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1.
Cureus ; 15(7): e41387, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37546102

ABSTRACT

BACKGROUND: Accidents may occur at any time and in any location. Unintentional accidents may have life-threatening consequences. Anyone with basic first aid knowledge can assess the situation and intervene to provide proper care. This research aims to assess public knowledge and attitudes toward first aid and its related aspects in Saudi Arabia. METHODS: A cross-sectional online survey was conducted between April and May 2023 to investigate first aid knowledge, attitude, and associated factors among the general public of Saudi Arabia. This study's population consisted of Saudi Arabians aged at least 18 who are part of the general community. This research adapted and used a previously developed questionnaire to evaluate the general public's knowledge, attitudes, and other characteristics about first aid in Saudi Arabia. A binary logistic regression analysis was utilized to determine the variables that influence their knowledge and attitude. RESULTS: A total of 1135 participants were involved in this study. Almost one-third of the study participants (36.0%) reported that they had received training in first aid. The vast majority of the study participants (94.5%) reported that they had heard of first aid before. The media was the most commonly reported source of information on first aid (37.6%). Choking (63.2%), breathing difficulty (61.7%), and fainting (56.7%) were the most commonly reported indications (injuries or accidents) that need first aid. The mean knowledge score for the study participants was 4.4 (SD: 2.8) out of 8 (55.0%), which represents a moderate level of knowledge of first aid. The mean attitude score for the study participants was 22.5 (SD: 2.7) out of 28 (80.4%), which reflects a positive attitude toward first aid. Binary logistic regression analysis identified that women, those who have a higher education level, medical students, those with a high monthly income (7500 Saudi Arabian rials (SAR) and above), and those who work in the healthcare sector were more likely to be knowledgeable about first aid (p<0.05). Participants aged 31 to 40 years and university students were more likely to have a positive attitude toward first aid (p<0.05). CONCLUSION: This research highlights the need to educate the public about first aid and emergency treatment. Even though one-third of participants have received first aid training, ongoing training is necessary. First aid information, especially on social media, is often unreliable. Choking, difficulty breathing, and syncope are typical first aid conditions, and awareness of dealing with choking is needed. Gender, socioeconomic status, and education influenced first aid knowledge and attitudes. Women, medical students, and healthcare workers knew more about first aid. Most participants supported first aid provision. This research strongly suggests improving awareness, providing inexpensive first-aid training, and targeting specific populations to improve first-aid knowledge and attitudes.

2.
Cureus ; 15(6): e40114, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37425509

ABSTRACT

BACKGROUND: Lack of public understanding and perception may lead to a general downplaying of inflammatory bowel disorder (IBD) symptoms as they affect a less socially acceptable area of the body, which may be a significant component in the everyday struggles of an individual with IBD. AIM: The aim is to assess the public knowledge of Crohn's disease and ulcerative colitis in Saudi Arabia. METHOD: This was an online survey study that examined public knowledge of IBD in Saudi Arabia for the duration between February and March 2023. Participants were invited to participate in this study using social media websites. The questionnaire tool comprised three sections: a sociodemographic characteristics section (seven questions), an awareness section (two questions), and a knowledge section (24 questions). A binary logistic regression analysis was utilized to identify the factors that influenced the participants' knowledge of Crohn's disease and ulcerative colitis. RESULTS: A total of 630 individuals participated in this study. Around 28% of the participants reported that they had never heard of, read about, or dealt with Crohn's disease. Around 16% of them reported that they had never heard of, read about, or dealt with ulcerative colitis. The mean overall knowledge score of the study participants was 8.3 (standard deviation: 2.4) out of 24, which is equal to 34.6% and represents a weak level of knowledge of IBD. The participants showed a weak level of knowledge for all sub-scales of knowledge related to IBD general knowledge, diet, treatments, and complications. The knowledge sub-scale level ranged between 30% and 36.7%. Females, the participants in the moderate and high-income category, those who lived in urban areas, those with a higher level of education, and those who reported having osteoarthritis were more likely to be knowledgeable about IBD compared to others (p≤0.001). CONCLUSION: In Saudi Arabia, a low level of IBD awareness was identified among the general population, supporting findings from other countries. Future research should aim to identify effective educational interventions to increase public awareness of this group of diseases, which would ultimately facilitate early diagnosis and improve patient outcomes.

3.
Nat Commun ; 13(1): 7759, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36522330

ABSTRACT

Histone modifications are deposited by chromatin modifying enzymes and read out by proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of the acetyl lysine reader BRD4 that binds to the acetylase p300 and enables formation of long-range intra- and interchromosomal interactions. We here examine how acetylation reading and writing enable formation of such interactions. We show that NUT contains an acidic transcriptional activation domain that binds to the TAZ2 domain of p300. We use NMR to investigate the structure of the complex and found that the TAZ2 domain has an autoinhibitory role for p300. NUT-TAZ2 interaction or mutations found in cancer that interfere with autoinhibition by TAZ2 allosterically activate p300. p300 activation results in a self-organizing, acetylation-dependent feed-forward reaction that enables long-range interactions by bromodomain multivalent acetyl-lysine binding. We discuss the implications for chromatin organisation, gene regulation and dysregulation in disease.


Subject(s)
Lysine , Nuclear Proteins , Acetylation , Nuclear Proteins/metabolism , Lysine/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Chromatin
4.
Mol Microbiol ; 118(1-2): 16-29, 2022 07.
Article in English | MEDLINE | ID: mdl-35615908

ABSTRACT

The proteasome system allows the elimination of functional or structurally impaired proteins. This includes the degradation of nascent peptides. In Archaea, how the proteasome complex interacts with the translational machinery remains to be described. Here, we characterized a small orphan protein, Q9UZY3 (UniProt ID), conserved in Thermococcales. The protein was identified in native pull-down experiments using the proteasome regulatory complex (proteasome-activating nucleotidase [PAN]) as bait. X-ray crystallography and small-angle X-ray scattering experiments revealed that the protein is monomeric and adopts a ß-barrel core structure with an oligonucleotide/oligosaccharide-binding (OB)-fold, typically found in translation elongation factors. Mobility shift experiment showed that Q9UZY3 displays transfer ribonucleic acid (tRNA)-binding properties. Pull-downs, co-immunoprecipitation and isothermal titration calorimetry (ITC) studies revealed that Q9UZY3 interacts in vitro with PAN. Native pull-downs and proteomic analysis using different versions of Q9UZY3 showed that the protein interacts with the assembled PAN-20S proteasome machinery in Pyrococcus abyssi (Pa) cellular extracts. The protein was therefore named Pbp11, for Proteasome-Binding Protein of 11 kDa. Interestingly, the interaction network of Pbp11 also includes ribosomal proteins, tRNA-processing enzymes and exosome subunits dependent on Pbp11's N-terminal domain that was found to be essential for tRNA binding. Together these data suggest that Pbp11 participates in an interface between the proteasome and the translational machinery.


Subject(s)
Archaeal Proteins , Proteasome Endopeptidase Complex , Archaea/metabolism , Archaeal Proteins/metabolism , Carrier Proteins , Crystallography, X-Ray , Proteasome Endopeptidase Complex/metabolism , Proteomics , RNA, Transfer
5.
Nat Commun ; 12(1): 4618, 2021 07 29.
Article in English | MEDLINE | ID: mdl-34326347

ABSTRACT

The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.


Subject(s)
Cell Nucleus/metabolism , Chromatin/metabolism , E1A-Associated p300 Protein/metabolism , Histone Acetyltransferases/metabolism , Histones/metabolism , Transcription Factors/metabolism , Acetylation , Cells, Cultured , E1A-Associated p300 Protein/chemistry , Humans , Protein Domains
6.
Nature ; 562(7728): 538-544, 2018 10.
Article in English | MEDLINE | ID: mdl-30323286

ABSTRACT

The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using two model transcription factors, IRF3 and STAT1, we demonstrate that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. We describe a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighbouring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling and the activation and dimerization of transcription factors control the activation of p300, and therefore explain why gene transcription is associated with chromatin acetylation.


Subject(s)
Protein Multimerization , Transcription Factors/chemistry , Transcription Factors/metabolism , p300-CBP Transcription Factors/chemistry , p300-CBP Transcription Factors/metabolism , Acetylation , Catalytic Domain , Chromatin/chemistry , Chromatin/metabolism , Crystallography, X-Ray , Enzyme Activation , Humans , Interferon Regulatory Factor-3/chemistry , Interferon Regulatory Factor-3/metabolism , Ligands , Lysine/chemistry , Lysine/metabolism , Models, Molecular , Protein Domains , STAT1 Transcription Factor/chemistry , STAT1 Transcription Factor/metabolism , Transcription, Genetic
7.
Cell Rep ; 24(13): 3477-3487.e6, 2018 09 25.
Article in English | MEDLINE | ID: mdl-30257209

ABSTRACT

Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.


Subject(s)
Histones/metabolism , Infertility, Male/genetics , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Protein Processing, Post-Translational , Spermatozoa/metabolism , Acetylation , Animals , Histone Code , Histones/chemistry , Male , Mice , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Protein Binding , Spermatogenesis , Xenopus , p300-CBP Transcription Factors/metabolism
8.
Sci Rep ; 7: 40948, 2017 01 19.
Article in English | MEDLINE | ID: mdl-28102317

ABSTRACT

We present a combination of small-angle neutron scattering, deuterium labelling and contrast variation, temperature activation and fluorescence spectroscopy as a novel approach to obtain time-resolved, structural data individually from macromolecular complexes and their substrates during active biochemical reactions. The approach allowed us to monitor the mechanical unfolding of a green fluorescent protein model substrate by the archaeal AAA+ PAN unfoldase on the sub-minute time scale. Concomitant with the unfolding of its substrate, the PAN complex underwent an energy-dependent transition from a relaxed to a contracted conformation, followed by a slower expansion to its initial state at the end of the reaction. The results support a model in which AAA ATPases unfold their substrates in a reversible power stroke mechanism involving several subunits and demonstrate the general utility of this time-resolved approach for studying the structural molecular kinetics of multiple protein remodelling complexes and their substrates on the sub-minute time scale.


Subject(s)
ATPases Associated with Diverse Cellular Activities/chemistry , ATPases Associated with Diverse Cellular Activities/metabolism , Archaea/enzymology , Scattering, Small Angle , Green Fluorescent Proteins/metabolism , Protein Conformation , Protein Folding
9.
Cranio ; 23(1): 67-73, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15727323

ABSTRACT

The aim of our study was the evaluation of seasonal influences on development and evolution of temporomandibular disorders (TMD). In a retrospective study based on data from 1997 and 1998, we analyzed the monthly number of patients at the Department of Prosthodontics. The total number of first time examinations during these two years was 11,747. Nine hundred and sixty-one (961) patients showed symptoms frequently found in TMD. These patients were submitted to a special TMD diagnosis based on the criteria of a validated craniomandibular index questionnaire. In 568 patients (group A1), a TMD was confirmed, in the other 393 patients (group A2), the disorder could not be confirmed. Dividing up the numbers of patients into summer and winter half years, we found statistically significant relationships between patient numbers and season in TMD patients (A1) as well as in all patients (group B). The distribution of the monthly numbers of TMD patients with its maximum in winter, however, was characteristically different from that of all patients with the maximum in summer. The number of TMD patients per month was significantly correlated to the mean daily sunshine duration per month. Parallels could be drawn to seasonal variations of symptoms in Seasonal Affective Disorders (SAD). As the mechanisms which influence the emergence of psychologically impacted disease in TMD patients might be comparable to SAD, we propose that a similar therapy may be applied.


Subject(s)
Seasons , Temporomandibular Joint Disorders/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Darkness , Female , Humans , Male , Middle Aged , Retrospective Studies , Seasonal Affective Disorder/etiology , Sunlight , Temporomandibular Joint Disorders/classification
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