bluuebunny/crossref_metadata_2025_split huggingface dataset:
dkNET (NIDDK Information Network): Research tools that assist scientists in improving the rigor and reproducibility of their research
Authors: Lin Ko‐Wei , Bandrowski Anita E. , Gillespie Tom , Go James , Hagstrom Stephanie , Hsu Chun‐Nan , Ozyurt Ibrahim B. , Grethe Jeffrey S. , Martone Maryann E. 
Published: June 2021

The use of problematic resources such as contaminated or misidentified cell lines and cross‐reactive antibodies lead to reproducibility problems. Research has shown that about twenty percent of published studies use contaminated cell lines [1]. Many factors, including the ability to easily retrieve alert information, result in the continued use of these resources wasting both time and money. Research Resource Identifiers (RRIDs) are unique identifiers for resources that assist finding, identifying, and tracking antibodies, cell lines, biological samples, organisms, and digital resources in the published literature [2]. RRIDs currently appear in over 8000 papers across 600 biomedical journals. Because authors have to supply RRIDs in their manuscripts ahead of publication, RRIDs provide a unique means for disseminating information about resource performance. For example, a search in the RRID portal (Nov 14, 2018) found 802 problematic cell lines (contaminated and/or misidentified cell lines) out of 101528 cell lines, as reported by the International Cell Line Authentication Committee (ICLAC). Analysis of cell lines in published papers using RRIDs vs those that didn't use RRIDs, showed the reported use of contaminated cell lines is significantly lower in papers with RRIDs than in the average paper [3], suggesting that making researchers aware of problematic resources may decrease their usage. To make it easier for researchers to find complete information, the NIDDK Information Network (dkNET.org) used RRIDs to develop several tools to help scientists enhance research rigor and reproducibility. dkNET introduced Resource Reports, a detailed overview of each resource identified by an RRID, including the characteristics of the resource, any warning and alert information, citation metrics from the biomedical literature and validation and rating information. Resource Reports let a researcher “follow” a resource, receiving up to date information on the usage of the resources they used (or created) in the literature. dkNET also offers a Rigor and Reproducibility tool that can generate an authentication report for grant applications in support of the NIH mandate on authentication of key biological resources. RRIDs and the associated tools and services make it easier for information on resource performance to be tracked and disseminated.Support or Funding InformationNIH NIDDK Grant U24DK097771This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Adolescent in Stress, Depression and Violence in NigeriaGertrude Bassey, George P. Einstein, Orien L. Tulp College of Medicine, Einstein Medical Institute, Montserrat, B.W.I
Authors: Bassey Gertrude 
Published: June 2021

BackgroundThe studies have examined how multiple settings and experiences of violence are associated with depression and how these influence teens to be violence perpetrators. This research sets out to trace how the experience of violence among teens can lead to depression and also lead to teens being violent themselves.MethodsYouths were asked several items to measure their levels of family conflict, amount of violence they have observed, and violent victimization. Self‐report questionnaires were administered to the 500 youths. Types of violence explored included: Psychological abuse, Physical violence in home, Intimate partner violence, School witnessed violence, School violence victimization, and Neighborhood witnessed violence.Multiple latent class analyses were performed to identify adolescents with common patterns of violence exposure and to find classes with the best fit.ResultsPrevention towards adolescents by school clinic, and individual counseling need to be followed. Law enforcement agencies need to respond to cases of violence. Symptoms of post‐traumatic stress disorder and depression is related to violence. Anxiety symptoms only to exposure to violence perpetrated by someone known to the child or in the home.ConclusionExposure to a high magnitude of violence within a single domain or multiple domains portrays significant risk for Depression and Anxiety. Violence is associated with the highest risk for psychopathology.The results suggest that it may be beneficial to direct efforts at prevention and treatment towards adolescents at high risk for violence within multiple domains of life, as these individuals may face greatest risk for depressive and anxiety disorders and also become perpetrators of violence.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cyclooxygenase‐2 Regulates the Renal Expression of Indoleamine 2,3‐dioxygenase
Authors: Mutsaers Henricus A.M. , Jensen Michael Schou , Olinga Peter , Nørregaard Rikke 
Published: June 2021

Chronic kidney disease (CKD) affects approximately 10% of the population. In CKD patients, the majority of metabolic pathways are in disarray, which most likely contributes to the wide variety of comorbidities observed in these patients. However, few studies have focused on the unique regulatory aspects of enzyme systems during CKD development and progression. The cyclooxygenase‐2 (COX‐2)/prostaglandin (PG) system plays a dominant role in the progression of renal injury. Interestingly, it has been shown that the COX‐2/PG system modulates the activity of indoleamine 2,3‐dioxygenase (IDO) in tumors. Catabolism of tryptophan by IDO gives rise to numerous biologically active metabolites implicated in CKD progression. Therefore, the aim of this project is to explore the interplay between the COX‐2 and IDO enzyme systems during renal injury.We studied the gene expression of IDO, COX‐2 as well as several fibrosis and inflammatory markers in human and murine precision‐cut kidney slices (PCKS) and COX‐2 KO mice. Furthermore, we evaluated the gene expression profile after treatment with butaprost, an EP2 receptor agonist, in hPCKS and following treatment with SC‐236, a selective COX‐2 inhibitor, in mPCKS.Our results demonstrated that IDO gene expression was markedly increased in both human and mouse PCKS during the first 24h of culturing, after which levels dropped again. This expression profile was similar to the gene expression of various cytokines (e.g. IL‐6 and CXCL1), suggesting a potential pro‐inflammatory role of IDO. In addition, in COX‐2 KO animals, constitutive gene expression of IDO was increased as compared to wild‐type mice, and the knockout animals appeared to be more prone to renal fibrosis. Moreover, treatment with butaprost suppressed IDO gene expression, while exposure to SC‐236 induced IDO mRNA expression as well as the gene levels of IL‐6 and IL‐8.Taken together, it appears that COX‐2 suppresses IDO gene expression. In addition, our findings suggest a potential pro‐inflammatory role of IDO. However, the precise role of IDO in CDK development and progression requires further study.Support or Funding InformationThis work was kindly supported by Lundbeckfonden, grant number R231‐2016‐2344.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Therapeutic potential of commercially‐available cannabidiol oil for Alzheimer's disease using Caenorhabditis elegans as a model
Authors: Flores‐Narvaez Molishka A , Ramos‐Ortolaza Dinah Lee 
Published: June 2021

Alzheimer's disease (AD) is a neurodegenerative disease linked to loss of cognitive and motor abilities. The neurodegeneration is thought to be caused, in part, by the accumulation of Aβ peptides in the brain. Currently, there is no cure for AD, and the available treatments are rather limited in scope. Most of them are aimed at treating the symptoms, not preventing or reversing the progression of the disease. Recent studies have suggested a therapeutic potential for cannabidiol (CBD), a component of the Cannabis sativa plant. Both, in vitro and in vivo studies have shown improvement in some of the physiological and cognitive signs of the disease, suggesting it may be a better therapeutic strategy compared to current treatments. Given CBD's therapeutic potential and the increase in availability of commercial over‐the‐counter CBD‐based oils, this study is aimed at assessing the therapeutic potential of these products using an invertebrate model of AD. To achieve our aim, we decided to use a transgenic Caenorhabditis elegans worm strain that expresses human Aβ in neurons (CL2355). This is an inducible strain that shows behavioral deficits that make it a suitable model for AD. Prior to treating the animals, a toxicity assay was performed with several concentrations of a commercially available CBD oil. Although more animals need to be tested, preliminary results showed no significant effect of the CBD oil on the worms' mortality. Once we determine the optimal concentration of CBD, Aβ expression will be induced in synchronized animals from the CL2355 strain by a temperature upshift. This will be followed by a 24‐hour exposure to the CBD oil or the vehicle. By the time the CBD exposure ends, the animals will be adults, and behavioral testing will be performed. Specifically, we will perform a thrashing and a short‐term associative learning assay to test for locomotor and memory deficits respectively. Results from this study will allow us to determine whether commercially‐available CBD oils can either prevent or alleviate some of the deficits associated with AD and will support the use of invertebrate models to further explore new possibilities for the development of therapeutic strategies for AD and other neurodegenerative disorders.Support or Funding InformationPUCPR‐PR Louis Stokes Alliances for Minority ParticipationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AMB‐FUBINACA (FUB‐AMB) and related "spice" compounds induce gene‐dose effects in mice lacking cannabinoid‐1 receptor (CB1R) alleles
Authors: Baumann Michael H. , Fedorko Julie M. , Prisinzano Thomas E. , Garibay Nancy 
Published: June 2021

Synthetic cannabinoids (SCs), commonly known as ‘K2' or 'spice’, are a constantly evolving class of new psychoactive substances that pose public health risks. Little information is available about novel SCs when they first emerge into the recreational drug marketplace. In this study, we investigated the pharmacology of AMB‐FUBINACA (FUB‐AMB) and 5F‐AMB, two recently encountered indazole‐based SCs responsible for mass intoxications and fatalities. The effects of known cannabinoid‐1 receptor (CB1R) agonists AM‐2201 and Δ9‐THC were examined for comparison. Groups of genetically‐engineered mice lacking CB1R alleles (CB1R −/− and CB1R +/−), and their C57Bl/6J wild‐type (WT) counterparts, received surgically‐implanted subcutaneous (s.c.) temperature transponders under isoflurane anesthesia. Beginning one week after surgery, mice received s.c. injection of either SCs or vehicle and were subjected to a “triad” test battery consisting of sequential assessment of: 1] body temperature, 2] catalepsy bar latency and 3] hot‐plate analgesia latency. All SCs induced significant dose‐ and time‐dependent hypothermia, catalepsy and analgesia in WT mice, which lasted up to 120 min. The rank order of potency was FUB‐AMB>5F‐AMB=AM‐2201>Δ9‐THC. Importantly, ED50 values in the triad test battery for FUB‐AMB (0.09–0.22 mg/kg, s.c.) were at least 50‐fold more potent than those associated with Δ9‐THC (12.72–30.37 mg/kg, s.c.), and SCs were more efficacious in their ability to produce hypothermia. Homozygous CB1R −/− mice were not affected by any dose of the compounds tested, whereas heterozygous CB1R +/− mice displayed responses intermediate between homozygous and WT. CB1R binding assays in WT mouse brain revealed that IC50 values for inhibition of [3H]SR141716 binding were 1.2, 2.2, 12.6 and 50.6 nM for FUB‐AMB, AM‐2201, 5F‐AMB and Δ9‐THC, respectively. Our findings demonstrate that newer indazole‐based SCs exert their effects via potent agonist actions at CB1R, and do not support the notion that SCs induce in vivo effects by non‐CB receptor mechanisms. Given the widespread abuse of synthetic cannabinoids, CB1R antagonists should be made available for overdose rescue, and medical marijuana could be deployed as an agonist treatment for dependence on these substances.Support or Funding InformationThis research was generously supported by IRP, NIDA, NIH (DA00523)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Corticotropin Releasing Factor Invigorates Cocaine‐Seeking via CRF‐R2 in the Nucleus Accumbens Core
Authors: Leonard Michael Z. , Miczek Klaus A. 
Published: June 2021

Adverse life events often precipitate the initiation of– and relapse to– cocaine use in drug‐dependent individuals. For example, acute stressors can potently exacerbate the extent to which drug‐related stimuli elicit craving to seek and procure drug, perhaps via peptidergic modulation of mesolimbic dopamine transmission. Indeed, dopaminergic signaling within nucleus accumbens core (NAcc) is critical to guiding motivated behavior in response to rewarding or aversive stimuli. The present studies, therefore, examine the site‐specific actions of the stress peptide corticotropin releasing factor (CRF) as a putative substrate for stress‐potentiated arousal. First, we assessed extent to which pharmacological manipulation of CRF within the NAcc alters instrumental responding for cocaine; and, in a second set of experiments, we begin to characterize the conditions under which CRF modulates local dopamine transmission. To that end, male Long‐Evans rats were trained to self‐administer cocaine intravenously under a chained schedule of reinforcement (FI‐FR) in order to dissociate appetitive (‘drug‐seeking’) from consummatory (‘drug‐taking’) behavior. Completion of a fixed interval (5min.) was followed by 10 min of continuously reinforced responding (0.4mg/kg cocaine; FR1) on another lever. After training, rats were microinjected with CRF (50 or 500ng/side) into the NAcc prior to self‐administration sessions. Microinfusion of CRF dose‐dependently increased responding during the fixed‐interval link of the chain schedule, but did not affect subsequent cocaine intake. These effects were CRF‐R2‐dependent, as CRF‐potentiated responding was prevented by pretreatment with Astressin‐2B (1000ng/side), but not CP376395 (500ng/side). Astressin‐2B was also sufficient to attenuate cocaine‐seeking responses when administered alone. Parallel microdialysis studies revealed CRF is endogenously released into the NAcc during acute stress exposure (i.e. social defeat) and, moreover, that perfusion of CRF into the NAcc is sufficient to elicit a robust increase in extracellular dopamine. Ongoing studies aim to clarify the role for CRF‐R2 in moderating this function in cocaine‐experienced rats. Taken together, these data suggest a role for CRF‐R2 in modulating appetitive drug‐seeking behavior, perhaps via interactions with NAcc dopamine, which may offer insight into the substrates of stress‐potentiated relapse. CRF‐R2 may therefore represent a worthy therapeutic target for cocaine use disorder, despite the initial clinical shortcomings of CRF‐R1‐related compounds.Support or Funding InformationNIDA grant DA031734 to KAMThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessing the cognitive‐enhancing effect of desformylflustrabromine in rat model of Aβ‐induced cognitive impairment
Authors: Deba Farah , Munoz Kemburli , Peterson Steven L , Hamouda Ayman K 
Published: June 2021

Accumulation of β‐Amyloid peptides (Aβ)‐containing plaques, perturbation of the neocortical cholinergic pathways, and loss of brain acetylcholine receptors (AChR) are hallmark characteristics of Alzheimer's disease (AD). Several AChR subtypes are expressed in the cortex and the hippocampus and play essential role in learning, memory, and neuronal survival during ageing. Indeed, three out of the only four FDA‐approved drugs for AD are inhibitors of acetylcholinesterase, the enzyme responsible for ACh degradation. In addition, stimulation of α4β2 nAChRs have been shown to protect against Aβ1‐42‐induced cell death in cultured cortical neurons and to improve working memory and cognition in abstinent smokers. Because drugs that enhance the α4β2 nAChR would be beneficial for the treatment of the cognitive decline associated with many neuropathologies including AD, we focus on selective targeting of the α4β2 nAChR using positive allosteric modulators (PAM). PAMs of nAChR enhance ACh signaling without alteration of cholinergic transmission due to the prolonged activation and desensitization of nAChRs seen with agonists. In this study, we examine the cognitive‐enhancing effect of the α4β2 nAChRs PAM, desformylflustrabromine (dFBr), in a rat model of cognitive impairment. dFBr isolated originally from the marine bryozoan Flustra foliacea then its chemical synthesis and interaction with nAChRs in vitro were illustrated. In two‐electrode voltage clamp recording from Xenopus oocyte, dFBr potentiated ACh‐induced currents of low‐sensitivity (α4)3(β2)2 and high‐sensitivity (α4)2(β2)3 nAChRs maximally by ~300 and ~400% and with IC50s of ~0.4 and ~2 μM, respectively. In preliminary study, we tested the effect of two daily treatments of 10 mg/kg dFBr on rats' performance in passive avoidance test measured 10 days after intracerebroventricular (ICV) injection of vehicle (sham) or Aβ1‐42. dFBr treatment increased retention time (the time spent in the light compartment before entering the dark compartment that is associated with mild foot shock) in both naive (sham injected) and rats with AD‐like cognitive impairment (Aβ1‐42 injected). Experiments are in progress to evaluate the effects of dFBr on rats' performance in other learning and memory paradigms such as the 8‐arm radial maze.Support or Funding InformationUniversity of Texas System Rising STARs Program FundThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
LW‐AFC Attenuates LPS‐Induced Neuroinflammation via Inhibiting Nuclear Factor‐ Kappa B Signaling
Authors: Liu Gang , Wang Jianhui , Zhou Wenxia , Zhang Yongxiang 
Published: June 2021

Neuroinflammation and activation of microglia have been recognized as important pathological events in Alzheimer's disease (AD). LW‐active fraction combination (LW‐AFC) is extracted from Liuwei Dihuang decoction (LW), a classic traditional Chinese medicinal prescription. It has been demonstrated that LW‐AFC had neuroprotective effects on AD animal models. However, whether anti‐inflammatory effect contributes to the neuroprotection of LW‐AFC has not been fully elucidated. The present study aimed to evaluate the effects of LW‐AFC on neuroinflammation and its underlying mechanisms. C57 mice were intraperitoneally injected with lipopolysaccharide (LPS) and treated with LW‐AFC (i.g.). The results revealed that LW‐AFC significantly improved the hippocampal long‐term potentiation (LTP) and decreased the contents of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in the serum and hippocampus of the LPS‐treated mice. In vitro study showed that LW‐AFC inhibited LPS‐induced activation of BV‐2 cells and markedly reduced the increases of TNF‐α and IL‐1β levels in the supernatant of LPS‐treated BV‐2 cells. In addition, LW‐AFC downregulated the expression level of NF‐κB in LPS‐treated BV‐2 cells. The present findings indicate that LW‐AFC might attenuate neuroinflammation both in animal and cell model, which may contribute to its neuroprotective effect in AD treatment.Support or Funding InformationProject supported by the National Natural Science Foundation of China (81503078)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Melanin‐concentrating hormone‐R1 in the locus coeruleus may be involved in the regulation of depressive‐like behavior
Authors: Zhang Yong‐He , Ye Hui , Cui Xiang‐Yu , Cui Su‐Ying 
Published: June 2021

BackgroundPrevious anatomical and behavioral studies have shown that melanin‐concentrating hormone (MCH) is involved in the modulation of emotional states. However, little is known about brain regions other than the dorsal raphe nucleus that relate the MCH‐ergic system to depressive states. Numerous studies have shown that the locus coeruleus (LC) is involved in the regulation of depression and sleep. Although direct physiological evidence is lacking, previous studies suggest that MCH release in the LC decreases neuronal discharge. However, remaining unclear is whether the MCH‐ergic system in the LC is related to depressive‐like behavior.MethodWe treated rats with an intra‐LC injection of MCH, intracerebroventricular injection of MCH, or chronic subcutaneous injections of corticosterone to induce different depressive‐like phenotypes. We then assessed the effects of the MCH receptor 1 antagonist SNAP‐94847 on depressive‐like behavior in the forced swim test (FST) and the sucrose preference test (SPT).ResultsThe intra‐LC and intracerebroventricular injections of MCH and chronic injections of corticosterone increased immobility time in the FST and decreased sucrose preference in the SPT. All of these depressive‐like behaviors were reversed by an intra‐LC microinjection of SNAP‐94847.ConclusionsThese results suggest that the MCH‐ergic system in the LC might play an important role in the regulation of depressive‐like behavior.Support or Funding InformationThis study was funded by grants from the National Natural Science Foundation of China (No. 81573407, 81872851, 81871038 and 81302746).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.