipid storage, lipolysis and β‐oxidation were observed between diets.

Increasing protein at the expense of carbohydrates in a hypercaloric diet attenuates fat mass gain but does not alter the expression of genes involved in energy storage in subcutaneous AT. Changes in total fat mass may be explained by changes in visceral fat.

This research was supported by the Dutch Dairy Organisation (NZO).
Kimchi Suppressed AOM/DSS Induced Colitis‐associated Colon Cancer in Balb/c Mice
Authors: Park Kun‐Young , Kim Hee‐Young , Kang Soon‐ah
Published: June 2021

We evaluated the preventive effect of kimchi prepared with different ingredients on Azoxymethane(AOM) / dextran sulfate sodium(DSS) induced colitis‐associated colon cancer(CAC). Mice (Balb/c, male) were injected with AOM (10mg/kg), and then the mice received 2% of DSS in the drinking water for 7 day. After injection of 2 weeks, methanolic extracts from commercial ‘J’ kimchi (JK), standard kimchi (SK), cancer preventive kimchi (CPK) and anti‐cancer kimchi (ACK) were orally administrated for the next 4 weeks. High dose of ACK significantly decreased the ratio of colon weight/length ((36.18±5.92 mg/cm, p<0.05), and showed the least tumor numbers than the other groups. Histological observation suggested that ACK (p<0.05) suppressed mucosal damages. ACK also significantly reduced mRNA and protein expressions of iNOS and COX‐2 (p<0.05) in the colon tissue. In addition, ACK incrreased p21 and p53 expressions in the colon tissue compared to the other groups(p<0.05). Those results suggest that kimchi has a suppressive effect on AOM/DSS‐induced CAC in Balb/c mice, especially anti‐cancer kimchi possibly be used as a health functional food to prevent colon cancer.
Association Between Single Nucleotide Polymorphism Pro198Leu of Glutathione Peroxidase and Normal Weight, Overweight and Obesity in Mexican Population
Authors: Hernandez Cesar , Parra Alicia , Trejo Cristina , Diaz Carmen , Olguin Atziri , Perez Ana
Published: June 2021

The study included Mexican participants with at least two generations of relatives born in Mexico. The control and study groups were selected from the Clinic of Nutrition of Health Department of the Universidad Iberoamericana from Mexico City. The control group included 45 participants with a body mass index (IMC) of: 18.5–24.9. The overweight group included 32 participants with IMC of: 25.0–29.9, and the obesity group included 48 participants with IMC >;30. DNA was isolated by DNAzol reagent. The identification of SNP Pro198Leu was done by Polymerase Chain Reaction technique using specific primers, follows of Restriction Fragment Length Polymorphism technique using the ApaI restriction enzyme. The frequency of polymorphism was analyzed by Xi squared and a p<0.05 was accepted as a statistical difference. The frequencies of SNP Pro198Leu (heterozygote: Pro/Leu plus homozygote: Leu/Leu) were 0.40, 0.68 and 0.60 in control, overweight and obesity groups, respectively. There was a statistical difference between overweight and control group (Xi2= 5.09; p=0.024; O/R= 3.3; I.C. 95% 1.26 – 8.58). There was not statistical difference between the obesity and control group or when the obesity group was stratified by degrees of disease. The polymorphisms Pro198Leu could be one of several genetic factors involved in the susceptibility to development overweight in the Mexican population. The Universidad Iberoamericana provided funding for the study.
Targeting mTOR signaling for the prevention of progenitor‐derived hepatocellular carcinoma
Authors: Sanders Jennifer A , Brilliant Kate , Francois Heather , Mills David
Published: June 2021

Progenitor cell activation occurs under conditions of severe liver injury and a subset of hepatocellular carcinomas (HCC) express progenitor cell markers. However, the signaling pathways involved in the initiation and progression of progenitor‐derived HCC have not been characterized. The objective of the present study was to characterize the effect of mTOR inhibition on the development and progression of progenitor‐marker positive hepatocellular carcinoma in an established rodent model. mTOR signaling was robustly activated during the early stages of preneoplastic foci development. However, activation of this pathway waned during the progression to persistent foci. To assess the functional role of mTORC1 in foci development and progression, the effect of the mTORC1 inhibitor, rapamycin, was studied. Rapamycin administration decreased the size of preneoplastic foci and the rate of cell proliferation within the foci at both early and late time points. These studies reveal a critical role for mTORC1 in the initiation of carcinogenesis therefore rapamycin may be an effective chemopreventative agent for progenitor‐derived HCC.
The role of sigma‐1 receptor in neuropathic pain.
Authors: Mirrielees Jennifer Ann
Published: June 2021

Sigma‐1 receptor (S1R) function has been correlated with the establishment of neuropathic pain via pharmacological and gene knockout studies. We have identified a novel role for S1R in pain as a modulator of the substance P receptor, NK1R. Here we describe an interaction between S1R and the non‐glycoyslated form of NK1R by co‐immunoprecipitation. Cell surface biotinylation reveals that this interaction is relevant both intracellularly and on the plasma membrane. We have additionally localized the interacting region of NK1R to the second transmembrane domain. Additionally, we report an enhancement of both NK1R mRNA and protein expression when co‐expressed with S1R in HEK293 cells, and a complementary reduction using S1R‐targeting shRNA. NK1R function as assessed by calcium transients is enhanced from 44.49% ± 5.40% of peak effect to 94.64% ± 8.46% by overexpression of S1R. We have also documented that 94.5% ± 7.3% of peptidergic dorsal root ganglion (DRG) neurons express S1R, providing substantial anatomical overlap with NK1R. To recapitulate our in vitro findings, we have demonstrated that S1R knockout mice exhibit greatly diminished NK1R expression in the DRG and spinal cord. We conclude that S1R acts to increase expression and activity of critical pain pathway signaling components via two distinct mechanisms: modulation of gene expression, and a direct protein:protein interaction.
Early effects of acute doxorubicin treatment include increased apical caspase expression and activation in liver, but not heart, of fasted animals
Authors: Dirks‐Naylor Amie Jeanette , Bero Joseph D. , Tran Ngan T.K. , Mabolo Raean , Yang Sendra , Kouzi Samir A.
Published: June 2021

Doxorubicin (DOX) is an effective chemotherapeutic agent, but known to cause cardiotoxicitv via induction of oxidative stress and apoptosis. DOX also causes hepatic toxicity, although mechanisms have not been as extensively described. Currently, the mechanism of DOX induced hepatic apoptosis is unknown. Moreover, despite the anorexic effects of DOX very few studies have controlled for this and, therefore, it is not clear whether changes in apoptosis markers and signaling in vivo are due to direct or indirect effects of DOX. Thus, we aimed to determine the early effects of DOX on expression and activation of apical caspases in heart and liver and to delineate these effects from mal consumption of food and water. Male F344 rats were injected IP with 20 mg/kg of DOX or saline. Once treated, all animals were fasted with no food or water until sacrifice 24 hours later. DOX did not affect expression or activation of caspase‐1, ‐8, ‐9, ‐12 in the heart at 24‐hour post treatment. However, DOX increased procaspase‐9 expression and caspase‐12 activation in liver. These results may suggest that at an early time point after acute DOX administration, the liver seems more vulnerable to DOX‐induced apoptosis compared to the heart. This may be explained by higher concentrations of DOX in liver compared to heart and/or the increased resistance to apoptosis in post‐mitotic cardiomyocytes compared to mitotic hepatocytes.
The analysis of the transmission rate of locally administered siRNA to blood
Authors: Kokuryo Toshio , Yokoyama Yukihiro , Nagino Masato
Published: June 2021

SiRNA is a promising therapeutic drug. Nek2 is a member of the serine/threonine kinase family. We previously reported the tumor suppressing effects of locally administered Nek2 siRNA (direct intra‐tumorous injection) in several cancer xenograft models. However, there is little information regarding to the pharmacokinetics of locally administered siRNA. This study sought to elucidate the transmission rate to blood and incidence of side effects after local administration of Nek2 siRNA in rat model. First, we mixed different amount of Nek2 siRNA with rat plasma (0, 1, 10, 100 and 500μM) and performed Northern blot analysis. Nek2 siRNA was detected in rat plasma in a concentration dependent manner. Next, the transmission of Nek2 siRNA to blood was evaluated after subcutaneous administration. Nek2 siRNA/biocollagen complexes were formed (500μM, 100μl) and were injected in femoral area. The blood was collected at different time point (5, 15, 30 and 60 min) and was analyzed by Northern blot. The detection of Nek2 siRNA in the blood was the highest at 15 min, and it disappeared within 1 h after the administration. There was no complication related to the local administration of Nek2 siRNA.

Our data suggest that the local administration of siRNA is a safe delivery procedure with little cytotoxicity. However, further investigation will be needed for the future clinical application of siRNA.
Effects of genetic strain and light intensity on blood physiological variables of broilers grown to heavy weights
Authors: OLANREWAJU HAMMED A , PURSWELL JOSEPH L. , COLLIER STEPHANIE D. , BRANTON SCOTT L.
Published: June 2021

The effects of genetic strain, light intensity and their interaction were examined on blood physiological variables of broilers maintained in environmentally‐controlled rooms in each of 4 trials. The study consisted of a factorial arranged in a randomized complete block design with 10 treatments of 2 strains (Ross × Ross 308 and 708) and exposure to 5 light intensities (25, 10, 5, 2.5, 0.2 lx). In each trial, chicks of 2 different strains were equally and randomly distributed into environmentally‐controlled rooms. Each room was randomly assigned one of five light intensities from d 22 to 56 d of age. Feed and water were provided ad libitum. Venous blood samples were collected on d 21 (base line) and d 56 of age. Ross × Ross 308 had significant (P ≤ 0.05) increases in BW, pCO2, Hct, Hb, Ca2+, Cl−, McHc, and angap along with significantly (P ≤ 0.05) reduced pH level, pO2, HCO3−, and glucose in comparison with Ross × Ross 708. The main effect of light intensity only affected pCO2, Ca2+, and Cl−. Acid‐base regulation in Ross × Ross 308 did not deteriorate despite increased blood pCO2, which consequently lowered blood pH due to a compensatory mechanism. Plasma corticosterone was not affected by treatments or strain. This study shows the positive impact on profits to commercial poultry producers that are using low lighting environment to reduce energy utilization costs without inducing physiological stress on broiler health.
TRPV4‐mediated responses of the rat isolated cremaster muscle artery
Authors: Murphy Timothy V , Kanagarajah Arjna , Senadheera Sevvandi , Sandow Shaun L
Published: June 2021

Transient receptor potential (TRP) channels are a family of ion channels with emerging roles in the vasculature. This study investigated the expression and function of TRPV4 channels in isolated, pressurized (70 mmHg) rat cremaster muscle arteries with myogenic tone. Immunohistochemistry showed TRPV4 was present at a low level in the endothelium and smooth muscle of the arteries. The TRPV4 activator RN1747 caused a concentration‐dependent dilation of the arteries (EC50 18.0 ± 0.2 μM, n = 14). The TRPV4 inhibitor RN1734 (10 and 30 μM) caused a modest rightward‐shift of the RN1747 concentration‐response curve. The Ca2+‐activated K+ channel (KCa) inhibitor TEA (1 mM) also inhibited responses to RN1747 and the effects of RN1734 and TEA were additive. RN1734 did not inhibit endothelium‐dependent vasodilation of the arteries induced by acetylcholine, but endothelium‐independent vasodilation caused by adenosine was inhibited by RN1734. TEA also inhibited responses to adenosine and the effects of RN1734 and TEA were additive. In conclusion, TRPV4 was present in the endothelium and smooth muscle of cremaster muscle arteries. Endothelium‐dependent acetylcholine‐mediated vasodilation did not occur via TRPV4 channels, but adenosine‐mediated vasodilation occurred via TRPV4. The role of KCa channels in TRPV4 responses remains to be clarified. RN1747 may be an agent of limited use in in vitro studies of the vasculature.
The SIRT6 deacetylase regulates aging‐associated heart failure by modulating IGF‐Akt signaling at the level of chromatin.
Authors: Gupta Mahesh , Sudaresan Nagalingam
Published: June 2021

The sirtuin SIRT6 is a chromatin bound enzyme which is implicated in extending lifespan of animals. However, the mechanism of longevity effects of SIRT6 is not known. This study was undertaken to test the effect of SIRT6 on the development of cardiac hypertrophy and heart failure. SIRT6 levels were significantly reduced in mouse aging hearts, and in hearts subjected to develop cardiac hypertrophy by trans‐aortic constriction or agonist infusion. To directly test the effect of SIRT6 deficiency on the development of cardiac hypertrophy, we deleted SIRT6 in the adult mouse heart (SIRT6KO). SIRT6KO mice spontaneously developed cardiac hypertrophy with sever fibrosis and degenerative changes in mitochondria. These hearts also expressed higher levels of aging associated cytoskeletal proteins, fibrotic markers and apoptotic genes. SIRT6KO hearts also had increased expression of several IGF‐Akt signaling related genes. Conversely, transgenic mice having cardiac specific overexpression of SIRT6 were resistant to develop cardiac hypertrophy, and these hearts had attenuated expression of aging associated proteins and IGF‐Akt signaling related genes. ChIP analyses reveled that SIRT6 regulates IGF‐Akt signaling genes by deacetylating H3K9. These data thus indicated that SIRT6 protects the heart from developing hypertrophy by blocking expression of IGF‐Akt signaling related genes at the level chromatin.
Differential effects of in vivo vs. cell culture hypoxia on neural progenitor cell expansion and differentiation
Authors: Ross Heather , Fitzpatrick Garrett , Sharififar Sharerah , Bernardo Joey , Sandhu Milap , Fuller David
Published: June 2021

We have recently shown that neonatal in vivo exposure to acute intermittent hypoxia (AIH) increases proliferation and neuronal differentiation in subsequently cultured subventricular zone–derived neurospheres (NS). Prior work has also established that stem cells cultured in sustained hypoxia (SH, 3% vs. 20% O2) demonstrate increased proliferation and neuronal differentiation. The objective of this study was to compare and contrast NS behavior when exposed to either SH during culture or AIH delivered in vivo just prior to cell harvest. Neurosphere forming cells were isolated from neonatal C57BL/6 mice or Sprague Dawley rats. For SH, cells were maintained in 3% O2 for the duration of culture. For AIH, neonates were subjected to alternating cycles (20×2 minutes) of 21% and 10% O2. Expansion analysis demonstrated that SH‐treated NS initially outperformed control and AIH‐treated NS. However, after extended culture (7–10 days), SH‐treated NS exhibited reduced expansion when compared to both controls and AIH‐treated NS (the latter outperformed controls at all time points, p<0.05). Thus, compared to SH, in vivo AIH pre‐conditioning yields a more robust NS population following prolonged culture. We conclude that hypoxia is a powerful tool for manipulating NS growth, and that the pattern of delivery may have differential “priming” effects during long‐term culture. Support: 5K12HD055929 (HHR); 1R01NS080180 (DDF).
Intermittent Hypoxia‐induced Pancreatic Beta Cell Dysfunction involves Mitochondrial ROS impaired Proinsulin processing
Authors: Wang Ning , Khan Shakil A , Nanduri Prabhakar R , Nanduri Jayasri
Published: June 2021

Sleep‐disordered breathing with apnea leads to several co‐morbidities including Type 2 diabetes. Intermittent hypoxia (IH) is a hallmark feature of recurrent apnea. In the present study, we examined the effects of chronic IH (30 days) on pancreatic beta cell function in C57BL6 mice. IH‐exposed mice exhibited elevated levels of fasting plasma insulin, but comparable glucose levels indicating development of insulin resistance. Glucose‐stimulated insulin secretion (GSIS) was impaired in IH exposed mice. IH had no significant effect on pancreatic beta cell morphology but exhibited decreased insulin content and elevated proinsulin to insulin ratio. mRNA and protein levels of prohormone convertase 1 (PC1), an enzyme involved in the proteolytic processing of proinsulin were down regulated in IH‐treated islets. IH increased mitochondrial reactive oxygen species (ROS) levels. Systemic administration of Mito‐tempol, a scavenger of mitochondrial ROS prevented the enhanced insulin secretion and restored the proinsulin levels to controls in IH exposed mice. These results suggest that mitochondrial ROS is an important cellular mechanism mediating IH induced beta cell dysfunction
Medical students applying newly learned anatomy knowledge as part of a mentoring and experiential learning environment with undergraduate and elementary students
Authors: Thang Christine Katie , Diaz Molly , Padilla Jessica , Ojukwu Kene , Lee Heajung , Schmalz Naomi , Wisco Jonathan
Published: June 2021

Anatomy Academy (AA) demonstrates the need for anatomy medical education to engage, motivate, and support mentorship that reinforces medical education, provides pre‐medical support, and promotes scientific knowledge and healthy lifestyles. AA pairs medical students with undergraduate and elementary school students in a curriculum consisting of anatomy, physiology, health education, and physical activity to supplement the California 5th grade PE standards. Each team consists of one medical, one undergraduate, and 5–6 5th grade students. Medical and undergraduate students lead the teams in learning followed by physical activity outdoors. Pre‐ and post‐ AA self‐evaluations are conducted to assess knowledge and confidence. Medical and undergraduate students reported feeling more confident in their teaching skills and scientific knowledge. 5th graders responded with higher knowledge scores and interest in science. Medical students enjoyed applying their medical knowledge through teaching and mentoring. Undergraduates found value in being mentored. This curriculum and framework could be utilized in the future to develop mentorship programs among students at different stages in their education. AA was supported by the Albert Schweitzer Fellowship and the UCLA Monica Salinas Fellowship.

Grant Funding Source: Albert Schweitzer Fellowship; UCLA Monica Salinas Fellowship