bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of individualized training based on force–velocity profiling on physical function in older men
Authors: Lindberg Kolbjørn , Lohne‐Seiler Hilde , Fosstveit Sindre H. , Sibayan Erlend E. , Fjeller Joachim S. , Løvold Sondre , Kolnes Tommy , Vårvik Fredrik T. , Berntsen Sveinung , Paulsen Gøran , Seynnes Olivier , Bjørnsen Thomas 
Published: March 2022

The study aimed to investigate the effectiveness of an individualized power training program based on force–velocity (FV) profiling on physical function, muscle morphology, and neuromuscular adaptations in older men. Forty‐nine healthy men (68 ± 5 years) completed a 10‐week training period to enhance muscular power. They were randomized to either a generic power training group (GPT) or an individualized power training group (IPT). Unlike generic training, individualized training was based on low‐ or high‐resistance exercises, from an initial force–velocity profile. Lower‐limb FV profile was measured in a pneumatic leg‐press, and physical function was assessed as timed up‐and‐go time (TUG), sit‐to‐stand power, grip strength, and stair‐climbing time (loaded [20kg] and unloaded). Vastus lateralis morphology was measured with ultrasonography. Rate of force development (RFD) and rate of myoelectric activity (RMA) were measured during an isometric knee extension. The GPT group improved loaded stair‐climbing time (6.3 ± 3.8 vs. 2.3% ± 7.3%, p = 0.04) more than IPT. Both groups improved stair‐climbing time, sit to stand, and leg press power, grip strength, muscle thickness, pennation angle, fascicle length, and RMA from baseline (p < 0.05). Only GPT increased loaded stair‐climbing time and RFD (p < 0.05). An individualized power training program based on FV profiling did not improve physical function to a greater degree than generic power training. A generic power training approach combining both heavy and low loads might be advantageous through eliciting both force‐ and velocity‐related neuromuscular adaptions with a concomitant increase in muscular power and physical function in older men.
A comparison of limited vs unlimited attempts with online homework grades in introductory statistics courses
Authors: Stewart Patrick 
Published: March 2022

AbstractOnline homework programs allow professors to preset how many attempts per homework problem each student is allowed to have. Some professors prefer to allow a limited number of extra attempts, and others prefer to allow students to have an unlimited number of extra attempts. Do these preferences lead to a difference in average homework grades? To study this question, seven statistics courses over the Fall 2020 and Spring 2021 semesters were analyzed. The Fall semester had a limited number of extra attempts for each homework problem, and the Spring semester had an unlimited number of extra attempts. The results of the study conclude that there is no statistically significant difference in average homework grades for most homework assignments. In any homework assignment with a statistically significant difference, there was a quantifiably small difference.
Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan
Authors: Liu Yi , Kong Xiaomu , Jiang Yongwei , Zhao Meimei , Gao Peng , Cong Xiao , Cao Yongtong , Ma Liang 
Published: March 2022

Background. The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). Methods. 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg). Results. Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients (

P

= 0.005 and

P

= 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199–6.705,

P

= 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients. Conclusions. The current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.
Structure of Soluble Dietary Fiber from Fresh Rice at the Medium-Milk Stage and Improvement of Insulin Resistance in HepG2 Cells
Authors: Zhang Aiwu , Li Ren , Wang Qi , Zhao Guoliang , Zhang Linyan , Jiang Peng , Liu Nian , Li Zhijiang 
Published: March 2022

Fresh rice (Oryza sativa ssp. japonica) at the medium-milk stage is rich in soluble dietary fiber (SDF), leading to potential effects on type 2 diabetes (T2D). In this study, we analyzed each monosaccharide, the relative molecular weight, and the molecular linkages of fresh rice (grain, stem, husk, and leaf) SDF. The examined fresh rice leaf SDF consisted of 31.9% glucose, 35.7% galactose, 15.3% arabinose, 11.7% mannose, and a small amount of rhamnose and xylose. The molecular weight (

M

w

) was

232.5
±
19.1
×

10

4

u

, and the radius of gyration (

R

g

) was

298.8
±
25.4

nm

. The glycosidic bonds consisted mainly of Araf and Glc/Gal and included 1,3-Araf, 1,5-Araf, and 3,5-Araf glycosidic bonds. The effect of fresh rice leaf SDF on insulin resistance (IR) in HepG2 cells showed that it could significantly enhance glucose consumption (

P
<
0.05

). It also decreased the malondialdehyde (MDA) content (

P
<
0.05

) and increased the total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities (

P
<
0.05

) in a dose-dependent manner. Therefore, fresh rice leaf SDF might be a good dietary supplement for treating T2D.
Rumdul (Sphaerocoryne affinis) Antioxidant Activity and Its Potential for Parkinson’s Disease Treatment
Authors: Nghi Ngo Binh Thao , Uyen Tran Thuc , Anh Huynh Man , Linh Dao My , Thao Dang Thi Phuong 
Published: March 2022

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized by progressive deterioration of motor function and loss of dopaminergic neurons in the substantia nigra. Although PD is more common in people over 60 years old, people with young-onset PD tend to increase recently. Up to now, there is no cure for PD; therapies mainly focus on reducing symptoms and improving patient quality of life. Thus, the requirement of exploring new medications is needed. There is a strong relationship between oxidative stress and PD. Therefore, antioxidant compounds have been considered as a novel therapy for PD. In this study, we indicated a new potential candidate for PD treatment, rumdul fruit (Sphaerocoryne affinis—a member of the Annonaceae family), due to evaluating its activities on the fly model of Parkinson. Our experimental results showed that rumdul fruit water extract (RFWE) has a strong antioxidant capacity with IC50 value in DPPH assay which was

85.62
±
1.05

μg/mL. The use of RFWE at concentrations of 3, 6, and 12 mg/mL could strongly ameliorate the locomotor disabilities and dopaminergic neuron degeneration. Although the RFWE at high concentrations like 12 mg/mL and 18 mg/mL could induce some side effects on fly development and viability, our data strongly demonstrated that RFWE effectively rescued PD phenotypes on the fly model. Although component in the plant extract, as well as the molecular mechanism helping to recover the phenotype, has not been elucidated yet, the research contributed strong scientific evidence for further research on applying rumdul as a novel natural source for PD treatment.
Abstract 15: Differential Activation of HIF1-α Is Associated with Reduced Arteriogenesis After Hindlimb Ischemia in PCAF
-/-
Mice
Authors: Bastiaansen A J , van der Pouw-Kraan T C , Peters H A , Quax P H , Nossent A Y 
Published: March 2022

Although arteriogenesis is generally considered to be a shear stress-driven process, hypoxia-inducible factor-1α (HIF-1α) has a strong stimulatory effect on arteriogenesis. Recently, it was shown that the P300/CBP-associated factor (PCAF) acetylates (and activates) HIF-1α at Lys674 and can act as a co-factor in transcriptional activation of HIF-1α target genes (1). We investigated whether PCAF plays a role in arteriogenesis.

Wildtype C57Bl/6 mice or C57Bl/6 PCAF
-/-
mice were subjected to double ligation of the femoral artery. Blood flow recovery was followed over time using Laser Doppler Perfusion Imaging (LDPI) and after 28 days, animals were sacrificed and adductor muscles harvested for immunohistochemistry. PCAF
-/-
mice showed marked decrease in blood flow recovery compared to wildtype mice. Also, when staining for α-SMA, less and smaller collateral arteries were observed in the adductor muscle of PCAF
-/-
mice compared to wildtype mice. To study which genes were regulated by PCAF during arteriogenesis, wildtype and PCAF
-/-
C57Bl/6 mice were sacrificed 24 hours after double femoral artery ligation. Gene expression profiles in the adductor muscles of the mice were obtained by microArray and compared to expression patterns in the adductor muscle before femoral artery ligation. Transcription factor binding site analyses showed strong up-regulation of a large number of HIF-1α induced genes in both mouse strains. However, besides a group of 93 jointly up-regulated HIF-1α induced genes, each strain also showed up-regulation of a different set of HIF1α induced genes. The most striking gene that was up-regulated in PCAF
-/-
mice only, was Sirtuin 1 (SIRT1). Recently, it was shown that SIRT1 counteracts PCAF by deacetylating Lys674 of HIF-1α, thereby blocking p300 recruitment to HIF-1α (2). Up-regulation of SIRT1 in PCAF
-/-
mice further contributes to differential activation of HIF-1α under ischemia. Although HIF-1α is activated and can still induce up-regulation of a specific subset of its target genes in PCAF
-/-
mice, this no longer leads to efficient recovery of blood flow after hind limb ischemia.

(1) Xenaki G et al. Oncogene 2008; 27(44)
(2) Lim JH et al. Mol Cell 2010; 38(6)
Abstract 307: Influence of Dendritic Cells on Cholesterol Absorption and Excretion: Implication in Atherogenesis
Authors: Deswaerte Virginie , Huby Thierry , Saint-Charles Flora , Proschogo Nicolas , Beliard Sophie , Pirault John , Lesnik Philippe , Jessup Wendy 
Published: March 2022

Atherosclerosis represents the chronic pathophysiological process implicated in the majority of cardiovascular (CV) diseases and constitutes one of the leading causes of death in the world. The development of atherosclerotic lesions is characterized by an accumulation of extracellular and intracellular lipids in the arterial wall. These phenomena are associated with a strong local immuno-inflammatory response characterized by the recruitment of various populations of leucocytes including monocytes, macrophages and dendritic cells (DCs).
DCs are central to the regulation of immunity and the polarization of the immune response. We recently demonstrated that the longevity/depletion of DCs directly impacts plasma cholesterol levels, which is the main risk factor for atherosclerosis.
To gain insight into the cellular and molecular mechanisms underlying the inverse relationship between DC numbers and cholesterolemia, we have evaluated the impact of DCs on cholesterol homeostasis, using CD11c-hBcl2/apoE KO mice, in which specific DC-expression of the anti-apoptotic transgene hBcl2 increase their longevity and numbers. Firstly, we quantified DC populations in the liver and in the intestine, which are the main organs involved in cholesterol metabolism. Secondly, we measured the rates of dietary cholesterol absorption, tissue cholesterol content and sterol and bile salt excretion. Thirdly, we analysed the expression of genes associated with cholesterol metabolism in the liver and the intestine.
We found an increase of DC numbers in the liver and in the intestine in the CD11c-hBcl2 apoE KO mice relative to control apoE KO mice. This increase of DC numbers was associated with reduced intestinal cholesterol absorption and fecal bile acid excretion, but also with greater fecal excretion of sterols. Finally, there were no differences in the cholesterol content of the intestine and the liver. Our results suggest that the decrease in plasma cholesterol level in CD11c-hBcl2 apoE KO mice relative to apoE KO mice could be due to both a decrease of intestinal cholesterol absorption and an increase in sterol excretion. The role of intestinal DCs in dietary cholesterol absorption and excretion is presently under investigation but the present study reveal that DCs are central to the atherosclerotic process, because they are implicated in cholesterol metabolism.
Abstract 337: Extensive Coronary Artery Atherosclerosis and Myocardial Infarction in SR-BI/LDLR Double Knockout Mice Fed 4 Different Atherogenic Diets
Authors: Fuller Mark T , Trigatti Bernardo L 
Published: March 2022

Mice lacking the HDL receptor, SR-BI, are susceptible to spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis and myocardial infarction (MI) in the context of an absence, or mutated form of apoE, respectively. We tested the effects of SR-BI deficiency on aortic sinus and CA atherosclerosis in LDL receptor deficient mice fed four different atherogenic diets; the HFCC and HFC diets are composed of 15% fat, 1.25% cholesterol and either contain or lack 0.5% sodium cholate, respectively, the HC diet is a normal chow diet supplemented with 2% cholesterol, and the western diet contains 21% butter fat and 0.15% cholesterol.
SR-BI/LDLR double knockout (dKO) mice fed the HFCC and HFC diets exhibited reduced survival; average survival was 3.5 and 9.5 weeks, respectively. Reduced survival was not observed in LDLR single knockout (sKO) control mice. Plasma lipoprotein cholesterol levels and triglyercide secretion rates were lower in dKO mice compared to sKO mice. Conversely, dKO mice developed significantly larger atherosclerotic plaques in their aortic sinuses compared to sKO mice, and severe occlusive CA atherosclerosis which was not observed in sKO mice. DKO mice fed the HC diet or western diet did not exhibit reduced survival up to 12 weeks of feeding, however CA atherosclerosis was still observed. CA atherosclerosis was accompanied by platelet positive staining and myocardial fibrosis, indicating MI. CA plaques in dKO mice were characterized by the presence of collagen and both CD68 and smooth muscle actin positive staining, indicating complex fibrous plaques consisting of both macrophages and smooth muscle cells. Plaque free CAs and CAs containing small, non-occlusive plaques stained positive for markers of activated endothelium. Importantly, dKO mice fed the HC diet had largest burden of atherosclerosis in their aortic sinuses whereas the extent of atherosclerosis in their CAs was the mild in comparison to that observed dKO mice fed the HFCC and HFC diets. This observation suggests that the development of atherosclerosis in the CAs and the aortic sinus are influenced by different factors.
Abstract 360: Molecular and Cellular Dynamics of Merlin in Vascular Cells via Mechanotransduction
Authors: Shan Chun X , McDonnell Brian , McGinn Ciaran , Dowling Paul , Cummins Philip , Murphy Ronan 
Published: March 2022

Endothelial integrity plays a pivotal role in normal blood vessel function and disruption of which will lead to the initiation and progression of atherosclerosis. The actin cytoskeleton which provides endothelial structural integrity can be greatly disrupted by many factors, such as inflammation and haemodynamic forces. Altered actin dynamics underpins many (patho-) physiological processes in endothelial cells such as migration, differentiation, proliferation and adhesion.
The ERM (ezrin/radixin/moesin) proteins which belong to erythrocyte 4.1 superfamily are actin adaptor proteins and play an important role in controlling cytoskeleton dynamics. This study focuses on one member of the ERM protein family- Merlin. Merlin (moesin, ezrin and radixin-like protein), has been well characterised as a tumour suppressor, contributing to brain tumours such as schwannoma and meningiomas. However, the role of merlin within the vasculature is poorly understood as is its function in various cellular processes such as migration, proliferation and cell adhesion.
In this current study we exposed Human Aortic Endothelial Cells (HAECs), in an in vitro model, to haemodynamic force (i.e. shear stress and cyclic strain) to exam its influence on the temporal and spatial expression of Merlin. We also investigate if Merlin mediates the regulation of Cell-ECM adhesion, migration and proliferation. Results demonstrate that the expression of Merlin is decreased by exposed to haemodynamic force. Furthermore, we have concluded that Merlin knock-down, via siRNA, decreases HAECs adhesion, migration and proliferation as studied in real-time by an xCELLigence system.
Abstract 389: Mitochondrial p27 Is Absolutely Required for Endothelial Cell Migration and ATP Production
Authors: Jakob Sascha , Beylebens Marius , Altschmied Joachim , Haendeler Judith 
Published: March 2022

The cell cycle inhibitor p27 has been shown to exert non-nuclear functions. Moreover, migration of fibroblasts depends on p27 expression. However, the underlying mechanisms of this phenomenon are largely unknown. Therefore, we first investigated the role of p27 in endothelial cell (EC) migration and showed that its downregulation abrogated migration. Since we previously demonstrated that migration of EC requires intact mitochondria, we analyzed whether it depends on the localization of p27 within the cell. We generated p27 variants, which are exclusively localized either in the nucleus (nucp27) or in the mitochondria (mitop27). Overexpression of mitop27 enhanced EC migration, whereas nucp27 decreased it. Along the same line, mitop27 induced ATP production, which is required for migratory processes. As a potential mechanism for the increased ATP production, we found that mitochondrial p27 interacts with prohibitin, which forms multimeric complexes thereby enhancing respiration and ATP production. Next, we analyzed, which domains in p27 are involved in these processes. Therefore, we created p27 deletion mutants and found that both the N- and the C-terminus are necessary for cell migration and ATP-production. These regions contain several phosphorylation sites, two of which (Ser 10 and Thr 187) are phosphorylated by pro-migratory stimuli. Thus, we cloned corresponding nonphosphorylatable (p27 S10A/T187A) and phosphomimetic (p27 S10D/T187D) mutants of mitop27. Overexpression of the nonphosphorylatable mutant decreased EC migration, while the phosphomimetic mutant increased it. Finally, we investigated the mitochondrial import mechanism of p27. Since p27 lacks a typical mitochondrial targeting sequence, we determined whether it interacts with cytosolic heat shock protein 60 (HSP60), which is known to import proteins into the mitochondria. Indeed, cytosolic p27 is associated with HSP60 and this association is increased under promigratory stimuli.
Taken together, these data demonstrate that mitochondrial p27 and its phosphorylation at the N- and C-termini are required for migration and ATP production and that p27 is imported into the mitochondria in a HSP60 dependent manner.
Abstract 460: Thioredoxin-1 and Its Interaction Partners Control Apoptosis in the Endothelium
Authors: Eckers Anna , Zschauer Tim-Christian , Kunze Kerstin , Jakob Sascha , Altschmied Joachim , Haendeler Judith 
Published: March 2022

In the endothelium, defense against oxidative stress as well as inhibition of apoptosis is mainly mediated by thioredoxin-1 (Trx-1). Trx-1 protein levels are reduced in aged endothelial cells (EC) in vitro and in vivo, leading to increased apoptosis sensitivity. Apoptosis is dependent on (i) cytoskeletal changes resulting in formation of stress fibers (thick bundles of actin), (ii) activation of caspase-3 and (iii) the redox status of the cell. The mechanisms how Trx-1 protects EC against apoptosis are not completely understood, but could involve protein-protein interactions.
We identified three proteins interacting with Trx-1: γ-actin, the p17 subunit of Caspase-3 and the AP-endonuclease 1/redox factor 1 (APEX1). We could show that H2O2-induced stress fiber formation in EC was prevented by exogenously applied or overexpressed Trx-1. Moreover, the interaction between Trx-1 and non-polymerized γ-actin precluded Trx-1 degradation, suggesting a mutual protection of both proteins. Secondly, we observed that Trx-1 overexpression reduces apoptosis induction by the p17 subunit of Caspase-3 in EC. This was corroborated by the identification of a disulfide bridge-dependent interaction of Trx-1 with cysteine 163 in p17 preventing association with the second subunit, p12, which is essential for full activation of Caspase-3. However, interaction of Trx-1 with other proteins is not necessarily dependent on disulfide bridge formation. We could demonstrate that APEX1 can protect EC against apoptosis. Interestingly, we found that Trx-1 and APEX1 associate with each other even after mutation of 3 (APEX1) or 2 (Trx-1) cysteines with the same efficiency as the wildtype proteins. It is conceivable that this interaction is required for the protective effect of APEX1.
Taken together, our data demonstrate the importance of Trx-1 in maintaining endothelial cell integrity mediated by interaction with other proteins, and that apoptosis protection of EC is not only due to its anti-oxidative capacity. Loss of Trx-1 in senescent EC therefore importantly contributes to the increased apoptosis sensitivity observed in during aging.