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
Members of the Flaviviridae family, including dengue virus (DENV) and yellow fever virus, cause serious disease in humans, whilst maternal infection with Zika virus (ZIKV) can induce microcephaly in newborns. Following infection, flaviviral RNA genomes are translated to produce the viral replication machinery but must then serve as a template for the transcription of new genomes. However, the ribosome and viral polymerase proceed in opposite directions along the RNA, risking collisions and abortive replication. Whilst generally linear, flavivirus genomes can adopt a circular conformation facilitated by long-range RNA-RNA interactions, shown to be essential for replication. Using an in vitro reconstitution approach, we demonstrate that circularization inhibits de novo translation initiation on ZIKV and DENV RNA, whilst the linear conformation is translation-competent. Our results provide a mechanism to clear the viral RNA of ribosomes in order to promote efficient replication and, therefore, define opposing roles for linear and circular conformations of the flavivirus genome.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765113 | PMC |
http://dx.doi.org/10.1093/nar/gkz686 | DOI Listing |
Voltage-sensitive calcium channels contribute to depolarization of both motor- and interneurons in animal studies, but less is known of their contribution to human motor control and whether blocking them has potential in future antispasmodic treatment in humans. Therefore, this study investigated the acute effect of Nimodipine on the transmission of human spinal reflex pathways involved in spasticity. In a double-blinded, cross-over study, we measured soleus muscle stretch- and H-reflexes, and tibialis anterior cutaneous reflexes in nineteen healthy subjects before and after Nimodipine (tab-let 60mg) or Baclofen (tablet 25mg).
View Article and Find Full Text PDFChemistry
December 2024
"Indian Institute of Science Education and Research Kolkata", Chemical Sciences, Research Complex, 741246, Mohanpur, INDIA.
The recent surge in emerging viral infections warrants the design of broad-spectrum antivirals. We aim to develop a lead molecule that targets a common biochemical feature of many enveloped viruses, membrane fusion. To achieve the broad-spectrum ability, instead of targeting the fusion machinery, we plan to modulate the physicochemical properties of the host and viral membranes to block fusion.
View Article and Find Full Text PDFMol Psychiatry
December 2024
Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences, Adams Super Center for Brain Studies and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 6997801, Israel.
Essential for brain formation and protective against tauopathy, activity-dependent neuroprotective protein (ADNP) is critical for neurogenesis and cognitive functions, while regulating steroid hormone biogenesis. As such, de novo mutations in ADNP lead to syndromic autism and somatic ADNP mutations parallel Alzheimer's disease progression. Furthermore, clinical trials with the ADNP fragment NAP (the investigational drug davunetide) showed efficacy in women suffering from the tauopathy progressive supranuclear palsy and differentially boosted memory in men (spatial) and women (verbal), exhibiting prodromal Alzheimer's disease.
View Article and Find Full Text PDFDrugs R D
December 2024
Galapagos SASU, Romainville, France.
Background And Objective: This study provides a physiologically based pharmacokinetic (PBPK) model-based analysis of the potential drug-drug interaction (DDI) between cyclosporin A (CsA), a breast cancer resistance protein transporter (BCRP) inhibitor, and methotrexate (MTX), a putative BCRP substrate.
Methods: PBPK models for CsA and MTX were built using open-source tools and published data for both model building and for model verification and validation. The MTX and CsA PBPK models were evaluated for their application in simulating BCRP-related DDIs.
J Cell Biol
February 2025
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Endocytosis, required for the uptake of receptors and their ligands, can also introduce pathological aggregates such as α-synuclein (α-syn) in Parkinson's Disease. We show here the unexpected presence of intrinsically perforated endolysosomes in neurons, suggesting involvement in the genesis of toxic α-syn aggregates induced by internalized preformed fibrils (PFFs). Aggregation of endogenous α-syn in late endosomes and lysosomes of human iPSC-derived neurons (iNs), seeded by internalized α-syn PFFs, caused the death of the iNs but not of the parental iPSCs and non-neuronal cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!