bluuebunny/crossref_metadata_2025_split huggingface dataset:
(Z)‐Bisdehydrodoisynolic Acid (BDDA), a Non‐Steroidal Uterotrophic and Potentially Neuroprotective Compound in Brain Injury, Induces Proestrus‐like Luteinizing Hormone Secretion and Lordosis Behavior in Ovariectomized Female Rats
Authors: Clough Rich W. , Viscomi Natalie S. , Arbogast Lydia , Hou Yuqing , Banz William J. 
Published: November 2023

Exploring therapeutic interventions in experimental Traumatic and Concussive Brain Injury (TBI, CBI) in rodents, we have previously reported that (Z)‐BDDA, a non‐steriodal but estrogenic compound of interest, significantly improved the rate and extent of behavioral improvement in rats subject to lateral fluid percussion brain injury (an experimental model of TBI). Z‐BDDA is a synthetic compound described as highly estrogenic based on uterotrophic activity in female rats. Estrogenicity in brain has not been established. Insofar as the effects of Z‐BDDA on TBI may be due to an “estrogenic” effect in brain, we sought to determine whether the compound does indeed have estrogenic effects on this organ. Accordingly, we explored the induction of Luteinizing Hormone (LH) secretion and lordosis behavior using a standardized priming model in ovariectomized (OVX) female rats. Female Sprague‐Dawley rats were OVXed under isofluorane anesthesia and assigned to various steroid treatment protocols intended to induce (preovulatory‐like) LH secretion sexual receptivity. Z‐BDDA (300 or 30 Ug/rat) or Estradiol Benzoate (EB, 10 ug/rat) was administered (sc) two weeks following OVX and some rats were also given progesterone (1mg/rat) 48 hours later. Lordosis behavior was assessed (at onset of dark‐phase) by placement in an arena containing a sexually mature male rat. Mount attempts by the male and lordotic responses in females were recorded to obtain a lordosis quotient. For endocrine studies, rats were treated as with the behavioral studies, but at onset of dark were euthanized and blood was collected immediately for LH measurement by radioimmunoassay. Our results confirmed a profound estrogenic effect of Z‐BDDA on both LH secretion and lordosis responding in female rats. Compared to control groups, Z‐BDDA was equipotent to EB in this priming model. Estrogenic compounds have shown high promise in the experimental brain injury literature but the use of estrogens per se, in the human context, is controversial. This warrants continued research with other compounds, such as Z‐BDDA, that are estrogenic and also have a variety of other attributes potentially beneficial in brain injury but that avoid the confounds of estrogen.Support or Funding InformationSupported by SIU School of Medicine and the SIUC Neuroscience Research Center.
Vexin (Vxn) Regulates Neurogenesis and Cell Cycle Exit Downstream of Proneural Factors
Authors: Moore Kathryn , Logan Mary , Al Diri Issam , Steele Michael , Vetter Monica 
Published: November 2023

Development of the retina is regulated by sets of proneural basic helix‐loop helix (bHLH) transcription factors that coordinate the generation of multiple cell types in a conserved sequence. These proneural bHLH factors promote the expression of target genes that regulate the timing of differentiation and maintain a balance between proliferation and differentiation. However, how these target genes mediate proneural effects remains incompletely understood. The objective of this study was to identify and characterize novel target genes of proneural bHLH factors. We identified vexin (vxn) as a novel target gene for Xenopus laevis proneural bHLH factors. In the developing Xenopus nervous system, Vxn is expressed by progenitors. Vxn encodes a novel protein with a predicted SH3‐family motif and is conserved across vertebrate species. To assess the function of vxn during retinal neurogenesis in Xenopus, we targeted retinal progenitors and performed RNA overexpression or knockdown using antisense vxn morpholinos (MO). We analyzed cell cycle exit, retinal neuron differentiation and changes in gene expression, and assessed subcellular location of Vxn protein.Vxn is transiently expressed as retinal progenitors initiate differentiation. Vxn overexpression at neural plate stages inhibited cell proliferation and promoted increased expression of the cyclin‐dependent kinase inhibitor p27Xic1. Both exogenously expressed epitope‐tagged mouse or Xenopus Vxn protein, as well as endogenous Vxn protein, localized to the cell membrane and the nucleus in both the neural plate and retina. We demonstrated that Vxn must localize to the nucleus to promote neural differentiation and cell cycle exit by generating forms of Vxn tagged with either nuclear export or nuclear localization sequences. Overexpression of either Xenopus or mouse vxn in retinal progenitors promoted increased differentiation of early born retinal neurons, and also strongly cooperated with the proneural factor Atoh7 to enhance retinal ganglion cell differentiation. Overexpression of vxn caused reduced retinal progenitor expansion resulting in reduced clone size. Conversely, MO knockdown of vxn inhibited retinal neuron differentiation, preferentially maintaining cells as retinal progenitors and reducing expression of terminal differentiation genes. Thus vxn is expressed in progenitors as they initiate neuronal differentiation, and appears to function in the nucleus to regulate cell cycle exit downstream of proneural bHLH factors during neural development.Support or Funding InformationSupported by NEI EY012274 to MLV. Thank you to Constance Dooley, Jianmin Zhang, Kaitllyn Phuong Le and Jacklyn Roberts for technical contributions.
Effects of Dietary Isoflavones, Age, and Stroke on Estrogen Pathway Activation in Male Rats
Authors: Hart Muriel Lynn , Huber Kalene , Grisley Elizabeth Dawn , Cheatwood Joseph L 
Published: November 2023

The effects of stroke can cause long lasting impairment on not only one's physical health but their quality of life and everyday function. Dietary modifications provide a potential solution to aid in neuroprotection and allow enhanced functional recovery post‐stroke. Previous investigation tested this, and found the addition of dietary soy compounds does show significantly improved functional recovery through behavioral tests in our rat models. Further studies aimed to identify specific effects on gene expression on the dietary inclusion of isoflavones alone, using Daidzein and Genistein, known neuroprotective estrogenic receptor activators. We not only examined the effect of isoflavone content on altered gene expression, but also age as another potential mediating factor either promoting or inhibiting anti‐inflammatory and neuroprotective pathways. In doing so, both adult and aged male Hooded Long Evan rats were separated into distinct dietary protein groups containing either Sodium Caseinate (CAS), or Sodium Caseinate with the isoflavones daidzein and genistein (CAS+ISO) two weeks before a permanent unilateral middle cerebral artery occlusion (MCAO). Tissue samples were collected from the injured hemisphere on Day +3 (n=6) and Day +0 (n=4; received no MCAO). Data were collected via a qPCR array after RNA extraction and cDNA synthesis, following the manufacturer's protocol guidelines (Qiagen). Expression of mRNA was compared between treatment groups based on age, isoflavone content, and stroke. Changes in mRNA expression greater than 2‐fold were considered significant. Detailed results will be presented on the poster.Support or Funding InformationNIH NCCAM (1R15AT006593; JLC) and DuPont Nutrition and Health
The Women in Science Undergraduate Organization at Otterbein University: Best Practices and Outreach Efforts
Authors: Hyatt Taylor B. , Bailey Hannah M. , Tansey John T. 
Published: November 2023

Otterbein University's Women in Science chapter has been restructured to better help its members reach their potential. We have written a formal constitution, organized professional events, and expanded our community outreach efforts. The constitution explains the foundation of our program and our goal of promoting the following:

A greater understanding of the contributions of women in all fields of science.
Providing an open environment for members to share and explore interests and career paths within the sciences.
As an organization, we attended a presentation given Dr Angelika Nelson of Ohio State University. We had the opportunity to speak with her after the presentation, ask her questions about her career as well as ask her advice on our own career paths. She was able to share personal experiences with us and also expand upon those to make them applicable to an undergraduate audience. It is our hope that our members can apply what they have learned to their future experiences. Women in Science also hopes to help engage with the local community. Last year, we participated in Otterthon, a fundraiser that benefits the Children's Miracle Network, and plan to continue this event annually. Members of Women in Science participated in Girl Day at Otterbein University. This event occurs every year but this year's focus was Science, Technology, Engineering, Art, and Mathematics (STEAM). Our representatives spoke with the middle school aged girls and helped with a liquid nitrogen ice cream demonstration. For the coming year, we have planned a science outreach night with a local elementary school. This night will incorporate approximately ten stations that each feature a different interactive activity for the children. We are expecting several hundred people to attend this event. We plan to partner with our ASBMB‐SC chapter to participate in Starry Night, a local interest festival that promotes interdisciplinary learning in STEAM fields. Annually, over 1500 visitors attended the festival. Our hope is that Women in Science will continue to grow in membership and opportunities available for our members.
Mentorship Training for Postdoctoral Researchers: Results from a Four Week Intervention Program
Authors: Pena Christopher George , Evans Teresa , Mustafa Shamim , Moreno Laura , McManus Linda 
Published: November 2023

The acquisition of mentoring skills in biomedical research has traditionally been a passive process via apprenticeships. Moreover, mentorship quality directly affects scientific productivity. Consequently, the National Institutes of Health (NIH) has strongly encouraged formal mentorship training for academic researchers including postdoctoral trainees (postdocs). While the acquisition of knowledge and skills in mentoring is encouraged, it is unclear whether postdocs value these skills and how greatly their mentoring ability can be improved by formal training. Furthermore, outcomes assessment following formal mentor training is necessary to ensure effective instruction. The present program and programmatic assessment was designed to address these important questions.The Offices of Postdoctoral Affairs and Career Development implemented a mentoring intervention program for postdoctoral trainees with the goals to increase awareness of trainee mentoring ability as well as improve trainee mentoring skills. This program, which consisted of four, two hour weekly sessions, included facilitated discussions and case studies centered around key competencies of mentoring: Elements of a mentoring relationship, effective communication, problem solving, and self‐evaluation. Program participants rated the importance and their development of 15 mentoring skills that aligned with these competencies in a pre and post intervention assessment via a Likert scale. Data were compiled across seven cohorts from 2012 to 2016 (n=34).All postdocs highly valued each of the mentoring skills prior to participation in this intervention program. These views were unchanged after intervention. In contrast to unchanged valuation of mentoring skills upon completion of the program, postdocs reported a substantial positive gain in skill development in all mentoring skills. The greatest skill improvement was ‘setting reasonable goals for a mentee’. The lowest skill improvement was ‘keeping a mentee engaged’.Postdoctoral research trainees highly value mentoring skills. Of importance, a formal process for mentorship training aids in trainee development of vital mentoring skills. Future studies are needed to address additional variables that may impact the outcomes of formal mentor training among postdoctoral trainees. Among these are trainee demographics including gender, area of research emphasis, duration of postdoctoral research training, trainee citizenship status, and the international location of predoctoral studies. Equally important will be consideration of the sustained impact of short term mentor training.Support or Funding InformationSupported in part San Antonio Biomedical Education and Research (SABER) K12 GM11726 and Clinical Translational Science Award (CTSA) 1KL2RR025766‐01.
Proxies For Success–How Application Changes Correlate To PhD Path Pursuit For a Small Diversity Research Program
Authors: Shadding Cherilynn R. , Whittington Dawayne 
Published: November 2023

STEM diversity research programs have shown progress in increasing the number of underrepresented students who pursue STEM at the highest degree levels. While many programs have delineated gains of program participants, fewer programs have outlined the path to their outcomes, namely the STEM Ph.D. Our program, Opportunities in Genomics Research (OGR) through two cycles of NIH funding showed significant increases in Ph.D. matriculation from cycle one to cycle two of funding. We explored typical measures such as GPA, institution classification, and graduate school ranking of participants and compared by cycles and found that these measures did not alone explain the improved outcomes. We examined changes we made to our application materials, where we increased the number of questions serving as proxies for gauging interest in pursuing a Ph.D. Our data show a significant correlation of pursuit of the Ph.D. path to increased proxies and proxy type (open‐ or close‐ended questions answered by applicant or referee). We believe that we are the first to statistically demonstrate that changes in application materials for diversity research programs correlates to improved program outcomes.Support or Funding Information2R25HG006687‐05
Design and Implementation of an Experiential Learning Workshop for Upper‐level Undergraduate Science Majors
Authors: Connelly Sandra J. , Johnson Rebecca , Mills Jeffrey L. 
Published: November 2023

Historically, science courses designed for majors lack critical thinking, application of concepts beyond the field of study, and fall short of an interdisciplinary approach to learning and investigation. Instructors often struggle with implementing curricular designs for interdisciplinary students, even in light of obvious STEM educational reform efforts nationwide (e.g. “Science for All Americans,” “Benchmarks for Science Literacy,” and “Standards for Technological Literacy: Content for the Study of Technology”). Course redesigns that have centered on problem‐based learning for both majors and non‐majors are typically limited to single discipline classes and have reported moderate success, but are not without their shortcomings as well – specifically engagement of students in topics and the lack of multidisciplinary approaches. Our objective was to design an experiential learning course for biology and chemistry majors that aligns with graduation requirements and addresses some of the aforementioned shortcomings. The primary focus of this implementation was to assure that the course reflected the fundamental needs of science curricula: critical thinking, conceptual application, experiential learning, and interdisciplinary learning and investigation. Students worked in interdisciplinary groups to solve real world problems, including soil pollution remediation, algae as a source of biofuels, antibiotic resistance, and waste stream remediation for a local cidery. We have assessed the learning gains of the students using the “Student Assessment of their Learning Gains” (pre‐ and post‐course), weekly individual progress reviews, oral presentations of research proposals and final results, peer reviews of group work, ePortfolios, and evaluation of the course faculty by an in‐house Instructional Designer. Qualitative assessments of student professional and personal dynamics in the course have also been compiled and will be presented. We propose the development of similar courses in multiple overlapping disciplines to break down the silos of learning and better prepare students for their future endeavors.Support or Funding InformationThe course design and implementation presented is funded by a Provost's Learning Innovations Grant at Rochester Institute of Technology.
Assessing Student Competencies Using Rubrics Associated with Figure Legends and Ability to Perform the Bradford Assay in a 400‐level Undergraduate Course on Proteomics
Authors: Shipman Richard , Grant Jennifer 
Published: November 2023

The University of Wisconsin Stout is the polytechnic of the UW‐System. Aligned with our core values, Proteomics (BIO‐425) is a 3‐credit lecture and laboratory course that emphasizes the use of hands‐on techniques, particularly microchromatographic and protein digestion strategies. In addition to learning techniques like in‐gel digestion of proteins and protein chemistry techniques, students also developed and tested their own protein purification strategy in a mini‐project format. At the heart of this course, assessments revolve around completion of laboratory reports that follow the Abstract/Introduction/Methods/Results/Discussion (AIMRD) commonly followed by scientific articles.One focus of our semester‐long course was to instruct students in the performance of the Bradford protein assay at the level of a professional in the field. R2 values for their standard curves, made using bovine serum albumin serial dilutions, were tracked over the semester. Data on student success with the Bradford assay, and particularly measures of student progress over the course of the semester, were evaluated. Time to competence appears to be the most effective measure of student success. On average it required three attempts for students to gain proficiency at the Bradford assay.A second measure of student success is the time to proficiency in creating graphs within lab reports. Here we report the rubric used to evaluate graphs submitted by students, which measures appropriateness of axis labels, titles, and figure legends. While development of this rubric is ongoing, the present version provides insight into the intellectual development of the students taking this course.In all, this presentation provides useful measures of student success that focus on data that can be harvested from lab reports submitted by the students. The authors are actively soliciting feedback on statistical measures that can be utilized to quantify learning outcomes in both formative and summative arenas.
Bypass and Misincorporation of DNA Polymerases at DNA‐Peptide Crosslinks
Authors: Sedgeman Carl Andrew , Guengerich F. Peter 
Published: November 2023

The DNA of all living organisms is constantly exposed to chemicals that can cause diverse harmful lesions, one of which is DNA‐peptide cross‐links. The formation of DNA‐peptide cross‐links (DPCs) has been shown to occur from the modification to DNA bases by bis‐electrophiles and concomitantly nuclear proteins such as glutathione and O6‐alkylguanine DNA alkyltransferase (AGT). These conjugates have been discovered in cells and can induce both DNA mutations and cell death. Our hypothesis is that some translesion DNA polymerases are capable of replicating past DNA‐peptide cross‐links. A corollary of our central hypothesis is that AGT cross‐linked to DNA causes mutations after being partially degraded by proteases. For the investigation of the bypass and miscoding ability of DPCs by translesion DNA polymerases, DNA replication assays have been performed in duplex DNA substrates containing an N6‐dA‐DPC formed by glutathione and peptides from the active site of AGT (3–15 aa). Preliminary results indicate that human Pols kappa and iota have low processivity past these adducts compared to Pol eta and Sulfolobus solfataricus Dpo4. Bypass by Pol eta yielded higher levels of misincorporation. Steady‐state kinetics similarly show that Pol eta has a greater proclivity for misincorporation compared to Pols kappa and iota.This work was supported in part by National Institutes of Health grants R01 ES010546 and T32 GM065086.
A Novel Small Molecule Inhibitor of Human DNA Polymerase Eta Modulates the Efficacy of Cisplatin in Cancer Cells
Authors: Zafar Maroof Khan , Maddukuri Leena , Penthala Narsima R , Ketkar Amit , Eddy Sarah , Reed Megan R , Crooks Peter A , Eoff Robert L 
Published: November 2023

Chemotherapeutic strategies involving platinum‐based drugs rely on DNA damage to limit tumor growth. Activation of DNA damage response pathways can modulate patient response to these types of therapies. For example, translesion DNA synthesis (TLS) by human DNA polymerase (pol) eta (η) can render platinum‐based chemotherapy ineffective through the direct bypass of DNA damage. Therefore, targeting hpol η with small‐molecule inhibitors is a promising strategy for combating chemoresistance in certain types of cancer, such as ovarian cancer, that rely on hpol η to survive genotoxic chemotherapy. The main objective of our study was to identify small molecule inhibitors of hpol η that modulate the efficacy of genotoxic anti‐cancer drugs in an effort to improve patient outcomes. Towards that end, the catalytic activity of hpol η was measured in the presence of eighty‐five novel indole thio‐barbituric acid (ITBA) and indole barbituric acid (IBA) derivatives. Several compounds that inhibit hpol η activity with low micromolar IC50s were identified from this initial screen. One of these compounds, PNR‐7‐02, an ITBA derivative with both N‐napthoyl moiety and 5‐chloro substituent on the indole ring inhibited hpol η activity with an IC50 value of 8 μM. PNR‐7‐02 also inhibited hRev1 and hpol lambda (λ) with low micromolar IC50, but inhibition by PNR‐7‐02 was approximately ten‐fold more potent against hpol η than B‐family pols. Michaelis‐Menten kinetic analysis revealed a partial competitive mechanism of inhibition of hpol η activity. Chemical labeling and molecular docking results further supported the kinetic mechanism of inhibition. A target‐dependent effect on cell viability was observed when comparing hpol η‐proficient and hpol η‐deficient HAP‐1 cells co‐treated with cisplatin and PNR‐7‐02. The calculated combination index values indicated a strong synergy between cisplatin and PNR‐7‐02 in hpol η‐proficient cells. This synergy was not evident in the hpol η knockout cells, supporting the idea that PNR‐7‐02 modulates cisplatin toxicity in a hpol η‐dependent manner. Results from cell sorting experiments were consistent with synergy observed between cisplatin and PNR‐7‐02. In summary, our lab has performed the first quantitative structure activity relationship for TLS pols to identify potent inhibitor of hpol η that sensitizes cancer cells to cisplatin treatment.Support or Funding InformationThis work was supported by NIH grants GM 084460 and CA 183895 (to R.L.E.).