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1.
Sci Total Environ ; 934: 173248, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38750732

RESUMEN

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.

2.
Commun Biol ; 7(1): 413, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594382

RESUMEN

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.


Asunto(s)
Células Madre Pluripotentes Inducidas , Ataxias Espinocerebelosas , Animales , Humanos , Ratones , Citocinas , Células Madre Pluripotentes Inducidas/patología , Ratones Transgénicos , Células de Purkinje/fisiología , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología , Ubiquitinas
3.
Genome Biol Evol ; 16(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38271267

RESUMEN

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.


Asunto(s)
Antozoos , Arrecifes de Coral , Humanos , Animales , Antozoos/genética , Ecosistema , Genómica , Genoma , Simbiosis/genética
4.
Mod Rheumatol ; 34(2): 352-358, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-36929382

RESUMEN

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.


Asunto(s)
Lupus Eritematoso Sistémico , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Femenino , Humanos , Detección Precoz del Cáncer , Japón/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Encuestas y Cuestionarios , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Persona de Mediana Edad
5.
Commun Med (Lond) ; 3(1): 170, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017287

RESUMEN

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is one of the most common hereditary peripheral neuropathies caused by duplication of 1.5 Mb genome region including PMP22 gene. We aimed to correct the duplication in human CMT1A patient-derived iPS cells (CMT1A-iPSCs) by genome editing and intended to analyze the effect on Schwann cells differentiated from CMT1A-iPSCs. METHODS: We designed multiple gRNAs targeting a unique sequence present at two sites that sandwich only a single copy of duplicated peripheral myelin protein 22 (PMP22) genes, and selected one of them (gRNA3) from screening their efficiencies by T7E1 mismatch detection assay. AAV2-hSaCas9-gRNAedit was generated by subcloning gRNA3 into pX601-AAV-CMV plasmid, and the genome editing AAV vector was infected to CMT1A-iPSCs or CMT1A-iPSC-derived Schwann cell precursors. The effect of the genome editing AAV vector on myelination was evaluated by co-immunostaining of myelin basic protein (MBP), a marker of mature myelin, and microtubule-associated protein  2(MAP2), a marker of neurites or by electron microscopy. RESULTS: Here we show that infection of CMT1A-iPS cells (iPSCs) with AAV2-hSaCas9-gRNAedit expressing both hSaCas9 and gRNA targeting the tandem repeat sequence decreased PMP22 gene duplication by 20-40%. Infection of CMT1A-iPSC-derived Schwann cell precursors with AAV2-hSaCas9-gRNAedit normalized PMP22 mRNA and PMP22 protein expression levels, and also ameliorated increased apoptosis and impaired myelination in CMT1A-iPSC-derived Schwann cells. CONCLUSIONS: In vivo transfer of AAV2-hSaCas9-gRNAedit to peripheral nerves could be a potential therapeutic modality for CMT1A patient after careful examinations of toxicity including off-target mutations.


Charcot-Marie-Tooth disease type 1A (CMT1A) is a common heritable form of the condition that develops when nerves in the body's extremities, such as the hands, feet and arms, are damaged due to an extra copy of PMP22 gene being incorrectly produced. Currently, no known therapies exist. Here, we developed a method to delete the additional copy of PMP22 gene by 20­40% to prevent overproduction. Our results show that this method can reduce PMP22 protein production, leading to near normal production in patient's nerve cells. Further safety assessments should now be undertaken. If the treatment is safe for patients it could become a therapeutic option for CMT1A patients.

6.
Mod Rheumatol Case Rep ; 8(1): 178-181, 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-37902453

RESUMEN

Eosinophilic granulomatous polyangiitis is a systemic vasculitis associated with bronchial asthma and eosinophilic sinusitis. Here, we describe an unusual presentation of eosinophilic granulomatous polyangiitis that initially manifested as swelling of the oral cavity floor and cervical soft tissue. A 58 year-old Japanese man was diagnosed with bronchial asthma during childhood but did not receive regular medication. Prior to this presentation, he had a persistent cough for over 1 month, and a local physician diagnosed him with bronchial asthma. However, 6 months later, his cough worsened, and a blood test revealed elevated eosinophil levels. Immediately afterward, swelling of the floor of the oral cavity and cervical soft tissue developed. Cellulitis was suspected and antimicrobial treatment was initiated; however, the symptoms persisted and abdominal pain developed. An endoscopic examination revealed duodenitis and a duodenal ulcer. The patient was diagnosed with eosinophilic granulomatous polyangiitis based on three items of the 2022 American College of Rheumatology/European College of Rheumatology classification criteria: obstructive airway disease, blood eosinophil count ≥1 × 109 cells/L, and extravascular eosinophilic infiltration with a score of 10. Oral prednisolone (70 mg/day), intravenous cyclophosphamide (500 mg/m2), and subcutaneous mepolizumab (300 mg every 4 weeks) were administered. The patient's symptoms improved after these treatments, and the eosinophil count and inflammatory marker levels declined. When swelling of the oral cavity floor and cervical soft tissue following an increase in eosinophilia and allergic symptoms occurs, it is crucial to consider the likelihood of eosinophilic granulomatous polyangiitis and collaborate with otolaryngologists and dentists to ensure its prompt identification.


Asunto(s)
Asma , Eosinofilia , Enfermedad Relacionada con Inmunoglobulina G4 , Masculino , Humanos , Persona de Mediana Edad , Prednisolona/uso terapéutico , Eosinofilia/diagnóstico , Eosinofilia/etiología , Edema , Boca
7.
Commun Biol ; 6(1): 1027, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853100

RESUMEN

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.


Asunto(s)
Antozoos , Simbiosis , Animales , Simbiosis/genética , Filogenia , Antozoos/genética , Transcriptoma , Perfilación de la Expresión Génica
8.
Biochem Biophys Res Commun ; 684: 149135, 2023 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-37879249

RESUMEN

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.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Proteínas Proto-Oncogénicas c-maf/genética , Proteínas Proto-Oncogénicas c-maf/metabolismo , Linfocitos B/metabolismo , Regulación de la Expresión Génica , Proliferación Celular
9.
Cell Rep ; 42(8): 112962, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37591248

RESUMEN

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.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Animales , Ratones , alfa-Sinucleína/genética , Encéfalo , Sistema Linfático , Western Blotting , Proteínas Mutantes
10.
DNA Res ; 30(4)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37358253

RESUMEN

Vestimentiferan tubeworms are representative members of deep-sea chemosynthetic ecosystems. In this study, we developed a draft genome and gene models and performed genomic and transcriptomic analyses of Lamellibrachia satsuma, the only vestimentiferan reported from the euphotic zone. The quality of the genome assembly and gene models is comparable to or higher than those of previously reported vestimentiferan tubeworms. Tissue-specific transcriptome sequencing revealed that Toll-like receptor genes and lineage-specific expanded bacteriolytic enzyme genes are highly expressed in the obturacular and vestimental regions, respectively, suggesting the importance of these tissues in defense against pathogens. On the other hand, globin subunit genes are expressed almost exclusively in the trunk region, supporting the hypothesis that the trophosome is the site of haemoglobin biosynthesis. Vestimentiferan-specific expanded gene families included chitinases, ion channels, and C-type lectins, suggesting the importance of these functions for vestimentiferans. C-type lectins in the trunk region, in particular, may be involved in recognition of pathogens, or in interactions between tubeworms and symbiotic bacteria. Our genomic and transcriptomic analyses enhance understanding of molecular mechanisms underlying the unique lifestyle of vestimentiferan tubeworms, particularly their obligate mutualism with chemosynthetic bacteria.


Asunto(s)
Ecosistema , Transcriptoma , Genoma , Bacterias/genética , Genómica , Simbiosis
11.
J Thorac Dis ; 15(3): 994-1008, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37065581

RESUMEN

Background: Although a bicuspid aortic valve (BAV) is known to be associated with progressive ascending aortic dilatation, the fate of the residual aorta after aortic valve and ascending aorta surgery is unknown. We reviewed surgical outcomes and explored serial changes in the size of the sinus of Valsalva (SOV) and distal ascending aorta (DAAo) in 89 patients with a BAV undergoing aortic valve replacement (AVR) and graft replacement (GR) of the ascending aorta. Methods: We retrospectively examined patients who underwent AVR and GR of the ascending aorta for BAV-and related disease and thoracic aortic dilatation at our institution between January 2009 and December 2018. Patients who underwent AVR alone or required intervention for the aortic root and aortic arch and patients with connective tissue diseases were excluded. Aortic diameters were examined using computed tomography (CT). Late CT more than 1 year after surgery was performed in 69 patients (78%) with a mean follow-up of 4.9±2.8 years. Results: The surgical indication for aortic valve etiology was stenosis in 61 patients (69%), regurgitation in 10 (11%), and mixed in 18 (20%). Preoperative maximum short diameters of the ascending aorta, SOV, and DAAo were 47.3±4.7, 36.0±5.2, and 37.2±3.6 mm, respectively. The diameter of the SOV increased non-significantly by 0.08±0.45 mm per year [95% confidence interval (CI): -0.12 to 0.11, P=0.150], while that of the DAAo increased significantly by 0.11±0.40 mm per year (95% CI: 0.02-0.21, P=0.005). One patient required reoperation 6 years postoperatively due to a pseudo-aneurysm at the proximal anastomotic site. No patient required reoperation due to progressive dilatation of the residual aorta. According to the Kaplan-Meier analysis, the long-term survival rates were 98.9%, 98.9%, and 92.7% at 1, 5, and 10 years postoperatively, respectively. Conclusions: Rapid dilatation of the residual aorta rarely occurred in patients with a BAV who underwent AVR and GR of the ascending aorta in the mid-term follow-up. For selected patients with a surgical indication for ascending aortic dilatation, simple AVR and GR of the ascending aorta may be sufficient surgical options.

12.
NPJ Biofilms Microbiomes ; 9(1): 15, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-37015942

RESUMEN

Black band disease (BBD) in corals is characterized by a distinctive, band-like microbial mat, which spreads across the tissues and often kills infected colonies. The microbial mat is dominated by cyanobacteria but also commonly contains sulfide-oxidizing bacteria (SOB), sulfate-reducing bacteria (SRB), and other microbes. The migration rate in BBD varies across different environmental conditions, including temperature, light, and pH. However, whether variations in the migration rates reflect differences in the microbial consortium within the BBD mat remains unknown. Here, we show that the micro-scale surface structure, bacterial composition, and spatial distribution differed across BBD lesions with different migration rates. The migration rate was positively correlated with the relative abundance of potential SOBs belonging to Arcobacteraceae localized in the middle layer within the mat and negatively correlated with the relative abundance of other potential SOBs belonging to Rhodobacteraceae. Our study highlights the microbial composition in BBD as an important determinant of virulence.


Asunto(s)
Antozoos , Cianobacterias , Animales , Antozoos/microbiología , Virulencia , Sulfuros
13.
Clin Exp Nephrol ; 27(6): 565-573, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36941501

RESUMEN

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.


Asunto(s)
Factor Natriurético Atrial , Insuficiencia Cardíaca , Humanos , Estudios Retrospectivos , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Diálisis Renal
15.
PeerJ ; 10: e13114, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35722256

RESUMEN

The density and diversity of Symbiodiniaceae associated with corals can be influenced by seasonal changes . This study provided the first annual investigation of Symbiodiniaceae density and diversity associated with Acropora humilis and Pocillopora cf. damicornis corals in the Gulf of Thailand using both zooxanthellae cell count and next-generation sequencing (ITS-1, ITS-2 regions) techniques, respectively. The results from this study indicated that zooxanthellae cell densities in both coral species differ significantly. The number of zooxanthellae was negatively correlated with the physical environment variable (light intensity). The diversity within A. humilis consisted of two genera, Cladocopium (Cspc_C3: 56.39%, C3w: 33.62%, C93type1: 4.42% and Cspf: 3.59%) and a small amount of Durusdinium (D1: 1.03%) whereas P. cf. damicornis was found to be 100% associated with Durusdinium (D1: 95.58%, D6: 1.01% and D10: 2.7%) suggesting that each coral species may select their appropriate genus/species of Symbiodiniaceae in response to local environmental stressors. The results of this study provided some information on the coral-Symbiodiniaceae relationship between seasons, which may be applied to predict the potential adaptation of corals in localized reef environments.


Asunto(s)
Antozoos , Dinoflagelados , Animales , Antozoos/fisiología , Estaciones del Año , Ambiente , Aclimatación
16.
Mol Biol Rep ; 49(9): 9101-9106, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35737176

RESUMEN

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.


Asunto(s)
Antozoos , Dinoflagelados , Animales , Antozoos/genética , Dinoflagelados/genética , Simbiosis
17.
Cell Rep Med ; 3(4): 100597, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35492247

RESUMEN

From genetic and etiological studies, autoimmune mechanisms underlying schizophrenia are suspected; however, the details remain unclear. In this study, we describe autoantibodies against neural cell adhesion molecule (NCAM1) in patients with schizophrenia (5.4%, cell-based assay; 6.7%, ELISA) in a Japanese cohort (n = 223). Anti-NCAM1 autoantibody disrupts both NCAM1-NCAM1 and NCAM1-glial cell line-derived neurotrophic factor (GDNF) interactions. Furthermore, the anti-NCAM1 antibody purified from patients with schizophrenia interrupts NCAM1-Fyn interaction and inhibits phosphorylation of FAK, MEK1, and ERK1 when introduced into the cerebrospinal fluid of mice and also reduces the number of spines and synapses in frontal cortex. In addition, it induces schizophrenia-related behavior in mice, including deficient pre-pulse inhibition and cognitive impairment. In conclusion, anti-NCAM1 autoantibodies in patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice. These antibodies may be a potential therapeutic target and serve as a biomarker to distinguish a small but treatable subgroup in heterogeneous patients with schizophrenia.


Asunto(s)
Moléculas de Adhesión de Célula Nerviosa , Esquizofrenia , Autoanticuerpos , Antígeno CD56/genética , Humanos , Moléculas de Adhesión de Célula Nerviosa/genética , Esquizofrenia/genética , Sinapsis/metabolismo
18.
BMC Ecol Evol ; 22(1): 71, 2022 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-35624412

RESUMEN

BACKGROUND: Scleractinian corals of the genus Montipora (Anthozoa, Cnidaria) possess some unusual biological traits, such as vertical transmission of algal symbionts; however, the genetic bases for those traits remain unknown. We performed extensive comparative genomic analyses among members of the family Acroporidae (Montipora, Acropora, and Astreopora) to explore genomic novelties that might explain unique biological traits of Montipora using improved genome assemblies and gene predictions for M. cactus, M. efflorescens and Astreopora myriophthalma. RESULTS: We obtained genomic data for the three species of comparable high quality to other published coral genomes. Comparative genomic analyses revealed that the gene families restricted to Montipora are significantly more numerous than those of Acropora and Astreopora, but their functions are largely unknown. The number of gene families specifically expanded in Montipora was much lower than the number specifically expanded in Acropora. In addition, we found that evolutionary rates of the Montipora-specific gene families were significantly higher than other gene families shared with Acropora and/or Astreopora. Of 40 gene families under positive selection (Ka/Ks ratio > 1) in Montipora, 30 were specifically detected in Montipora-specific gene families. Comparative transcriptomic analysis of early life stages of Montipora, which possesses maternally inherited symbionts, and Acropora, which lacks them, revealed that most gene families continuously expressed in Montipora, but not expressed in Acropora do not have orthologs in Acropora. Among the 30 Montipora-specific gene families under positive selection, 27 are expressed in early life stages. CONCLUSIONS: Lineage-specific gene families were important to establish the genus Montipora, particularly genes expressed throughout early life stages, which under positive selection, gave rise to biological traits unique to Montipora. Our findings highlight evolutionarily acquired genomic bases that may support symbiosis in these stony corals and provide novel insights into mechanisms of coral-algal symbiosis, the physiological foundation of coral reefs.


Asunto(s)
Antozoos , Animales , Antozoos/genética , Evolución Biológica , Arrecifes de Coral , Genómica , Simbiosis/genética
19.
Sci Rep ; 12(1): 2854, 2022 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-35190599

RESUMEN

Although numerous dinoflagellate species (Family Symbiodiniaceae) are present in coral reef environments, Acropora corals tend to select a single species, Symbiodinium microadriaticum, in early life stages, even though this species is rarely found in mature colonies. In order to identify molecular mechanisms involved in initial contact with native symbionts, we analyzed transcriptomic responses of Acropora tenuis larvae at 1, 3, 6, 12, and 24 h after their first contact with S. microadriaticum, as well as with non-native symbionts, including the non-symbiotic S. natans and the occasional symbiont, S. tridacnidorum. Some gene expression changes were detected in larvae inoculated with non-native symbionts at 1 h post-inoculation, but those returned to baseline levels afterward. In contrast, when larvae were exposed to native symbionts, we found that the number of differentially expressed genes gradually increased in relation to inoculation time. As a specific response to native symbionts, upregulation of pattern recognition receptor-like and transporter genes, and suppression of cellular function genes related to immunity and apoptosis, were exclusively observed. These findings indicate that coral larvae recognize differences between symbionts, and when the appropriate symbionts infect, they coordinate gene expression to establish stable mutualism.


Asunto(s)
Antozoos/genética , Antozoos/fisiología , Dinoflagelados/fisiología , Larva/genética , Larva/fisiología , Simbiosis/genética , Simbiosis/fisiología , Transcriptoma , Animales , Arrecifes de Coral , Ecosistema
20.
Genome Biol Evol ; 13(12)2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34878117

RESUMEN

Massive corals of the genus Porites, common, keystone reef builders in the Indo-Pacific Ocean, are distinguished by their relative stress tolerance and longevity. In order to identify genetic bases of these attributes, we sequenced the complete genome of a massive coral, Porites australiensis. We developed a genome assembly and gene models of comparable quality to those of other coral genomes. Proteome analysis identified 60 Porites skeletal matrix protein genes, all of which show significant similarities to genes from other corals and even to those from a sea anemone, which has no skeleton. Nonetheless, 30% of its skeletal matrix proteins were unique to Porites and were not present in the skeletons of other corals. Comparative genomic analyses showed that genes widely conserved among other organisms are selectively expanded in Porites. Specifically, comparisons of transcriptomic responses of P. australiensis and Acropora digitifera, a stress-sensitive coral, reveal significant differences in regard to genes that respond to increased water temperature, and some of the genes expanded exclusively in Porites may account for the different thermal tolerances of these corals. Taken together, widely shared genes may have given rise to unique biological characteristics of Porites, massive skeletons and stress tolerance.


Asunto(s)
Antozoos , Anémonas de Mar , Animales , Antozoos/genética , Arrecifes de Coral , Genoma , Genómica , Anémonas de Mar/genética , Secuenciación Completa del Genoma
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