Questionnaire survey on the prevention and development of cervical cancer in patients with systemic lupus erythematosus in Japan.

OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.

Identification of small compounds that inhibit multiple myeloma proliferation by targeting c-Maf transcriptional activity.

Multiple myeloma displays the clonal B cell expansion and the overproduction of monoclonal immunoglobulins. Genetic translocations at 14q32, particularly with partners like 16q23, lead to the dysregulation of oncogene expression, including the significant enhancement of c-Maf. This aberrant expression of c-Maf has prompted research into strategies for targeting this transcription factor as a potential therapeutic avenue for multiple myeloma treatment. In this study, we introduce a screening pipeline to test small compounds for their ability to inhibit c-Maf. Using a luciferase indicator driven by the Ccl8 gene promoter, we identified two small compounds that inhibit transcriptional activity of c-Maf. These molecules impede the proliferation of c-Maf-expressing myeloma cells, and repress the expression of c-Maf target genes such as ITGB7 and CCR1. Importantly, these molecules target c-Maf-expressing multiple myeloma cells, but not c-Maf-negative myeloma cells, showing potential for tailoring therapeutic intervention. In conclusion, our screening pipeline is effective to explore leads for a novel c-Maf inhibitor for multiple myeloma therapy.

Assessing fluid volume and determining outcomes of acute heart failure using plasma human atrial natriuretic peptide.

BACKGROUND: The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied. METHODS: We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP. RESULTS: Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06-11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Cardiac disfunctions were significantly associated with the high hANP level. CONCLUSIONS: The hANP level is indicative of both fluid volume and cardiac dysfunction. A threshold hANP level of 100 pg/mL can serve as a predictive marker for AHF and a practical indicator for volume control.

Eighteen Coral Genomes Reveal the Evolutionary Origin of Acropora Strategies to Accommodate Environmental Changes.

The genus Acropora comprises the most diverse and abundant scleractinian corals (Anthozoa, Cnidaria) in coral reefs, the most diverse marine ecosystems on Earth. However, the genetic basis for the success and wide distribution of Acropora are unknown. Here, we sequenced complete genomes of 15 Acropora species and 3 other acroporid taxa belonging to the genera Montipora and Astreopora to examine genomic novelties that explain their evolutionary success. We successfully obtained reasonable draft genomes of all 18 species. Molecular dating indicates that the Acropora ancestor survived warm periods without sea ice from the mid or late Cretaceous to the Early Eocene and that diversification of Acropora may have been enhanced by subsequent cooling periods. In general, the scleractinian gene repertoire is highly conserved; however, coral- or cnidarian-specific possible stress response genes are tandemly duplicated in Acropora. Enzymes that cleave dimethlysulfonioproprionate into dimethyl sulfide, which promotes cloud formation and combats greenhouse gasses, are the most duplicated genes in the Acropora ancestor. These may have been acquired by horizontal gene transfer from algal symbionts belonging to the family Symbiodiniaceae, or from coccolithophores, suggesting that although functions of this enzyme in Acropora are unclear, Acropora may have survived warmer marine environments in the past by enhancing cloud formation. In addition, possible antimicrobial peptides and symbiosis-related genes are under positive selection in Acropora, perhaps enabling adaptation to diverse environments. Our results suggest unique Acropora adaptations to ancient, warm marine environments and provide insights into its capacity to adjust to rising seawater temperatures.

Calcification rates of a massive and a branching coral species were unrelated to diversity of endosymbiotic dinoflagellates.

BACKGROUND: To explore the possibility that endosymbiotic dinoflagellates (Symbiodiniaceae) are associated with coral calcification rates, we investigated the diversity of symbiotic algae in coral colonies with different calcification rates within massive and branching corals (Porites australiensis and Acropora digitifera). METHODS AND RESULTS: Genotyping symbiotic algae from colonies with different calcification rates revealed that all the colonies of both species harbored mainly Cladocopium (previously clade C of Symbiodinium). The Cladocopium symbionts in P. australiensis were mainly composed of C15 and C15bn, and those in A. digitifera of C50a and C50c. We did not detect clear relationships between symbiont compositions and calcification rates within the two coral species. CONCLUSIONS: Our results suggest that different coral calcification rates within species may be attributed to genetic factors of coral hosts themselves and/or within symbiont genotypes.

De novo transcriptome assembly from the gonads of a scleractinian coral, Euphyllia ancora: molecular mechanisms underlying scleractinian gametogenesis.

BACKGROUND: Sexual reproduction of scleractinians has captured the attention of researchers and the general public for decades. Although extensive ecological data has been acquired, underlying molecular and cellular mechanisms remain largely unknown. In this study, to better understand mechanisms underlying gametogenesis, we isolated ovaries and testes at different developmental phases from a gonochoric coral, Euphyllia ancora, and adopted a transcriptomic approach to reveal sex- and phase-specific gene expression profiles. In particular, we explored genes associated with oocyte development and maturation, spermiogenesis, sperm motility / capacitation, and fertilization. RESULTS: 1.6 billion raw reads were obtained from 24 gonadal samples. De novo assembly of trimmed reads, and elimination of contigs derived from symbiotic dinoflagellates (Symbiodiniaceae) and other organisms yielded a reference E. ancora gonadal transcriptome of 35,802 contigs. Analysis of 4 developmental phases identified 2023 genes that were differentially expressed during oogenesis and 678 during spermatogenesis. In premature/mature ovaries, 631 genes were specifically upregulated, with 538 in mature testes. Upregulated genes included those involved in gametogenesis, gamete maturation, sperm motility / capacitation, and fertilization in other metazoans, including humans. Meanwhile, a large number of genes without homology to sequences in the SWISS-PROT database were also observed among upregulated genes in premature / mature ovaries and mature testes. CONCLUSIONS: Our findings show that scleractinian gametogenesis shares many molecular characteristics with that of other metazoans, but it also possesses unique characteristics developed during cnidarian and/or scleractinian evolution. To the best of our knowledge, this study is the first to create a gonadal transcriptome assembly from any scleractinian. This study and associated datasets provide a foundation for future studies regarding gametogenesis and differences between male and female colonies from molecular and cellular perspectives. Furthermore, our transcriptome assembly will be a useful reference for future development of sex-specific and/or stage-specific germ cell markers that can be used in coral aquaculture and ecological studies.

RADseq population genomics confirms divergence across closely related species in blue coral (Heliopora coerulea).

BACKGROUND: Heliopora coerulea, the blue coral, is the octocoral characterized by its blue skeleton. Recently, two Heliopora species were delimited by DNA markers: HC-A and HC-B. To clarify the genomic divergence of these Heliopora species (HC-A and HC-B) from sympatric and allopatric populations in Okinawa, Japan, we used a high throughput reduced representation genomic DNA sequencing approach (ezRAD). RESULTS: We found 6742 biallelic SNPs shared among all target populations, which successfully distinguished the HC-A and HC-B species in both the sympatric and allopatric populations, with no evidence of hybridization between the two. In addition, we detected 410 fixed SNPs linking functional gene differences, including heat resilience and reproductive timing, between HC-A and HC-B. CONCLUSIONS: We confirmed clear genomic divergence between Heliopora species and found possible genes related to stress-responses and reproduction, which may shed light on the speciation process and ecological divergence of coral species.

Evaluating the occurrence of cryptic invasions of a rocky shore barnacle, Semibalanus cariosus, between the north-eastern Pacific and Japan.

Many coastal barnacles are introduced to non-native regions. However, data are lacking on cryptic invasion, which is defined as an invasion that remains unrecognised because the invader is mistaken for a native or previously introduced species or clade. In this work, cryptic invasions of an intertidal barnacle, Semibalanus cariosus, between Japan and the north-eastern Pacific were evaluated based on population genetic analyses. A significant genetic differentiation was found between the Japanese and north-eastern Pacific populations, suggesting a limited introduction of non-native genotypes between these regions. Haplotype frequencies did not differ significantly between the past (museum samples collected in 1971 from Hokkaido, Japan) and present Japanese populations, implying the rare occurrence of human-mediated migration from the north-eastern Pacific to Japan. Migrate-n analysis revealed a low level of directional gene flow in S. cariosus from the north-eastern Pacific to Japan, possibly by natural stepping-stone dispersal via directional water currents or human-mediated transport.

[Surgical Treatment for Anomalous Aortic Origin of Coronary Arteries].

Anomalous aortic origin of coronary arteries is rare. We report 3 cases of surgical treatment for anomalous aortic origin of coronary arteries. Case 1 was a 38-year-old man who was saved by the use of an automated external defibrillator from cardiopulmonary arrest while exercising. The coronary angiogram showed the right coronary artery arising from the left coronary sinus of Valsalva and being located between the aorta and the pulmonary trunk. He underwent coronary artery bypass grafting (CABG) using the right internal thoracic artery with ligation of proximal part of right coronary artery to prevent sudden death. Case 2 was a 76-year-old woman with the left coronary artery arising from the right coronary sinus of Valsalva and proximal left anterior descending coronary artery stenosis. She underwent CABG. Case 3 was a 58-year-old man with severe aortic valve regurgitation. He underwent aortic valve replacement. During weaning from cardiopulmonary bypass, the electrocardiogram revealed ST-segment elevation. Transesophageal echocardiography showed intramural segment of the left coronary artery and obstruction of the left coronary blood flow. Repair was accomplished by unroofing the intramural segment. All the cases were successfully treated by surgical treatment.

Induction of apoptosis in Caco-2 cells by exogenously added O2⁻ produced by a nanodevice.

The effects of reactive oxygen species on cells have attracted considerable attention in relation to oxidative stress and related disorders. Superoxide (O2(-)) is the primary reactive oxygen species formed in animals as a byproduct or purposeful product of enzymes. We recently established an O2(-)-generating nanodevice that produces O2(-) continuously even in culture medium, by improving an original nanodevice. The new nanodevice, named Device II, efficiently induced cell death in Caco-2 cells in a time- and dose-dependent manner. Catalase largely recovered the cell viability, while superoxide dismutase rather lowered the viability. Flow cytometric and fluorescence microscopic analyses revealed that phosphatidylserine was exposed on the cells and that caspase-3 was activated in the cells after treatment with Device II. These findings indicated that exogenously added O2(-) caused apoptosis in Caco-2 cells through its derivative H2O2.

Blunt Abdominal Aortic Injury Associated with L2 Vertebral Fracture.

Blunt abdominal aortic injury (BAAI) is very rare. In general, BAAI occurs in high-energy accidents. Here, we present a case of BAAI in a low-energy accident. A 70-year-old female was injured after falling 3 m. Her vital signs were stable. She had lumbar fractures (L1, L2) and BAAI associated with a fragment of the fractured L2 vertebral body. On the fifth posttrauma day, we performed an operation because computed tomography showed a bone fragment of the lumbar fractures (L1, L2) threatening the abdominal aorta. The aortic injury site was transected, and the fragment of the L2 vertebral body was removed. Even in low-energy accidents, BAAI should be considered. BAAI with stable vital signs can be electively treated.

[Giant Left Atrium with Mitral Regurgitation in Williams Syndrome: Report of a Case].

A 43-year-old woman with a history of mitral regurgitation and Williams syndrome was admitted for the treatment of congestive heart failure. A computed tomography scan showed a giant left atrium. No other cardiac abnormalities were observed. She received mitral valve replacement with a mechanical valve prosthesis and underwent left atrium volume reduction with a suture technique and modified Maze procedure. After the operation, the cardiac rhythm returned to sinus rhythm and chest radiography showed normal cardiothoracic ratio. Congestive heart failure did not recur.

Successful management of threatened aortic rupture late after rib fracture caused by blunt chest trauma.

A 62-year-old man was crushed in a car accident and diagnosed with a fractured left ninth rib, pulmonary and heart contusion, hemopneumothorax, and descending aortic injury based on a computed tomography scan. He underwent chest tube drainage and was intubated for mechanical ventilation because a bone fragment of the ninth rib threatened to penetrate the descending aorta. On the second posttrauma day, computed tomography showed the bone fragment of the ninth rib approaching the descending aorta. He underwent graft replacement of the injured portion of the descending thoracic aorta, and we removed the fractured left ninth rib.

Genomic Data Reveal Diverse Biological Characteristics of Scleractinian Corals and Promote Effective Coral Reef Conservation.

Reef-building corals (Scleractinia, Anthozoa, Cnidaria) are the keystone organisms of coral reefs, which constitute the most diverse marine ecosystems. Since the first decoded coral genome reported in 2011, about 40 reference genomes are registered as of 2023. Comparative genomic analyses of coral genomes have revealed genomic characters that may underlie unique biological characteristics and coral diversification. These include existence of genes for biosynthesis of mycosporine-like amino acids, loss of an enzyme necessary for cysteine biosynthesis in family Acroporidae, and lineage-specific gene expansions of DMSP lyase-like genes in the genus Acropora. While symbiosis with endosymbiotic photosynthetic dinoflagellates is a common biological feature among reef-building corals, genes associated with the intricate symbiotic relationship encompass not only those shared by many coral species, but also genes that were uniquely duplicated in each coral lineage, suggesting diversified molecular mechanisms of coral-algal symbiosis. Coral genomic data have also enabled detection of hidden, complex population structures of corals, indicating the need for species-specific, local-scale, carefully considered conservation policies for effective maintenance of corals. Consequently, accumulating coral genomic data from a wide range of taxa and from individuals of a species not only promotes deeper understanding of coral reef biodiversity, but also promotes appropriate and effective coral reef conservation. Considering the diverse biological traits of different coral species and accurately understanding population structure and genetic diversity revealed by coral genomic analyses during coral reef restoration planning could enable us to "archive" coral reef environments that are nearly identical to natural coral reefs.

Asymmetric genetic population structures at the range edges of a mangrove whelk.

Many marine species are distributed across incredibly wide geographical ranges spanning thousands of kilometers often due to movement along prevailing ocean currents. However, data are lacking on genetic connectivity among populations of such widespread species within or among ecoregions, possibly due to the lack of appropriate datasets. In this study, we investigated the genetic structure of populations of the mangrove whelk, Terebralia palustris, using mitochondrial cytochrome oxidase subunit I (COI) sequences. Sequences generated for this study from Okinawa, Japan, were compared to samples from the coast of East Africa analyzed in a previous study. Interestingly, despite considerable distance separating them, the African and Japanese populations share major haplotypes and do not show clear genetic differentiation. At lower latitudes, core African populations exhibited higher genetic diversity than either the more southerly African and Japanese populations. Genetic ß-diversity revealed that the northern edge population in Japan has a greater proportion of ßSNE (the nestedness-resultant component), indicating contemporary migration, whereas the southern edge population in Africa is characterized by a predominant ßSIM (the turnover component), suggesting historical demography. A potential cause of this dissimilarity could be due to the strong Kuroshio Current along the Ryukyu Islands, which may promote larval dispersal. These differing patterns suggest that there may be divergent responses to future climate change at the population level at the periphery of the range of T. palustris.

Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.

Better understanding of the earliest molecular pathologies of all neurodegenerative diseases is expected to improve human therapeutics. We investigated the earliest molecular pathology of spinocerebellar ataxia type 1 (SCA1), a rare familial neurodegenerative disease that primarily induces death and dysfunction of cerebellum Purkinje cells. Extensive prior studies have identified involvement of transcription or RNA-splicing factors in the molecular pathology of SCA1. However, the regulatory network of SCA1 pathology, especially central regulators of the earliest developmental stages and inflammatory events, remains incompletely understood. Here, we elucidated the earliest developmental pathology of SCA1 using originally developed dynamic molecular network analyses of sequentially acquired RNA-seq data during differentiation of SCA1 patient-derived induced pluripotent stem cells (iPSCs) to Purkinje cells. Dynamic molecular network analysis implicated histone genes and cytokine-relevant immune response genes at the earliest stages of development, and revealed relevance of ISG15 to the following degradation and accumulation of mutant ataxin-1 in Purkinje cells of SCA1 model mice and human patients.

C-terminal truncation of Noxa1 greatly enhances its ability to activate Nox2 in a pure reconstitution system.

Noxa1 activates Nox2 together with Noxo1 and Rac in a pure reconstitution system, but the resulting activity is considerably lower than that induced by p67(phox) and p47(phox). In this study, we found that C-terminal-truncated forms of Noxa1 exhibited higher activities than full-length Noxa1. Of the truncations examined, Noxa1(1-225) showed the highest ability for activation. Kinetic studies revealed that Noxa1(1-225) had a threefold higher Vmax value than full-length Noxa1 with a similar EC50 value. The affinities of Noxo1 and RacQ61L were not much altered by the truncation. Conversely, the affinity of FAD for the Nox2 complex was enhanced after the truncation. In the absence of Noxo1, Noxa1(1-225) showed much higher activity with a lower EC50 than full-length Noxa1. Noxa1(1-225) showed comparable activity to that of p67(phox) with either Noxo1 or p47(phox), although the stability was lower than that with p67(phox) and p47(phox). These findings indicate that the role of the C-terminal half of Noxa1 is autoinhibition. The data suggest a two-step autoinhibition mechanism, comprising self-masking to interrupt the binding to the oxidase, and holding of the activation domain in a suboptimal position to the oxidase. This study reveals that when both types of inhibition are released, Noxa1 achieves high-level superoxide production.

Mutant α-synuclein propagates via the lymphatic system of the brain in the monomeric state.

Prion-like protein propagation is considered a common pathogenic mechanism in neurodegenerative diseases. Here we investigate the in vivo propagation pattern and aggregation state of mutant α-synuclein by injecting adeno-associated viral (AAV)-α-synuclein-A53T-EGFP into the mouse olfactory cortex. Comparison of aggregation states in various brain regions at multiple time points after injection using western blot analyses shows that the monomeric state of the mutant/misfolded protein propagates to remote brain regions by 2 weeks and that the propagated proteins aggregate in situ after being incorporated into neurons. Moreover, injection of Alexa 488-labeled α-synuclein-A53T confirms the monomeric propagation at 2 weeks. Super-resolution microscopy shows that both α-synuclein-A53T proteins propagate via the lymphatic system, penetrate perineuronal nets, and reach the surface of neurons. Electron microscopy shows that the propagated mutant/misfolded monomer forms fibrils characteristic of Parkinson's disease after its incorporation into neurons. These findings suggest a mode of propagation different from that of aggregate-dependent propagation.

Genes possibly related to symbiosis in early life stages of Acropora tenuis inoculated with Symbiodinium microadriaticum.

Due to the ecological importance of mutualism between reef-building corals and symbiotic algae (Family Symbiodiniaceae), various transcriptomic studies on coral-algal symbiosis have been performed; however, molecular mechanisms, especially genes essential to initiate and maintain these symbioses remain unknown. We investigated transcriptomic responses of Acropora tenuis to inoculation with the native algal symbiont, Symbiodinium microadriaticum, during early life stages, and identified possible symbiosis-related genes. Genes involved in immune regulation, protection against oxidative stress, and metabolic interactions between partners are particularly important for symbiosis during Acropora early life stages. In addition, molecular phylogenetic analysis revealed that some possible symbiosis-related genes originated by gene duplication in the Acropora lineage, suggesting that gene duplication may have been the driving force to establish stable mutualism in Acropora, and that symbiotic molecular mechanisms may vary among coral lineages.