bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acrolein Modification of Apolipoprotein A‐I Alters Protein Stability and Antimicrobial Activity
Authors: Hong Hea Jin , Weers Paul 
Published: November 2023

Human apolipoprotein A‐I (apoA‐I) isa major component of high density lipoprotein and has an important role in cholesterolefflux. The protein also has antimicrobial properties, capable of neutralizing lipopolysaccharides (LPS) and destabilizing inner membranes of gram‐negative bacteria. Previous studies have shown that acrolein modifies the ɛ‐amino sidechains of lysine residues of apoA‐I. Acrolein is a highly reactive αβ unsaturated aldehyde and is generated mostly by cigarette smoking or during oxidation of lipids and amino acids. Acrolein‐modified apoA‐I has been detected in humana therosclerotic lesions and studies have shown that acrolein impairs lipid transport, leading to severe heart disease. The current study aims to investigate the effect of acrolein exposure on the antimicrobial activity of apoA‐I. The protein, containing 21 lysine side‐chains, was modified by acrolein and analyzed by SDS‐PAGE. At a 20‐fold molar ratio of acrolein to lysine, acrolein modification was evident by the appearance of oligomers caused by crosslinking. As the molar ratio of acrolein to protein increased, the intensity of the apoA‐Iband at 28 kDa decreased while heavily cross‐linked apoA‐I appeared with protein bands at 63, 98, and 126 kDa. Acrolein modification was further verified by western blot using an antibody (mab5F6) that specifically detects acrolein modified lysine residues in proteins. This confirmed the presence of acrolein‐modified lysine in the oligomers. To examine the structural changes of the modified protein, α‐helical content and the stability of the protein was measured using circular dichroism. The α‐helical content of acrolein modified apoA‐I was similar to unmodified protein (helical content of ~55%). However, the midpoint of guanidine‐induced denaturation increased from 0.97 (unmodified protein) to1.50 M (acrolein modified protein), indicating a significant increase in protein stability. This suggests that while modification did not alter the secondary structure, the tertiary structure was altered due to cross‐linking. To examine the binding of cross‐linked apoA‐I to phosphatidylglycerol, vesicles entrapped with calcein were used. Addition of apoA‐I to the vesicles resulted in calcein release as indicated by the increase in fluorescence intensity. The percentage of calcein released by apoA‐I decreased from 87.5 ± 2.3% to 4.7 ± 0.13% when the protein was modified by acrolein. This shows that acrolein‐modified apoA‐I binds phosphatidylglycerol less effectively, possibly due to loss of electrostatic interaction with the anionic vesicles or by the increase in protein stability caused by crosslinking.Support or Funding InformationResearch reported in this presentation was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number SC3GM089564.
PIP2 mediated influence on Serotonin Transport Function
Authors: Hofmaier Tina , Anderluh Andreas , Kudlacek Oliver , Stockner Thomas , Schütz Gerhard , Sitte Harald 
Published: November 2023

The serotonin transporter (SERT) plays a key function in the termination of serotonergic neurotransmission. SERT is the main pharmacological target in treating depressive disorders and also a target for various drugs of abuse. Drugs like amphetamine‐type stimulants (ATS) reverse the direction of transport which finally leads to an increased serotonin concentration in the synaptic cleft. Transmembrane proteins get in close contact with the lipid environment and are partitioned in specific lipid microdomains. In a previous study we already implicated the phosphatidylinositol PIP2, a major signaling molecule, to influence amphetamine effects at SERT and elucidated a specific binding interface (Buchmayer, Schicker et al. 2013). We explored a positively charged SERT area using a computational approach and identified a putative second binding site which is close to the inner leaflet of the plasma membrane. Moreover by using single molecule analysis we could show that this interaction stabilizes the oligomeric state of SERT. Disruption of the PIP2 binding site on SERT as well as depletion of PIP2 at the plasma membrane resulted in decreased oligomerization which was also examined using single molecule fluorescence microscopy.ResultsManipulating cellular PIP2 levels had an effect on amphetamine‐induced substrate efflux. Neutralizing of this positively charged SERT area led to a loss of this effect.DiscussionWe could show that both binding sites are necessary for a stable PIP2‐SERT interaction. Neutralization of positive charges within the binding sites abolished PIP2 modulation of amphetamine induced efflux. By drastically reducing intracellular PIP2 levels we could show an decreased amphetamine induced efflux in SERT. This effect could not be observed in mutant SERT indicating a loss of PIP2 mediated effect on substrate efflux. Further we could show that SERT not only interacts with PIP2 but also other phosphatidylinositol species. This interaction is almost lost upon neutralization of both binding sites.Support or Funding InformationThe work of was financially supported by the Austrian Science Foundation/FWF
Fostering Remembering: Strategies for Helping Students Link Prerequisite Knowledge to Learning Biochemistry
Authors: Taylor Ann T.S. , Novak Walter R.P. 
Published: November 2023

Biochemistry is built on the fundamentals of chemistry and biology. It is often the fifth chemistry‐related course a student takes. However, students’ ability to transfer information from prior courses is limited, assuming they learned it correctly the first time. Making connections between new material and prior knowledge, and that the prior knowledge is recalled correctly are fundamental assumptions in the constructivist model of learning. How can Biochemistry educators foster these connections and correct errors in prerequisite knowledge? In this study, the effect of a collection of activities that explicitly link general and organic chemistry concepts to biochemistry ideas was tested either alone or in conjunction with regularly integrated clicker questions connecting pre‐requisite concepts to course material. Performance on a pre‐ and post‐test covering key pre‐requisite concepts, performance on Biochemistry exams, and student self evaluation of their confidence in the concepts from prior courses was collected. Use of the pre‐class activities alone was not sufficient to improve understanding of the pre‐requisite concepts; however, in combination with integrative clicker questions, student performance on a pre‐requisite concept inventory was improved. These gains were seen both at a private liberal arts college and at a R1 research institution.Support or Funding InformationThis work was supported by NSF‐DUE grant #1140711 and the Haines Fund for the Study of Biochemistry at Wabash College.
Exploring the Impact of Jargon on Student Learning in Biology: Student Understanding, and Self‐Perception of Understanding, of Technical Vocabulary
Authors: McDonnell Lisa , Zukswert Jenna , Barker Megan 
Published: November 2023

The ability to communicate and collaborate is a core concept in biology education1, and includes mastery of both conceptual ideas as well as technical vocabulary. The “jargon load” is a particularly prominent hurdle in introductory biology courses, which are notorious for the vast quantity of new terms, often more than in a high school language course2. Previous research has shown that the jargon load can negatively impact learning3, 4. However, little work has been done to widely characterize student understanding of biology‐specific jargon, and to distinguish between types of jargon that may differently impede student learning. The purpose of this study was to assess students’ actual and self‐perceived understanding of various biological terms presented in first‐ and second‐year undergraduate biology courses in order to determine 1) the types of terms that students struggle with most, and 2) identify common errors in their understanding. In three large undergraduate biology classes, students were given an online survey about the specific terms they had seen in the course; the survey prompted them to assess their recognition and understanding of each term, as well as give definitions in their own words. In total, there were 93 vocabulary terms with over 2,400 student responses. The terms were grouped into thematic categories to facilitate analysis.Our results indicate that students struggle the most with Molecular terms (names of molecular structures). Interestingly, there was a significant difference between student's self‐perceived understanding and their actual understanding, and these differences vary between types of jargon. The least accurate self‐assessment was found for the following categories: Information (describing information transfer processes), and Incompatible Ambiguity (terms with precise scientific meanings that are used less precisely in everyday language). Analysis revealed that students often showed an overestimation of understanding: a significantly large proportion of incorrect definitions were submitted despite a high proportion of students self‐reporting that they understood the terms. For example, for terms in the Incompatible Ambiguity category, 83% of students claimed they understood the terms, but only 26% of the definitions submitted were correct.The findings of this research provide insights about which technical vocabulary may indeed be jargon, and possibly create a barrier to developing deeper conceptual understanding. Additionally, our results shed light on the variation in types of jargon, and highlight a need to consider student understanding of different types of jargon to support learning and scientific literacy.Support or Funding InformationThis work was supported by a Teaching and Learning Enhancement Fund grant from the University of British Columbia.
Developing Science Leaders Through Applied Learning Experiences
Authors: Richardson John M 
Published: November 2023

Future generations of scientists will be expected to find innovative solutions to problems that are greater in scale and magnitude that what we have ever faced before. Since these challenges will be faced early in an academic career, young scientists will not have the opportunity to develop the necessary skills over a lifetime before they are called upon to lead. To address this gap a partnership has been formed between the leadership studies program and the chemistry and biology faculty at Austin College to develop a curriculum of leadership skills in order to prepare our graduates to work on these new scientific frontiers. This curriculum is rich in intentional instruction of awareness, ability, and commitment through a complete integration into the existing scientific learning environment. Instruction is layered into courses and laboratory components at every level of the curriculum to give the students multiple opportunities to develop their skills from freshman through senior year. The work presented will discuss the vision for this interdisciplinary partnership, define our model for developing professionalism and leadership from within the academic disciplines, and report some early results from the classroom. The STEM Teaching and Research (STAR) Leadership program provides the foundation not only for successful professional careers, but also for increased civic and community engagement.Support or Funding InformationSupport for this work was provided by the W.M. Keck Foundation
The Small World Initiative™: An Innovative Crowdsourcing Platform for Antibiotics
Authors: Barral Ana Maria , Makhluf Huda , Broderick Nichole A. , Kurt Erika L. 
Published: November 2023

The Small World Initiative™ (SWI) is an innovative program that encourages students to pursue careers in science and sets forth a unique platform to crowdsource new antibiotics. It centers around an introductory biology course through which students perform original hands‐on field and laboratory research in the hunt for new antibiotics. Through a series of student‐driven experiments, students collect soil samples, isolate diverse bacteria, test their bacteria against clinically‐relevant microorganisms, and characterize those showing inhibitory activity. This is particularly relevant since over two thirds of antibiotics originate from soil bacteria or fungi. SWI's approach also provides a platform to crowdsource antibiotic discovery by tapping into the intellectual power of many people concurrently addressing a global challenge and advances promising candidates into the drug development pipeline. This unique class approach harnesses the power of active learning to achieve both educational and scientific goals.Formulated in 2012 at Yale University by Jo Handelsman, the current Associate Director of Science at the White House, the course is now in 109 institutions in 32 states, Puerto Rico, and nine countries. We will present course data on enrollment and curriculum integration as well as highlight implementation at National University. We will discuss our preliminary student evaluation results, which show the compelling impact of the program in comparison to traditional introductory courses. Ultimately, the mission of the program is to provide an evidence‐based approach to teaching introductory biology concepts in the context of a real‐world problem. This approach has been shown to be particularly impactful on underrepresented STEM talent pools, including women and minorities.Support or Funding InformationFunding for the first two years of the SWI was provided by the Leona and Harry B. Helmsley Charitable Trust.
Problematic 15‐PGDH: The Link between 15‐PGDH and Uncontrolled Tissue Growth
Authors: Chyong Donian , Alluri Anisha , Arpornsuksant Ty , Hu Michael , Jain Supriya , Williams Megan , Baxley Ann , Link Tina , Na Hye‐Kyung 
Published: November 2023

15‐Hydroxyprostaglandin dehydrogenase (15‐PGDH) is the key enzyme that catalyzes the degradation of prostaglandin E2 (PGE2). The expression of 15‐PGDH is ubiquitously down‐regulated in various cancers. Whereas, overexpression of 15‐PGDH in cancer cells causes apoptosis, cell cycle arrest, and inhibition of metastasis, and hence considered as a tumor suppressor. Hypermethylation of CpG islands in the gene promoter region is an important mechanism to silence the expression of 15‐PGDH and contributes to cancer formation. 15‐PGDH physiologically antagonizes cyclooxygenase‐2 (COX‐2), an enzyme involved in inflammation and carcinogenesis. Therefore, downregulation of 15‐PGDH and overexpression of COX‐2 may coordinately increase the levels of PGE2 and exacerbate the carcinogenic process. 15‐Deoxy‐Δ 12,14 ‐prostaglandin J2, a product of the COX‐2 enzymatic pathway, upregulates the expression of 15‐PGDH in breast cancer MDA‐MD‐231 cells in a negative feedback loop. 15‐PGDH is directly regulated by the TGF‐tumor suppressor pathway. In addition to cancer research, current research involves investigating 15‐PGDH as a potential avenue for tissue regeneration. Inhibition of 15‐PGDH has been found to potentiate hematopoietic recovery in mice receiving a bone marrow. 15‐PGDH has also been found to play a central role in determination of active prostaglandin concentrations during pregnancy and may be competitively regulated by progesterone and cortisol. Mutations in the gene coding for 15‐PGDH can also cause digital clubbing, the swelling of the distal parts of the finger. Research on 15‐PGDH will unlock treatment methods for patients suffering from a wide variety of illnesses. We printed a 3D model of the 15‐PGDH protein structure to investigate the relationship between structure and function.Support or Funding InformationWalton High School SMART (Students Modeling a Research Topic) Team is sponsored by Milwaukee School of Engineering.
A Phenylalanine Fiasco: The Structure of Phenylalanine Hydroxylase and its Impact on Phenylketonuria
Authors: Kahn Jenna , Koh Ally , Luckcuck Rachel , McNeice Jules , Walter Ellie , Yao Wendy , Baxley Ann , Link Tina 
Published: November 2023

Phenylketonuria (PKU) is a devastating metabolic disease that is unfortunately common: it affects between 1 in 10,000 and 1 in 15,000 newborns in the United States. This disorder is caused by mutation in the gene for phenylalanine hydroxylase (PheOH), a biopterin‐dependent aromatic amino acid hydroxylase which catalyzes the breakdown of phenylalanine (Phe) into tyrosine (Tyr). Structurally, it comprises a catalytic domain, a regulatory domain in the N‐terminus, and a C‐terminal domain responsible for tetramerization of the monomers. It catalyzes the hydroxylation of Phe to Tyr, which is the rate‐limiting step in the breakdown of phenylalanine. There are over 500 documented mutations on the PheOH gene, but the most common ones disrupt tetramer assembly, increase sensitivity to proteolytic cleavage and aggregation, or remove essential structures such as the C‐terminus. These mutations can cause a buildup of blood Phe, leading to hyperphenylalaninemia (HPA) and PKU. PKU, the most severe form of HPA, is an autosomal recessive disorder characterized by the total or near‐total absence of PheOH. Untreated, PKU causes a buildup of Phe at the blood‐brain barrier, which leads to severe intellectual disabilities in affected individuals. If detected early and treated carefully, people with PKU can lead fairly normal lives; however, any neurological damage already incurred is irreversible. Using x‐ray crystallography, researchers have created models of the structure of PheOH. Understanding the structure of PheOH is essential to developing new therapies to treat PKU. We created a model of PheOH using 3D modeling and printing technology that highlights several of the most common PKU‐causing mutations, located at the juncture between the catalytic and tetramerization domains.Support or Funding InformationWalton High School SMART (Students Modeling a Research Topic) Team is sponsored by Milwaukee School of Engineering.
Combining molecular visualization with bench methods in a hypothesis‐driven undergraduate biochemistry lab course
Authors: Craig Paul A. , Mills Jeffrey L. , Daubner Colette , Pikaart Michael J. 
Published: November 2023

We are seeking to incorporate authentic inquiry into an undergraduate biochemistry lab course. Students on six campuses are combining computational (“in silico”) and wet lab (“in vitro”) techniques as they characterize proteins whose three dimensional structures are known but to which functions have not been previously ascribed. The in silico modules include protein visualization with PyMOL, structural alignment using Dali and ProMOL, sequence exploration with BLAST and Pfam, and ligand docking with PyRX and Autodock Vina. The goal is to predict the function of the protein and to identify the most promising substrates for the active sites. In the wet lab, students express and purify their target proteins, then conduct enzyme kinetics with substrates selected from their docking studies. Their learning as students and their growth as scientists is being assessed in terms of research methods, visualization, biological context, and mechanism of protein function. The lab course is an extension of successful undergraduate research efforts at RIT and Dowling College. The modules that are developed will be disseminated to the scientific community via a web site (promol.org), including both protocols and captioned video instruction in the techniques involved. Over the course of the project, we will also be following changes in faculty and teaching assistant competence in two areas: effective teaching with structural biology tools and the development of skills in the area of measuring learning gains by students. As we conduct the lab on these different campuses, we will also focus on advantages of our approach and barriers to implementation that exist on each campus, from the level of student acceptance and faculty training, to resources that are needed to changes in the culture at the departmental and institutional levels. As we analyze the feasibility of this approach on other campuses, we will seek input from other potential adopters about their level of interest and the barriers that they anticipate on their campuses.Support or Funding InformationThis project is supported in part by NSF IUSE 1503811.
Unhealthy Weight Among Mothers and Young Children in the Middle East and North African Region
Authors: Jones Rebecca , Cunningham Solveig 
Published: November 2023

BackgroundPrevious studies have documented the emergence of double‐burden households in poorer countries, or households that have both underweight and overweight or obese persons.MethodsWe used nationally representative data from the most recent Demographic and Health Survey (2001–2012) in the six countries in the MENA Region (n=21,481) with available data (Azerbaijan, Egypt, Jordan, Mauritania, Morocco, and Turkey) to examine weight status amongst mothers and their child under age 5 years in a part of the world where increases in obesity have been noted. Under‐nutrition households were defined as underweight mother and thin child; over‐nutrition households as overweight or obese mother and overweight child; and double burden households as underweight mother and overweight child or overweight or obese mother and thin child. Survey‐adjusted multinomial logistic regression was used to quantify predictors of household weight pattern.ResultsAcross the MENA region, 7.3% of households were double burden and 11.0% were over‐nutrition households; only 0.3% were under‐nutrition households. Households in urban settings, with private water access, male children, and older mothers, were more likely to be over‐nutrition or double burden households compared to normal‐weight households. Wealthier households were more likely to have over‐nutrition pairs. Compared to over‐nutrition households, double burden households were poorer and more likely to have a child with lower birth weight.ConclusionThese nationally representative data demonstrate the existence of double burden households in the MENA region, the seeming disappearance of underweight mother‐child pairs, and the social context of household weight status.