bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitrosative Stress in an Ovine Model of Acute Lung Injury
Authors: Esechie Aimalohi , Enkbaatar Perenlei , Horvath Eszter , Jonkam Collette , Hamahata Atsumori , Traber Lillian , Traber Daniel 
Published: June 2021

AIM: elucidate changes involved in nitrosative stress using an ovine model of ALI.METHOD: Sheep (n=5 per group) were surgically instrumented for chronic study. 5 days after surgery, the animals were randomly allocated as follows: Injury (instrumented; 3rd degree 40% total body surface area flame burn and insufflation with 48 breaths of cotton smoke under deep anesthesia) and sacrificed at the following time points post‐injury: T=4hr, 8hr, 12hr, and 24hr; control (instrumented; no injury). Data is reported as mean ± SEM. RESULTS: Pulmonary gas exchange decreased 24h post burn and smoke injury (p < 0.05) and correlated with increased lung water content at 18h and 24 h (p< 0.05). Inducible nitric oxide synthase (iNOS) expression increased after injury compared with the control groups; peak iNOS expression was at 12h post burn and smoke inhalation (p < 0.05 vs control). Plasma nitrate/nitrite (NOx) correlated with protein expression: plasma NOx values increased 12h post injury (p = 0.046). 3‐nitrotyrosine (index of reactive nitrogen species) increased after burn and smoke inhalation compared to control (p < 0.05, n=5). DNA damage was assessed by measuring repair enzyme, poly (ADP) ribose polymerase (PARP) which increased in the injury group (p < 0.05 vs control).CONCLUSION: Therapeutic interventions to mediate excess free radical production could ameliorate impaired pulmonary function associated with ALI.
Irreversible damage to rostral pontine nuclei in adult awake goats does not alter the ventilatory regulation of eupneic PaCO2 and the ventilatory response to hypercapnia
Authors: Bonis Joshua M , Davis Suzanne , Kiner Tom , Krause Katie , Qian Baogang , Pan Lawrence , Forster Hubert 
Published: June 2021

Controversies regarding the role of rostral pontine nuclei (RPN) in the control of breathing have prompted us to chronically implant microtubules into the rostral pons of 6 goats to assess the regulation of eupneic PaCO2 and the ventilatory response to hypercapnia following irreversible damage to RPN. All goats recovered uneventfully and 3 weeks after implantation PaCO2 and CO2 sensitivity were within normal limits. Whole body CO2 sensitivity was assessed by increasing inspired CO2 to 3, 5, and 7% at 5‐minute intervals, subsequent to breathing room air for 30 minutes. CO2 sensitivity was expressed as ΔVI/ΔPaCO2. Arterial blood was sampled during the control and min 4 of each hypercapnic level. As shown in the Table, CO2 sensitivity and resting PaCO2 were unaffected following sequential RPN damage (microtubule implantation, microdialysis probe insertion, and intra‐cranial ibotenic acid injection, respectively). We conclude that damage to RPN does not alter regulation of eupneic PaCO2 and the ventilatory response to hypercapnia.
CO2 sensitivity and resting PaCO2 are not significantly changed subsequent to RPN damage.

Pre‐implant
Post‐implant
Post‐microdialysis
Post‐ibotenic acid

CO2 sensitivity (l/min/mmHg)
2.24
2.25
2.08
2.30

Resting PaCO2 (mmHg)
40.24
39.57
38.67
40.00

No significant difference between variables by one‐way ANOVA (P<0.05). Supported by the Department of Veterans Affairs and NIH HL25739.
The Influence of Sex and Obesity Phenotype on Meal Fatty Acid Metabolism Before and After Weight Loss
Authors: Santosa Sylvia , Hensrud Donald D , Votruba Susanne B , Jensen Michael D 
Published: June 2021

Objectives: To determine whether meal fatty acid (FA) metabolism differs by sex and obesity phenotypes and to examine how weight loss (WtL) through diet and exercise affects meal FA trafficking.Methods: Before WtL (study 1) 13 obese men (ObM), 9 upper body obese (UbO) and 8 lower body obese (LbO) women consumed a standard meal containing [3H]triolein followed by subcutaneous abdominal and gluteal fat biopsies. Indirect calorimetry was measured by 5 h substrate oxidation. Whole/regional fat distribution was measured using DXA and CT scan. Participants then enrolled in a structured WtL program, after which 23 returned for study 2.Results: There were no differences (p=0.32) in meal FA oxidation between groups. Abdominal uptake of meal FA in LOb was greater than in UOb (p=0.026) and ObM (p<0.001). LOb took up more meal FA in the lower body than ObM (p=0.001). Participants who returned for study 2 lost 14 ± 1.1 kg. After WtL, uptake of meal FA in upper body subcutaneous fat increased (p=0.028) in UOb and ObM (p=0.046) and decreased in lower body fat (p=0.025) in ObM. WtL led to reduced 5 h postprandial total fat oxidation and increased 24 h meal FA oxidation.Conclusion: Changes in uptake of meal FA after WtL followed a pattern indicative of body fat distribution maintenance. These results highlight the potential importance of meal fat uptake in modulating body fat distribution in obesity.Funding: NIH RO1 DK45343, DK50456 and R00585.
Signal transduction by stress‐activated MAP kinases
Authors: Davis Roger J 
Published: June 2021

The JNK group of stress‐activated MAP kinases consists of ten protein kinases that phosphorylate the NH2‐terminal activation domain of c‐Jun on Ser‐63 and Ser‐73 causing increased transcriptional activity. JNK protein kinase activity is increased in response to treatment of cells with pro‐inflammatory cytokines or exposure to environmental stress. Activated JNK is phosphorylated on Thr and Tyr within the tripeptide motif Thr‐Pro‐Tyr located in kinase sub‐domain VIII. Mutational analysis demonstrates that JNK activation requires the phosphorylation of both Thr and Tyr within this motif. This phosphorylation is mediated by dual specificity protein kinases, including MKK4 and MKK7.The function of the JNK signaling pathway has been studied using a combination of biochemical and genetic approaches. Genetic analysis of JNK signaling in Drosophila demonstrates that JNK is required for early embryonic morphogenesis. Similarly, disruption of the JNK signaling pathway in mice using homologous recombination demonstrates that JNK is required for embryonic viability. In contrast, mice with genetically engineered selective defects in JNK signaling are viable, but exhibit changes in stress‐induced gene expression and apoptosis. These studies provide insight into the role of the JNK stress‐activated MAP kinase pathway in the cellular response to environmental stress, including apoptosis and cell survival.
Antioxidant dietary supplements enhance DNA repair capacity in free‐living humans
Authors: Neuhouser Marian L. , Gu J. , Schmezer P. , Ulrich C. , White E. 
Published: June 2021

Dietary antioxidants, particularly from dietary supplements, provide protection against free radical‐induced oxidative stress. We used the comet assay (single cell gel electrophoresis) on viable lymphocytes from fasting blood to assess DNA damage and repair capacity in users of antioxidant dietary supplements in Washington State. Participants (n = 121) were aged 50–74 years, 55.4% male, 93% never/former smokers and 64.5% were overweight/obese. Detailed inventories obtained information on supplement use; 85.9% reported using at least one antioxidant‐containing dietary supplement; over half used > one supplement; 8.3% were long‐term high‐dose users of either vitamin C or E (defined as ≥ 1000 mg of vitamin C or 800 IU vitamin E/day for ≥ 5 years). In multivariate‐adjusted regression models, the highest doses of supplemental vitamin C, E or beta‐carotene (vs. no supplements) were associated with enhanced DNA repair capacity (all p< 0.05). Associations were attenuated when antioxidants from food + supplements were considered. Long term use (> 5 years) of vitamins C or E was associated with better DNA repair capacity. Compared to non‐users of dietary supplements, long‐term users of vitamin C or E had a 1.7 fold (p = 0.007) and 1.5 fold (p = 0.01) increases in DNA repair capacity, respectively.Conclusion: use of DNA antioxidant dietary supplements may enhance DNA repair capacity. Supported by R03CA105336,R01CA74846.
Nutritional Management of Very Low Birthweight Infants: Effects of Different Feeding Regimens on Calcium Absorption
Authors: Hicks Penni Davila , Grifin Ian J , Hawthorne Keli M , Abrams Steven A 
Published: June 2021

Background: Adequate nutrition is a key aspect of care for very low birth weight (VLBW) infants. However, it is difficult to provide adequate nutrition to VLBW infants who have health problems which require fluid restriction and increased caloric density feedings. The effects of these changes on growth, calcium (Ca) metabolism and bone mineral status are unknown.Objective: To compare the effects of different feeding strategies on Ca absorption in VLBW infants.Methods: Stable isotopes were used to evaluate Ca absorption in preterm infants fed fortified human milk (HM) (n=8) or preterm formula (PF) (n=8). Infants were fed at either 24 or 27 kcal/oz HM or PF. After 2 weeks on the study diet 2 mg of 44Ca was given with a feeding and 20μg of 46Ca was given IV.Results: There was no difference in gestational age for HM or PF (mean = 27.1 weeks) or birthweight for HM, 1050 ± 179g and PF, 1085 ± 301g (mean ± SD). Mean Ca absorption was 50.5 ± 19.9% for HM and 54.1 ± 17.6% for PF (p = 0.4). Ca intake was 223 ± 14 mg/kg for HM and 221 ± 10 mg/kg for PF (p = 0.6). Total Ca absorption was 113 ± 46 mg/kg for HM and 119 ± 37 mg/kg for PF (p = 0.6).Discussion: Currently used feeding approaches provide Ca comparable to the in utero accretion rates.
Overweight and Obesity in elderly people adults in Mexico
Authors: Nasu Lucia Cuevas , Levy Teresa Shamah , Hernandez Salvador Francisco Villalpando , Aguilar Alejandra Jimenez 
Published: June 2021

This study describes the prevalence of overweight (OW) and obesity (O) (BMI 30 kg/m2) and assesses its association with socioeconomic (SES), demographic, and nutritional status indicators. Data from the National Health and Nutrition Survey in Mexico (ENSANUT 2006) on 5480 elderly people (aged 60–99 y) were analyzed. Models of logistic regression were used and they were adjusted by design of the survey. Prevalence of OW on men was 43.9 and women 38.9% (p< 0.05) and O on men was estimated on 20.2 and women 35.5% (p<0.05); high waist circumference: (men 69.5 and women 73.7%). The risk of OW+O was positively associated with urban residence (OR=1.4, p<0.05); level of education (OR=1.4, p<0.05), waist circumference (OR=16.9, p<0.001) and previous diagnostic of obesity (OR=4.2, p<0.001). Smoking (OR=0.7, p<0.05), being beneficiary of food assistance programs (OR=0.9, p>0.05), and age (OR=0.9, p<0.001) were not associated with the risk for OW+O. Results demonstrate a high prevalence of overweight and obesity in elderly adults in Mexico. It is a priority to enact strategies and programs to prevent and control it. Although, smoke diminishes the possibility of suffering overweight and obesity, we are far from endorsing it.Supported by Ministery of Health, Mexico.
Bone mass is associated with vitamin D status in lactating adolescent mothers
Authors: Bezerra Flávia F. , Mendonça Laura M.C. , Donangelo Carmen M. 
Published: June 2021

The aim of the present study was to investigate the association between serum concentrations of vitamin D [25(OH)D] and bone mass in 28 lactating Brazilian adolescents (15–18y). Total body mineral content (TBMC), total body (TBMD) and lumbar spine (L2–L4, LSBMD) bone mineral density were assessed by DXA. Serum 25(OH)D and iPTH were assessed by radioimmunoassay and chemiluminescent assay, respectively. 25(OH)D varied in a range between 49–75.5 nmol/L and correlated negatively with iPTH (r= −0.56, P<0.01). Positive correlations were observed between 25(OH)D and the following bone measurements: TBMC (r= 0.48, P<0.01), TBMD (r= 0.40, P<0.05), TBMD z score (r= 0.53, P<0.01) and LSBMD z score (r= 0.40, P<0.05). In a stepwise linear regression, 25(OH)D appeared as a modest, but significant factor influencing TBMD and TBMD z score (Table).Our results indicate that the lactating adolescent mothers studied had serum 25(OH)D concentrations below the proposed cutoff (≤ 80nmol/L) to define deficiency. Moreover, these results suggest that bone mass may benefit from improving vitamin D status during lactation in adolescent mothers.Financial support: CNPq and FAPERJ (Brazil).
Increasing entrée portion size does not always increase children's energy intake at a meal.
Authors: Johnson Susan L , Ross Erin Sundseth , Grunwald Gary , Burger Kyle , Fisher Jennifer O 
Published: June 2021

Children's energy intake has been reported to increase as a function of the portion size of foods offered to them. However, these studies have routinely used one “amorphous” entrée, macaroni and cheese, to test these effects. We investigated the effects of increasing the portion size of two entrees (one unit and one amorphous food; hotdogs and macaroni and cheese, respectively) on children's (3–6 y) energy intake at lunch. Entrées were provided in small or large portions along with fixed amounts of other foods. We measured entrée and total food intake (in g and kcal) across 5 presentations of each portion size of each entrée. A linear mixed model with repeated measures was used to test main effects for portion size and presentation and a portion*presentation interaction. Overall, the portion size of the entrée marginally influenced the amount of entrée consumed (kcal, p<.12; g, p<.01) however it did not impact total energy consumed at the meal (p<.96). When examined by type of entrée, children ate significantly more (in kcal and g) of the large size of the amorphous entrée (p<.02) but not of the unit entrée (p<.15). Increases in portion size resulted in a large increase in entrée intake (25–34%) but only a 4% increase in total energy intake at the meal. Our findings suggest that children do not always respond to increases in portion size by increasing total energy intake.(Research Support: The National Cattlemen's Beef Association)
Desmocollin 2 regulates proliferation in the intestinal epithelial cell line SK‐CO15 through activation of the small GTPase Rap1
Authors: Kolegraff Keli , Nava Porfirio , Severson Eric , Koch Stefan , Laukoetter Mike , Parkos Charles , Nusrat Asma 
Published: June 2021

Desmosomes (DMs) are essential for maintaining tissue integrity. In simple epithelial cells, two DM transmembrane cadherins referred to as desmoglein‐2 (Dsg2) and desmocollin‐2 (Dsc2) associate with underlying cytokeratin filaments via cytoplasmic plaque proteins. While DM regulation of epithelial mechanical properties is well established, their role in regulation of cell growth and morphogenesis is incompletely understood. Our studies were focused on defining the function of Dsc2 in simple intestinal epithelial cells (IEC). By knocking down Dsc2 with shRNA in a model IEC cell line SK‐CO15, we observed that loss of Dsc2 expression induced IEC proliferation as determined by BrdU incorporation and 3D cyst formation assays. Studies to determine the mechanism by which Dsc2 knockdown induced proliferation revealed increased activation of a small GTPase, Rap1, and down‐regulation of cell‐cell and cell‐matrix adhesion proteins JAM‐A, E‐cadherin, and β1‐integrin. Furthermore, over‐expression of Dsc2 decreased Rap1 activity. These findings support a role for Dsc2 in controlling intestinal epithelial cell adhesion and proliferation through regulation of Rap1.Supported by NIH DK‐59888 (A.N.) and CCFA fellowship award (P.N.)
Neutrophil‐selective transgenic RNA interference in vivo
Authors: Cullere Xavier , Lauterbach Michael , Tsuboi Naotake , Mayadas Tanya 
Published: June 2021

Tissue specific silencing of genes has applications for genetic engineering. Current strategies rely on Cre/Lox technology in mice requiring the generation of multiple transgenic lines and breeding strategies. Here we pursued a method to silence genes in neutrophils using an miRNA strategy. As proof of principle, we chose CD18 as the target gene since it is an abundantly expressed surface protein. CD18 specific miRNA hairpin driven by the myeloid specific MRP8 promoter resulted in a >90% reduction in CD18 protein levels in neutrophils and monocytes with no observable decrease in T cells and only a partial diminution in macrophages. Neutrophil CD18 silencing resulted in mild neutrophilia, splenomegaly and significant defects in neutrophil trafficking in irritant dermatitis. Our data demonstrate the utility of using miRNA approaches to silence genes in neutrophils which are terminally differentiated cells with a short half life that largely precludes their genetic manipulation in vitro. Furthermore, the mouse model provides a valuable tool to examine the contribution of CD18 on neutrophils to Leukocyte Adhesion Deficiency I (LADI), a complex inherited disorder in which reduced or absent CD18 expression in multiple leukocyte subsets leads to impaired innate and adaptive immune responses.Note: XC, ML and NT contributed equally. Supported by: NIH KO1AR054984 (XC), HL065095 and AR050800 (T.N.M), and a Arthritis Foundation fellowship (NT).
Pyruvate‐enhanced cardioplegia preserves myocardial Hsp 70 and endothelial NOS in a porcine model of cardiopulmonary bypass
Authors: Flaherty Devin C , Ryou Myoung Gwi , Hoxha Besim , Sun Jie , Ferlitch Heather R , Olivencia‐Yurvati Albert H , Mallet Robert T 
Published: June 2021

Background: The use of pyruvate‐fortified cardioplegia to arrest the heart during cardiopulmonary bypass (CPB) enhances post‐surgical recovery of cardiac function, compared with conventional cardioplegia solutions. Pyruvate's energy‐yielding and antioxidant effects wane as pyruvate is cleared from the circulation, yet its functional benefits persist, suggesting a protein‐mediated cardioprotective mechanism.Hypothesis: Pyruvate cardioplegia during CPB prevents subsequent depletion of the cytoprotective proteins eNOS and Hsp‐70. Methods: After sternotomy, swine were subjected to 60 min cardioplegic arrest and 30 min myocardial reperfusion on CPB, then were weaned from bypass. The crystalloid portion of the 4:1 blood:crystalloid cardioplegia contained 24 mM lactate or pyruvate. Left ventricular myocardium was sampled at 4 h post‐CPB for extraction and immunoblot detection of Hsp70 and eNOS; actin served as loading control. Sham pigs underwent the same surgical and analytical procedures, but without CPB.Results: Actin‐normalized myocardial eNOS and Hsp‐70 contents fell by 32 and 68%, respectively, and NOS activity fell from 132 ± 10 to 91 ± 6 nmol/min/g protein in the lactate cardioplegia group, vs. respective sham values (P < 0.05). Pyruvate cardioplegia prevented loss of eNOS and Hsp70, and maintained NOS activity at 134 ± 8 nmol/min/g protein (P < 0.05 vs. lactate group).Conclusions: Cardioplegic arrest on CPB can deplete myocardium of the cytoprotective proteins eNOS and Hsp70. Protection of these proteins by pyruvate‐enriched cardioplegia may support improved post‐CPB cardiac performance.Support: Osteopathic Heritage Foundation 02‐18‐522
Human Amniotic Fluid‐Derived Stem Cells: A Novel Source of Dopaminergic Neurons?
Authors: Santos Cesar C. , Klorig David , Chun So Young , Atala Anthony , Soker Shay 
Published: June 2021

The aim of our study is to investigate whether human amniotic fluid derived stem cells (hAFSC) can be used for regenerative applications in neurodegenerative diseases like Parkinson's disease (PD).To yield dopaminergic cells, hAFSC were cultured in a 2 stage culture media systems that include growth factors to mimic the normal midbrain dopaminergic development. At different time points during differentiation differentiated cells were analyzed using RT‐PCR and immunostaining. At the end of differentiation the amount of cellular dopamine quantified and a whole‐cell voltage clamp recording was performed.The hAFSC at end of the expansion phase expressed nestin and Nurr1 and their expression was enhanced by exposure to hypoxic culture condition. At the end of terminal differentiation, cells look bipolar and pyramidal and showed expression of Girk2. After recording the inward currents, barium was added to the bath to block the Girk‐specific inward current. A reduction in the amplitude of the currents evoked by the same hyperpolarizing voltage step protocol in the presence of barium indicated the presence of Girk‐mediated potassium channel. Terminally differentiated cells secreted dopamine in a dose response manner, yielding approximately 2nM/100,000 cells.In this study we showed that hAFSC can be successfully differentiated into dopamine secreting neuron‐like cells that express neuronal genes.
Progenitor‐Derived Endothelial Cell Therapy Restores Erectile Function
Authors: Rodríguez Sergio , Chen Kuo‐Liang , Atala Anthony , Yoo James 
Published: June 2021

IntroductionWe examined whether endothelial cell therapy could restore normal erectile function in a diabetic rat model. We investigated the feasibility of using endothelial progenitor cells (EPC), obtained from peripheral blood, as a source of endothelial cells for therapy.Materials and MethodsEPC, isolated from peripheral blood of donor rats, were induced into an endothelial cell lineage. The culture expanded endothelial cells were labeled with red fluorescent dye and injected directly into the dysfunctional corpora of diabetic rats, and followed for up to 12 weeks. Erectile function was assessed by intracavernous pressure and the corporal tissues were retrieved for analyses.Results and DiscussionThe progenitor and differentiated endothelial cell phenotypes were confirmed with cell specific antibodies. The animals injected with cells showed a substantial improvement in intracavernous pressure and their erectile function was restored to normal levels. Histologically, the implanted cells that were labeled with the fluorescent dye tracer PKH26 survived and integrated into the corporal tissue within the injected region.ConclusionsThis study demonstrates that the EPC‐derived endothelial cells are able to restore normal erectile function in a diabetic rat model. This cell‐based technology may be a viable treatment modality for diabetic patients with erectile dysfunction.
Erythropoietin Producing Cells for the Treatment of Renal Failure Induced Anemia
Authors: Egydio Fernanda , Aboushwareb Tamer , Stern Kathryn , Gyabaah Kenneth , Moore Philip , Zhang Yuanyuan , Atala Anthony , Yoo James 
Published: June 2021

IntroductionAnemia is an outcome of chronic renal failure due to the kidney's decreased ability to produce erythropoietin (EPO). We investigated whether supplementation of erythropoietin producing cells would be a possible treatment option for renal failure induced anemia.Materials and MethodsMice renal cells were culture expanded and characterized for EPO expression. The levels of EPO production was measured in the cells grown under normoxic and hypoxic conditions. Renal cells mixed in collagen gel were implanted subcutaneously in athymic mice followed by retrieval at 14 and 28 days after implantation for analyses.Results and DiscussionThe cultured renal cells expressed EPO at each subculture stage. Western Blots detected EPO protein in the kidney cells of all passages tested. ELISA Assay showed that the renal cells grown under hypoxic condition produced EPO. Histologically, the retrieved implants showed cell survival and tissue formation in vivo. Presence of EPO producing cells were confirmed using EPO specific antibodies.ConclusionsThese results demonstrate that EPO producing renal cells can be grown, stably express EPO in culture, and are able to form tissue in vivo. This study shows that EPO producing cells may be used as a potential treatment option for anemia caused by chronic renal failure.