bluuebunny/crossref_metadata_2025_split huggingface dataset:
Science Advocacy Serves Communities and Scientists
Authors: Kozlovich Shannon , Bushana Piryanka , Szlenk Christopher 
Published: April 2020

Science is largely funded by taxpayer dollars, and because of this, scientists have a responsibility to ensure that their research is being effectively communicated back to taxpayers and the policy makers who determine the distribution of those funds. The importance and impact of effective science communication is compounded when research is used to inform legislative action. Science impacts policy, and policy can impact science. However, formal education of scientists does not usually include specific training on interacting with science policy. Immersive service learning modalities should be integrated into formal science training programs, especially for Masters and Ph.D. programs. These programs are training our future scientists and should be responsible for introducing a fundamental understanding of the interaction between science and policy to trainees. Currently, service learning opportunities for science policy, communication, and advocacy are being organized by student organizations. This project describes strategies for engaging trainees in science policy ‐ starting with simple and easy policy actions, and delving into more complex event planning and group organizing. We aim to distribute this as a model for the types of educational resources that should be adopted into the curricula of formal science training programs. We propose that formal service‐learning projects around science policy, communication, and advocacy can serve as opportunities to practice integrating scientific knowledge and expertise into dissemination of scientific advancements to the general public and policy makers. Similar trainings are integrated into many clinical health professional programs. After all, service‐learning facilitates learning that persists over a career and a lifetime. Whether advocating for evidence‐based policies, policies which impact the scientific enterprise or STEM education, practicing skills pertinent to science policy can help scientists gain comfort in translating their experiences and experiments into lasting change for the benefit and advancement of humanity and human health.Support or Funding InformationThis work was supported in part by the National Cancer Institute grant CA‐113710(fellowship support for S. Kozlovich), the Research!America Civic Engagement Grant, generous funding from the Associated Students of Washington State University HealthSciences (ASWSUHS), and the Washington State University Health Sciences campus Services and Activities fee committee.
5‐Aminosalicylic Acid Treatment Affects the Rate of Caloric Intake in Fattening Ground Squirrels
Authors: Witman Nathan , Bradley Rachel , Roberts Emily , Kovalenko Ivanna , Duddleston Khrystyne , Kurtz Courtney 
Published: April 2020

Obesity is the second leading cause of preventable death in the United States. Though prevalent, very little is known about the biological mechanisms that lead to obesity. A connection between increased gut permeability and the consequent immune response in systemic tissues exists in obese humans and mice. Systemic inflammation brought on by this immune response has been shown to decrease tissue efficacy and lead to adverse effects, such as insulin resistance. Recently, it was shown in mice on a high‐fat diet that 5‐aminosalicylic acid (5‐ASA, mesalazine), a gut‐specific anti‐inflammatory drug, attenuated insulin resistance and metabolic inflammation. We used a natural model of rapid adiposity, fattening 13‐lined ground squirrels (Ictidomys tridecemlineatus) during their active season, to examine the effects of 5‐ASA on caloric intake, body mass, glucose tolerance and inflammation. These squirrels normally double their adipose mass during their active season in preparation for hibernation. We found that the rate of caloric intake was significantly affected by 5‐ASA treatment and that these squirrels tended to eat more while gaining equal or less mass during the same period. Adipose depot mass was not different between groups but did differ between males and females. Despite a trend in the early weeks of 5‐ASA treatment, glucose tolerance did not differ between treated and control squirrels. Examination of pro‐ and anti‐inflammatory cytokines in white adipose depots and gut tissues revealed trends toward increased IL‐4 and TNF in visceral adipose of treated squirrels. Our results suggest that 5‐ASA treatment has different effects on development of metabolic inflammation in ground squirrels versus mice. Further studies are needed to determine if a higher dose would prove more effective in these seasonal hibernators.Support or Funding InformationSupported by NIH award 1R15GM124586‐01A1
Post‐Exercise Central Hypotension is Associated with Changes in Forward Pulse Wave Amplitude and Reflected Pulse Wave Timing in Young, Healthy Individuals
Authors: Patik Jordan C. , Stock Joseph M. , Chouramanis Nicholas V. , Mehrer Justin D. , Chirinos Julio A. , Edwards David G. 
Published: April 2020

In the hours following moderate intensity aerobic exercise (AE), persistent dilation of the arterial circulation supplying previously exercised muscle decreases total peripheral resistance (TPR) and contributes to post‐exercise hypotension. In addition to the effect of vasodilation on TPR, the diameter and tone of arterial vessels also influences central blood pressures via changes in the amplitude of forward (Pf) and backward (Pb) pulse waves, as well as the apparent wave reflection return timing (i.e. reflected wave transit time, RWTT). Prior research has assessed these parameters over a limited timeframe (e.g. 15 min) and relied on synthesized aortic flow waves rather than measured left ventricular outflow. As such, the prolonged post exercise effects of AE on pulse wave characteristics and central blood pressure are unclear.PurposeThis study aimed to characterize changes in pulsatile hemodynamics in the two hours following AE. We hypothesized that Pf and Pb would be reduced, and RWTT would be increased post‐AE relative to baseline (BL).MethodsTwelve young, recreationally active participants (8M/4F, 26±3 years, VO2max: 50.8±14.3 ml·kg−1·min−1) were studied at BL and then every 20 min after completing 60 min of upright cycling at 60% VO2max. At each timepoint, central pressure waveforms were derived from radial artery applanation tonometry and aortic inflow waves were acquired via echocardiographic pulsed‐Doppler assessment of blood velocity in the left ventricular outflow tract. Pressure and flow waves were averaged over 10 cardiac cycles and pressure‐flow relations were determined offline via wave separation analysis.ResultsAs expected, brachial systolic blood pressure (SBP) was decreased across the 120 min period post‐AE relative to BL (time effect P<0.001) while TPR was only reduced at 20 min (Δ−15±5%, P<0.05 vs BL) and cardiac output (CO) was maintained at all timepoints (time effect P=0.12). The nadir in central SBP occurred at 60 min post‐AE (Δ−11±2%, P<0.001 vs BL). At 60 min post‐AE, Pf and Pb were reduced by Δ−14.3±2.5% and Δ−24.2±3.3%, respectively (each P<0.001 vs BL) and RWTT was increased (Δ19.5±5.3% P<0.02 vs BL). The percent change in central SBP from BL to 60 min was related to changes in RWTT (r=−0.79, P=0.02) and Pf (r=0.65, P=0.02) but not Pb (r=0.38, P=0.22), CO (r=0.27, P=0.40) or TPR (r=0.14, P=0.66).ConclusionsThese data highlight the contribution of changes in pulsatile hemodynamic parameters, in contrast to changes in non‐pulsatile parameters (CO and TPR), to reductions in central BP following moderate intensity AE.Support or Funding InformationSupported by NIH grants R01‐HL104106 and P20‐GM113125
Comparative Neuromorphology of Purkinje Neurons Across Species
Authors: Liu Yi Fan , Bradley Stefanie , Bailey Craig D.C. , Vickaryous Matthew K. 
Published: April 2020

Neuromorphology of cells vary both across and within species, the differences of which contribute to a variety of cellular functions. Purkinje cells (PCs) in the cerebellum play a key role in the fine tuning of motor control and movement, and are characterized by their large soma and distinctive pattern of dendritic branching. However, outside of few selected taxa, the neuromorphology of PCs have not been well characterized. Here, we investigate PC neuromorphology in a representative reptile (leopard gecko), mammal (laboratory mouse), and bird (domestic chicken). Using a modified Golgi‐Cox protocol, differences in PC neuromorphology were quantified using Sholl and branched structure analyses. While PCs in all species demonstrated elaborate patterns of dendritic arborization, we quantified species‐specific differences in both cell size and branching complexity. The average dendritic length of PCs in geckos and mice were comparable, while those of chickens were almost twice as long. Chicken PCs are also characterized by a greater dendritic diameter and dendritic volume. Mouse and chicken PCs were significantly more complex than those of geckos, based on the number of dendritic terminals. Taken together, our findings demonstrate that even within the same cell type, there is considerable neuromorphological variation between species, potentially related to aspects of phylogeny, ecology, and functional morphology.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants 400358 to MKV and 2019‐04989 to CDCB
Structural details of GEF‐mediated Sar1 activation
Authors: Joiner Aaron , Fromme Chris 
Published: April 2020

The first trafficking step of the eukaryotic secretory pathway is the packaging of cargo proteins into COPII‐coated vesicles that exit the endoplasmic reticulum (ER). COPII vesicle coat proteins are recruited to the ER membrane via direct interaction with the activated (GTP‐bound) form of the Sar1 GTPase. Sar1 is activated on the surface of the ER by Sec12, a membrane‐anchored GEF (guanine nucleotide exchange factor). Here we report the crystal structure of the complex between Sar1 and the cytoplasmic domain of Sec12, representing a snapshot of the activation reaction. This structure provides detailed insight into the mechanism of Sar1 activation. The structure reveals that despite structural homology to the RCC1 GEF, a distinct surface of the beta‐propeller fold of Sec12 interacts with Sar1 to displace nucleotide. The structural results suggest that the cytoplasmic domain of Sec12 may adopt an unexpected orientation relative to the membrane surface. This orientation would position Sar1 on the ER membrane so that binding to GTP and engagement of its amphipathic N‐terminal helix with the lipid leaflet can occur simultaneously. Together with accompanying functional data, our results provide a structural explanation for the critical regulatory step of COPII vesicle biogenesis.Support or Funding InformationThis work was funded by the National Institutes of Health grant
R01GM116942 to J.C.F.Alfred P. Sloan Foundation Fellowship and NSF GRFP DGE‐1650441 to A.J.
c‐Fos Responses Produced by the Central Microinjection of Salvinorin B in Conscious Rats
Authors: Ali Aboozar B. , Gonzalez Christopher , Lee Eunice , Rockey Anna , Hall Allison , Franklin Cynthia , Rangel Yolanda , Helmut Gottlieb B. 
Published: April 2020

Intracerebroventricular (ICV) injection of kappa opioid agonists produces a marked diuresis in rats via inhibition of vasopressin secretion. Salvinorin B (Sal B) is a plant‐derived high‐affinity ligand for the kappa opioid receptor (KOR). Previous studies have proposed that Sal B has similar potency and efficacy as other synthetic kappa agonists in mediating the CNS effects of KOR activation. The present study examines the effects of Sal B on renal function and the expression of the proto‐oncogene c‐Fos in several hindbrain regions. Sal B effects were compared to either acetonitrile or saline vehicle treated animals. Sal B is a highly lipophilic drug and past studies utilized drug dissolving vehicles (e.g., DMSO) that produced significant cardiovascular and renal effects. In this study, we dissolved Sal B in acetonitrile/saline (1:9 dilution) to minimize solvent viscosity and cardiovascular effects.MethodsAnimals were habituated to a metabolic cage and injected with either Sal B, acetonitrile or saline. Urine samples were collected during the habituation period and used as an additional control. On the day of the experiment, urine was collected during two 15 min control periods followed by six 15 min periods beginning 15 min after the ICV injection into the lateral ventricle. After 90 minutes, animals were perfused with phosphate buffer and PFA. Brains were removed and cut on a cryostat (40 μm thick). Brain sections were processed for c‐Fos using a commercially available antibody. Sections were double labeled with dopamine beta‐hydroxylase (DBH; CY3 Anti‐mouse) to define anatomically specific hindbrain regions.ResultsICV Sal B failed to produce any significant changes to renal function (urine volume, sodium and potassium excretion rate) as compared to control vehicle. Sal B decreased c‐Fos expression in the medial nucleus of the solitary tract (NTS‐m) and rostral ventrolateral medulla (RVLM), and noradrenergic cell group (A5).ConclusionPrevious studies suggested that Sal B has affinity for the KOR; however, our results indicate that Sal B lacks efficacy and does not produce diuretic or anti‐natriuretic effects associated to synthetic kappa opioid agonists. In addition, KOR agonists increase renal sympathetic nerve activity via changes to cardiovascular controlling centers in the brain. Sal B decreased c‐Fos expression in certain hindbrain regions, but further studies are necessary to determine the role Sal B plays in these regions.
Effects of the Gut Microbiome on Aged‐Related Cognitive Decline and Inflammation
Authors: Lee Juneyoung , Venna Venugopal R. , Durgan David J. , McCullough Louise D. , Bryan Robert M. 
Published: April 2020

IntroductionAging is associated with low level inflammation and cognitive decline. We tested the hypothesis that the gut microbiome has a major role in these age‐related changes and that this age‐related decline is transferrable through the gut microbiome in mice.MethodsFor this study we gavaged a suspension of fresh fecal contents from aged (~20 months) or young (~3 months) BL/6 mice into germ‐free BL/6 mice (N=10 per group). The absence of gut bacteria in germ‐free mice reduced competition and enhanced the colonization of the aged or young microbiomes. Gavages began in the germ‐free mice at 12 weeks of age and were repeated monthly for 3 months. Behavioral testing and collection of fecal samples occurred over the study period. After 3 months, mice were euthanized, and the brain and colon were harvested for assessing the inflammatory state using flow cytometry. Bacterial community structures and relative abundances were measured in fecal samples by sequencing the bacterial 16S rRNA gene. Short‐chain fatty acids (SCFA) were measured in feces using LC‐MS.ResultsMice with an aged microbiome demonstrated depressive‐like behavior, impaired short‐term memory, and impaired spatial memory for at least 3 months after the initial gavage using the tail‐suspension (P=0.008), the Novel Object Recognition (P<0.001), and the Barnes Maze (P=0.019) tests respectively. The aged microbiome increased inflammation as revealed by flow cytometry studies. In brain γΔ T cells were increased (P=0.017) with an aged microbiome. In the gut, leukocytes were increased (P<0.001) and Tregs were decreased (P=0.029) with an aged microbiome. Mice with aged and young microbiomes showed clear differences in bacterial α diversity (Simpsons and Fisher, P<0.001 for both) and β diversity (weighted and unweighted PCoA, P=0.001 for both). At 3 months after the initial gavage, the bacteria families, Defluviitaleaceae and Lactobacillaceae, were significantly decreased in mice with aged microbiomes (P<0.001 and P=0.01 respectively). Fecal SCFAs, including acetate, propionate, and butyrate (P<0.01 for each), were decreased in mice with an aged microbiome. These 3 SCFAs are gut protective and anti‐inflammatory. Of note, Lactobacillus, a SCFA‐producing genus, was decreased 3‐fold in mice with an aged microbiome (P=0.009).ConclusionWe conclude that the gut microbiome has a major role in aged‐related cognitive impairment and inflammation. Furthermore, cognitive decline and an enhanced inflammatory state associated with aging can be transferred via the gut microbiome. Thus, manipulating the gut microbiome can protect from the detrimental effects associated with aging.Support or Funding InformationRO1 AG058463 (RMB and LDM)RO1 NS103592 (LDM and RMB)
Effect Of Sodium Azide And DDVP On Liver And Kidney Parameters Of Albino Rats
Authors: Agbasi Patrick Ugochukwu , Chukwu Leo Clinton , Ugorji Toochukwu Nze , Anyiam Chioma Kesiah , Daniel Jovita Ada 
Published: April 2020

BackgroundIn the Sub Sahara Africa, organophosphorous insecticides are extensively and intensively used in the living houses, offices and even against pests to preserve foods and agricultural products to preserve farm produce. Sodium azide (a herbicide) is also extensively used in the farms to control weeds. These conditions have necessitated this study.PurposeThis research is designed to investigate the effect of low dose DDVP (dichlorvos) and sodium Azide co‐administration on some kidney and liver biochemical parameters of Albino rats bearing in mind the rising cases of liver diseases and kidney failures.MethodSeven groups of five rats each were used for the study. Group A was used as control and received no chemical treatment, groups B and C were injected with 1% and 3% LD50 of Sodium Azide respectively, while groups D and E received 1% and 3% LD50 of DDVP respectively. Equally, group F received combined doses of 1% LD50 of DDVP and 1% LD50 of Sodium Azide while group G received 3% LD50 of DDVP and 3% of LD50 Sodium Azide. The chemicals were administered at alternate days for twenty one days. At the end of twenty one days study period, the animals were anesthetized with chloroform and blood were aspirated through cardiac puncture into empty clean 5ml containers and then allowed to clot. The serum were then separated and frozen before kidney and liver parameters were carried out.ResultsSodium Azide caused significant reduction in liver transaminases, alkaline phosphotase and elecyrolytes (Na and K) while the creatinine level was not affected. DDVP, caused significant increases in the transaminases, Alkaline phosphotases while also causing causing significant reductions in urea, creatinine and the electrolytes when compared to control. Sodium Azide and DDVP caused significant reduction of the transaminases and urea while the creatinine level is unaffected.ConclusionSodium Azide caused significant reduction in liver transaminases, alkaline phosphotase and elecyrolytes (Na and K) while DDVP caused significant increases in the enzymes and reductions in the urea and creatinine. Co‐administration of DDVP and Sodium Azide produced significant reduction of the transaminases, alkaline phosphotase and urea.
The inhibitory effects of Ganoderma Lucidum on NFκB related inflammatory cytokines in activated BV‐2 microglial cells
Authors: Hilliard Aaron , Mendonca Patricia , Soliman Karam F.A. 
Published: April 2020

Neurodegenerative diseases have increased significantly over the last five years, and the increase in the elderly with Alzheimer’s and dementia requires increased attention and research design to combat this critical problem. Ganoderma Lucidum extract (GLE) is a potent ancient Asian remedy for extending the life and treatment of a variety of disease states. In the current study, we investigate the neuroprotective potential effects of Ganoderma Lucidum on LPS‐activated BV‐2 microglial cells. The LPS activated BV‐2 cells have been largely used as a model to illustrate the pro‐inflammatory process involved in the activation of signaling transduction pathways associated with neuronal injury. The methodology used in this work included cell viability, nitric oxide assay, screening of pro‐inflammatory cytokines using mouse cytokine arrays, individual ELISAs to validate data from the arrays, and RT‐PCR to investigate a possible signaling pathway for GLE neuroprotective effect in activated BV‐2 microglial cells. Cell viability results showed that increasing concentrations of GLE, ranging from 0.5 to 1.3 mg/ml, induced BV‐2 cytotoxicity in a dose‐response manner (IC50: 0.79 mg/ml). Also, the results obtained indicate that lower concentrations of GLE (< 0.5mg/ml) showed to be potent in reducing the release of nitric oxide in activated BV‐2 cells. The results from the cytokine arrays showed that GLE decreased the expression of several pro‐inflammatory cytokines including Granulocyte Colony Stimulating Factor (G‐CSF), Interleukin 1‐alpha (IL1‐α), Monocyte chemotactic protein‐5 (MCP‐5), Macrophage Inflammatory Protein 3 Alpha (MIP3‐α), and Regulated on Activation Normal T Expressed and Secreted (RANTES). The data obtained were further validated using individual ELISA, and the results showed that GLE was able to decrease the expression of each one of the downregulated proteins in the cytokine arrays. RT‐PCR was performed using different genes that are involved in the NFκB signaling activation. The results also showed that GLE decreases the mRNA expression of CHUK, NFκB 1/p150, and IKBKE, which are genes that participate in the NFκB translocation to the nucleus, and subsequent release of pro‐inflammatory cytokines. The findings suggest that GLE may be a new potential therapeutic option for decreasing inflammatory responses seen in Alzheimer’s and dementia patients.Support or Funding InformationSupported by a NIMHD Grant U54 007582
Mechanistic role of Gαo in striatal cAMP signal transduction
Authors: Muntean Brian S. , Sutton Laurie P. , Zucca Stefano , Dao Maria , Patil Dipak N. , Birnbaumer Lutz , Martemyanov Kirill A. 
Published: April 2020

The G protein alpha subunit o (Gαo) is abundantly expressed in the nervous system and pathogenic mutations in its gene (GNAO1) cause movement disorder. In contrast to the other Gα subunits, Gαo has been relatively understudied and its function remains mechanistically ill defined. Using biochemical assays, optical imaging in primary neurons, and genetic mouse models we define mechanisms of Gαo action on the cAMP generating enzyme – adenylyl cyclase (AC) in a neuron subtype selective manner. Here, we show that Gαo transduces striatal signals to enable motor learning by opening an alternate signaling channel regulating dynamics of neuromodulatory interrogation of dopamine to the second messenger cAMP. We find that Gαo is a critical modifier of striatal AC activity through horizontal interplay with other G protein subunits. Gαo modulates Gβγ availability to impact processing of signaling by AC that sensitizes stimulatory inputs (Gαs/olf) while diminishing efficacy of inhibitory inputs (Gαi). These processes accompany adjustments in electrophysiological properties of striatal neurons that compromise motor learning in a circuit‐selective fashion. Based on our findings we propose a model for Gαo in programming motor command processing of GPCR signals to cAMP.Support or Funding InformationThis work was supported by funding from the following NIH grants: DA041207 (to BSM), DA048579 (to SZ), and DA036596, DA026405 (to KAM).