bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does adult weight scale as height squared? An across gender and race‐ethnicity analysis (130.1)
Authors: Heymsfield Steven , Thomas Diana , Peterson Courtney , Heo Moonseong , Hong Sangmo , Choi Woong 
Published: June 2021

A key and often‐challenged BMI assumption is that weight (W) scales to height (H) squared across men, women, and all race‐ethnic groups. This hypothesis was tested in similarly conducted US and Korean HANES studies that included 7309 men and 6204 women with complete DXA scans for %fat and regional body mass (head, trunk, arms, legs), and who were non‐Hispanic (NH) white, NH black, Mexican American, or Korean. Gender and race/ethnicity‐specific H powers were derived with log(W) as allometric regression model dependent variable and log(H) as independent variable with adjustments for log(age) and log(%fat). H powers (±SE; table) all centered around 2.0; no significant sex‐race/ethnicity differences in H powers were present at a 2‐sided 0.05 significance level. Relative to W, regional mass H powers scaled in the sequence: legs (~2.2) > arms (~1.9) & trunk (~2.0) > head (~0.8). W thus scales very close to 2.0 across men, women, and the evaluated race/ethnicity groups and reflects the weighted scaling of different body regions. Weight adjusted for H2 is an appropriate means of adjusting W for between‐individual H differences regardless of gender or race/ethnicity.
H Powers

H Power±SE
NH White
NH Black
Mex Am
Korean

Men
1.97±0.08
2.03±0.15
2.16±0.12
1.96±0.04

95% CI
1.81‐2.14
1.74‐2.32
1.86‐2.35
1.88‐2.04

Women
2.12±0.08
2.19±0.14
2.10±0.10
2.09±0.05

95% CI
1.97‐2.26
1.92‐2.46
1.90‐2.30
2.00‐2.19
Metabolic syndrome in TLR5 deficient mice is associated with microbiota dependent MUFA enriched hepatic lipids (133.6)
Authors: Chassaing Benoit , Kumar Manish , Gewirtz Andrew , Vijay‐Kumar Matam 
Published: June 2021

Obesity (leptin deficiency) is associated with elevated monounsaturated fatty acids (MUFA) specifically palmitoleate (C16:1) and oleate (C18:1) in tissue neutral lipids. Toll Like Receptor 5 (TLR5), an innate immune receptor for bacterial flagellin is required for gut microbiota homeostasis. Accordingly, mice lacking TLR5 (TLR5KO) develop spontaneous low‐grade gut inflammation and metabolic syndrome, which are microbiota dependent. Here, we examined whether metabolic syndrome in TLR5KO mice is associated with elevated MUFA levels. We analyzed fatty acid composition of total lipid (TL), triglycerides (TG), cholesterol esters (CE) and phospholipid (PL) fractions of the tissue lipids in age and gender matched TLR5KO and their WT littermates. We also analyzed MUFA levels in high‐fat fed, TLR2 or 4 deficient TLR5KO, calorie restricted, microbiota ablated, germ‐free (GF) and conventionalized GF‐WT mice transplanted with either WT or TLR5KO microbiota. TLR5KO mice displayed elevated hepatic TG and CE and substantially elevated C18:1 in TL, TG and CE but not in PL when compared to WT mice. Interestingly, in TLR5KO mice C16:1 levels were comparable to WT mice. Such elevated C18:1 was restricted to hepatic lipids and not in serum and adipose tissue lipids. The elevated C18:1 was also observed in high fat fed and calorie restricted TLR5KO mice. In addition, deletion of TLR2/4 did not prevent accumulation of C18:1 in TLR5KO mice hepatic lipids. However, in microbiota‐ablated (via antibiotics) as well as GF TLR5KO mice, C18:1 levels were comparable to WT mice. Finally, the pronounced C18:1 accumulation in hepatic lipids was recapitulated in GF‐WT mice transplanted with microbiota from TLR5KO mice than WT microbiota recipients. Collectively, these data demonstrate that gut microbiota dysbiosis in TLR5KO mice drives hepatic lipogenesis probably via generating precursors for MUFA (short chain fatty acids) that may result in hepatic insulin resistance finally culminating into metabolic syndrome.Grant Funding Source: NIH K01 and R03
Skeletal muscle fat accumulation and increased fatty acid saturation are related to worsening glucose control in older adults (133.8)
Authors: Dunville Keagan , Kim Jung Eun , Li Junjie , Conley Travis , Cheng Ji‐Xin , Talavage Thomas , Couture Cortni , Campbell Wayne 
Published: June 2021

Increased inter‐muscular adipose tissue (IMAT) content and intra‐myocellular lipid (IMCL) fatty acid saturation (FAS) are implicated in insulin resistance (IR), but potential relationships require further investigation because of limited data. This study examined the associations between IMAT content, IMCL FAS, and fasting plasma glucose concentrations in 10 men and women, age range 65‐76 y, plasma glucose 101±11 mg/dL (range 87‐114 mg/dL). Thigh muscle and adipose tissue volumes (magnetic resonance imaging) and the FAS of vastus lateralis IMCL (from muscle biopsies using Coherent Anti‐scattering Raman Spectroscopy and Spontaneous Raman Spectroscopy) were quantified. IMAT volume, standardized with respect to muscle tissue volume (ratio 0.10±0.02), was positively correlated with the ratio of saturated to unsaturated fatty acids in IMCL (r=0.709, p=0.02). IMAT volume and IMCL FAS were both positively associated with plasma glucose concentration (β=300.6, p=0.02, and β=105.4, p=0.02, respectively). These results suggest that inter‐muscular fat accumulation and increased myocellular fatty acid saturation are related to each other and both may contribute to worsening glucose control.Grant Funding Source: Supported by NIH UL1 TR000006, Purdue Ingest Behav Res Ctr, Amer Egg Board, Dairy Res Inst
TGFβ activates insulin‐like growth factor 1‐mediated signaling pathway in human liver cancer cells (144.9)
Authors: Ungerleider Nathan , Han Chang , Wu Tong 
Published: June 2021

Transforming growth factor β (TGFβ) potently inhibits the growth of human epithelial cells. However, neoplastic epithelial cells become resistant to TGFβ‐mediated mitoinhibition, and the mechanisms for this alteration during tumorigenesis are not fully understood. In this study, we demonstrate that TGFβ sensitises PLC/PRF/5 cells (Human hepatocellular carcinoma cell line) to insulin‐like growth factor 1 (IGF1), and enhances cell survival in the presence of sorafenib, a therapeutic agent used to treat advanced stage HCC. Firstly, we observed that TGFβ significantly increased mRNA and protein expression of insulin like growth factor 1 receptor (IGF1R) in PLC cells. To test how this result would affect IGF1 signaling, PLC cells were treated with TGFβ for up to 72 hrs, then treated with IGF1 for 30 min. PLC cells pretreated with TGFβ had a much greater response to IGF1 treatment, exhibiting significantly increased levels of pIGF1R and pAkt compared with IGF1 treatment only. Since IGF1 is a pro‐survival mitogen, we further tested whether an increase in IGF1 sensitivity would reduce apoptosis in the presence of sorafenib. The cells were treated with TGFβ for 48 hrs before the incubation with sorafenib for up to 24 hrs. We found that TGFβ pretreatment led to a significant reduction in both cleaved caspase 7 and cleaved PARP, and a significant increase in cell viability compared with sorafenib treatment only. Taken together, our data suggest that TGFβ can regulate the survival of HCC cells via the activation of IGF1 pro‐survival pathway and prevent Sorfafenib‐induced apoptosis.Grant Funding Source: NIH/NCI
Endothelial cell IQGAP1 is an important regulator of the transendothelial migration of leukocytes (146.1)
Authors: Sullivan David , Muller William 
Published: June 2021

In order to mount an appropriate inflammatory response, leukocytes must cross the endothelium to gain access to the target tissue and carry out their essential role. During this process (referred to as transendothelial migration, TEM) membrane from a novel endothelial cell compartment, the Lateral Border Recycling Compartment (LBRC), is delivered to the migrating leukocyte to supply it with several requisite proteins. In a proteomic screen, we discovered that IQGAP1 is associated with the LBRC and is required for its function during TEM. IQGAP1 is a large soluble scaffolding protein that integrates signals from diverse pathways to regulate cytoskeletal remodeling, Rho family GTPase activity, and other downstream readouts. Although it has been implicated in a variety of processes in other systems, its role in TEM remains unclear. In addition to being localized to the cytoplasm, in endothelial cells it is also enriched at lateral borders. Genetic ablation of IQGAP1 expression arrests leukocytes on the apical side of endothelial cells and prevents the targeted delivery of the LBRC similar to the phenotype of blocking PECAM. Expression of a full length GFP‐tagged IQGAP1 construct completely restores this defect and also shows that endothelial IQGAP1 is enriched around the leukocyte during TEM. Furthermore, using fluorescently tagged IQGAP1 truncation constructs, we have identified the domains of IQGAP that are required for its localization and function under resting conditions and during TEM. These data suggest that IQGAP1 is an important factor in the regulation of LBRC function. Preliminary studies in IQGAP1 knockout mice support a role for IQGAP in TEM in vivo.Grant Funding Source: Supported by F32 AI084454 to DPS and R21 HL102519, R01 HL046849, and R37 HL064774 to WAM
Regulation of cardiac fibroblast population and cell fate by Scleraxis (15.2)
Authors: Bagchi Rushita , Roche Patricia , Aroutiounova Nina , Schweitzer Ronen , Czubryt Michael 
Published: June 2021

Fibroblasts are cells of mesenchymal origin that constitute majority of the cardiac non‐myocyte population. They play a contributory role in development and structure of the myocardium, cellular signaling and electromechanical function of the heart‐ both in healthy and diseased conditions. Scleraxis (Scx) has been demonstrated to play a vital role in human collagen gene regulation and synthesis of extracellular matrix (ECM) components. Genetic ablation of Scx caused marked changes in the matrix composition of hearts of Scx null (KO) mice. Based on these observations, we hypothesized that the overall changes occurring in the myocardium may be due to a net change in population of the contributory synthetic fibroblasts. Using single‐cell suspensions from Scx KO and wildtype (WT) hearts, flow cytometry analysis was performed. There was a significant reduction (>40%) in DDR2 positive fibroblasts in Scx KO hearts compared to WT samples. There was also a trending decrease in the population of cells that stained positive for α‐smooth muscle actin (αSMA), a marker of activated contractile myofibroblast phenotype. Gene and protein expression analyses of fibroblast/ myofibroblast markers (vimentin, periostin, EDA‐fibronectin, SMemb) exhibited an overall downregulation of these proteins in myocardium devoid of Scx‐ thus suggesting involvement of Scx in fibroblast cell fate regulation. We hypothesized that Scx may also be responsible for modulating the process of fibroblast phenoconversion‐ a phenomenon that is known to accompany cardiac remodeling. qPCR and immunoblotting analyses of Scx KO hearts demonstrated a significant downregulation of αSMA expression. shRNA‐mediated knockdown of Scx gene expression in primary cardiac proto‐myofibroblasts resulted in marked diminution of this myofibroblast marker protein, thereby demonstrating a direct role of Scx in fibroblast phenoconversion. These findings identify Scx as a novel regulator of cardiac fibroblast population and cell fate.Grant Funding Source: Supported by the Canadian Institutes of Health Research and St. Boniface Research Foundatio
Efferocytosis ő autophagy crosstalk in alveolar macrophages exposed to cigarette smoking (151.7)
Authors: Petrusca Daniela , Van Demark Mary , Hubbard Walter , Twigg Homer , Petrache Irina 
Published: June 2021

Alveolar macrophages (AM) apoptotic cell clearance function (efferocytosis) is dysregulated in COPD due to cigarette smoke (CS) exposure via production of ceramides and sphingosine (SHP). CS also alters the maturation of the autophagosomes (AP) blocking the autophagic flux. We hypothesized that impairment of both AP maturation and efferocytosis share an identical mechanism of cytoskeletal derangement linked to HDAC6 inactivation and sphingosine accumulation. AM obtained via bronchoalveolar lavage from human smoker and non‐smoker donors or from Sprague Dawley rats exposed to CS (3 months) were subject to engulfment assays quantified by flow cytometry. HDAC6 was evaluated by real‐time PCR or Western blot. Both CS and SPH significantly impaired efferocytosis in rat and human AM (50% and 80% inhibition; p<0.05, respectively). HDAC6 protein activity was markedly impaired by CS exposure. This effect was in part mediated by SPH production, since a ceramidase inhibitor, MAPP, restored both HDAC6 levels and improved autophagic flux. Moreover, HDAC6 inhibition with BML‐281 or siRNA significantly impaired efferocytosis, as well as bafilomycin treatment, an inhibitor of AP maturation (by up to 7‐fold; p<0.05). Whole protein HDAC6 overexpression significantly restored the efferocytosis impairment induced by CS but overexpression of the HDAC6 catalytic mutant did not. These results indicate a novel role of HDAC6 in efferocytosis. The impairment of both autophagic flux and efferocytosis may be mechanistically linked at the level of sphingolipid regulation of cytoskeletal effectors activity such as HDAC6. Improvement in AP maturation may help restore efferocytosis, an essential step in the resolution of pulmonary inflammation.Grant Funding Source: ALA RG‐1966666‐N and NIH‐HL077328
A novel approach to investigate the assembly of the NOD‐like receptor inflammasomes (152.7)
Authors: Giles Nichole , Sierecki Emma , Polinkovsky Mark , Schroder Kate , Alexandrov Kirill , Gambin Yann 
Published: June 2021

The NLRP3 and NLRP12 inflammasome complexes are a subset of the Nod‐like receptor family, known to play a key role in the innate immune system. They act by activating caspase‐1 in response to pathogens, as well as endogenous and environmental stimuli. The NLRP3 inflammasome consists of the sensing protein, NLRP3, adaptor protein ASC, and pro‐caspase‐1. The proposed structure of the complex is based on the effector domains on the proteins, although the assembly of the active complex remains unclear. Even less is known about the NLRP12 inflammasome.We used a combination of Leishmania tarentolae cell‐free expression system, AlphaScreen, and single molecule fluorescence spectroscopy to investigate the assembly of NLRP3 and NLRP12 inflammasomes. Our results suggest that the NLRP3 and NLRP12 inflammasomes have different mechanisms of assembly. We observed NLRP3 and NLRP12 forming oligomers of distinct size. While NLRP3 can bind to ASC and pro‐caspase‐1 independently, association of NLRP12 with pro‐caspase‐1 requires ASC. Interestingly, we observed that aggregation of ASC is concentration dependent and nucleation of ASC has characteristics of the seeding model proposed for prions.Grant Funding Source: Australian Research Council
Development of lifelong learning strategies using inquiry guided learning projects in a first year anatomy course (211.6)
Authors: Bentley Danielle 
Published: June 2021

Biomedical science courses are often crammed with mandatory content. As a result, students may develop passive learning strategies; relying on the instructor to ‘give them’ knowledge. For instance, students self‐report (pre‐semester survey, 10‐pt Likert) a lack of confidence in the exploration of research on a scientific topic (6.4 ± 1.1) outside of formal instruction. To evade this passivity and to promote lifelong learning strategies, Inquiry Guided Learning Projects (IGLPs) have been developed for first year Gross Anatomy; piloted in 2012, then evaluated/reformatted and integrated in 2013. Aligned with student desires to develop skills in effective communication (8.1 ± 1.8) and resource acquisition (8.5 ± 1.9) IGLPs facilitation include 4 novel Information Sessions and 3 Check‐Ins that guide students through the Information Search Process (ISP); initiation, selection, exploration, formulation, collection, and presentation. The guiding aspect was imperative, as students indicate poor self‐perceived abilities of research question selection (6.6 ± 1.7), answer exploration using peer‐review literature (6.4 ±1.2), and effective scientific communication (6.3 ± 1.5). The effect of IGLPs on change over time in student‐perceived confidence and self‐reported ability in all ISP stages will be tested with a repeated measures ANOVA. IGLPs prepare students to be active learners; confident in their ability for academic discovery following formal education.Grant Funding Source: Supported by CIHR CGS Doctoral Research Award
Towards enhanced understanding of protein folding in the cell (219.1)
Authors: Gierasch Lila 
Published: June 2021

Major challenges arise when we attempt to apply lessons from study of protein folding in vitro to folding of a protein in vivo where conditions are very different from high‐dilution test tube experiments. Strikingly, proteins generally fold successfully in vivo, even at concentrations higher than the threshold for aggregation, because the protein homeostasis network, including chaperones and degradation machinery, facilitates folding under cellular conditions. This talk will describe two aspects of the function of the protein homeostasis network: 1) Using primarily NMR, we have studied the allosteric mechanism of the Hsp70 chaperone family and found that nucleotide‐dependent substrate affinity is a consequence of ligand‐modulation of domain conformational ensembles. 2) We are exploring how the E. coli protein homeostasis network modulates protein folding. Predictions from our computational model, FoldEco (Powers et al., Cell Reports 1, 265 [2012]), are being tested experimentally. Up‐regulation of the protein homeostasis network benefited several test proteins, as did enhanced expression of the Lon degradation enzyme. Over‐expression of individual chaperones had substrate‐dependent effects. These results suggest that the cell handles the folding load of the proteome by concerted action of the proteostasis network.Supported by NIH grants GM027616 and GM101644.
Caretakers receiving SNAP are responsive to education to reduce preschool child sugar‐sweetened beverage consumption (252.8)
Authors: Ferris Ann , Wakefield Dorothy , Lora Karina , Quesada Catalina 
Published: June 2021

A RCT, directed at low‐income parents at early childcare centers, evaluated whether an 8‐week brief intervention using the information‐motivation‐behavior theoretical framework would decrease the children’s home SSB consumption. The control group received a sham home food safety curriculum. Caretakers of 364 children completed the study, 357 of whom completed a 2‐day (weekend) food record for the child and provided information on child beverage consumption by use of an inventory of beverages in the home (HBI) at baseline and 6 months later. Fourteen percent did not consume SSB at either time point. Consumption estimates from food records and HBI among consumers were significantly correlated (r=0.32, p<0.0001). Baseline SSB consumption by either measure did not differ between intervention and control groups. Children who consumed SSBs did not change consumption over the course of the study. In contrast, children in families receiving SNAP benefits (45%) did reduce consumption over the course of the study (p=0.02) whether measured by diet records (kcal from SSB/d median (min, max), intervention: ‐9.8 [‐262, 336], control: 29.7 [‐421, 290]) or the home beverage inventory ((kcal from SSB/d ‐intervention: 0.0 [‐58, 32], control: 2.6 [‐55, 26]). SNAP recipients are responsive to reducing preschool child SSB consumption after participating in eight short interactive sessions.Grant Funding Source: USDA/NRI 2008‐55215‐19071
Tea flavonoids stimulate mineralization in osteoblast‐like cells (259.7)
Authors: Nash Leslie , Ward Wendy 
Published: June 2021

Epidemiological studies suggest that habitual tea consumption is associated with higher bone mineral density. Rooibos tea, in particular, is a rich source of flavonoids, including rutin, orientin, hyperoside, and luteolin, that may favorably modulate cellular processes such as hydroxyapatite production. The study objective was to determine if individual flavonoids (0.001µM‐100µM) promoted mineralization in Saos2 cells. Mineralization was quantified by alizarin red staining at day 21, while alkaline phosphatase activity, a marker of osteoblast cell activity, was determined at days 3, 7 and 10. Rutin (25µM), orientin (0.01µM), hyperoside (5µM) and luteolin (5µM) resulted in higher (p<0.05) mineral production than control. Higher mineral production was associated with higher alkaline phosphatase activity (p<0.05) for rutin (25µM), orientin (0.1µM), hyperoside (1µM) and luteolin (1µM) as early as 3 days into the mineralization process. Maximum enzyme activity was dependent on the flavonoid. Mitochondrial activity, a marker of cellular proliferation, reflected the mineralization data. In conclusion, flavonoids can positively influence mineral production in osteoblasts and this is, in part, due to higher osteoblast activity. Thus, tea flavonoids are a promising area for future research investigating dietary approaches for bone health.Grant Funding Source: Supported by a NSERC Discovery Grant for W. Ward
Lipodomic analysis reveals that gamma‐tocotrienol exerts anticancer effects by inhibition of dihydroceramide desaturase and activation of sphingomyelin hydrolysis (260.6)
Authors: Jang Yumi , Jiang Qing 
Published: June 2021

Our previous studies suggest that gamma‐tocotrienol (γTE), a vitamin E form rich in palm oil, has potent anticancer activities in cancer cells via modulation of sphingolipid metabolism. Here employing liquid chromatography tandem mass spectrometry, we investigated temporal changes of sphingolipid by γTE treatment in human colon cancer HCT‐116 cells. Incubation with γTE for 2 h resulted in accumulation of dihydrosphingosine and dihydroceramides (dhCer), and these changes intensified during prolonged treatment. In contrast, γTE treatment led to significant decrease in C16:0‐ceramide (Cer) from 2 to 8 h, but showed no difference at 16 h or increase at 24 h, compared with controls. Meanwhile, γTE led to decrease in C24:1‐Cer and C24:0‐Cer from 6 to 24 h, but increase in C18:0‐Cer from 16 h. Interestingly, sphingomyelins (SM) declined from 8 h but cells showed obvious apoptosis (PARP cleavage) or autophagy (LC3 increase) only at 16 h or longer treatment with γTE. With 13C3, 15N‐labeled L‐serine, we further evaluated the effect of γTE on de novo sphingolipid. We observed that γTE had no effect on total de novo sphingolipid biosynthesis, while induced increases in labeled dhCer, dhSM and SM, but decreases in labeled Cers and sphingosine, during 2‐6 h. These data indicate that γTE may inhibit dhCer desaturase (DEGS). Consistently, γTE inhibited the DEGS activity as indicated in situ and in vitro assays. Moreover, the decrease in endogenous SM without affecting de novo SM suggests that SM hydrolysis likely occurred. Studies are undertaken to evaluate the role of SM hydrolysis in γTE‐induced anticancer effects. These results indicate that γTE modulates enzyme activities in sphingolipid metabolism, which play roles in regulating cell death.Grant Funding Source: Supported by grants R21 CA152588 and R01AT006882 from National Institutes of Health