Structural and functional characterization of AfsR, an SARP family transcriptional activator of antibiotic biosynthesis in < i > Streptomyces < /i >
by Yiqun Wang, Xu Yang, Feng Yu, Zixin Deng, Shuangjun Lin, Jianting ZhengStreptomyces antibiotic regulatory proteins (SARPs) are widely distributed activators of antibiotic biosynthesis.Streptomyces coelicolor AfsR is an SARP regulator with an additional nucleotide-binding oligomerization domain (NOD) and a tetratricopeptide repeat (TPR) domain. Here, we present cryo-electron microscopy (cryo-EM) structures and in vitro assays to demonstrate how the SARP domain activates transcription and how it is modulated by NOD and TPR domains. The structures of transcription initiation complexes (TICs) show that the SARP domain forms...
Source: PLoS Biology: Archived Table of Contents - March 1, 2024 Category: Biology Authors: Yiqun Wang Source Type: research
The computational structure of consummatory anhedonia
Trends Cogn Sci. 2024 Feb 28:S1364-6613(24)00006-8. doi: 10.1016/j.tics.2024.01.006. Online ahead of print.ABSTRACTAnhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment aspect, termed 'consummatory anhedonia', in particular poses fundamental questions about how the brain constructs rewards: what processes determine how intensely a reward is experienced? Here, we outline limitations of existing computational conceptualisations of consummatory anhedonia. We then suggest a richer reinforcement learning (RL) account ...
Source: Trends Cogn Sci - February 29, 2024 Category: Neuroscience Authors: Anna F Hall Michael Browning Quentin J M Huys Source Type: research
The computational structure of consummatory anhedonia
Trends Cogn Sci. 2024 Feb 28:S1364-6613(24)00006-8. doi: 10.1016/j.tics.2024.01.006. Online ahead of print.ABSTRACTAnhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment aspect, termed 'consummatory anhedonia', in particular poses fundamental questions about how the brain constructs rewards: what processes determine how intensely a reward is experienced? Here, we outline limitations of existing computational conceptualisations of consummatory anhedonia. We then suggest a richer reinforcement learning (RL) account ...
Source: Trends Cogn Sci - February 29, 2024 Category: Neuroscience Authors: Anna F Hall Michael Browning Quentin J M Huys Source Type: research
The computational structure of consummatory anhedonia
Trends Cogn Sci. 2024 Feb 28:S1364-6613(24)00006-8. doi: 10.1016/j.tics.2024.01.006. Online ahead of print.ABSTRACTAnhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment aspect, termed 'consummatory anhedonia', in particular poses fundamental questions about how the brain constructs rewards: what processes determine how intensely a reward is experienced? Here, we outline limitations of existing computational conceptualisations of consummatory anhedonia. We then suggest a richer reinforcement learning (RL) account ...
Source: Trends Cogn Sci - February 29, 2024 Category: Neuroscience Authors: Anna F Hall Michael Browning Quentin J M Huys Source Type: research
How is helping behavior regulated in the brain?
Trends Cogn Sci. 2024 Feb 27:S1364-6613(24)00036-6. doi: 10.1016/j.tics.2024.02.009. Online ahead of print.ABSTRACTIn humans and other animals, individuals can actively respond to the specific needs of others. However, the neural circuits supporting helping behaviors are underspecified. In recent work, Zhang, Wu, and colleagues identified a new role for the anterior cingulate cortex (ACC) in the encoding and regulation of targeted helping behavior (allolicking) in mice.PMID:38418366 | DOI:10.1016/j.tics.2024.02.009 (Source: Trends Cogn Sci)
Source: Trends Cogn Sci - February 28, 2024 Category: Neuroscience Authors: Meng Zhang Guohua Chen Rongfeng K Hu Source Type: research
Treating Tourette Together: An Agenda for Patient-Centered Research Focused on Comprehensive Behavioral Intervention for Tics
Behav Ther. 2024 Mar;55(2):263-276. doi: 10.1016/j.beth.2023.06.005. Epub 2023 Jul 1.ABSTRACTTo establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day ...
Source: Behavior Therapy - February 28, 2024 Category: Psychiatry & Psychology Authors: Christine A Conelea Shannon Bennett Michael Himle Sara Hamilton Carolyn Hunt Diana Shineman Carol Mathews Matthew Capriotti Source Type: research
How is helping behavior regulated in the brain?
Trends Cogn Sci. 2024 Feb 27:S1364-6613(24)00036-6. doi: 10.1016/j.tics.2024.02.009. Online ahead of print.ABSTRACTIn humans and other animals, individuals can actively respond to the specific needs of others. However, the neural circuits supporting helping behaviors are underspecified. In recent work, Zhang, Wu, and colleagues identified a new role for the anterior cingulate cortex (ACC) in the encoding and regulation of targeted helping behavior (allolicking) in mice.PMID:38418366 | DOI:10.1016/j.tics.2024.02.009 (Source: Trends Cogn Sci)
Source: Trends Cogn Sci - February 28, 2024 Category: Neuroscience Authors: Meng Zhang Guohua Chen Rongfeng K Hu Source Type: research
Treating Tourette Together: An Agenda for Patient-Centered Research Focused on Comprehensive Behavioral Intervention for Tics
Behav Ther. 2024 Mar;55(2):263-276. doi: 10.1016/j.beth.2023.06.005. Epub 2023 Jul 1.ABSTRACTTo establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day ...
Source: Behavior Therapy - February 28, 2024 Category: Psychiatry & Psychology Authors: Christine A Conelea Shannon Bennett Michael Himle Sara Hamilton Carolyn Hunt Diana Shineman Carol Mathews Matthew Capriotti Source Type: research
NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells
Exp Mol Med. 2024 Feb 27. doi: 10.1038/s12276-024-01174-6. Online ahead of print.ABSTRACTThe P53-destabilizing TBC1D15-NOTCH protein interaction promotes self-renewal of tumor-initiating stem-like cells (TICs); however, the mechanisms governing the regulation of this pathway have not been fully elucidated. Here, we show that TBC1D15 stabilizes NOTCH and c-JUN through blockade of E3 ligase and CDK8 recruitment to phosphodegron sequences. Chromatin immunoprecipitation (ChIP-seq) analysis was performed to determine whether TBC1D15-dependent NOTCH1 binding occurs in TICs or non-TICs. The TIC population was isolated to evaluate...
Source: Molecular Medicine - February 27, 2024 Category: Molecular Biology Authors: Hye Yeon Choi Yicheng Zhu Xuyao Zhao Simran Mehta Juan Carlos Hernandez Jae-Jin Lee Yi Kou Risa Machida Mauro Giacca Giannino Del Sal Ratna Ray Hyungjin Eoh Stanley M Tahara Lin Chen Hidekazu Tsukamoto Keigo Machida Source Type: research
Developing and validating the model of tumor-infiltrating immune cell to predict survival in patients receiving radiation therapy for head and neck squamous cell carcinoma
CONCLUSIONS: The TICS model supports a personalized medicine approach to RT for HNSCC. Increased prevalence of TIIC within the tumor microenvironment (TME) confers a better prognosis for patients undergoing treatment for HNSCC.PMID:38410204 | PMC:PMC10894341 | DOI:10.21037/tcr-23-2345 (Source: Cell Research)
Source: Cell Research - February 27, 2024 Category: Cytology Authors: Ting Xu Mengting Xu Yiying Xu Xiaojun Cai Michael J Brenner Joshua Twigg Zhaodong Fei Chuanben Chen Source Type: research
NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells
Exp Mol Med. 2024 Feb 27. doi: 10.1038/s12276-024-01174-6. Online ahead of print.ABSTRACTThe P53-destabilizing TBC1D15-NOTCH protein interaction promotes self-renewal of tumor-initiating stem-like cells (TICs); however, the mechanisms governing the regulation of this pathway have not been fully elucidated. Here, we show that TBC1D15 stabilizes NOTCH and c-JUN through blockade of E3 ligase and CDK8 recruitment to phosphodegron sequences. Chromatin immunoprecipitation (ChIP-seq) analysis was performed to determine whether TBC1D15-dependent NOTCH1 binding occurs in TICs or non-TICs. The TIC population was isolated to evaluate...
Source: Molecular Medicine - February 27, 2024 Category: Molecular Biology Authors: Hye Yeon Choi Yicheng Zhu Xuyao Zhao Simran Mehta Juan Carlos Hernandez Jae-Jin Lee Yi Kou Risa Machida Mauro Giacca Giannino Del Sal Ratna Ray Hyungjin Eoh Stanley M Tahara Lin Chen Hidekazu Tsukamoto Keigo Machida Source Type: research
Curiosity and the dynamics of optimal exploration
Trends Cogn Sci. 2024 Feb 26:S1364-6613(24)00028-7. doi: 10.1016/j.tics.2024.02.001. Online ahead of print.ABSTRACTWhat drives our curiosity remains an elusive and hotly debated issue, with multiple hypotheses proposed but a cohesive account yet to be established. This review discusses traditional and emergent theories that frame curiosity as a desire to know and a drive to learn, respectively. We adopt a model-based approach that maps the temporal dynamics of various factors underlying curiosity-based exploration, such as uncertainty, information gain, and learning progress. In so doing, we identify the limitations of pas...
Source: Trends Cogn Sci - February 27, 2024 Category: Neuroscience Authors: Francesco Poli Jill X O'Reilly Rogier B Mars Sabine Hunnius Source Type: research
NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells
In this study, researchers focused on a protein called TBC1D15 (oncofetal protein), which interacts with another protein, NOTCH1, to influence TIC behavior. Using mouse models and human cell lines, the team investigated how TBC1D15 affects TICs and explored potential therapeutic strategies. The study revealed that TBC1D15 promotes the self-renewal and growth of TICs by interacting with NOTCH1 and affecting mitochondrial function. The researchers also identified small molecules that can disrupt the TBC1D15-NOTCH1 interaction, offering a new approach to target TICs in cancer treatment. The results showed that interfering wit...
Source: Experimental and Molecular Medicine - February 27, 2024 Category: Molecular Biology Authors: Hye Yeon Choi Yicheng Zhu Xuyao Zhao Simran Mehta Juan Carlos Hernandez Jae-Jin Lee Yi Kou Risa Machida Mauro Giacca Giannino Del Sal Ratna Ray Hyungjin Eoh Stanley M. Tahara Lin Chen Hidekazu Tsukamoto Keigo Machida Source Type: research
The neurobiology of interoception and affect
Trends Cogn Sci. 2024 Feb 22:S1364-6613(24)00009-3. doi: 10.1016/j.tics.2024.01.009. Online ahead of print.ABSTRACTScholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of how signals from the body are transduced, transmitted, compressed, and integrated by the brains of humans to produce affective states. We suggest that to understand how the body contributes to affect, we first need to understand information flow through the nervous system's interoceptive pathways. We outline such a model and discuss how unique ...
Source: Trends Cogn Sci - February 23, 2024 Category: Neuroscience Authors: M J Feldman E Bliss-Moreau K A Lindquist Source Type: research
The neurobiology of interoception and affect
Trends Cogn Sci. 2024 Feb 22:S1364-6613(24)00009-3. doi: 10.1016/j.tics.2024.01.009. Online ahead of print.ABSTRACTScholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of how signals from the body are transduced, transmitted, compressed, and integrated by the brains of humans to produce affective states. We suggest that to understand how the body contributes to affect, we first need to understand information flow through the nervous system's interoceptive pathways. We outline such a model and discuss how unique ...
Source: Trends Cogn Sci - February 23, 2024 Category: Neuroscience Authors: M J Feldman E Bliss-Moreau K A Lindquist Source Type: research
