Review
Pharmacology & Pharmacy
Yining Luo, Jingchun Gao, Xukai Jiang, Ling Zhu, Qi Tony Zhou, Michael Murray, Jian Li, Fanfan Zhou
Summary: This article summarizes the structure-interaction relationships of human PepTs and their substrates and discusses the potential applications of this information in therapeutic optimization and drug development.
Review
Chemistry, Multidisciplinary
Jianming Xiang, Richard F. Keep
Summary: This mini-review provides an overview of the role of the solute carrier 15 (SLC15) family of proton-coupled oligopeptide transporters (POTs) in the brain, with a focus on Pept2 (Slc15A2) and PhT1 (Slc15A4). These transporters play a crucial role in the transport of di- and tripeptides, peptidomimetics, and drugs in the brain. The review highlights the pioneering work of David E. Smith in elucidating the impact of PepT2 at the choroid plexus and brain parenchymal cells, and discusses recent findings and future directions in brain POT research, including localization, regulatory pathways, transporter structure, species differences, and disease states.
PHARMACEUTICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Maxime Killer, Giada Finocchio, Haydyn D. T. Mertens, Dmitri I. Svergun, Els Pardon, Jan Steyaert, Christian Loew
Summary: Proton-coupled Oligopeptide Transporters (POTs) mediate the uptake of short di- and tripeptides. This study determined the structure of DtpC and provided insights into its ligand specificity using cryogenic electron microscopy (cryo-EM). The research highlights the value of nanobodies for structure determination of low molecular weight integral membrane proteins.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Cell Biology
Caihong Wang, Chu Chu, Xiang Ji, Guoliang Luo, Chunling Xu, Houhong He, Jianbiao Yao, Jian Wu, Jiangning Hu, Yuanxiang Jin
Summary: This review provides a comprehensive overview of the structure, function, and regulation of PepT2 in mammals. The essential roles of PepT2 in the kidney and brain, as well as its medical and pharmacological significance in the absorption and disposal of peptide-like drugs, are discussed. Understanding PepT2 is of emerging interest in nutrition, medical, and pharmacological research.
Article
Biology
Bochuan Teng, Joshua Kaplan, Ziyu Liang, Kevin Saejin Chyung, Marcel P. Goldschen-Ohm, Emily Ruth Liman
Summary: Otopetrin proteins (OTOPs) are proton-selective ion channels that detect acids or regulate pH. This study found that zinc activates murine OTOP3 (mOTOP3), but not mOTOP2. Swapping the extracellular linkers between the two channels eliminated Zn2+ activation of mOTOP3 and conferred activation on mOTOP2. These findings provide insight into the gating mechanisms of OTOP channels and have potential implications for drug discovery.
Review
Biochemistry & Molecular Biology
Charles W. Carter, Peter R. Wills
Summary: Bioenergetics, genetic coding, and catalysis are crucial processes of biology that are hard to emerge without pre-existing historical context. Resolving paradoxes through coupling is essential in understanding the underlying contradictions in these processes.
Article
Multidisciplinary Sciences
Zhongneng Zhou, Zijing Chen, Xiu-Wen Kang, Yalin Zhou, Bingyao Wang, Siwei Tang, Shuhua Zou, Yifei Zhang, Qiaoyu Hu, Fang Bai, Bei Ding, Dongping Zhong
Summary: In this study, the photocycle of the FMN-Gln-Tyr motif in the BLUF domain of OaPAC was investigated using computational simulations. The results show that forward PCET is concerted, while only the wild-type protein proceeds with an ultrafast reverse PCET process.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Takwa S. Aroankins, Sathish K. Murali, Robert A. Fenton, Qi Wu
Summary: This study revealed protein post-translational modifications by SUMOylation in the aldosterone-sensitive kidney distal convoluted tubule, highlighting the important role of SUMOylation in the physiological regulation of Pept2 trafficking by aldosterone.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Namrata Shukla, Shantanu Kadam, Ranjith Padinhateeri, Ullas Kolthur-Seetharam
Summary: This study identifies kinetic parameters encoding the effects of insulin concentration and nutrient on information flow, illustrating the crucial role of dynamic phosphorylation events in the selective control of signal transduction, and highlighting a kinetic basis for insulin resistance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Thi Tuong Vy Phan, Myunggi Yi
Summary: The voltage-gated proton channel Hv1 plays important roles in various biological processes, including cancer progression. Researchers have proposed a novel gating mechanism for Hv1 through molecular dynamics simulations, which may contribute to the development of new drugs.
Article
Biology
Max-Aylmer Dreier, Philipp Althoff, Mohamad Javad Norahan, Stefan Alexander Tennigkeit, Samir F. El-Mashtoly, Mathias Luebben, Carsten Koetting, Till Rudack, Klaus Gerwert
Summary: The study demonstrates that the anion channelrhodopsin GtACR1 operates with a highly conducting C=N-anti-photocycle, without the inactivation observed in CrChR2, showing the potential for optimized optogenetic tools. The importance of the central constriction site amino acid Glu-68 in molecular gating mechanisms is highlighted, suggesting that canceling out poorly conducting photocycles could enhance channelrhodopsin efficiency for optogenetic applications.
COMMUNICATIONS BIOLOGY
(2021)
Article
Engineering, Multidisciplinary
Saber Jafarizadeh, Darryl Veitch, Farzad Tofigh, Justin Lipman, Mehran Abolhasan
Summary: This study explores the impact of nonuniform coupling strength on synchronization, finding that adding any edge to a connected graph can only improve synchronizability in the optimal measure, while some proposed structural parameters do not have a simple relationship with the optimal synchronizability measure.
IEEE TRANSACTIONS ON NETWORK SCIENCE AND ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Elena Buhl, Tom Resler, Rebecca Lam, Marvin Asido, Ernst Bamberg, Ramona Schlesinger, Christian Bamann, Joachim Heberle, Josef Wachtveitl
Summary: The study reveals the correlation between channel opening of CrChR2 and retinal isomerization, photocycle, and protein channel activity. The photocycle of the R120H variant is intact despite deficient channel activity. Analysis of the amide I mode shows impairment of the ultrafast protein response after retinal excitation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Satoshi Uchida, Yuto Yamaberi, Masakazu Tanaka, Makoto Oba
Summary: Prolonging protein expression from mRNA is a challenge in mRNA nanomedicine development. mRNA complexed with helix foldamer oligopeptides containing arginine and alpha-aminoisobutyric acids showed higher intracellular stability and maintained efficient protein translation for three days.
Article
Nanoscience & Nanotechnology
Pradip Das, Debarati Mukherjee, Bishnupada Mandal, Sasidhar Gumma
Summary: The study successfully synthesized a novel ternary composite and fabricated mixed matrix membranes with higher selectivity. Introducing noble metal nanoparticles and carbon 2D materials simultaneously into the MOF improved the proton conduction, demonstrating the potential to overcome challenges associated with direct methanol fuel cells.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Psychology, Clinical
Maureen McHugo, Suzanne Avery, Kristan Armstrong, Baxter P. Rogers, Simon N. Vandekar, Neil D. Woodward, Jennifer Urbano Blackford, Stephan Heckers
Summary: This study suggests that hippocampal dysfunction in early psychosis does not worsen over a period of 2 years and highlights the need for longer-term longitudinal studies.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Behavioral Sciences
Ashley N. Clausen, Kelene A. Fercho, Molly Monsour, Seth Disner, Lauren Salminen, Courtney C. Haswell, Emily Clarke Rubright, Amanda A. Watts, M. Nicole Buckley, Adi Maron-Katz, Anika Sierk, Antje Manthey, Benjamin Suarez-Jimenez, Bunmi O. Olatunji, Christopher L. Averill, David Hofmann, Dick J. Veltman, Elizabeth A. Olson, Gen Li, Gina L. Forster, Henrik Walter, Jacklynn Fitzgerald, Jean Theberge, Jeffrey S. Simons, Jessica A. Bomyea, Jessie L. Frijling, John H. Krystal, Justin T. Baker, K. Luan Phan, Kerry Ressler, Laura K. M. Han, Laura Nawijn, Lauren A. M. Lebois, Lianne Schmaall, Maria Densmore, Martha E. Shenton, Mirjam van Zuiden, Murray Stein, Negar Fani, Raluca M. Simons, Richard W. J. Neufeld, Ruth Lanius, Sanne van Rooij, Saskia B. J. Koch, Serena Bonomo, Tanja Jovanovic, Terri DeRoon-Cassini, Timothy D. Ely, Vincent A. Magnotta, Xiaofu He, Chadi G. Abdallah, Amit Etkin, Christian Schmahl, Christine Larson, Isabelle M. Rosso, Jennifer Urbano Blackford, Jennifer S. Stevens, Judith K. Daniels, Julia Herzog, Milissa L. Kaufman, Miranda Olff, Richard J. Davidson, Scott R. Sponheim, Sven C. Mueller, Thomas Straube, Xi Zhu, Yuval Neria, Lee A. Baugh, James H. Cole, Paul M. Thompson, Rajendra A. Morey
Summary: PTSD is associated with accelerated aging markers. Young males with PTSD showed higher brain age difference compared to male controls, while old males with PTSD exhibited lower brain age difference compared to male controls of all ages.
BRAIN AND BEHAVIOR
(2022)
Article
Psychiatry
Maureen McHugo, Baxter P. Rogers, Suzanne N. Avery, Kristan Armstrong, Jennifer Urbano Blackford, Simon N. Vandekar, Maxwell J. Roeske, Neil D. Woodward, Stephan Heckers
Summary: Neuroimaging studies have shown that there is hippocampal hyperactivity in patients with schizophrenia, with the hyperactivity spreading to other regions as the illness progresses. However, there is limited evidence for changes in basal hippocampal function following the onset of psychosis. This study used fractional amplitude of low frequency fluctuations (fALFF) to investigate the hypothesis of progressive hippocampal hyperactivity in patients with non-affective psychosis. The findings indicate that there is higher fALFF in the anterior and posterior hippocampus in the early stage of psychosis, but there is evidence for the normalization of fALFF over time. This suggests that hippocampal fALFF may be a marker of vulnerability to psychosis or an acute illness state, rather than a persistent feature of the illness.
SCHIZOPHRENIA RESEARCH
(2022)
Article
Biology
Philip W. Fowler, Carla Wright, Helen Spiers, Tingting Zhu, Elisabeth M. L. Baeten, Sarah W. Hoosdally, Ana L. Gibertoni Cruz, Aysha Roohi, Samaneh Kouchaki, Timothy M. Walker, Timothy E. A. Peto, Grant Miller, Chris Lintott, David Clifton, Derrick W. Crook, A. Sarah Walker
Summary: Tuberculosis is a respiratory disease that can be treated with antibiotics. It is important to test the susceptibility of each infection to different antibiotics for a good treatment outcome. Through the BashTheBug project on the Zooniverse citizen science platform, volunteers can accurately determine the minimum inhibitory concentration (MIC) of multiple drugs.
Article
Psychology, Clinical
Bunmi O. Olatunji, Rebecca C. Cox, Jennifer Urbano Blackford
Summary: Research has investigated fear acquisition and extinction in PTSD context, as well as the reconditioning of fear post-extinction. Findings suggest that combat-exposed veterans show significant responses to fear stimuli in certain conditions, while genetic polymorphism may influence the reacquisition of fear.
BEHAVIOUR RESEARCH AND THERAPY
(2022)
Article
Infectious Diseases
Timothy M. Walker, Paolo Miotto, Claudio U. Koser, Philip W. Fowler, Jeff Knaggs, Zamin Iqbal, Martin Hunt, Leonid Chindelevitch, Maha R. Farhat, Daniela Maria Cirillo, Inaki Comas, James Posey, Shaheed V. Omar, Timothy E. A. Peto, Anita Suresh, Swapna Uplekar, Sacha Laurent, Rebecca E. Colman, Carl-Michael Nathanson, Matteo Zignol, Ann Sarah Walker, Derrick W. Crook, Nazir Ismail, Timothy C. Rodwell
Summary: This study aimed to generate a WHO-endorsed catalogue of mutations for drug resistance prediction in Mycobacterium tuberculosis complex (MTBC) and provide a global standard for interpreting molecular information. The research analyzed MTBC isolates from 45 countries and identified mutations associated with resistance to different antituberculosis drugs. The findings can encourage the implementation of molecular diagnostics by national tuberculosis programs.
Article
Biochemistry & Molecular Biology
[Anonymous]
Summary: This study presents a comprehensive resistance prediction for tuberculosis using a large dataset of Mycobacterium tuberculosis isolates. The data includes whole-genome sequencing and minimum inhibitory concentrations to 13 antitubercular drugs. The dataset provides valuable information on the genotypic and phenotypic characteristics of drug resistance, and has the potential to advance our understanding of rare resistance phenotypes. The open-source nature of the data compendium encourages future research in the field.
Article
Psychology, Biological
Kalina J. Michalska, Brenda Benson, Elizabeth J. Ivie, Jessica F. Sachs, Simone P. Haller, Rany Abend, Daniel R. McFarlin, Jennifer Urbano Blackford, Daniel S. Pine
Summary: Excessive fear responses to uncertain threat are a key feature of anxiety disorders, and this study aims to explore the neural mechanisms behind it in both youth and adults. The findings suggest that certain brain regions are involved in fear regulation, response inhibition, and cognitive control, which may provide insights for treatment development and research in youth mental health.
INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
(2023)
Article
Biophysics
Vanessa Leone, Richard T. Bradshaw, Caroline Koshy, Paul Suhwan Lee, Cristina Fenollar-Ferrer, Veronika Heinz, Christine Ziegler, Lucy R. Forrest
Summary: Membrane transporters are essential for cellular function by mediating the passage of molecules across membranes. The cytoplasmic regions of these proteins are required for modulating their activity, but obtaining atomic-resolution descriptions of these regions can be challenging. This study focuses on BetP, a membrane protein whose autoregulation depends on its cytoplasmic segments, and uses molecular simulations to investigate the structure and dynamics of these segments. The results provide insights into the molecular mechanism of autoregulation and reveal an intricate interplay between the three protomers of BetP.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Nynke A. Groenewold, Janna Marie Bas-Hoogendam, Alyssa R. Amod, Max A. Laansma, Laura S. Van Velzen, Moji Aghajani, Kevin Hilbert, Hyuntaek Oh, Ramiro Salas, Andrea P. Jackowski, Pedro M. Pan, Giovanni A. Salum, James R. Blair, Karina S. Blair, Joy Hirsch, Spiro P. Pantazatos, Franklin R. Schneier, Ardesheer Talati, Karin Roelofs, Inge Volman, Laura Blanco-Hinojo, Narcis Cardoner, Jesus Pujol, Katja Beesdo-Baum, Christopher R. K. Ching, Sophia Thomopoulos, Andreas Jansen, Tilo Kircher, Axel Krug, Igor Nenadic, Frederike Stein, Udo Dannlowski, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Alexandra Winter, Michael Erb, Benjamin Kreifelts, Qiyong Gong, Su Lui, Fei Zhu, Benson Mwangi, Jair C. Soares, Mon-Ju Wu, Ali Bayram, Mesut Canli, Rasit Tukel, P. Michiel Westenberg, Alexandre Heeren, Henk R. Cremers, David Hofmann, Thomas Straube, Alexander G. G. Doruyter, Christine Lochner, Jutta Peterburs, Marie-Jose Van Tol, Raquel E. Gur, Antonia N. Kaczkurkin, Bart Larsen, Theodore D. Satterthwaite, Courtney A. Filippi, Andrea L. Gold, Anita Harrewijn, Andre Zugman, Robin Buelow, Hans J. Grabe, Henry Voelzke, Katharina Wittfeld, Joscha Boehnlein, Katharina Dohm, Harald Kugel, Elisabeth Schrammen, Peter Zwanzger, Elisabeth J. Leehr, Lisa Sindermann, Tali M. Ball, Gregory A. Fonzo, Martin P. Paulus, Alan Simmons, Murray B. Stein, Heide Klumpp, K. Luan Phan, Tomas Furmark, Kristoffer N. T. Mansson, Amirhossein Manzouri, Suzanne N. Avery, Jennifer Urbano Blackford, Jacqueline A. Clauss, Brandee Feola, Jennifer C. Harper, Chad M. Sylvester, Ulrike Lueken, Dick J. Veltman, Anderson M. Winkler, Neda Jahanshad, Daniel S. Pine, Paul M. Thompson, Dan J. Stein, Nic J. A. Van der Wee
Summary: Limited convergence exists in neuroimaging investigations of subcortical brain region volumes in social anxiety disorder (SAD). Variations in methodological approaches and sample selection based on age and clinical characteristics may contribute to inconsistent findings. A global mega-analysis initiated by the ENIGMA-Anxiety Working Group revealed subtle volumetric alterations in subcortical regions in SAD patients. Differences were found in putamen and pallidum volumes, with additional factors such as comorbid anxiety disorders and age of SAD onset influencing these volumetric differences.
MOLECULAR PSYCHIATRY
(2023)
Article
Substance Abuse
Elizabeth A. Flook, Brandee Feola, Margaret M. Benningfield, Marisa M. Silveri, Danny G. Winder, Jennifer Urbano Blackford
Summary: Rodent evidence supports the role of BNST in abstinence symptoms in AUD, and this study demonstrates intrinsic BNST connectivity differences in abstinent individuals compared to controls. Specifically, the BNST-hypothalamus connectivity was found to be lower in the abstinent group, and there were sex differences in both group and individual analyses.
ALCOHOL AND ALCOHOLISM
(2023)
Article
Psychology, Clinical
Brandee Feola, Elizabeth A. Flook, Hannah Gardner, K. Luan Phan, Harry Gwirtsman, Bunmi Olatunji, Jennifer Urbano Blackford
Summary: Posttraumatic stress disorder (PTSD) has a significant impact on many veterans. This disorder involves alterations in both the fear and anxiety networks, and the role of the BNST in combat veterans with PTSD has yet to be examined. The findings of this study suggest that veterans with PTSD have heightened BNST activation and stronger connectivity with multiple fear and anxiety regions.
JOURNAL OF TRAUMATIC STRESS
(2023)
Article
Infectious Diseases
Alice E. Brankin, Philip W. Fowler
Summary: Fluoroquinolone resistance is a threat to tuberculosis treatment, and Whole Genome Sequencing (WGS) with detection of catalogued resistance-associated mutations is a promising method for susceptibility testing. However, the sensitivity of this method is often less than 90% due to the masking of minor alleles. It is important to detect these minor resistance-conferring alleles in WGS or any sequencing-based approach for diagnosing fluoroquinolone resistance. Importance: rating 7/10.
JAC-ANTIMICROBIAL RESISTANCE
(2023)
Article
Biochemistry & Molecular Biology
Joanne L. Parker, Takafumi Kato, Gabriel Kuteyi, Oleg Sitsel, Simon Newstead
Summary: The kidney in mammals maintains blood homeostasis by selectively taking up, retaining or eliminating toxins, drugs and metabolites. Organic anion transporters (OATs) are responsible for recognizing and excreting metabolites and toxins in the nephron. Inhibition of OATs is therapeutically used to enhance drug efficacy and reduce nephrotoxicity. This study presents cryogenic-electron microscopy structures of OAT1 bound to alpha-ketoglutarate, tenofovir, and probenecid, providing molecular insights into alpha-ketoglutarate driven drug elimination and the allosteric regulation of organic anion transport by chloride in the kidney.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Giacomo Fiorin, Lucy R. Forrest, Jose D. Faraldo-Gomez
Summary: All lipid membranes have inherent morphological preferences and resist deformation. The effects of cholesterol on bending rigidity are lipid-specific and arise from differences in the torsional dynamics of the acyl chains. Enhanced-sampling all-atom molecular dynamics simulations allow for the direct quantification of both bending and tilt moduli and provide insights into the contributing factors and molecular mechanisms of curvature generation at each length scale.