bluuebunny/crossref_metadata_2025_split huggingface dataset:
MK‐STYX alters localization dynamics of autophagosomes and phenotypic dynamics of lysosomes
Authors: Mattei Andrew M. , Christian Patrick , Hinton Shantá D. 
Published: June 2021

MK‐STYX[MAPK (mitogen‐activated protein kinase)phosphoserine/threonine/tyrosine‐binding protein] is a pseudophosphatase, a member of the dual‐specificity family subfamily of MAPK phosphatases (MKPs)that lack the essential nucleophilic cysteine in its signature motif required for catalytic activity. MK‐STYX maintains its three dimensional fold and ability to bind proteins; it is involved in cellular pathways such as those for stress response, apoptosis, and neuronal differentiation. Previously, were ported that MK‐STYX interacts with G3BP‐1 [Ras‐GAP (GTPAse‐activating protein) SH3 (Src homology 3) domain binding protein‐1], and inhibits stress granule formation. Stress granules, cytoplasmic storage sites for mRNA, form as a protective mechanism against stress caused by UV irradiation, hypoxia, and heat shock. Stress induces stress granules, and involves many cellular mechanisms such as post‐translational modifications, protein‐protein interactions, and microtubule networks. Furthermore, stress granules are targeted and cleared by autophagy, an initiated response to cellular stress. They are responsible for the degradation of cellular components. Therefore, autophagy is essential for cellular degradation. Since autophagy and MK‐STYX each negatively affect stress granule assembly, we sought to determine whether MK‐STYX has a role in autophagy. Pursuing the role of MK‐STYX in regulating autophagy will enhance our understanding of MK‐STYX's mechanism in the stress response pathway. Our studies show that MK‐STYX causes cytosolic TFEB (Transcription factor E‐Box; the autophagy “master switch”) to form perinuclear aggregates independent of nutrient status. Whereas, MK‐STYXactive (active mutant in which catalytic activity has been “restored”), only increased TFEB cytosolic aggregates in serum starved cells, suggesting that the catalytic signature motif of MK‐STYX may play a role in stress responses. TFEB is also found to localize to the lysosomal surface, acting as negative regulator of lysosomal and autophagosomal biogenesis. MK‐STYX alters lysosomal and autophagosomal dynamics; oversized lysosomes are observed in the presence of MK‐STYX. Furthermore, autophagosomes localize to the distal ends of HEK/293 cellular extensions in the presence of MK‐STYX. Autophagy plays a major role in major cellular processes ranging from initial developmental stages to the onset of progressive human pathologies such as neurodegenerative diseases and cancer. These studies suggest that MK‐STYX may have an important role in autophagy.Support or Funding InformationThis work was supported by the National Science Foundation Grant MCB1113167 to S.D.H.; Coco Award to S.D.H.; Howard Hughes Medical Research Institute grant through the Undergraduate Science Education Program to the College of William and Mary (HHMI Summer Fellowships to P.C. and A.M.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MK‐STYX‐Induced PC‐12 Neurites are Dopaminergeric
Authors: Swack Ben D. , Banks Dallas , Dahal Arya 
Published: June 2021

MK‐STYX [MAPK (mitogen‐activated protein kinase) phosphoserine/threonine/tyrosine‐binding protein] is a pseudophosphatase. There is compelling evidence that this unique catalytically inactive member of the protein tyrosine phosphatase family is a regulator in neuronal processes such as neurite outgrowth. We previously reported that MK‐STYX dramatically increases the number of primary neurites in rat pheochromocytoma (PC‐12) cells through the RhoA signaling pathway. Transmission electron microscopy data demonstrate that MK‐STYX‐ induced neurites form synapse‐like structures. PC‐12 cells have been shown to communicate through synaptic release of dopamine and norepinephrine. Dopamine release is modulated by phosphatases IA‐2 (islet antigen 2) and calcineurin. Because MK‐STYX is an atypical phosphatase, we wanted to determine if neurites induced in the presence of MK‐STYX retain their dopaminergic qualities. In this report, we show that this is the case. Using an ELISA assay for dopamine, we found that PC‐12 cells expressing MX‐STYX had similar dopamine concentrations as control cells, suggesting the synapses are dopaminergic in both conditions. These data provide evidence that MK‐STYX has a role in neuronal signaling.Support or Funding InformationThis work was supported by the National Science Foundation Grant MCB1113167 to S.D.H.; Coco Award to S.D.H.; Howard Hughes Medical Research Institute grant through the Undergraduate Science Education Program to the College of William and Mary; a DuPont Fund Student‐Faculty Research Team Stipend awarded to A.D. and S.D.H. through a grant by the Jessie Ball Grant Fund to the William and Mary Scholars for Undergraduate Research Experience program; Ferguson Awards to D.A.B., A.D., and C.S., and the Dintersmith Honors Fellowship to A.D.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The TRPV4‐TAZ signaling axis in matrix stiffness‐ and TGFβ1‐induced epithelial‐mesenchymal transition
Authors: Rahaman Shaik O. , Sharma Shweta , Goswami Rishov 
Published: June 2021

Epithelial to mesenchymal transition (EMT) is a critical event in development, tissue regeneration, fibrogenesis, and oncogenesis. Emerging data support a role for both a mechanical signal, and a biochemical signal, e.g., transforming growth factor β1 (TGFβ1) in EMT. However, the mechanisms by which these signals regulate EMT are not well understood. Here, we report evidence that transient receptor potential vanilloid 4 (TRPV4), a calcium‐permeable channel sensitive to both matrix stiffness and TGFβ1 stimuli, is a likely mediator of EMT. We found that antagonism of TRPV4 blocked both matrix stiffness‐ and TGFβ1‐induced EMT in normal human primary epidermal keratinocytes (NHEKs), as determined by changes in morphology and alterations in expression of EMT markers including E‐cadherin, N‐cadherin, and α‐smooth muscle actin (α‐SMA). In a murine skin fibrosis model, TRPV4 deletion resulted in decreased expression of the mesenchymal marker, α‐SMA, and increased expression of epithelial marker, E‐cadherin. Mechanistically, we found that: i) TRPV4 activity was essential for the nuclear translocation of TAZ (transcriptional coactivator with PDZ‐binding motif) in response to matrix stiffness and TGFβ1; ii) Antagonism of TRPV4 activity inhibited both matrix stiffness‐induced and TGFβ1‐induced expression of TAZ proteins; and iii) TRPV4 antagonism suppressed both matrix stiffness‐induced and TGFβ1‐induced activation of Smad2/3, but not of AKT. Altogether, these data identify a novel role for TRPV4 in regulating EMT in response to both matrix stiffness and TGFβ1.Support or Funding InformationAHA (13SDG17310007), Startup grant from University of Maryland, NIH (1R01EB024556‐01), and NSF (CMMI‐1662776) grants to SOR.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
JAZ proteins promote growth and reproduction by restraining transcriptional programs that link primary and specialized metabolism
Authors: Guo Qiang , Major Ian , Yoshida Yuki , Howe Gregg 
Published: June 2021

Plants constantly experience attack from surrounding organisms. Because they cannot escape from the environment, plants have evolved a sophisticated immune system to defend themselves against pests and pathogens. However, mounting a defense response is often accompanied by a decrease in growth. The antagonistic relationship between growth and defense has been interpreted as the plant's “dilemma” of how to distribute limited resources between these two fundamental processes. Jasmonic acid (JA) and its derivatives are a class of lipid‐derived hormones that mediate plant immunity against insect herbivores and necrotrophic pathogens, as well as growth, reproduction, and several other physiological processes. JA is perceived by its receptor CORONATINE INSENSITIVE 1 (COI1), which mediates the degradation of the JASMONATE ZIM DOMAIN (JAZ) transcriptional repressors by the 26S proteasome. JAZ degradation releases JA‐responsive transcription factors such as MYC2 from repression, thereby initiating JA responses. Despite the importance of JA in mediating growth‐defense tradeoffs, the mechanism by which JA effects carbon resource allocation between growth and defense is poorly understood. In this study we demonstrate strong constitutive activation of JA signaling pathway in an Arabidopsis mutant (jazD) that lacks ten members of JASMONATE ZIM DOMAIN (JAZ) family proteins. This mutant displayed elevated defense against insect herbivores, stunted growth of vegetative tissues, as well as compromised seed reproduction. Metabolic phenotypes of jazD discerned from global protein and transcript profiling were indicative of elevated carbon allocation to protein‐ and amino acid‐based defense compounds. The strong defense sink in jazD leaves was linked to increased respiration and hallmarks of carbon starvation, whereas area‐based photosynthetic efficiency was unaffected. These findings establish a role for JAZ proteins in promoting growth and reproductive success through restraint of transcriptional programs that link primary metabolism to specialized metabolism. Our data suggest that JAZs adjust growth‐defense balance to match anticipated changes in carbon availability, potentially avoiding detrimental effects of carbon limitation that arise during growth‐to‐defense transitions.Support or Funding InformationThis research was funded by the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, US Department of Energy through grant DE–FG02–91ER20021.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sinorhizobium meliloti Bacteriophage HMSP‐1‐Susan: Genome Sequence, Molecular Characterization and Implications for Symbiosis
Authors: Fleagle Brennon , Imamovic Aldina , Martinez‐Vaz Betsy 
Published: June 2021

Bacteria of the genus Sinorhizobium are plant‐growth promoting microbes that form symbiotic relationships with legumes. These bacteria are important in agriculture because of their ability to convert atmospheric nitrogen gas to ammonia. Ammonia is used to synthesize proteins that are essential for plant growth. Bacteriophages are bacterial viruses that decrease microbial populations in soils and other environments. Despite extensive research on the molecular mechanisms governing the process of nitrogen fixation in Sinorhizobium, little is known about the biotic factors that influence the persistence of these bacteria in soil and impact their ability to fix nitrogen. The presence of bacteriophages in soils has been shown to select for specific types of Sinorhizobium strains and to affect the populations nitrogen‐fixing bacteria. In spite of this observation, there are only a limited number of Sinorhizobium phages that have been characterized. The goal of this project was to carry out a molecular characterization of phage HMSP‐1, a bacteriophage isolated from an agricultural soil that infects strains of Sinorhizobium. Viral DNA was isolated and used to obtain the complete nucleotide sequence of HMSP‐1. Genome analyses revealed that HMSP‐1 is a double stranded DNA virus of 52 kb in size. The genome has a GC content of 52.5% and encodes 96 proteins. 83% percent of these proteins were classified as hypothetical proteins of unknown function. HMSP‐1 did not have significant DNA sequence homology to known bacteriophages; these data suggest HMSP‐1 is novel bacterial virus. We investigated the effects of bacteriophage HMSP‐1 on plant growth and the numbers of Sinorhizobium associated with the model legume, Medicago truncatula. No significant differences in growth or microbial numbers were found between the plants exposed to the phage and unexposed the controls. These data suggest that under the conditions tested, HMSP‐1 does not affect the bacterial populations associated with Medicago truncatula.Support or Funding InformationThe work was supported by grant 1237993 from the National Science Foundation and the Hamline University Ridgeway Fund for Undergraduate Collaborative Research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
“Community Problem Based Learning to Prepare Students for Real‐World STEM Opportunities”
Authors: Tabor Aaron James , Woodruff Robert , Kesler Kenric M. , Bell Mindy , Ross Danielle K. , Neilson Brent , Gray Ron 
Published: June 2021

iCREATE is an NSF‐funded project between the CAVIAT School District and Northern Arizona University's Center for Science Teaching and Learning. The project is designed to engage community partners in a dual‐enrollment (DE) high school bioscience course to positively impact the number of students interested in pursuing bioscience‐related careers and opportunities. The project integrates community collaborations, innovative course design, and modern science technologies to engage students in an authentic problem in their community. A high school level bioscience course has been designed and implemented through CAVIAT, a regional collaboration between school districts to provide high quality career and technical education (CTE) courses. Through the course, project partners engage students in examining community needs regarding the authentic problem of tracking the spread of influenza‐like‐illnesses (ILI) across the Northern Arizona region. Students work with project partners in an effort to design innovative, technology‐rich solutions to address the ILI problem. The university and industry partners bring current knowledge in bioscience and technological understanding of geospatial technologies to the classroom. In this study, we examine the ways in which the project impacts participating students' self‐efficacy, interest in STEM careers, and plan to take part in further internship opportunities. Initial pilot study findings indicate students enjoyed the course, the many challenges it offered, and the opportunity to interact with researchers and community members. Additionally, students' career interest and science motivation increased compared to the control group.Support or Funding InformationNational Science Foundation NSF‐1513198This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Establishing Practices Integrating Commuter Students – Year 1
Authors: Watters Michael K. , Capaldi Mindy , Bugajski Kristi , Schmitt Karl , Schoer Jon , Dahlke‐Goebbert Bonnie 
Published: June 2021

The EPIC grant focuses on the integration of STM (Science, Technology, & Mathematics) commuter students into the Valparaiso University (VU) campus community through shared undergraduate research experiences, as well as skill‐building and social activities. Goals of the EPIC grant include improving recruiting and retention of STM students, increasing the number of STM graduates prepared for research careers, and increasing the number of research intensive majors within STM departments. Students are recruited with scholarships averaging $5,300 per year.During year 0 the EPIC program developed the infrastructure and tools to recruit, select, enroll, and support the first cohort of students in fall 2017. We report the results of our recruitment initiatives on the poster. In year 1 we refined these practices to include earlier and more varied contact with high schools. Recruitment of the second cohort is underway.Assessment procedures were initiated through the establishment of pre‐EPIC baselines measuring retention, academic, and demographic data for STM students at VU. Data were collected through institutional research and multiple student surveys. This data includes GPAs, STM student retention, graduation rates, and the impact of undergraduate research. Some data is broken down demographically according to gender, race, ethnicity, and commuter status. Preliminary analysis revealed several notable results, such as a 44% retention rate for STM students remaining in their original major and 25% of VU STM students from the 2012 freshman cohort not graduating at all. Additionally, VU commuters are less likely to be retained in a STM major and are less likely to graduate. This group of students is the primary focus of the EPIC program; we predict that our model will improve their retention numbers.Support or Funding InformationThis work was supported by award # 1564855 from the National Science Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Type III Polyketide Synthase Involved in Tropane and Granatane Alkaloid Biosynthesis
Authors: Kim Neill , D'Auria John C. 
Published: June 2021

The lack of data concerning the enzymes and genes responsible for the production of tropane and granatane alkaloids has hindered endeavors to metabolically engineer important pharmacologically active specialized metabolites. It is important to understand how biochemical pathways perform when they originate from evolutionarily diverse families. It is hypothesized that a type III polyketide synthase enzyme is involved in the extension and subsequent cyclization of the second ring in the bicyclic tropane and grantane core structure. This represents a new class of type III polyketide synthases in which the heterocyclic starter molecule is charged and also lacks a Coenzyme A thioester. Putative polyketide synthase enzymes were identified in the Erythroxylum coca and Punica granatum cDNA transcriptome database and heterologously expressed in Pichia pastoris. LC‐MS/MS analysis has revealed the formation of a 4‐(1‐methyl‐2‐pyrrolidinyl)‐3‐oxobutanoate intermediate that is hypothesized to lead to the second ring formation. Understanding how evolutionary changes have occurred in type III polyketide synthases from different metabolic pathways that determine the development and expansion of chemical diversity to produce high valued compounds will be a powerful tool for bioengineering pharmaceuticals.Support or Funding InformationNational Science FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nutrient sensing and mitochondrial Coenzyme Q biosynthesis: Are they connected by a phosphatase?
Authors: Awad Agape M. , Venkataramanan Srivats , Nag Anish , Galivanche Anoop R. , Bradley Michelle C. , Neves Lauren , Douglass Stephen , Johnson Tracy L. , Clarke Catherine F. 
Published: June 2021

Coenzyme Q (also termed ubiquinone or Q) is an electron carrier in the mitochondrial respiratory chain that functions as an essential component in energy metabolism processes, while also serving as a vital lipid soluble antioxidant. Sufficient de novo Q biosynthesis is crucial for human health. Saccharomyces cerevisiae (baker's yeast) serves as an excellent model for studies on Q because of its powerful molecular genetics and the functional identity of yeast and human COQ genes. Coenzyme Q biosynthesis in S. cerevisiae occurs in the mitochondria and, currently, fourteen known mitochondrial proteins are responsible for facilitating this process—Coq1–Coq11, Yah1 (ferredoxin), Arh1 (ferredoxin reductase), and Hfd1 (aldehyde dehydrogenase). Many of the Coq proteins associate in a high molecular weight complex (“CoQ‐Synthome”) that localizes in the inner mitochondrial membrane. Previous work indicated that the stability of the Q biosynthetic complex (as well as the phosphorylation status of several Coq polypeptides, including Coq3, Coq5, Coq7, and potentially Coq6) relied on the presence of Coq8, the putative kinase of the system. Thus, the role of phosphorylation may provide novel information as to how the CoQ‐synthome is regulated. Indeed, intriguing links have been discovered that relate Coq polypeptides and phosphorylation status with nutrient availability and regulatory genes. Most recently, a link has been found between a nutrient sensing gene, SNF2, and the spicing efficiency of PTC7, the phosphatase responsible for controlling a key regulation site in Q biosynthesis. Our objectives are to further investigate these regulatory links. Such studies will aid our understanding and treatment of multiple diseases caused by CoQ‐deficiencies and provide novel insight in longevity and issues related to aging in humans.Support or Funding InformationThis work was supported by the National Science Foundation, Grant MCB‐1330803 and the National Institute of General Medical Sciences (GM‐085474), Whitcome Pre‐doctoral Fellowship in Molecular Biology, and the Ruth L. Kirschstein National Service Award GM‐007185.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The PAH1‐encoded Phosphatidate Phosphatase Plays a Role in Lipogenesis in the Oleaginous Yeast Yarrowia lipolytica
Authors: Hardman Derell , Ukey Rahul , Fakas Stylianos 
Published: June 2021

The PAH1 gene encodes for phosphatidate phosphatase (PAP), the enzyme that catalyzes the dephosphorylation of phosphatidic acid to yield diacylglycerol and Pi. PAP activity is essential for the biosynthesis of the storage lipid triacylglycerol (TAG) in several eukaryotes (e.g. Saccharomyces cerevisiae). In Yarrowia lipolytica, TAG accumulates during lipogenesis and is responsible for the increase in cellular lipid content under these conditions. We hypothesized that under lipogenic conditions, lack of the Y. lipolytica PAH1 homolog (i.e. pah1Δ) should result in a reduction of lipid content and diminished TAG levels. To examine this hypothesis, we cultivated the Y. lipolytica wild type and pah1Δ strains in a lipogenic (8% glucose) medium, and analyzed their growth and lipid profiles. The results showed that the pah1Δ mutant exhibited increased growth but a lower lipid content in comparison to the wild type. However, the pah1Δ mutant was able to synthesize TAG, although to a lesser extent than the wild type. These results indicate that the Y. lipolytica PAH1 homolog contributes to, but is not essential for, TAG biosynthesis during lipogenesis.Support or Funding InformationThis research was supported by Evans‐Allen Grant no.1005735 and Capacity Building Grants Program Grant no.1007503 from the USDA National Institute of Food and Agriculture, as well as the Strengthening Historically Black Graduate Institutions Program under Title III of the Higher Education Act of 1965.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.