bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution and Development of The Mandibular Coronoid Process in Mammals
Authors: Anthwal Neal , Tucker Abigail 
Published: June 2021

The coronoid process of the mammalian dentary bone is an evolutionary novel structure reflecting the new role of the dentary in mammals as an attachment site for the muscles of mastication. Previous studies have shown that the size and shape of the coronoid is correlated to the bite force required by the adult animal, and is dependent upon the mechanical force acting upon it during development. However little is known about the developmental programme leading to the specification of the processWe demonstrate that the paired homeobox transcription factor Pax9 is expressed in the ossifying front of the future coronoid process, and that Pax9 expressing cells contribute to the coronoid process, but not the other mandibular processes. In Pax9 mutants the coronoid is absent, however the temporalis muscle, which attaches to it, develops normally. Histological and gene expression studies indicated that the muscle attachment site remains. Loss of the coronoid is therefore driven by changes in the intrinsic patterning of the bone. In contrast other mouse mutants lacking the coronoid, such as the Tbx1 null, loss of the coronoid is a consequence of the loss of the muscle acting on the developing bone. Changes to this structure can therefore be influenced by intrinsic and extrinsic factors. The relative size of the coronoid process varies considerably across mammals, with herbivores, such as the guinea pig having a reduced or absent coronoid, while carnivores can have extremely large coronoid processes. The contribution of genes such as Pax9 and Tbx1 to changes in size of this processes on other mammals have therefore also been investigated. Our data implicates cooption of Pax9 in to the osteogenic program of the dentary enabled the development of the coronoid process, a key component in the emergence of the novel jaw.
Fibrinogen Regulates MMP‐9 Processing of VEGF‐induced Angiogenesis and Tumor Growth in Osteosarcoma
Authors: Moore Stephanie , Ohba Tetsuro , Cates Justin , Cole Heather , Mignemi Nicholas , ichikawa Jiro , Hirotaka Haro , Schwartz Herbert , Schoenecker Jonathan 
Published: June 2021

PurposeOsteosarcoma (OGS) is the most common primary malignant bone tumor in children and adolescents. Traditionally, fibrin, the essential structural matrix protein of a blood clot, is thought to enhance tumor adhesion and provide a matrix to support tumor growth. Evidence strongly supports that major angiogenic factors, such as vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP‐9), can bind fibrin in a concentration‐dependent manner. Therefore, we designed experiments to determine the effects of fibrin on OGS tumor angiogenesis by interacting with VEGF and MMP‐9.MethodsAggressive murine OGS cells are intratibially injected into Balb/C mice. OGS establishment is determined by radiographic analysis, micro‐CT, histology, and angiography.ResultsOpposed to traditional beliefs surrounding fibrin's role in tumor establishment, this work has shown that the loss of fibrin promotes the proliferation and vascularity of OGS, therefore promoting tumor establishment and disease progression.imageTherefore, we have confirmed that fibrin does play a role in tumor angiogenesis through its interaction with VEGF, however we have also shown for the first time that MMP‐9 is a novel intermediary factor for this interaction.ConclusionsIn this study, we have demonstrated that fibrin can inhibit tumor angiogenesis by inhibiting MMP‐9 activity and by sequestering VEGF that is cleaved by MMP‐9. This finding demonstrates a novel synergistic relationship between fibrin and MMP‐9 in the progression of OGS, while also identifying new therapeutic targets.
Lipid Transport Involving Chloroplast Envelope Membranes in Plants and Algae
Authors: Benning Christoph , Hurlock Anna , Warakanont Jaruswan 
Published: June 2021

Lipid trafficking between the endoplasmic reticulum (ER) and chloroplasts is essential in plant cells and involves two transport complexes in the inner and outer envelope membrane, respectively. The TGD1,2,3 ABC transporter complex so named after the accumulation of trigalactosyldiacylglycerol in the Arabidopsis mutants, consists of a permease (TGD1), an ATPase (TGD3), and substrate binding protein (TGD2). It is located in the inner envelope membrane, but TGD2 is proposed to reach out to the outer envelope membrane to facilitate lipid transfer. TGD4 forms a complex in the outer envelope membrane. TGD2 as well as TGD4 bind phosphatidic acid. However, the actual transported substrates remain to be defined. Novel in vivo and in vitro approaches are applied to address this issue.Until recently, the green alga Chlamydomonas was not thought to utilize lipid precursors from the ER for the assembly of chloroplast lipids. However, the isolation and analysis of a TGD2 loss‐of‐function mutant of Chlamydomonas suggest that ER to chloroplast lipid transfer takes place in this alga. However, phenotypes of the respective mutants in Arabidopsis and Chlamydomonas differ in specific aspects that may shed new light onto the function of these complexes in Chlamydomonas and Arabidopsis.
Tree Nuts Improve Glycemic Control: A Systematic Review and Meta‐Analysis of Randomized Controlled Dietary Trials
Authors: Viguiliouk Effie , Kendall Cyril , Blanco Mejia Sonia , Cozma Adrian , Ha Vanessa , Mirrahimi Arash , Jayalath Viranda , Augustin Livia , Chiavaroli Laura , Leiter Lawrence , de Souza Russell , Jenkins David , Sievenpiper John 
Published: June 2021

BackgroundTree nut consumption is associated with reduced diabetes risk, however, results from randomized controlled trials (RCTs) on glycemia have been inconsistent.AimWe conducted a systematic review and meta‐analysis of RCTs to assess the effect of tree nuts on glycemic control.MethodsWe searched MEDLINE, EMBASE, CINAHL, and Cochrane databases through 8 August 2014 for relevant RCTs 蠅3‐weeks reporting HbA1c, fasting glucose (FBG), fasting insulin (FPI), and/or HOMA‐IR. Two independent reviewers extracted relevant data. Data were pooled using generic inverse variance random effects models and expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed (Cochran's Q) and quantified (I2).Results31 trials (n=1645) met the eligibility criteria. Diets emphasizing tree nuts significantly lowered FBG (MD=‐0.11 mmol/L, 95% CI:‐0.18, ‐0.03 mmol/L), FPI (MD=‐4.79 pmol/L, 95% CI:‐8.12, ‐1.46 pmol/L) and HOMA‐IR (MD=‐0.45, 95% CI:‐0.81, ‐0.09) compared with isocaloric control diets. No effects were observed for HbA1c, however the direction of effect favoured tree nuts.LimitationsMajority of trials were of poor quality and short duration.ConclusionPooled analyses show diets higher in tree nuts improve glycemic control. Longer, higher quality trials are needed.Funding International Tree Nut Council Nutrition Research & Education Foundation
Physical Activity Between Menarche and First Pregnancy and Risk of Breast Cancer
Authors: Malik Vasanti , Liu Ying , Rosner Bernard , Cespedes Elizabeth , Sturgeon Kathleen , Joshi Amit , Tobias Deirdre 
Published: June 2021

BackgroundA longer interval between age at menarche and 1st pregnancy is a known breast cancer risk factor. Whether physical activity during this period can mitigate cancer risk is unknown. Methods. We analyzed 65569 parous women in the Nurses' Health Study II who reported their physical activity at ages 12 to 34 in 1997. Multivariable relative risks (RRs) were estimated using Cox proportional hazards regression. Results. 2078 breast cancer cases occurred between 1989 and 2011. As expected, a longer interval between menarche and 1st pregnancy was associated with greater breast cancer risk (RR=1.04 per additional yr, 95% CI 1.03‐1.05); overall, this relationship did not vary by physical activity level before 1st pregnancy. However, an inverse association between physical activity before 1st pregnancy and breast cancer risk was observed for women with a menarche to 1st pregnancy interval of <10 yrs (RR=0.59 for highest vs lowest quartile of activity, 95% CI 0.39‐0.90), with no association in women with longer intervals.ConclusionPhysical activity before 1st pregnancy did not modify the association between the interval from menarche to 1st pregnancy and breast cancer risk, except among women with an interval of <10 yrs, in which early physical activity was inversely associated with breast cancer risk.Supported by: NIH U54 CA155626, CA155850, CA155496 and U01 CA116850
High fat diet induced obesity is associated with increased abundance of pro‐inflammatory Lactobacillus in Peyer's patches of small intestine
Authors: Sun Jin , Qi Ce , Qiao Yi , Jiang Wei , Xiao Hang 
Published: June 2021

We investigated the association between microbiome composition in peyer's patches in small intestine and high‐fat diet‐induced obesity in mice. C57L/6J male mice were fed either low fat (10% calories from fat, CT) or high fat (50% calories from fat) diets for 25 weeks, and the high‐fat diet‐fed mice were classified to obesity prone (OP) or obesity resistant (OR) based on their body weight gains. Microbiome was harvested from peyer's patches analyzed for bacterial composition. Our results showed that the numbers of peyer's patches inhabiting Lactobacillus were significantly lower in OP mice. Further selection of Lactobacillus generated 52, 18 and 22 isolates from CT, OP and OR mice, respectively. They belonged to 13 different phenotypes. Lactobacillus reuteri was the most abundant strain, but its abundance in OP mice was much lower. There were 8 subgroups of these L. reuteri. L. reuteri L3 and L. reuteri L8 were the specific strain found in CT and OP mice, respectively. Oxidative resistant Lactobacillus was much higher in high‐fat diet‐fed mice. Co‐cultured with peyer's patches cells, L8 induced higher production of pro‐inflammatory cytokine such as IL‐6, IL‐12 and TNF‐alpha, whereas, L3 induced higher production of anti‐inflammatory cytokine such as IL‐10. Overall, our results suggested that high‐fat diet may induce oxidative stress in small intestine that promotes the growth of pro‐inflammatory Lactobacillus strains with high resistance to oxidative stress, and these phenomena is specific for OP mice. This work was supported by National Natural Science Foundation of China (No. 31201805).
Lingonberries have Anti‐obesity Effects and Modulate the Gut Microbiota in High‐fat Fed C57BL/6J Mice
Authors: Heyman‐Lindén Lovisa , Kotowska D , Sand E , Holm C , Fåk F , Berger K 
Published: June 2021

This study aimed to investigate if the ability of lingonberries to prevent diet‐induced obesity is associated with an altered gut microbiota. Furthermore, two different batches of lingonberries were tested.C57BL/6J mice were fed high‐fat (HF) diet (control) or HF diet supplemented with lingonberries (20% w/w) from two different batches (Lingon1 and Lingon2) for 11 weeks. The composition of cecal gut microbiota was assessed by 16S rRNA gene sequencing (MiSeq, Illumina). Lingonberry intake was found to prevent weight gain, hepatic steatosis and other metabolic parameters associated with obesity. However, these effects were more prominent in mice fed HF diet supplemented with Lingon1, compared to Lingon2. Interestingly, both lingonberry batches reduced the plasma levels of lipopolysaccharide binding protein and the inflammatory marker serum amyloid A (SAA). Lingonberry intake significantly increased beta diversity of cecum microbiota and positively correlated with the abundance of Akkermansia spp. The relative abundance of Parabacteroides spp negatively correlated with SAA, and tended to be reduced in the microbiota of mice receiving Lingon1.We conclude that lingonberries exert anti‐obesity effects when supplemented to a HF diet in mice, but the magnitude varies depending on which batch of berries is used. Regardless of the berry source, lingonberries promote changes of gut microbiota and lower endotoxemia and low‐grade inflammation in mice. Further discerning the microbiota of mice receiving lingonberries may provide additional knowledge to correlate changes in gut microbiota with protection against obesity. Supported by: Lund University Antidiabetic Food Centre, a VINNOVA Excellence Center.
Low Serum Sphingolipids in Attention Deficit Hyperactivity Disorder (ADHD)
Authors: Henríquez‐Henríquez Marcela , Solari Sandra , Allende Fidel , Quiroga Teresa , Kim Benjamin , Deckelbaum Richard , Worgall Tilla 
Published: June 2021

BackgroundADHD is the most prevalent neurodevelopmental disorder in children and has been associated with a lag in neuronal maturation. Sphingolipids are essential for myelination, neuronal function and development. We hypothesized that serum sphingolipid profiles are different in ADHD.ObjectiveTo characterize the serum sphingolipid profile in ADHD patients and two independent control groups: non‐affected relatives and non‐affected subjects without family history of ADHD.MethodSphingolipid profiles were determined by mass spectrometry in 77 participants (28 ADHD, 28 related controls and 21 unrelated controls). Diagnosis was based on the criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM IV‐TR). Groups were compared by parametrical statistics.ResultsAll major sphingomyelins (C16:0, C18:0, C18:1 and C24:1), ceramide C24:0 and deoxyceramide C24:1 were significantly decreased in ADHD at relative reductions between 20‐30%. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity, 78% specificity and an estimated negative predictive value of 97%.ConclusionSerum sphingomyelin and select ceramides are decreased in ADHD patients. Longitudinal studies are required to evaluate if these findings reflect an ADHD specific pathomechanisms. Low serum sphingomyelins levels are a potential biomarker for ADHD.Grant support: None
Structure‐Function Analysis of Ursolic Acid and its Analogs to Identify Their Anti‐inflammatory Mechanism of Action
Authors: Nguyen Huynh Nga , Kim Hong Seok , Ullevig Sarah , Asmis Reto 
Published: June 2021

We showed that ursolic acid (UA), a pentacyclic triterpenoid with anti‐inflammatory properties, reduces atherosclerotic lesion size and monocyte dysfunction in diabetic mice. We proposed that UA protects monocytes against metabolic stress‐induced monocyte dysfunction or “priming,” by preventing the induction of Nox4, the rate‐limiting step promoting hyper‐responsiveness to chemoattractants and accelerated chemotaxis induced by metabolic stress. We have also demonstrated that UA rescues MKP‐1 protein expression and activity in metabolically primed cells. The aim of this study was to investigate nine of UA's naturally occurring analogs and identify the structural features of UA required to inhibit monocyte priming and prevent Nox4 induction. We determined the doses (0.03 ‐ 3 μM) at which UA and its analogs blocked metabolic stress‐induced acceleration of chemotaxis in response to MCP‐1 in metabolically primed THP‐1 monocytes. Only the UA analogs hederagenin (IC50 = 0.64 μM), oleanolic acid (IC50 = 1.9 μM), and uvaol (IC50 = 2.46 μM), protected monocytes against metabolic priming. UA was the most potent analog (IC50 = 0.1 μM). All protective analogs also prevented Nox4 induction and rescued MKP‐1 from degradation. Our data suggests that hederagenin, oleanolic acid and uvaol prevent monocyte priming and dysfunction through the same mechanism as UA and thus may all be atheroprotective. Identifying the structural features responsible for UA's beneficial effects will enable us to develop more potent, dietary supplements for the prevention of atherosclerosis and other monocyte‐mediated diabetic complications.​ Funding Source: Supported by a grant to RA from the NIH (R01‐AT006885)
Complementary Feeding Pattern Reduces the Impact of Diarrhea on Relative Weight: A Longitudinal Analysis of the Interaction of Diet and Diarrhea on Weight‐for‐length in Cebu Infants
Authors: Wright Melecia , Adair Linda 
Published: June 2021

Undernutrition and diarrheal disease are major contributors to infant morbidity and mortality worldwide. We investigated the combined roles of infant feeding and diarrhea on relative weight (weight‐for‐length z scores or WFL) in 2814 infants from the Cebu Longitudinal Health and Nutrition Survey. Indicator coding was used to create eight primary predictors based on combinations of current breastfeeding status (breastfed/BF vs non‐breastfed/NBF), high or low diversity score (DDS) in the complementary feeding diet (consumption of 4+ or <4 of 7 possible food groups) and presence of diarrheal disease (sick vs healthy with respect to diarrheal disease). WFL was predicted using sex‐stratified, fixed‐effects longitudinal models that also adjusted for age and energy from complementary foods.

Table 1 Results of longitudinal regression of WFL on dietary and diarrhea patterns during infancy

Boys&amp;#39; Beta
95% CI
p
Girls&amp;#39; Beta
95% CI
p

Diet x diarrhea pattern

Healthy + NBF + Low DDS
‐0.141*
(‐0.221, ‐0.062)
0.001
‐0.114*
(‐0.208, ‐0.020)
0.018

Healthy + BF + Low DDS
0.009
(‐0.062,0.080)
0.801
0.048
(‐0.035,0.132)
0.257

Healthy + NBF + High DDS
‐0.127*
(‐0.216, ‐0.037)
0.006
‐0.093+
(‐0.195,0.009)
0.073

Healthy + BF + High DDS
Referent
n/a
n/a
Referent
n/a
n/a

Sick + NBF + Low DDS
‐0.319*
(‐0.404, ‐0.235)
&amp;lt;0.001
‐0.224*
(‐0.324, ‐0.125)
&amp;lt;0.001

Sick + BF + Low DDS
‐0.148*
(‐0.228, ‐0.069)
&amp;lt;0.001
‐0.064
(‐0.155,0.026)
0.164

Sick + NBF + High DDS
‐0.224*
(‐0.332, ‐0.116)
&amp;lt;0.001
‐0.152*
(‐0.276, ‐0.029)
0.016

Sick + BF + High DDS
‐0.101
(‐0.241,0.038)
0.154
‐0.091
(‐0.237,0.056)
0.224

Age
‐2.232*
(‐2.402, ‐2.062)
&amp;lt;0.001
‐2.090*
(‐2.263, ‐1.917)
&amp;lt;0.001

Age‐squared
0.770*
(0.700,0.840)
&amp;lt;0.001
0.708*
(0.638,0.778)
&amp;lt;0.001

Energy intake
‐0.286*
(‐0.428, ‐0.143)
&amp;lt;0.001
‐0.427*
(‐0.573, ‐0.281)
&amp;lt;0.001

Age x energy intake
0.375*
(0.275,0.475)
&amp;lt;0.001
0.481*
(0.378,0.584)
&amp;lt;0.001

Intercept
0.719*
(0.593,0.845)
&amp;lt;0.001
0.627*
(0.495,0.759)
&amp;lt;0.001

Within strata of diarrhea status or diet diversity, non‐breastfed babies were thinner than their breastfed counterparts. Interestingly, regardless of breastfeeding status, diarrhea was consistently related to lower WFL in babies with low diet diversity but diarrhea did not significantly reduce the WFL of babies with high diet diversity. Furthermore, amongst non‐breastfed boys with diarrheal disease, infants with high diet diversity had significantly higher relative weight than those with low diet diversity.imageThese findings suggest that high diversity in the complementary diet may mitigate the detrimental impact of diarrhea on infant nutritional status.
Pulsatile Delivery of Cortisol Regulates Lipid Storage in Adipocytes in Vitro and Human Adipose Gene Expression in Vivo
Authors: Karastergiou Kalypso , Pramyothin Pornpoj , Port Ava , Apovian Caroline , Lee Mi‐Jeong , Fried Susan 
Published: June 2021

Glucocorticoids (GC) regulate the distribution and function of human adipose tissue, and their pathophysiological effects are attributed to changes in their concentration. We hypothesized that the diurnal cortisol rhythm contributes to its effects.Microarray analysis and qPCR were used to identify genes with expression changes as circulating cortisol declines between 9:00 and 15:00, in human abdominal subcutaneous adipose tissue of healthy volunteers (n=5). Placebo or a single, physiological dose of cortisol were administered out of phase (11:30) to identify genes with expression changes dependent on the cortisol rhythm. A novel in vitro model was established to study the long‐term effects of pulsatile versus constant GC in human adipocytes.We identified 280 genes significantly upregulated and 292 downregulated from 9:00 to 15:00. Cortisol changed the expression pattern of 191 (33.4%) genes. We verified changes in the clock gene PER1, the GC receptor co‐chaperone FKBP5, and KLF15, a regulator of circadian nitrogen homeostasis. In vitro, pulsatile GC established rhythmic clock gene expression in human adipocytes, led to enlarged lipid droplets and lower basal lipolysis and de novo fatty acid synthesis compared to constant GC.These findings suggest that higher turnover of triglycerides may occur in patients with disrupted glucocorticoid rhythm and contribute to increased cardiometabolic risk.Research support: NIH DK080448, P30 DK046200 and UL1‐TR000157.
The Association Between Serum Prostate‐Specific Antigen and Glycemic Index, Glycemic Load, and Metformin in Individuals with Diabetes: a Cross‐sectional Analysis
Authors: Jayalath Viranda , Ireland Christopher , Augustin Livia , Nishi Stephanie , Mirrahimi Arash , De Souza Russell , Kendall Cyril , Jenkins David 
Published: June 2021

BackgroundImproving glycemic control with Metformin therapy, glycemic index (GI), and glycemic load (GL) have been protectively associated with prostate cancer risk. No studies have yet assessed the relationship between GI, GL, and Metformin on serum prostate‐specific antigen (PSA), a controversial‐yet‐widely used marker of prostate health.MethodsA cross‐section analysis of baseline PSA data from men with type 2 diabetes mellitus (T2DM) who previously completed a trial at this research center was conducted. Multivariate linear regression quantified associations between PSA and log‐PSA with GI, GL, and Metformin dose.ResultsData were available from 317 men, with a mean PSA of 1.41±0.09ng/mL. Medians exposures (ranges) were 80 (56 – 96) for GI, 164 (62 – 386) for GL, and 1500mg (0 ‐ 3000 mg) for Metformin; 90% of men were under Metformin therapy. Neither PSA nor log‐PSA were significantly related to GI or GL. A negative trend was seen with PSA and metformin dose (p=0.09) in multivariate models. PSA was 24% lower among individuals taking 蠅2000mg of Metformin (n=125) compared to individuals taking <1000mg (n=62) (p=0.06). Log‐PSA significantly decreased by 0.15±0.09 ng/mL for every 1000mg increase in Metformin dose (r=‐0.38, p=0.02).ConclusionsMetformin, but not GI or GL, inversely related with log‐PSA in a sample of men with T2DM. Modification of PSA‐test sensitivity as a marker of prostate cancer with diet and Metformin warrants attention.Funding CIHR, Barilla, Loblaw Brands ltd
Incidence of Pulmonary Fibrosis in Lungs of CUX‐1 Transgenic Mice
Authors: Helgeson Scott , Harris Ethan , Herndon Betty , Vanden Heuvel Gregory , Baybutt Richard , Molteni Agostino 
Published: June 2021

CUX‐1 is a transcriptional repressor gene and part of the network controlling G1‐S phase transition by repressing the cyclin‐kinase inhibitors p21 and p27. CUX‐1 transgenic mice develop polycystic kidneys, reduced spermatogenesis, and liver fibrosis as a consequence of aberrant repression of p27. We reported that these mice also show severe pulmonary inflammation with vasculitis, bronchitis, bronchiectasis, and diffuse presence of fibroblasts.This study reports the presence of collagen using Image J software (NIH program) on slides of lungs of CUX‐1 mice stained by trichrome. Wild type mice were used as controls. An average of seven photographs at 400x magnification were taken on the lungs of each mouse.Collagen presence and intensity was 17.06% in lungs of CUX‐1 mice versus 8.73% the wild type mice (p<0.05). Fibrosis was mostly evident in the basal membrane and musculature of the ectasic bronchi and the peribronchial arteries. CUX‐1 mice also showed medial thickening, reduced lumen patency (64% versus 76% in wild type, p 0.015), and reduced media/adventitia ratio (42% versus 64% in wild type, p 0.018). Fibroblasts were particularly evident in the adventitia. Data using a specific rat stain for SMA‐1 confirm those ones observed with trichrome.Our data quantitatively confirms the presence of severe pulmonary fibrosis in these mice. Would some patients with polycystic kidney disease also have aberrant repression of p21 and p27 and develop pulmonary fibrosis?