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1. Don’t Drink and Fly: Alcohol Resistance Behavior in Drosophila Informs us about Genes that Contribute to Alcoholism

   Echeverria, Jennifer S.; Key, S. Catherine (April 2022, Advances in biology laboratory education)

   Thueck, Suzanne; Ettinger, Audrey J. (Ed.)

   Many undergraduate students understand that model organisms are important for understanding how biology works, but may not make the connection that animal models such as Drosophila melanogaster can be used to understand such human conditions as Alcohol Use Disorder (AUD) and Fetal Alcohol Syndrome (FAS). To address this knowledge gap, we introduced an inquiry-based laboratory module in which students perform hands-on Ethanol Behavior Mobility Assays (EMBAs) using flies with either different Alcohol Dehydrogenase (ADH) alleles or different developmental exposure to ethanol. The lab module contains a bioinformatic component for students to explore the evolutionary conservation of the ADH gene between flies and humans. The implementation of this exercise in a sophomore/junior-level Genetics course led to a high level of student satisfaction and a more integrated view of the role of model organisms in studying AUD and FAS. Funding acknowledgements: ABLE Roberta Williams Laboratory Teaching Initiative Grant and NSF HBCU-UP TIP Grant # 1912188. 

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2. Transcriptomic changes due to early, chronic intermittent alcohol exposure during forebrain development implicate WNT signaling, cell‐type specification, and cortical regionalization as primary determinants of fetal alcohol syndrome

   https://doi.org/10.1111/acer.14590  

   Fischer, Máté; Chander, Praveen; Kang, Huining; Mellios, Nikolaos; Weick, Jason P. (April 2021, Alcoholism: Clinical and Experimental Research)

   Abstract BackgroundFetal alcohol syndrome (FAS) due to gestational alcohol exposure represents one of the most common causes of nonheritable lifelong disability worldwide. In vitro and in vivo models have successfully recapitulated multiple facets of the disorder, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic mechanisms underlying FAS. MethodsIn this study, we utilized an in vitro human pluripotent stem cell‐based (hPSC) model of corticogenesis to probe the effects of early, chronic intermittent alcohol exposure on the transcriptome of first trimester‐equivalent cortical neurons. ResultsWe used RNA sequencing of developing hPSC‐derived neurons treated for 50 days with 50 mM ethanol and identified a relatively small number of biological pathways significantly altered by alcohol exposure. These included cell‐type specification, axon guidance, synaptic function, and regional patterning, with a notable upregulation of WNT signaling‐associated transcripts observed in alcohol‐exposed cultures relative to alcohol‐naïve controls. Importantly, this effect paralleled a shift in gene expression of transcripts associated with regional patterning, such that caudal forebrain‐related transcripts were upregulated at the expense of more anterior ones. Results from H9 embryonic stem cells were largely replicated in an induced pluripotent stem cell line (IMR90‐4), indicating that these patterning alterations are not cell line‐specific. ConclusionsWe found that a major effect of chronic intermittent alcohol on the developing cerebral cortex is an overall imbalance in regionalization, with enrichment of gene expression related to the production of posterodorsal progenitors and a diminution of anteroventral progenitors. This finding parallels behavioral and morphological phenotypes observed in animal models of high‐dose prenatal alcohol exposure, as well as patients with FAS. 

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3. Plasma Concentrations of High Mobility Group Box 1 Proteins and Soluble Receptors for Advanced Glycation End-Products Are Relevant Biomarkers of Cognitive Impairment in Alcohol Use Disorder: A Pilot Study

   https://doi.org/10.3390/toxics12030190  

   Rodríguez_de_Fonseca, Fernando; Medina-Paz, Francisco; Sapozhnikov, Mira; Hurtado-Guerrero, Isaac; Rubio, Leticia; Martín-de-las-Heras, Stella; Requena-Ocaña, Nerea; Flores-López, María; Fernández-Arjona, María_del Mar; Rivera, Patricia; et al (March 2024, Toxics)

   Alcohol use disorder (AUD) is a major component in the etiology of cognitive decline and dementia. Underlying mechanisms by which long-term alcohol abuse causes cognitive dysfunction include excessive oxidative stress and inflammation in the brain, activated by increased reactive oxygen/nitrogen species (ROS/RNS), advanced glycation end-products (AGEs) and high-mobility group box 1 protein (HMGB1). In a pilot study, we examine the potential clinical value of circulating biomarkers of oxidative stress including ROS/RNS, HMGB1, the soluble receptor for AGE (sRAGE), the brain biomarker of aging apolipoprotein D (ApoD), and the antioxidant regulator nuclear factor erythroid 2-related factor 2 (NRF2) as predictive indices for cognitive impairment (CI) in abstinent patients with AUD (n = 25) compared to patients with established Alzheimer’s disease (AD, n = 26) and control subjects (n = 25). Plasma concentrations of sRAGE were evaluated with immunoblotting; ROS/RNS with a fluorometric kit; and HMGB1, ApoD, and NRF2 by ELISA. Abstinent AUD patients had higher sRAGE, ROS/RNS (p < 0.05), and ApoD (p < 0.01) concentrations, similar to those of AD patients, and lower NRF2 (p < 0.01) concentrations, compared to controls. These changes were remarkable in AUD patients with CI. HMGB1, and sRAGE correlated positively with duration of alcohol use (rho = 0.398, p = 0.022; rho = 0.404, p = 0.018), whereas sRAGE correlated negatively with periods of alcohol abstinence (rho = −0.340, p = 0.045). A predictive model including ROS/RNS, HMGB1, sRAGE, alcohol use duration, and alcohol abstinence periods was able to differentiate AUD patients with CI (92.3% of correct predictions, ROC-AUC= 0.90) from those without CI. In conclusion, we propose ROS/RNS, HMGB1, and sRAGE as stress biomarkers capable of predicting cognitive impairment in AUD patients. 

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4. Engaging Nontraditional Students by CURE‐ing Microbes on Ocean Plastics

   Barral, AM (April 2019, The FASEB journal)

   It is well known that learning occurs best when students are engaged with a topic that interests them or has relevance for important aspects of their lives. In coastal California, the health of the ocean is a serious local concern, and ocean plastics are ubiquitous. We have developed a course‐based undergraduate research experience (CURE) on an existing research project addressing microbes colonizing floating plastic marine debris. The objective of the project is to increase student engagement and persistence in biology. The project (recently awarded an NSF education grant focused on Hispanic students) brings together National University (NU), an undergraduate teaching institution serving non‐traditional students, with Scripps Institution of Oceanography (SIO), a world‐renowned research‐oriented institution at UC San Diego. A modular design allows students from different biology courses (both non‐majors and majors) to participate in field and laboratory research while also interacting with research scientists and graduate students. Module contents range from classroom material including experimental design, hypothesis testing, and data analysis, to laboratory activities such as deployment of test materials, microbiology and molecular biology techniques, as well as bioinformatics. Assessment of the project involves surveys and focus groups to evaluate student engagement, as well as institutional metrics such as retention in the BS Biology program. A pilot involving a non majors general biology course visiting SIO was well‐received by students. Currently (November 2018) an extended intervention is underway with a majors general biology course. During the first week of class students learned about the research project via video material and class lectures. A half day visit to SIO provided them with field trip experience, laboratory activities, presentation about plastic research, and interactions with scientists and graduate students. In successive laboratory activities, students observed colony morphology, performed Gram stainings and colony PCR, practiced Blast searches and developed simple phylogenetic trees. We conclude that the framework can be successfully implemented in spite of time and logistical challenges. We anticipate implementing and disseminating this CURE as a widely applicable model for biology and ocean science education centered on contemporary topics of immediate interest to students. Support or Funding Information This project is funded by the NSF‐HSI grant #1832545 

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5. Joint Active User Detection, Channel Estimation, and Data Detection for Massive Grant-Free Transmission in Cell-Free Systems

   https://doi.org/10.1109/SPAWC53906.2023.10304473  

   Sun, Gangle; Cao, Mengyao; Wang, Wenjin; Xu, Wei; Studer, Christoph (September 2023, IEEE 24th International Workshop on Signal Processing Advances in Wireless Communications (SPAWC))

   Cell-free communication has the potential to significantly improve grant-free transmission in massive machine-type communication, wherein multiple access points jointly serve a large number of user equipments to improve coverage and spectral efficiency. In this paper, we propose a novel framework for joint active user detection (AUD), channel estimation (CE), and data detection (DD) for massive grant-free transmission in cell-free systems. We formulate an optimization problem for joint AUD, CE, and DD by considering both the sparsity of the data matrix, which arises from intermittent user activity, and the sparsity of the effective channel matrix, which arises from intermittent user activity and large-scale fading. We approximately solve this optimization problem with a box-constrained forward-backward splitting algorithm, which significantly improves AUD, CE, and DD performance. We demonstrate the effectiveness of the proposed framework through simulation experiments. 

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