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Nucleic Acids Research Jan 2022Small RNAs capable of self-cleavage and ligation might have been the precursors for the much more complex self-splicing group I and II introns in an early RNA world....
Small RNAs capable of self-cleavage and ligation might have been the precursors for the much more complex self-splicing group I and II introns in an early RNA world. Here, we demonstrate the activity of engineered hairpin ribozyme variants, which as self-splicing introns are removed from their parent RNA. In the process, two cleavage reactions are supported at the two intron-exon junctions, followed by ligation of the two generated exon fragments. As a result, the hairpin ribozyme, here acting as the self-splicing intron, is cut out. Two self-splicing hairpin ribozyme variants were investigated, one designed by hand, the other by a computer-aided approach. Both variants perform self-splicing, generating a cut-out intron and ligated exons.
Topics: Genetic Engineering; RNA; RNA Splicing; RNA, Catalytic
PubMed: 34928378
DOI: 10.1093/nar/gkab1239 -
Journal of Molecular Microbiology and... 2013Bacterial microcompartments are large proteinaceous structures that act as metabolic organelles in many bacterial cells. A shell or capsid, which is composed of a few... (Review)
Review
Bacterial microcompartments are large proteinaceous structures that act as metabolic organelles in many bacterial cells. A shell or capsid, which is composed of a few thousand protein subunits, surrounds a series of sequentially acting enzymes and controls the diffusion of substrates and products into and out of the lumen. The carboxysome and the propanediol utilization microcompartment represent two well-studied systems among seven or more distinct types that can be delineated presently. Recent structural studies have highlighted a number of sophisticated mechanisms that underlie the function of bacterial microcompartment shell proteins. This review updates our understanding of bacterial microcompartment shells, how they are assembled, and how they carry out their functions in molecular transport and enzyme organization.
Topics: Bacteria; Macromolecular Substances; Organelles
PubMed: 23920492
DOI: 10.1159/000351347 -
Soins; La Revue de Reference Infirmiere 2022The ten French units for difficult patients are secure psychiatric services which receive people suffering from mental pathologies who could have committed or have...
The ten French units for difficult patients are secure psychiatric services which receive people suffering from mental pathologies who could have committed or have committed dangerous acts. Among the mental health structures presented in this dossier, the units for difficult patients are those which admit prisoners with psychological disorders and problems of dangerousness for the longest period of time. As fully-fledged care facilities, they offer intensive and multi-professional care.
Topics: Humans; Mental Disorders; Prisoners; Mental Health
PubMed: 36681503
DOI: 10.1016/j.soin.2022.11.007 -
American Family Physician Apr 2000Dreams occur during all stages of sleep. Nightmares are common. They can be associated with poor sleep and diminished daytime performance. Frequent nightmares are not... (Review)
Review
Dreams occur during all stages of sleep. Nightmares are common. They can be associated with poor sleep and diminished daytime performance. Frequent nightmares are not related to underlying psychopathology in most children and in some "creative" adults. However, recurrent nightmares are the most defining symptom of post-traumatic stress disorder and may be associated with other psychiatric illnesses. Night terrors are arousal disorders that occur most often in children and usually occur early in the sleep period. Patients with rapid-eye-movement behavior disorder often present with nocturnal injury resulting from the acting out of dreams. Dream disorders may respond to medication, but behavioral treatment approaches have shown excellent results, particularly in patients with post-traumatic stress disorder and recurrent nightmares.
Topics: Diagnosis, Differential; Dreams; Humans; Mental Disorders; Night Terrors; Patient Education as Topic; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Teaching Materials
PubMed: 10779247
DOI: No ID Found -
Soins; La Revue de Reference Infirmiere 2022The intensive psychiatric care units are intermediate health structures between the sector psychiatric services and the units for difficult patients. Prisoners can be...
The intensive psychiatric care units are intermediate health structures between the sector psychiatric services and the units for difficult patients. Prisoners can be treated there under article D. 398 of the Code of Criminal Procedure.
Topics: Humans; Prisoners
PubMed: 36681504
DOI: 10.1016/j.soin.2022.11.008 -
Bioinformation 2020The heat shock protein Hsp90 is a molecular chaperon that uses ATP and interacts with various co-chaperone proteins, acting as adapters, in order to carry out the...
The heat shock protein Hsp90 is a molecular chaperon that uses ATP and interacts with various co-chaperone proteins, acting as adapters, in order to carry out the maturation of its target proteins. In physiological conditions, the heat shock proteins (HSPs) favour post-translational modification, protein folding and sub-cellular transport of their "client" proteins. In stress conditions, many misfolded proteins accumulate exposing their hydrophobic residues and these are recognized by HSPs which prevent the aggregation and favour the correct folding. In case this is no longer possible, HSPs mediate elimination of such misfolded proteins, mainly by ubiquitin-proteasome system.
PubMed: 32025156
DOI: 10.6026/97320630016017 -
Current Opinion in HIV and AIDS Jul 2015Long-acting injectable antiretroviral therapy (ART) formulations hold great promise in helping to close the significant gap between efficacy and effectiveness in HIV... (Review)
Review
PURPOSE OF REVIEW
Long-acting injectable antiretroviral therapy (ART) formulations hold great promise in helping to close the significant gap between efficacy and effectiveness in HIV treatment by eliminating the requirement for lifelong daily pills. However, significant systems-level and individual challenges to implementation of long-acting ART in HIV treatment are anticipated.
RECENT FINDINGS
Studies of long-acting ART formulations are burgeoning, but the drugs are still in early phases of investigation and key knowledge gaps in pharmacokinetics and pharmacodynamics, as well as their effectiveness in settings with the largest burden of HIV disease and in key populations, remain. Extrapolating from the literature on implementation barriers to using long-acting contraception on a global scale, we explore the implementation barriers to rolling-out long-acting ART, including country approval and endorsements; prioritization of patient populations for preferred use, clinic infrastructure requirements, steady supply chains, decentralization of care, provider and patient training programs, and laboratory monitoring; and the need to examine patient preferences and conduct rigorous implementation science research to effectively scale-up this intervention.
SUMMARY
Long-acting ART for HIV treatment harbors exciting potential to shift treatment paradigms. Current knowledge gaps in the use of these agents remain, leading to multiple anticipated systems-level and individual-level barriers to implementation. Addressing these gaps and barriers will help fulfill the promise of these agents against the pandemic.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Delayed-Action Preparations; HIV Infections; Humans
PubMed: 26049955
DOI: 10.1097/COH.0000000000000158 -
American Family Physician Aug 2013Sleep disorders are common and affect sleep quality and quantity, leading to increased morbidity. Patients with sleep disorders can be categorized as those who cannot... (Review)
Review
Sleep disorders are common and affect sleep quality and quantity, leading to increased morbidity. Patients with sleep disorders can be categorized as those who cannot sleep, those who will not sleep, those with excessive daytime sleepiness, and those with increased movements during sleep. Insomnia, defined as difficulty initiating or maintaining sleep that results in daytime impairment, is diagnosed using history findings and treated with cognitive behavior therapy, with or without sleep hypnotics. Restless legs syndrome is characterized by an urge to move the legs that worsens with rest, is relieved by movement, and often occurs in the evening or at night. Restless legs syndrome is treated based on the frequency of symptoms. Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis. It is diagnosed using a sleep log or actigraphy, followed by overnight polysomnography and a multiple sleep latency test. Narcolepsy is treated with stimulants, such as modafinil; selective serotonin reuptake inhibitors; or gamma hydroxybutyric acid (sodium oxybate). Patients with snoring and witnessed apneas may have obstructive sleep apnea, which is diagnosed using overnight polysomnography. Continuous positive airway pressure is the most common and effective treatment for obstructive sleep apnea. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in the patient acting out dreams with possible harmful consequences. It is diagnosed based on history and polysomnography findings, and treated with environmental safety measures and melatonin or clonazepam.
Topics: Actigraphy; Central Nervous System Stimulants; Cognitive Behavioral Therapy; Continuous Positive Airway Pressure; Humans; Hypnotics and Sedatives; Narcolepsy; Polysomnography; Practice Guidelines as Topic; REM Sleep Behavior Disorder; Restless Legs Syndrome; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 23944726
DOI: No ID Found -
ELife Nov 2017A disordered region at the N-terminus of the glucocorticoid receptor can fine tune how cells respond to a hormone via an allosteric mechanism.
A disordered region at the N-terminus of the glucocorticoid receptor can fine tune how cells respond to a hormone via an allosteric mechanism.
Topics: Acting Out; Allosteric Regulation; Frustration; Models, Molecular; Transcription Factors
PubMed: 29160204
DOI: 10.7554/eLife.32762 -
Journal of Hospital Medicine Dec 2021Guidelines recommend against initiating long-acting opioids during acute hospitalization, owing to higher risk of overdose and morbidity compared to short-acting opioid...
Guidelines recommend against initiating long-acting opioids during acute hospitalization, owing to higher risk of overdose and morbidity compared to short-acting opioid initiation. We investigated the incidence of long-acting opioid initiation following hospitalization in a retrospective cohort of Medicare beneficiaries with an acute care hospitalization in 2016 who were ≥65 years old, did not have cancer or hospice care, and had not filled an opioid prescription within the preceding 90 days. Among 258,193 hospitalizations, 47,945 (18.6%) were associated with a claim for a new opioid prescription in the week after hospital discharge: 817 (0.3%) with both short- and long-acting opioids, 125 (0.1%) with long-acting opioids only, and 47,003 (18.2%) with short-acting opioids only. Most long-acting opioid claims occurred in surgical patients (770 out of 942; 81.7%). Compared with beneficiaries prescribed short-acting opioids only, beneficiaries prescribed long-acting opioids were younger, had a higher prevalence of diseases of the musculoskeletal system and connective tissue, and had more known risk factors for opioid-related adverse events, including anxiety disorders, opioid use disorder, prior long-term high-dose opioid use, and benzodiazepine co-prescription. These findings may help target quality-improvement initiatives.
Topics: Aged; Analgesics, Opioid; Hospitals; Humans; Medicare; Patient Discharge; Retrospective Studies; United States
PubMed: 34797996
DOI: 10.12788/jhm.3721