bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II‐Induced Neuroinflammation Contributes to Sympathetic Overactivity in Hypertensive Rats.
Authors: Wang Weizhong , Tan Xing , Wang Yangkai
Published: June 2021

Neuroinflammation has been reported to contribute to cardiovascular dysfunction in hypertension. Increased angiotensin II (Ang II) in the rostral ventrolateral medulla (RVLM) plays an important role in sympathetic overactivity in hypertension. The goal of this present work is to determine the role of Ang II in the RVLM on neuroinflammation in spontaneously hypertensive rats (SHRs). In normotensive WKY rats, intracerebroventricular injection of Ang II (2 weeks) produced a significant increase in blood pressure and renal sympathetic nerve activity, but also increased the content and expression of the proinflammatory sytokine inteleukin‐1 beta, inteleukin‐6, and tumor necrosis factor‐alpha in the RVLM. In SHRs, intracerebroventricular injection of the AT1R antagonist losartan significantly decreased blood pressure and sympathetic outflow, accompanied with reduction in proinflammatory sytokine content and expression. Overexpression of angiotensin‐converting enzyme 2 (ACE2) in the RVLM leads to a significant reduction in blood pressure and sympathetic activity in SHRs. Moreover, mRNA expression of inteleukin‐1 beta, inteleukin‐6, and tumor necrosis factor‐alpha was reduced in SHRs treated with ACE2 overexpression (2 weeks) in the RVLM. Based on the present data, it is suggested that AngII plays an important role in mediating neuroinflammation in the RVLM of hypertensive rats. This work was supported by NSFC (81170240 and 81370363)
Central cyclooxygenase inhibition during the course of lung injury attenuates breathing frequency
Authors: Litvin David , Nethery David , Campanaro Cara , Dick Ted , Jacono Frank
Published: June 2021

Ventilatory pattern is a neurally integrated output that is altered by lung injury. Work in our lab has provided evidence that ventilatory pattern changes persist in situ, and are concurrent with elevated IL‐1β expression, astrogliosis and altered synaptic efficacy in the nucleus of the tractus solitarii (nTS), a brainstem region critical for viscerosensory integration. Most recently, we observed that microinjection of exogenous IL‐1β into the nTS of naïve rats evokes some of the ventilatory pattern changes observed during lung injury. Collectively, these findings suggest that lung injury exerts influence over the neural control of breathing in part through the action of neuroinflammation. We therefore hypothesized that inhibiting neuroinflammation during the course of lung injury would attenuate breathing frequency (FR) and reduce IL‐β expression in the nTS. To test this hypothesis, we continuously administered either vehicle or indomethacin (IND), a cyclooxygenase‐1/2 (COX‐1/2) inhibitor, into the right lateral ventricle of bleomycin lung‐injured rats (bleo) via Alzet pump. We plethysmographically recorded breathing pattern and densitometrically measured brainstem IL‐1β immunoreactivity (IR) at day 7 of lung injury. We observed a significant (P<0.05) attenuation of FR in bleo rats receiving IND (161±56bpm, n=10) as compared to bleo rats receiving vehicle (217±66bpm, n=10). The level of IL‐1β IR detected within the nTS of IND treated bleo rats was reduced. Taken together, our results indicate that ventilatory pattern changes, which occur in the setting of lung injury, are in part dependent upon the central action of COX‐1/2, and are associated with decreased IL‐1β expression in the nTS.
High‐Mobility Group Box 1 (HMGB1) in Angiotensin II induced hypertension
Authors: Nair Anand , Ebenezer Philip , Francis Joseph
Published: June 2021

Hypertension is the most critical predisposing factor for the development of cardiovascular diseases. While effective pharmacological control of hypertension using angiotensin receptor blockers has been implemented, the clinical course of the disease remains progressive. Consequently, new and innovative approaches for treating hypertension are needed. A growing body of evidence suggests that inflammatory cytokines play important roles in the pathophysiology of cardiovascular disease. Our lab has shown that blocking inflammatory molecules and their transcription factor, nuclear transcription factor kappa B (NF‐kB), within the paraventricular nucleus (PVN) attenuates sympathetic activity and hypertension. However, it remains unknown how inflammation is activated during the development of hypertension. We proposed that the interaction between the inflammatory cytokine protein high‐mobility group box 1 (HMGB1) and its toll‐like receptor, TLR4, results in the up‐regulation of NF‐kB, thereby contributing to the development of hypertension. We performed in vitro and in vivo studies to understand the role played by HMGB1 in the development of hypertension. We treated mouse Neuro‐2a cells with control medium or medium containing Angiotensin II (AngII). Immunofluorescence and immunoblot analysis of AngII‐treated N2a cells correlated increases in HMGB1 levels with up‐regulation of inflammatory markers. In addition, we examined the levels of HMGB1 in the PVN from AngII and saline‐treated rats using RT‐PCR and western blotting. AngII treatment resulted in an increase in blood pressure and this was accompanied by an increase in HMGB1 in the PVN of rats. These findings indicate a potential for HMGB1 in the PVN as a possible mechanism of AngII‐induced hypertension.
Carotid Body Ablation Reverses the Hypertension and Autonomic Changes Induced by Intermittent Hypoxia
Authors: Del Rio Rodrigo , Andrade David , Iturriaga Rodrigo
Published: June 2021

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea syndrome, enhances carotid body (CB) chemosensory discharges in normoxia, eliciting sympathetic overactivation and hypertension. We propose that the enhanced CB chemosensory drive plays a crucial role in the generation of the hypertension during CIH. To study the origin of higher blood pressures during CIH, we performed selective ablation of the CB once animals became hypertensive following CIH exposure. Male Sprague‐Dawley rats (200 g) were exposed to CIH (5% O2, 12 times/h, 8 h/day) and arterial blood pressure (BP) was measured with radiotelemetry. After 3 weeks of CIH, under anesthesia both CBs were cryogenically destroyed with an ice cold needle, and rats were kept one more week in CIH. The effectiveness of this maneuver was confirmed by the disappearance of the ventilatory response to NaCN. After 3 weeks of CIH exposure, rats displayed hypertension (BP~10 mmHg), enhanced hypoxic ventilatory response and reduced baroreflex sensitivity (BRS) from 2.28±0.05 to 1.76±0.10 ms/mmHg. The ablation of the CBs markedly decreases the elevated BP, reduced the enhanced ventilatory response to hypoxia and normalized BRS to 2.52±0.12 ms/mmHg. We found that the cardiorespiratory alterations induced by CIH are critically dependent on functional CB chemoreceptors. Also, our results showed that the CIH‐induced hypertension was abolished by ablation of the CB despite the continuous exposure to CIH stimulation. Thus, our results indicate that the CB plays a pivotal role in the progression and maintenance of the CIH‐induced hypertension.

Supported by Puente 28/2014 PUC
Mutations for Worse or Better: Low Fidelity DNA Synthesis by SOS DNA Polymerase V is a Tightly‐Regulated Double‐Edged Sword
Authors: Goodman Myron , Erdem Aysen , Jaszczur Malgorzata , Bertram Jeffrey , Woodgate Roger , Cox Michael
Published: June 2021

Mutations are almost always bad typically with negative consequences. But mutations can also be good by serving as the engine driving evolution. A specialized DNA polymerase (pol) family, the Y‐family, is present spanning bacteria to humans, whose central role is to copy past damaged DNA template bases that block replication. There's no free lunch however, because the costs of fully replicating the genome are often mutations frequently targeted at lesion sites, but occasionally occurring within undamaged template regions. The “error‐prone” DNA polymerase V, is induced in response to DNA damage by the Escherichia coli SOS regulon, and is responsible for the lion's share of chromosomal mutations by copying past aberrant template bases. We will discuss the great lengths to which the cell goes to limit the access of pol V to work just in the vicinity of damaged DNA by imposing tight regulation temporally, spatially in the cell, and internally within pol V. The key self‐regulatory feature centers on the recent surprising discovery that the polymerase contains an intrinsic DNA‐dependent ATPase activity. We will discuss how ATP and ATP hydrolysis conspire to determine how and when the polymerase is activated, allowing it to bind to DNA and perform translesion synthesis, and then deactivated, causing its release from DNA.
Build a Successful Career in Industry by Attaining Multidisciplinary Knowledge and Experience
Authors: Urh Marjeta
Published: June 2021

Academic curriculum rarely includes information on how to find a job and build a career after graduate school; career development has become your own responsibility. Finding a job and building a successful career in industry requires planning, and my presentation will be focused on what can be done to prepare for a job in industry. There are two major aspects to preparation for a job in industry; first is to understand the differences between research environments in industry and academia. The better you understand the industrial work environment, the better you will be at presenting yourself as someone who could make a contribution. The second aspect in preparation for an industrial job is to explore the idea of building a career in industry, not as an alternative to an academic position, but rather as a career path of choice. Understanding of these aspects will help you understand whether building a career in industry is something you want to pursue and will find challenging and fulfilling. Another important consideration of building a career in industry is to understand that there are many different research positions and career paths in industry. Finding the right position is key to a successful and fulfilling career. I will address how multidisciplinary knowledge, experience and skills can help you prepare for the job you desire in an extremely competitive job field.
A Protein‐Based Breakfast Increases Postprandial Fat Metabolism in Overweight and Obese Children
Authors: Baum Jamie , Gray Michelle
Published: June 2021

Breakfast is a key component of a healthy diet and can positively impact children's health. However, there has been a steady decline in breakfast consumption in children over the past 40 years. The objective of this study was to determine if breakfast macronutrient composition (protein (PRO)‐based breakfast [22% protein, 45% carbohydrate, 26% fat] or an isocaloric carbohydrate (CHO)‐based breakfast [4% protein, 67% carbohydrate, 29% fat]) can influence postprandial (pp) substrate utilization in overweight/obese (OW; n=13) versus normal weight (NW; n=16) children ages 8‐11 years old. We found no significant difference in fasting respiratory quotient (RQ) between groups. There was no difference in postprandial RQ area under the curve (AUC) between OW and NW or between PRO and CHO breakfasts. OW had significantly higher fasting VO2 (oxygen consumption) values (P = 0.02) and VCO2 (carbon dioxide production) values (P = 0.01) compared to NW. OW had significantly higher pp AUC VO2 in response to the PRO breakfast compared to NW children (P < 0.05). There was a trend (P = 0.06) for OW to burn more kcal from CHO during fasting and there was no significant pp response between NW and OW or PRO and CHO breakfasts. Finally, there was no significant different in fasting kcal from fat between OW and NW groups, however OW burned significantly higher kcal from fat following the PRO breakfast (31%) compared to the CHO breakfast and NW children consuming PRO and CHO breakfasts (28% and 28%, respectively). These data suggest that consumption of a PRO breakfast has the potential to modulate postprandial substrate utilization by increasing kcal used from fat in OW children. Funded by the American Egg Board/Egg Nutrition Center.
Black Raspberries Prevent Angiotensin II‐Induced Senescence in Vascular Smooth Muscle Cells
Authors: Feresin Rafaela , Zhao Yitong , Salazar Gloria
Published: June 2021

The incidence of cardiovascular diseases (CVDs) is strongly associated with the physiological changes that occur with aging. Activation of the angiotensin II (Ang II) signaling pathway during aging increases the level of reactive oxygen species (ROS) leading to vascular senescence and therefore CVDs. Epidemiological studies correlate consumption of fruits and vegetables, in particular berries, with decreased incidence of CVDs, which is mainly attributed to the polyphenol content of these foods. However, the molecular mechanism mediating the protective effect of berries is not completely understood. Black raspberries (BRB) have a high polyphenol content and a powerful antioxidant capacity. Thus, the purpose of the present study was to determine the protective role of BRB polyphenol extract (PE) in Ang II‐induced senescence in vascular smooth muscle cells (VSCMs). Polyphenols were extracted from BRB using ethanol, purified by fractionation with chloroform and ethyl acetate, and total polyphenol content of crude and purified extracts was determined by Folin‐Ciocalteu method. Treatment of VSMCs with Ang II (100 nM) increased ROS levels, decreased catalase expression and increased senescence associated β‐galactosidase; thus, promoting vascular senescence. Pre‐incubation with BRBPE (200 and 400 μM) prevented Ang II‐induced increases in ROS levels and catalase downregulation leading to decreased senescence. Thus far, our findings indicate that BRBPE may enhance vascular health.
Adherence to the DASH Diet and Risk of Incident Chronic Kidney Disease: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Rebholz Casey , Crews Deidra , Grams Morgan , Levey Andrew , Miller Edgar , Appel Lawrence , Coresh Josef
Published: June 2021

Introduction

There are established guidelines for optimal dietary intake for the prevention of hypertension and cardiovascular disease. Evidence is lacking for effective dietary patterns for the prevention of chronic kidney disease (CKD).

Methods

We conducted prospective analyses of ARIC study participants without CKD at baseline (1987‐89, N=15,100). A score was created to assess adherence to the Dietary Approaches to Stop Hypertension (DASH) diet. Incident CKD was defined as an ICD‐9/10 code for a CKD‐related hospitalization or death, end‐stage renal disease, or decreased kidney function [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or 蠅25% eGFR decline from baseline] from baseline through 2011.

Results

There were a total of 2,351 incident CKD cases during a median follow‐up of 21 years. Participants with a DASH diet adherence score in the lowest tertile were at an increased risk of CKD (Table). Of the individual components of the DASH diet adherence score, low intake of magnesium and calcium and high intake of sodium were strongly associated with increased risk of CKD.

Table. Risk of Incident Chronic Kidney Disease According to Tertile of DASH Diet Score

Low AdherenceTertile 1
Moderate AdherenceTertile 3
High AdherenceTertile 3
P‐value for trend

% (n)
‐‐
39% (6,017)
36% (5,500)
25% (3,911)
‐‐

IR (95% CI)
‐‐
9.29 (8.72, 9.90)
8.51 (7.95, 9.11)
8.48 (7.82, 9.19)
0.01

HR (95% CI)
Model 1
1.14 (1.02, 1.27)
1.02 (0.91, 1.13)
1 [Reference]
0.002

HR (95% CI)
Model 2
1.13 (1.01, 1.26)
1.01 (0.91, 1.13)
1 [Reference]
0.003

Conclusions

Higher adherence to the DASH diet may be associated with lower risk for developing CKD, independent of demographic characteristics, caloric intake, hypertension, diabetes, and kidney function. Further study is required to determine whether following a diet that is high in fruits, vegetables, and low‐fat dairy, and low in sodium, which has been shown to prevent hypertension and cardiovascular disease, might also prevent the development of CKD.
Additive Effects of Interpersonal Counseling and Mass Media on Psychosocial Determinants of Exclusive Breastfeeding among Vietnamese Mothers
Authors: Nguyen P , Kim S , Nguyen T , Hajeebhoy N , Tran L , Ruel M , Rawat R , Frongillo E , Menon P
Published: June 2021

The pathways through which behavior change interventions impact breastfeeding (BF) practices have not been well studied. This study aimed to 1) examine separate and interactive effects of mass media (MM) and interpersonal counseling (IPC) on BF‐related psychosocial factors; and 2) assess the pathways through which intervention exposure affects exclusive breastfeeding (EBF). Survey data from mothers with children < 2 y (n=2045) from the process evaluation of Alive & Thrive's programs in Viet Nam were used. Exposure to MM only, IPC only, both, or neither was 51%, 5%, 19%, and 25%, respectively. Multiple linear regression showed consistent additive effects of MM+IPC on BF knowledge (b= 2.8, 11.5, and 14.4 for MM, IPC, and both, respectively), intention (b= 6.2, 14.9, and 18.0 for MM, IPC, and both), beliefs (b= 5.3, 12.7, and 16.8 for MM, IPC, and both), social norms (b= 5.0, 13.6, and 16.5 for MM, IPC, and both) and self‐efficacy (4.3, 14.6, and 17.4 for MM, IPC, and both). Women who viewed TV spots more frequently, recalled more messages, and those who received the recommended number of IPC visits had a higher score on psychosocial factors. Compared to no exposure, IPC and MM+IPC exposure were associated with 23.5% and 31.2% higher EBF, respectively. Structural equation modeling revealed that 90% of the total effect of IPC only or MM+IPC on EBF practice was explained by the psychosocial factors. The findings suggest that combining different behavior change modalities can lead to greater changes in psychosocial factors, which in turn positively affects breastfeeding behaviors.

Funding: Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI360
The Role of ZnT2 in the Mammary Gland during Lactation
Authors: Lee Sooyeon , Soybel David , Kelleher Shannon
Published: June 2021

Successful lactation requires optimal regulation of mammary gland (MG) differentiation, milk secretion and milk composition. We and others have reported four “loss‐of‐function” mutations in the zinc (Zn) transporter ZnT2 that reduce milk Zn levels by ~75% causing transient neonatal Zn deficiency. However, ZnT2 plays multifactorial roles in MG biology and effects of ZnT2 dysfunction have not been explored. We used lactating ZnT2‐null (ZnT2ko) mice to identify consequences of loss of ZnT2 function during lactation. Similar to women with mutations in ZnT2, lactating ZnT2ko mice had significantly lower milk Zn levels. In addition, we found that the major milk components, b‐casein, lactose and fat were significantly reduced by ~40% in ZnT2ko mice. Lactating ZnT2ko mice had substantial defects in MG architecture and function including fewer, condensed and disorganized alveoli and reduced Stat5 activation. Morphological analysis revealed lipid droplet accumulation in engorged mammary epithelial cells (MECs) lining the alveoli, indicating secretory inactivation. Electron microscopy illustrated that MECs were unpolarized and severely disorganized with swollen mitochondria and fragmented endoplasmic reticulum and lipid accumulation. Consequently, milk volume was significantly reduced and less than 50% of ZnT2ko dams had surviving litters. Taken together, our results establish that ZnT2 is a critical regulator of MG function to ensure optimal milk quality and function during lactation. Finally, our study suggests that women with mutations in ZnT2 may be at risk for sub‐optimal milk composition and insufficient lactation.
Estimating the Sugars Content of Simulated Diets that Follow Eating Well with Canada's Food Guide
Authors: St‐Pierre Sylvie , Gilbert Jo‐Anne , Elvidge Lisa‐Anne
Published: June 2021

Canada's Food Guide (CFG) recommends choosing foods lower in fat, sugar and salt and provides guidance to choose foods lower in added sugars. Added sugar levels in CFG's dietary patterns have never been estimated.

Objectives

Estimate the proportion of calories coming from added and free sugars in CFG's dietary patterns; and assess these results against the World Health Organisation (WHO) guidance on sugars.

Methods

Sugar‐containing foods were assigned to 3 categories: a) naturally occurring sugars source b) added sugars source or, c) free sugars source. Secondly, we simulated 8000 diets (500 for each age/sex group) consistent with CFG's dietary patterns and estimated their sugars content. Specifically, the grams of total sugars of a food having only naturally‐occurring sugars were all counted as naturally occurring sugars; the grams of total sugars of foods containing a mix of naturally occurring sugars and added or free sugars were all counted as added sugars and/or as free sugars. [This conservative methodology tends to overestimate added/ free sugar content.]

Results

Mean percentage of energy (E) from total sugars was 21% (17‐24%). Added and free sugars estimates were respectively 3%E (1.7‐5.2%) and 7%E (4.5‐10%). Top contributors of sugars were from naturally occurring sources such as milk products, vegetables and fruits. An assessment of the nutrient distributions of the simulated diets against the Dietary Reference Intakes showed a low prevalence of nutrient inadequacy and an adequate energy level.

Conclusion

These results showed that the sugar content of CFG dietary patterns is in line with the WHO sugar's recommendations. Adopting CFG's guidance leads to low levels of added/free sugars in the diets while meeting nutrient and energy requirements.
The Effect of Soy‐Dairy Protein Blend Supplementation during Resistance Exercise Training
Authors: Reidy Paul , Borack Michael , Markofski Melissa , Dickinson Jared , Deer Rachel , Husaini Syed , Walker Walker , Igbinigie Sherry , Cope Mark , Mukherjea Ratna , Jennings Kristofer , Volpi Elena , Rasmussen Blake
Published: June 2021

Soy‐dairy protein blend (PB) ingestion prolongs the muscle protein synthesis response to a bout of resistance exercise. The efficacy of PB supplementation with resistance exercise training (RET) has not been evaluated in chronic studies. Our aim was to determine the effect of PB supplementation during RET on lean body mass (LBM), muscle thickness and strength. Healthy young men participated in supervised whole body progressive RET at 60‐80% 1 maximum (1‐RM), 3d/wk for 3 months. Participants were randomized to one of three treatments to ingest 22g protein as soy‐dairy protein blend (PB, N=23), whey protein isolate (WP, N=22) or an isocaloric placebo, 22g maltodextrin (MP, N=23) daily. Whole body lean mass (LBM), muscle strength (dynamometry & 1‐& 8‐RM testing) and vastus lateralis muscle thickness (MT) were assessed at pre & post RET. All treatments increased LBM (p<0.05). PB exhibited a trend for greater LBM change compared to MP (0.92 kg: ‐0.12, 1.95); however, there was no difference in LBM change between WP & MP. Muscle strength (RM tested) and thickness increased similarly for all treatments. All treatments increased isometric knee extension and flexion torque (P<0.05). Both protein‐supplemented treatments increased isokinetic knee extension torque (P<0.05). In conclusion, a soy‐dairy protein blend may enhance LBM during a 3 month RET period, and minor differences in strength between treatments were observed.
A Diet High in Protein Reduces Weight Gain, Food Intake and Liver Weight in Obese Zucker Rats
Authors: French William , Shouse Stephanie , Gu Xuan , Lee Sun‐Ok , Baum Jamie
Published: June 2021

It has become a challenge to find effective treatments and preventive strategies to reduce obesity and diabetes (T2DM). There are several approaches to treating these diseases, including nutrition therapy. Diets high in protein are linked with weight reduction and improved insulin resistance. Therefore, the objective of this study was to examine the effects of a long‐term, high protein (pro) diet (40%) vs a moderate pro diet (20%) on body composition and metabolism using a genetic model of obesity/T2DM. Male, lean (L) and obese (O) Zucker rats (n = 8‐10 per group) were housed 2/cage and placed in one of four groups: L20, L40, O20 or O40. Animals were provided ad libitum access to diet and water for 12 weeks. At 12 weeks, animals were fasted for 8 hours, then trunk blood and tissues were collected. L had lower food intake (P < 0.05) than O, and O40 had significantly lower food intake (P < 0.05) than O20. Animals fed 40% pro had significantly lower weight gain (P < 0.05) than those fed 20% pro. L had more muscle mass and lower fat mass than O (P < 0.05). However, L40 had significantly lower fat mass than L20. O40 had lower liver weights (P < 0.05) than O20. There was no difference in fasting glucose and O had higher fasting insulin. Fasting free fatty acids were higher in animals fed the 20% pro diet. There was no difference in basal phosphorylation of Akt, AMPK, mTOR or 4E‐BP1. There was no difference in basal BCAA between L20 and O20. L40 and O40 had significantly higher basal levels of BCAA (P < 0.05). We conclude that higher protein diets have the potential to reduce weight gain and alter metabolism in obese rats. Funded by Arkansas Biosciences Institute.
Platform Technologies for Routine Generation of Advanced Organotypic Three Dimensional Cell Culture Models
Authors: Przyborski Stefan
Published: June 2021

Technologies are now available that enable researchers to preserve the native 3D structure of cells in vitro. These can be broadly divided into three areas: aggregate‐based methods; hydrogels and extra‐cellular matrices; and inert scaffold‐based technologies. Combining these technologies allows for the creation of more sophisticated models and more physiologically relevant cell‐based assays. This is achieved by recreation of more in vivo‐like cell and tissue structure and function. Anatomically, tissues in the body are mostly composed of different cell types that are often highly organized in relation to each other. Often cells are arranged in distinct layers that enable signaling and cell‐to‐cell interactions. Recreation of this architecture has a profound effect on cell behavior and significant impact on research and discovery. Our work highlights the application of scaffolds in combination with hydrogels and cell aggregates to support the growth and differentiation of cells as multilayered tissue‐like structures to study biological mechanisms in neurobiology, epithelial and cancer.
Local Vitamin D Metabolism is Differentially Regulated by MKP‐1 in Osteoclasts Stimulated with RANKL vs. LPS
Authors: Valerio Michael , Kirkwood Keith
Published: June 2021

Recent reports indicate that the substrate level activity of Vitamin D (VD) regulates local inflammatory cytokine production, including mediators that regulate osteoclast (OC) formation. MKP‐1, a phosphatase which controls p38 and JNK MAPK signaling has been shown to be dependent on VD. Conversely, VD‐dependent genes involved in VD metabolism (Cyp27b1, Cyp24a1) and bone turnover (RANKL) are regulated by MKP‐1, resulting in abnormal VD activity and reduced OC. Interestingly, we reported that MKP‐1 positively regulates RANKL‐induce OC formation, but also reported that it negatively regulates OC formation in pre‐OC stimulated with pathogenic Lipopolysaccaride (LPS). Given the recent reports of VD's regulation of the inflammatory microenvironment, the objective of these experiments was to investigate the role of MKP‐1 on VDR‐dependent gene expression in RANKL vs. LPS‐stimulated pre‐OC. WT and MKP‐1‐/‐ bone marrow cells were obtained and isolated for pre‐OC using magnetic sorting for CD11bloCD115+ monocytes, stimulated with MCSF and RANKL (50ng/ml) or LPS (100ng/ml) for 96hrs. mRNA was and measured for expression of VD metabolism using qPCR. By adding LPS, Vdr expression was significantly up‐regulated in the MKP‐1‐/‐ population (P<0.01), however, expression of Cyp27b1 was significantly blunted in MKP‐1‐/‐ OC (P<0.05). Cyp24a1 was not induced by LPS. In conclusion, MKP‐1 neg. regulates VDR and + regulates Cyp27b1 in OC in response to LPS, not RANKL, contrary to what has been observed in osteoblasts. In all, MKP‐1 does not inhibit VDR nuclear activity in OC cells stimulated with LPS, but may play a role in the regulation of enzymes involved in local VD activation.
Shiitake‐Derived β‐Glucan, Lentinan, Reduces CCL3/MIP‐1α Production via Down‐Modulation of TLR2‐ And TLR4‐Mediated NFκB Activation And TLR2 Expression in Human THP‐1 Monocytes
Authors: Dai Xiaoshuang , Percival Susan
Published: June 2021

High levels of the chemokine CCL3/MIP‐1α are associated with various human diseases. In our previous study, shiitake mushrooms (Lentinula edodes), consumed as a whole food, had an inhibitory effect on MIP‐1α production in human ex vivo PBMC. We hypothesized that this effect was due to lentinan, a β‐1,3;1,6‐glucan, acting in an anti‐inflammatory manner, and that the change in MIP‐1α production was under Toll‐like receptor (TLR) and NF‐kB regulation. This study examined the mechanism using the human THP‐1 monocyte cell line. Pam3CSK4 and LPS were used as TLR ligands to induce TLR2 and TLR4 activation, respectively. We showed that lentinan attenuated TLR2‐ and TLR4‐induced MIP‐1α production and NF‐kB activation of the THP‐1 cells. Flow cytometric analysis revealed that both surface and intracellular levels of TLR2 were decreased by lentinan. However, neutralization of TLR2 did not blunt the inhibitory effect of lentinan, suggesting that the effect was not due to TLR2 alone. Cytochalasin D, a β‐glucan internalization inhibitor, cancelled the inhibition of MIP‐1α production by lentinan, suggesting that the inhibitory activity of lentinan requires particle internalization. We conclude that the down‐modulation of TLR2 expression, suppression of NF‐kB activation and attenuation of MIP‐1α production by lentinan may all play important roles in the anti‐inflammatory effect of shiitake mushrooms. It is possible that lentinan may be effective as an anti‐inflammatory agent to prevent or control the diseases associated with excessive MIP‐1α production. Partially funded by US Mushroom Council, Australian Mushroom Growers Assn. and UF AES.
Changes in Intake and Major Food Sources of Flavonoids among U.S. Adults between 1999‐2002 and 2007‐2010
Authors: Kim Kijoon , Vance Terrence , Chun Ock K.
Published: June 2021

Epidemiologic evidence has implicated that dietary flavonoids or flavonoid rich foods are associated with a reduced risk of certain chronic diseases. However, incomplete food composition data and changes in diet over time likely affect the accuracy of flavonoid intake estimates. The current study was conducted to: 1) demonstrate an updated method of combining food consumption data and USDA flavonoid database; 2) estimate the current intake and major food sources of dietary flavonoids of US adults; and 3) determine if dietary intake and sources of flavonoids changed during the past decade. Differences over time in the average daily intake and food sources of flavonoids were estimated using 24‐hour dietary recall data from NHANES 1999‐2002 (n = 8,833) and 2007‐2010 (n = 9,801). The total flavonoid intake of US adults aged 蠅19 years was similar between 1999‐2002 (201.8 mg/d) and 2007‐2010 (199.9 mg/d) with tea being the major food source of flavonoids. However, intake of anthocyanidins increased during this period, which was mostly attributable to greater consumption of berries and wine in 2007‐2010 (p < 0.001) and coincided with per capita food consumption from USDA food availability data. This study demonstrates temporal trends in the dietary sources and intake of flavonoids in the US over the past decade and provides a basis for further research on the health effects of flavonoid consumption.
Development and Validation of a Novel Household Grocery Food Purchase Quality Score
Authors: Brewster Philip , Guenther Patricia , Jordan Kristine , Hurdle John
Published: June 2021

Burdensome surveys and convenience sampling limit the ability to assess the quality of grocery food purchases. Our goal was to develop a metric for assessing such purchase data unobtrusively and at scale. We obtained de‐identified 2012 sales transaction data for 92,314 households in 4 geographic locations and re‐classified 1,888 higher‐order food descriptors into the 29 categories of USDA's Food Plan market baskets, which comply with the Dietary Guidelines. The standardized expenditure share for each category was the weighted average of all sex‐age groups used in the Food Plans. Quality of food purchases was evaluated by comparing the observed to the standardized expenditure share for each category. The 29 categories were then grouped into 10 food groups related to the Healthy Eating Index‐2010‐‐Total Vegetables, Greens and Beans, Total Fruit, Whole Fruit, Whole Grains, Dairy, Total Protein Foods, Seafood and Plant Proteins, Refined Grains, and Sweets‐‐and scored. Households who never purchased tobacco (n=71,475) had higher mean total scores (39.6 out of a possible 70) than those who did (36.3) (p<0.01) as well as higher scores for 8 of the 10 food groups (p<0.01). Thus, construct validity was established. This approach can be applied using longitudinal data to describe population‐level food purchase quality patterns and trends.

Support: NIH grant T15‐LM007124; University of Utah Funding Incentive Seed Grant
Validation of Instruments to Assess Home Food Environment of Pre‐adolescents: A Pilot Study
Authors: Nepper Martha , Ludemann McKena , Chai Weiwen
Published: June 2021

Objective

To validate a Home Food Assessment tool (HFA) to evaluate the availability, visibility and accessibility of actual home foods and a 30‐day Home Food Environment Survey (HFES) to assess the foods regularly present in the homes of pre‐adolescents.

Methods

Thirteen pairs of parents and their children (9 to 12 years) participated in the study. The HFA was completed by the research staff and parents independently for criterion validity. Kappa statistics was used to compare parent and staff reports. Parents also completed HFES during the home visit and one week after for test/retest reliability. Cronbach's alpha was used to test the internal consistency of the instruments.

Results

Of the 23 healthy and unhealthy items from HFA, moderate to outstanding agreement (0.41 – 1.00) between research staff and parents was observed on 21, 14, and 18 items for availability, visibility, and accessibility, respectively. Agreement levels for items of fresh fruits and vegetables ranged from moderate to outstanding (0.41‐1.00), with the exception of four items. Internal consistency for 12 healthy food, 11 unhealthy food, 18 fresh fruit, and 14 fresh vegetable items were 0.94, 0.91, 0.90, and 0.87, respectively. For HFES, test and retest scores were significantly correlated except for two reduced‐fat items. The total scores of the available healthy (r=0.87, P =0.0001) or unhealthy items (r=0.85, P=0.0005) from the HFA were positively correlated to those from HFES.

Conclusion

Our results demonstrated that HFA and HFES are participant‐friendly, reliable and valid instruments to assess the home food environment of pre‐adolescents. These two instruments complement each other and are useful for future research in exploring the relationship between home food environment and weight status of pre‐adolescents.
The Home Food Environment and a Young Child's Weight Status
Authors: Emond Jennifer , Gilbert‐Diamond Diane , Ma Yu , Grewal Dhrev , Ailawadi Kusum
Published: June 2021

The majority of a young child's diet is from foods available in the home. We investigated how a home's nutritional profile associates with a young child's weight. Data were from a national household panel completed 2006‐2008. Participants scanned all foods and beverages purchased for the home with a handheld UPC‐barcode scanner and data were linked to a nutritional database. Households completed a survey including demographics, weight and height for all household members. Analyses were limited to families with young children 2‐12 years old with a year of purchase data and complete anthropometric data (N=4,276). A series of adjusted logistic regression models fit the odds of a young child in the home being overweight (蠅85th age and sex adjusted BMI percentile) on the nutritional profile of the home. Households purchased 985 calories in packaged foods per capita daily. Total calories purchased increased with head of household weight status. Thirty‐nine percent of homes had at least one young child who was overweight. In a logistic regression model adjusted for household size, dual vs. single head of household, head of household weight status and total protein and total calories in the home, total levels of fat in the home was statistically, positively associated with a child being overweight. Results were similar when further adjusting for total levels of sodium in the home and sodium was statistically, positively associated with a child being overweight: aOR 4th vs. 1st quartile 1.73 (p=0.001). In conclusion, a greater availability of foods high in fat and sodium in the home may be obesogenic for young children.

Funded by Norris Cotton Cancer Center.
Changes in Growth and Feed Efficiency in Chickens Supplemented with Supernutritional and Excess Selenium are Associated with Changes in Appetite
Authors: Li Jinlong , Cao Changyu , Wang Lili , Jiang Xiuqing , Zhang Cong , Xu Jingxiu
Published: June 2021

Selenium (Se) is an essential nutrient for the chicken. We recently reported that both insufficient and excess Se decreased growth in chickens (Biol Trace Elem Res 159:174(2014)). Oral Se administration to Se‐deficient chickens has been reported to increase appetite within hours. To better understand the relationship of Se status with growth and appetite, 1‐day‐old Hy‐Line White chickens were fed a low Se diet (Se‐L, 0.028 mg/g) supplemented with 4 levels of dietary Se (0 to 5.0 mg Se/kg) as Na2SeO3 for 8 wk. Body weight (BW) and feed intake (FI) were decreased significantly by Se‐L and Se‐excess (Se‐E, 5.0 mg/kg) vs. Se‐adequate (Se‐A, 0.15 mg/kg), whereas Se‐supernutrition (Se‐S, 3.0 mg/kg) increased BW and FI as compared to Se‐A birds. FI relative to metabolic size (FI/BW0.67) of Se‐S birds was significantly higher than other groups. Se‐S lowered and Se‐E increased blood glucose relative to Se‐A and Se‐L birds. At 8 wk, gene expression of Neuropeptide Y (NPY) in hypothalamus was increased by Se‐S but leptin receptor (LEPR) mRNA levels were unchanged relative to Se‐A birds, suggesting that increased FI in Se‐S birds was due to increased appetite. In Se‐E birds, LEPR mRNA levels were increased at 8 wk, suggesting appetite was decreased in Se‐E birds. There were no differences in NPY or LEPR mRNA in Se‐L vs. Se‐A birds. In summary, these results demonstrate that changes in growth and feed efficiency with supernutritional Se and excess Se are associated with changes in appetite. Support: China NECT‐1207‐02; 1252‐NCET‐009 and 2012RBC52.
Effect of Mouse Strain on Dietary CLA and Coconut Oil‐Induced Lipolysis
Authors: Barnes Kimberly , Chen Qiannan , Dartigue Vincent
Published: June 2021

Dietary conjugated linoleic acid (CLA)‐induced lipolysis and body fat loss are enhanced in mice fed coconut oil (CO); however, differences between mouse strains have been observed. This study was designed to evaluate the response to CLA and oil source in 4 common mouse strains. Male CF‐1, ICR, NIH, and Swiss Webster mice (3‐wk‐old, n = 24 per strain) were fed diets containing either soy oil (SO) or CO for 6 weeks, followed by 0 or 0.5% CLA (replacing base oil w/w) for 12 days. Tissue weights were measured for the calculation of a body fat index (BFI): epididymal + retroperitoneal fat pads/body weight*100. Epididymal and retroperitoneal fat pads were pooled and used for ex vivo lipolysis analysis and real time RT‐PCR. We detected an oil*CLA interaction (P = 0.03) on BFI where SO‐fed mice were the fattest and CO+CLA‐fed mice were the leanest, and a main effect of strain (P < 0.001) where Swiss Webster mice were the fattest and NIH mice the leanest, but no diet by strain interactions. Lipolysis was stimulated by both CO (P < 0.001) and CLA (P = 0.002) with no effect of strain. No differences in the mRNA expressions of UCP1, UCP2, UCP3, or CPT1 were detected but UCP1 expression was positively correlated (r = 0.26, P = 0.01) with lipolysis. As expected, the BFI was negatively correlated (r = ‐0.43, P < 0.001) with lipolysis but positively correlated (r = 0.35, P = 0.001) with serum NEFA. In conclusion, we found that mouse strain does not significantly impact the response to CLA and/or CO and no evidence of increased UCP expression in the adipose tissue of CLA‐fed mice.
Dietary Flax Oil Enriches Adipose Tissue Phospholipids in Long Chain n‐3 PUFA and Reduces Adiposity
Authors: Torchon T Emmanuelle , Das Suchita , Voy Brynn
Published: June 2021

Consumption of diets enriched in long‐chain omega‐3 polyunsaturated fatty acids (LC n‐3 PUFA) has been associated with reduced adiposity and metabolic benefits in humans and animals, including poultry. Avians express unique elongase enzymes that, relative to humans, enhance their capacity to produce eicosapentaenoic acid (EPA, 20:5, n‐3) and docosahexaenoic acid (DHA, 22:6, n‐3) from alpha‐linolenic acid (ALA; 18:3, n‐3). We tested the hypothesis that enriching adipose tissue in ALA would reduce adiposity in broiler chickens by activating lipid‐responsive nuclear receptors and upregulating expression of genes involved in fatty acid oxidation, comparable to what we have previously found for fasting (Ji et al., 2012). Cobb 500 broiler chicks were fed isocaloric diets containing either 8% flaxseed oil (flax) or 8% lard from hatch to 21 days of age (DS1), or from 21‐42 days of age (DS2). Adipose neutral lipid fatty acid profiles reflected the dietary fat composition. Both EPA and DHA were undetectable in adipose phospholipids (PL) from the lard group but were present in birds consuming flax, while arachidonic acid was increased in PL of the lard group. In both DS1 and DS2, flax diets significantly (p<0.05) reduced adiposity and abdominal adipose weight, with no effect on body weight. Plasma non‐esterified fatty acid (NEFA) levels were significantly lower in flax vs. lard birds in both studies (p=0.0062, DS1 and p=0.014, DS2). Despite the significant reduction in adiposity, we did not find evidence for upregulation of genes involved in fatty acid oxidation based on QPCR of abdominal adipose tissue. In conclusion, these studies demonstrate that dietary enrichment in ALA reduces adiposity, but the mechanisms remain to be determined.
A High Throughput Image‐based Screening Reveals Novel Autophagy Inducers For Treating Drug‐Induced Liver Injury
Authors: Li Yuan , McGreal Steven , Zhao Jean , Huang Ruili , Xia Menghang , Ding Wen‐Xing
Published: June 2021

Objective

To identify novel autophagy modulators using a high throughput image‐based screening and to explore their mechanisms of regulation and the application for drug‐induced liver injury.

Methods

The library of pharmacologically active compounds (LOPAC) was screened in mouse embryonic fibroblasts (MEFs) stably expressing GFP‐LC3. Compounds were tested at different concentrations with or without lysosome inhibitor chloroquine (CQ), and GFP‐LC3 puncta were quantified to measure the autophagic flux. Mechanisms of autophagy induction of several selective positive compounds and the protection against acetaminophen (APAP)‐induced liver injury in mice were determined.

Results

The primary screening revealed 173 compounds with sufficient hit efficacy. The confirmation study indicated several novel autophagy inducers, inhibitors, and compounds showing dual‐effect at different concentrations. Indatraline hydrochloride (IND), chlorpromazine hydrochloride (CPZ) and fluphenazine dihydrochloride (FPZ) were able to increase autophagy in a dose‐ and time‐dependent manner in MEF and other cancer cells. Mechanistically all three compounds inhibited mTOR, a key regulator of autophagy. Moreover, CPZ significantly suppressed APAP‐induced liver injury either co‐treated with or given 2 hours post APAP administration.

Conclusion

We identified known and novel autophagy inducers through the high throughput image‐based screening. CPZ significantly suppressed APAP‐induced liver injury by inducing autophagy.

[R01 AA020518, R01 DK 102142, P20 RR021940 (COBRE)]
“How We Learn May Not Always Be Good For Us” – Analytics of Students' Study Strategies, Educational Resource Choices, and Learning Success in a Medical Histology Course
Authors: Hortsch Michael , Holaday L. , Selvig D. , Burk‐Rafel J. , Zureick A , Purkiss J.
Published: June 2021

Histology is a traditional component of many biomedical education programs. This project set out to find common characteristics among students, who did well or were challenged by histology and to exam the effectiveness of different teaching approaches. Three M1 classes at the University of Michigan were surveyed about their educational background, attitudes towards learning histology, and use of learning strategies. These characteristics were correlated with students' histology exam results. This analysis demonstrated a preference of students to use electronic over traditional learning tools. A positive indicator is in‐person participation in teacher‐guided learning experiences. Students watching lectures by video rather than going to lectures performed significantly worse. A preliminary analysis of what influences the efficiency of live lectures versus video recording indicates that frequent interruptions of the learning process correlate with decreased scores. These results indicate that the effectiveness of a teaching strategy is often determined by the way it is offered to and used by learners.
BMPER‐mediated BMP signaling promotes cardiac development
Authors: Dyer Laura , Wu Yaxu , Saha Arnab , Cyr Chelsea , Moser Martin , Pi Xinchun , Patterson Cam
Published: June 2021

The bone morphogenetic protein (BMP) signaling pathway regulates multiple aspects of cardiac development and endothelial cell biology. BMP signaling is tightly regulated by numerous factors, including BMP‐binding endothelial cell precursor‐derived regulator (BMPER), which can both promote and repress BMP signaling activity. In the embryonic heart, BMPER expression is limited to the endothelial cells and the endothelial‐derived cushions, suggesting that BMPER may play a role in both coronary vascular and cardiac valve development. Indeed, the coronary arteries of BMPER‐/‐ embryos are either atretic or connected distal to the semilunar valves. In vitro, BMPER‐/‐ endothelial cells have impaired tube formation and migratory ability compared with wild‐type endothelial cells. Additionally, recombinant BMPER promotes wild‐type ventricular endothelial migration in a dose‐dependent manner. Recent findings suggest that BMPER modulates epithelial‐mesenchymal transition in the developing valves, further supporting the critical role of this regulator during normal cardiac development. Together, these results indicate that BMPER‐regulated BMP signaling is critical for coronary plexus remodeling and cardiac valve formation.