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Abstract The COVID-19 pandemic has profoundly affected global health system, significantly altering not only the acute management of viral infection, but also management strategies for chronic diseases. This study aimed to investigate the impact of COVID-19 infection on exacerbation rates and the economic burden in patients with COPD. We conducted a retrospective cohort study using data from the national insurance reimbursement data of South Korea. Eligible participants included COPD patients diagnosed with COVID-19 between January and December 2020. We analyzed exacerbation rates, healthcare utilization, and medical costs pre- and post-COVID-19 infection. In 3,445 COPD patients who were infected by COVID-19, COVID-19 infection resulted in increased annual moderate-to-severe and severe exacerbations compared to pre-COVID-19 infection (IRR = 1.062 [95%CI 1.027–1.099]; IRR = 1.315 [95%CI 1.182–1.481], respectively). Among previously non-exacerbators, 11.2% of patients transitioned to exacerbator after COVID-19 infection. Older age, comorbidities and use of triple therapy were the factors associated with transitioners. Direct medical costs escalated significantly from approximately $6810 to $11,032, reflecting the increased intensity of care after COVID-19 infection. COVID-19 infection has significantly increased rate of exacerbations in patients with COPD and imposed a heavier economic burden on healthcare system. Among non-exacerbators, substantial number of patients transitioned to exacerbators after COVID-19 infection.

Copyright of Darüşşifa Journal of Islamic Medical History Research is the property of Darussifa Journal of Islamic Medical History Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mouse embryonic stem cells (ESCs) possess a pluripotent developmental potential and a stable karyotype. An exception is the frequent loss of one X chromosome in female ESCs derived from inbred mice. In contrast, female ESCs from crosses between different Mus musculus subspecies often maintain two X chromosomes and can model X chromosome inactivation. Here we report that combined mutations of Hira and Cdk8 induce rapid loss of one X chromosome in a Mus musculus castaneus hybrid female ESC line that originally maintains two X chromosomes. We show that MEK1 inhibition, which is used for culturing naive pluripotent ESCs is sufficient to induce X chromosome loss. In conventional ESC media, Hira and Cdk8 mutant ESCs maintain both X chromosomes. Induction of X chromosome loss by switching to naive culture media allows us to perform kinetic measurements for calculating the chromosome loss rate. Our analysis shows that X chromosome loss is not explained by selection of XO cells, but likely driven by a process of chromosome elimination. We show that elimination of the X chromosome occurs with a rate of 0.3% per cell per division, which exceeds reported autosomal loss rates by 3 orders of magnitude. We show that chromosomes 8 and 11 are stably maintained. Notably, Xist expression from one of the two X chromosomes rescues X chromosomal instability in ΔHiraΔCdk8 ESCs. Our study defines mutations of Hira and Cdk8 as molecular drivers for X chromosome elimination in naive female ESCs and describes a cell system for elucidating the underlying mechanism. [ABSTRACT FROM AUTHOR]

Appropriate responses to environmental challenges are imperative for the survival of all living organisms. Exposure to low‐dose stresses is recognized to yield increased cellular fitness, a phenomenon termed hormesis. However, our molecular understanding of how cells respond to low‐dose stress remains profoundly limited. Here we report that histone variant H3.3‐specific chaperone, HIRA, is required for acquired tolerance, where low‐dose heat stress exposure confers resistance to subsequent lethal heat stress. We found that human HIRA activates stress‐responsive genes, including HSP70, by depositing histone H3.3 following low‐dose stresses. These genes are also marked with histone H3 Lys‐4 trimethylation and H3 Lys‐9 acetylation, both active chromatin markers. Moreover, depletion of HIRA greatly diminished acquired tolerance, both in normal diploid fibroblasts and in HeLa cells. Collectively, our study revealed that HIRA is required for eliciting adaptive stress responses under environmental fluctuations and is a master regulator of stress tolerance. [ABSTRACT FROM AUTHOR]

Kepuasan konsumen merupakan tujuan yang ingin dicapai oleh setiap perusahaan. Faktor produksi memiliki peran penting untuk mencapai tujuan perusahaan. Namun, setiap tempat, proses, peralatan, sikap, dan lingkungan kerja memiliki potensi bahaya dan risiko kerja. Penelitian ini berupaya mengidentifikasi potensi bahaya dan merumuskan strategi untuk meminimalisir risiko pada lantai produksi industri di bidang furnitur. Adanya indikasi tingkat kecelakaan kerja yang sering terjadi mendorong penting untuk dilakukan penelitian ini. Penelitian ini menemukan sebanyak 33 potensi bahaya pada proses produksi, terdiri dari 37% termasuk kategori tinggi, 24% kategori ekstrem dan medium, sementara bahaya kategori rendah sebesar 15%. Faktor peralatan dan fasilitas kerja dan lingkungan kerja merupakan faktor terbanyak yang memiliki sumber risiko, dan diikuti oleh faktor mesin produksi dan sikap pekerja. Penelitian ini menekankan bahwa faktor peralatan dan fasilitas kerja dan lingkungan yang mendukung dapat mencegah terjadinya kecelakaan kerja. Berdasarkan kerangka operasional HAZOP, penelitian ini menawarkan beberapa strategi untuk meminimalisir tingkat risiko pada proses produksi produk furnitur berdasarkan faktor-faktor sumber risiko. [IMPLEMENTATION OF HIRA AND HAZOP METHODS TO MINIMIZE POTENTIAL HEALTH AND SAFETY HAZARDS IN THE FURNITURE INDUSTRY] Customer satisfaction is the ultimate goal to be achieved by every company. Production factors play an important role in achieving the company's goals. However, every place, process, equipment, attitude, and work environment has potential hazards and occupational risks. This research seeks to identify potential hazards and formulate strategies to minimize risks on industrial production floors in the furniture sector. The indication of the level of work accidents that often occur encourages the importance of this research. This study found 33 potential hazards in the production process, consisting of 37% in the high category, 24% in the extreme and medium categories, and 15% in the low category. Work equipment and facilities and the work environment were the most common sources of risk, followed by production machinery and worker attitudes. This study emphasized that the factors of equipment and work facilities and a supportive environment can prevent work accidents. Based on the HAZOP method, this research offers several strategies to minimize the level of risk in the production process of furniture products based on risk source factors. Keywords: Hazard Analysis; Risk Assessment; Work Accident; HIRA; HAZOP

This article discusses a case study of a newborn with tetralogy of Fallot and features similar to DiGeorge syndrome. The child underwent genetic testing, including chromosomal microarray analysis and whole exome sequencing, which identified a de novo variant in the HIRA gene resulting in the loss of the start codon. The HIRA gene has been associated with hematopoiesis, neurodevelopment, and cardiac development. This case adds to the current knowledge of HIRA-related phenotypes and suggests a potential association between HIRA gene variants and tetralogy of Fallot. [Extracted from the article]

‘Rivayetlerin tefsiri’ şeklinde ifade edebileceğimiz şerhlerin, Tefsir meseleleri ile yakından ilgilendikleri, rivayetleri anlama ve anlamlandırma noktasında özellikle müracaat edilmesi gerektiği düşünülmektedir. Zira şerh edebiyatı Tefsir ve diğer ilimlere de katkı sağlayacak, yeni bakış açıları sunacaktır. Ancak bu hadisenin Tefsir ilmi ile doğrudan veya dolaylı olarak irtibatlı konularına dair şerhler henüz kapsamlı bir araştırmaya tâbi tutulmamışlardır. Bu itibarla Hira hadisesi ve bu çerçevede gelişen konular, Tefsir ilmi muvacehesinden şerh edebiyatı içerisinde araştırılmıştır. Söz konusu hadisenin şârihler tarafından değerlendirmesine yer verilirken Tefsir ilmi ile ilgili meselelere yaklaşımlarına, bu meseleleri nasıl yorumladıklarına ve şârihler arasında süregelen tartışmalara ulaşılmaya çalışılmıştır. Bu takip sonucunda hadisenin gerçekleşme hali, vahyin başlangıcı, ilk inen âyetler, Hz. Peygamber’in (sav) ümmîliği gibi konulara ve bunlar çerçevesindeki tartışmalara ulaşılmıştır. Tefsiri ilgilendiren yönleri itibarıyla; hadisenin gerçekleşme hali üzerinden ‘rüyada Kur’ân vahyi gelmiş midir?’ sorusunun cevabı, vahyin türlerinden bazıları, ilk inen âyetler üzerine gelişen/genişleyen tartışmalar ve Resulullah’ın (sav) vahiyle eğitiminin başlangıcı hakkında malumatlar tespit edilmiştir.

Abstract Background Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts. Results We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes. Conclusion Our results provide an evolutionary perspective on H3.3’s conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.

Quiescence (G0) is a reversible non-dividing state that facilitates cellular survival in adverse conditions. Here, we demonstrate that the HIRA histone chaperone complex is required for the reversibility and longevity of nitrogen starvation-induced quiescence in Schizosaccharomyces pombe. The HIRA protein, Hip1 is not required for entry into G0 or the induction of autophagy. Although hip1Δ cells retain metabolic activity in G0, they rapidly lose the ability to resume proliferation. After a short period in G0 (1 day), hip1Δ mutants can resume cell growth in response to the restoration of a nitrogen source but do not efficiently reenter the vegetative cell cycle. This correlates with a failure to induce the expression of MBF transcription factor-dependent genes that are critical for S phase. In addition, hip1Δ G0 cells rapidly progress to a senescent state in which they can no longer re-initiate growth following nitrogen source restoration. Analysis of a conditional hip1 allele is consistent with these findings and indicates that HIRA is required for efficient exit from quiescence and prevents an irreversible cell cycle arrest. [ABSTRACT FROM AUTHOR]

Bu çalışmada Cahiliye döneminden risalete Sāsānīlerin Arap Yarımadası’ndaki dinî ve siyasi varlığı, Kur’an-ı Kerim’in bahse konu ettiği mecūs kavramının tarihsel arka planına temasla irdelenecektir. Bu çerçevede Cahiliye Arabı’nın İran/Pers kültür havzasıyla münasebetinin boyutu, mecūs kavramının odağa alınmasıyla tartışılacaktır. Bu kavramın oluşum sürecinde Ḥīre’nin ve Güney Arabistan’ın Arap-Pers etkileşimindeki kayda değer rolüne temas edilecektir. Özellikle Sāsānī hakimiyetinin Arap Yarımadası’na bakan yüzü olan Ḥīre’nin konumu, kültürel etkileşimin zemini olarak öne çıkmaktadır. Bu yolla Sāsānīlerin bu coğrafyadaki kadim tarihine ışık tutulurken mecūs ifadesiyle dinî bağlama işaret edilecektir. Böylelikle Kur’an’ın kullandığı mecūs kavramının Cahiliye Arabı’nın zihin dünyasında bir karşılığının olduğu ve dolayısıyla Sāsānīlerin dinî anlayışının Arap Yarımadası’nda bu kavram üzerinden varlık bulduğu ortaya çıkarılacaktır. Aynı zamanda risalet sürecinde Mecūsīlere ilişkin onların da Ehl-i kitap gibi kabul edilmeleri hususu, Cahiliye Arabı’nın anlam dünyasıyla arz ettiği paralellik açısından bahse konu edilecektir.

Copyright of Burdur Theology Journal / Burdur İlahiyat Dergisi is the property of Burdur Mehmet Akif Ersoy Universitesi lahiyat Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

For shade‐intolerant plants, changes in light quality through competition from neighbors trigger shade avoidance syndrome (SAS): a series of morphological and physiological adaptations that are ultimately detrimental to plant health and crop yield. Phytochrome‐interacting factor 7 (PIF7) is a major transcriptional regulator of SAS in Arabidopsis; however, how it regulates gene expression is not fully understood. Here, we show that PIF7 directly interacts with the histone chaperone anti‐silencing factor 1 (ASF1). The ASF1‐deprived asf1ab mutant showed defective shade‐induced hypocotyl elongation. Histone regulator homolog A (HIRA), which mediates deposition of the H3.3 variant into chromatin, is also involved in SAS. RNA/ChIP‐sequencing analyses identified the role of ASF1 in the direct regulation of a subset of PIF7 target genes. Furthermore, shade‐elicited gene activation is accompanied by H3.3 enrichment, which is mediated by the PIF7‐ASF1‐HIRA regulatory module. Collectively, our data reveal that PIF7 recruits ASF1‐HIRA to increase H3.3 incorporation into chromatin to promote gene transcription, thus enabling plants to effectively respond to environmental shade. Synopsis: In Arabidopsis, the transcription factor PIF7 plays a dominant role in ameliorating the impact shade conditions have on fitness. In this study, a PIF7‐ASF1‐HIRA regulatory module is found to mediate H3.3 incorporation at a subset of shade‐responsive loci, leading to shade‐induced gene expression and morphological adaptation. PIF7 recruits the ASF1‐HIRA complex under shade conditionsASF1 and HIRA positively regulate shade‐induced hypocotyl elongation and define changes in gene expressionShade increases ASF1 and H3.3 enrichment in the chromatin of a subset of PIF7 target genesA PIF7‐ASF1‐HIRA regulatory module is responsible for H3.3 incorporation in the shade [ABSTRACT FROM AUTHOR]

Background: Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts. Results: We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes. Conclusion: Our results provide an evolutionary perspective on H3.3's conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways. [ABSTRACT FROM AUTHOR]

Abstract Background Histone cell cycle regulator (HIRA) complex is an important histone chaperone that mediates the deposition of the H3.3 histone variant onto chromatin independently from DNA synthesis. However, it is still unknown whether it participates in the expression control of retrotransposons and cell fate determination. Methods We screened the role of HIRA complex members in repressing the expression of retrotransposons by shRNA depletion in embryonic stem cells (ESCs) followed by RT-qPCR. RNA-seq was used to study the expression profiles after depletion of individual HIRA member. RT-qPCR and western blot were used to determine overexpression of HIRA complex members. Chromatin immunoprecipitation (ChIP)-qPCR was used to find the binding of H3.3, HIRA members to chromatin. Co-immunoprecipitation was used to identify the interaction between Hira mutant and Ubn2. ChIP-qPCR was used to identify H3.3 deposition change and western blot of chromatin extract was used to validate the epigenetic change. Bioinformatics analysis was applied for the analysis of available ChIP-seq data. Results We revealed that Hira, Ubn2, and Ubn1 were the main repressors of 2-cell marker retrotransposon MERVL among HIRA complex members. Surprisingly, Ubn2 and Hira targeted different groups of retrotransposons and retrotransposon-derived long noncoding RNAs (lncRNAs), despite that they partially shared target genes. Furthermore, Ubn2 prevented ESCs to gain a 2-cell like state or activate trophectodermal genes upon differentiation. Mechanistically, Ubn2 and Hira suppressed retrotransposons by regulating the deposition of histone H3.3. Decreased H3.3 deposition, that was associated with the loss of Ubn2 or Hira, caused the reduction of H3K9me2 and H3K9me3, which are known repressive marks of retrotransposons. Conclusions Overall, our findings shed light on the distinct roles of HIRA complex members in controlling retrotransposons and cell fate conversion in ESCs.

The risk matrix can be discovered by first identifying the hazards at the work stages. The cleaning service occupation has a risk of hazards during work. Cleaning service occupation becomes a job which often intersects with biological, ergonomic, physical, chemical and psychological hazards. If these hazards are not handled properly, they can cause work accidents, illness and even fatality. Identifying hazards at work is the initial stage before conducting risk assessment and mapping. The study aims to map the level of risk in the cleaning service occupation. The study used a quantitative analytical method with an observational approach. Data was collected by doing observation and filling out Hazard Identification Risk Assessment (HIRA) form. The result reveals several levels of risk appearing in the risk matrix for cleaning service employees. Most of the risk matrix levels seen in the cleaning service occupation are "high risk", and "moderate risk" appears in a small percentage. According to the result, the recommended actions are controlling the hazard through repairing work tools followingthe physiology of cleaning service workers, providing periodic recess on each work shift, socializing regarding the nature and types of materials and how to handle chemicals properly, and providing appropriate PPE facilities for the type of activity occupation.

Copyright of Journal of the Faculty of Divinity of Ankara University / Ankara Üniversitesi İlahiyat Fakültesi Dergisi is the property of Ankara Universitesi Ilahiyat Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Engineering (17264073) is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study provides an overview of the current status of clonorchiasis and cholangiocarcinoma (CCA), and their relationship in Korea during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service of Korea. Cluster, trend, and correlation analyses were performed. Gyeongsangnam-do and Seoul had the highest average number of cases (1,026 and 4,208) and adjusted rate (306 and 424) for clonorchiasis and CCA, respectively. The most likely clusters (MLC) for clonorchiasis and CCA were Busan/Gyeongsangnam-do/Ulsan/Daegu/Gyeongsangbuk-do (Relative Risk; RR=4.55, Likelihood Ratio; LLR=9,131.115) joint cluster and Seoul (RR=2.29, LLR=7,602.472), respectively. The MLC for clonorchiasis was in the southeastern part of Korea, while that for CCA was in the southern part. Clonorchiasis showed a decreasing trend in the southeastern districts, while increased in the southwestern districts. Cities in the central region had a decreasing trend, while the western districts had an increasing trend. In most adults (30-59), infection rate of clonorchiasis showed a significant decrease until 2018, while thereafter increased, although not significant. CCA showed a sharply decreasing tendency. The incidence of clonorchiasis and CCA were positively correlated. In general, the correlation was weak (r=0.39, P<0.001), but it was strongly positive around the 4 river basins (r=0.74, P<0.001). This study might provide an analytic basis for developing an effective system against clonorchiasis and CCA. [ABSTRACT FROM AUTHOR]

This study was done to provide an overview of the latest trichomoniasis status in Korea by finding disease clusters and analyzing temporal trends during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service (HIRA) of Korea. SaTScan and Joinpoint programs were used for statistical analyses. Gyeonggi-do had the highest average population and highest number of cases. The high incidence of T. vaginalis infections were observed among women aged 40-49 and 30-39 years (33,830/year and 33,179/year, respectively). Similarly, the 40-49 and 30-39 age group in men showed the highest average cases (1,319/year and 1,282/year, respectively). Jeollabuk-do was the most likely cluster, followed by Busan/Gyeongsangnam-do/Ulsan/Daegu and Jeju-do and Gwangju. Urban and rural differences were prominent. Trichomoniasis has decreased significantly in most clusters, except for Incheon. Trichomoniasis was decreasing in women recently after peaking around 2014. Men showed different trends according to age. Trichomoniasis was increasing in the 10-39 age groups, but decreasing in the 40-59 age groups. This study might provide an analytic basis for future health measures, policy-makers, and health authorities in developing effective system for prevention of trichomoniasis. [ABSTRACT FROM AUTHOR]

Background: Histone cell cycle regulator (HIRA) complex is an important histone chaperone that mediates the deposition of the H3.3 histone variant onto chromatin independently from DNA synthesis. However, it is still unknown whether it participates in the expression control of retrotransposons and cell fate determination. Methods: We screened the role of HIRA complex members in repressing the expression of retrotransposons by shRNA depletion in embryonic stem cells (ESCs) followed by RT-qPCR. RNA-seq was used to study the expression profiles after depletion of individual HIRA member. RT-qPCR and western blot were used to determine overexpression of HIRA complex members. Chromatin immunoprecipitation (ChIP)-qPCR was used to find the binding of H3.3, HIRA members to chromatin. Co-immunoprecipitation was used to identify the interaction between Hira mutant and Ubn2. ChIP-qPCR was used to identify H3.3 deposition change and western blot of chromatin extract was used to validate the epigenetic change. Bioinformatics analysis was applied for the analysis of available ChIP-seq data. Results: We revealed that Hira, Ubn2, and Ubn1 were the main repressors of 2-cell marker retrotransposon MERVL among HIRA complex members. Surprisingly, Ubn2 and Hira targeted different groups of retrotransposons and retrotransposon-derived long noncoding RNAs (lncRNAs), despite that they partially shared target genes. Furthermore, Ubn2 prevented ESCs to gain a 2-cell like state or activate trophectodermal genes upon differentiation. Mechanistically, Ubn2 and Hira suppressed retrotransposons by regulating the deposition of histone H3.3. Decreased H3.3 deposition, that was associated with the loss of Ubn2 or Hira, caused the reduction of H3K9me2 and H3K9me3, which are known repressive marks of retrotransposons. Conclusions: Overall, our findings shed light on the distinct roles of HIRA complex members in controlling retrotransposons and cell fate conversion in ESCs. [ABSTRACT FROM AUTHOR]

Prohibitin (PHB) is a highly conserved, ubiquitously expressed, multifunctional protein with a well‐characterized function as a chaperone‐stabilizing mitochondrial proteins. Recently it was reported that nuclear PHB participates in HIRA chaperone complexes and regulates downstream gene expression via cell cycle independent deposition of H3.3 into DNA. However, the role of PHB in cancer progression remains controversial with conflicting reports in the literature, perhaps due to its cell type‐dependent subcellular localization. Here, we report that the increased expression of nuclear PHB is positively correlated with metastasis of breast cancer cell lines. We showed PHB participates in the HIRA complex by interacting with HIRA through the linker region of the PHB domain and stabilizes all components of the HIRA complex in breast cancer. Overexpression of nuclear PHB resulted in a higher enrichment of histone H3.3 deposited by the HIRA complex at the promoters of mesenchymal markers. This coincided with an increased gene expression level of these markers, and induced EMT in breast cancer. Overall, these molecular and structural mechanisms suggest that nuclear PHB could hold promise as a potential target for cancer therapy.

The harbormaster activities of the fishing port are considered to be routine activities without taking into account the hazards resulting from work for fisheries supervisors. This study aims to identify and assess the magnitude of the consequences of the hazards of harbormaster fishing activities. The Hazard Identification and Risk Assessment (HIRA) method was used in data analysis in this study. The results showed that the harbormaster officers' activities at the fishing port consisted of 3 main activities. The results of the analysis using the HIRA method show that the three main activities have an impact on eight types of consequences, namely fatalities, injuries, evaquation, property damage, critical infrastructure, environmental damage, business financial impact and psychosocial impact. The greatest value of the consequences of fishing port harbormaster activities lies in the inspection of fishing vessel departure activities. The total value of consequences is 64, including the consequence criteria 6, namely extreme. The harbormaster activities of fishing harbor in the pre harbormaster activity giving the biggest consequence value are 24 including moderate criteria. Harbormaster fishing port activities as a whole provide the greatest danger consequences of injuries and property damage.

Kojic acid (KA) is a representative secondary metabolite of Aspergillus oryzae , but the underlying molecular mechanisms that regulate KA production are unknown. This study tried to find a genetic factor of KA production in A. oryzae , with a special focus on liquid cultures. We screened a gene predicted to encode HirA, a subunit of the histone chaperon, the HIR complex. A gene disruption strain of hirA showed decreased KA production in liquid culture, whereas it showed increased KA production in plate culture. We confirmed that a decrease/increase of KA production observed by hirA disruption was caused by altered expression of kojA and kojR. These observations suggested the regulatory role of histone chaperon in secondary metabolism in filamentous fungi. So far as we know, this report is the first showing that disruption of a gene resulted in the opposite effect on KA production in liquid and plate cultures in A. oryzae. [ABSTRACT FROM AUTHOR]

The highly repetitive and transcriptionally active ribosomal DNA (rDNA) genes are exceedingly susceptible to genotoxic stress. Induction of DNA double-strand breaks (DSBs) in rDNA repeats is associated with ataxia-telangiectasia-mutated (ATM)-dependent rDNA silencing and nucleolar reorganization where rDNA is segregated into nucleolar caps. However, the regulatory events underlying this response remain elusive. Here, we identify protein UFMylation as essential for rDNA-damage response in human cells. We further show the only ubiquitin-fold modifier 1 (UFM1)-E3 ligase UFL1 and its binding partner DDRGK1 localize to nucleolar caps upon rDNA damage and that UFL1 loss impairs ATM activation and rDNA transcriptional silencing, leading to reduced rDNA segregation. Moreover, analysis of nuclear and nucleolar UFMylation targets in response to DSB induction further identifies key DNA-repair factors including ATM, in addition to chromatin and actin network regulators. Taken together, our data provide evidence of an essential role for UFMylation in orchestrating rDNA DSB repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The HIRA histone chaperone complex is comprised of four protein subunits: HIRA, UBN1, CABIN1, and transiently associated ASF1a. All four subunits have been demonstrated to play a role in the deposition of the histone variant H3.3 onto areas of actively transcribed euchromatin in cells. The mechanism by which these subunits function together to drive histone deposition has remained poorly understood. Here we present biochemical and biophysical data supporting a model whereby ASF1a delivers histone H3.3/H4 dimers to the HIRA complex, H3.3/H4 tetramerization drives the association of two HIRA/UBN1 complexes, and the affinity of the histones for DNA drives release of ASF1a and subsequent histone deposition. These findings have implications for understanding how other histone chaperone complexes may mediate histone deposition., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: About 250 million people around the world are chronically infected with the hepatitis B virus (HBV). Those people are at risk of developing hepatocellular carcinoma. The HBV genome is organized as a minichromosome in the infected hepatocyte and is associated with histones and non-histone proteins. In recent years, many groups have investigated the transcriptional regulation of HBV mediated by post-translational modifications on the histones associated with the covalently closed circular DNA (cccDNA). Our aim is to investigate the role of the histone variant H3.3. Materials and methods: An in vitro HBV replication model system based on the transfection of linear HBV genome monomeric molecules was used. We then either ectopically expressed or reduced the levels of H3.3, and of its histone chaperone HIRA. Viral intermediates were quantified and the level of H3K4me3 using Chromatin immunoprecipitation (ChIP) assay was measured. Results: Histone variant H3.3 ectopically expressed in cells assembles into the viral cccDNA, correlating with increasing levels of the active histone mark H3K4me3 and HBV transcription. The opposite results were found upon diminishing H3.3 levels. Furthermore, the assembly of H3.3 into the cccDNA is dependent on the histone chaperone HIRA. Diminishing HIRA levels causes a reduction in the HBV intermediates. Conclusions: Histone variant H3.3 positively regulates HBV transcription. Importantly, the characterization of the viral chromatin dynamics might allow the discovery of new therapeutic targets to develop drugs for the treatment of chronically-infected HBV patients.

Introduction and Objectives: About 250 million people around the world are chronically infected with the hepatitis B virus (HBV). Those people are at risk of developing hepatocellular carcinoma. The HBV genome is organized as a minichromosome in the infected hepatocyte and is associated with histones and non-histone proteins. In recent years, many groups have investigated the transcriptional regulation of HBV mediated by post-translational modifications on the histones associated with the covalently closed circular DNA (cccDNA). Our aim is to investigate the role of the histone variant H3.3. Materials and methods: An in vitro HBV replication model system based on the transfection of linear HBV genome monomeric molecules was used. We then either ectopically expressed or reduced the levels of H3.3, and of its histone chaperone HIRA. Viral intermediates were quantified and the level of H3K4me3 using Chromatin immunoprecipitation (ChIP) assay was measured. Results: Histone variant H3.3 ectopically expressed in cells assembles into the viral cccDNA, correlating with increasing levels of the active histone mark H3K4me3 and HBV transcription. The opposite results were found upon diminishing H3.3 levels. Furthermore, the assembly of H3.3 into the cccDNA is dependent on the histone chaperone HIRA. Diminishing HIRA levels causes a reduction in the HBV intermediates. Conclusions: Histone variant H3.3 positively regulates HBV transcription. Importantly, the characterization of the viral chromatin dynamics might allow the discovery of new therapeutic targets to develop drugs for the treatment of chronically-infected HBV patients. [ABSTRACT FROM AUTHOR]

Prohibitin (PHB) is a highly conserved, ubiquitously expressed, multifunctional protein with a well‐characterized function as a chaperone‐stabilizing mitochondrial proteins. Recently it was reported that nuclear PHB participates in HIRA chaperone complexes and regulates downstream gene expression via cell cycle independent deposition of H3.3 into DNA. However, the role of PHB in cancer progression remains controversial with conflicting reports in the literature, perhaps due to its cell type‐dependent subcellular localization. Here, we report that the increased expression of nuclear PHB is positively correlated with metastasis of breast cancer cell lines. We showed PHB participates in the HIRA complex by interacting with HIRA through the linker region of the PHB domain and stabilizes all components of the HIRA complex in breast cancer. Overexpression of nuclear PHB resulted in a higher enrichment of histone H3.3 deposited by the HIRA complex at the promoters of mesenchymal markers. This coincided with an increased gene expression level of these markers, and induced EMT in breast cancer. Overall, these molecular and structural mechanisms suggest that nuclear PHB could hold promise as a potential target for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Hospitals are complex places with a large number of employees, patients, furniture, equipment, etc. Healthcare workers (HCWs), patients, or the general public are vulnerable to injuries and illness due to unseen hazards at the workplace. This study aims to identify the hazards and assess the risks at a hospital to ensure safety for HCWs, patients, and the public and generate awareness about the same. It helps in reducing the financial obligation of the institution due to the treatment of illnesses of staff, absenteeism, and service disruption and slows down manpower turnover. Hazard Identification and Risk Assessment (HIRA) helps reduce human errors and promote safe behavior., Objective: This study aims to identify and study the hazards in a hospital, assess the risks associated with the hazards, and recommend methods to reduce or eliminate the hazards based on the outcomes of the study., Methodology: An observational study was conducted at a 1000-bed tertiary-level teaching public sector hospital in eastern India. A checklist was used for direct observation, conducting staff interviews, and document reviews. A risk scoring tool was used, and hazards were ranked as per the risk score., Results: Thirty-eight hazards were identified in the study and classified under the categories of natural, physical, chemical, biological, ergonomic, psychological, and safety. The fire risk and occurrence of cyclones had the highest risk scores., Conclusions: The study identified hazards through direct observations, record reviews, and staff interviews. These findings can guide the prioritization of areas requiring necessary action in risk reduction, ensuring a safe workplace for healthcare workers (HCWs), patients, and the public. They can also help the institution shift from a reactive approach to a proactive method for HCW safety., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sahoo et al.)

Chin Kook Rhee,1 Kyungjoo Kim,1 Hyoung Kyu Yoon,2 Jee-Ae Kim,3 Sang Hyun Kim,4 Sang Haak Lee,5 Yong Bum Park,6 Ki-Suck Jung,7 Kwang Ha Yoo,8 Yong Il Hwang7 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Pharmaceutical Policy Evaluation Research Team, Research Institution, 4Big Data Division, Health Insurance Review and Assessment Service, Wonju, 5Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, 6Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for early COPD during a 6-year period. Methods: Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES) data. We linked the KNHANES data of patients with early COPD to National Health Insurance data. Results: A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV1) was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D) index value was 0.9. In total, 110 patients utilized health care for COPD in 2007, and this number increased to 179 in 2012. The total mean number of days used per person increased from 4.9 in 2007 to 7.8 in 2012. The total medical cost per person also increased from 248.8 US dollar (USD) in 2007 to 780.6 USD in 2013. A multiple linear regression revealed that age, lower body mass index, lower FEV1 (%), and lower EQ-5D score were significantly associated with medical costs. Conclusion: Even in early COPD patients, some of them eventually progressed and utilized health care for COPD. Keywords: early COPD, KNHANES, NHI, HIRA, utilization, cost

HIRA is the histone chaperone responsible for replication-independent incorporation of histone variant H3.3 within gene bodies and regulatory regions of actively transcribed genes, and within the bivalent promoter regions of developmentally regulated genes. The HIRA gene lies within the 22q11.2 deletion syndrome critical region; individuals with this syndrome have multiple congenital heart defects. Because terminally differentiated cardiomyocytes have exited the cell cycle, histone variants should be utilized for the bulk of chromatin remodeling. Thus, HIRA is likely to play an important role in epigenetically defining the cardiac gene expression program. In this study, we determined the consequence of HIRA deficiency in cardiomyocytes in vivo by studying the phenotype of cardiomyocyte-specific Hira conditional-knockout mice. Loss of HIRA did not perturb heart development, but instead resulted in cardiomyocyte hypertrophy and susceptibility to sarcolemmal damage. Cardiomyocyte degeneration gave way to focal replacement fibrosis and impaired cardiac function. Gene expression was widely altered in Hira conditional-knockout hearts. Significantly affected pathways included responses to cellular stress, DNA repair and transcription. Consistent with heart failure, fetal cardiac genes were re-expressed in the Hira conditional knockout. Our results suggest that transcriptional regulation by HIRA is crucial for cardiomyocyte homeostasis.

Background: The most typical cardiac abnormality is conotruncal defects (CTDs) in patients with 22q11 deletion syndrome (22q11DS). HIRA (histone cell cycle regulator) gene, as one of the candidate genes located at the critical region of 22q11DS, was reported as possibly relevant to CTD in animal models. This study aimed to analyze the level of expression of the HIRA gene in tetralogy of Fallot (TOF) patients and the potential DNA sequence variations in the promoter region. Methods: The messenger RNA (mRNA) expression was examined with quantitative real-time polymerase chain reaction in 39 myocardial tissues of the right ventricular outflow tract (RVOT) from TOF patients and 4 myocardial tissues of RVOT from noncardiac death children. The protein expression was detected using immunohistochemistry in 12 TOF patients and 4 controls. A total of 100 TOF cases and 200 healthy controls were recruited for DNA sequencing. Results: The mRNA and protein expressions of the HIRA gene in the myocardium of the TOF patients were both significantly lower as compared to the controls (P < 0.05). Five single nucleotide polymorphisms (SNPs), including g.4111A>G (rs1128399), g.4265C>A (rs4585115), g.4369T>G (rs2277837), g.4371C>A (rs148516780), and g.4543T>C (rs111802956), were found in the promoter region of the HIRA gene. There were no significant differences of frequencies in these SNPs between the TOF patients and the controls (P > 0.05). Conclusion: The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of TOF.

Perkembangan industri yang semakin meningkat pesat membuat setiap industri harus siap berkompetisi dengan pesaing lainnya untuk mendapatkan suatu keunggulan. Keunggulan kompetisi dipengaruhi oleh beberapa faktor selain dilihat dari segi kualitas, keunggulan kompetisi tersebut dipengaruhi oleh manajemen sumber daya yang baik. Dimana apabila suatu perusahaan mempunyai sumber daya yang baik maka akan meningkatkan keuntungan secara tidak langsung dan dapat meningkatkan produktivitas. Oleh karena itu dalam meningkatkan sumber daya yang ada maka suatu perusahaan perlu adanya sistem manajemen kesehatan dan keselamatan kerja (SMK3) yang baik juga.Pada penelitian ini dilakukan kegiatan observasi identifikasi potensi bahaya kerja pada mesin dilantai produksi guna untuk mencegah bahaya kerja pada mesin dilantai produksi. Dimana dalam hal ini data input yang dibutuhkan data layoutperusahaan, data lingkungan fisik kerja, data observasi potensi bahaya. Data input tersebut digunakan untuk diolah dan dianalisis dengan menggunakan metode Hazard Identification and Risk Assesstment(HIRA) dan Failure Mode Effect Analyze(FMEA). Sehingga outputyang didapatkan untuk mengetahui kategori resiko potensi bahaya kerja di mesin lantai produksi, mengetahui nilai rankresiko terbesar dan penyebab resiko terbesar tersebut.

El estudio de la producción literaria medieval sobre la vida de Muḥammad debe ir de la mano del estudio de su historia, empresa para la que disponemos de rica información en una variedad de fuentes. La biografía de Muḥammad por Ibn Isḥāq y su epítome por Ibn Hišām fueron productos de su época. Un caso de auto-censura aplicado por uno de los informantes de Ibn Isḥāq y dos casos de censura aplicados por Ibn Hišām, quien omitió muchos de los materiales de su predecesor, contribuyen a una mejor comprensión del contexto social y político de la biografía del Profeta.

Perlindungan terhadap keselamatan dan kesehatan kerja masih jauh dari yang diharapkan karena masih banyak terjadi kecelakaan kerja serta potensi bahaya kerja yang dapat membahayakan tenaga kerja. Penerapkan sistem manajeman keselamatan dan kesehatan kerja (SMK3) perlu dilakukan secara optimal. Penerapan SMK3 di perusahaan belum tentu berbanding lurus terhadap potensi bahaya (hazard) yang ada di lingkungan sekitar perusahaan. Penelitian ini bertujuan untuk mengetahui nilai risiko potensi bahaya kerja dan kategori potensi bahaya kerja di perusahaan serta mengetahui faktor penyebab terbesar terjadinya kecelakaan kerja di perusahaan. Penelitian ini menggunakan pendekatan metode HIRA dan FTA. Hasil yang diperoleh menunjukkan bahwa penerapan SMK3 telah sesuai dengan undang-Undang yang berlaku, namun nilai resiko potensi bahaya bagian fluid utility menunjukkan tingkat keparahan bahaya kerja kecil dan kemungkinan terjadinya potensi bahaya kerja juga kecil, nilai kategori potensi bahaya kerja perlu dikendalikan dengan prosedur rutin. Faktor penyebab potensial terjadinya potensi bahaya adalah suara mesin bising, Standard Operational procedure (SOP) belum terpasang secara ergonomis, terdapat benda asing yang menghalangi jalan, temperatur ruangan meningkat 50C dari temperatur normal.

Summary The histone chaperone HIRA is involved in depositing histone variant H3.3 into distinct genic regions, including promoters, enhancers, and gene bodies. However, how HIRA deposits H3.3 to these regions remains elusive. Through a short hairpin RNA (shRNA) screening, we identified single-stranded DNA binding protein replication protein A (RPA) as a regulator of the deposition of newly synthesized H3.3 into chromatin. We show that RPA physically interacts with HIRA to form RPA-HIRA-H3.3 complexes, and it co-localizes with HIRA and H3.3 at gene promoters and enhancers. Depletion of RPA1, the largest subunit of the RPA complex, dramatically reduces both HIRA association with chromatin and the deposition of newly synthesized H3.3 at promoters and enhancers and leads to altered transcription at gene promoters. These results support a model whereby RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation. [ABSTRACT FROM AUTHOR]

The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence. [ABSTRACT FROM AUTHOR]

Many causal mutations of intellectual disability have been found in genes involved in epigenetic regulations. Replication-independent deposition of the histone H3.3 variant by the HIRA complex is a prominent nucleosome replacement mechanism affecting gene transcription, especially in postmitotic neurons. However, how HIRA-mediated H3.3 deposition is regulated in these cells remains unclear. Here, we report that dBRWD3, the Drosophila ortholog of the intellectual disability gene BRWD3, regulates gene expression through H3.3, HIRA, and its associated chaperone Yemanuclein ( YEM), the fly ortholog of mammalian Ubinuclein1. In dBRWD3 mutants, increased H3.3 levels disrupt gene expression, dendritic morphogenesis, and sensory organ differentiation. Inactivation of yem or H3.3 remarkably suppresses the global transcriptome changes and various developmental defects caused by dBRWD3 mutations. Our work thus establishes a previously unknown negative regulation of H3.3 and advances our understanding of BRWD3-dependent intellectual disability. [ABSTRACT FROM AUTHOR]

Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogeneinduced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression. [ABSTRACT FROM AUTHOR]

Meiosis is characterized by two chromosome segregation rounds (meiosis I and II), which follow a single round of DNA replication, resulting in haploid genome formation. Chromosome reduction occurs at meiosis I. It relies on key structures, such as chiasmata, which are formed by repair of double-strand breaks (DSBs) between the homologous chromatids. In turn, to allow for segregation of homologs, chiasmata rely on the maintenance of sister chromatid cohesion. In most species, chiasma formation requires the prior synapsis of homologous chromosome axes, which is mediated by the synaptonemal complex, a tripartite proteinaceous structure specific to prophase I of meiosis. Yemanuclein (Yem) is a maternal factor that is crucial for sexual reproduction. It is required in the zygote for chromatin assembly of the male pronucleus, where it acts as a histone H3.3 chaperone in complex with Hira. We report here that Yem associates with the synaptonemal complex and the cohesin complex. A genetic interaction between yem1 (V478E) and the Spo11 homolog mei-W68, modified a yem1 dominant effect on crossover distribution, suggesting that Yem has an early role in meiotic recombination. This is further supported by the impact of yem mutations on DSB kinetics. A Hira mutation gave a similar effect, presumably through disruption of Hira -- Yem complex. [ABSTRACT FROM AUTHOR]