bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of glucocorticoid regulated gene expression and skeletal muscle atrophy in glucocorticoid receptor mutant mice
Authors: Watson Monica L , Baehr Leslie , van der Brandt Jens , Reichardt Holger , Tuckermann Jan , Bodine Sue , Furlow J. David
Published: June 2021

Glucocorticoids (GCs) are important regulators of skeletal muscle mass and exert their actions primarily via GC receptors (GR) that interact with GC response elements (GREs) near target genes. However, many GR target genes lack clear GREs and there may be nongenomic effects of GCs. In addition, actions of GCs on skeletal muscle mass and function may be exerted outside the myotubes themselves. To investigate skeletal muscle transcriptional responses to GCs leading to atrophy and metabolic changes, we examined the dexamethasone (DEX) induced gene expression in two mouse lines: 1. GR dimerization mutant mice (GRdim) that ubiquitously express GR with an impaired ability to dimerize at certain GREs and 2. muscle specific GR knockout mice (muGRKO). Induction of the muscle atrophy associated MuRF1 gene is blunted in GRdim mice but fully prevented in muGRKO mice; induction of another important atrophy gene, MAFbx, is unaffected in GRdim mice but is also completely blocked in muGRKO mice. In both models, extracellular matrix genes like collagen 1A1 are repressed by DEX, as expected. We hypothesize that the skeletal muscle GR is important for mediating high dose GC induced atrophy, however the deleterious effects of GCs in muscle structure and function may not be muscle cell autonomous. The GRdim and muGRKO mice will be useful models to determine the importance of the GR and its target genes in several muscle atrophy models. This work was funded by NIH RO1 DK75801 and NIH Training Grant 2T32GM007377‐31A1.
Global diastolic function is preserved during passive heat stress due to augmented left ventricular untwisting
Authors: Nelson Michael D , Haykowsky Mark J , Petersen Stewart R , DeLorey Darren S , Cheng‐Baron June , Thompson Richard B
Published: June 2021

This study tested the hypothesis that augmented left‐ventricular untwisting rate (basal to apical diastolic rotation) maintains diastolic function during whole‐body passive heat stress. Cardiac MRI was used to measure biventricular function (volumes), pressure gradients, filling velocities, and left ventricular twist and untwisting during normothermia and whole‐body passive heat stress (HS, ~1 °C above baseline). Despite the reduced filling pressure during HS, left ventricular early diastolic inflow velocity, early diastolic annular tissue velocities and intraventricular pressure gradients were maintained (p > 0.05). Consistent with our hypothesis, left ventricular twist and untwisting were augmented during HS, suggesting that LV untwisting was responsible for the maintenance of diastolic function under conditions of reduced atrial pressure. This study provides a novel mechanistic explanation for maintained diastolic function during passive heating.
Impact of sex hormones on cutaneous neurovascular responses in humans
Authors: Brunt Vienna E , Miner Jennifer A , Martini Emily R , Smith Michael M , Kaplan Paul F , Minson Christopher T
Published: June 2021

Purpose

We examined the impact of estradiol (E2) and progesterone (P4) on skin local heating (LH) to 42°C and reactive hyperemia (RH) responses in 23 healthy young women.

Methods

Subjects were studied for 3 trials over 10–12 days. Endogenous sex hormones were suppressed with a gonadotropin‐releasing hormone antagonist (GnRHa). Subjects were studied on day 4 (trial 1) of GnRHa only. Subjects were studied 3–4 days later (trial 2) following treatment with either 0.1mg/day E2 by transdermal patch or 200mg/day P4 orally. Subjects were studied again 3–4 days later (trial 3), following treatment with both E2 and P4. Subjects underwent identical LH and RH protocols on all study days.

Results

All blood flow values are given as percent of maximum cutaneous vascular conductance (%CVCmax). E2 alone increased initial peak CVC from 71 ± 2 to 79 ± 2% (p=0.01). P4 alone increased initial peak CVC from 73 ± 2 to 78 ± 2% (p=0.01). E2 alone increased nadir CVC from 56 ± 3 to 65 ± 2% (p=0.02). P4 increased nadir CVC from 62 ± 2 to 66 ± 3% (p=0.07). Neither E2 nor P4 increased plateau CVC, although a small statistically significant increase was seen between suppression and P4 alone (p=0.04). No significant changes were seen between trials 2 and 3 for either group. No differences were observed for the RH response.

Conclusions

Both E2 and P4 increase initial peak and nadir CVC when added back following GnRH suppression.

Supported by NIH Grant HL081671
Effect of stratum corneum hydration on the composition of sweat collected by an occlusive sweat patch
Authors: Mack Gary W. , Taylor Penny
Published: June 2021

We tested the hypothesis that sweat trapped on the skin with an occlusive sweat patch will leach electrolytes from the stratum cornea (SC) and alter sweat composition. 20 subjects completed 40 minutes of moderate exercise in the heat and select skin sites were hydrated before exercise by adhering cylinders of distilled water to the skin. SC samples were taken before and after exercise using a tape stripping method and sweat samples were collected with an occlusive sweat patch. SC hydration was verified by a reduction in [K+]SC (p < 0.05). SC hydration decreased [K+]sweat (8.14 ± 0.46 to 6.56 ± 0.46 mmol/l,) and [lactate] sweat (11.64 ± 1.36 to 8.82 ± 1.11 mmol/l) at hyperhydrated skin sites (p < 0.05). Without an occlusive sweat patch [Na+]SC and [K+]SC increased after sweating (p < 0.05) but not with an occlusive sweat patch. Our data indicate that during normal sweating the SC “dehydrates” resulting in an increase in the SC electrolyte concentration. An occlusive dressing traps sweat on the skin and prevents water movement out of the SC (rather than electrolyte leaching) and thereby produces a more concentrated sweat.
Is there a delay in the activation of non‐noradrenergic vasoconstriction during cold exposure in human skin?
Authors: Simmons Grant Hannigan , Fieger Sarah M , Minson Christopher T , Halliwill John R
Published: June 2021

This study tested the hypothesis that cutaneous vasoconstriction during brief cold exposure occurs entirely through noradrenergic mechanisms. In 6 subjects, 2 microdialysis (MD) fibers were placed in the forearm skin. A control fiber received lactated ringers and the other received 5mM yohimbine (α‐adrenergic blockade). Skin blood flow was assessed at each site (laser‐Doppler flowmetry) and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure). Subjects were exposed to 10 min of cold stress (water‐perfused suit). CVC was reduced by 64 ± 9 % in the control site (P<0.05 vs. baseline) but unchanged in the yohimbine site during cold stress. In a follow‐up protocol (n=3) we added a third MD site with yohimbine + 1mM propranolol and extended the cold stress to 30 min. CVC was reduced in the control site throughout cold stress, but showed vasoconstriction during only the second half of the cold stress in both yohimbine and yohimbine + propranolol sites. Thus, short duration cold exposure can elicit cutaneous vasoconstriction mediated solely through noradrenergic mechanisms, whereas more prolonged cold stress also activates non‐noradrenergic vasoconstriction. Supported by the Evonuk and ACSM Foundations
The Application of Gold Nanoprobes Using an In Vitro Tissue Slice Preparation for the Phenotypical Classification, Connectivity Assessment, and Electrophysiological Recording of Hypothalamic Thermoregulatory Neurons
Authors: Mendoza Karl C , McLane Virginia D , Kim Sarah , Griffin John D.
Published: June 2021

Thermoregulatory neurons in the anterior hypothalamus form synaptic networks, which affect responses that regulate body temperature. In order to characterize these pathways of activation, connections to efferent control areas, like the dorsomedial hypothalamus or the raphe pallidus, require identification. Traditional retrograde labeling using fluorescent dyes may label neurons with axon terminals near an injection site, but also label passing axon fibers. Here, we describe a novel methodology for retrograde neuronal labeling in live tissue slices, by using nanometer‐sized, gold nanoprobes, which allow for specific neuronal entry, via axon terminals in close proximity to their injection site. Upon entry, these nanoprobe complexes diffuse to the soma, where they are readily visualized and quantified. Depending on nanoprobe specifications, this method is highly specific for particular neuronal populations, thereby enabling targeted electrophysiological recording.
Intrauterine maternal food restriction programs neuroendocrine changes that shorten the reproductive lifespan of female offspring
Authors: Keen‐Rhinehart Erin Marie , Desai Mina , Ross Michael G
Published: June 2021

Prenatal stress programs HPG axis dysfunction, possibly shortening reproductive lifespan in females. We hypothesized that female rats exposed to food restriction (FR) in utero would exhibit neuroendocrine changes evident at birth, puberty and adulthood, indicating shortened reproductive lifespan. Dams were either fed ad libitum (AL) or were 50% FR from p10 to p21. At birth, hypothalamic gonadotropin releasing hormone (GnRH) and hypothalamic and ovarian estrogen receptor‐alpha (ER‐alpha) protein expression were measured by western blot. Age and body weight at puberty as well as estrous cyclicity at 8 and 10 mo. of age were observed. Rats were sacrificed at 10 mo. to examine ovarian histology and plasma hormones. At birth, hypothalamic GnRH (1±0.1 vs. 0.5±0.1, p<0.05) was decreased, and ER‐alpha was increased in the hypothalamus (1±0.4 vs. 3.2±0.7, p<0.05) but decreased in the ovary (1±0.1 vs. 0.6±0.1, p<0.05). FR rats had reduced body weight at puberty and by 10 mo. their estrous cycles had stopped. At sacrifice FR rats had decreased estradiol (17.5±1 vs. 11±2 pg/ml, p<0.05), increased luteinizing hormone (0.28±0.05 vs. 0.58±0.1 ng/ml, p<0.05) and abnormal ovarian histology, consistent early with reproductive aging. HPG axis regulation is inextricably linked to energy balance, and prenatal FR programs shortened reproductive lifespan, possibly to ensure reproduction in a potentially harsh environment.
Differential effects of monoamine reuptake inhibitors on food intake and energy expenditure in a mouse model of diet‐induced obesity
Authors: Martin William J. , Kim Yoon Yi , Obedencio Glenmar , Tsuruda Pamela R , Shen Fei
Published: June 2021

Dopamine (DA), norepinephrine (NE) and serotonin (5‐HT) modulate feeding behavior and energy homeostasis. Here, we investigated effects of sibutramine (Sib), duloxetine (Dlx), and atomoxetine (Atx) on acute food intake (FI), daily FI and body weight (BW) gain over 28 d in diet‐induced obese (DIO) mice. Sib is a balanced reuptake inhibitor at transporters for DA (DAT), 5‐HT (SERT) and NE (NET), whereas Dlx and Atx are selective for SERT and NET, respectively. Mice, fed a high fat diet for 12 wk, weighed 40–44 g prior to receiving chronic twice daily oral dosing for 28 d. FI, BW, serum leptin levels and weight of adipose tissue were measured and compared to free concentrations of compounds in serum and brain. Sib (1–10 mg/kg), Dlx (3–30 mg/kg) and Atx (3–30 mg/kg) dose‐dependently decreased food intake 4 and 8 hr after a single dose (hypophagia rank order of potency: Sib = Dlx > Atx). From 7 – 28 d, daily FI was equivalent in all groups of mice. At the highest doses tested, BW decreased significantly in Sib‐ and Atx‐treated mice at day 28 (~10% compared to vehicle), whereas BW was unchanged by the end of chronic Dlx treatment. On day 29, all compounds decreased serum leptin levels. Atx‐induced decrease in BW was accompanied by a reduction in total brown adipose tissue. These results suggest that the balance of activity at DAT, SERT and NET differentially influences acute hypophagia, energy expenditure and sustained weight loss.
Differences in POMC and TRPV 3 expression in the brainstem of Obese Prone and Obese resistant rats
Authors: Hu Jay , Choo June , Ma Sheng‐Xing
Published: June 2021

The aim of this study is to examine and establish the differences in pro‐opiomelanocortin (POMC) and Transient Receptor Potential Vannilloid 3 (TRPV3) expression in the brainstem between Obese Prone (OP) and Obese Resistant (OR) rats. OP and OR rats were fed for seven days on a high fat diet. Food intake, blood pressure, blood glucose, and body weight measurements were taken and compared between OP rats and OR controls. The animals were then sacrificed by transcardial perfusion and fixed with 4% paraformaldehyde. Immunohistochemistry was performed on the coronal brainstem sections with polyclonal antibodies raised against TRPV3 and POMC. The sections were quantified using a microscope with reticule grid to measure the number of positive cells over a 200×200um area in the hypoglossal nucleus (HN) and medial nucleus tractus solitarius (mNTS). The results show that food intake and body weight were significantly reduced in OR rats compared to OP rats. (P<0.05, n = 7) POMC positive staining neurons were significantly reduced in the HN and (mNTS) in OP compared to OR rats. OP rats also have a significant increase in TRPV3 positive staining neurons in the HN and mNTS. We conclude that lower POMC and higher TRPV3 expressions in the HN and mNTS play a role in central regulation of food intake, which contribute to development of hyperphagia and obesity in OP rats. Supported by NIH (AT004620, and AT004504) and ADA 7‐07‐RA‐100 to S. Ma.
Aging is associated with a dysregulated human skeletal muscle microRNA‐499 and ‐208b expression following resistance exercise
Authors: Drummond Micah J , Fry Christopher S , Glynn Erin L , Timmerman Kyle L , Volpi Elena , Rasmussen Blake B
Published: June 2021

MicroRNAs (miRNA) are novel post‐transcriptional gene regulators associated with skeletal muscle myogenesis and tissue regeneration. Sarcopenia is associated with resistance to anabolic stimuli such as exercise and nutrition. Therefore, we hypothesized that skeletal muscle miRNA expression after exercise would be dysregulated in older humans and may play a role in the etiology of this anabolic resistance. To address our hypothesis, young (n=5) and older (n=5) male subjects participated in a single bout of leg resistance exercise and vastus lateralis muscle biopsies were sampled at Basal, 6 and 24h postexercise. Samples were analyzed utilizing real‐time PCR for gene expression levels of miR‐1, ‐206, ‐499, and ‐208b. We found that miR‐499 and ‐208b expression were upregulated at 6h postexercise in young (P<0.05) but unchanged in older subjects. MiRNA‐1 and ‐206 were downregulated at 6 and 24h postexercise in both groups (P<0.05). Myostatin (predicted target of miR‐499 and ‐208b) expression was decreased at 6 and 24h postexercise in both groups. IGF‐1 (predicted target of miR‐1 and ‐206) expression was elevated at 6 and 24h postexercise only in the young. We conclude that a bout of heavy resistance exercise alters the expression of human skeletal muscle miRNAs, however, aging is associated with an inability of exercise to alter miR‐499 or ‐208b. Identifying gene targets of these miRNAs will be the focus of future work.

Supported by NIA P30 AG‐024832 (MJD) & NIAMS grant R01 AR049877 (BBR)
Impact of activated T cells on rat skeletal muscle satellite cell function
Authors: Dumke Breanna Raine , Lees Simon James
Published: June 2021

Sarcopenia is an age‐associated loss of skeletal muscle mass and strength. Recent evidence suggests that an age‐associated loss of satellite cell functionality contributes to sarcopenia. Current research also suggests that T cells of the immune system may play a role in skeletal muscle repair via signaling with satellite cells. The objective of the present study was to further examine the influence of activated T cells on satellite cells. Satellite cells were collected from the gastrocnemius and plantaris from 3‐(young) and 32‐mo‐old (old) animals and T cells were harvested from the spleen of using Dynabead isolation with anti‐CD3. T cells were activated for 48 hours with co‐stimulation of 100 IU/ml Interleukin‐2 (IL‐2) and 5 μg/ml of anti‐CD28. Co‐stimulation increased 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation (proliferation) of T cells from 15.27% (SEM=7.93, n=3) in control to 61.97% (SEM= 10.52, n=3). Additionally, T cell cytokines increased satellite cell proliferation by 23.98% (SEM=5.69, n=4) in young satellite cells but decreased by 0.69% (SEM=5.65, n=3) in old satellite cells. These data suggest that aging may alter T cell‐induced satellite cell function. These findings have implications for developing strategies aimed at increasing satellite cell proliferation and the regenerative capacity of aged skeletal muscle. Supported by Colorado Space Grant.
Characterization of a novel transcriptional feedback loop regulating lipid metabolism
Authors: Bagattin Alessia , Hugendubler Lynne , Mueller Elisabetta
Published: June 2021

The peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC‐1α) is a transcriptional coactivator that plays a key regulatory function in mitochondrial biogenesis and lipid metabolism. It is highly induced upon cold exposure in brown fat, exercise in skeletal muscle and fasting in liver. The function of PGC‐1α has been extensively studied, but not much is known about how PGC‐1α activity is regulated. In order to identify novel PGC‐1α modulators, we characterized novel interacting molecules from nuclear liver extracts via biochemical purification followed by mass‐spectrometry analysis. Among a number of interactors we chose to study ACOX1 (Acyl Coenzyme A Oxidase). ACOX1 is the first and rate‐limiting enzyme of the peroxisomal fatty acid β‐oxidation and its expression is known to be under the control of PPARα, a transcription factor involved in fatty acid metabolism, potently coactivated by PGC‐1α. By in vitro pull‐down assay and by co‐immunoprecipitation in Hek293 cells, we reconfirmed that PGC‐1α interacts with ACOX1. ACOX1 is able to increase the transcriptional activity of the PGC‐1α/PPARα complex in luciferase assays. These results suggest that ACOX1 is able to modulate its own expression by enhancing the activity of its own transcriptional regulator PGC‐1α, creating a positive feedback loop that regulates lipid metabolism.

Supported by the Intramural Research Program of NIDDK, NIH.
Isovaleryl‐CoA Dehydrogenase: Dehydrogenate This!
Authors: Grabon Nick , Bougie Beth , Cira Matt , Erovick Colin , Fahey Anne , Jeletz Kelsey , Kukla Eleanore , Murphy Matt , Rohman Tim , Sass Alyssa , Tiffany Laura , Wolff Sam , Tiffany Karen , Kim Jung‐Ja
Published: June 2021

Although rare, isovaleric acidemia (IVA) is a potentially fatal metabolic disorder that affects one in every 250,000 people in the US. IVA results from lack of an enzyme, isovaleryl‐CoA dehydrogenase (IVD), involved in the breakdown of leucine. Without this enzyme, leucine catabolism stops and organic acids accumulate within the body, causing symptoms of IVA, including vomiting, diarrhea, and fatigue. IVD belongs to a family of related enzymes called acyl‐CoA dehydrogenases. IVD catalyzes the dehydrogenation, or removal of a pair of hydrogen atoms, of a small, branched‐chain substrate, isovaleryl‐CoA, during the third step of leucine catabolism. Glutamate 254 of IVD removes one hydrogen as a proton from the substrate, and flavin adenine dinucleotide, FAD, a cofactor of the enzyme, takes away the other hydrogen from the substrate. The three‐dimensional structure of IVD, as determined through X‐ray diffraction, illustrates how a small‐branched chain substrate is able to fit into the active site of this enzyme and enables further investigation of how mutation of the IVD gene could affect IVD function, thus resulting in IVA. To further understand the structural impact on substrate specificity, a physical model of IVD has been designed and built by the Cedarburg High School SMART (Students Modeling a Research Topic) Team using 3D printing technology. Supported by a grant from NIH‐NCRR‐SEPA.
Inhibiting Dihydrofolate Reductase as a Treatment for Tuberculosis
Authors: Kleinhans Kaylin , Brandl Corrine , Brandl Lauren , Ebert Grace , Jirschele Ryan , Maala Nicole , Neumeyer Paige , Schneider Gavin , Schuh Luke , Weyker Emily , Olson Andrew , Sem Daniel
Published: June 2021

One‐third of the world's population is infected by Mycobacterium tuberculosis (M.tb). Two million people die each year from tuberculosis (TB), the disease caused by this bacterium. TB primarily affects the lungs and is easily transmitted. One way to kill M. tb might be to inhibit the enzyme dihydrofolate reductase (DHFR). DHFR catalyzes the production of tetrahydrofolate by transferring a hydrogen ion (H−) from NADPH to dihydrofolate, thereby releasing tetrahydrofolate and NADP+. Tetrahydrofolate is essential to the bacteria's survival, and is a cofactor that is needed for the synthesis of the DNA base thymine. Isoniazid is one antibiotic already used to treat TB by targeting several TB proteins that are necessary for building M. tb cell walls and inhibiting DHFR. Unfortunately, strains of M. tb are evolving resistance to isoniazid, so next generation antibiotics are needed. A variation of isoniazid could be designed to avoid resistance, and to inhibit DHFR, thereby targeting bacterial DNA synthesis. The Valders SMART Team (Students Modeling A Research Topic), using 3D printing technology, created a physical model of DHFR and a possible inhibitor of tetrahydrofolate production. Supported by a grant from NIH‐NCRR‐SEPA.
Modeling Dihydrofolate Reductase
Authors: Jennewein Maddy , Bitar Kenny , Rangel Ben , Ryan Colby , Soundarajaran Guataum , Worthen Amanda , Moerder Susan , Bhabha Gira
Published: June 2021

Dihydrofolate reductase (DHFR) is a ubiquitous enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). THF is crucial for purine and thymidylate synthesis, precursors to DNA and RNA. Inhibition of DHFR leads to cessation of cell proliferation because the cell is unable to build DNA and RNA. DHFR is a small protein with an α/β structure, consisting of a central eight‐stranded beta sheet surrounded by four alpha helices. The protein has two subdomains, the adenosine binding subdomain (residues 36–108), the binding site for the adenosine moiety of the cofactor, and the loop subdomain, which consists of three loops, the most important being the Met20 loop (residues 9–24). The active site is in the hydrophobic cleft between the two subdomains. The Met20 loop lies above the active site and protects substrates from the solvent. The Met 20 loop assumes two main conformations (“closed” and “occluded”) correlated with the five distinct intermediates of the DHFR catalytic cycle. It is “closed” in the E:NADPH intermediate and the model Michaelis intermediate, E:NADP+:folate. It is “occluded” in the three product complexes, E:NADP+:THF, E:THF and E:NADPH:THF. The Francis Parker SMART Team (Students Modeling A Research Topic) used 3D printing to create models of DHFR in both formations. Supported by a grant from the HHMI Pre‐College Program.
Effect of Methylglyoxal on BV‐2 Cells
Authors: Gorgis Tanya , Habib Nawaf , Mungre Sue
Published: June 2021

Inflammation is believed to play a role in complications seen in diabetic patients. Methylglyoxal (MG) a normal molecule in the cell is believed to increase under diabetic conditions. MG may activate macrophages that release pro‐inflammatory cytokines. We used BV‐2 cells to determine the effect of MG on the viability and activation of macrophages. Our results show that MG causes proliferation of BV‐2 cells. There is increased production of nitric oxide suggesting that cells are activated. Curcumin, an antioxidant reduced nitric oxide production by about 30%. These results suggest that activated macrophage cause inflammatory conditions in diabetes due to oxidative stress and antioxidant have a protective effect
PHOSPHORYLATION REGULATION OF MIXED LINEAGE LEUKEMIA 5
Authors: Deng Lih Wen , Liu Jie
Published: June 2021

The human Mixed Lineage Leukaemia‐5 (MLL5) gene is frequently deleted in myeloid malignancies. Emerging evidence suggest that MLL5 has important functions in adult hematopoiesis and chromatin regulatory network, and participates in regulating the cell cycle machinery. To further investigate its cellular regulatory functions, we studied the expression and post‐translational modification of MLL5 throughout the cell cycle. Our results demonstrated that MLL5 is regulated by cell cycle‐dependent phosphorylation, and reduced phosphorylation modification of MLL5 is associated with the inhibition of cell cycle progression. Our data provides a molecular foundation for further investigation on the mechanisms of cell cycle transition or epigenetic regulatory role of MLL5 with the phosphorylation signalling network.
Cofacially‐Arrayed Polybenzenoid Nano Structures
Authors: Yacoob Zeechan , Vogt Caleb , Jordan Patrick , Rosas Jose , Knight‐Boehm Kienan , Lopez Hector , Buchanan‐Nogueron Fernando , Zausch Nicholas , Khan Qateeb , Bro Judson , Gill Payton , Klusman Jacob , Lessila Alexander , Sekeran Jed , Ulschmid Caden , Klestinski Keith , Vogt David , Rathore Rajendra
Published: June 2021

Based on Moore's Law, every 18 months the number of transistors that can be placed per unit area on a microchip will double. However, by the year 2017 this trend will cease to exist due to the size restrictions imposed by silicon, the main component of microchips; this has led to the birth of molecular electronics. An organic molecule that has been extensively tested for its potential in molecular electronics is DNA. However, recent research has shown that DNA cannot function as a molecular wire due to its fragile nature. This is why Raj Rathore's group is developing organic molecular wires based on robust macromolecular structures. The specific assembly designed to study the wire behavior consists of a triad which is made up of polyfluorenes as an electron donor site, a spacer unit (or wire) made of polyphenylenes, and an electron donor‐acceptor complexation site composed of hexamethylbenzene (HMB). A chloranil molecule—an electron acceptor—complexes with the HMB of the triad, and when a laser is shined on HMB/CA complex, a hole is introduced in the molecular wire which will travel 30 Å to the polyfluorene donor, via an electron hopping mechanism. The Marquette University High School SMART Team (Students Modeling A Research Topic) created a physical model of this molecular wire using 3D printing technology. Supported by a grant from NIH‐NCRR‐SEPA.
Isolation and Purification of hSug1 and its Possible Ligands; Components of the Regulation of Major Histocompatibility Complex Class II Expression
Authors: Inostroza‐Nieves Yaritza , Zavala‐Ruiz Zarixia
Published: June 2021

Major histocompatibility complex class II (MHC II) genes are a cell‐surface glycoproteins that presents antigens derived from extracellular pathogens to CD4+ T lymphocytes. The most important regulatory factor of MHC II expression is class II transactivator (CIITA), which functions as an integrator of most pathways that influence the expression of MHC II. CIITA plays a critical role in regulating MHC II transcription, even though it does not bind directly to the MHC II promoter. Therefore, we asked how is regulated the recruit of CIITA to the promoter. It was recently found a role for components of the 26S proteosome, specially the 19S complex, as mediators of the assembly of transcriptional systems. Recent biochemical studies have provided evidence that the 19S complex is involved directly in transcription. Essentially, the 19S proteosome ATPases Sug1 plays important roles in regulating CIITA activity and MHC II expression, in part by regulating promoter recruitment of CIITA. Also, Sug1 is involved in the H4 acetylation in the MHC II promoter by CREB binding protein (CBP). To understand the structural and function of Sug1 in MHC II regulation, we purified recombinant hSug1 and six CBP's domains to study the interaction of these with hSug1 in vitro and we observe the interaction of hSug1 with CBP domains TAZ1 and TAZ2. Also we expressed CIITA in insect and mammalian cells planning to investigate its interaction with hSug1.
Dietary iron deficiency alters emotional behavior and impairs motor coordination in young rats
Authors: Li Yuan , Kim Jonghan , Wessling‐Resnick Marianne
Published: June 2021

The objective of this study was to evaluate the effect of iron deficiency anemia induced by diet in young rats on emotional, cognitive, and motor functions. Three‐week old male Sprague‐Dawley rats were weighed, ranked and assigned to be pair fed standard chow (200 ppm iron) or iron‐deficient diet (2–6 ppm iron). After one month, hematocrit values were 42.1 and 16.2% (p<0.05; n=8), liver non‐heme iron values were 131.2 and 11.6 ppm (p<0.05; n=8), and serum iron values were 47.33 and 23.27 μM (p<0.05; n=8) respectively. Elevated plus maze was used to study emotional behavior. Iron deficiency anemic (IDA) rats had fewer entries to open arms (0.3 vs 1.8, p<0.05; n=8) and spent less time in open arms (0.88 vs 13.0 sec, p<0.05; n=8). Novel object recognition in open field was employed to study learning and memory, and this test did not show significant difference between IDA and control (CON) rats in neither short‐term nor long‐term memory trial. Motor skills were measured on a standard accelerating rotarod device. The peak speed attained on rotarod by IDA rats was significantly lower than CON rats (22.5 vs 29 rpm, p<0.05; n=8). These data show that IDA rats behave more anxiously and their motor coordination is impaired by iron deficiency.

This study was supported by NIH R01 ES014638.
Protection of SNpc neurons by water soluble CoQ10 in a paraquat induced rat model of Parkinson's disease: The role of neurotrophic factors
Authors: Facecchia Katie , Sandhu J. K. , Sikorska M. , Somayajulu‐Nitu M. , Dadwal P. , Rafo N. , Church K. , Cohen J. , Borowy‐Borowski H , Pandey S. , Weinstock Shelley
Published: June 2021

Parkinson's disease (PD) is a common neurodegenerative disorder that results from the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Studies show that mitochondrial dysfunction/oxidative stress is a major contributor to this disease. Currently there is no treatment to halt the progression of PD. Recently we have shown that water‐soluble coenzyme Q10 (WS‐CoQ10, NRC technology licensed to Zymes LLC) prevents the loss of dopaminergic neurons in the SNpc and ameliorates the symptoms of paraquat (PQ)‐inducted PD in the rat model. We have observed that there is activation of astroglia in the brains of WS‐CoQ10 treated animals. Whether this activation plays a role in protecting SNpc neurons is unknown. It is possible that activated astroglia cells produce neurotrophic factors that may protect neurons under oxidative stress. We analyzed brain tissue samples from PQ treated PD rats fed with either placebo or WS‐CoQ10 for DA neurons, activation of astroglia and levels of various neurotrophic growth factors. We observed significant protection of DA neurons in the SNpc, activated astroglia and increased levels of BDNF and GDNF in WS‐CoQ10 fed rats. These results indicate that WS‐CoQ10 treatment could activate astroglia that produce high levels of BDNF and GDNF and could provide protection to the DA neurons against PQ toxicity and may be used to halt PD progression.

Funded by CIHR.
Effects of Zinc Deficiency on Colonic Microbiota
Authors: Shore Amanda , Nieves Carmelo , Maki Alyssa , Ukanova Maria , Mai Volker , Cousins Robert , Langkamp‐Henken Bobbi
Published: June 2021

The purpose of this study was to evaluate colonic microbiota composition in response to a dietary zinc deficiency in mice. Male, 12‐wk‐old CD‐1 mice (n=5/ diet group) were fed a zinc adequate (ZA, 30.0 ppm) or a zinc deficient (ZD, 0.85 ppm) diet for 4 weeks. Transcript levels of colonic metallothionein (MT) and the zinc transporter (Zip4) were measured by qPCR as markers of zinc status. MT mRNA levels decreased by 0.55 fold (p=0.032) while Zip4 mRNA levels increased 2.88 fold (p=0.016). ZD mice didn't experience weight loss normally associated with deficiency. However, there was a difference in weight gain (6.9%± 1.6 vs. 3.6%± 1.1, p=0.01) in ZA and ZD mice, respectively. Microbiota composition was analyzed by denaturing gradient gel electrophoresis (DGGE) analysis and 16S rRNA sequencing. Initial DGGE profiling suggested that ZA and ZD groups differed in intestinal microbiota composition. 454 based 16S rRNA sequencing identified various phylotypes that, at the level of 99% identity, showed significant differences (p≤0.05) between the two diet groups. Weighted UniFrac analysis of overall microbiota composition indicated that ZD grouped separately from ZA, suggesting that a 4‐week zinc deficient diet alters overall colon microbiota composition in mice. Sponsored by the University of Florida University Scholars Program
Substance P triggers two different signaling pathways with opposing actions on M current mediated by intracellular Ca2+ rises and oxidative modification
Authors: Ooi Lezanne , Linley John , Gamper Nikita
Published: June 2021

Substance P (SP) is an important signaling molecule in pain and inflammation. Since M‐type K+ channels are critical in controlling excitability of neurons, we investigated crosstalk between M current and SP in sensory neurons from trigeminal ganglia (TG) and dorsal root ganglia (DRG). In CHO cells expressing SP receptors, SP produced a robust transient increase in cytosolic Ca2+ and translocation of probes for PIP2 and diacylglycerol indicated that SP signals through a Gq/11‐protein coupled receptor pathway. In DRG neurons SP caused significant M current augmentation, whereas TG neurons responded with both M current inhibition and augmentation. Inhibition was mediated by intracellular Ca2+ rises, whereas activation was completely reversed by the reducing agent DTT and mimicked by bath application of H2O2, suggesting this pathway is mediated by an oxidation mechanism. This was supported by imaging experiments with a reactive oxygen species‐sensitive dye and a superoxide anion probe. Thus in sensory neurons SP triggers two different signaling pathways, mediated by intracellular Ca2+ rises and reactive oxygen species, with opposing actions on M current.
Anthocyanins target AMPK/mTOR and AMPK/Wnt pathways in exerting anti‐tumor effects in colon cancer or hepatocarcinoma cells
Authors: Yun‐Kyoung Lee , Park Song Yi , Kim Young‐Min , Lee Won Sup , Park Ock Jin
Published: June 2021

AMP‐activated kinase, a sensor of cellular energy status, has emerged as a potent target for cancer prevention and/or treatment. Thus, the application of dietary origin AMPK activators could link to an effective strategy of cancer control. We have found that the activation of AMPK with anthocyanin extracted from Meoru exerted growth inhibitory effects through regulation of mTOR or GSK3β/β‐catenin pathway in HT‐29 colon and Hep3B cells respectively. In both types of cancer cells, the growth signal IGF‐1 stimulated mTOR or Wnt pathway components. AMPK appeared to inhibit phosphorylation of mTOR possibly through interacting with one of the subunit, raptor. The effect of anthocyanins on cancer cell survival and AMPK/mTOR pathway was compared with a classical mTOR inhibitor rapamycin, and anthocyanins were found to inhibit growth through mTOR comparable to rapamycin. Moreover, anthocyanins stimulated β‐catenin degradation through GSK3β activation, and it seemed to be regulated by AMPK. This work has shown that the cell energy controller AMPK can control two important cell growth regulators mTOR and Wnt, and the modulation of AMPK/mTOR or AMPK/Wnt pathways by phytochemicals such as anthocyanins can further strengthen the use of phytochemicals for cancer control. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (NO. R01‐2008‐000‐20131‐0)]
Changes in physical activity upon entry to elementary school
Authors: Jauregui Alejandra , Hernández Salvador Villalpando , Baltazar Eduardo Rangel , Hernández Jessica Castro , Zamudio Yaveth Adriana Lara
Published: June 2021

Objective

To compare the physical activity performed in the last year of kindergarten and the first grade elementary school in a cohort of Mexican children.

Methods

Physical activity (7 d triaxial accelerometry) and anthropometry data of 257 prescholers (111 boys & 146 girls) from Cuernavaca, Morelos were measured in the last year of kindergarten and first grade of elementary school. Daily activity counts, and time spent in inactivity, sendentary, light and moderate/vigorous activity were calculated. For weekdays, counts/hr during school time and leisure time were calculated. Longitudinal analyses were performed using multilevel generalized linear models controlling by potential confusing factors.

Results

Daily activity counts were 8.2% lower (p<0.001) in elementary school than in kindergarten. Sedentary activity increased 32 min/d (15.8–48.2) and moderate/vigorous activity decreased 21.3 min/d (8.6–34.0) in elementary school compared to preschool. On weekdays, PA decrease occurred during school time (Kindergarten: 7.8 counts/hr IC95% 7.5, 8.1; Elementary school: 5.8 counts/hr IC95% 5.5, 6.1) but not during leisure time (Kindergarten: 5.6 counts/hr IC95% 5.3, 5.9; Elementary school: 5.3 counts/hr IC95% 5.0, 5.6). When stratifying by baseline BMI category, changes were only observed in children with normal BMI.

Conclusion

The results of this study show a decrease in PA upon entry to elementary school. This might explain the sudden increase of obesity prevalence in school age children.
The effect of food and weight‐related cues on physiological stress measures in premenopausal women differing in their levels of cognitive dietary restraint
Authors: Sanghera Mandeep K. , Linden Wolfgang , Bedford Jennifer L. , Barr Susan I.
Published: June 2021

Cognitive dietary restraint (CDR) reflects a perception of constantly monitoring or attempting to limit food intake to control weight. Higher cortisol levels have been observed in women with high vs low CDR. This study assessed whether food and weight‐related cues differentially activate the physiological stress response in 70 healthy women aged 19–35 with low (0–5; n=35) or high (13–21; n=35) scores on the Three Factor Eating Questionnaire Restraint subscale. Participants completed questionnaires on eating attitudes, stress, anxiety, depression and physical activity (PA) in the presence of food temptations. Concurrently, blood pressure, heart rate and salivary cortisol measures were obtained every 15 min for 90 min. Results showed significant between‐group differences in eating attitudes while anthropometric, general perceived stress, anxiety, depression and PA variables were similar. Although women with high CDR perceived the protocol as more stressful, physiological measures did not differ by CDR level. Participants also provided 4 saliva samples collected within 1 hr of awakening to assess the awakening cortisol response (ACR); no between‐group differences were observed. In conclusion, women with high and low CDR had similar physiological stress responses after cue exposure; however, this may have been the result of a weak stressor. Supported by Canadian Institutes of Health Research 79563.
Muscle overuse affecting the triceps surae muscle in one leg leads to similar muscle/neuropeptide changes in the exercised and the non‐exercised leg – Studies using an animal model
Authors: Song Yafeng , Stål Per , Yu Jiguo , Lorentzon Ronny , Forsgren Sture
Published: June 2021

Objective

A rabbit model for investigating the effects of muscle overuse affecting the triceps surae muscle, including examinations on the magnitude of a neuropeptide which can have pro‐inflammatory properties (substance P [SP]), was used.

Method

A “kicking machine” was used for New Zealand white rabbits during 1, 3 and 6 weeks of exercise (2h of exercise every second day). Electrical stimulation was given in the plantar flexion phase. Specimens from the experimental (exercised) side as well as from the contralateral side were taken. Morphologic evaluations, immunohistochemistry and ELISA were applied.

Results

The muscle morphology was affected in response to the exercise in the muscles of both legs. SP immunoreactions were noted for inflammatory cells and neurokinin‐1 receptor was expressed in inflammatory cells and necrotic muscle fibers. ELISA analyses revealed that the SP levels in the soleus muscle part were significantly increased in both the exercised and the non‐exercised leg after 3 and 6 weeks of training, as compared to non‐exercised animals.

Conclusions

Muscle overuse via this model leads to changes also in the muscle on the contralateral side. The observations show that examining the contralateral side in this animal model is defenetely not optimal when evaluating the response to the exercise. The occurrence of bilateral changes may be related to effects that are inforced via the nervous system.
Effects of 30‐day diet cycling on weight loss and resting energy expenditure in women participating in the Curves® fitness program: a preliminary long‐term analysis
Authors: Simbo S , Culbertson J , Mardock M , Byrd M , Oliver J , Cannon C , Jung Y , Khanna D , Koozehchian M , Dalton R , Kim H , Lockard B , Rasmussen C , Kreider R
Published: June 2021

25 women (34±7 yrs, 89±19 kg; 43±5% body fat) were assigned to a high carbohydrate (HC, n=13) or high protein (HP, n=12) diet group. Subjects consumed 1,200 kcals/d for 1‐wk and 1,500 kcals/d for 3‐wks. Subjects then followed a 2,200 kcals/d maintenance diet for 4 wks and then repeated diet cycles. Diets were 25% fat with either 45% CHO or 45% PRO. Subjects participated in the Curves circuit training program 3‐d/wk and walked for 30‐min 3‐d/wk. Data were analyzed by repeated measures ANOVA and are presented as means ± SD changes from baseline after 1, 2, 3, 4, & 5 months, respectfully. Time effects were observed in weight loss (−5.1±5.0, −7.2±6.1, −9.1±7.8, −10.8±9.3, −11.4±10.4 lbs, p=0.001) and fat loss (−4.0±3.0, −5.9±3.1, −6.5±3.9, −8.5±5.8, −8.8±6.4 lbs, p=0.001) with no significant differences were seen between groups in weight loss (HC −4.1±4.1, −6.1±5.8, −8.5±8.4, −9.5±8.9, −10.7±10.7; HP −6.0±5.8, −8.2±6.4, −9.6±7.6, −12.0±9.8, −12.1±7.6 lbs, p=0.79) and fat loss (HC −4.3±3.4, −5.5±2.6, −6.1±3.7, −8.3±5.5, −8.6±6.2; HP −3.8±2.7, − 6.2±3.7, −6.8±4.2, −8.7±6.3, −9.0±6.8 lbs, p=0.79). REE declined over time (−0.91±1.7, −1.23±2.4, −0.93±2.3, −0.35±2.3, −0.35±2,1 kcal/kg/d, Q p=0.01) with no differences between groups. Preliminary findings suggest that following 30‐day cycles of dieting/maintenance can promote gradual weight loss while allowing for a maintenance in REE.
Use of dietary supplements in relation to sociodemographic factors in pregnant women in the TEDDY study
Authors: Yang Jimin , Aronsson Carin , Uusitalo Ulla , Ballard Lori , Hay Kristen , Joslowski Gesa , Hummel Sandra , Riikonen Anne , Norris Jill , Virtanen Suvi
Published: June 2021

The Environmental Determinants of Diabetes in Youth (TEDDY) is a longitudinal study that aims to identify environmental exposures that may affect islet autoimmunity and the development of type 1 diabetes among children at high genetic risk. Participating mothers recalled dietary supplement use during pregnancy 3‐month postpartum. Descriptive analyses and chi‐square test were used to analyze data from 3,630 mothers in 4 countries. Over 90% of the mothers used at least 1 type of supplement during pregnancy (94% in the US, 85% in Finland, 93% in Germany, and 89% in Sweden, p<0.01). Among users, 48% took multivitamin/mineral (MVM), 16% took single supplements (SS), and others took both. Iron was the mostly taken SS in all TEDDY countries (n=1340), followed by calcium in the US, vitamin D in Finland, and folic acid in Germany and Sweden. Vitamin D‐containing MVM and SS were taken by 2,323 mothers, of them 49% were from the US. Among 456 fatty acid supplement users, 250 took the formulations without other nutrients. Probiotics users were 10‐fold more in the US and Finland than in Germany and Sweden. Overall, dietary supplement use was associated with higher education, non‐smoking, non‐drinking, and 1st‐child delivery (p<0.01). Sociodemographic factors did not notably affected the average duration of supplementation which ranged from 17.5 weeks for single iron product to 37.6 weeks for probiotics‐containing MVM.
Supplement with encapsulated vegetable and fruit juice powder concentrate improves microcirculation and ultrastructure in human skin
Authors: Boddie Anita M , Heinrich Ulrike , Garbe Birgit , Wiebusch Mathilde , Tronnier Hagen
Published: June 2021

Aim

To determine changes in skin physiological parameters during the intake of vegetable and fruit juice powder concentrate (JPC) vs. placebo capsules over 12 wk. Changes in microcirculation, hydration properties, transepidermal water loss (TEWL), and changes in ultrastructure of the skin (thickness and density) were determined.

Methods

Microcirculation measurements were performed with an O2C device (Lea Instruments, Giessen, DE). Hydration was assessed by Corneometer CM 825. Barrier function of the skin, TEWL, was measured on a Tewameter (Courage & Khazaka Electronics, Cologne, DE) and skin thickness and density using ultrasound (B‐Scan, Dermascan C, Cortex Technology, DK).

Subjects

52 female (age 40–65) subjects were randomly assigned in a double blind fashion to either the JPC group or placebo group. All tests were performed at baseline, wk 6 and wk 12.

Results

Percent change and significance (p<0.05) were assessed. At wk 12, compared to placebo, the JPC group had:

Significant improvement of microcirculation by 36% (flow 1 mm depth),

Significant improvement of the skin thickness by 6% and skin density by 17%, and

Significant increase of skin hydration by 9% and a decrease of TEWL by 4% (ns).

Conclusion

The JPC group had improved skin microcirculation and ultrastructure, skin hydration and barrier function. The placebo group showed no significant changes. Support: NSA (TN, USA)
Effects of a short‐term group fitness intervention on body composition and exercise motivation in college students
Authors: Hamre Megan , Hongu Nobuko , Lee Vinson R. , Welter Gale S. , Farr Joshua Nicholas , Going Scott B.
Published: June 2021

The purpose of this study was to test the impact of a short‐term group fitness intervention on body weight, percent body fat, and attitude toward physical activity in college students. Twenty sedentary students (mean age 20.4±1.4 yr) were classified as healthy or overweight (BMI >25 kg/m2) and, then randomized into exercise and control groups. The exercise group participated in four aerobic fitness classes per week for 4 weeks, while the control subjects remained sedentary. Percent body fat was measured by BodPod and attitude toward physical activity was measured via questionnaire at baseline and the end of the study. Using univariate analysis of variance, we found significant differences in change in percent body fat between the healthy‐control and overweight‐control groups (−1.1 ± 0.8 vs. 1.8 ± 0.9%, P=0.034) and between the healthy‐exercise and the overweight‐control groups (−2.2 ± 1.0 vs. 1.8 ± 0.9%, P=0.010). These findings support the notion that even at a young age, overweight individuals are more susceptible to weight gain and may need increased amounts of exercise or encouragement in addition to restricted diets to produce weight loss. Using the motivation questions, 80% of participants reported that group fitness provided motivation to continue exercise.

Supported by the University of Arizona Honors College and The Marshall Foundation.