bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin E Modulates the Expression of the Hepatic Alpha Tocopherol Transfer Protein (TTP)
Authors: Thakur varsha , Morley Samantha , Manor Danny 
Published: June 2021

Alpha tocopherol is the most biologically active form of the vitamin E, which is selectively retained in the body. The hepatic tocopherol transfer protein (TTP) regulates body‐wide levels of vitamin E by facilitating the selective secretion of ‐tocopherol from hepatocytes to circulating lipoproteins. We studied whether vitamin E affects the expression of TTP in cultured HepG2 cells engineered to inducibly express the protein. Treatment with vitamin E (100ìM RRR‐alpha‐tocopherol for 48 hours) increased the steady‐state levels of TTP by attenuating the rate at which the protein is degraded by the proteasome. Fractionation studies indicated that treatment with tocopherol induced translocation of a fraction of the TTP protein from the soluble to the insoluble fraction of the cell. In vitro,vitamin E significantly protected TTP against proteolytic degradation by trypsin.These observations suggest that vitamin E imparts a distinct conformation on TTP that is associated with localization to a specific cellular compartment, and with decreased availability for proteasomal degradation.μμαααααα
Amniotic fluid stem cells: growth, characterization and differentiation
Authors: Janz Felipe Lara , Debes Adriana , Duarte Sergio , Cavaglieri Rita , Moron Antonio Fernandes , Zugaib Marcelo , Bydlowski Sergio Paulo 
Published: June 2021

Amniotic fluid (AF) present different cellular types in its composition and a specific group of these cells shows multipotent characteristics as high proliferation ratio and increased differentiation ability. The aim of our study is to better characterize these cells and evaluate their plasticity. AF cells were investigated regarding the expression of undifferentiation markers (Oct‐4, Sox‐2, Nanog) by RT‐PCR, surface protein identification by flow cytometry and differentiation assays into adipogenic, chondrogenic and osteogenic lineage, confirmed with Alizarin Red, H&E and Oil Red O stains respectively. AF cells showed high proliferation ratios and expressive doubling time. They also expressed pluripotent stem cell‐specific genes (Oct‐4, Sox‐2, Nanog) and were positive for mesenchymal membrane markers (CD29, CD44, CD133). They were also capable to differentiate into distinct lineages: adipocytes, osteocytes and chondrocytes. In conclusion, AF is a promising source of mesenchymal stem cells with high differentiation potential.Research governmental support: by CNPq.
Weight loss attenuates oxidative stress related‐coronary vasoconstriction in obese adolescents
Authors: Gao Zhaohui , Momen Afsana , Novick Marsha , Williams Ronald J. , Cyran Stephen E. , Blaha Cheryl , Mast Jessica , Spilk Samson , Leuenberger Urs A. , Sinoway Lawrence I. 
Published: June 2021

Obesity is a risk factor for cardiovascular disease. Obesity is also a disease of oxidative stress (OS) in which cardiac output and myocardial oxygen consumption is increased. We have shown that hyperoxia (breathing 100% O2; H) can evoke coronary vasoconstriction by the oxidative quenching of NO. To examine if weight loss (WL) would alter the H related‐coronary constriction seen in obese adolescents, we measured coronary blood velocity (CBV) during H using Doppler Echocardiography before and after a 4‐week diet‐and‐exercise regimen in 6 obese male adolescents (age 15 ~ 18 yrs, BMI, 36.5±5.7 kg/m2). Three age and BMI‐matched controls were also studied. Coronary vascular resistance (CVR) was calculated as diastolic blood pressure (BP)/CBV. WL (10.1±3.1 kg) was associated with a reduction in BP, HR and rate‐pressure product (RPP) (all P<0.05). Before weight loss H increased CVR by 37±6%, whereas after WL CVR increased by only 19±6% (P<0.05) with H. CVR responses remained constant in the 3 time control subjects. Thus weight loss: 1) reduces HR, BP, and RPP; and 2) attenuates the OS related‐coronary constriction seen in obese adolescents. We speculate that: 1) the higher RPP before WL led to a higher NO production and impressive H induced constriction; 2) after WL, NO levels were reduced (less coronary flow due to lower RPP) and the effects of H were attenuated.Supported by R01 HL070222 (LS) and Tobacco Settlement Funds (LS).
Can leptin induce fever?
Authors: Steiner Alexandre A , Krall Catherine M , Liu Elaine 
Published: June 2021

It is unclear whether physiological acute rises in circulating leptin (an adipocyte‐derived hormone) can cause fever. We studied the effects of recombinant leptin on the body temperature (Tb) and plasma leptin of rats that were food‐deprived (lower baseline leptin) or free‐feeding (higher baseline leptin). The biological activity of leptin was confirmed by its ability to suppress food intake. In food‐deprived (24 h) rats kept in a cool environment (22 °C), iv infusion of leptin (250 μg/kg) elevated Tb from hypothermic to normothermic values, but it did not raise Tb to febrile values. Such an effect coincided (120 min post‐infusion) with a rise in plasma leptin to a level (7.8 ± 0.6 ng/mL) often found when the endogenous production of leptin is activated. Increasing the leptin dose to 1,000 μg/kg did not further elevate Tb in food‐deprived rats. In free‐feeding rats kept in a cool (22 °C) or warm (28 °C) environment, leptin infusion did not alter Tb, even when a dose of 3,500 μg/kg raised plasma leptin to a level (75.2 ± 12.6 ng/mL at 120 min) that is substantially above the endogenous level of leptin in leptin‐responsive rats. We conclude that an acute rise in plasma leptin does not induce fever in rats.SupportScholarship of discovery grant, Albany College of Pharmacy & Health Sciences
New method of calculating alveolar CO2 transport
Authors: Caucha Luis Jhony , Cruz Julio Cesar , Rueda Luis Antonio 
Published: June 2021

Cruz proposed that the expirogram of CO2 does not represent the process of gas exchange (FASEB J. 21:609.4, 2007). It represents a simple alveolar gas dilution by the tidal volume that does not reach the residual volume (RV). Caucha et al. showed that phase II is formed by the distribution of regional dead spaces (FASEB J. 22:763.6, 2008). However, this latter model could not predict which anatomic Weibel's model generations were involved. Thus, here, we modify Caucha's model by separating the convection‐diffusion process (method 1) in three different steps (method 2): 1. Convection. 2. Convection‐diffusion and 3. Diffusion. As a result, new alveolar CO2 concentrations at the apex and base regions of the lung were found (see figure, interrupted and continuous lines for method 1 and 2, respectively). This picture was obtained after searching the generations involved: the first 8 generations (step 1), generations 9th‐19th (step 2) and the last 5 generations (step 3), which produced the simulated expirogram similar to the experimental curve. In conclusion, the analysis presented follows our theory of alveolar gas mixing; during inspiration, the alveolar CO2 is diluted by the tidal volume (figure), and during expiration, the uneven emptying of parallel regions of the lung generates the expirogram.Supported in part by ONG ‐ Centro de Enseñanza Investigación y Servicios.
Influence of chocolate formulation factors on in vitro bioaccessibility and bioavailability of catechins in humans
Authors: Neilson Andrew Peter , George Judy , Mattes Richard D. , Janle Elsa M. , Matusheski Nathan V. , Ferruzzi Mario G 
Published: June 2021

Conflicting data exist regarding the effect of carbohydrate and milk on bioavailability of catechins from chocolate. To test the effects of these ingredients, solid [reference dark (SD), high sucrose (SHS), high milk solids (SMS)] and beverage [high sucrose (LHS), artificial sweetener (LAS)] chocolate products providing physiologically relevant levels of epicatechin (EC, 30 mg/serving) were formulated. Subjects (n=6) consumed one serving of chocolate, and serum pharmacokinetics were monitored for 6 h. Subjects consumed all 5 products in a crossover design. Plasma Cmax and AUC0‐6h of EC from SMS samples were not significantly different from the reference SD chocolate, but were significantly lower than SHS as well as both beverages. Plasma Cmax of EC from the LHS beverage was also significantly higher than the reference SD chocolate. Recovery of EC through in vitro digestion (bioaccessibility) did not differ between formulations. Furthermore, EC accumulation by Caco‐2 intestinal cells exposed to in vitro digesta from each product for 1 h were not significantly different, but retention of EC over 1 h was significantly greater in cells exposed to digesta from SMS product than other solid products. These data suggest that gastric emptying and intestinal cell retention are the main mechanisms by which formulation factors may alter the pharmacokinetic properties of catechins from chocolate. Supported by Kraft Foods.Grant Funding SourceKraft Foods Global
Unraveling the complexity of Echinacea fractions to identify alkylamides and ketones important for anti‐inflammatory bioactivity
Authors: LaLone Carlie A. , Rizshsky Ludmila , Solco Avery , Nikolau Basil , Murphy Patricia , Birt Diane F. 
Published: June 2021

Third round fractions produced via bioactivity guided semi‐preparative reversed phase HPLC fractionation of Echinacea angustifolia were analyzed by GC‐MS to identify constituents important for the anti‐inflammatory properties of the botanical. Two fractions were of interest due to their ability to inhibit lipopolysaccharide induced PGE2 production in RAW264.7 mouse macrophage cells and their GC‐MS chromatograms having peaks for known and synthetically available compounds. When identification and quantification from GC‐MS revealed that major constituents present in one fraction (1 µg/ml) were alkylamide 10 (0.15 µM) and ketone 23 (0.24 µM), and that the other fraction (1 µg/ml) consisted of alkylamide 11 (3.6 µM), these constituents were screened at the concentrations present in the fraction using the PGE2 assay. The combination of alkylamide 10 and ketone 23 did not explain the bioactivity of its respective fraction, but alkylamide 11 was partially explanatory of the bioactivity, accounting for 30% reduction of PGE2 production compared to 81% reduction of PGE2 identified with the fraction. Chemically synthesized ketones 21 and 23 were also shown to individually inhibit PGE2 and nitric oxide production at a concentration as low as 1µM, providing a basis to study these constituents further for anti‐inflammatory potential. Funding: 9 P50 AT004155‐06 from ODS/NCCAM, NIH.Grant Funding Source9 P50 AT004155‐06 from ODS/NCCAM, NIH
Effect of protein intake and weight loss on bone in overweight‐obese postmenopausal women
Authors: Sukumar Deeptha , Zurfluh Robert , Kwon Jane , Schneider Stephen , Stahl Theodore , Shapses Sue 
Published: June 2021

High protein intake is a popular method to achieve weight (wt) reduction; however its effect on bone remains controversial. Understanding whether dietary protein intake influences bone mass during caloric restriction was the goal in this study while controlling for dietary calcium. We examined 40 postmenopausal women (58 ¡À 5 years; BMI of 32.4 ¡À 5.7 kg/m2), who were assigned to caloric restriction and 1.2 g Ca/day with either a normal (NP, 18%, n =20) or higher (HP, 30%, n =20) protein intake and a low fat intake (28%). Bone measurements using dual energy x‐ray absorptiometry were performed at baseline, and 6 and 12 months after wt loss. Here we report the data after 6 months of wt loss (‐7.3 ¡À 4%) that did not differ significantly between groups. Total body bone mineral density and lumbar spine bone mineral content decreased (p<0.05) more in the NP (‐2.0% and ‐1.6% respectively) compared to HP group (‐0.1 % and 1.2% respectively). In a subset of women (n=22), bone turnover markers were measured and showed no changes, but there was a trend (p¡Ü0.08) for a greater increase in serum 25‐hydroxyvitamin D and parathyroid hormone in the NP than HP group, that requires confirmation in the entire group. These data suggest that higher dietary protein attenuates bone loss during wt reduction in postmenopausal women. Further analysis of the mechanisms mediating these changes is being addressed.SUPPORT: NIḦCAG12161, Busch Biomedical GrantGrant Funding SourceNIA‐NIH
Long‐term caloric restriction increases apoptosis and decreases cell stress response, despite an elevation in antioxidant enzyme capacity in the skeletal muscle of the Cu/Zn‐SOD mutant G93A mouse, an animal model of ALS
Authors: Patel Barkha , Tarnopolsky Mark A , Hamadeh Mazen J 
Published: June 2021

Despite its life‐extending properties, long‐term caloric restriction (CR) hastens clinical onset and shortens life span in the G93A mouse, an animal model of ALS (Hamadeh et al, 2005; Hamadeh and Tarnopolsky, 2005). We previously reported that CR increased lipid peroxidation (MDA) in this model (Patel et al, 2007). We hypothesized that CR would increase apoptosis and decrease cell stress response, with an incomplete compensatory upregulation of antioxidant enzymes. We investigated the effect of long‐term CR on the protein content of antioxidant enzymes (GPx1, GR), and markers of cell stress response (Hsp70) and apoptosis (Bax, caspase 9, cleaved caspase 9) in 99 d quadriceps of G93A mice. Starting at age 40 d, 27 mice were divided into ad libitum (AL, 14; 7 males) or CR (13; 7 males; 60% of AL). GPx1 increased in CR vs. AL mice (37%, P = 0.019) and in CR vs. AL females (56%, P = 0.012), with no change in GR. GPx1/GR was higher in CR vs. AL females only (88%, P = 0.013). Hsp70 was lower in CR vs. AL mice (62%, P = 0.002) and in males vs. females (37%, P = 0.030). Bax was higher in CR vs. AL mice (41%, P = 0.027) and in CR vs. AL females (52%, P = 0.048). Bax/Bcl‐2 was elevated in CR vs. AL mice (68%, P = 0.040) and in CR vs. AL females (2.3‐fold, P = 0.029). There were no differences in caspases. We conclude that CR increases apoptosis in the G93A mouse due to impairment in cell stress response and an incomplete compensatory upregulation of antioxidant enzymes.Grant Funding SourceHamilton Health Sciences Foundation, NSERC, Faculty of Health‐York University
Coffee increases antioxidant enzyme capacity in the brain of male G93A mice, an animal model of amyotrophic lateral sclerosis (ALS)
Authors: Seevaratnam Rajini , Raha Sandeep , Tarnopolsky Mark A , Hamadeh Mazen J 
Published: June 2021

Oxidative stress is implicated in several neurodegenerative diseases including ALS. Coffee (COF) consumption increases antioxidant status and reduces oxidative stress. To determine whether this effect is due to its single or combined constituents, we studied the effect of COF, caffeine (CAF) and chlorogenic acid (CHLA) on food intake (FI), body weight (BW), body condition (BC), motor performance (MP), ability to move (AM), clinical score (CS), and antioxidant enzyme protein content (MnSOD; CAT; GR) in the brain of 108‐d old male G93A mice. Starting at age 40‐d, 21 mice were randomly divided into control (CON, 6), COF (5), CAF (5) or CHLA (5). Compounds were added to the food, equivalent to amounts found in 5‐10 cups of coffee/day (mg/g BW). FI increased over time (P < 0.001); all groups consumed more than CON (COF, 21%, P = 0.014; CAF, 22%, P = 0.018; CHLA, 12%, P = 0.086). BW increased and BC decreased over time (P < 0.001) with no differences between groups. MP increased over time (P < 0.001) and was higher in COF vs. all groups (CON, 6%; CAF, 27%; CHLA, 40%; NS). CAT was higher in COF vs. all groups (CON, 61%, P = 0.002; CAF, 25%, P = 0.028; CHLA, 22%, P = 0.023). There were no significant differences in CS, AM, MnSOD and GR. We conclude that COF, independent of CAF or CHLA, is protective in male G93A mice by improving motor performance and increasing antioxidant enzyme capacity.Grant Funding SourceHHSF, NSERC, York U‐Health
Vitamin D Therapy Reduces Blood Pressure: A Case Series
Authors: Judd Suzanne E , Raiser Sara , Kumari Meena , Tangpricha Vin 
Published: June 2021

We investigated the effect of vitamin D repletion on resolution of hypertension in non‐whites using a pilot study. Subjects were recruited from the Atlanta Veterans Affairs Medical Center (VAMC) in Atlanta, GA. Subjects received a total dose of 600,000 IU D3 or placebo (n=3) taken weekly either over 3 weeks (n=2) or 12 weeks (n=3) or were given 0.5 ug calcitriol (n=2) taken twice daily for one week. We used a 24 hour ambulatory blood pressure (24 aBP) monitor to assess blood pressure. The calcitriol group experienced a 13% reduction in mean systolic aBP while the placebo group only decreased by 4% (p<0.001). One week after conclusion of calcitriol therapy 24 aBP pressure returned to pretreatment levels. In pooled analysis of all subjects randomized to vitamin D3, the mean 24 aBP decreased by 5% (p<0.001) in the group using D3. Compared with placebo, this change was not significant. Sub‐analysis demonstrated the individual experiencing the largest reduction in blood pressure using vitamin D3 had the highest plasma renin activity. Calcitriol had a strong rapid effect on blood pressure reduction while the effect of D3 may be limited to individuals with high plasma renin activity. Vitamin D therapy may be an effective intervention for reducing blood pressure.Grant Funding SourceASN and CF Foundation
Innate defense responses in Muc2 deficient mice: an important role for goblet cells
Authors: Burger‐van Paassen Nanda , Bouma Janneke , dez Bruijn Adrianus CJM , van der Sluis Maria , Van Seuningen Isabelle , Van Goudoever Johannes B , Renes Ingrid B 
Published: June 2021

BackgroundAbsence of a mucus layer, as in Muc2 knockout (KO) mice, leads the induction of colitis due to aberrant bacterial‐epithelial interactions. We hypothesize that innate defense molecules, i.e. bactericidal peptides, are upregulated in Muc2KO mice to compensate for loss of the mucus layer.AimTo study the innate defense response in Muc2KO mice.MethodsColonic tissue of Muc2KO and wild type (WT) mice was collected up to 28 days after birth. Expression of the bactericidal peptides; regenerating gene (Reg)3β, Reg3γ and angiogenin (Ang)4 was studied by qPCR, in situ hybridization and/or immunohistochemistry. Additionally, influx of T cells into the mucosa was studied as marker for inflammation.ResultsCompared to WT mice, Reg3β and Reg3γ mRNA levels were increased up to 50 fold in KO mice at 14 days, and a further increase was seen at 28 days. In contrast, Ang4 expression was observed in the colon of WT mice, but not in the colon of KO mice. Finally, the number of infiltrating T cells in the colon increased with age in KO mice.ConclusionsStrong upregulation of Reg3β and Reg3γ in the colon of KO mice suggests increased innate defense capacity to compensate for the loss of intestinal barrier function. Reg3 gene expression correlates with the increased influx of T‐cells, implying a role for Reg3 peptides in intestinal inflammation. Absence of Ang4 expression in KO mice might indicate diminished bactericidal activity.
Interleukin‐1 receptor activates Rho kinase to disrupt epithelial tight junctions during Helicobacter pylori infection
Authors: Lapointe Tamia K , O'Connor Pamela M , Ménard Daniel , Buret Andre G 
Published: June 2021

The ability of H. pylori (Hp) to modulate tight junction (TJ) permeability may contribute to the development of gastric ulcers and adenocarcinomas. Rho kinase (ROCK) and interleukin (IL)‐1β are known to modulate tight junction (TJ) function. While Hp induces IL‐1β expression, the role of this proinflammatory cytokine and ROCK in Hp‐mediated TJ disruption remains elusive.AIMThis study investigated the role of ROCK and IL‐1β in Hp‐mediated TJ disruption in human gastric epithelial (HGE‐20) cells.RESULTSHGE‐20 monolayers challenged with either Hp or IL‐1β showed an increase in ROCK activity 6 h post infection, which coincided with redistribution and loss of claudin‐4. Inhibition of ROCK prior to bacterial challenge prevented these effects. Hp infection also induced IL‐1 receptor (IL‐1R) phosphorylation. Nevertheless, no increase in IL‐1β could be detected in supernatants of infected monolayers and treatment with co‐culture conditioned media failed to induce IL‐1R phosphorylation. While an IL‐1β neutralizing antibody did not prevent Hp‐induced IL‐1R activation, the use of an IL‐1R blocking antibody prior to infection prevented Hp‐mediated ROCK activation and claudin‐4 loss.CONCLUSIONThese findings suggest that the mechanism by which Hp disrupts gastric epithelial barrier structure involves IL‐1R ‐dependent activation of ROCK, which mediates claudin‐4 disruption. This work was funded by CIHR.
Mesenchymal regulation of mineralization and bone mineral density in the jaw skeleton
Authors: Yu Jane , Jheon Andrew H. , Eames Brian F. , Schneider Richard A. 
Published: June 2021

Proper bone mineral density (BMD) is crucial for skeletal function. Loss of BMD can lead to osteoporosis and fractures. From an evolutionary perspective, BMD helps couple morphology to the environment. For example, in aquatic mammals a higher BMD enables negative buoyancy during diving. BMD is governed by systemic and local factors throughout the life of an organism. On a cellular level, BMD is affected by osteoblasts, which secrete bone matrix that then mineralizes. During craniofacial development, osteoblasts are derived from neural crest mesenchyme (NCM). We use an avian chimeric system that exploits differences in morphology and maturation rates between quail and duck to investigate the role of NCM in establishing BMD. We unilaterally transplant quail NCM into duck, which maintains the host side as an internal control, and we analyze mineralization at the molecular and histological levels. We assess mineral deposition rates in quail, duck, and chimeric embryos by injecting fluorescent labels and by whole‐mount staining. We also measure BMD using DEXA. We find that duck have a slower rate and longer period of mineralization correlated with higher BMD, which is significant since duck use their bills for filter feeding and for diving. In chimeras, quail donor NCM alters the rate of mineral deposition. Thus, species‐specific differences in BMD have likely evolved through NCM‐mediated changes in mineralization.Grant Funding SourceDepartmental Startup
Mechanisms of protein translocation across membranes
Authors: Rapoport Tom A 
Published: June 2021

Many proteins in bacteria are transported during their biosynthesis across or are integrated into the plasma membrane, a process that is similar to protein translocation across endoplasmic reticulum (ER) membrane in eukaryotes. Transport occurs through a protein‐conducting channel that is formed from a conserved heterotrimeric membrane protein complex (SecY or Sec61 complex). The channel associates with different partners in different translocation pathways. In bacteria, the SecY channel can associate with the translating ribosome (co‐translational translocation) or with the cytoplasmic ATPase SecA (post‐translational translocation).The crystal structure of an archaeal SecY complex shows the architecture of the closed channel. The structure suggests that a single SecY copy forms the translocation pore, a prediction that was confirmed for SecA‐mediated translocation by disulfide bridge crosslinking experiments. However, translocation appears to be mediated by oligomers of the SecY complex; nucleotide‐binding fold 1 (NBF1) of SecA interacts with a non‐translocating SecY copy, while other domains of SecA "push" the polypeptide chain through a neighboring SecY copy.A recently determined crystal structure shows one copy of SecA in its transitions state of ATP hydrolysis bound to one copy of SecY complex. The latter corresponds to the translocating SecY copy. Both SecA and SecY undergo major conformational changes upon interaction. The structure suggests mechanisms for how SecA moves polypeptides through the SecY channel. In addition, the data reveal that SecA binding opens the lateral gate of SecY for signal sequence intercalation, and induces plug movement. These results indicate that the channel is opened for translocation in two distinct steps, induced by SecA and signal sequence binding.