bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breastmilk contains primitive stem cells from the lactating breast with multi‐lineage differentiation potential
Authors: Hassiotou Foteini , Filgueira Luis , Trengove Naomi , Lai Ching Tat , Hartmann Peter 
Published: June 2021

The remodelling of the mammary gland during pregnancy/lactation is fuelled by mammary stem cells. Because most of our knowledge on these cells comes from the resting gland, recent efforts have focused on the lactating gland in which these cells are activated. We non‐invasively accessed stem cells from the human lactating gland via freshly expressed breastmilk. We performed ex vivo analysis of the cell subpopulations present in breastmilk using numerous phenotypic and functional stem cell and differentiation markers for various lineages. A population displaying the phenotypic profile of mammary stem cells previously characterised in the resting gland (CD49f+/CD29+) was identified, able to self‐renew and differentiate in vitro into the two main mammary epithelial subtypes. In addition, a population expressing the pluripotency markers Oct‐4, Sox‐2, Nanog, SSEA‐4, Tra‐1–60 and Tra‐1–81 was identified. Culture of these cells in stem cell and differentiation media revealed the potential both for self‐renewal and differentiation into cells originating from the three germ layers. The identified subpopulations were also localised in paraffin‐embedded human lactating tissues. Based on these results, a new cellular hierarchy is proposed for the human mammary gland, at the top of which sits a cell population with potential pluripotency, which can be easily accessed via breastmilk.Grant Funding Source : Women and Infants Research Foundation, Medela AG
Initial Characterization of the Cellular Basis for Bladder Regeneration in a Rodent Model
Authors: Peyton Charles , Burmeister David , Andersson Karl-Erik , Christ George 
Published: June 2021

PurposeA better understanding of intrinsic mammalian organ regeneration would benefit the field regenerative medicine. Our prior work shows functional bladder recovery in rats after removal of ~70% of the bladder (subtotal cystectomy/STC). Our objective is to begin identifying the spatiotemporal characteristics of cellular response to STC.MethodsTrigone‐sparing STC was performed on 12‐week‐old female Fischer F344 rats. At 1, 3, 5, and 7 days post‐STC, bladders were harvested 2 hours after IP 50mg/kg 5‐Bromo‐2’‐deoxyuridine (BrdU). Fluorescent BrdU labeling was used to quantify and localize S‐phase cells within the bladder wall. Immunohistochemistry for Shh, Gli‐1 and BMP‐4 was also performed. Normal rat bladders served as controls.ResultsSparse BrdU labeling was observed in native bladders (Fig. 1). The total number of BrdU‐positive cells/400x HPF was significantly higher post‐STC at all time points. A time‐depended location change in the percentage of BrdU‐positive cells was seen. Increased positive staining for Shh, Gli‐1 and BMP‐4 was also noted post‐STC.ConclusionsSTC induced a robust proliferative response with quantifiable spatiotemporal characteristics and up‐regulation of key targets in the Shh developmental pathway. Future studies will identify the cell source(s) and details of the molecular pathways that modulate functional bladder regeneration.
Brain‐derived neurotrophic factor receptor TrkB exists as a preformed dimer in living cells
Authors: Maruyama Ichiro , Shen Jianying 
Published: June 2021

BackgroundNeurotrophins and their receptors play crucial roles in the development and functioning of nervous systems. It is widely believed that neurotrophin‐induced dimerization of the receptors initiates the transmembrane signalling. However, it is still controversial whether the receptor molecules have a monomeric or dimeric structure on the cell surface before its ligand binding.FindingsUsing chemical cross‐linking, bimolecular fluorescence complementation assay and luciferase fragment complementation assay, in this study, we show the brain‐derived neurotrophic factor (BDNF) receptor TrkB exists as a homo‐dimer before ligand binding. We also report that the receptor fs intracellular domain is critical for the formation of the dimeric structure, since mutant receptors lacking its intracellular domain failed to have the homodimeric structure, and that the dimer is formed in the endoplasmic reticulum before the newly synthesized receptors reach the cell surface.ConclusionsMost, if not all, of the TrkB receptor has a preformed, yet inactive, homodimeric structure before BDNF binding. The intracellular domain of TrkB plays a crucial role in the spontaneous dimerization of the newly synthesized receptors, which occurs in ER. These findings provide new insight into an understanding of a molecular mechanism underlying transmembrane signaling mediated by neurotrophin receptors.
Alternate day fasting (ADF) with a high fat background diet produces similar weight loss and cardio‐protection when compared to ADF with a low fat background diet
Authors: Klempel Monica Catherine , Kroeger Cynthia M , Varady Krista A 
Published: June 2021

BackgroundAlternate day fasting (ADF) with a low‐fat (LF) background diet facilitates weight loss and is cardio‐protective in obese individuals. Whether these beneficial effects can be reproduced by a high‐fat (HF) ADF diet is not known.ObjectiveThis study examined the effects of an ADF‐HF versus ADF‐LF diet on body weight, body composition and cardiovascular disease (CVD) risk in obese humans.MethodsThirty‐three obese subjects were randomized to an ADF‐HF or ADF‐LF diet for 10 weeks. All food was provided during the study.ResultsBody weight was reduced (P < 0.0001) by 4.9%, and 4.2% in the ADF‐HF and ADFLF group, respectively. Waist circumference decreased (P < 0.0001) by 7.6%, and 7.5% in the ADF‐HF and ADF‐LF groups, respectively. LDL cholesterol was reduced (P < 0.0001) by 19.1%, and 24.8%, whereas triglycerides were lowered (P = .0001) by 13.3% and 14.3%, in the ADF‐HF and ADF‐LF group, respectively. There were no changes in blood pressure or heart rate.ConclusionThese findings suggest that an ADF‐HF diet is equally as effective as an ADF‐LF diet in helping obese subjects lose weight and improve CVD risk factors.
Novel positive allosteric modulators of the human α7 nicotinic acetylcholine receptor
Authors: Miller Marc A. , Gu Ruo-Xu , Feuerbach Dominik , Ye Yong , Wei* Dong-Qing , Arias Hugo R. 
Published: June 2021

The pharmacological activity of a series of novel amide derivatives was characterized on several nicotinic acetylcholine receptors (AChRs). Ca2+ influx results indicate that these compounds are not agonists of the human (h) α4β2, α3β4, α7, and α1β1γδ AChRs; but are specific positive allosteric modulators (PAMs) of hα7 AChRs. Radioligand binding results indicate that PAMs do not inhibit binding of [3H]methyllycaconitine but enhance binding of [3H]epibatidine to hα7 AChRs, indicating that these compounds do not directly, but allosterically, interact with the hα7 agonist sites. Hydrogen bond interactions between the amide group of the PAMs and the hα7 AChR binding site are found to be critical for their activity. The dual PAM and antagonistic activities elicited by these compounds might be therapeutically important in treating diseases such as depression and drug addiction.We thank the National Institute on Drug Abuse (NIDA) for the gift of phencyclidine.
Central arterial stiffness is positively associated with parent‐reported inactivity and systolic blood pressure in children
Authors: Price Paula Holland , Lee Joshua F. , Bartholomew John B. , Brothers R. Matthew 
Published: June 2021

Carotid‐femoral arterial pulse wave velocity (central PWV), “an index of central arterial stiffness”, has become a recognized physiologic measure of vascular pathology. Central PWV is gaining acceptance as an indicator of overall atherosclerotic disease and shows potential as a screening tool for atherosclerotic disease in hypertensive adults. There is evidence that atherosclerotic disease begins in childhood, however, the mechanism is poorly understood. An association between fitness and central PWV has been reported in children. This pilot study explores the association between inactivity and central PWV in children. Central arterial stiffness of thirteen subjects, ages 8–13 years, was measured by carotid‐femoral PWV. Parents of the subjects reported the child's inactivity behavior on a typical day. Central PWV was found to correlate with inactivity (correlation coefficient=.656, p<0.05) and was also found to correlate with systolic blood pressure (correlation coefficient=0.667, p<0.02). These data indicate that inactivity may be a strong predictor of central arterial stiffness in children.Funding Source: University of Texas at Austin
The role of CaMKII activation in the regulation of carnitine palmitoyl transferase and lipid oxidation in rats muscle
Authors: Mukwevho Emmanuel 
Published: June 2021

The mismatch between high fatty acids supply and mitochondrial fatty acid oxidation in skeletal muscle has been associated with insulin resistance, the hallmark of type II diabetes (Holloway et al., 2009). In this study we wanted to investigate the role of CaMKII activation in the reduction of lipids and whether carnitine palmitoyl transferase (CPT)‐1, the rate limiting step oxidation was involved. Improved mitochondrial fatty acid oxidation is seen as a crucial step in the reduction of lipids that interferes with insulin signaling pathway.In this study, male Wistar rats were used. The exercise regime was designed for 5 days, where each session per day was 5 × 12 min with 3 minutes rests, after which gastrocnemius muscle was excised after 18h of the 5th day. Using GC‐MS (Gas chromatography mass spectroscopy) with flame ionization detector (FID), we found that CaMKII activation resulted in significant reduction in total lipid content. When KN93 (CaMKII inhibitor) was injected in the muscle prior exercise, the content of lipid was significantly higher than of muscle of the exercised rat without KN93, however similar to that of non‐exercised rat muscle. Exercise also resulted in increased CPT‐1 protein content whereas inclusion of KN93 prior exercise significantly altered the observed CPT‐1 upregulation. These observations indicate that CaMKII plays a significant role in lipid oxidation metabolism.
Thirteen days of normobaric intermittent hypoxia increases SpO2 in a 71‐year‐old male
Authors: Kambis Kenneth Wicker , Yasukawa Mihio , Moran Thomas , Sobel Bart 
Published: June 2021

PURPOSENormobaric Intermittent Hypoxic Exposure (NIHE) is thought to reduce risk of Acute Mountain Sickness (AMS) during subsequent exposure to higher altitudes by increasing arterial oxygen saturation of hemoglobin (SpO2). The purpose of this study was to evaluate the effect of 13d of NIHE on older adult SpO2.METHODSA 71 y.o., 185 cm tall, 84 kg, healthy male informed volunteer, participated in this IRB approved study. A former marathoner, BR has a history of mitral valve replacement (1995) and hemorrhagic stroke (2001). After a thorough physical examination and stress test by a cardiologist, he was pronounced in superior fitness and approved for the study. BR was exposed to normobaric hypoxic simulated altitudes of 2438 m to 5486 m in ~300 m increments for 3–4h/d for 13d. Every 15 minutes of exposure, SpO2 and heart rate (HR) were measured. On d0 and on d13, BR was exposed to 6 normobaric hypoxic simulated altitudes (1830 m – 4663 m).RESULTSDuring 13d of NIHE, SpO2 was reduced from d1 (2486 m) to d13 (5486 m; r= −0.947, P< 0.001). When the d0 SpO2 values at the 6 simulated altitudes were compared to d13 values, significant increases (P<0.05) were found.CONCLUSIONSNIHE appears to be a safe and effective method of increasing SpO2 in older adults preparing for strenuous high altitude exertion. Supported by: The Foundation for Aging Studies and Exercise Science Research and, The Borgenicht Program at William & Mary
Validation of Epigenetic Markers in Endometriosis
Authors: Colon Mariano , Colon Maricarmen , Monteiro Janice , Baez Perla , Ruiz Abigail , Flores Idhaliz 
Published: June 2021

Endometriosis is a gynecological disease that affects 1 in 10 women during their reproductive years, cause incapacitating pelvic pain and infertility. Endometriosis is characterized by the growth of endometrial tissue outside the uterine cavity. Endometriosis has no cure, its diagnosis can only be done via surgery, there are no non‐invasive markers and its etiology is unknown. Epigenetic mechanisms may play an important role in the etiology of this disease. The modification of histones by acetylation and methylation of lysine residues has been shown to regulate gene expression by changing chromatin structure. We have shown by ELISA that endometriotic lesions have high levels of acetylated histone 3 at lysine residue 9 (H3K9ac).AimTo measure H3K9ac levels using immunohistochemistry (IHC).MethodsUsing a Tissue Microarray (TMA) composed of 163 biopses (endometriotic lesions and control tissues) we will assess levels of H3K9ac by IHC. Troubleshooting experiments identified the 1:100 as the appropriate dilution of the antibody.ResultsWe expect that endometriotic lesions will express lower levels of H3K9ac than controls. Also, we expect that endometrium of patients express higher levels of H3K9ac than endometrioctic lesions. IHC will be able to show the cell specificity (i.e., glands vs. stroma) and will confirm the nuclear localization of this histone mark. In addition, we will be able to determine possible differences in this mark by lesion type (ovarian vs. peritoneal). These results will help understand how genes are regulated in endometriosis, and may support the use of novel treatments for this incurable disease. R25GM096955
Vitamin E and nonalcoholic fatty liver disease (NAFLD)
Authors: Thakur Varsha , Ulatowski Lynn , Parker Robert , Zhang Renliang , Liu Xiuli , Manor Danny 
Published: June 2021

Nonalcoholic fatty liver disease consists of a continuum of hepatic injuries, from simple steatosis to nonalcoholic steatohepatitis (NASH), and accounts for the majority of chronic liver diseases in the Western world. The penetrance of NAFLD is especially high amongst obese individuals. Presently, no effective treatment option is available for this disease, and it sometimes progresses to cirrhosis and liver cancer. Multiple lines of evidence indicate that oxidative stress may be an important factor in the pathological progression of NAFLD. Moreover, dietary supplementation with the antioxidant vitamin E was shown to be efficacious in attenuating pathologic progression in human NAFLD patients (Sanyal et al NEJM 2010).To gain mechanistic insights into the effects of vitamin E on NAFLD, we examined the presence and progression of liver injury in a genetic model of vitamin E deficiency, namely mice lacking the alpha‐tocopherol transfer protein (αTTP). When placed on a vitamin E deficient diet, TTP‐null mice displayed many hallmarks of NAFLD, namely accumulation of macro‐ and micro‐vesicular lipid droplets, hepatic injury evidenced by elevation of circulating alanine aminotransferase, increased hepatic collagen deposition, and inflammation of the liver, evidenced by marked increase in TNFα. Importantly, many of these parameters normalized upon dietary supplementation with vitamin E. Interestingly, dietary supplementation with vitamin E did not prevent lipid deposition in the TTP‐null livers, indicating that TTP is essential for mediating the full complement of benefits associated with vitamin E supplementation. (This work was supported by NIH grant ROIDK067494).
The SUMO Ligase PIAS1 Promotes the Progression and Survival of Solid Tumors of Different Histopathological Origins
Authors: Constanzo Jerfiz D , Rabellino Andrea , Konstantinidou Georgia , Schuster Katja , Scaglioni Pier 
Published: June 2021

Protein inhibitor of activated STAT‐1 (PIAS1) regulates cell signaling via posttranslational modifications of proteins. PIAS1 conjugates small ubiquitin like modifiers (SUMO‐chains) onto target proteins. Our lab discovered that PIAS1 SUMOylates the promyelocytic leukemia (PML) tumor suppressor. This event promotes degradation of the tumor suppressor (PML) aiding tumor progression.Thus, we hypothesized that PIAS1 will promote cell survival and progression in human cancers where it is highly expressed, representing an unexplored vulnerability in these cancers. We performed gain and loss of function experiments to test PIAS1 effect on tumorigenesis with transformation assays, and studied cell survival after PIAS1 depletion using RNAi. Ectopic overexpression of Pias1 protein in NIH3T3 and mouse embryonic fibroblasts (MEFs) promotes colony formation and loss of contact inhibition in culture. PIAS1 depletion using shRNA in non‐small cell lung cancer (NSCLC) and breast cancer cell lines leads to increased PML levels, following susceptibility to apoptosis and impaired cell proliferation. Moreover, siRNA depletion of PIAS1 in NSCLC cell line H460 reduces cell spreading and impairs migration in wound healing assays. Our findings show for the first time a novel role for the SUMO ligase PIAS1 in tumor progression and survival. Our findings lay the groundwork for the study of PIAS1 in human cancers.
The changing influence of wealth, education and urbanization on overweight and obesity in Guatemalan women between 1995 and 2008
Authors: Kanter Rebecca , Fort Meredith P. , Ramirez Manuel , Martorell Reynaldo 
Published: June 2021

Overweight and obesity (BMI≥25.0) prevalence in Guatemalan women (15–49y) was examined in the 1995, 1998, 2002, and 2008 National Maternal and Infant Health Surveys (ENSMI). Associations with socio‐demographic factors (age, education, ethnicity, urban‐rural, parity, and wealth) were analyzed using STATA SE 12.0. Survey weighted logistic regression models adjusted for age and parity assessed associations between BMI≥25.0 and socio‐demographic factors. Prevalence of BMI≥25.0 was 34.1% in 1995 and 59.4% in 2008; and BMI≥30.0 rose from 7.9% to 22.4%. Tests for trend (p<0.0001) confirmed BMI≥25.0 increased in most socio‐demographic groups over time. In 1995, high wealth (OR = 5.97, CI: 4.23, 8.43, p<0.001) and urban areas (OR = 1.32, CI: 1.08, 1.62, p<0.01) were associated with a BMI≥25.0. In 1998, 2002, and 2008, education and urban areas were significantly positively associated with BMI≥25.0. In 1995, education (OR = 1.81, CI: 1.19, 2.75, p<0.01) and high wealth (OR = 7.07, CI: 3.99, 12.52, p<0.001) were associated with BMI≥30.0; in 1998 wealth was not significant. From 2002 and 2008 the association with BMI≥30.0 and education decreased (OR = 1.97, CI: 1.55, 2.50, p<0.001; OR = 1.52, CI: 1.30, 1.78, p<0.001), while urban areas increased (OR = 1.34, CI: 1.05, 1.72, p<0.05; OR = 1.67, CI: 1.42, 1.95, p<0.001). Education, and urban areas explain more of the increase in BMI≥25.0 from 1995 to 2008. This research was not funded.Grant Funding Source: None
Iron Status in Multiples and Their Neonates
Authors: Ru Yuan , Pressman Eva K , Guillet Ronnie , Cooper Beth M , Katzman Philip J , Caveglia Sarah , O'Brien Kimberly 
Published: June 2021

Women carrying multiples are at high risk for iron deficiency anemia. Low maternal iron (Fe) status may impact neonatal Fe stores and may have long‐term adverse functional consequences. In this study, maternal Fe status will be longitudinally followed across pregnancy in 125 women carrying multiples, all of whom receive standard Fe‐containing prenatal supplements. Data on 33 pregnant women are available to date, including 9 sets of triplets and 24 sets of twins. Average gestational age at delivery was 34 ± 3.72 weeks. Maternal and umbilical cord serum was analyzed for Fe status indicators and inflammatory markers. Maternal anemia was evident in 64.7% of women at term. Maternal ferritin values averaged 17.89 ± 7.28 μg/L; 71.4% of women had depleted ferritin stores (< 20 ug/L) by mid‐gestation. Transferrin receptor averaged 4.15 ± 3.08 mg/L; fully 35.7% of women had values indicative of tissue iron insufficiency (>; 4.4 mg/L). Mean neonatal umbilical cord hemoglobin concentrations at birth were 14.23 ± 3.37 g/dL; 25.8% of neonates were anemic (< 13.0 g/dL). Cord ferritin averaged 104.82 ± 66.51 μg/L (n=25) and cord hepcidin was positively associated with maternal mid‐gestation hepcidin (n=11 pairs, p<0.0001). More data in this high‐risk population is needed to assess determinants of anemia and risk factors for anemia in this group given the increase in multiple births in the United States.Grant Funding Source: Gerber Foundation
Sociodemographic, clinical, and lifestyle factors associated with prostate cancer aggressiveness in a population‐based study
Authors: Vance Terrence M , Wang Ying , Su L. Joseph , Fontham Elizabeth T. H. , Bensen Jeannette T. , Mohler James L. , Chen Ming‐Hui , Chun Ock K. 
Published: June 2021

This study aimed to determine the associations between sociodemographic, clinical, and lifestyle factors and prostate cancer (PCa) aggressiveness. Data are from the North Carolina‐ Louisiana Prostate Cancer Project, a population‐based study of incident PCa in African Americans (AA) (n=925) and Caucasian Americans (CA) (n=1,059). Medical record abstraction and structured questionnaires were used to collect data. PCa patients with higher aggressiveness were greater among AA than CA. Aggressive cases were greater among men older at diagnosis, not married, less educated, with lower income, without previous screenings or health insurance, and with greater BMI and waist‐hip ratio (WHR) than their counter parts (p<0.05). When stratified by race, several factors were found to differ between AA and CA, including age, marital status, education, poverty, health insurance status, PSA screening, and supplement use (p<0.05). These results suggest that differences in several sociodemographic, clinical, and lifestyle factors may contribute to the disparity in PCa aggressiveness observed between AA and CA.Grant Funding Source: NIH Cancer Epidemiology Small Grant #1R03CA159421–01A1.
Dietary intake of sleep‐deprived, on‐call anesthesiology residents
Authors: Taylor Matthew Kenneth , Gibson Cheryl A. , Unruh Gregory K. , Ptomey Lauren T. , Spaeth Kendra R. , Sullivan Debra K. 
Published: June 2021

BACKGROUNDSleeping habits are relevant to the health of medical residents as sleep‐deprivation has been linked to increased energy intake and obesity risk.OBJECTIVETo evaluate effects of nights on call and amount of sleep time on dietary intake of anesthesiology residents.METHODS27 anesthesiology residents were recruited to participate in this crossover design study evaluating dietary intake on two occasions, 1) after receiving ≥8 hours of sleep and 2) after receiving ≤4 hours of sleep on‐call. Dietary data were collected at two breakfast buffets where participants were allowed to select food choices ad‐libitum. Food items were weighed previous to and after service, including plate waste. 24‐hour food recall was utilized to collect dietary intake data for the rest of that day. Participants were unaware that dietary intake was evaluated at each breakfast buffet.RESULTS20 participants (15 M, 12 F; 32 ± 5.6 years) completed the study. No significant difference was observed between total energy (791 ± 672.8 kcal vs. 737.5 ± 470.5 kcal) or macronutrient intake. Intake of fat as percent of energy greater than IOM recommendations was observed in the sleep‐deprived group (36.9 ± 8.3%).CONCLUSIONSleep‐deprivation related to on‐call shifts did not result in increased energy intake by anesthesiology residents; however, sleep‐deprivation was related to greater than IOM recommended fat intake as percent of energy.