bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAIN DERIVED NEUROTROPHIC FACTOR CHANGES IN RESPONSE TO SUCROSE INTAKE IN ADOLESCENT RATS
Authors: Simsek Zinar Darius , Sanroman Dolores Vazquez , Curtis Kathleen 
Published: April 2020

Sugar intake is a natural stimulus, like sodium or stress, and activates similar neural circuits involved in mediating reward. Sugar intake may lead to a sensitization of the reward system, changing the response to subsequent rewarding experiences. BDNF plays an important role in the survival, maintenance and growth of many types of neurons and is expressed abundantly in the nucleus accumbens (NAcc) and prefrontal cortex (PFC). Rodents maintained on energy‐rich diets containing high levels of sugar show impaired learning and memory performance, and recent evidence indicates that such deficits may be related to the effects of these diets on the regulation of brain‐derived neurotrophic factor (BDNF) in the brain. Nevertheless, it is not clear how sucrose intake translates into decreased BDNF levels in brain reward areas. The specific aim of this study, therefore, addresses the lack of information on the role of sugar intake, as a natural reward, in BDNF expression in the PFC and NAcc.HypothesisAnimals pre‐exposed to sucrose intake in early adolescence are more likely to maintain elevated levels of sucrose intake which is related to changes in BDNF levels in PFC and NAcc.Methods1) We have determined preferred sucrose concentration in adolescent rats using a chronic intermittent sucrose intake model. 2)We have determined if early sucrose intake affects adult sucrose intake and examined changes in BDNF levels of expression in the PFC and NAcc. On PND28, (pre‐adolescents period) rats were assigned to sucrose (5% or 15%) or tap water groups. From PND28 (adolescent period) to PND32 rats had 2hr access to sucrose or water each day. After 8 weeks, rats were re‐exposed to sucrose or water and after the last sucrose intake session, animals were sacrificed. Brains were extracted and prepared for immunoassay analysis (ELISA) for identifying Pro and Mature BDNF levels.ResultsAdolescent rats showed significantly higher levels of sucrose intake at the 5% concentration than the 15% concentration. Both ProBDNF levels and Mature BDNF levels in the PFC showed statistically significant differences among the groups, whereas there is not any statistically significant change among groups in NAcc.ConclusionOur study demonstrated for the first time that sucrose ingestion affects BDNF levels in PFC but not in NAcc in the brain when adolescent rats are pre‐exposed to sucrose intake.Support or Funding InformationOklahoma State University Vice President office of research 2019
Effects of food intake on relaxin 3 (Rxn3) mRNA expression in the muscle of Atlantic salmon
Authors: White Taylor , Moyers Macy , Kostner Danica LeAnn , Wertz Blaine , Peterson Brian C. , Kobayashi Yass 
Published: April 2020

The Rxn3 is a protein that belongs to the insulin‐like/relaxin superfamily and affect various physiological functions, including growth, food intake, and reproduction. Evidence in rodents suggests that Rxn3 is involved in the regulation of food intake and critical for proper development of muscle and bones. The roles that the insulin‐like/relaxin superfamily plays in regards to growth and metabolism is largely unknown in fish, including Atlantic salmon. Recently, we identified the mRNA sequence for the Atlantic salmon Rxn3 by screening the database using channel catfish insulin‐like 5 polypeptide mRNA sequence. Given the possible role of Rxn3 in muscle function and nutrient metabolism, changes in the expression of Rxn3 mRNA in response to the changes in food intake were examined. Juvenile Atlantic salmon (n=72, 6 fish per tank) were assigned to either receive food every day (control, n=4 tanks) or fasted for 14 days (fasted, n=4 tanks). Additionally, fish were fasted for 7 days and fed daily for the subsequent 7 days (refed, n=4 tanks). Muscle samples were collected from fish at the end of 14 days, and expression of Rx3 mRNA was measured using real‐time PCR. Expression of Rxn3 mRNA was similar among the three feeding treatments, suggesting that muscle expression of Rxn3 is not affected by changes in food intake. Given the preliminary nature of the study, further investigations are warranted to define the role of Rxn3 on the regulation of growth, food intake, and nutrient metabolism in Atlantic salmon.Support or Funding InformationThis project was partially funded by Kansas IDeA Network of Biomedical research Excellence (K‐INBRE) under the NIGMS/NIH grand P20GM103418.
Impact of Natural and Anthropogenic Perturbations on Animal Behavior: A Cellular Approach
Authors: Mattei Gabriela Angelica Rosado , Miller Mark W. 
Published: April 2020

The nervous systems of gastropod molluscs contain large neurons that can be identified in all specimens. They are therefore useful for elucidating the cellular basis of behavior and its modification due to extrinsic factors. Our studies examine two tropical marine gastropod species, Bursatella leachii and Dolabrifera dolabrifera, to determine the impact of natural perturbations and anthropogenic contaminants on identified neurons and motor circuits. Here, we report a census for Bursatella leachii during 2019 and compare it to previous years. We find a reduced population that may be recovering during the two years since the major hurricanes of 2017. Specimens were collected to perform immunohistochemistry with the goal of characterizing the localization of specific neurotransmitters in the nervous system. We found that the catecholamine dopamine is likely to be involved in the regulation of feeding and reproductive behaviors. RNA was also extracted from the CNS of Bursatella in order to generate a nervous system transcriptome. These observations provide a platform for future investigation of the impact of natural and man‐made disturbances on the cellular control of behavior in these model organisms.Support or Funding InformationFunding: NIH (USA): RCMI MD007600, NIGMS‐RISE R25 GM061838 NSF (USA): CREST HRD‐1137725
Higher Weekly Walking Volume Improves Cardiac Autonomic Profile and Arterial Stiffness Index in Hypertensive Elderly
Authors: Neto Octávio Barbosa , Bilharinho Frederico , Resende Elisabete Aparecida Mantovani , Resende Luiz Antônio Pertili , da Silva Marco Antônio Vieira , Sordi Carla Cristina 
Published: April 2020

BackgroundThe practice of daily aerobic exercise such as healthy walking could have an important effect on cardiovascular parameters. However, there is still little evidence of how much weekly walking volume is enough to influence cardiovascular autonomic modulation and arterial stiffness on hypertension.PurposeTo assess effects of weekly walking volume on cardiac autonomic function and arterial stiffness index in elderly hypertensive.MethodsSixty hypertensive elderly with 71.7 ± 3.4 years old were allocated in physically inactive (PI, n=30) and active (PA, n=30) groups. Hemodynamic parameters of heart rate (HR), peripheral blood pressure (SYS, DIA, MBP), cardiac autonomic modulation by the method of HR variability in both the time (root mean square of successive differences (RMSSD) and percentage of RR intervals differing by <50ms (pNN50)) and frequency domains (low and high frequency (LF, HF), and LF/HF ratio), stiffness (augmentation index; AIX, pulse wave velocity; PWV) and total vascular conductance (TVC), and central blood pressure (cSYS, cDIA) were measured in baseline conditions.ResultsThe average of weekly walk in PA group was 312.4 ± 36.5 min. vs. 57.7 ± 47.9 min. in PI group (p <0.001). Pronounced resting bradycardia was observed in PA group (62.1 ± 8.7 bpm) in comparison with PI group (75.7 ± 9.1; p=0.0). Brachial SYS (124.3 ± 7.6 mmHg) DIA (76.5 ± 7.4 mmHg) and MBP (92.4 ± 7.4 mmHg) were lowers in PA than PI group (133.6 ± 6.0 mmHg; p=0.003), (82.7 ± 7.6 mmHg; p=0.032) and (99.4 ± 7.0 mmHg; p<0.05), respectively. The PA group showed higher cardiac parasympathetic modulation than PI group, evidenced by an increase in RMSSD (PI: 43.8 ± 23.9 vs. PA: 69.4 ± 29.4 ms; p=0.047), pNN50 (22.7 ± 3.9 vs. 40.7 ± 5.1 %; p=0.038) and in cardiac HF band (PI: 59.9 ± 5.8 vs. PA: 67.0 ± 3.7 nu; p=0.005). There were no differences in sympathetic modulation between PA and PI groups. The PI group had higher PWV (10.3 ± 1.2 m/s), AIX (36.4 ± 8.0 %) and TVC (1.4 ± 0.1 s*mmHg/ml) when compared to PA group (PWV = 9.1 ± 0.7 m/s; p = 0.005), (AIX = 23.5 ± 13.6 %; p = 0.003) and (TVC = 1.2 ± 0.1 s*mmHg/ml; p <0.001). Additionally, the cSYS (119.5 ± 14.0 mmHg) and cDIA (76.2 ± 18.3 mmHg) were lower in PA than PI (135.8 ± 20.6 mmHg; p=0.045 and 91.8 ± 20.5 mmHg; p=0.034), respectively.ConclusionThese findings suggest that a higher weekly volume of walking improves baseline hemodynamic parameters and provides greater vagal modulation at rest, concomitant with attenuation of arterial stiffness evidencing that this type of intervention has important cardiovascular safety.Support or Funding InformationCAPES, CNPq, FAPEMIG, UFTM.
The synthesis and investigation of the catalytic properties of symmetric Schiff‐base ligand metal complexes
Authors: Wolfe Charles A. , Mueller Paul H. , Deifel Nicholas P. 
Published: April 2020

An ongoing project investigating the synthesis and catalytic properties of symmetric heterometallic Schiff‐base ligand complexes has been instigated. A novel symmetric Schiff‐Base ligand metal complex has been synthesized, characterized through IR spectroscopy, NMR spectroscopy, and LC mass spectrometry. The catalytic activity of this Schiff‐Base ligand has been investigated using cyclic voltammetry, mass spectrometric study, and UV‐vis spectroscopy. With the long‐term goal being a publication of results, this study aims to contribute to the fields of inorganic and biochemistry.Support or Funding InformationBarry Goldwater Scholarship Foundation
Types of Neurons in the Spinal Trigeminal Nucleus of the Camel Brain: Golgi Study
Authors: Bataineh Ziad M. 
Published: April 2020

The camel lives in hot desert and eats thorny plants. It is exposed to severe environmental conditions such as dust, high temperature and thorny plants. These sensations from the face area may affect the development of neurons in the camel’s spinal trigeminal nucleus which contain the second‐order neurons of the sensory pathways for pain and temperature from the face area. Neurons in the spinal trigeminal nucleus of the camel were studied by Golgi impregnation.AimsThe aims of this study were to describe the different types of neurons in the spinal trigeminal nucleus and to compare these neurons with their counterparts in other species.MethodBlocks (2–4mm thick) of camel brainstem preserved in 10% formalin for months were cut and processed by two variations of Golgi Kopschi method (Fox and Braintenberg staining methods). Transverse sections (100 μm thick) were cut and examined under the light microscope. Well‐impregnated neurons were studied, measured and photographed.ResultsNeurons were classified based on differences in size and shape of their cell bodies, density of their dendritic trees, morphology and distribution of their appendages.In the spinal trigeminal nucleus of the camel, at least twelve types of neurons were identified. These neurons include, stalk, islets, octubus‐like, lobulated, boat‐like, pyramidal, multipolar, round, oval and elongated neurons. They have large number of different forms of appendages not only for their dendrites but also for their cell bodies. Neurons with unique large dilatations especially at their dendritic branching points were found. These neuronal types were found in the three divisions of the spinal trigeminal nucleus namely the spinal trigeminal caudalis, spinal trigeminal interpolaris and spinal trigeminal oralis. The morphological features of these neurons were described and compared with their counterparts in other species.ConclusionFinding of neurons with variation in number and shape, in addition, to variation in number and shape of the appendages on the cell bodies and dendrites may indicate the presence of a very complex information processing for pain and temperature at the level of the spinal trigeminal nucleus in the camel. Together with the presence of cells with unique features such as large dilated parts for dendrites, may suggest that, the spinal trigeminal nucleus in the camel serves as center for sensations processing and not only as relay nucleus for the pain and temperature pathways from the face. This study will improve our understanding of the function of the spinal trigeminal nucleus and contribute to our understanding of comparative neuroanatomy and neurophysiology.Support or Funding InformationResearch Grant 100/2011 from the Deanship of Scientific Research at Jordan University of Science and Technology
Targeting the Upstream Open Reading Frame of Gadd34 to Treat Sepsis‐induced Acute Kidney Injury
Authors: Kidwell Ashley , Maier Bernhard , Dagher Pierre , Hato Takashi 
Published: April 2020

Sepsis‐induced acute kidney injury (AKI) remains a major clinical problem with no effective therapies established to date. We have previously shown that bacterial sepsis causes global translation shutdown via phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). Under physiological conditions, eIF2α phosphorylation is tightly counter‐regulated by two eIF2α holophosphatases since excessive phosphorylation of eIF2α is deleterious. Of the two holophosphatases, growth arrest DNA‐inducible gene 34 (Gadd34) is the only stress‐inducible regulatory subunit. Using ribosome profiling, or Ribo‐Seq, we found that Gadd34 is translationally repressed during late phase sepsis even though eIF2α is already heavily phosphorylated. This failure of Gadd34 induction could explain the sustained phosphorylation of eIF2α and translation shutdown that contributes to delayed renal recovery in sepsis. The 5′‐untranslated region (UTR) of Gadd34 has multiple upstream open reading frames (uORFs) that are conserved across mammalian species. Our Ribo‐Seq analysis of kidneys from septic animals revealed high ribosomal occupancy of a specific Gadd34 uORF, but not the main protein coding sequence (CDS), consistent with a model in which the uORF serves as a translational inhibitor of the downstream CDS. With these findings, the objective of the investigation was to analyze the effect of disrupting translation in the uORF of Gadd34 in septic states.To investigate the inhibitory role of the Gadd34 uORF, we designed plasmid constructs, which consisted of a full length Gadd34 5′‐UTR and luciferase reporter CDS in‐frame with a single nucleotide mutation introduced to abolish the uORF start codon. The uORF point mutation led to a two‐fold increase in luciferase signal compared with the wild‐type control, confirming the inhibitory property of the Gadd34 uORF. Next, we designed antisense oligonucleotides (ASOs) complementary to the upstream portion of the uORF. Interestingly, masking the uORF with ASOs resulted in sequence‐specific increases in translation of the downstream CDS, possibly due to enhanced leaky ribosomal scanning. Finally, we tested the applicability of the ASO approach in vivo using a mouse model of endotoxin‐induced kidney injury. Despite late intervention at eight hours post‐endotoxin challenge, intravenous administration of Gadd34 uORF ASOs significantly reduced renal tissue damage as determined by the levels of hepatitis A virus cellular receptor 1/kidney injury molecule 1 (Havcr1/KIM1). Collectively, these findings indicate that translational suppression of Gadd34 in late phase sepsis is a maladaptive response that could be therapeutically modulated by targeting its uORF.Support or Funding InformationThis work was supported by NIH grants K08‐DK113223, R01‐DK080063 and a Veterans’ Affairs Merit grant 1I01BX002901.
Up‐Regulation of Interleukin‐10 Expression in Dendritic Cells as an Important Role in The Immunomodulation By Strongyloides stercoralis
Authors: Sutaveesup Vittawin , Sodsai Pimpayao , Nuchprayoon Surang , Sanprasert Vivornpun 
Published: April 2020

Strongyloidiasis is a parasitic disease caused by Strongyloides stercoralis. Infection in the immunocompromised hosts such as organ transplants, SLE patients, or HIV and HIPV infected patients can cause severe strongyloidiasis. About 90% of patients with severe strongyloidiasis are dead. Infected patients have high levels of Th2, and Treg related cytokines, including IL‐4, IL‐5, IL‐9, IL‐10, IL‐13, and TGF‐β. These cytokines are then decreased to normal levels after the treatments. Parasites have several mechanisms to suppress or evade the host’s immune response, such as suppressing the expression of co‐stimulatory molecules on antigen presenting cells (APCs), stimulating apoptosis of APCs, or stimulating Th2 and Treg responses. Dendritic cells (DCs) play a crucial role in linking the innate and adaptive immune systems against pathogens by engulfing antigens and presenting to naïve T cells with appropriate cytokines. To understand the mechanisms of S. stercoralis to evade the host’s immune responses, we studied the alteration of antigen presentation process and cytokines productions by DCs stimulated with S. stercoralis. We treated murine dendritic cell line (DC2.4) with S. stercoralis L3s crude antigen and measured the expressions of genes related with antigen presentation and cytokine productions by quantitative real‐time PCR; including MHC‐II, CD40, CD80, TLR‐2, TLR‐4, IL‐6, IL‐10, TNF‐α, and TGF‐β. The results showed that the expression of TLR2 and CD40 were significantly increased after the stimulation by crude antigens for 1 hr and 3 hrs, respectively. Likewise, the significant up‐regulation of IL‐10 expression of dendritic cells was also detected. While the expression levels of IL‐6 were not changed, TNF‐α expression levels were significantly increased. Our result suggested that S. stercoralis modulate the host’s immune response through the induction of Treg response by IL‐10 production by dendritic cells, not by the suppression the expression of co‐stimulatory molecules on antigen presenting cells.Support or Funding Information1. The Ratchadaphiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number RA62/026 2. Overseas Academic Presentation Scholarship for Graduate Students from the Graduate School, Chulalongkorn University
A New Mouse Strain to Study Motoneurons in Pompe Disease
Authors: Singer Michele L. , Lavassani Emmanuelle , Pope Megan K. , Harfe Brian D. , Haney Meghan Green , Corti Manuela , Byrne Barry J. , Fuller David D. 
Published: April 2020

Pompe disease is a lysosomal storage disorder resulting from a deficiency in the lysosomal enzyme acid α‐glucosidase (GAA). The most severe form of the disease is associated with complete or near complete absence of functional GAA which results in cardiorespiratory failure and death within the first year of life. The only approved treatment for Pompe disease is human recombinant GAA (enzyme replacement therapy (ERT)) which improves overall survival rates but the recombinant protein does not reach the central nervous system. Respiratory impairment in Pompe disease has historically been attributed to muscle weakness but an accumulation of studies of Pompe patients and animal models indicate that motoneuron pathology is functionally relevant. In an effort to better understand the role of motoneurons in Pompe disease, we used breeding strategies to create a new mouse model with motoneuron histopathology features seen in Pompe disease while also allowing easy visualization of motoneurons via a fluorescent tag. Chat‐cre mice (Jackson) were crossed with Gaa−/− mice (Taconic). The resulting heterozygous strain were crossed with eYFP+/+ mice (courtesy Dr. Brian Harfe). Further breeding resulted in homozygous mice which were Chat‐cre+/+/Gaa−/−/eYFP+/+. These mice were then crossed to a Flox‐Gaa+/+ (Taconic) to create a heterozygous strain (Chat‐cre+/−/Gaa+/−/eYFP+/−/Flox‐Gaa+/−). Further inbreeding produced mice that were Chat‐cre+/+/Gaa+/−/eYFP+/+/Flox‐Gaa+/+. The intent of this final cross was to produce mice in which alpha motoneurons express eYFP but do not express GAA. Histological evaluation of the brainstem and spinal cord of these mice showed robust eYFP expression in the brainstem including the hypoglossal motor nucleus, nucleus ambiguous, and facial motor nucleus. In the cervical spinal cord, alpha motoneurons throughout the ventral horn also had robust fluorescence. This included putative phrenic motoneurons as determined based on location and size. The robust eYFP expression was restricted to motoneurons which indicates that motoneurons are Gaa−/− (based on the breeding scheme). Ongoing studies are evaluating GAA protein expression in peripheral tissues, glycogen accumulation in motoneurons, and also brainstem and spinal cord motoneuron loss over the lifespan. In addition, the eYFP signal in motoneurons will permit rigorous evaluation of motoneuron transduction efficacy in gene therapy experiments.Support or Funding Information2R01HD052682‐11A1 (DDF/BJB)
Involvement of transcriptional/epigenetics mechanisms in mediating the inhibitory effect of chronic alcohol exposure, and effect of alcohol metabolites on intestinal uptake of biotin.
Authors: Srinivasan Padmanabhan M. , Ramamoorthy Kalidas , Chu Brain D. , Juburi Saleh A.L. , Said Hamid M. 
Published: April 2020

Biotin is indispensable for normal cellular metabolism, proliferation and survival. The vitamin acts as a co‐factor for multiple carboxylases that play critical roles in fatty acid, glucose and amino acid metabolism. Emerging evidence has also shown important roles for biotin in immune function and in gene expression, as well as in the maintenance of intestinal integrity and homeostasis. Humans and other mammals cannot synthesize biotin, and thus, must obtain the vitamin from exogenous sources (diet and the gut microbiota) via absorption in the gut. We had previously observed that chronic alcohol feeding/exposure leads to a significant inhibition in small intestinal and colonic biotin uptake (Am J Physiol Gastrointest Liver Physiol 300: G494–G501, 2011). The aim of this study was to elucidate the role of transcriptional/epigenetic factors in mediating the inhibitory effect of chronic alcohol on intestinal uptake of biotin, and to study the effect of alcohol metabolites on biotin uptake in the large intestine. Our results showed that the inhibition in biotin uptake by intestinal epithelial Caco‐2 cells upon chronic exposure to alcohol is associated with a decrease in the expression of KLF‐4, a key transcription factor involved in the regulation of SLC5A6. We also observed (using Chip‐qPCR) that exposure of Caco‐2 cells to alcohol to lead to decrease in the euchromatin histone markers (activators‐H3K4me3 and H3K9Ac) and an increase in the heterochromatin histone marker (repressor – H3K27me3) at the SLC5A6 P1 promoter. However, DNA methylation status appeared to be unaltered in these cells upon alcohol exposure. We confirmed the above effects of alcohol on histone modifications in vivo using small intestinal mucosa from mice chronically fed alcohol. We also examined the effect of the alcohol metabolites ethyl oleate (3 mM), ethyl palmitate (3 mM) and acetaldehyde (500 μM) on biotin uptake by human colonic epithelial NCM460 cells and observed a significant inhibition in carrier‐mediated biotin uptake in these cells. Studies are in progress to delineate the exact molecular mechanism(s) involved in this inhibitory effect. This study show, for the first time, that exposure of small intestinal epithelial cells to alcohol alters the epigenetic profile at the SLC5A6 promoters and the expression of an important nuclear factor that drive promoter activity, and that these changes contribute to the inhibition in biotin uptake. Further, the results show that relevant alcohol metabolites inhibit biotin uptake by colonic epithelial cells.Support or Funding InformationDVA and the NIH (DK‐56061, DK58057, and AA 018071