bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of the murine Voltage Dependent Anion Channel 1 (mVDAC1) at 2.3 Å resolution
Authors: Ujwal Rachna , Cascio Duilio , Colletier Jacques‐Philippe , Faham Salem , Zhang Jun , Toro Ligia , Ping Peipei , Abramson Jeff 
Published: June 2021

VDAC constitutes the primary pathway for the exchange of metabolites across the outer mitochondrial membrane. It acts as a scaffold for modulator proteins and is implicated in mitochondria‐dependent cell death. Because of its critical role in mitochondrial biology, we sought to obtain the crystal structure of VDAC as a first step to understanding its gating mechanism, in vivo regulation and interaction with other proteins. mVDAC1 was expressed in E. coli, purified from inclusion body and refolded. The purified protein was biochemically characterized to ensure that its identity, proper fold and electrophysiological properties are the same as the native protein.We present the structure of mVDAC1 at 2.3 Åresolution crystallized in lipidic bicelles to preserve the native conformation. mVDAC1 adopts a β‐barrel architecture composed of 19 β‐strands, thus displaying a new fold for β‐barrel membrane proteins resulting from an odd number of strands. The N‐terminus is located inside the barrel and forms an α‐helix halfway down the pore resulting in a partial narrowing at the center. This orientation of the helix is ideally suited to gate metabolite flux through the channel. The mVDAC1 structure presented here represents the first high resolution crystal structure of a eukaryotic β‐barrel membrane protein providing critical information for our understanding of its role in mitochondrial physiology. Funding: NIH and AHA.
Enhanced liver regeneration with percutaneous, pulsed, near infrared light: a pilot study
Authors: Russ Tiffany Cherelle , Beeston John , Fisher Robert 
Published: June 2021

PurposeThe aim of this study was to determine if photobiomodulation (light therapy), on rats who receive 70% Partial Hepatectomy, enhances both rate and amount of hepatic growth after one week, compared with liver enhancement as a result of Prograf and a control group. Methods and Materials: Twenty‐four male Lewis rats were randomly selected and placed into four groups. Their diet consists of normal rat chow and a 20% glucose solution after surgery. An acclimation period of one week is required pre‐operatively. The left and medial lobes of the liver, 70% in total, will be removed or suture‐ligated. This leaves each animal with only its right and caudate lobes for metabolic function. Group one receives no light and no Prograf (Tacrolimus). The livers of these animals are expected to regenerate naturally. Group two receives one five‐minute treatment of light therapy for five days and no Prograf, group three receives a combination of the two treatments, and group four receives the hepatic stimulus (Tacrolimus).ResultsThe results of this experiment are pending due to the need of further investigation. It is still in progress.ConclusionIf the effects of this light treatment prove to be substantial, then patients who suffer from various liver afflictions and require partial hepatectomy because of these ailments can obtain a faster and less morbid recovery. (Source of Research support: NIDDK)
Visualizing skull in prenatal mice with syndromic craniosynostosis
Authors: DeLeon Valerie Burke , Perlyn Chad A , Prajapati Suresh I , Keller Charles 
Published: June 2021

Crouzon syndrome is characterized by premature fusion of multiple cranial sutures and profound facial dysmorphology. Improved treatment requires better understanding of the mechanisms of malformation. This study quantifies the progression of cranial dysmorphology in the Fgfr2+/C342Y mouse model of Crouzon syndrome. Samples of affected and wild‐type littermates were obtained at six developmental time points: E15.5, E17.5, P1, P7, P14, and adult. 3D reconstructions of the skull were created from microCT images using density thresholds. However, as this technique is dependent on the ossification of bone, and dysmorphology may arise earlier in development, we applied a novel method that allows us to visualize developing cranial tissues. Specifically, E15.5 samples were treated with radioopaque stain prior to microCT imaging, and cranial primordia were segmented manually. Morphometric analysis (EDMA) was used to compare shape of affected and wild‐type samples at each time point.Results indicate that dysmorphology originates in the prenatal period, when significant differences are apparent in the anterior cranial base and, to a lesser extent, the face. Significant brachycephaly becomes evident postnatally. These results confirm that dysmorphology in the mouse model of Crouzon syndrome arises prior to the bony fusion of the sutures, and that the primary defect may be localized to the anterior cranial base.
Differential regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Chemerin and CMKLR1
Authors: Shanmugam Muruganandan , Roman Alexandra , Sinal Christopher 
Published: June 2021

Adipocytes and osteoblasts are derived from a common mesenchymal stem cell progenitor within the bone marrow. Previous studies have identified an inverse relationship between adipocyte and osteoblast differentiation of these cells in bone marrow. Work from our laboratory identified chemerin as a novel adipokine that together with its cognate receptor, CMKLR1 plays an indispensable role in regulating adipocyte differentiation of 3T3‐L1 preadipocytes. In the present study we hypothesized that chemerin and its cognate receptor, CMKLR1 is also essential for adipocyte differentiation of bone marrow‐derived mesenchymal stem cells and may simultaneously competitively suppress the alternate osteoblastogenic program. Knockdown of chemerin or CMKLR1 by short hairpin loop RNAs (shRNA) in murine bone marrow primary mesenchymal stem cells abrogated preadipocyte clonal expansion, adipogenic gene expression and lipid accumulation along with the promotion of mineralization and osteoblastogenic gene expression. Thus we conclude that chemerin is essential for bone marrow mesenchymal stem cell adipogenesis and may negatively impact osteoblastogenesis in these cells.Funding:1. Canadian Institutes of Health Research2. Nova Scotia Health Research Foundation
Euglena gracilis contains an Ubiquitin‐S27a homologue
Authors: Torres‐Marquez M Eugenia , Diaz‐Mireles Edith 
Published: June 2021

Ubiquitination is a widely expressed process in eukaryotic cells. For this postraductional modification to take place, the presence of ubiquitin is necessary. Unicellular organisms, such as the parasite Giardia, have been shown to contain this 8.5kDa polypeptide. However, this ubiquitin finding does not clarify whether the presence of this polypeptide is an adaptation to the host on those organisms or the origin of the posttranslational modifier is related to eukaryotic cell evolution. Thus, the search for a ubiquitin homologue in free living protists, such as Euglena gracilis; becomes relevant as to understand the evolution of signal transduction elements. We were able to find in a E. gracilis cDNA library an Ubiquitin‐S27a protein, which consists of two main domains. The N‐terminal domain is the ubiquitin protein formed by the first 76 amino acids with a molecular weight of 8.5 kDa and a theoretical pI: 6.56. The C‐terminal ribosomal protein S27a is 81 amino acids long with a molecular weight of 9.3 kDa and a pI of 9.88. We are currently scrutinizing in our laboratory whether the ubiquitin‐like protein found in E. gracilis has a role as a protein modifier or as a chaperone at ribosomal assembly.Partly supported by Grant DGAPA219508
TRIBUTYLTIN CAUSES ACTIVATION OF C‐RAF IN HUMAN NATURAL KILLER CELLS
Authors: Celada Lindsay J. , Whalen Margaret 
Published: June 2021

The toxic chemical Tributyltin (TBT) has been found in human blood. TBT is employed in wood preservation, in marine paints as an antifouling agent, as an antifungal in textiles and industrial water systems, among other things. Human natural killer cells (NK) are a subset of lymphocytes capable of destroying tumor cells, virally infected cells, and antibody‐coated cells. It has been shown that TBT is able to diminish the lytic function of NK cells. Previous studies have demonstrated that exposure to TBT leads to the activation of Mitogen‐Activated‐Protein‐Kinase (MAPK) and MAPK‐Kinase (MAP2K) in NK cells. The focus of this study is to examine whether TBT also results in the activation of MAPK Kinase‐Kinase (MAP3K), c‐Raf, at an exposure time of ten minutes in NK cells. Activation/phosphorylation of c‐Raf (Ser338) was seen with exposure to 300, 200, 100, and 50 nM TBT (2 fold at 300‐100 nM and 1.45 fold at 50 nM). Increased phosphorylation of Ser259 was also seen with 300‐200 nM TBT (2 and 1.7 fold, respectively). Exposures to 300, 200, and 100 nM TBT increased phosphorylation of Ser289/296/301, 2.5, 2.0, and 2.4 fold, respectively. One hour exposures of NK cells to these same concentrations of TBT (300‐ 25 nM) are currently being carried out to see if the effect continues or if it is short‐lived.Supported by NIH grant S06 GM008092‐33
Analgesic properties of an indigenous polyherbal preparation
Authors: IROANYA ONYEKACHI OGBONNAYA , OKPUZOR JOY ELISABETH , MBAGWU HERBERT , OJOBO PETER DOUGLAS 
Published: June 2021

The Pharmacological effect of the polyherbal preparation of an aqueous extract obtained from the leaves of Gongronema latifolia, Vernonia amygdalina and Ocimum gratissimum was evaluated for its analgesic effect and acute toxicity. The effects of the preparation was studied using various in vivo models of analgesic effects (central and peripheral acting analgesics) in mice and the potent inhibitory activity against acetic acid induced mouse writhing , hot plate and formalin induced pain tests.In control mice, the reaction time to the mouse writhing assay was 91 ± 12.00. The mice injected with 10mg\kg of 0.6% acetic acid (i.p.) presented 68.9% writhes in 15 minutes while treatment with the extract at 2000mg\kg, 4000mg\kg and 8000mg\kg of the extract significantly (P <0.05) and dose dependently reduced the number of writhes by 61.9% , 65.7% and 66.6% writhes respectively in 15 minutes. The extract demonstrated a dose dependent relationship in the hot plate and formalin induced pain assay. The highest dose of the extract presented a significant inhibition 138.5% in comparism to that produced by Morphine 180.8% for the hot plate assay while for the formalin induced pain assay, the highest dose exhibited a significant inhibition of 46% while Acetylsalicylic acid produced a significant inhibition of 49%.The single oral dose of the Polyherbal extract at 16000mg\kg (p.o.) and 2500mg\kg (i.p.) did not produce mortality or significant change in the general behaviour of the mice.The data obtained shows that this polyherbal preparation possesses analgesic activity.
Grain of paradise extracts increase energy expenditure in humans
Authors: Suzuki Isao , Sugishima Yuuki , Sugita Jun , Ikemoto Takeshi , Shimizu Yasutake , Murata Tamami , Akazawa Yumiko , Mori Kenji , Inoue Shintaro 
Published: June 2021

ObjectiveGrain of paradise (GP; Aframomum melegueta) is an herbaceous plant from the ginger family. Two components of GP, paradol and gingerol, are structurally similar to capsaicin, a pungent compound with anti‐obese actions. Our group investigated the effects of GP‐extracts on energy expenditure and the prevention of obesity.MethodsWe investigated the effects of GP‐extracts on norepinephrine (NE)‐induced lipolysis in 3T3‐L1 cells, on the progression of obesity in high fat diet (HFD)‐induced obese mice, and on body weight and energy expenditure in humans receiving repeated doses of the extracts for 4 weeks.ResultsGP‐extracts accelerated lipolysis in 3T3‐L1 cells. In the obese mice, the extracts prevented HFD‐induced elevations in body and adipose tissue weights. In humans, the energy expenditure observed after the intake of GP‐extracts differed significantly from that observed before the intake.ConclusionGP‐extracts intake enhances the energy expenditure and basal metabolism in humans, possibly via an acceleration of lipolysis followed by fat combustion. The effects of GP‐extracts on energy expenditure are thought to be caused by paradol and gingerol major components of the extract.
Effects of kale extracts on inflammatory processes in vitro
Authors: Kuntz Sabine , Kunz Clemens , Rudloff Silvia 
Published: June 2021

BackgroundThe nutritional impact of vegetables such as kale (Brassica oleraceae) has long been expected to reveal anti‐inflammatory potential. Therefore, we investigated whether water (ws) and fat soluble (fs) extracts of green cabbage affects cytokine induced expression of endothelial cell adhesion molecules as well as the adhesion of leukocytes to endothelial cells (HUVEC).MethodsHUVEC were incubated with extracts from green cabbage for 24 h and then activated with TNF‐alpha. 5 h later, the expression of ICAM‐1 and VCAM‐1 was determined by RT‐PCR and leukocyte adhesion was measured using a flow model.ResultsThe exposure of HUVEC to ws‐ and fs‐ extracts from green cabbage significantly reduced the TNF‐alpha induced expression of cell adhesion molecules. These effects were concentration dependent inhibiting ICAM‐1 expression by 45.5 ± 5.3 % for the ws and 66.8 ± 6.3 % for the fs cabbage extract when compared to controls; VCAM‐1 expression was reduced by 87.5 ± 6.9 % and 76.1 ± 9.4 % for the ws and fs extracts, respectively. At this concentration of cabbage extracts, we also observed a reduced adhesion of leukocytes to HUVEC to about 50 % of the controls.ConclusionThe inhibitory effect of water and fat soluble ingredients of green cabbage on the expression of cell adhesion molecules in activated endothelial cells as well as on leukocyte adhesion confirmed their anti‐inflammatory potential.
Inhibitiory role of curcumin in adipogenesis
Authors: Kim Choon Young , Kim Kee‐Hong 
Published: June 2021

Adipogenesis has been suggested to be a target mechanism to treat and prevent obesity. Induction of inflammatory response and oxidative stress has been observed in the process of adipogenesis. Curcumin having anti‐oxidative and anti‐inflammatory properties brought us to test the hypothesis that curcumin inhibits adipogenesis. We found that curcumin significantly inhibits 3T3‐L1 preadipocyte adipogenesis in vitro in a dose‐dependent manner and a complete inhibition of adipogenesis was observed at 30 µM. Interestingly, curcumin inhibits cell viability of proliferating 3T3‐L1 preadipocytes in a dose‐dependent manner but not in differentiating 3T3‐L1 cells. We also revealed that the inhibitory effect of curcumin on 3T3‐L1 preadipocyte differentiation is limited to the early stage (Day 0 to 2) of adipogenesis. Image analysis of cellular uptake of curcumin revealed the presence of curcumin in the differentiating 3T3‐L1 adipocytes. Furthermore, we found that curcumin significantly reduced mRNA expression levels of adipogenic transcription factors, including peroxisome proliferator‐activated receptorγ (PPARγ) and CAATT/enhancer binding proteinα (C/EBPα), but not C/EBPβ. Taken together, our results support that curcumin has anti‐adipogenic property in vitro and this is likely due to inhibition of mRNA expression of PPARγ and C/EBPα in the early stage of adipogenesis.Grant Funding SourceStart‐up research fund
Anti‐Inflammatory Effects of Xanthones from Mangosteen in Primary Cultures of Human Adipocytes
Authors: Bumrungpert Akkarach , Kalpravidh R. , Chitchumroonchokchai C. , Chuang C. , West T. , Kennedy A. , McIntosh M. 
Published: June 2021

The xanthones, α‐ and γ‐ mangostin (MG), are major bioactive compounds found in mangosteen reported to have anti‐inflammatory activities in several murine models. Given the association between chronic, low grade inflammation and obesity, we examined the anti‐inflammatory effects of α‐ and γ‐ MG in primary cultures of human adipocytes in the presence or absence of lipopolysaccharide (LPS). α‐ and γ‐MG significantly decreased LPS induction of inflammatory adipocytokines (i.e., TNF‐α, IL‐1β, IL‐6, IL‐8, and MCP‐1). Moreover, α‐ and γ‐ MG attenuated LPS activation of the mitogen‐activated protein kinases (MAPK) c‐jun NH2‐terminal kinase (JNK), extracellular signal‐related kinase (ERK), and p38. γ‐ MG was more effective than α‐ MG on an equimolar basis. Furthermore, γ‐MG, but not α‐MG, attenuated LPS‐mediated IκB‐α degradation and nuclear factor‐κB (NF‐κB) transcriptional activity. In conclusion, these data demonstrate for the first time that α‐ and γ‐ MG attenuate LPS‐mediated inflammation in human (pre)adipocytes by inhibiting MAPK or NF‐κB signaling. These data suggest that MG has the potential to attenuate chronic inflammation associated with obesity. (Supported by National Research Council of Thailand)Grant Funding SourceNational Research Council of Thailand
Wild Blueberries (V. angustifolium) Protect Lymphocytes against DNA Damage in Sprague Dawley Rats
Authors: Del Bò Cristian , Riso Patrizia , Ciappellano Salvatore , Martini Daniela , Gardana Claudio , Porrini Marisa , Klimis‐Zacas Dorothy J. 
Published: June 2021

The effect of wild blueberry consumption on lymphocyte resistance against oxidative stress was evaluated in Sprague‐Dawley (SD) rats. Sixteen, 5 week‐old SD rats were fed a control (C) or a wild blueberry (WB) diet for 8 weeks. Anthocyanin (ACN) profile in urine and feces was analyzed by LC‐MS/MS. Ex vivo protection from H2O2‐induced DNA damage (500 µmol/L) was evaluated in lymphocytes by the comet assay. No significant differences were detected in body weight between the WB (459 ± 21 g) and C (444 ± 20 g) diet groups or in liver weight (19.4 ± 2.9 g vs. 19.0 ± 1.6 g for WB and C diets respectively). After 8 weeks on the WB diet, ACN concentration in feces and urine was 25.9 ± 9.2 µg/g and 127.6 ± 46.3 ng/ml, while only traces were detected in plasma. No ACNs were found in rats fed the C diet. Metabolites of ACNs (i.e. gallic and hippuric acids) were present in urine and feces of the WB group. Wild blueberry consumption improved lymphocyte protection against oxidative stress. Levels of DNA damage were significantly lower in rats fed the WB diet compared to those on the C diet (11.2 ± 4.1% vs. 17.2 ± 8.0% DNA in tail, p=0.05).We have documented that wild blueberry ACNs are bioavailable in SD rats fed a WB diet for 8 weeks. Additionally, wild blueberry consumption reduced lymphocyte DNA damage from oxidative stress which may have implications on degenerative disease.This work was supported by a Cariplo Foundation Grant.
ANTIDIABETIC AND ANTIDYSLIPIDEMIA EFFECTS OF CHUNGKUKJANG AND RED GINSENG‐CHUNGKUKJANG IN MILD HYPERGLYCEMIC SUBJECTS
Authors: Shin Su‐Kyoung , Kwon Joong‐Ho , Jeong Yong‐Jin , Jeon Sun‐Min , Kim Hye‐Jin , Choi Ji‐Young , Do Gyeong‐Min , Choi Myung‐Sook 
Published: June 2021

Red ginseng and Chungkukjang are well known as typical Korean functional foods that exhibit various bioactivities. This study was conducted to investigate blood glucose‐lowering activity of chungkukjang and red‐ginseng chungkukjang in hyperglycemic subjects. They were randomly divided into the control (starch, 2g/day), chungkukjang (CH, 20g/day) and red‐ginseng chungkukjang (RGCH, 20g/day) groups. Fasting blood glucose concentration was significantly lowered by 26% in CH group and 18% in RGCH group after 8 weeks compared to the initial value (p<0.001). The levels of blood HbA1c was significantly lowered in the CH group compared to the before supplementation (p<0.05). Total cholesterol and LDL‐cholesterol level were significantly lowered in both the CH (p<0.05) and RGCH (p<0.01) groups than in the control group. FFA level was significantly lowered in experimental groups (p<0.001). Erythrocyte TBARS level was significantly lowered in the CH and RGCH groups compared to respective initial values (p<0.01). It is considered that CH and RGCH are beneficial for regulating fasting blood glucose level and blood lipids level in the mild hyperglycemic subjects.Grant Funding SourceThe second stage of Brain Korea 21
Moderate energy deprivation increases ubiquitin proteasome activity in physically active adults following endurance exercise
Authors: Carbone John W , Pasiakos Stefan M , Vislocky Lisa M , Anderson Jeffrey M , Giardina Charles , Bruno Richard S , Rodriguez Nancy R 
Published: June 2021

The ubiquitin proteasome, the major proteolytic nanomachine in skeletal muscle, is influenced by energy state and endocrine environment. No studies have examined the effect of an acute energy deficit on proteasome activity in humans.PURPOSEThis study assessed the effect of an acute energy deficit on 26S proteasome activity at rest and following endurance exercise in physically active adults.METHODSMen (n=11) and women (n=7) participated in a 20d, two‐phase diet intervention: weight maintenance, WM; and energy deficient, ~80% of energy requirements, ED. Dietary protein (1.5 g·kg−1·d−1) and fat (~30% of total calories) were constant for WM and ED. 26S activity was measured, using a fluorescence‐based assay, following exercise (45min run, 65% VO2peak) and at rest for WM and ED diet interventions. Plasma insulin levels were determined by ELISA.RESULTS26S activity increased by 24% (P < 0.05) for ED versus WM post‐exercise. Insulin was lower (P < 0.05) for ED (14 ± 1 μIU/mL) compared to WM (19 ± 2 μIU/mL). The reduction in insulin was inversely correlated to 26S activity (r=0.55, P < 0.01).CONCLUSIONSThese findings suggest that ubiquitin proteasome activity was upregulated in response to an acute, moderate energy deficit that is potentiated following a bout of endurance exercise. Further research is warranted to investigate the effects of energy homeostasis on the regulation of skeletal muscle proteolysis.
A Mixed Protein Diet at the Upper End of the Acceptable Macronutrient Distribution Range for Protein Increases Renal Fibrosis in the Pig Model
Authors: Aukema Harold , Jia Yong , Hwang Sun Young , House James , Ogborn Malcolm , Weiler Hope , O Karmin 
Published: June 2021

The acceptable macronutrient distribution range (AMDR) for protein has been set at 10‐35% of energy. The current study assessed the consequences of long‐term consumption of a mixed high protein diet at the upper end of the AMDR on the pig kidney.MethodsUsing whole protein sources, adult female pigs were given either normal (NP, 15% of energy) or high protein (HP, 35% of energy) isocaloric diets for 4 or 8 months. The protein in the NP diet was derived from animal and plant sources in a 2:1 ratio; the increased protein in the HP diet was achieved by increasing egg and dairy protein. Glomerular volume and renal fibrosis were quantified by image analysis. The renal inflammatory marker monocyte chemoattractant protein‐1 (MCP‐1) and the growth factor transforming growth factor beta‐1 (TGFβ1) were determined by ELISA.ResultsPigs given the HP diet at 4, but not 8 months, had lower body weights and body fat, higher renal MCP‐1 levels and a trend towards higher glomerular filtration rates. At 8 months, kidney and glomerular volume, and tubulointerstitial fibrosis were significantly higher in pigs given the HP diet, while proteinuria and renal TGFβ1 expression did not differ.ConclusionDespite the potential benefits on body composition, long‐term intakes of protein at the upper limit of the AMDR may compromise renal health in healthy female pigs. Supported by CIHR.