bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLA2 activity declines during skeletal myoblast differentiation
Authors: Burkholder Thomas J 
Published: June 2021

Phospholipase A2 (PLA2) activity contributes to muscle differentiation, regeneration and damage, but the complement of cellular PLA2 expression is poorly defined. Stretch induced differentiation of myoblasts is dependent on prostaglandin F2alpha, a downstream metabolite of PLA2, and stretch induced signaling in myotubes is dependent on PLA2 activity. The PLA2 superfamily include calcium activated cPLA2, calcium independent iPLA2, and small, secreted sPLA2 families. Real time, quantitative PCR was used to determine the expression of cPLA2 alpha‐epsilon and iPLA2 alpha‐zeta in hindlimb muscles and differentiating myoblasts from C57 Bl/6 mice. Greatest expression was found of pla2g4e and pla2g6b, with little difference among muscles. Only pla2g6a showed any correlation with myosin heavy chain isoform. Expression of pla2g4a and c declined ten‐fold during differentiation. Calcium activated PLA2 activity declined in parallel with pla2g4a expression, and calcium‐independent PLA2 activity was not detectable in differentiating myoblasts. These results suggest that PLA2 and eicosanoid signaling within muscle may be highly dependent on cells other than myofibers.Supported by DC005017
Impaired sweating in multiple sclerosis leads to increased reliance on skin blood flow for heat dissipation
Authors: Davis Scott L. , Korkmas Melissa A. , Crandall Craig G. , Frohman Elliot M. 
Published: June 2021

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that can disrupt autonomic function, leading to impaired thermoregulatory function. The aim of this study was to test the hypothesis that control of sweating and skin blood flow (SkBF) is impaired in MS during whole‐body heating (WBH). Sweat rate (SR) and SkBF were assessed in dorsal forearm skin in females diagnosed with MS (n=4, age=39±4 yrs) and matched healthy controls (n=4; age=36±6 yrs) during normothermia (NT) and WBH (increased internal temperature ~1.0 °C). Cutaneous vascular conductance (%CVCmax) was calculated from the ratio of SkBF to mean arterial pressure and normalized to maximal responses obtained by local heating (42 °C for 30 min) following WBH. Sweating (ΔSR from NT) was impaired in MS patients (0.53±0.34 mg/cm2/min) compared to controls (0.99±0.07 mg/cm2/min; P=0.04). Cutaneous vasodilation (Δ%CVCmax from NT) was higher in the MS group (62.6±5.1%) compared to controls (41.6±6.3%; P=0.01). No group differences in cutaneous vasodilation were observed during local heating (P=0.92). Impaired sweating in MS may arise from impairments in neural control of sudomotor pathways or neural‐induced changes in eccrine sweat glands. Interestingly, larger increases in cutaneous vasodilation to WBH suggest neural control of SkBF is intact and may compensate for impairments in sweating in an attempt to adequately dissipate heat in MS patients.Supported by National MS Society Grant RG4043A1/1
Nesfatin‐1 Influences the Excitability of Neurons in the Nucleus of the Solitary Tract
Authors: Mimee Andrea V , Hoyda Ted D , Ferguson Alastair V 
Published: June 2021

Nesfatin‐1 is a recently discovered neuropeptide that has been shown to decrease food intake in animals when injected both intracerebroventricularly and peripherally. In situ hybridization and immunohistochemical studies have revealed the expression of nesfatin‐1 throughout the brain and, in particular, in the nucleus of the solitary tract (NTS), a medullary structure with important roles in the regulation of feeding. In order to shed light on the mechanisms by which nesfatin‐1 exerts its satiety‐promoting actions, this study examined the effect of nesfatin‐1 on the excitability of NTS neurons. Whole‐cell current clamp recordings from rat NTS neurons in slice preparation were performed and the effects of bath application of nesfatin‐1 (10nM) on membrane potential examined. Of 14 cells tested, 43% (6/14) were influenced by nesfatin‐1. Depolarizing effects were seen in 50% of responsive cells (mean depolarization = 5.1 ± 1.4 mV, n=3) while the remaining 50% of cells hyperpolarized (mean hyperpolarization = −8.6 ± 0.9 mV, n=3) in response to nesfatin‐1. These findings identify the NTS as a potential site at which nesfatin‐1 acts to influence central control of food intake.Research support provided by NSERC, CIHR, and HSFC.
Design elements of a longitudinal course in human structure
Authors: Metzger Keith , Gannon Patrick , Rennie William 
Published: June 2021

Human structure, defined here as a spectrum of relationships from cellular to gross, is traditionally taught as a series of relatively short isolated courses that may or may not be integrated. At our School of Medicine, topics encompassed under the umbrella of structure include gross anatomy, embryology, histology, gross/histopathology and clinical imaging. These topics are presented within a single, lab‐based course spanning the first 100 weeks of the four year curriculum. The “Structure” course emphasizes the integration of basic science and clinical concepts in an active learning environment. Learning sessions within the longitudinal course are themselves integrated within each 9–12 week systems‐based course.Design of the Structure course involved a significant degree of input from clinicians who serve as primary facilitators for student learning. Presentation of topics includes: 1) broad primary exposure with subsequent expansion of depth and complexity, 2) an internally integrated organization, in which multiple aspects of individual structural topics are presented in a single session, and 3) use of active pedagogies including small‐group learning and problem‐based dissection. It is our expectation that this approach will facilitate the advancement of students through increasing levels of cognition, promote retention and enhance the clinical application of structural topics.
Mechanisms of Aldosterone Action on NCC
Authors: Ko Benjamin , Moddes Lauren , Cooke Leslie , Hoover Robert S 
Published: June 2021

Aldosterone increases NCC function and protein expression in whole animal studies at 72 hours but more acute effects of aldosterone on NCC activity have not been studied. We have recently demonstrated that in a mammalian cell model with robust native NCC activity (mDCT15), aldosterone stimulated NCC activity by 26% at 6 hrs and by 52% at 24 hrs. However, the mechanism by which this acute stimulation was mediated is unknown. To examine this question, mDCT15 cells were incubated with either 100nM aldosterone or vehicle (DMSO) for 6 or 24 hours. Cells were then surface biotinylated and surface expression was assessed by Western blotting. Total NCC protein expression remained unchanged compared to control in both the 6 and 24 hour treatment groups. Furthermore, NCC surface expression did not change in the 6 or 24 hour aldosterone treated groups compared to control. This suggests that the effects of aldosterone upon NCC are not primarily mediated by increased surface expression, but instead due to an increase in individual transporter activity. Further work is needed to characterize this mechanism.Research support: NIH‐NIDDK K08 DK070668, DK081728.
CCL23 upregulates expression of Epidermal Growth factor Receptor and inhibits EGF‐induced proliferation of endothelial cells
Authors: Kim Jee Young , Kwon Taek Hwan , Han Kyu Yeon , Lee Tae Hoon , Kim Jiyoung 
Published: June 2021

It has been recently reported that human CCL23 (also known as MPIF‐1, MIP3, or CKβ8) promotes endothelial cell migration and tube formation, while it has no effect on proliferation of endothelial cells. In this study, we conducted DNA microarray analysis to determine gene expression alterations in response to the treatment of HUVECs with CCL23 using 22,000 human genes microarray. We found that the CCL23‐dependent modulation in the expression of genes represented a wide variety of functional categories including genes important in the cell growth and maintenance. Based on the microarray analysis data, we focused on up‐regulation of Epidermal Growth Factor Receptor (EGFR) by CCL23, which was identified by reverse transcription‐polymerase chain reaction, quantitative real‐time polymerase chain reaction and Western blot. EGF stimulated proliferation of HUVECs, which was significantly inhibited by pretreatment of CCL23 in dose‐dependent manner. EGF‐stimulated phosphorylation of ERK was reduced in CCL23‐treated cells, while phosphorylation of STAT1 was increased by CCL23, indicating that STAT1 is involved in the inhibition of EGF‐induced proliferation of endothelial cells by CCL23.This research is supported by a grant from National Research Foundation of Korea.
A promiscuous ubiquitin ligase controls cell cycle through a unique mechanism
Authors: Glenn Kevin Andrew , Wen Hsiang M. , Kim Namhun , Mallinger Adam , Gonzalez‐Alegre Pedro 
Published: June 2021

ObjectiveIdentify the cullin partner proteins for FBG1.MethodsWestern blots of proteins co‐immunoprecipatating with FBG1 identified partner proteins. Growth rates determined by replicate cell counting via a hemocytometer or Countess automated counter. Cell cycle analysis was by FACS.During cell proliferation, protein degradation is strictly regulated by two complementary ubiquitin ligase complexes, the SCF (Skp, Cullin, F‐box) and APC/C (Anaphase Promoting Complex/Cyclosome) ubiquitin ligases. SCF complexes degrade proteins during the G1 phase, but as DNA synthesis begins, the SCF complexes are degraded and APC/C complexes are activated. This study explores an unexpected interaction between APC‐2 and SCFFBG1. We found that FBG1 is a promiscuous ubiquitin ligase with many partners. Immunoprecipitation experiments demonstrate that FBG1 and APC2 interact directly. Site‐directed mutagenesis shows that this interaction requires a D‐Box within FBG1. Unexpectedly, we demonstrate that co‐expression with FBG1 increases total APC2 levels. Finally, FACS analysis demonstrates that FBG1 induces S‐phase arrest, illustrating the functional consequences of this interaction. In summary, we have discovered a novel APC2 inhibitory activity of FBG1 independent of its ubiquitin ligase function.Funding: V.A. RCD and Ellison New Scholars in Aging Award.
Phylogenetic analysis of the domains that conform the NADPH oxidases
Authors: Julián‐Sánchez Adriana , Magis‐Weinberg Lucía , Riveros‐Rosas Héctor 
Published: June 2021

NADPH oxidases (Nox) are eukaryotic enzymes used deliberately to produce superoxide radicals. In a previous work (Mol. Microbiol (2003) 50: 1241), we show evidence that suggests that Nox evolutionarily derived from ferric reductases, which have been described in animals, plants, fungi and bacteria. Both are membrane proteins and contain a cytochrome b as well as flavin, and possess three different domains: a FAD binding domain, a NADP+ binding domain, and a ferric reductase domain. In this work a phylogenetic independent analysis was made for each one of these domains, to obtain additional insight about the origin of Nox.The analysis was carried out in silico, starting from the protein sequences obtained on public databases (PFAM, NCBI and SwissProt), that possess the NADP+ binding domain (565 sequences), FAD binding domain (607 sequences) and ferric reductase domain (1012 sequences). The domain alignments were built with Clustal_X (corrected manually with BLASP results). Phylogenetic analysis was performed in MEGA 4.0. The results show that in the three analyzed domain, all the Nox comprise a monophyletic group; however, its relationship with the ferric reductases (the proposed ancestral group) is not so clear when the domains in an independent way are analyzed. This contrast to the obtained results with the complete sequences. Supported partially by DGAPA‐UNAM grant IN208510‐3.
Signal perception and transmission in histidine autokinases: Insights from the Agrobacterium tumefaciens VirA/VirG system
Authors: Lin Yi‐Han , Gao Rong , Binns Andrew N , Lynn David G 
Published: June 2021

VirA, the histidine autokinase found in Agrobacterium tumefaciens, is activated in response to several signaling cues, among which the plant‐derived phenolic molecule being the most critical. The cytoplasmic linker domain is responsible for phenol sensing, and a coiled‐coil was predicted to bridge the linker domain to the kinase. Using yeast transcription factor GCN4, the possible signal‐induced rotational motion in the coiled‐coil was examined. Through different insertions between GCN4 and the coiled‐coil, the signal‐independent ratcheted activities were observed. Random mutagenesis and functional library screening also indicated several constitutively on mutants in the coiled‐coil, which enabled the dimerization interface to be established. Together with the structure model of the linker domain, generated by homology modeling, and the possible phenol binding site, probed by computational docking, the model for phenol perception and the associated motion in the signaling module of VirA is proposed.This work is supported by NSF‐IOS‐0818613.
An anti‐inflammatory peptide combination reduces oxidative effect of plasma from cardiomyopathy patients
Authors: Elboudwarej Omeed , Kim J. Brian , Hama Susan , Hough Greg , Fonarow Gregg 
Published: June 2021

BackgroundPatients with cardiomyopathy are under increased oxidative pressure and their plasma shows a high plasma inflammatory index (PII). In the present study, our group tested whether the combination of the anti‐inflammatory peptides apoJ[113–122] and FREL would effectively reduce the PII.MethodsPlasma from 10 patients with heart failure was incubated with 0.5 μg/ml apoJ[113–122], with 2 μg/ml FREL, or with a combination of the two peptides. The plasma was then diluted 2000‐fold and incubated with human endothelial cells. To determine the PII, we used a monocyte chemotactic assay (MCA) to quantify the plasma‐induced inflammation of the endothelial cells.ResultsTreatment of plasma with a combination of peptides has an additive effect on improving the PII. The PII value was reduced by 80% with apoJ[113–122] alone, 52% with FREL alone, and 127% in combination.ConclusionTreatment of plasma with a combination of peptides resulted in additional improvement of the PII. One potential explanation is that these peptides have an additive effect in sequestering or preventing the formation of different lipid oxidation products, possibly by forming biochemical complexes that are more active than the peptides are individually. Grant source: U.S. Public Health Service Grants HL‐30568 and HL‐34343 and the Laubisch, Castera, and M.K. Gray Funds at the University of California Los Angeles.
Maternal α‐linolenic acid supplementation during gestation and lactation alters postnatal brain development in the offspring
Authors: LUPU DANIEL , RAGAB AMR S , CRACIUNESCU CORNELIU N , NICULESCU MIHAI D 
Published: June 2021

Perinatal nutrition influences postnatal brain development, with long‐lasting effects on learning, memory and brain aging. ω‐3 fatty acids are essential for normal brain development. This study established that maternal perinatal α‐linolenic acid (ALA) availability modulates postnatal hippocampal development.C57BL/6 female mice were fed either an ALA control (C, 2 groups) or an ALA deficit diet (D, 2 groups) for 30 days prior to, and during gestation. One day prior to delivery and during the lactation period (20 days), mice from one C group and one D group were switched on an ALA supplemented diet (CS and DS, respectively). The remaining two groups continued on their initial diet until postnatal day 20 (P20, CC and DD, respectively). At P20, mothers and pups were sacrificed. Within the dentate gyrus of male pups (DG), mitosis and early neuronal differentiation were increased in the CS group, while apoptosis was increased in the DD group. Fatty acid (FA) profiling in the maternal livers and serum, and in the pups’ brains revealed changes of several ω‐3, −6, −9, and saturated FAs.Perinatal ALA availability contributes to the postnatal development of the DG by altering the proliferation and early neuronal differentiation of neural precursors. Changes within FAs are induced by maternal ALA availability.Funded by a grant to MN from the UNC Center for Excellence in Children's Nutrition sponsored by Mead Johnson Nutrition.
Effects of essential amino acid supplementation on markers for anabolic and catabolic response to resistance exercise in female subjects
Authors: Mascher Henrik , Apró William , Pontén Marjan , Ekblom Björn , Blomstrand Eva 
Published: June 2021

The anabolic effect of essential amino acids (EAA) in connection with resistance exercise is well documented. Among the EAA, leucine has been suggested to play a key role, however, this has not previously been studied in female subjects. The aim of this study was to compare the effect of EAA with and without leucine (EAA‐leu) on the anabolic response through the mammalian target of rapamycin (mTOR) signaling pathway. In addition, gene expression of two ubiquitin ligases (MAFbx and MuRF‐1) was measured as they are involved in muscle protein breakdown. Eight female subjects performed leg press exercise twice, separated by one month, during which they were randomly supplied one of the two supplements in flavored water. Muscle biopsies were taken from the vastus lateralis before exercise and 1 and 3h following exercise. Ingestion of EAA led to a 3‐fold larger increase (p<0.05) in p70S6k phosphorylation 1h after exercise, whereas phosphorylation of mTOR increased similarly in both conditions. The mRNA content of the two ubiquitin ligases was reduced 3h following exercise (MAFbx 35%, ns and MuRF‐1 40%, p<0.05) when a mixture of EAA was ingested, but no significant changes were seen when EAA‐leu was ingested. The results support the idea that leucine has a particularly important role in stimulating p70S6k, a key enzyme regulating protein translation, but may also reduce expression of genes involved in protein degradation.The study was supported by funds from the Swedish School of Sport and Health Sciences, Stockholm, Sweden.
Supporting Breastfeeding: A Course for Hospital‐Based Nurses
Authors: Baker Susan S , Auld Garry , Weddig Jennifer 
Published: June 2021

ObjectiveTo determine if a one‐credit online course and practicum results in changes in the knowledge, behaviors, skills, and attitudes of hospital‐based nurses’ in relation to breastfeeding best practices.MethodsThe course and practicum were designed to increase nurses’ knowledge in the area of breastfeeding initiation. Data were collected from the treatment (n=50) and comparison (n=45) groups before and after the course and practicum to assess change in knowledge, behaviors, skills and attitudes.Assessment tools included the Coventry University Breastfeeding Assessment, an online attitudes and skills pre/post test created and tested for reliability and validity; and a hospital chart review of a subset of nurses to assess changes in nursing skills and behaviors in breastfeeding initiation best practices.ResultsData have been collected. Preliminary analyses indicate that the treatment group increased knowledge, improved attitudes, and improved breastfeeding initiation support behaviors while the comparison group did not have any improvement in knowledge, attitudes or behaviors.ConclusionsThe course is an effective way to educate healthcare professionals about evidence‐based breastfeeding initiation best practices.This research was partially funded by Medela and the Colorado Breastfeeding Coalition
Decursinol protects PC12 cells from β‐amyloid25‐35‐induced neurotoxicity via the activation of NF‐E2 related factor 2
Authors: Jung Sang‐won , Li Li , Li Wei , Park Sung‐ki , Kim Yong‐ho 
Published: June 2021

One of the pathological hallmarks of Alzheimer's disease is the progressive accumulation of beta‐amyloid(Aβ) and Aβ insult to neuronal cells has been identified as one of the major causes of the disease. Decursinol, found in the roots of Angelica gigas Nakai, has been traditionally used to treat anemia and other various diseases. In this study, we investigated protective effects of decursinol on beta‐amyloid25–35(Aβ25–35)‐induced cell death in PC12 cells. Following exposure PC12 cells to 25μM Aβ25–35 for 24 hrs significant increased the lipid peroxidation(MDA), decreased the activities of antioxidant enzymes(superoxide dismutase, glutathione peroxidase, catalase) and the level of glutathione(GST) content which were accompanied by decreased cell viability, activity of GST and transactivation of activator NF‐E2‐related factor‐2(Nrf2) which mediates GST gene transcription. Besides, pretreatment of PC12 cells with decursinol for 3 hrs significantly reversed the effect of Aβ by decreasing the oxidative stress and increasing the activation of Nrf2 and GST activity level. These data indicate decursinol protected PC12 cells against Aβ‐induced neurotoxicity through the inhibition of oxidative damage through activation of Nrf2.This research is supported by Biohealth Products Research Center(BPRC) of Inje University.
Maternal awareness of the WHO guidelines on infant feeding is related to HIV status, feeding practices, and stunting in Andhra Pradesh, India
Authors: Singh Akriti , Ramakrishna G. S. , Grizas Alexandra P. , Humphries Debbie 
Published: June 2021

Family Health International's Balasahyoga program provides child growth monitoring and nutrition counseling to HIV/AIDS affected households in Andhra Pradesh.ObjectivesTo assess awareness of the WHO guidelines on infant feeding among HIV+ and HIV− mothers, and to determine whether awareness of the guidelines is related to feeding practices and infant nutritional status.MethodsA cross‐sectional assessment of Balasahyoga program participants (HIV+ N=44) and neighborhood controls (HIV− N=41), with infants 6–12 months of age, was conducted in Guntur and West Godavari districts of Andhra Pradesh. The mothers were interviewed regarding feeding practices and anthropometric measurements were taken of mothers and infants.ResultsHIV+ mothers were 3.23 times more likely to be aware of the WHO guidelines than HIV− mothers (unadjusted, p=0.02). Infants of HIV+ mothers were 5.88 times more likely to be stunted than infants of HIV− mothers (unadjusted, p=0.01). Guideline‐aware HIV+ mothers were more likely to have ever breastfed (p=0.003) and less likely to have stunted infants (p=0.01) than guideline‐unaware HIV+ mothers.ConclusionAmong the HIV+ mothers, awareness of the WHO guidelines is positively associated with breastfeeding and infant nutritional status. This initial finding emphasizes the importance of guideline implementation and evaluation of further educational interventions for HIV+ mothers.