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Limitations Of Genetic Testing, Tony N. Jelsma

Faculty Work Comprehensive List

"Knowing about a pathogenic variant may sharpen our awareness of our mortality, but it should not fundamentally change our perspective on life."

Posting about the advantages and disadvantages of genetic screening from In All Things, an online hub that offers insight into maintaining and faithful and orthodox Reformed Christian worldview while fearlessly engaging in every aspect of contemporary life – until all is made new.

Limitations of Genetic Testing

Science Communication Tools: Rubrics For Generating Posters And Manuscripts That Are Authentic To The Practice Of Science, Tamarah Lynne Adair, Swati Agrawal, Yesmi P. Ahumada-Santos, Regina Alvarez, Kirk Anders, Rebekah F. Hare

Biology Faculty Scholarship

Traditional undergraduate science courses often prioritize content mastery over authentic engagement with the scientific process. Course-based research, also referred to as course-based undergraduate research experiences (CUREs), addresses this limitation by immersing students in authentic scientific practice. In course-based research, assessment practices can also mirror the authentic scientific practice, where extensive formative feedback supports refinement of skills and understanding. Here, we present two rubrics designed to support the teaching and assessment of science communication in a way that reflects how scientists prepare to disseminate their research findings. One rubric is for creating scientific posters and another for writing short-format manuscripts. Developed …

Winner's Curse Free Robust Mendelian Randomization With Summary Data, Zhongming Xie, Wanheng Zhang, Jingshen Wang, Chong Wu

Faculty, Staff and Student Publications

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses using summary data may still produce biased causal effect estimates due to the winner’s curse and pleiotropy issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner’s curse and screens out invalid genetic instruments with pleiotropic effects. …

Eepd1 Evolved A Unique Dna Clamping Dimer Protecting Reversed Replication Forks, Runze Shen, Altaf H Sarker, Yue Chen, Min Liu, Sunetra Roy, Andrew S Arvai, Albino Bacolla, Zamal Ahmed, Panagiotis Katsonis, Michal Hammel, Isao Kuraoka, Miaw-Sheue Tsai, Corydon Irie, Lukas Webb, Olivier Lichtarge, Chi-Lin Tsai, Susan E Tsutakawa, Katharina Schlacher, John A Tainer

Faculty, Staff and Student Publications

Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, plus molecular and cell biology to define EEPD1 structure, assembly, and function at stalled DNA replication forks. Results imply EEPD1 surprisingly requires both unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)2] domains to clamp double-stranded (ds) DNA at reversed DNA replication forks for fork protection. Small-angle X-ray Scattering (SAXS), crystal, and cryo-EM structures unveil an …

Structure–Activity Modeling And Hybrid Machine Learning-Based Prediction Of Bioactivity In Pyrazole Derivatives For Drug Discovery Applications, Kader Şahi̇n, Serhat Kiliçarslan, Serdar Durdaği, Emi̇n Saripinar

Turkish Journal of Biology

Background/aim: Pyrazole derivatives are of growing interest due to their diverse pharmacological activities. However, their biological activity is often highly sensitive to subtle structural modifications. Existing quantitative structure–activity relationships (QSAR) approaches frequently fail to capture the conformational flexibility and nonlinear structure–activity relationships (SAR) of such heterocyclic scaffolds, creating a gap in the accurate prediction of their biological profiles. Therefore, there is a strong need for more robust and predictive computational frameworks. This study addresses this gap by integrating four-dimensional (4D)-QSAR descriptors with hybrid machine learning (ML) techniques to improve predictive accuracy and provide a more reliable tool for structure-based drug …

Role Of Piezo1 Channels Expressed In Pvn In Regulating Sympathetic Nerve Activity And Arterial Blood Pressure In Rats, Yue Chen, Wei Guo, Jichun Wang, Min Wang, Yuying Yang, Gregory Miodonski, Enshe Jiang, Qing Hui Chen, Yi Yang, Renjun Wang

Michigan Tech Publications

Mechanosensitive Piezo1 channels participate in regulating pain sensitivity, insulin secretion, and vascular tension; however, their expression in the autonomic paraventricular nucleus (PVN) and role in modulating sympathetic outflow and cardiovascular function remain unstudied. In this study, unilateral PVN microinjection of the Piezo1 channel blocker Dooku1 (0.1, 1, 10, 100, and 200 pmol) administered to anesthetized male rats increased renal sympathetic nerve activity (RSNA) and mean artery pressure (MAP) in a dose-dependent manner, with maximum increases of 93 ± 30% (p < 0.0001) and 21 ± 5 mmHg (p < 0.0001), respectively, elicited by Dooku1 at 100 pmol. Similarly, PVN microinjection of the peptide Piezo1 channel blocker GsMTx4 (1 nmol) significantly increased RSNA (p < 0.001) and MAP (p < 0.0001). Conversely, PVN-microinjected Piezo1 channel activators Yoda1 (5 nmol) and Jedi2 (5 nmol) did not significantly alter RSNA or MAP. Western blot and qRT-PCR analyses of the hypothalamic PVN showed abundant Piezo1 mRNA and protein expression. Immunofluorescence detection showed that Piezo1 was expressed in pre-sympathetic PVN neurons with axons projecting to the rostral ventrolateral medulla. We conclude that Piezo1 channels expressed in the autonomic PVN neurons play an important role in regulating sympathetic outflow and cardiovascular function.

Cover And Contents

Turkish Journal of Biology

No abstract provided.

Innovative Approaches For Lung Cancer Screening And Interception, Jianjun Zhang, Matthew D Park, Tej Pandya, Elaine Shum, Jia Wu, Simon Heeke, Ramin Salehi-Rad, Thomas U Marron, Zhubo Wei, Hui Li, Torsten G Blum, John V Heymach, Steven M Dubinett, Pan-Chyr Yang, Charles Swanton, Miriam Merad

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results …

Supt16h-Associated Neurodevelopmental Disorder And Neurocristopathy: Genetic And Phenotypic Spectrum, Eunhye Lee, Seungmin Sim, Hee-Jung Choi, Eugene Y Liang, Carolyn Le, Roya Bina, Ryan Cohen, Elizabeth George, Soo Yeon Kim, Gifty Bhat, Erin Falsey, Richard Sidlow, Kristin Clinard, Shay Ben-Shachar, Eleina England, Beatriz Menendez, Isabella Herman, Shelly Nielsen, Jaya Punetha, Priya Bhola, J Austin Hamm, Megan A Keeney, Nike Sitzman, Sara Berger, Lakshmi Mehta, Alison J Conn, Lilian Downie, Myla Ashfaq, Hope Northrup, Ange-Line Bruel, Sylvie Odent, Justin O Szot, Noelia Nunez Martinez, Sunju Park, Julie Refkin, Jean-Marc Good, Fabienne Maurer, Cédric Le Caignec, David J Coman, Erin Anderson, Linda J Richards, Ryan J Dean, Caleb Yang, Chulwon Choi, Byung Joon Hwang, Jin Sook Lee, William B Dobyns, Murim Choi, Elliott H Sherr, Jong-Hee Chae, Yun Kee, Emanuela Argilli

Faculty, Staff and Student Publications

SUPT16H encodes a subunit of the FACT (FAcilitates Chromatin Transcription) complex, a histone chaperone essential for maintaining chromatin integrity during transcription, replication, and DNA repair. Pathogenic de novo SUPT16H missense variants have previously been linked to neurodevelopmental disorders in eight individuals. Here, we expand the genotypic and phenotypic spectrum by identifying 24 additional individuals harboring ultrarare heterozygous missense or truncating variants, who share overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and characteristic craniofacial dysmorphism. To elucidate the underlying mechanisms, we generated a supt16h knockout zebrafish model using CRISPR/Cas9. The supt16h loss-of-function (LOF) model recapitulated key patient phenotypes …

Role Of Developmental Plasticity In Tethered Flight Performance Of The Oriental Fruit Fly, Bactrocera Dorsalis (Hendel) (Diptera: Tephritidae), Thabang P. Moropa, Steve B.S. Baleba, Christopher W. Weldon

All Peer-Reviewed Publications

This study investigated the effect of nutrition on development of wings and adult body condition of Bactrocera dorsalis (Hendel), an exotic pest of Asian origin and a species of economic importance in South Africa. Six host fruit types were used to rear B. dorsalis: mango, guava, orange, grapefruit, papaya and apple. One day after emergence, adults were used for tethered flight assessments using computerised flight mills. Additional flies were assessed in terms of wing morphology using geometric morphometrics, flight muscle mass, and lipid content. There were significant differences in the larval and pupal developmental time as well as larval and …

Selenium-Thioredoxin Axis Contributes To Ferroptosis Resistance In Pancreatic Cancer Cells, Arslan Amer, Micah Olamide Idowu, Aqsa Ahsan, Alyssa A. Abbas, Tahiyat Alothaim, Xiaohu Tang

Michigan Tech Publications

Pancreatic ductal adenocarcinoma (PDAC) shows substantial heterogeneity in cysteine dependence and ferroptosis sensitivity. We identify two PDAC subtypes distinguished by EMT status: mesenchymal-like cells are highly cysteine-dependent and rapidly undergo ferroptosis upon cystine deprivation or system xc⁻ inhibition, whereas epithelial-type cells are ferroptosis-resistant. Selenium supplementation protects cells from erastin-induced ferroptosis, and this protection persists even when intracellular glutathione (GSH) is depleted, supporting an additional GPX4-independent protective mechanism. Sepp1 knockdown does not alter sensitivity, indicating that selenium’s protective effect is independent of Sepp1. Instead, epithelial-type cells rely on both cytosolic and mitochondrial thioredoxin reductases (TrxR1 and TrxR2) to maintain ferroptosis …

Increased Neuronal Activity Restores Circadian Function In Drosophila Models Of C9orf72-Als/Ftd, Sho Inami, Benjamin P. Jenny, Oghenerukevwe Akpoghiran, Sara I. Gallagher, Alexandra K. Strich, Ayako Tonoki, Davide Trotti, Aaron R. Haeusler, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Circadian rhythm disruptions are common across neurodegenerative diseases, but their link to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains unclear. The C9orf72 hexanucleotide repeat expansion is the most prevalent genetic cause of ALS/FTD. Here, we used Drosophila models expressing pathogenic arginine-rich dipeptides (PR or GR) or GGGGCC hexanucleotide repeats to investigate circadian deficits in C9orf72-ALS/FTD. We found that circadian rhythmicity and period length were altered in a repeat number-, dosage-, expression pattern-, and age-dependent manner. Additionally, we observed lower levels of the neuropeptide PDF, a key regulator of free-running circadian rhythms, as well as decreased projection complexity and …

Identification Of Berbamine Hydrochloride As A Novel Coagulation Factor Vii Inhibitor By Natural Product Library Screening Using Zebrafish As A Model, Jyotheeswaran Panapakam, Jillian Via, Ambarish Kumar, Ritu Adhikary, Edgar M. Elizondo, Jabila Mary, Rajeev Azad, Art Groven, Pubur Jagadeeswaran

Faculty Publications - Biological Sciences

Current antithrombotic drugs cause gastrointestinal and intracranial hemorrhage and interact with dietary components and other medications. Thus, there is a need for alternative antithrombotic drugs that have fewer side effects. We screened 547 natural products (NPs) for lethality and found 321 NPs were non-lethal to zebrafish larvae. Laser-induced venous thrombosis on larvae incubated with 321 NPs identified 76 NPs with prolonged time to occlusion of the vessel (TTO). Out of these, 43 were already identified platelet inhibitors and the remaining 33 NPs were tested using laser-induced arterial, ferric chloride-induced, and phenylhydrazine-induced thrombosis assays. Of the 33 NPs tested, 4 prolonged …

Gender Differences In College Students’ Physical Activity Self-Efficacy, Social Comparison Beliefs, And External Frames Of Reference, Ken Murfay, Sarah Pyszczynski, Sarah Collins

International Journal of Physical Activity and Health

This study examined whom college-aged individuals believe observing would more likely increase their physical activity self-efficacy (PASE) for a physical skill, whom they are more likely to compare their abilities to within a physical education (PE) class, how often they compare themselves to others in PE, and what students’ PASE scores were. Based on the mean scores for each question, students were more likely to compare themselves to a student than a teacher, friend than a non-friend, and similar or higher skilled peer than a lower skilled peer. To increase students’ confidence for a physical skill, students had higher levels …

External Validation Of The Proliferation Saturation Index Model In Predicting Tumour Volume Regression In Patients With Non-Small Cell Lung Cancer Undergoing Radiation Therapy, Sarah Barrett, Mohammad Zahid, Conor K Mcgarry, Heiko Enderling, Gerard M Walls, Laure Marignol

Faculty, Staff and Student Publications

Background: The Proliferation Saturation Index (PSI) model is a patient-specific mathematical model designed to simulate and predict tumour volume regression (TVR) during radiation therapy (RT) using early treatment response dynamics. This study validates the PSI model in an independent external cohort of patients with non-small cell lung cancer (NSCLC) using previously derived model parameters.

Methods: In a cohort of 71 patients, treated with definitive RT alone (55Gy/20#) tumour volume measurements extracted from 6 Cone Beam CT (CBCT) scans acquired on days 1, 2 and 3 and weekly thereafter. Model predictions of TVR at final CBCT (CBCT6) were made using tumour …

Hp1Β Recruits Ring1a To Ubiquitinate Histone H2a For Brca1-Mediated Resection Of Double-Stand Breaks, Vijaya Charaka, Raj K Pandita, Chi-Lin Tsai, Xiaoyan Wang, Sharmista Chakraborty, Kenneth S Ramos, Sandhik Nandi, Fransisca Leonard, Vipin Singh, Partha S Sarkar, Clayton R Hunt, John A Tainer, Chandrima Das, Tej K Pandita

Faculty, Staff and Student Publications

Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Addressing Population Aging: Innovative Approaches To Aging Research In China, Jingyi Li, Jinghui Lei, Qun Chu, Weiqi Zhang, Moshi Song, Yaojin Peng, Guanghui Liu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The increasing prevalence of aging and associated diseases poses a substantial challenge worldwide. In recent years, the field of aging research has achieved numerous breakthroughs. Nevertheless, challenges still persist. This study offers a comprehensive analysis of the advancements within China’s aging research, highlighting current challenges and proposing strategy and policy recommendations. These suggestions draw from various areas, including research paradigms and key issues, efficient resource management, development of essential technological research and innovation ecosystems, international collaboration, and considerations of ethics and governance. The aim is to provide valuable insights and guidance for enhancing the quality and impact of aging research …

Partial Mitochondrial Genome Of The Enigmatic Bermuda Fireworm Odontosyllis Enopla Verrill, 1900 (Annelida, Syllidae, Eusyllinae) And Its Phylogenetic Implications, Lynette D. Wyant, Brendan A. Cruz, Aydanni D. Gonzalez, Joshua M. Kovalcik, Maria A. Carolus, Lauren C. Hutto, Hope Chutjian, Jude C. Roman, Anneau Cappelmann, John J. Ankney, Aidan Popp, James B. Wood, D. Tye Pettay, Mercer R. Brugler

Natural Sciences Faculty Publications

The Bermuda fireworm, Odontosyllis enopla Verrill, 1900, is a marine polychaete that displays a unique bioluminescent mating ritual. Despite the first sighting of O. enopla more than 534 years ago, molecular data have been limited. Several syllid mitogenomes are currently available; however, there are only three published genes for O. enopla: two partial mitochondrial genes (16S [508 bp] and cox1 [653 bp]; 1,161 bp total) and one partial nuclear gene (18S [1,339 bp]). This study bioinformatically mined previously published transcriptomes of O. enopla for mitochondrial reads and subsequently assembled and annotated a partial mitochondrial genome (10,172 bp). The partial mitogenome …

A Case Study Of Suspected Sheep Losses Due To Chokecherry Not Death Camas, Kevin D. Welch, Clint A. Stonecipher, Stephen T. Lee, Daniel Cook, Benedict T. Green

Poisonous Plant Research (PPR)

Death camas (Zigadenus paniculatus) is a toxic plant often associated with poisoning cases in livestock, especially in sheep, in the spring on mountain foothills. Consequently, when sheep are found dead in mountain foothills, and death camas is present, it is often implicated as the potential cause of death. However, this may be over simplistic as there may be other plants that may also contribute to, or are the cause of, death in sheep. In this study, we present a case of approximately 200 sheep out of a band of 400 that died within 24 hours of beginning to …

Crispr Spacers Reveal Diverse And Abundant Thermococcales Viruses In Hydrothermal Vents, Ryan Catchpole, Justin Mclean, Emily St John, Anna-Louise Reysenbach, Mart Krupovic, Michael P. Terns

Biology Faculty Publications and Presentations

Viruses are the most pervasive biological entities on Earth and they profoundly shape host ecology and evolution. However, for many microbial lineages, knowledge of their viromes remains limited, especially for those inhabiting remote environments, including deep-sea ecosystems. Here, we leverage one of the most extensively cultivated and genomically characterized archaeal lineages, the Thermococcales, to identify novel viral genomes. By utilizing CRISPR spacers from isolates and spacer arrays reconstructed from metagenomes, we mined mobile genetic elements (MGEs) in 1,172 publicly available and newly sequenced hydrothermal vent metagenomic datasets. Comparative genomics and identification of viral hallmark proteins revealed 620 viral genomes across …

Adipocyte-Specific Deletion Of Sine Oculis Homeobox Homolog 1 Inhibits Lipolysis And Reduces Skin Fibrosis, Nancy Wareing, Tingting W Mills, Scott Collum, Minghua Wu, Lucy Revercomb, René Girard, Hui Liu, Alexes Daquinag, Mikhail Kolonin, Marka Lyons, Brian Skaug, Weizhen Bi, Meer A Ali, Haniyeh Koochak, Anthony R Flores, Yuntao Yang, W Jim Zheng, William R Swindell, Shervin Assassi, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited Systemic sclerosis (SSc) is characterized by dermal fibrosis accompanied by loss of dermal white adipose tissue (DWAT), yet the mechanisms linking adipocyte depletion to fibroblast activation remain unclear. Here we identify the transcription factor SIX1 as a central regulator coupling adipogenic repression with profibrotic signaling. SIX1 expression was increased in skin biopsies from two independent SSc cohorts and localized to fibroblast and perivascular stromal cells. In mice, ubiquitous or adipocyte-specific deletion of Six1 preserved DWAT, reduced collagen accumulation, and selectively decreased pro-fibrotic mediators. In cultured …

Cml-Like Biology Is A Unifying Feature Of Myeloid/Lymphoid Neoplasms With Tyrosine Kinase Fusions In Lymphoid Blast Phase Comment On: Multilineage Involvement In Abl-Class Fusion-Positive Pediatric B-Cell Acute Lymphoblastic Leukemia: Cml-Like Biology, Wei J Wang, Shimin Hu

Faculty, Staff and Student Publications

No abstract provided.

Determinasi Minimum Dietary Diversity Pada Anak Usia 6-23 Bulan: Analisis Survei Kesehatan Indonesia 2023, Elfys Ferdynan, Besral Besral

Jurnal Biostatistik, Kependudukan, dan Informatika Kesehatan

Keragaman pangan minimum atau minimum dietary diversity (MDD) merupakan indikator penting kualitas konsumsi pangan anak usia 6-23 bulan. Pemenuhan MDD berperan dalam mendukung pertumbuhan optimal dan pencegahan malnutrisi, termasuk stunting. Penelitian ini bertujuan untuk menganalisis faktor-faktor yang berhubungan dengan pemenuhan MDD pada anak usia 6-23 bulan di Indonesia. Data yang digunakan adalah data Survei Kesehatan Indonesia 2023 dengan desain potong lintang. Subjek penelitian adalah 17.991 anak usia 6-23 bulan. Analisis yang dilakukan menggunakan regresi logistik biner dengan penyesuaian desain complex samples. Hasil penelitian menunjukkan bahwa faktor yang meningkatkan peluang pemenuhan MDD secara signifikan meliputi usia anak 12-23 bulan, …

Anti-Apoptotic Bcl-2 Binds To All Three Ip3r Isoforms, Thereby Limiting The Ca2+-Flux Properties Of Ip3r Homo-Tetramers, Ian De Ridder, Claire Cauwelier, Larry E Wagner Ii, Jens Loncke, Vikas Arige, Irina I Serysheva, David I Yule, Geert Bultynck

Faculty, Staff and Student Publications

Anti-apoptotic B-cell lymphoma 2 (BCL-2) controls inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca²+ signalling. As cells typically express all three IP3R isoforms in variable abundances that assemble in hetero-tetrameric channels, the specific effects of BCL-2 on each isoform remain unclear. Here, we employed a reductionist approach using HEK293 cells triple-IP3R knockout reconstituted with a single IP3R isoform to elucidate the impact of BCL-2 on Ca2+ signalling by homo-tetrameric IP3R channels. Co-immunoprecipitation experiments demonstrated that BCL-2 interacts with each IP3R isoform. Live-cell Ca²+ imaging revealed that BCL-2 overexpression suppresses Ca²+ signals evoked by any of the three IP3R isoforms. Moreover, BCL-2 overexpression impaired …

Protecting ‘Punks’: The Shortcomings Of The Prison Rape Elimination Act, Rachel Goldsmith

Binghamton University Undergraduate Journal

Prisoner-on-prisoner sexual abuse is widespread in US male prisons, with inmates “turning each other out” by sexually assaulting each other. While the Prison Rape Elimination Act (PREA) received unanimous support in Congress in 2003, motivated by the Human Rights Watch Report “No Escape: Male Rape in Prisons,” scholars argue that the PREA fails to protect prisoners from prison rape: for example, its standards may be ineffective or criminalize consensual sex between prisoners. This essay will examine the shortcomings of the PREA, drawing on current legal scholarship, and propose solutions to enhance the law's effectiveness in protecting prisoners. The US government …

Recent Advances In The Pharmacological Properties Of Scutellarin: Mechanistic Insights And Therapeutic Potential, Hind A. Satar, Emad Yousif, Ahmed Ahmed, Muna Bufaroosha

AUIQ Complementary Biological System

Scutellarin, a flavonoid glycoside primarily derived from Scutellaria baicalensis, has garnered increasing scientific interest for its multifaceted pharmacological properties. This review summarizes recent advances in our understanding of scutellarin's therapeutic effects, including its antioxidant, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities. Emphasis is placed on elucidating its molecular mechanisms of action, such as modulation of the NF-κB, Nrf2, and PI3K/Akt pathways, and its role in regulating oxidative stress, inflammation, and apoptosis. Additionally, we discuss formulation innovations, including nanoparticle and liposomal delivery systems, aimed at overcoming scutellarin's poor oral bioavailability and enhancing therapeutic performance. Key limitations in current research …

International Society Of Sports Nutrition Position Stand: Effects Of Dietary Antioxidants On Exercise And Sports Performance, Drew E. Gonzalez, Broderick L. Dickerson, Brandon M. Roberts, Jennifer A. Kurtz, Adam M. Gonzalez, Matthew J. Mcallister, Jeffrey L. Heileson, Richard J. Bloomer, Shawn M. Arent, Darren G. Candow, Jeffrey R. Stout, Karen A. Hecht, Bill Campbell, Chad M. Kerksick, Douglas Kalman, Jose Antoino, Richard B. Kreider

Faculty Publications

Following a comprehensive review, the International Society of Sports Nutrition (ISSN) has developed an official position on the role of dietary antioxidants in exercise and sport. Antioxidants play a complex, context-dependent role in vivo; they can facilitate recovery from exercise but may also hinder training adaptations when consumed at supraphysiological doses. While endogenous antioxidant systems can effectively maintain redox balance, dietary sources, particularly whole foods, can help mitigate excessive oxidative stress following intense/heavy training or inadequate recovery. The influence of dietary antioxidants depend on timing, dosage, type, and individual factors. The ISSN’s official position encompasses the following: (1) Redox balance …

Tumor Microenvironment Transcriptional Activity Enables Robust Stratification Of Chemotherapy Response In Triple-Negative Breast Cancer, Yaoyi Dai, Xiaoxi Pan, Shuai Guo, Shuangxi Ji, Shaolong Cao, Matthew D Montierth, Yujie Jiang, Jeffrey T Chang, Leming Shi, Shabnam Shalapour, Gloria V Echeverria, Lucy Yates, Johan Staaf, Bora Lim, Yinyin Yuan, Wenyi Wang

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …