bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron supplementation and iron deficiency anemia impact malaria pathogenesis (LB472)
Authors: Clark Martha , Goheen Morgan , Kasthuri Raj , Cerami Carla 
Published: June 2021

Iron deficiency is the most widespread nutritional deficiencies in the developing world and iron is commonly administered compounds through mass distribution campaigns. However, recent evidence suggests that iron deficiency may protect against malaria and that iron supplementation may increase susceptibility to malaria, complicating recommendations for universal supplementation in malaria‐endemic regions. It has been previously hypothesized that iron deficiency inhibited malaria growth through iron deprivation, as is the case with other pathogens. However, our work has generated a novel hypothesis for the effect of iron deficiency and iron supplementation on parasite growth ‐ namely that changes in RBC physiology and RBC age population structure drive resistance of RBCs from IDA donors and increased susceptibility of RBCs from iron supplemented IDA donors to malaria Using an in vitro system with RBCs from donors with well‐defined physiological iron states, we have investigated the cellular mechanisms associated with malaria protection by iron‐deficiency anemia (IDA). We described multiple IDA impacts on parasites, including attenuated invasion of IDA red blood cells (RBCs) and reduced production of parasite progeny. We demonstrate that as iron deficient individuals increase their rate of erythropoiesis in response to iron supplementation, their RBCs becomes more susceptible to infection. Additionally, we show that the replacement of iron deficient RBCs with young normocytic iron‐replete RBCs increases susceptibility to P. falciparum infection. Our results provide a cautionary message to well‐intentioned public health workers who follow the current World Health Organization recommendation to routinely provide iron supplements to iron‐deficient children.Grant Funding Source: National Institute of Child Health and Human Development under award number U01HD061235
A Preliminary Consumer Survey for Aesthetic Design and Development of a Mobile Health Application for DIY Diagnosis of 21 Common Acute Diseases (LB478)
Authors: Stewart Kennedy , Skibsted Michele , Federico Niksha , Federico Tessya , Federico Cybele , Esmaeli‐Azad Babak 
Published: June 2021

The myriad shortcomings of the healthcare system are self‐evident. Issues ranging from lack of access, to high cost of services, to widely variable quality of care are endemic not only in the US but also worldwide. Efforts to address these issues have met with limited success. To effect real change, fundamental movement in current practice, technologies generated by a synergy of fresh ideas, emerging technologies, and “disruptive” integration and approaches is necessary. Key to widespread adoption will be a focus on the user rather than the devices and technical capabilities. Technology by itself is not transformative ‐ it requires framing and usability that provides value to individuals and groups of people.We are currently developing a mobile health solution for self diagnosis of 21 indications as a solution for the Qualcomm Medical Tricorder X Prize Competition: team “SMART McCoy”. Medical testing generally evokes fear and discomfort, presenting significant barriers to be overcome before an instrument is adopted for regular at‐home use. A key element to our solution lies in the user experience and interface engaging people to medically test themselves. This unique capability is brought to bear on the challenge of making the Tricorder technical capabilities friendly, engaging and even fun using virtual human and avatar interface. Through collaboration our team has close ties with the entertainment industry, especially in games and narrative, and these “soft skills” will be applied to bringing digital health to analog humans.To determine consumer experience and refine our design and development strategies, we have devised a consumer survey based on questions and answers that attempt to engage consumers to test their own ailments using our mobile health solutions. Results of this preliminary survey, our conclusions, and modifications to the mobile health solution for the Qualcomm Medical Tricorder X Prize Competition will be presented.
Tungsten Carbide‐Cobalt Nanoparticle induced miR‐21 Expression and PDCD4 Inhibition in JB6 Cells Involves a ROS‐ Mediated ERK Pathway (LB486)
Authors: Ding Min 
Published: June 2021

Tungsten Carbide‐Cobalt Nanoparticle induced miR‐21 Expression Involves ROS‐ Mediated ERK PathwayMin Ding1, Lichao Hou1,, Linda Bowman1, Terence G. Meighan1, Jun Liu2 Xianglin Shi3, 1Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505, 2Department of Physiology & Pharmacology, West Virginia University, Morgantown WV 26505 3Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40503Abstract Tungsten Carbide‐Cobalt (WC‐Co) nanoparticle composites have wide applications because of their hardness and toughness. WC‐Co has been classified as ‘probably carcinogenic’ to humans by the IARC. Earlier studies demonstrated that the tumor suppressor gene (PDCD4 and its upstream regulator miR‐21 may be considered as oncogenes for novel cancer prevention or anti‐cancer therapies. The present study examined the alterations of miR‐21‐PDCD4 signaling in JB6 cells after exposure to WC‐Co nanoparticles. The results showed that (1) WC‐Co caused PDCD4 inhibition in JB6 cells; (2) Exposure of cells to WC‐Co caused a significant increase of miR‐21, the upstream regulator of PDCD4, expression; (3) Inhibition of ERKs with U0126 reversed WC‐Co‐induced PDCD4 inhibition, but inhibition of p38 with SB203580 did not; and (4) ROS scavengers, N‐acetyl‐L‐cysteine and catalase, reversed the inhibitory effect of WC‐Co on PDCD4 expression, while superoxide dismutase promoted the inhibition. These findings demonstrate that WC‐Co nanoparticles induce miR‐21 expression and PDCD4 inhibition, which may be mediated through ROS, especially endogenous H2O2 and ERK pathways. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of WC‐Co‐induced carcinogenesis.Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for occupational Safety and Health.Grant Funding Source: US Government
Role of ROS Generation in Tungsten Carbide‐Cobalt Nanoparticles Induced Apoptosis in JB6 Cells (LB487)
Authors: Ding Min 
Published: June 2021

Role of ROS Generation in Tungsten Carbide‐Cobalt Nanoparticles Induced Apoptosis in JB6 CellsMin Ding1, JinshunZhao2, Linda Bowman1, Stephen Leonard1, JunLiu3 Vincent Castranova11Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV2Department of Preventive Medicine, Ningbo University, Ningbo, Zhejiang 3152113Department of Physiology & Pharmacology, West Virginia University, Morgantown WV 26505Tungsten Carbide‐Cobalt (WC‐Co) nanoparticle composites have wide applications because of their hardness and toughness. In this study, apoptosis and related signaling induced by WC‐Co were investigated. Electron spin resonance (ESR) and fluorescent staining indicated that both WC‐Co nano‐ and fine particles stimulated reactive oxygen species (ROS) generation. Catalase inhibits WC‐Co‐induced ROS as well as mitochondrial membrane permeability damage, indicating that H2O2 may play an important role in the cytotoxicity induced by WC‐Co. Further studies indicated that WC‐Co nanoparticles elicited a higher cytotoxicity and apoptotic induction than fine particles. Western‐blot analysis showed an activation of pro‐apoptotic factors including Fas, FADD, caspase 3, 8 and 9, BID, and BAX. Lamin A and beta‐actin were cleaved. Interestingly, WC‐Co particles also induced Bcl‐2, an anti‐apoptotic factor, up‐regulation. In addition, both cytochrome c and AIF were up‐regulated and released from mitochondria to the cytoplasm. The results demonstrate that apoptosis induced by WC‐Co involve both 'extrinsic' and 'intrinsic' apoptotic pathways and nanoparticles exhibit higher cytotoxicity and apoptotic induction than fine particles.Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the National Institute for occupational Safety and Health.Grant Funding Source: US Government
The male gender bias in autism may be due to preferential depletions of oxytocin and arginine‐vasopressin receptors positive neurons exposed to certain fragrances during fetal development (LB502)
Authors: Sealey Leanna , Bagasra omar 
Published: June 2021

The male gender bias in autism may be due to preferential depletions of oxytocin and arginine‐vasopressin receptors positive neurons exposed to certain fragrances during fetal development Leanna Sealey and Omar Bagasra M.D. Ph.D.Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. There is also evidence of impoverished language and empathy, and a profound inability to adopt another's viewpoint ‐ a failure to construct a “theory of mind” for interpreting another person's thoughts and intentions. In developed countries, it is now reported that 1%–1.5% of children have ASD, and in the US 2013 CDC report, approximately one in 80 children suffer from ASD. Although there is no reliable neurophysiological marker associated with ASDs, low levels of plasma oxytocin (OXY) and arginine‐vasopressin (AVP) have been reported. We have hypothesized that synthetic fragrances, which many of us are exposed to on a daily have potential to cause neurological damage to developing fetuses.Notably, the alarming rise in ASD parallels the rise in production of synthetic fragrances from petrochemicals and carcinogenic benzene‐based compounds. Numerous studies have shown that children with autism have significantly lower levels of OXY in plasma samples than their typical peers. Furthermore, in normal children, lower concentrations of OXY in plasma are associated with lower social and cognitive functioning. Here we show that male neuroblastoma cell lines, but not the female, exposure to fentomoles concentrations of certain fragments results in depletions of both OXY and AVP receptor + neurons. Our studies are the first to reveal a direct connection between fragrance exposures as the potential neuropathic agent that may cause autism and explains the gender bias.Grant Funding Source: Department of Education
Development of a quantitative assay for detecting pro‐inflammatory bacteria genes directly in human stool samples by real‐time Polymerase Chain Reaction (rtPCR) (LB515)
Authors: Gomez‐Moreno, BS Ramon , Baerga‐Ortiz, PhD Abel 
Published: June 2021

The human intestinal microbiota plays a key role in the maintenance of health and also in the development of intestinal disorders. Numerous studies have established the definitive association between the presence of certain intestinal bacteria in the flora and the development of gastrointestinal disorders. In this work, we developed an rtPCR assay for the detection of intestinal bacteria pro‐inflammatory genes directly from human stool samples. As a test case, we chose the pks genomic island genes that are present in some strains of intestinal Escherichia coli, and have been shown to induce, megalocytosis (figure 1), DNA damage, and aberrant inflammatory response. Metagenomic DNA was extracted from anonymous stool samples and used as the template for a rtPCR reaction. The fluorophore SYBR Green I was used to visualize the real time amplification response. The linearity for the SYBR Green I response with increasing amounts of input DNA was recorded in a standard curve with a correlation value of 0.9856. The fluorescence signal was detected in all pks+ samples after 18.97 cycles for HUO33, 19.24 cycles for HUO37, 16.61 cycles for HUO38 and 24.39 cycles for HUO47. As for the pks‐ samples, three of the samples the fluorescence signal was detected at cycle 9.65 for HUO31, 10.83 cycles for HUO39 and cycle 16.02 for HUO50. The fluorescence signal detected in pks‐ sample could be attributed to contamination between sample and non‐specific amplification. However, no fluorescence signal was detected in the negative control and the blank. Work is underway for the optimization of this assay towards the screening of patient samples.Grant Funding Source: This work is supported by the National Science Foundation (NSF) grant CHE0953254 to ABO and the National Institute of Health (NIH) grant R25GM061838 (MBRS RISE Program) to RGM
A high sensitive Homocysteine (hsHCY) assay improves the clinical usefulness of this cardiovascular and cancer predictive biomarker (LB520)
Authors: Liang Genqing , Jaffe Anna , Larkin Jamie , Jaffe Russell 
Published: June 2021

Elevated plasma Homocysteine (HCY) levels predict accelerated chronic diseases. A clinical limitation has been leakage into plasma of red cell HCY starting shortly after phlebotomy. A more stable specimen is needed especially at lower values.Specimens (N=20) were collected in EDTA tubes (current preferred specimen) and a novel cell preservative. Specimens were stored at 4±1°C until analysis. Plasma was isolated and analyzed at 0.5, 4, 8, 24, 48, 72, and 96 hours after phlebotomy using a Diazyme™ Analyzer 700 and statistically analyzed by one‐way ANOVA.HCY levels started to increase within 30 minutes in EDTA specimens while the new cell preservative sample values were stable for at least 48 hours. Indeed initial HCY levels in EDTA samples were typically 32% higher the new preservative (p<0.0001). This suggests that HCY is released to plasma from red blood cells in EDTA samples starting minutes after phlebotomy and less so in EAB cell preservative.Initial and more precise HCY can be measured and maintained for at least 48 hours when the EAB cell preservative is used as specimen anticoagulant. EDTA in contrast allows HCY increase that starts within minutes after blood draw. The reported cell preservative allows a more stable and accurate HCY assay for this predictive biomarker. More studies are needed to confirm the clinical and global predictive significance of this biomarker.
A cell adhesion molecule (Ig‐SF/hemolin) from caterpillar regulates cell survival and induces extracellular matrix components in human osteoarthritic chondrocytes (LB528)
Authors: Alvarez‐Flores Miryam , Bosch Rosemary , Antonioli Eliane , Pereira‐Junior Edgard , Ferretti Mario , Cohen Moises , Chudzinski‐Tavassi Ana 
Published: June 2021

Background: Losac is a hemolin from Lonomia obliqua caterpillar that promotes blood coagulation through proteolytic activation of factor X. In HUVECs, Losac increased cell proliferation and inhibited the apoptosis induced by starvation. Additionally, we have observed the cytoprotective effect of rLosac in other cell types, such as neurons and fibroblasts. Recombinant Losac (rLosac) was obtained from bacteria system. This report aims to investigate the potential of rLosac as a chondroprotective agent in human articular chondrocytes and to analyze its capacity to stimulate the production of extracellular matrix molecules and to reduce senescence. Methods: Primary cultures of human chondrocytes were prepared from cartilage of osteoarthritic knee joints obtained from 4 donors (age range: 68‐83) undergoing total knee replacement surgery. The study was carried out in full accordance with local ethics guidelines, and cartilage samples were collected after obtaining written informed consent of the donors. Chondrocytes were treated with rLosac and several parameters were measured: specific senescence‐associated beta‐galactosidase activity, cell viability by the MTT assay, production of extracellular matrix molecules by western blot and immunofluorescence microscopy, and cell cycle by flow cytometry. Results: rLosac was found to be an effective anti‐apoptotic agent, as evidenced by the strong inhibition of cellular death. The cytoprotective effect was observed specially starting from 48h and 72h of treatment, even in the presence of IL‐1β (50 ng/ml) to induce an inflammatory environment. Moreover, rLosac was able to reduce the expression of β‐galactosidade after 6 days of treatment. In addition, rLosac stimulated the production of collagen type I, laminin and fibronectin, and to increase the expression of the receptor of collagen type I, and to decrease the expression of IL‐1β. Conclusion: rLosac has the potential to become a therapeutic agent for protection of articular cartilage against the progression of osteoarthritic diseases.Grant Funding Source: CETICs/FAPESP (Processo No. 2013/07467‐1), CAPES, INCTTox‐CNPq
Biosensor‐based identification and characterization of three distinct calmodulin‐binding domains in the human angiotensin II receptor type 1A (LB569)
Authors: Ehlers Kevin , VerMeer Mark , Tran Quang‐Kim 
Published: June 2021

The angiotensin II receptor type 1A (AT1R) is responsible for many effects of angiotensin II (AngII). Calmodulin (CaM) is essential for many cell functions due to its interactions with many proteins. We tested the idea that signaling via AT1R involves CaM at the receptor level via multiple binding domains. AT1R coimmunoprecipitates with CaM in vascular smooth muscle under resting conditions, association that is enhanced by stimulation with AngII or thapsigargin. To identify all CaM‐binding domains in AT1R and characterize their binding properties, we generated FRET biosensors in which each the 4 sub‐membrane domains (SMDs) in AT1R is flanked by enhanced variants of yellow and cyan fluorescence protein. We named these biosensors BSAT1Rx, with x denoting the amino acid numbering of the SMD sequence. In response to purified Ca2+‐saturated CaM, BSAT1R125‐141, BSAT1R215‐242 and BSAT1R309‐327, corresponding to SMD2, SMD3 and the juxta membranous segment SMD4 in human AT1R, display drastic responses that are characteristic of conformational changes caused by direct binding of CaM. BSAT1R53‐64, corresponding to SMD1, does not response to Ca2+‐CaM. Titrations of biosensor responses with purified CaM yielded Kd values of 44.7±1.00, 0.36± 0.05, and 0.51±0.01 microM, respectively for SMD2, 3, and the juxta‐membranous segment of SMD4. The respective EC50(Ca2+) values of these interactions were 4.1±0.11, 0.13 ± 0.006, and 1.26 ± 0.09 microM, determined by monitoring concurrent responses of the respective BSAT1Rx and a suitable Ca2+ indicator. The entire SMD3 is involved in interaction with CaM, as a truncated domain (a.a. 215‐232) displays substantial decreases in affinity and Ca2+ sensitivity. These data demonstrate that CaM is involved in AngII signaling via direct interactions with multiple domains in AT1R and allow prediction of interactions between CaM and individual SMDs under distinct physiological scenarios, including resting and stimulated conditions.Grant Funding Source: National Institutes of Health
Anti‐depressant, cognitive, anxiolytic and anti‐convulsant evaluation of Lophira alata (Ochnaceae) stem bark in mice (LB629)
Authors: Iniaghe Loretta , Igbe Ighodaro , Magaji Mohammed , Tabot Tabot , Maduka Ijeoma 
Published: June 2021

Background: Stem bark and leaves of Lophira alata (Family: Ochnaceae) have been used traditionally for their anti‐psychotic, anti‐convulsant, analgesic and sedative properties.Objective/Aim: The study was carried out to evaluate some neuropharmacological properties of the aqueous extract of the stem bark of Lophira alata in animal models.Methods: Anxiolysis, depression, anti‐convulsion, memory and cognition were evaluated using animal models of these central nervous system indices.Results: Oral administration of Lophira alata extract (200‐800mg/kg) caused a significant (p<0.05) non‐dose dependent increase in the period of vigorous activity in both the forced swim and tail suspension tests. In the novel object recognition test, administration of the extract resulted in a positive discrimination index score; spontaneous alteration performance was slightly enhanced in the Y‐maze test. While significant decrease (p<0.05) in upwards climbs in the staircase test was recorded, number of head dips were not significantly reduced (p>0.05) in the hole board test. In the Pentylenetetrazole induced convulsion, a non‐dose dependent increase in onset of tonic‐clonic seizures and modest protection from death was recorded. These effects were comparable to standard drugs‐Imipramine, Diazepam, Scopolamine and Phenobarbitone.Conclusion: The results obtained suggest that the aqueous stem bark leaf extract of Lophira alata possesses neuropharmacological properties which may account for its use in Ethnomedicine.Grant Funding Source: Supported by personal funds
Lumbriculus variegatus as a model organism for studying angiogenesis during tissue regeneration (LB696)
Authors: Henry Charmaine 
Published: June 2021

Lumbriculus variegatus is an aquatic oligochaete that is often used to study epimorphic regeneration following removal of head or tail segments. In this pattern of regeneration, the cut surface forms a blastema in which undifferentiated cells begin to regenerate the lost tissues. L. variegatus fully regenerates lost tail segments within two to three weeks. While several studies have investigated the regeneration of neural networks during epimorphosis in L. variegatus, little is known about its pattern of angiogenesis during regeneration. We used L. variegatus cultures along with light microscopy and image capturing and analysis for daily in vivo documentation of the structural changes that occur during angiogenesis in regenerating tail segments. The transparent cuticle, closed circulatory system and erythrocruorin pigment in the plasma made the living vasculature visible for microscopic analysis. The branching pattern of new vasculature was easily observed. Pulsations of the dorsal blood vessel allowed tracking of blood flow to determine when new vessels became patent. A brief application of the anesthetic Tricaine reduced locomotion and facilitated the capturing of images. We suggest that this organism is a useful model to study the effects of angiogenic stimulators or inhibitors during wound healing and tissue regeneration.Grant Funding Source: Supported by Baker University Faculty Development Fund
Correlative super‐resolution light microscopy and electron microscopy determines spatial Ryanodine receptor type 2 distribution in mouse ventricular myocytes (LB707)
Authors: Das Tapaswini , Hakozaki Hiroyuki , Nitu Florentin , Bers Donald , Ellisman Mark , Cornea Razvan , Hoshijima Masahiko 
Published: June 2021

Couplons are uniquely formed microdomains which utilize calcium (Ca) as a primary messenger to trigger Ca release from the sarcoplasmic reticulum (SR) via SR‐localized ryanodine receptors (RyRs), leading to cell contraction. Despite the critical role these sites play in excitation‐contraction coupling, our quantitative understanding of couplon biology remains limited largely due to the fact that their size falls between the most practical performance limits of light and electron microscopic methods, rendering them difficult to visualize. Here we present cutting‐edge correlated microscopic imaging technologies for detailing the multi‐scale organization and distribution of RyRs in ventricular cardiomyocytes. Electron microscope (EM) tomography provides the unique ability to resolve organelle geometries and to quantify the 3D ultrastructure of couplons at an isotropic resolution of 3‐5 nm. To map RyR distribution, instead of relying on typical immunostaining techniques that are limited in resolution by the size of the antibodies, we used fluorophore‐tagged FKBP12.6 recombinant protein in light microscopy (LM). This probe provides the advantage of stoichiometrically labeling RyR2, which also makes it ideal for super resolution LM imaging. Thus, the molecular details attained by super resolution LM are correlated with high‐resolution 3D geometric maps reconstructed using EM tomography to determine the spatial distribution of RyR tetramers.Grant Funding Source: Supported by Human Frontier Science Program