Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
Line Number: 71
Backtrace:
File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
Line Number: 8919
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
The development of antiviral drugs against the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) responsible for the recent Covid-19 pandemic is crucial, as treatment options remain limited and vaccination does not prevent (re)infection. Two relatively underexplored targets of this virus are the 3'-5' exoribonuclease (ExoN) and the 2'-O-methyltransferase (2'-O-MTase), both essential for viral viability. The non-structural proteins Nsp14 and Nsp16 exhibit enzymatic activities for ExoN and 2'-O-MTase, respectively, especially when in complex with their co-factor protein Nsp10. The study focuses on the use of target-directed dynamic combinatorial chemistry (tdDCC) to identify binders of Nsp10, aiming to disturb the protein-protein interactions (PPI) involving Nsp10-Nsp14, as well as Nsp10-Nsp16. We synthesised the hits and evaluated them to assess Nsp10 affinity, ExoN and 2'-O-MTase activities inhibition, and antiviral activity in hCoV-229E and SARS-CoV-2-infected whole-cell settings. This study reports a novel class of ExoN and/or 2'-O-MTase inhibitors exhibiting antiviral activity against coronaviruses.
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http://dx.doi.org/10.1002/chem.202403390 | DOI Listing |
Unlabelled: The cat eye syndrome chromosome region candidate 2 (CECR2) protein is an epigenetic regulator involved in chromatin remodeling and transcriptional control. The CECR2 bromodomain (CECR2-BRD) plays a pivotal role in directing the activity of CECR2 through its capacity to recognize and bind acetylated lysine residues on histone proteins. This study elucidates the binding specificity and structural mechanisms of CECR2-BRD interactions with both histone and non-histone ligands, employing techniques such as isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy, and a high-throughput peptide assay.
View Article and Find Full Text PDFJ Theor Biol
December 2024
Institute of Evolution, Centre for Ecological Research, 1121 Budapest, Hungary; Center for the Conceptual Foundations of Science, Parmenides Foundation, 82343 Pöcking, Germany. Electronic address:
Building on the algorithmic equivalence between finite population replicator dynamics and particle filtering based approximation of Bayesian inference, we design a computational model to demonstrate the emergence of Darwinian evolution over representational units when collectives of units are selected to infer statistics of high-dimensional combinatorial environments. The non-Darwinian starting point is two units undergoing a few cycles of noisy, selection-dependent information transmission, corresponding to a serial (one comparison per cycle), non-cumulative process without heredity. Selection for accurate Bayesian inference at the collective level induces an adaptive path to the emergence of Darwinian evolution within the collectives, capable of maintaining and iteratively improving upon complex combinatorial information.
View Article and Find Full Text PDFACS Chem Biol
December 2024
Esya Ltd., 84 Wood Lane, London W12 0BZ, U.K.
Lysosomal storage disorders (LSDs) and adult neurodegenerative disorders like Alzheimer's disease (AD) share various clinical and pathophysiological features. LSDs are characterized by impaired lysosomal activity caused by mutations in key proteins and enzymes. While lysosomal dysfunction is also linked to AD pathogenesis, its precise role in disease onset or progression remains unclear.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of oncology, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.
Introduction: The Xihuang Pill (XHP), a venerated traditional Chinese medicine, has demonstrated significant anti-cancer capabilities. Despite its proven efficacy, the scarcity of comprehensive pharmacological studies limits the widespread application of XHP. This research endeavor seeks to demystify the therapeutic underpinnings of XHP, particularly in the realm of colorectal cancer (CRC) therapy.
View Article and Find Full Text PDFRev Endocr Metab Disord
December 2024
Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
Growth hormone (GH) secretion is pulsatile, entropic, and nycthemeral and is mainly controlled by the hypothalamus through two neurohormones, the stimulating growth hormone releasing hormone (GHRH) and the inhibiting somatostatin. Shortly after its discovery and synthesis, GHRH was intensely investigated diagnostically to define GH secretion. The nascent enthusiasm for using GHRH as a single diagnostic tool to investigate GH deficiency (GHD) dropped down quickly due to a flawed reproducibility.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!