RESUMO
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of the disease. Here, we examined the pathophysiological role of Kallikrein 6 (Klk6), a serine protease produced by oligodendrocytes (OLs), in EAE using Klk6 knockout (Klk6-/-) mice. Compared with Klk6+/+ (wild-type) mice, Klk6-/- mice showed milder EAE symptoms, including delayed onset and milder paralysis. Loss of Klk6 suppressed matrix metalloprotease-9 expression and diminished the infiltration of peripheral inflammatory cells into the CNS by decreasing blood-brain barrier (BBB) permeability and reducing expression levels of inflammatory cytokines, chemokines and their receptors. Scanning electron microscopic analysis revealed demyelination characterized by myelin detachment from the axons in the early phase of EAE progression (days 3-7) in Klk6+/+ mice but not in Klk6-/- mice. Interestingly, anti-MOG (myelin oligodendrocyte glycoprotein) autoantibody was also detected in the cerebrospinal fluid (CSF) and spinal cord on day 3 after MOG immunization. Furthermore, treatment of primary cultured OLs with anti-MOG autoantibody induced oligodendroglial morphological changes and increases in myelin basic protein and Klk6 expression. We also developed a novel enzyme-linked immunoabsorbent assay method for detecting activated KLK6 in human CSF. In human autopsy brain samples, expression of active KLK6 was detected in OLs using an antibody that specifically recognizes the protein's activated form. Taken together, our findings demonstrate that Klk6 secreted by OLs plays a critical role in the pathogenesis of EAE/MS and that it might serve as a potential therapeutic target for MS.
Assuntos
Progressão da Doença , Encefalomielite Autoimune Experimental/metabolismo , Calicreínas/metabolismo , Oligodendroglia/metabolismo , Sequência de Aminoácidos , Animais , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Calicreínas/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
We report a case of a male patient with a 19-year history of monoclonal and later polyclonal gammopathy who subsequently developed tetraparesis, bulbar palsy, and respiratory failure. Autopsy findings showed degeneration of the hypoglossal nuclei, prominent neuronal loss and atrophy in the anterior horn of the whole spinal cord despite the presence of mild astrocytosis, degeneration of the gracilis on one side, and infiltration of inflammatory cells, which included B cells and plasma cells in the anterior and posterior roots of the lumbar spinal cord, iliopsoas muscle, and perivascular area of the cervical cord. On immunostaining, cytoplasmic inclusions of phosphorylated transactivation response DNA-binding protein of 43 kDa were observed in the motor neurons and astrocytes of the hypoglossal nuclei and whole spinal cord. The final diagnosis was paraneoplastic lower motor neuron disease with sensorimotor neuropathy due to Waldenström's macroglobulinemia.
Assuntos
Doença dos Neurônios Motores/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso Periférico/etiologia , Macroglobulinemia de Waldenstrom/complicações , Autopsia , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Doenças do Sistema Nervoso Periférico/patologia , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Although deep-sea ferromanganese nodules are a potential resource for exploitation, their formation mechanisms remain unclear. Several nodule-associated prokaryotic species have been identified by amplicon sequencing of 16S rRNA genes and are assumed to contribute to nodule formation. However, the recent development of amplicon sequence variant (ASV)-level monitoring revealed that closely related prokaryotic populations within an operational taxonomic unit often exhibit distinct ecological properties. Thus, conventional species-level monitoring might have overlooked nodule-specific populations when distinct populations of the same species were present in surrounding environments. Herein, we examined the prokaryotic community diversity of nodules and surrounding environments at the Clarion-Clipperton Zone in Japanese licensed areas by 16S rRNA gene amplicon sequencing with ASV-level resolution for three cruises from 2017 to 2019. Prokaryotic community composition and diversity were distinct by habitat type: nodule, nodule-surface mud, sediment, bottom water and water column. Most ASVs (~80%) were habitat-specific. We identified 178 nodule-associated ASVs and 41 ASVs associated with nodule-surface mud via linear discriminant effect size analysis. Moreover, several ASVs, such as members of SAR324 and Woeseia, were highly specific to nodules. These nodule-specific ASVs are promising targets for future investigation of the nodule formation process.
Assuntos
Ferro , Manganês , Água , Oceano Pacífico , RNA Ribossômico 16S/genética , Genes de RNArRESUMO
BACKGROUND: The objective of our study was to develop a novel capacitive force sensor that enables simultaneous measurements of yaw torque around the pressure axis and normal force and shear forces at a single point for the purpose of elucidating pressure ulcer pathogenesis and establishing criteria for selection of cushions and mattresses. METHODS: Two newly developed sensors (approximately 10 mm × 10 mm × 5 mm (10) and 20 mm × 20 mm × 5 mm (20)) were constructed from silicone gel and four upper and lower electrodes. The upper and lower electrodes had sixteen combinations that had the function as capacitors of parallel plate type. The full scale (FS) ranges of force/torque were defined as 0-1.5 N, -0.5-0.5 N and -1.5-1.5 N mm (10) and 0-8.7 N, -2.9-2.9 N and -16.8-16.8 N mm (20) in normal force, shear forces and yaw torque, respectively. The capacitances of sixteen capacitors were measured by an LCR meter (AC1V, 100 kHz) when displacements corresponding to four degrees of freedom (DOF) forces within FS ranges were applied to the sensor. The measurement was repeated three times in each displacement condition (10 only). Force/torque were calculated by corrected capacitance and were evaluated by comparison to theoretical values and standard normal force measured by an universal tester. RESULTS: In measurements of capacitance, the coefficient of variation was 3.23% (10). The Maximum FS errors of estimated force/torque were less than or equal to 10.1 (10) and 16.4% (20), respectively. The standard normal forces were approximately 1.5 (10) and 9.4 N (20) when pressure displacements were 3 (10) and 2 mm (20), respectively. The estimated normal forces were approximately 1.5 (10) and 8.6 N (10) in the same condition. CONCLUSIONS: In this study, we developed a new four DOF force sensor for measurement of force/torque that occur between the skin and a mattress. In measurement of capacitance, the repeatability was good and it was confirmed that the sensor had characteristics that enabled the correction by linear approximation for adjustment of gain and offset. In estimation of forces/torque, we considered accuracy to be within an acceptable range.
Assuntos
Condutometria/instrumentação , Testes de Dureza/instrumentação , Manometria/instrumentação , Palpação/instrumentação , Fenômenos Fisiológicos da Pele , Transdutores de Pressão , Capacitância Elétrica , Desenho de Equipamento , Análise de Falha de Equipamento , Estudos de ViabilidadeRESUMO
Three new species of free-living marine nematodes, Phanodermopsis dordi sp. nov., Halalaimus shinkai sp. nov., and Oxystomina hakureiae sp. nov. are described from the abyssal sediments of the Clarion-Clipperton Fracture Zone, North Pacific. Phanodermopsis dordi sp. nov. differs from the congeners by having papilliform anterior sensilla and a long conical tail with an acute tip. Halalaimus shinkai sp. nov., belonging to Keppner's group 2 based on the presence of caudal alae and the absence of precloacal sensillum or pore, can be distinguished from all of the members of this group by the presence of lateral pieces of gubernacula. Oxystomina hakureiae sp. nov. differs from the congeners by the short setiform anterior sensilla, the amphid located posterior to cephalic sensilla, the conico-cylindrical tail in both sexes, the spicules with a velum and a capitulum, the presence of the gubernacula and the precloacal setae, and the diorchic and monodelphic reproductive systems. The amended dichotomous keys to the species of Phanodermopsis, Halalaimus group 2, and Oxystomina are provided. A new combination Nemanema arenaria (Bussau, 1990) comb. nov. transferred from Oxystomina is also provided.
Assuntos
Enoplídios , Nematoides , Animais , Feminino , MasculinoRESUMO
The gastric-brooding asterinid sea star, Smilasterias multipara, broods from late August to early November in the shallow sublittoral zone of southeastern Australia. We observed males and females spawning in the laboratory. They shed gametes through gonopores on the sides of the arms. The eggs were orange, about 1.0 mm in diameter, and heavier than seawater. They were externally fertilized by sperm, and placed into the stomach of the female by the tube feet. Twenty-four hours after fertilization, the first cleavage occurred. Cleavage was equal, total, and radial. Development via a non-feeding lecithotrophic brachiolaria was direct, there being no planktrotrophic bipinnaria or brachiolaria larva. Embryos developed, through wrinkled blastula and gastrula stages, into brachiolariae with arms. All of the surfaces of the brachiolaria were covered by cilia. At metamorphosis, a starfish rudiment appeared on the posterior portion of the larval body, while the anterior portion of the larval body was absorbed. Two months after fertilization, metamorphosis was complete. After metamorphosis, juveniles in the stomach grew six pairs of tube feet in each arm. Juveniles, 3 mm in diameter, emerged from the mouth of the mother in early November. Developmental evidence suggests that this asteroid has evolved mechanisms for the protection of larvae and juveniles from gastric digestion.
Assuntos
Metamorfose Biológica , Morfogênese/fisiologia , Estrelas-do-Mar/embriologia , Estrelas-do-Mar/crescimento & desenvolvimento , Animais , Austrália , Feminino , Masculino , Especificidade da Espécie , Estrelas-do-Mar/fisiologiaRESUMO
A new species of echinoderid kinorhynch, Echinoderes sensibilis, is described and illustrated using light and electron microscopy. The specimens were collected from masses of the red algae Corallina pilulifera growing in intertidal pools in Tanabe Bay, Honshu Island, Japan. Diagnostic characters of E. sensibilis include the presence of middorsal spines on segments 6-10; lateral spines/tubules on segments 4, 7-12; remarkable trapezium-like subventral fields of minute cuticular hairs on segments 5-12. The positions of numerous sensory spots, large sieve areas, glandular tubes and the shape of terminal tergal and sternal extensions are also diagnostic. All taxonomic characters used for this description are illustrated by SEM. Echinoderes sensibilis constitutes the fifty-eight valid species of the genus Echinoderes and the fourteenth species described from the Pacific Ocean. This is the third representative of Pacific kinorhynchs found only in the intertidal zone and the first Pacific Echinoderes living on red macroalgae in intertidal pools.