Article
Cell Biology
Abdellatif Benraiss, John N. Mariani, Ashley Tate, Pernille M. Madsen, Kathleen M. Clark, Kevin A. Welle, Renee Solly, Laetitia Capellano, Karen Bentley, Devin Chandler-Militello, Steven A. Goldman
Summary: Huntington's disease (HD) is characterized by defective oligodendroglial differentiation and white matter disease. This study reveals a link between oligodendrocyte progenitor cell (OPC) dysfunction and impaired myelin maintenance in adult HD patients. The downregulation of genes associated with oligodendrocyte differentiation and myelinogenesis is identified as a major driver of this dysfunction, and Tcf7l2 signaling is found to be a potential therapeutic target.
Article
Dermatology
Ajith Welihinda, Puja Ravikumar, Manmeet Kaur, Jordan Mechanic, Shruti Yadav, Gyeong Jin Kang, Edward Amento
Summary: The study shows that enhancing A(2A)R responsiveness to adenosine through positive allosteric modulation can effectively inhibit the progression of psoriasis, reducing inflammation and symptoms.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Danielle A. Clarkson-Townsend, Katie L. Bales, Karen E. Hermetz, Amber A. Burt, Machelle T. Pardue, Carmen J. Marsit
Summary: The study reveals that developmental chronodisruption may affect placental embryo expression, leading to increased placental immune cell expression and a pro-inflammatory tissue environment, without affecting embryo count, placental weight, or fetal sex ratio.
Article
Immunology
Zuozhen Tian, Frances S. Shofer, Alec Z. Sandroni, Lan Zhao, Carla R. Scanzello, Yejia Zhang
Summary: The study found that the expression of human interleukin (IL) 8 in mice affected their behavior, especially in reduced locomotion and climbing in male mice. Furthermore, the eating and drinking time of mice changed with age and were influenced by the expression of hIL8. These changes in natural behaviors in control mice are consistent with functional decline with age.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Amelie M. Borie, Sena Agezo, Parker Lunsford, Arjen J. Boender, Ji-Dong Guo, Hong Zhu, Gordon J. Berman, Larry J. Young, Robert C. Liu
Summary: This study examines the role of oxytocin in the nucleus accumbens during pair bonding in prairie voles. The researchers found that oxytocin's actions change with social experience, regulating the trajectory of social interactions and potentially promoting the maintenance of a pair bond by inhibiting aggressive responses.
Article
Physiology
Natalia C. Osipchuk, Athena M. Soulika, Alla F. Fomina
Summary: Modulation of RyRs by administering RyR inhibitor dantrolene or introducing a gain-of-function RYR1-p.R163C mutation significantly affects the clinical progression of experimental autoimmune encephalomyelitis in mice. Daily administration of 5 or 10 mg/kg dantrolene reduces the severity of EAE clinical symptoms and dampens inflammation in the spinal cord. Mice with the gain-of-function RYR1-p.R163C mutation show faster and more severe development of EAE clinical symptoms.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Laura del Bosque-Plata, Eduardo Martinez-Martinez, Miguel Angel Espinoza-Camacho, Claudia Gragnoli
Summary: TCF7L2 is the most potent locus for type 2 diabetes (T2D) risk and is consistently associated with the disease across diverse populations with different genetic origins. The exact mechanisms by which TCF7L2 affects T2D are still not well understood.
Article
Cell Biology
Ye Yang, Manjun Shen, Li Li, Yujun Long, Lu Wang, Bing Lang, Renrong Wu
Summary: This study reveals that olanzapine, a type of atypical antipsychotic, worsens metabolic abnormalities in mice with pancreatic beta-cell-specific Tcf7l2 deletion, possibly mediated by reduced expression of GLP-1R.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Maria Amalia Di Castro, Stefano Garofalo, Alessandro Mormino, Laura Carbonari, Erika Di Pietro, Eleonora De Felice, Myriam Catalano, Laura Maggi, Cristina Limatola
Summary: Cytokines, such as interleukin-15 (IL-15), play important roles in modulating the central nervous system (CNS). In this study, the authors found that exposure to IL-15 enhances GABA release and reduces glutamatergic currents in hippocampal slices. Chronic treatment with IL-15 has negative effects on memory formation. Serotonin is involved in mediating these effects, as a selective 5-HT3A receptor antagonist prevents the effects on inhibitory neurotransmission and improves performance in a memory test.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Biochemistry & Molecular Biology
Feng Zhang, Jia Xu, Yanzhou Hu, Jingjing Fang, Minglan Yang, Kunlun Huang, Wentao Xu, Xiaoyun He
Summary: Diallyl trisulfide (DATS) in garlic oil can improve bone microstructure, promote collagen synthesis, regulate gut microbiota, alter serum metabolism, and prevent bone loss by upregulating osteogenic gene expression.
Article
Cell Biology
Mengshi Sun, Mingze Ma, Bowen Deng, Na Li, Qionglin Peng, Yufeng Pan
Summary: This study reveals how hunger state affects female receptivity in fruit flies by elucidating the inhibitory role of adipokinetic hormone receptor neurons on sexual receptivity through interaction with specific neurons. The research also discovers that certain neurons suppress the activity of sex-promoting neurons through GABA signaling, integrating multiple internal and external cues for decision-making.
Article
Neurosciences
Chang Youn Lee, Sung-Ae Hyun, Moon Yi Ko, Hye Ryeong Kim, Jaerang Rho, Kee K. Kim, Woo-Yang Kim, Minhan Ka
Summary: Early-life exposure to bisphenol A (BPA) disrupts the self-renewal and differentiation of neural progenitors during cortical development, leading to reduced neuron number and increased glial cells in the cerebral cortex. Additionally, synaptic formation and transmission are suppressed in the cerebral cortex after maternal BPA exposure, resulting in behavioral deficits likely mediated by activating autophagy.
Article
Neurosciences
Soroush Darvish-Ghane, Brendan Lyver, Amanda Facciol, Diptendu Chatterjee, Loren J. Martin
Summary: The study demonstrates that chronic inflammatory injury leads to mechanical hypersensitivity and transient anxiety. Inflammatory pain induces alterations in dopaminergic inputs and excitatory transmission in pain-related cortical regions.
Article
Cell Biology
Suraj J. Pathak, Zeyu Zhou, Danielle Steffen, Tommy Tran, Yael Ad, Jon J. Ramsey, Jennifer M. Rutkowsky, Keith Baar
Summary: A 2-month isocaloric ketogenic diet in middle-aged female mice has been found to enhance cognitive behavior, including anxiety, memory, and willingness to explore. This improvement may be associated with the interaction between muscle and brain.
Article
Biochemistry & Molecular Biology
Chenxi Nie, Xiaoqing Xie, Huicui Liu, Xiaojin Yuan, Qingyu Ma, Aobai Tu, Min Zhang, Zhifei Chen, Juxiu Li
Summary: Consumption of dietary advanced glycation end products (AGEs) can damage the intestinal barrier, while the prebiotic galactooligosaccharides (GOS) can improve intestinal health. This study found that GOS can ameliorate AGE-induced intestinal barrier damage by modulating the intestinal microbiota.
Article
Oncology
Shawn H. R. Lee, Maoxiang Qian, Wentao Yang, Jonathan D. Diedrich, Elizabeth Raetz, Wenjian Yang, Qian Dong, Meenakshi Devidas, Deqing Pei, Allen Yeoh, Cheng Cheng, Ching-Hon Pui, William E. Evans, Charles G. Mullighan, Stephen P. Hunger, Daniel Savic, Mary Relling, Mignon L. Loh, Jun J. Yang
Summary: A risk locus between BCL11A and PAPOLG was identified in a study on ALL cases, with a subtype-specific effect on TCF3-PBX1 ALL. The risk variant may distally modulate the transcription of the adjacent gene REL through a regulatory DNA element activated uniquely in ALL cells with the TCF3-PBX1 fusion.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Neurosciences
Lex J. Gomez, James C. Dooley, Greta Sokoloff, Mark S. Blumberg
Summary: The study suggests that the primary motor cortex (M1) can receive sensory input directly from the thalamus independent of the primary somatosensory cortex (S1) at early developmental stages. The processing of self-generated and other-generated movements varies between S1 and M1 before they establish the interactive relationship typical of adult functionality.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Behavioral Sciences
Xinzhu Zhou, Amanda M. Barkley-Levenson, Patricia Montilla-Perez, Francesca Telese, Abraham A. Palmer
Summary: The study aimed to investigate the role of Azi2 in methamphetamine sensitivity by creating mutant Azi2 alleles and analyzing their effects on the locomotor response to methamphetamine. While the mutant allele increased sensitivity, contrary to GWAS results, lower Azi2 levels did not necessarily decrease the response. Despite no direct correlation between Azi2 and Slc6a3, the Azi2 mutation altered the expression of important genes and pathways related to methamphetamine sensitivity.
GENES BRAIN AND BEHAVIOR
(2021)
Article
Neurosciences
Ryan M. Glanz, James C. Dooley, Greta Sokoloff, Mark S. Blumberg
Summary: During the first postnatal week in rats, the primary motor cortex (M1) is mainly activated by self-generated forelimb movements and exhibits modulation by movement amplitude. By postnatal day 12 (P12), M1 population-level activity becomes more sparse, with a reduced tuning to movement amplitude.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Substance Abuse
Spencer B. Huggett, Emma C. Johnson, Alexander S. Hatoum, Dongbing Lai, Jenani Srijeyanthan, Jason A. Bubier, Elissa J. Chesler, Arpana Agrawal, Abraham A. Palmer, Howard J. Edenberg, Rohan H. C. Palmer
Summary: The study demonstrates that rodent gene expression studies can help identify genetic contributions to some substance use traits in humans, but with less specificity than expected. The results show that rodent gene-sets are enriched for specific traits in human GWAS, with enrichment increasing as trait heritability increases.
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2021)
Article
Psychology, Clinical
E. E. Levitt, A. Oshri, M. Amlung, L. A. Ray, S. Sanchez-Roige, A. A. Palmer, J. MacKillop
Summary: This study examines the relationship between delay discounting and multiple psychiatric conditions and finds significant associations between delay discounting and several disorders. The findings provide support for delay discounting as a transdiagnostic indicator and suggest further research is warranted.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Genetics & Heredity
Jennifer Zou, Shyam Gopalakrishnan, Clarissa C. Parker, Jerome Nicod, Richard Mott, Na Cai, Arimantas Lionikas, Robert W. Davies, Abraham A. Palmer, Jonathan Flint
Summary: Combining samples in genetic association studies for complex traits can identify more loci, but replication between studies may be challenging. The Winner's Curse effect, study heterogeneity, and trait differences are factors that affect replication, and integrating various information can assign variants to different confidence levels.
G3-GENES GENOMES GENETICS
(2022)
Article
Behavioral Sciences
Sandra Sanchez-Roige, Samuel A. Barnes, Jazlene Mallari, Rebecca Wood, Oksana Polesskaya, Abraham A. Palmer
Summary: The membrane glycoprotein M6B (Gpm6b) is involved in neuronal differentiation, myelination, and inactivation of the serotonin transporter. Recent studies have shown its association with psychiatric disorders. A mutant allele of Gpm6b was created in mice, leading to deficits in delay discounting but enhanced reward sensitivity and behavioral flexibility.
GENES BRAIN AND BEHAVIOR
(2022)
Article
Oncology
Xujie Zhao, Maoxiang Qian, Charnise Goodings, Yang Zhang, Wenjian Yang, Ping Wang, Beisi Xu, Cheng Tian, Ching-Hon Pui, Stephen P. Hunger, Elizabeth A. Raetz, Meenakshi Devidas, Mary Relling, Mignon L. Loh, Daniel Savic, Chunliang Li, Jun J. Yang
Summary: We identified 54 common variants in the ARID5B gene that are significantly associated with leukemia risk. These variants modulate cis-regulatory elements at the locus, disrupting the binding of MEF2C and affecting the expression of ARID5B. Additionally, one of the variants is also associated with lymphocyte percentage and count in the general population.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Multidisciplinary Sciences
Thomas A. Sasani, David G. Ashbrook, Annabel C. Beichman, Lu Lu, Abraham A. Palmer, Robert W. Williams, Jonathan K. Pritchard, Kelley Harris
Summary: This study used BXD mouse lines to identify loci that influence germline mutagenesis. They found that a quantitative trait locus on chromosome 4 affects the accumulation rate of C>A germline mutations in mice, primarily due to the activity of different alleles of the DNA repair gene Mutyh. These alleles are also present in wild populations, indicating that common genetic variation modulates germline mutagenesis.
Editorial Material
Neurosciences
Elizabeth G. Atkinson, Sevim B. Bianchi, Gordon Y. Ye, Jose Jaime Martinez-Magana, Grace E. Tietz, Janitza L. Montalvo-Ortiz, Paola Giusti-Rodriguez, Abraham A. Palmer, Sandra Sanchez-Roige
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Hematology
Daniel C. Ferguson, J. Robert McCorkle, Kelly R. Barnett, Erik J. Bonten, Brennan P. Bergeron, Kashi Raj Bhattarai, Wenjian Yang, Colton Smith, Baranda S. Hansen, Richa Bajpai, Qian Dong, Robert J. Autry, Yoshihiro Gocho, Jonathan D. Diedrich, Kristine R. Crews, Shondra M. Pruett-Miller, Kathryn G. Roberts, Wendy Stock, Charles G. Mullighan, Hiroto Inaba, Sima Jeha, Ching-Hon Pui, Jun J. Yang, Mary Relling, William E. Evans, Daniel Savic
Summary: The study identified LASP response genes in ALL cell lines and patient samples, revealed the role of the ATF4 transcription factor in ALL cell lines, and highlighted the significance of SLC7A11 in LASP resistance and sensitivity.
Article
Oncology
Brennan P. Bergeron, Jonathan D. Diedrich, Yang Zhang, Kelly R. Barnett, Qian Dong, Daniel C. Ferguson, Robert J. Autry, Wenjian Yang, Baranda S. Hansen, Colton Smith, Kristine R. Crews, Yiping Fan, Ching-Hon Pui, Shondra M. Pruett-Miller, Mary Relling, Jun J. Yang, Chunliang Li, William E. Evans, Daniel Savic
Summary: Glucocorticoids (GCs), as a common drug in the treatment of childhood acute lymphoblastic leukemia (ALL), face challenges of drug resistance. This study investigated the gene regulatory response to GCs in ALL cell lines and discovered disruptions in cis-regulatory elements that are associated with GC resistance. Integrating these findings with genetic and epigenetic datasets from primary ALL cells, the study also identified cis-regulatory disruptions that impact GC resistance in childhood ALL.
Article
Multidisciplinary Sciences
Xujie Zhao, Ping Wang, Jonathan D. Diedrich, Brandon Smart, Noemi Reyes, Satoshi Yoshimura, Jingliao Zhang, Wentao Yang, Kelly Barnett, Beisi Xu, Zhenhua Li, Xin Huang, Jiyang Yu, Kristine Crews, Allen Eng Juh Yeoh, Marina Konopleva, Chia-Lin Wei, Ching-Hon Pui, Daniel Savic, Jun J. Yang
Summary: FLT3 is overexpressed in ZNF384-rearranged ALL, with exclusive activation of an intergenic enhancer element at the FLT3 locus and global enrichment of active enhancers within ZNF384 binding sites. Downregulation of ZNF384 decreases FLT3 activation and sensitizes ALL cells to FLT3 inhibitor gilteritinib. Moreover, gilteritinib shows significant anti-leukemia efficacy as a monotherapy in patient-derived xenograft models of ZNF384-rearranged ALL.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Axel Guilbaud, Farzan Ghanegolmohammadi, Yijun Wang, Jiapeng Leng, Alexander Kreymerman, Jacqueline Gamboa Varela, Jessica Garbern, Hannah Elwell, Fang Cao, Elisabeth M. Ricci-Blair, Cui Liang, Seetharamsing Balamkundu, Charles Vidoudez, Michael S. Demott, Kenneth Bedi, Kenneth B. Margulies, David A. Bennett, Abraham A. Palmer, Amanda Barkley-Levenson, Richard T. Lee, Peter C. Dedon
Summary: DNA damage is a major cause of genomic instability in various diseases. Traditional analytical methods provide limited insight into the spectrum of DNA lesions in living organisms. In this study, untargeted chromatography-coupled tandem mass spectrometry (LC-MS/MS) was used to explore the landscape of DNA modifications in rat and human tissues. A total of 114 potential DNA adducts were identified in heart, liver, brain, and kidney tissues of rats, and 111 in human heart and brain tissues using the LC-MS/MS approach. Subsequent targeted analysis revealed species, tissue, age, and sex biases in the DNA adducts. This study demonstrates the potential of adductomics in discovering disease-driving DNA adducts and provides a valuable resource for characterizing new forms of DNA damage and developing biomarkers for aging and disease.
NUCLEIC ACIDS RESEARCH
(2023)