bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐HT2 and 5‐HT2B Receptor Antagonism Regulates Fibrotic Potential of Peritoneal Fibroblasts in CAPD by Targeting TGF‐β1‐Src‐ERK1/2‐STAT3 Pathway
Authors: Chaturvedi Saurabh , Agarwal Vikas , Prasad Narayan 
Published: April 2020

Peritoneal fibrosis (PF) results in ultrafiltration failure in continuous ambulatory peritoneal dialysis (CAPD) patients. 5‐hydroxytryptamine (5‐HT; serotonin) induces extracellular matrix (ECM) synthesis in peritoneal fibroblasts in a transforming growth factor beta 1 (TGF‐β1) dependent manner. We evaluated anti‐fibrotic role of inhibitors of 5‐HT2 (Terguride) and 5‐HT2B (SB204741) in human peritoneal fibroblasts (HPFB) of CAPD patients. Peritoneal fibroblasts isolated fromCAPD patients (n=6) and controls (n=8), were incubated with 5‐HT (1μM)/TGF‐β1 (10ng/ml) for 1 hour and later with 5‐HT (1μM)/TGF‐β1 (10ng/ml) and terguride or SB204741 (1μM, each) for 24 hours (Post‐treatment strategy). In pre‐treatment strategy, cells were pre‐treated with terguride or SB204741 (1μM, each) for 1 hour and later with only 5‐HT (1μM)/TGF‐β1 (10ng/ml) for 24 hours. Real time PCR for pro‐fibrotic TGFB1, Type 1 collagen (COL1A1), Type 2 collagen (COL1A2), Actin alpha 2 (ACTA2), Connective tissue Growth factor (CTGF) and Fibronectin 1 (FN1) and anti‐fibrotic genes Matrix mettaloproteinase‐2/Tissue inhibitor of metalloproteinase (MMP2/TIMP1) expression was performed. Type I collagen and α‐SMA, phosphorylation status of Smad‐3, ERK1/2, Src and STAT‐3 was examined by western blotting.In 5‐HT/TGF‐β1stimulated HPFB, upregulated pro‐fibrotic gene expressionwas observed, which significantly reduced on co‐culture with 5‐HT2/5‐HT2B inhibitors, with no effect on anti‐fibrotic genes mRNA expression. In 5‐HT stimulated HPFB, treatment with both 5‐HT inhibitors decreased type 1 collagen and α‐SMA with reduced ERK1/2 phosphorylation (figure 1), however, Smad‐3 phosphorylation remain unaltered (figure 2). In 5‐HT/TGF‐β1 simulated HPFB, 5‐HT inhibitors decreased STAT3 phosphorylation, without affecting Src phosphorylation. 5‐HT receptor antagonists attenuate 5‐HT/TGF‐β1 mediated pro‐fibrotic potential of HPFB by suppressingTGF‐β1‐Src‐ERK1/2‐STAT3 pathway.Support or Funding InformationThis project received funding from intramural grant(Grant No ‐ 2017‐1‐IMP‐95) of Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Indaziflam herbicidal action: a potent auxin signaling inhibitor
Authors: Behnami Sara , Bonetta Dario 
Published: April 2020

Cellulose biosynthesis is a common feature of land plants. Therefore, cellulose biosynthesis inhibitors (CBIs) are useful tools in decoding fundamental aspects of cellulose biosynthesis. Here, we characterize the herbicide indaziflam, which has a unique mode of action for resistance management and appears to prevent plant growth by inhibiting cellulose biosynthesis and causes radial swelling and ectopic lignification; typical responses to treatment with CBIs. Previous work has demonstrated that Arabidopsis thaliana mutants that are indaziflam resistant can be identified through forward genetic screening. Since indaziflam is also active in the moss Physcomitrella patens, we took advantage of this system to attempt to understand the mode of action of indaziflam.Using UV‐induced mutagenesis, we generated mutants in Physcomitrella patens that were resistant to 30μM of indaziflam (izr), interestingly among the izr mutants; some were cross‐resistant to synthetic auxin 2,4‐D and NAA, which is predicted that indaziflam affects multiple pathways required for plant growth and development, since auxin affects the production and remodeling of plant cell wall either directly or indirectly. The izr mutants displayed a phenotype similar to that of auxin treated wild type plants, with small, undifferentiated, and leafless filaments, so we tested their responses to exogenous auxin, and it appears mutants were insensitive to synthetic auxin and started differentiation of chloronema to caulonemal filaments and gametophore development. To positionally clone the causative mutations, we have generated segregating populations by crossing the izr mutants with the Villersexel (Vx) wild type using a protoplast fusion technique.Our screen was designed to select mutant lines with indaziflam and auxin resistance; as a result, it establishes how critical elements within the indaziflam mode of action can refine auxin repressor activity, and have the long‐term developmental outcome. As a herbicide, indaziflam could potentially be used for weed management and eliminate the effects of these invasive grasses.Support or Funding InformationNSERC (The Natural Sciences and Engineering Research Council of Canada)
Mapping of the Neural Circuits that Control Intrinsic Lung Function
Authors: Sun Xin , Verheyden Jamie , Su Yujuan , Barr Justinn , Xu Albert 
Published: April 2020

The lung is commonly known as the gas‐exchange organ. However, given its vast surface area and direct exposure to the atmospheric environment, it is also an under‐recognized major sensory organ. The lung is exposed to signals such as oxygen, carbon dioxide, allergens, pollutants, pathogens, and subjected to mechanical stretch. Little is known on how these stimuli are sensed, processed and translated into distinct physiological outputs, including immune cell infiltration, airway tone and pulmonary blood pressure, all responses at the core of lung diseases. The lung is richly innervated. Multiple lines of evidence support that neural innervation controls many aspects of lung function. In this NIH SPARC funded research, we have used an array of cutting‐edge technologies to map the pattern determine the specific role of the neurons in modulating lung responses to inputs. Knowledge on the anatomical architecture as well as molecular code of the lung innervating neurons will set the foundation for modulating these circuits with precision.Support or Funding InformationNIH 1OT2OD023857‐01S3
Sodium Caprate Increases Electrogenic Anion Secretion via TRPV4, ATP‐P2Y and VIP‐VPAC1 Pathways in Rat Duodenum
Authors: Akiba Yasutada , Kaunitz Jonathan D. 
Published: April 2020

Although luminal short‐chain (SCFA) and long‐chain fatty acids (LCFA) stimulate mucosal protective duodenal bicarbonate secretion (DBS), the role of medium‐chain fatty acids (MCFA) in DBS has not been studied. Thus, we examined the effects of MCFA on DBS in vivo and short‐circuit current (Isc) in the Ussing chamber.MCFA (C6‐C12, 0.1 – 30 mM) were applied to the mucosal or serosal bath of the Ussing chamber mounted with the muscle‐stripped mucosa‐submucosa preparations of rat proximal duodenum. A duodenal loop was perfused with sodium caprate (C10, 1 mM) in anesthetized rats with total CO2 output measured.Among MCFA, sodium caprate (C10) dose‐dependently (1 – 30 mM luminally and 0.1 – 3 mM serosally) increased Isc, which was sustained > 10 min after reaching a plateau, whereas other MCFA (C6, C8, and C12) had little effect. The luminal caprate (10 mM)‐induced Isc increase was delayed by luminal addition of ibuprofen (1 mM), a sodium‐dependent monocarboxylate transporter‐1 (SMCT‐1) inhibitor. In contrast, serosal caprate (1 mM)‐induced Isc increase was partially inhibited by serosally applied ruthenium red (0.1 mM), the selective TRPV4 antagonist HC067047 (0.1 mM), suramin (0.5 mM) and abolished by the VPAC1 antagonist PG97‐269 (1 μM), whereas capsaicin pretreatment (10 μM), the selective TRPA1 antagonist HC030031 (0.1 mM), atropine (10 μM), or selective 5‐HT3 or 5‐HT4 receptor antagonists had no effect. The selective TRPV4 agonist GSK1016790 (10 μM) increased Isc, whereas the selective MCFA receptor GPR84 agonist ZQ16 had little effect on Isc. Luminal perfusion of caprate increased the rate of DBS in vivo.These results suggest that luminal caprate is absorbed via SMCT1, followed by stimulation of DBS via the TRPV4‐ATP/P2Y‐VIP/VPAC1 pathways in rat duodenum. This provides a new therapeutic pathway to enhance duodenal mucosal defenses.Support or Funding InformationVA Merit Review and Shire Pharmaceuticals
Evaluating Chlorophyll and Nitrogen Production in Edible Plant Sources Grown Under 5 Gigahertz Radiofrequency Radiation Emissions
Authors: Tabor Aaron J. , Greyeyes Shawna , Wilson Kobe 
Published: April 2020

By 2022 the demand for constant connectivity to high speed wireless communication networks is predicted to skyrocket with over 12 billion mobile devices and almost half a billion public Wi‐Fi hot spots. Both 5th generation (5G) cellular networks and current IEEE 802.11 Wi‐Fi can transmit radiofrequencies in the 5 Giga Hertz (5 GHz) range. Higher frequencies, such as those in the 5 GHz range, have been shown to be more harmful to humans and biological systems than lower frequencies. Although not well understood, frequencies generated in this range by newly established 5G cellular networks, and common Wi‐Fi 5 GHz networks, may pose a danger to biological systems which could have a significant impact on human health.This work looks to examine the effects of 5 GHz radiofrequency radiation on chlorophyll production and nitrogen levels in green leafy plants, in particular spinach. Chlorophyll is the most important intermediate in the conversion of light to organic matter in photosynthesis. Nitrogen is known to be directly proportional to chlorophyll content and is found in high amounts within enzymes, proteins, and thylakoid membranes required for photosynthesis. Spinach is known to have high levels of chlorophyll and has been chosen as the plant for testing. Using a TYS‐B Portable Chlorophyll Meter, chlorophyll and nitrogen levels will be non‐destructively measured over 5 weeks of growth under close bombardment from 5 GHz generated radio emissions in treatment groups and control groups shielded from all radio frequency emissions.If statistical significance suggests chlorophyll and nitrogen levels are decreased between treatment and control groups, further investigation may be warranted to assess the impact on human and plant health. Lower chlorophyll levels could decrease overall group weight and may contribute to a decline in pollinators. Decreased pollinators and lower crop yields could cost consumers billions of dollars in lower availability. As high frequency radio emissions continue to increase across the globe, any information would be available in determining possible dangers from these new technologies.Support or Funding Information• Bridges to Baccalaureate Grant awarded through National Institute of General Medical Sciences, Coconino Community College NIH Grant # 1R25GM102788‐01
Effects of amino acid composition on the requirements for J‐proteins by artificial prions
Authors: Miller Sarah C. , Hayward Rachel E. , Cole Sierra J. , Singh Atul K. 
Published: April 2020

Yeast prions are non‐Mendelian transmissible agents that are able to induce abnormal folding of specific proteins. The composition of yeast prions is usually in‐register, cross‐beta amyloid structures. Prion‐forming proteins have domains with unusual amino acid content that is typically rich in glutamine and/or asparagine. The chaperone protein network in yeast regulates the correct folding of proteins and is inexorably linked to the spreading of prions to daughter cells during division through a process called fragmentation. Specifically, the core “prion fragmentation machinery” at least minimally includes the proteins Hsp104, Hsp70 and one Hsp40, also known as a J‐protein. The relationship between the amino acid content of the prion‐forming domain (PrD) and chaperone proteins required for fragmentation, if any, is still unclear. Here we explored a system of engineered prions that resemble the Sup35 protein of S. cerevisiae, with single heterologous amino acids interspersed between polyQ sequences every fifth residue in the PrD of the construct. This domain determines the likelihood of a protein to form aggregates in vivo, and so by controlling the amino acid content in this region we can study the impact of specific amino acids and their interactions with chaperone proteins in the propagation of yeast prions. Specifically, requirements for the Hsp40 Sis1 is being investigated using multiple approaches, including plasmid‐shuffling experiments and repression of Sis1 levels using tetracycline. Strains have also been developed to test for requirements for additional J‐proteins for prion propagation. Overall, the long‐term goal for this research is to gain a deeper understanding of the relationship between amino acid content and chaperone protein interactions in prion propagation.Support or Funding InformationThis work was supported by the Lafayette College Chemistry Department, the EXCEL research scholarship program (
www.lafayette.edu), the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R15GM110606, and the Henry Dreyfus Teacher Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Dreyfus Foundation.
Impact of Monosodium Glutamate and Corticosterone in the Hippocampus: Glucocorticoid Regulation and Caspase‐3 mediated Microvascular and Neuronal Apoptosis
Authors: Mathew Smita , Joy Keerikkattil Paily 
Published: April 2020

Does monosodium glutamate (MSG) trigger stress circuitry axis and induce apoptosis in the hippocampus? If so, does it mimic the effect of corticosterone (CORT)? In order to test this hypothesis, we put forth a Glutamate model and CORT‐ induced model system in rats to study the modality of glucocorticoid response and apoptotic signaling cascade. Young adult (2‐month‐old) male Wistar rats weighing about 50–100 g body weight were divided into 4 groups. Group I control rats were injected with saline (NaCl 0.9%) and Group II rats with MSG at a dose of 4 mg/kg body weight. Group III control was ethanol‐saline injected and Group IV was CORT injected at 3 mg/kg body weight. Rats were injected subcutaneously with test materials or vehicles for 7 days and maintained for 8, 15 and 30 days and were sacrificed by decapitation. The MSG model showed an enhanced glucocorticoid receptor (GR) (Nr3c1) gene expression in the hippocampus on day 8, as an immediate response to stress, though not significant. This was followed by a down regulation on day 15 and day 30. Bax, a pro‐apoptotic factor gene showed an insignificant upregulated expression in the hippocampus on day 8, 15 and 30. This indicates the activation of Bax‐ dependent apoptotic pathways at the mRNA level. In the CORT model, GR (Nr3c1) gene expression in the hippocampus showed a very significant downregulation on day 8. Noticed an insignificant activation on day 15 and 30. Bax gene showed a very significant downregulation on day 8, an immediate time point. Day 15 and Day 30 displayed an insignificant up and down regulation. Immunohistochemical analysis revealed the Caspase‐3 mediated death program activation in the microvasculature and neurons of the hippocampus upon MSG and CORT exposure. In the hippocampus field CA1, CA2 and CA3 and dentate gyrus displayed prominent Caspase‐3 immunoreactivity in the microvessels, suggesting potential blood‐brain barrier (BBB) breach. A leaky BBB can transcend vasculotoxic and neurotoxic proteins to invade the brain. Probable events like this can pave way for the neurons and glial cells to be exposed to high levels of glutamate circulating in the blood, which can lead to receptor ‐ mediated neurotoxicity. Neuronal apoptosis is also activated in the hippocampus upon exposure to MSG and CORT. Our results suggest the potential disruption in the brain neural connectivity and neural synchronization upon exposure to MSG and CORT. Recent reports also state that BBB dysfunction and neuronal loss can be attributed and linked to neurodegenerative disorders like Alzheimer’s. Furthermore, MSG mimics the CORT in triggering‐Bax and Caspase dependent apoptotic signaling cascade, to suggest that MSG is a stressor and a neurotoxin. Our results raise concern over the use of MSG as a food additive which needs public awakening and awareness.Support or Funding InformationCUSAT Postdoctoral Fellowship‐Dr. Smita Mathew. U.O. No.Ac. B3/PDF/2016‐17(b) dt. 10.5.2017
A Study on Reduction of Occupational Stress of the Hi‐Tech Employees by Schumann Resonances
Authors: Lee Peiying , Hung Jiayi 
Published: April 2020

This study is expected to explore the impact of Schumann resonances on the work stress of high‐tech industry practitioners. Schumann wave, or Schumann resonance, is described as “the heartbeat of the earth”. It is a low‐frequency wave (7.83 Hz) that can penetrate any substance. If the human body is often stimulated by Schumann waves, it can receive a larger amount of natural energy to let natural spirit more healthy. The high‐tech industry has always been the focus of Taiwan’s economic growth. Most of the employees engaged in high‐tech industries face enormous work pressures, which in turn affect work efficiency and personal quality of life. In recent years, natural therapy and cranial neurology often explore the relationship between cranial nerve cells and Schumann wave. Therefore, the purpose of this study is to understand whether the use of Schumann wave can alleviate the work pressure of high‐tech industry employees.This study is divided into two parts: one is the use of heart rhythm analysis, brain wave instrument, gas field camera to analyze the effect of the Schumann wave; the second is to analyze the high‐tech industry employees after using Schumann wave, under work pressure Whether to achieve the phenomenon of mitigation; finally explore the current situation of the work pressure of high‐tech industry employees, how the industry should respond to human resources management. It is hoped that the results of this research will provide high‐tech industry employees with solutions to work control and workload, to adjust their work pressure, to reduce the imbalance of work and life of such employees, and to enhance the personal life of the work. Positive benefits.Support or Funding InformationFunding of this study is supported by Tzu Chi University of Science and Technology and the PI Semiconductor Corp., Taiwan.
Hippo pathway interacts with Wnt pathway to regulate the neural crest cells
Authors: Wang Jun 
Published: April 2020

The neural crest (NC) cells are migratory multipotent cells during embryogenesis, which differentiate into various derivatives and contribute significantly to tissues and organs. The Hippo pathway is a conserved anti‐growth fundamental pathway, yet its role in NC remains poorly understood. We found that Hippo pathway plays pivotal roles in NC cells proliferation, migration and differentiation, based on data obtained from comprehensive studies using in vivo NC conditional knock‐out mouse models and in vitro NC cells. Deficiency of Hippo effectors Yap and Taz caused defects in NC‐derived structures in mice such as vascular and cranial bone defects, as well as failure of NC cells to proliferate, migrate and differentiate. Notably, our motif analysis of ATAC‐seq (assay for transposase‐accessible chromatin with high‐throughput sequencing) data in mouse craniofacial tissues and human NC cells indicated that genome‐wide, 38.9% genes have enriched Tead (Yap/Taz cofactor) motifs are also enriched in Tcf/Lef (β‐catenin cofactors) motifs, suggesting that Hippo interacts with Wnt to coordinately regulate gene expression in NC cells. Wnt‐β‐catenin pathway, another fundamental pathway, has been shown to play a key role in NC cells. Our co‐IP data uncovered a direct interaction between Yap/Taz and β‐catenin in NC cells. Furthermore, our RNA‐seq data in mouse craniofacial tissues and Reverse Phase Protein Array (RPPA) data in mouse NC cells indicated that many known Wnt target genes important for cell migration and fate determination were also regulated by Yap/Taz. In addition, Yap/Taz‐Tead and Tcf/Lef‐β‐catenin complexes coordinately and directly regulate the expression of these genes. Together, our findings uncover novel roles of hippo‐Yap pathway in regulating NC cells, which partially functions through interaction with Wnt‐β‐catenin pathway.Support or Funding InformationThis work was supported by grants from the National Institutes of Health (R56HL142704, R03DE025873, K01DE026561 to J.W.).
PHYTOCHEMICAL COMPOSITION, ANTI‐INFLAMMATORY AND ANTI‐MICROBIAL ACTIVITIES OF SOME SELECTED SEAWEED IN EASTERN CAPE, SOUTH AFRICA
Authors: Oyedeji Adebola Omowunmi , Saibu Gbemisola Morounke , Nakin Motebang Dominic , Oyedeji Opeoluwa , Meyer Mervin 
Published: April 2020

IntroductionSea algae are widely consumed in the worldwide especially in South Africa. Most of these plants contain some phytochemicals with various potential biological activities. The present study investigated the presence of phytochemical constituents, and anti‐microbial and anti‐inflammatory potentials of methanol extracts of Eklonia radiate(ER) and Jania verucosa (JV).Materials and MethodsMarine macro‐algae were collected from two different rocky shores areas in East coast (Mbashe and Port St John rivers), Mthatha in South Africa during low tides. The collected marine macro‐algae were rinsed with distilled water and dried at room temperature (25°C). The samples were grinded and extracted with methanol. Qualitative phytochemical analysis for alkaloids, cardiac glycosides, flavonoids, glycosides, phenols, resins, saponins, steroids, tannins and terpenoids were done by following standard procedures. Anti‐microbial assay were performed against six different bacterial pathogens, while In vitro anti‐inflammatory activities of both extract were evaluated using albumin denaturation assay. Diclofenac was used as a standard drug for the anti‐inflammatory activity.ResultsPhytochemical screening revealed the presence of tannins, saponins, flavonoids, steroids, alkaloids, reducing sugars and terpenoids and polyphenols in both extracts. The average minimum inhibitory concentration (MIC) values of the plants extracts ranged from 0.156–5.0mg/ml after 24 h of incubation. Methanol extract of Jania verucosa had the most significant biological activity with the least MIC values of (0.16 mg/ml),while the anti‐microbial activities of methanol extracts of JE and ER gave different zones of inhibition on the five (E.coli, K. Pnemonia, MRSA, P.aureginosa and S.epidemidis) pathogens while there was no growth inhibition on S.pyogene isolates tested on both extracts. The results showed that ER and JV extracts at a concentration range of 0.312‐ 0.02mg/ml significantly (p<0.05) protects the heat induced protein denaturation.Discussion and ConclusionFrom the result, it can be concluded that the presence of phytochemicals present in the extracts could be responsible for the anti‐microbial activity. Further work should be done to isolate the bioactive compound (s) and biological activities of these seaweed.