Review
Oncology
Qier Zhou, Zhiwei Zhang, Songkai Long, Wanjun Li, Baiyun Wang, Na Liang
Summary: The kappa-opioid receptor (KOR) is associated with various types of cancer and understanding this association may facilitate the development of new antitumor therapies.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Pharmacology & Pharmacy
Keith M. Olson, Andrea L. Devereaux, Payal Chatterjee, Savanah L. Saldana-Shumaker, Amanda Shafer, Adam Plotkin, Ram Kandasamy, Alexander D. MacKerell, John R. Traynor, Christopher W. Cunningham
Summary: This study investigates the structure-activity relationships of benzylideneoxymorphone analogs in order to develop analgesics with reduced tolerance and side effects. One compound, nitro-BOM (NBOM), showed high-efficacy antinociception but also exhibited tolerance and toxicity upon repeated administration. Despite these issues, NBOM provides an important tool for understanding MOPr/DOPr pharmacology.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Kanako Miyano, Yuki Yoshida, Shigeto Hirayama, Hideki Takahashi, Haruka Ono, Yoshiyuki Meguro, Sei Manabe, Akane Komatsu, Miki Nonaka, Takaaki Mizuguchi, Hideaki Fujii, Yoshikazu Higami, Minoru Narita, Yasuhito Uezono
Summary: The study found that OT acts as a positive allosteric modulator of KOR and MOR, enhancing G protein signaling without affecting beta-arrestin signaling.
Article
Chemistry, Medicinal
Wei-Jie Fang, Thomas F. Murray, Jane Aldrich
Summary: The study investigates the cyclization of Dyn A analog arodyn to limit conformational flexibility and enhance affinity and selectivity for kappa opioid receptors. Both cis and trans isomers of cyclized peptides exhibit competitive antagonism of kappa opioid receptors similar to arodyn, providing important information for the design of next-generation cyclic arodyn analogs.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Article
Chemistry, Medicinal
Hongsong Feng, Rui Wang, Chang-Guo Zhan, Guo-Wei Wei
Summary: In this study, a deep generative model combining a stochastic differential equation (SDE)-based diffusion model with a pretrained autoencoder is proposed. The model efficiently generates molecules targeting multiple opioid receptors and evaluates their ADMET properties. Molecular optimization is performed to enhance the pharmacokinetic properties of lead compounds. Advanced binding affinity predictors are built using molecular fingerprints, providing a valuable tool for evaluating the pharmacological effects of the generated molecules.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Christiane Muehle, Massimiliano Mazza, Christian Weinland, Claudia von Zimmermann, Patrick Bach, Falk Kiefer, Valery Grinevich, Iulia Zoicas, Johannes Kornhuber, Bernd Lenz
Summary: This study analyzed the OXTR serum concentrations in patients with AUD, finding a correlation between higher OXTR levels in male patients with alcohol-related readmissions. However, OXTR concentrations did not significantly differ between male and female patients with AUD and controls. The study also found lower OXTR concentrations in female smokers compared to non-smokers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Selin Ozkan-Kotiloglu, Dilek Kaya-Akyuzlu, Safak Yalcin-Sahiner, Nagihan Ayaz
Summary: The aim of this study was to evaluate the association between OPRK1 rs963549 and rs997917 and opioid use disorder (OUD) and related phenotypes. A total of 208 individuals with (n = 100) and without (n = 108) OUD participated in the study. OPRK1 rs963549 and rs997917 were analyzed using PCR-RFLP. Craving, opioid withdrawal, and the intensity of depressive and anxiety symptoms were measured using appropriate scales. The results showed a trend of association between OPRK1 rs963549 variation and decreased opioid withdrawal. There were no significant associations between OPRK1 rs963549 and rs997917 polymorphisms and craving, depression, or anxiety symptoms. Neither single OPRK1 SNPs nor OPRK1 haplotypes were associated with OUD.
Article
Biology
Karen L. Bales, Forrest D. Rogers
Summary: This paper reviews the literature on the neuroendocrine mechanisms for the emotional consequences of partner loss, with a special focus on hypothesized interactions between oxytocin, corticotropin-releasing hormone and the kappa opioid system.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Cell Biology
Ha Jung Lee, Seong Hyun Kim, Yong Hwan Kim, So Hyun Kim, Gyeong Seok Oh, Ji-Eun Bae, Joon Bum Kim, Na Yeon Park, Kyuhee Park, Eunbyul Yeom, Kwiwan Jeong, Pansoo Kim, Doo Sin Jo, Dong-Hyung Cho
Summary: Selective autophagy, specifically melanophagy, can be induced by activating kappa-opioid receptors and inhibiting protein kinase A (PKA) activation, resulting in reduced melanin content. The chemical nalfurafine hydrochloride acts as a potent inducer of melanophagy and can suppress excessive melanin production in melanocytes. Moreover, forskolin, a PKA activator, can restore PKA activation and reverse the decrease in melanin content caused by nalfurafine hydrochloride, suggesting the involvement of PKA in melanophagy.
Article
Neurosciences
Lihua Sun, Jing Tang, Heidi Liljenback, Aake Honkaniemi, Jenni Virta, Janne Isojarvi, Tomi Karjalainen, Tatu Kantonen, Pirjo Nuutila, Jarmo Hietala, Valtteri Kaasinen, Kari Kalliokoski, Jussi Hirvonen, Harry Scheinin, Semi Helin, Kim Eerola, Eriika Savontaus, Emrah Yatkin, Juha O. Rinne, Anne Roivainen, Lauri Nummenmaa
Summary: The study found that both humans and rats exhibit significant seasonal variations in cerebral MOR availability, primarily associated with seasonal changes in photoperiod. Changes in daylength were shown to influence MOR availability in the brain, impacting behaviors and physiological responses.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Substance Abuse
Selin Ozkan-Kotiloglu, Dilek Kaya-Akyuzlu, Rabia Yurdakul, Mukaddes Asena Yildirim, Inci Ozgur-Ilhan
Summary: Variations in KOR are associated with the risk of AUD and the intensity of depressive symptoms at admission in Turkish males. However, the PDYN gene seems to be unrelated to AUD, depression, anxiety, and craving.
ALCOHOL AND ALCOHOLISM
(2023)
Article
Cell Biology
Jin Niu, Chen Wu, Min Zhang, Zhen Yang, Zhenhua Liu, Feng Fu, Jun Li, Na Feng, Xiaoming Gu, Shumiao Zhang, Yali Liu, Rong Fan, Juan Li, Jianming Pei
Summary: In this study, it was found that the selective kappa-opioid receptor agonist U50,488H can inhibit calcification of rat vascular smooth muscle cells (VSMCs) by reducing PFKFB3 expression and lactate content. These findings suggest a potential drug target and strategy for the clinical treatment of vascular calcification.
Article
Multidisciplinary Sciences
Jessica M. Halow, Rachel Byron, Megan S. Hogan, Raquel Ordonez, Mark Groudine, M. A. Bender, John A. Stamatoyannopoulos, Matthew T. Maurano
Summary: The study investigates the genetic effects on DNA accessibility in vivo across multiple cell and tissue types using highly diverged hybrid mice, providing a foundation for quantitatively predicting the cell-type specific effects of non-coding variation on TF activity.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Christos Karoussiotis, Aggeliki Sotiriou, Alexia Polissidis, Alexandra Symeonof, Danae Papavranoussi-Daponte, Vassiliki Nikoletopoulou, Zafiroula Georgoussi
Summary: Recent evidence suggests that G protein-coupled receptors (GPCRs) directly sense autophagy and opioid receptors regulate neuronal plasticity and neurotransmission through an unknown mechanism. In this study, the researchers demonstrate that the selective kappa-opioid receptor (kappa-OR) agonist U50,488H induces autophagy in a time- and dose-dependent manner in neuronal cells, upregulating specific autophagic markers. Molecular analysis reveals that kappa-OR activation upregulates the becn1 gene through the ERK1,2-dependent activation of the CREB transcription factor. Furthermore, sub-chronic administration of U50,488H in mice leads to increased autophagic markers and decreased synaptic proteins in the hippocampus, while administration of the kappa-OR selective antagonist nor-binaltorphimine (norBNI) blocks autophagy induction and stress-induced reduction of synaptic proteins in the hippocampus. These findings provide new insights into the role of autophagic machinery in the regulation of brain plasticity by kappa-OR signaling.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Dermatology
Rosanna Marsella, Kim Ahrens, Rachel Wilkes, Michael Soeberdt, Christoph Abels
Summary: This study demonstrated the efficacy of 1% topical kappa-opioid agonist in dogs with atopic dermatitis; however, a crossing of pruritus scores on Day 17 resulted in no significant effect on pruritus, and over time, the active ingredient showed decreasing efficacy after the first 3 weeks.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Genetics & Heredity
Kaitlin Sikkink, Paula Delk, Leah Wetherill, Amy Breman, Melissa Wesson
Summary: This study investigated the factors influencing genetic counselors' participation in research activities by surveying their workplace and graduate training experiences. The results showed that the counselors' interest and motivation in research, as well as their perceived intimidation by the research process, were the most significant factors.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Genetics & Heredity
Paula Delk, Isabella Bowling, Courtney Schroeder, Theodore E. Wilson, Melissa Wesson, Leah Wetherill
Summary: This study investigated the perceptions of program leaders and clinical supervisors on the professionalism demonstrated by genetic counseling graduate students. The results showed that patient care was considered the most important domain and had the most strengths. However, there were lapses in professional behavior in terms of self-awareness, time management, and thoroughness. Participants suggested that education strategies from ACGC may improve the professional behavior of genetic counseling students and emphasized the importance of considering diverse professional and cultural backgrounds.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Biochemistry & Molecular Biology
Dina Popova, Isabel Gameiro-Ros, Mark M. Youssef, Petronio Zalamea, Ayeshia D. Morris, Iya Prytkova, Azadeh Jadali, Kelvin Y. Kwan, Chella Kamarajan, Jessica E. Salvatore, Xiaoling Xuei, David B. Chorlian, Bernice Porjesz, Samuel Kuperman, Danielle M. Dick, Alison Goate, Howard J. Edenberg, Jay A. Tischfield, Zhiping P. Pang, Paul A. Slesinger, Ronald P. Hart
Summary: Synonymous and noncoding single nucleotide polymorphisms (SNPs) in the KCNJ6 gene have been associated with increased frontal theta oscillations in individuals with alcohol use disorder (AUD). Excitatory glutamatergic neurons derived from subjects with KCNJ6 variants showed altered synaptic transmission and cellular morphology. Lower expression of GIRK2 and increased excitability were observed in neurons with KCNJ6 variants. Interestingly, exposure to ethanol reversed these effects in variant neurons. Ectopic overexpression of GIRK2 mimicked the effects of ethanol. In conclusion, KCNJ6 variants decrease GIRK2 expression and increase excitability, but these effects can be mitigated by ethanol.
MOLECULAR PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Nathaniel S. Thomas, Jessica E. Salvatore, Sally I-Chun Kuo, Fazil Aliev, Vivia V. McCutcheon, Jacquelyn M. Meyers, Kathleen K. Bucholz, Sarah J. Brislin, Grace Chan, Howard J. Edenberg, Chella Kamarajan, John R. Kramer, Samuel Kuperman, Gayathri Pandey, Martin H. Plawecki, Marc A. Schuckit, Danielle M. Dick
Summary: This study tested whether the childhood/adolescent home environment mediates genetic risk for alcohol problems across generations within families. The results showed that parental relationship discord and divorce partially mediated the transmission of genetic risk for alcohol problems from parents to children, predicting earlier ages of regular drinking, intoxication, greater lifetime maximum drinks, and more lifetime AUD criteria in European ancestry families. However, there was no evidence of indirect effects of parental alleles via relationship discord or divorce on offspring alcohol outcomes in African ancestry families.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Emma C. Johnson, Sarah M. C. Colbert, Paul W. Jeffries, Rebecca Tillman, Tim B. Bigdeli, Nicole R. Karcher, Grace Chan, Samuel Kuperman, Jacquelyn L. Meyers, John Nurnberger, Martin H. Plawecki, Louisa Degenhardt, Nicholas G. Martin, Chella Kamarajan, Marc A. Schuckit, Robin M. Murray, Danielle M. Dick, Howard J. Edenberg, Deepak Cyril D'Souza, Marta Di Forti, Bernice Porjesz, Elliot C. Nelson, Arpana Agrawal
Summary: This study found that genetic risk for schizophrenia is associated with cannabis-related paranoia, feeling depressed or anhedonia, social withdrawal, and cognitive difficulties. Even in individuals without clinical features, regular cannabis use may increase the likelihood of reporting unusual experiences related to cannabis use.
SCHIZOPHRENIA BULLETIN
(2023)
Article
Genetics & Heredity
Rachel W. Scouten, Melissa Wesson, Leah Wetherill, Gail H. Vance, Paula R. Delk
Summary: Program-level clinical remediation aims to help underperforming students in genetic counseling training programs gain clinical skills. This study surveyed program leaders to explore the remediation landscape, identifying areas of underperformance, remediation activities, and outcomes.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Genetics & Heredity
Taylor A. A. Steyer, Priscila D. D. Hodges, Caroline E. E. Rouse, Wilfredo Torres-Martinez, Leah Wetherill, Karrie A. A. Hines
Summary: Hispanic individuals have lower uptake of genetic counseling and testing, and this study aimed to determine if satisfaction with genetic counseling or mode of delivery preference differs between English- and Spanish-speaking individuals. Spanish-speaking individuals preferred in-person visits, while English-speaking individuals preferred virtual visits. Factors such as waiting time, work arrangements, and childcare affected their preferences.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Genetics & Heredity
Hannah Gage, Leah Wetherill, Katelynn Anderson, Erin Conboy, Kathryn Haider
Summary: This study explored the motivations of parents of pediatric patients for pursuing genetic testing and the topics they would like to discuss during their visit. Results showed that parents were primarily motivated by the opportunity to learn about their child's prognosis, formal diagnosis, and possible treatment options. They were most interested in discussing prognosis, adaptations for vision loss, and testing logistics. Although parents reported satisfaction with the care received, there was room for improvement in terms of their understanding of prognosis and the support resources provided.
OPHTHALMIC GENETICS
(2023)
Review
Behavioral Sciences
Emma E. Johnson, Jessica Salvatore, Dongbing K. Lai, Alison I. Merikangas, John A. Nurnberger, Jay Tischfield, Xiaoling Xuei, Chella Kamarajan, Leah P. Wetherill, John Rice, John Kramer, Samuel A. Kuperman, Tatiana M. Foroud, Paul Slesinger, Alison M. Goate, Bernice J. Porjesz, Danielle Dick, Howard Edenberg, Arpana Agrawal
Summary: This review summarizes the genetic approaches and outcomes of the family-based Collaborative Study on the Genetics of Alcoholism (COGA). COGA was established during the linkage era to identify genes influencing the risk for alcohol use disorder (AUD) and related issues, and it became one of the first AUD-focused studies to adopt a genome-wide association (GWAS) approach. COGA's family-based setup, multimodal assessment using gold-standard clinical and neurophysiological data, and the availability of longitudinal phenotyping continue to offer valuable insights into the etiology of AUD and related disorders.
GENES BRAIN AND BEHAVIOR
(2023)
Review
Behavioral Sciences
Arpana Agrawal, Sarah J. Brislin, Kathleen K. Bucholz, Danielle Dick, Ronald P. Hart, Emma C. Johnson, Jacquelyn Meyers, Jessica Salvatore, Paul Slesinger, Laura COGA Collaborators, Laura Almasy, Tatiana Foroud, Alison Goate, Victor Hesselbrock, John Kramer, Samuel Kuperman, Alison K. Merikangas, John I. Nurnberger, Jay Tischfield, Howard J. Edenberg, Bernice Porjesz
Summary: The Collaborative Study on the Genetics of Alcoholism (COGA) is a family based and diverse sample that aims to investigate the causes and consequences of Alcohol Use Disorders (AUD) and their related psychiatric comorbidities. Through questionnaires, brain function data, and genomic analyses, COGA explores the cellular and molecular mechanisms underlying AUD. COGA serves as a valuable scientific resource, not only providing data for research, but also promoting data sharing and communicating scientific findings to the broader community. Furthermore, COGA has the potential to nurture early career investigators and generate independent research in the field of gene-brain-behavior research on AUD.
GENES BRAIN AND BEHAVIOR
(2023)
Article
Mathematics, Interdisciplinary Applications
Susanne Bruins, Jouke-Jan Hottenga, Michael C. Neale, Rene Pool, Dorret I. Boomsma, Conor V. Dolan
Summary: Genotype-environment interaction refers to the moderation of genetic effects by the environment or environmental effects by genes on a phenotype. This article introduces genotype-environment interaction models and proposes a test based on the classical twin design. Simulation studies and empirical data analysis demonstrate the feasibility of this approach for detecting genotype-environment interaction, although its power depends on the heritability of the phenotype and the strength of genetic effects.
MULTIVARIATE BEHAVIORAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Chenglong Yu, Andrew Bakshi, Gerald F. Watts, Alan E. Renton, Brian Fulton-Howard, Alison M. Goate, Pradeep Natarajan, Daniel I. Chasman, Liubov Robman, Robyn L. Woods, Robyn Guymer, Rory Wolfe, Le Thi Phuong Thao, John J. Mcneil, Andrew M. Tonkin, Stephen J. Nicholls, Paul Lacaze
Summary: The study identified genetic variants in the CETP gene region associated with cardiovascular resilience during aging, individuals carrying these variants had better lipid profiles and reduced risk of ASCVD.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Psychiatry
Jacquelyn L. Meyers, Vivia V. McCutcheon, Kristina A. Horne-Osipenko, Lawrence R. Waters, Peter Barr, Grace Chan, David B. Chorlian, Emma C. Johnson, Sally I-Chun Kuo, John R. Kramer, Danielle M. Dick, Samuel Kuperman, Chella Kamarajan, Gayathri Pandey, Dzov Singman, Stacey Subbie-Saenz de Viteri, Jessica E. Salvatore, Laura J. Bierut, Tatiana Foroud, Alison Goate, Victor Hesselbrock, John Nurnberger, Martin H. Plaweck, Marc A. Schuckit, Arpana Agrawal, Howard J. Edenberg, Kathleen K. Bucholz, Bernice Porjesz
Summary: Increases in alcohol use, particularly among women, have been reported since the beginning of COVID-19 pandemic. This study investigated the associations between COVID-19-related stressors, coping activities, and changes in drunkenness frequency among individuals with a history of Alcohol Use Disorders (AUD). The results showed that individuals with prior AUD symptoms reported greater increases in drunkenness frequency since the start of the pandemic, especially among women. These findings highlight the need for intervention and prevention strategies targeting this vulnerable group.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Margaret Hackl, Lola Cook, Leah Wetherill, Laurence E. Walsh, Paula Delk, Rebeca De Leon, Janfreisy Carbonell, Rossy Cruz Vicioso, Priscila Delgado Hodges
Summary: Genetic testing for Parkinson's disease is growing globally, and genetic counseling plays a crucial role in providing information and promoting understanding. This study conducted a survey in the Dominican Republic to assess knowledge, attitudes, and interest in genetic testing and counseling among individuals affected by PD. The results showed a positive attitude towards genetic testing, high interest in genetic testing for PD, and strong interest in meeting with a genetic counselor.
NPJ PARKINSONS DISEASE
(2023)
Article
Genetics & Heredity
Rachel Sundstrom, Leah Wetherill, Katie Sapp, Molly McPheron, Melissa Lah
Summary: This study examines the impact of factors such as partner involvement, unique challenges of PKU, and different types of PKU treatment on relationship satisfaction. The findings suggest that higher relationship satisfaction is associated with increased partner involvement, better health, and adherence to recommended PKU treatments. Patients utilizing both diet and pharmaceutical treatment reported the highest relationship satisfaction.
JOURNAL OF COMMUNITY GENETICS
(2023)