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BACKGROUND: Local translation at synapses is important for rapidly remodeling the synaptic proteome to sustain long-term plasticity and memory. While the regulatory mechanisms underlying memory-associated local translation have been widely elucidated in the postsynaptic/dendritic region, there is no direct evidence for which RNA-binding protein (RBP) in axons controls target-specific mRNA translation to promote long-term potentiation (LTP) and memory. We previously reported that translation controlled by cytoplasmic polyadenylation element binding protein 2 (CPEB2) is important for postsynaptic plasticity and memory. Here, we investigated whether CPEB2 regulates axonal translation to support presynaptic plasticity. METHODS: Behavioral and electrophysiological assessments were conducted in mice with pan neuron/glia- or glutamatergic neuron-specific knockout of CPEB2. Hippocampal Schaffer collateral (SC)-CA1 and temporoammonic (TA)-CA1 pathways were electro-recorded to monitor synaptic transmission and LTP evoked by 4 trains of high-frequency stimulation. RNA immunoprecipitation, coupled with bioinformatics analysis, were used to unveil CPEB2-binding axonal RNA candidates associated with learning, which were further validated by Western blotting and luciferase reporter assays. Adeno-associated viruses expressing Cre recombinase were stereotaxically delivered to the pre- or post-synaptic region of the TA circuit to ablate Cpeb2 for further electrophysiological investigation. Biochemically isolated synaptosomes and axotomized neurons cultured on a microfluidic platform were applied to measure axonal protein synthesis and FM4-64FX-loaded synaptic vesicles. RESULTS: Electrophysiological analysis of hippocampal CA1 neurons detected abnormal excitability and vesicle release probability in CPEB2-depleted SC and TA afferents, so we cross-compared the CPEB2-immunoprecipitated transcriptome with a learning-induced axonal translatome in the adult cortex to identify axonal targets possibly regulated by CPEB2. We validated that Slc17a6, encoding vesicular glutamate transporter 2 (VGLUT2), is translationally upregulated by CPEB2. Conditional knockout of CPEB2 in VGLUT2-expressing glutamatergic neurons impaired consolidation of hippocampus-dependent memory in mice. Presynaptic-specific ablation of Cpeb2 in VGLUT2-dominated TA afferents was sufficient to attenuate protein synthesis-dependent LTP. Moreover, blocking activity-induced axonal Slc17a6 translation by CPEB2 deficiency or cycloheximide diminished the releasable pool of VGLUT2-containing synaptic vesicles. CONCLUSIONS: We identified 272 CPEB2-binding transcripts with altered axonal translation post-learning and established a causal link between CPEB2-driven axonal synthesis of VGLUT2 and presynaptic translation-dependent LTP. These findings extend our understanding of memory-related translational control mechanisms in the presynaptic compartment.
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Plasticidad Neuronal , Proteínas de Unión al ARN , Transmisión Sináptica , Proteína 2 de Transporte Vesicular de Glutamato , Animales , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Plasticidad Neuronal/fisiología , Transmisión Sináptica/fisiología , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/genética , Ratones Noqueados , Axones/metabolismo , Axones/fisiología , ARN Mensajero/metabolismo , ARN Mensajero/genética , Masculino , Biosíntesis de ProteínasRESUMEN
The zwitterionic groups possess strong dipole moments, leading to inter- or intrachain interactions among zwitterionic polymers. This study aims to demonstrate the interaction of polyzwitterions poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and poly(carboxybetaine methacrylate) (PCBMA) with electrified surfaces, despite their electrically neutral nature. We studied the adsorption of polyzwitterions and their monomers on electrified surfaces by using an electrochemical quartz crystal microbalance with dissipation (EQCM-D). The interaction between zwitterionic molecules and charged surfaces is explored by adjusting the surface potentials. Interestingly, the adsorption of polyzwitterions can be influenced by external potential, primarily due to the formation of polyzwitterions restricting the mobility of zwitterionic groups, affecting the adsorption behavior of polyzwitterions based on the surface potential. The impact is determined by the arrangement of positive and negative ions within the zwitterionic groups, which are the dipole orientation. Additionally, surface potentials determine the adsorption rate, amount, and chain conformation of the adsorbed thin polyzwitterion layers. The effect of ionic strength was investigated by introducing electrolytes into the aqueous solutions to assess the range of influenced surface potentials.
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The glycoprotein CD44 is a key regulator of malignant behaviors in breast cancer cells. To date, hyaluronic acid (HA)-CD44 signaling pathway has been widely documented in the context of metastatic bone diseases. Core 1 ß1,3-galactosyltransferase (C1GALT1) is a critical enzyme responsible for the elongation of O-glycosylation. Aberrant O-glycans is recognized as a hallmark in cancers. However, the effects of C1GALT1 on CD44 signaling and bone metastasis remain unclear. In this study, IHC analysis indicated that C1GALT1 expression positively correlates with CD44 in breast cancer. Silencing C1GALT1 accumulates the Tn antigen on CD44, which decreases CD44 levels and osteoclastogenic signaling. Mutations in the O-glycosites on the stem region of CD44 impair its surface localization as well as suppress cell-HA adhesion and osteoclastogenic effects of breast cancer cells. Furthermore, in vivo experiments demonstrated the inhibitory effect of silencing C1GALT1 on breast cancer bone metastasis and bone loss. In conclusion, our study highlights the importance of O-glycans in promoting CD44-mediated tumorigenic signals and indicates a novel function of C1GALT1 in driving breast cancer bone metastasis. IMPLICATIONS: Truncation of GalNAc-type O-glycans by silencing C1GALT1 suppresses CD44-mediated osteoclastogenesis and bone metastasis in breast cancer. Targeting the O-glycans on CD44 may serve as a potential therapeutic target for blocking cancer bone metastasis.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/genética , Glicosilación , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Osteogénesis , Polisacáridos/metabolismo , Transducción de SeñalRESUMEN
Neisseria gonorrhoeae (GC) is a obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat this global health issue. AS101 [ammonium trichloro(dioxoethylene-O,O'-)tellurate], a tellurium-based compound previously used as an immunomodulatory agent, was found to have antimicrobial effects against Klebsiella pneumoniae via a high-throughput drug screening and showed antibacterial activity against Acinetobacter spp. This study aimed to evaluate the in vitro anti-gonococcal activity of AS101, including its antimicrobial activity, biofilm and infectivity inhibition, and potential underlying mechanisms. The agar-dilution-based MIC was used. The inhibition of GC microcolony formation and continual growth by AS101 was assessed by microscopy. The effect of AS101 on GC infectivity was evaluated by infecting endocervical ME180 and colorectal T84 epithelial cell lines. The mode of action was evaluated by a time-killing curve, transmission electron microscopy (TEM), and the level of reactive oxygen species (ROS). The MICs of MS11 and WHO GC isolates were both found to be 0.05 µg/mL. The biofilm formation, continual growth, and infectivity of two epithelial cell lines were significantly decreased with AS101 treatment. The time-kill curve, similar to that of azithromycin, suggested that AS101 is a bacteriostatic antimicrobial. However, TEM and ROS levels implied a mode of action different from that of azithromycin. Our findings highlighted the robust anti-gonococcal activities of AS101, which potentiates its use as a future antimicrobial for GC. IMPORTANCE Neisseria gonorrhoeae is an obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat the global health issue. This study aimed to evaluate the in vitro anti-gonococcal activity of a previous immunomodulatory agent, AS101, and its underlying mechanisms. Here, we report that AS101 possesses remarkable anti-gonococcal activity. These findings supported further studies on in vivo experiments and formulations for the clinical application of AS101 as an anti-gonococcal agent.
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Background: Sweating and increased skin temperature caused by exercise can reduce physical activity and the willingness to exercise in adolescents with atopic dermatitis. This study was conducted to investigate the exercise load capacity of adolescents with atopic dermatitis and analyzed their exercise behavior and motivation. Methods: Adolescents with and without atopic dermatitis were assigned to the atopic dermatitis group and control group (n = 27 each). Both groups completed a cardiopulmonary exercise test and questionnaires to assess their exercise capacity, weekly exercise volume, exercise motivation, and self-efficacy, respectively. Results: The ratio of measured forced vital capacity to the predicted forced vital capacity and the peak oxygen consumption of the atopic dermatitis group were significantly lower than those of the control group. The Godin Leisure-Time Exercise Questionnaire scores of the atopic dermatitis group were significantly lower than those of the control group. As for the Behavioral Regulation in Exercise Questionnaire 2, the scores for the introjected and identified regulations of the atopic dermatitis group were significantly lower than those of the control group. Regarding the Multidimensional Self-Efficacy for Exercise Scale, the scheduling efficacy and total scores of the atopic dermatitis group were significantly lower than those of the control group. Conclusions: Adolescents with atopic dermatitis had lower peak exercise capacity and lower weekly exercise volume. Furthermore, they lacked the negative feelings toward inactivity and the self-confidence to plan regular exercise independently. The results of this study suggest that adolescents with atopic dermatitis should be encouraged to engage in regular indoor exercise.
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Dermatitis Atópica , Adolescente , Ejercicio Físico , Humanos , Conducta Sedentaria , Autoeficacia , Encuestas y CuestionariosRESUMEN
Conducting polymers (CPs) have gained attention as electrode materials in bioengineering mainly because of their mechanical softness compared to conventional inorganic materials. To achieve better performance and broaden bioelectronics applications, the surface modification of soft zwitterionic polymers with antifouling properties represents a facile approach to preventing unwanted nonspecific protein adsorption and improving biocompatibility. This feature article emphasizes the antifouling properties of zwitterionic CPs, accompanied by their molecular synthesis and surface modification methods and an analysis of the interfacial phenomenon. Herein, commonly used methods for zwitterionic functionalization on CPs are introduced, including the synthesis of zwitterionic moieties on CP molecules and postsurface modification, such as the grafting of zwitterionic polymer brushes. To analyze the chain conformation, the structure of bound water in the vicinity of zwitterionic CPs and biomolecule behavior, such as protein adsorption or cell adhesion, provide critical insights into the antifouling properties. Integrating these characterization techniques offers general guidelines and paves the way for designing new zwitterionic CPs for advanced biomedical applications. Recent advances in newly designed zwitterionic CP-based electrodes have demonstrated outstanding potential in modern biomedical applications.
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Polímeros , Agua , Adsorción , Adhesión Celular , Polímeros/química , Propiedades de Superficie , Agua/químicaRESUMEN
Bacterial pathogens are well equipped to adhere to and initiate infection in teleost fish. Fish skin mucus serves as the first barrier against environmental pathogens. The mucus harbors commensal microbes that impact host physiological and immunological responses. However, how the skin mucosal microbiota responds to the presence of pathogens remains largely unexplored. Thus, little is known about the status of skin mucus prior to infection with noticeable symptoms. In this study, we investigated the interactions between pathogens and the skin mucosal microbiota as well as the fish skin immune responses in the presence of pathogens. Striped catfish (Pangasianodon hypophthalmus) were challenged with different concentrations of the bacterial pathogen Aeromonas hydrophila (AH), and the skin immune response and the mucosal microbiota were examined by quantitative PCR (qPCR) and 16S rRNA gene sequence analysis. We determined that the pathogen concentration needed to stimulate the skin immune response was associated with significant mucosal microbiota changes, and we reconfirmed these observations using an ex vivo fish skin model. Further analysis indicated that changes in the microbiota were attributed to a significant increase in opportunistic pathogens over AH. We concluded that the presence and increase of AH result in dysbiosis of the mucosal microbiota that can stimulate skin immune responses. We believe that our work sheds light on host-pathogen-commensal microbiota interactions and therefore contributes to aquaculture fish health. IMPORTANCE The fish skin mucosal microbiota is essential in modulating the host response to the presence of pathogens. Our study provides a platform to study both the correlation and causation of the interactions among the pathogen, fish skin, and the skin mucosal microbiota. Based on these findings, we provide the first mechanistic information on how mucosal microbiota changes induced by the pathogen AH result in skin disturbance with immune stimulation in striped catfish in the natural state and a potential direction for early-infection screening. Thus, this study is highly significant in the prevention of fish disease.
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Bagres , Microbiota , Aeromonas hydrophila , Animales , Disbiosis/veterinaria , ARN Ribosómico 16S/genéticaRESUMEN
A surface with a gradient physical or chemical feature, such as roughness, hardness, wettability, and chemistry, serves as a powerful platform for high-throughput investigation of cell responses to a biointerface. In this work, we developed a continuous antifouling gradient surface using pyrogallol (PG) chemistry. A copolymer of a zwitterionic monomer, sulfobetaine methacrylate, and an amino monomer, aminoethyl methacrylate, were synthesized (pSBAE) and deposited on glass slides via the deposition of self-polymerized PG. A gradient of pSBAE was fabricated on glass slides in 7 min in the presence of an oxidant, ammonium persulfate, by withdrawing the reaction solution. The modified glass slide showed a wettability gradient, determined by measuring the water contact angle. Cell adhesion and protein adsorption were well correlated with surface wettability. We expect that this simple and faster method for the fabrication of a continuous chemical gradient is applicable for high-throughput screening of surface properties to modulate biointerfaces.
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Gonorrhea is the second most common sexually transmitted infection, which is primarily localized but can be disseminated systemically. The mechanisms by which a localized infection becomes a disseminated infection are unknown. We used five pairs of Neisseria gonorrhoeae isolates from the cervix/urethra (localized) and the blood (disseminated) of patients with disseminated gonococcal infection to examine the mechanisms that confine gonococci to the genital tract or enable them to disseminate to the blood. Multilocus sequence analysis found that the local and disseminated isolates from the same patients were isogenic. When culturing in vitro, disseminated isolates aggregated significantly less and transmigrated across a polarized epithelial monolayer more efficiently than localized isolates. While localized cervical isolates transmigrated across epithelial monolayers inefficiently, those transmigrated bacteria self-aggregated less and transmigrated more than cervical isolates but comparably to disseminating isolates. The local cervical isolates recruited the host receptors of gonococcal Opa proteins carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) on epithelial cells. However, the transmigrated cervical isolate and the disseminated blood isolates recruit CEACAMs significantly less often. Our results collectively suggest that switching off the expression of CEACAM-binding Opa(s), which reduces self-aggregation, promotes gonococcal dissemination.
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A hydrogel surface with a nano-phase-separated structure was successfully fabricated by grafting a fluorine-containing polymer using activators regenerated by electron transfer atom transfer radical polymerisation (ARGET ATRP). The modified hydrogel surface exhibits water repellency and high elasticity with maintaining transparency.
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The surface modification of soft zwitterionic polymer brushes with antifouling properties represents a facile approach to enhancing the performance of bioelectronics. Ionic strength and applied potentials play a crucial role in controlling polymer brushes' conformation and hydration states. In this study, we quantitatively investigated and compared poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(sulfobetaine methacrylate) (PSBMA) brushes at different salt concentrations and applied surface potentials. Initiator-containing poly(3,4-ethylenedioxythiophene) films (poly(EDOT-Br)) were prepared by electropolymerization. After the conducting polymer was deposited, polymer brushes grew from the electrode surface through surface-initiated atom-transfer radical polymerization (SI-ATRP). Polymer brushes were carefully characterized for their surface morphologies using an atomic force microscope (AFM). The force volume method measured using AFM enabled the analysis of the Young's modulus of the two polymer brushes. Hydration states and protein binding behaviors of polymer brushes were examined using quartz crystal microbalance with dissipation (QCM-D). We further integrated a potentiostat with the QCM-D to conduct an electrochemical QCM-D study. The energy dissipation and frequency changes corresponded to the ion adsorption on the film surface under different ionic strengths. The results of both hydration states and nonspecific protein binding behavior indicate that PMPC brushes have greater ionic strength independency, implying the conformation of the unchanged PMPC brushes. Moreover, we illustrated how the surface potential influences nonspecific and specific binding behavior on PMPC brushes on PEDOT films compared with electrified poly(EDOT-PC) electrodes. We concluded that PMPC brushes exhibit unique behaviors that are barely affected by ion concentration, and that the brushes' modification results in less influence by surface potential due to the finite Debye length influencing the electrode surface to outer environment in an NaCl aqueous solution.
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Polímeros , Tecnicas de Microbalanza del Cristal de Cuarzo , Adsorción , Concentración Osmolar , Propiedades de Superficie , AguaRESUMEN
Teleost fish skin serves as the first line of defense against pathogens. The interaction between pathogen and host skin determines the infection outcome. However, the mechanism(s) that modulate infection remain largely unknown. A proper tissue culture model that is easier to handle but can quantitatively and qualitatively monitor infection progress may shed some lights. Here, we use striped catfish (Pangasius hypophthalmus) to establish an ex vivo skin explant tissue culture model to explore host pathogen interactions. The skin explant model resembles in vivo skin in tissue morphology, integrity, and immune functionality. Inoculation of aquatic pathogen Aeromonas hydrophila in this model induces epidermal exfoliation along with epithelial cell dissociation and inflammation. We conclude that this ex vivo skin explant model could serve as a teleost skin infection model for monitoring pathogenesis under various infection conditions. The model can also potentially be translated into a platform to study prevention and treatment of aquatic infection on the skin in aquaculture applications.
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Aeromonas hydrophila/patogenicidad , Acuicultura , Enfermedades de los Peces/patología , Infecciones por Bacterias Gramnegativas/patología , Piel/inmunología , Animales , Bagres , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/microbiologíaRESUMEN
Oenothera laciniata Hill is a perennial herb traditionally used to alleviate inflammatory complications. This study investigated the antioxidant and anti-melanogenic activities of O. laciniata. The methanolic extract (OLM) of O. laciniata and its different fractions, including ethyl acetate (OLEF), n-butanol (OLBF), and water (OLWF) fractions, were prepared. Antioxidant activities were evaluated by total phenolic content, the radical-scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPHâ¢), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+â¢), and superoxide anion (O2-â¢), reducing capacity, and metal chelating ability. OLM and its fractions exhibited potent antioxidant activity in these in vitro assays, with a correlation between radical-scavenging activity and total phenolic content. OLM and its fractions inhibited the mushroom tyrosinase activity superior to the reference control, ascorbic acid. In B16-F10 melanoma cells, OLM and its fractions significantly decreased melanin production and tyrosinase activity. Mechanistic investigations revealed that OLM and its fractions inhibited tyrosinase and TRP-2 expressions via downregulating MITF and phosphorylated CREB and differentially inducing ERK or JNK phosphorylation. Additionally, OLM and its fractions caused no significant cytotoxicity towards B16-F10 or skin fibroblast cells at concentrations used in these cellular assays. These findings demonstrated the potential of O. laciniata extracts as the ideal skin protective agent with dual antioxidant and anti-melanogenic activities.
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Eukaryotic mRNAs are 5' end capped with a 7-methylguanosine, which is important for processing and translation of mRNAs. Cap methyltransferase 1 (CMTR1) catalyzes 2'-O-ribose methylation of the first transcribed nucleotide (N1 2'-O-Me) to mask mRNAs from innate immune surveillance by retinoic-acid-inducible gene-I (RIG-I). Nevertheless, whether this modification regulates gene expression for neuronal functions remains unexplored. Here, we find that knockdown of CMTR1 impairs dendrite development independent of secretory cytokines and RIG-I signaling. Using transcriptomic analyses, we identify altered gene expression related to dendrite morphogenesis instead of RIG-I-activated interferon signaling, such as decreased calcium/calmodulin-dependent protein kinase 2α (Camk2α). In line with these molecular changes, dendritic complexity in CMTR1-insufficient neurons is rescued by ectopic expression of CaMK2α but not by inactivation of RIG-I signaling. We further generate brain-specific CMTR1-knockout mice to validate these findings in vivo. Our study reveals the indispensable role of CMTR1-catalyzed N1 2'-O-Me in gene regulation for brain development.
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Metiltransferasas/genética , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína 58 DEAD Box/genética , Proteína 58 DEAD Box/metabolismo , Femenino , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Guanosina/análogos & derivados , Guanosina/genética , Masculino , Metilación , Metiltransferasas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/fisiología , Caperuzas de ARN/metabolismo , ARN Mensajero/metabolismo , Ribosa , Transducción de SeñalRESUMEN
Although early detection and intervention may improve the outcome of the congenital cytomegalovirus (cCMV) infection, few studies assessed the real-world clinical practice for cCMV patients. We analyzed medical claims data to assess the patterns of diagnoses and medical care for cCMV patients.We used a subset of medical claims database (JMDC Claims Database) in Japan, covering 207,547 newborns between April 2010 and March 2017 and observed for at least 6 months. The diagnosis of cCMV and related symptoms and sequelae and medical care, including essential examinations and antiviral treatment, were identified using standardized codes.Overall, we identified 53 (25.5 per 100,000 newborns) cCMV patients diagnosed within 6 months after birth; of these, 83% were diagnosed within 1 month and 68% had at least 1 cCMV-related symptom at birth. Objective hearing tests and fundus examinations were performed within 6 months in 60% and 30% of patients, respectively. Antivirals were prescribed in 26% of patients. During the observation period (medianâ=â33 months), sensorineural hearing loss (49%) and developmental problems (28%) were commonly identified as cCMV-related sequelae. The proportions of the patients continuously followed up with objective hearing tests up to 36 months were 30% in total and 56% in antiviral-treated patients, respectively.The cCMV patients did not necessarily receive a timely diagnosis nor continuous follow-ups in usual clinical practice. Although the universal screening for cCMV may, if implemented, facilitate early diagnosis, it should be accompanied by strategic follow-up plans to support timely interventions.
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Infecciones por Citomegalovirus/diagnóstico , Tamizaje Neonatal , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/tratamiento farmacológico , Bases de Datos Factuales , Diagnóstico Precoz , Femenino , Pérdida Auditiva Sensorineural/complicaciones , Humanos , Recién Nacido , Revisión de Utilización de Seguros/estadística & datos numéricos , Japón , MasculinoRESUMEN
Immunotherapy using dendritic cells (DCs) is a promising treatment modality for cancer. However, the limited number of functional DCs from peripheral blood has been linked to the unsatisfactory clinical efficacies of current DC-based cancer immunotherapies. We previously generated proliferating antigen-presenting cells (APCs) by genetically engineering myeloid cells derived from induced pluripotent stem cells (iPSC-pMCs), which offer infinite functional APCs for broad applications in cancer therapy. Herein, we aimed to further enhance the antitumor effect of these cells by genetic modification. GM-CSF gene transfer did not affect the morphology, or surface phenotype of the original iPSC-pMCs, however, it did impart good viability to iPSC-pMCs. The resultant cells induced GM-CSF-dependent CD8+ T cell homeostatic proliferation, thereby enhancing antigen-specific T cell priming in vitro. Administration of the tumor antigen-loaded GM-CSF-producing iPSC-pMCs (GM-pMCs) efficiently stimulated antigen-specific T cells and promoted effector cell infiltration of the tumor tissues, leading to an augmented antitumor effect. To address the potential tumorigenicity of iPSC-derived products, irradiation was applied and found to restrict the proliferation of GM-pMCs, while retaining their T cell-stimulatory capacity. Furthermore, the irradiated cells exerted an antitumor effect equivalent to that of bone marrow-derived DCs obtained from immunocompetent mice. Additionally, combination with immune checkpoint inhibitors increased the infiltration of CD8+ or NK1.1+ effector cells and decreased CD11b+/Gr-1+ cells without causing adverse effects. Hence, although GM-pMCs have certain characteristics that differ from endogenous DCs, our findings suggest the applicability of these cells for broad clinical use and will provide an unlimited source of APCs with uniform quality.
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Células Dendríticas , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Animales , Antígenos de Neoplasias/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Activación de Linfocitos , Ratones , Linfocitos T CitotóxicosRESUMEN
Ring-averaged velocity distribution function of ions at a fixed guiding center position is a fundamental quantity in the gyrokinetic plasma physics. We have developed a diagnostic tool for the ring averaged velocity distribution function of ions for laboratory plasma experiments, which is named as the ring-averaged ion distribution function probe (RIDFP). The RIDFP is a set of ion collectors for different velocities. It is designed to be immersed in magnetized plasmas and achieves momentum selection of incoming ions by the selection of the ion Larmor radii. To nullify the influence of the sheath potential surrounding the RIDFP on the orbits of the incoming ions, the electrostatic potential of the RIDFP body is automatically adjusted to coincide with the space potential of the target plasma with the use of an emissive probe and a voltage follower. The developed RIDFP successfully measured the equilibrium ring-averaged velocity distribution function of a laboratory magnetized plasma, which was in accordance with the Maxwellian distribution having an ion temperature of 0.2 eV.
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Almost of HIV/AIDS cases in Taiwan occur in the age range of 20 to 29 yrs. Many of the reported cases are in the college-age and infection might have occurred through unprotected sexual behaviors. This study was to identify the effectiveness of a video-based intervention has important implications for health provider to plan evidence-based address the specific needs of college students.The research design of this study was based on TranstheoreticalModel (TTM). In addition, through an experimental design with groups: (i) to evaluate the effectiveness of a video-based intervention on the TTM stages of change,condom use self-efficacy, perceived benefits of and barriers to condom use by Taiwanese college students and (ii) to explore the factors affecting the TTM constructs for condom use. Overall, students have higher score in the pretest HIV knowledge scale, pretest self-efficacy scale and perceived benefits scale than the posttest. The score in perceived barriers scale of condom use also reduced after receiving intervention. This result shows that the videos and health education intervention can be effective in changing the college's intention to use condoms.
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Condones/estadística & datos numéricos , Infecciones por VIH/prevención & control , Educación en Salud/métodos , Estudiantes , Grabación de Cinta de Video , Conocimientos, Actitudes y Práctica en Salud , Humanos , Modelos Psicológicos , Autoeficacia , Taiwán , UniversidadesRESUMEN
Passing the national licensure examination for registered nurses (NCLEX-RN) in the US is a critical outcome of the nursing program. Research has been conducted to identify which nursing students are at risk for not passing the NCLEX-RN test. The purpose of this study was to investigate whether any of several student covariates can be used to accurately identify associate in science in nursing (ASN) students that are at-risk for failing the NCLEX-RN test. Covariates included in the study were demographics, students' pre-admission grade point average (GPA), the scores of test of essential skills (TEAS), and the assessment technologies institute® (ATI)'s comprehensive scores for a pre-RN examination test. Chi-squared automatic interaction detection, or CHAID analysis, was used to develop the model. One covariate, ATI comprehensive test scores, was found to accurately identify all at-risk ASN students. The model explained that students identified as "at-risk" had a failure rate nearly two-and-a-half times as high as the general population.
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Interpretación Estadística de Datos , Graduación en Auxiliar de Enfermería/clasificación , Graduación en Auxiliar de Enfermería/estadística & datos numéricos , Evaluación Educacional/métodos , Concesión de Licencias/estadística & datos numéricos , Modelos Estadísticos , Estudiantes de Enfermería/clasificación , Adolescente , Adulto , Simulación por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudiantes de Enfermería/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: Patients with severe osteogenesis imperfecta (OI; MIM number 259420) suffer from low bone mass, fractures, and bone pain since birth, and have poor prognosis. This study assessed the outcome of patients with severe OI who were treated with cyclic pamidronate prior to the age of 1 year. METHODS: The six patients, who had bone fractures either in utero or in their 1st month of life, were treated with cyclic pamidronate from a mean age of 2.8 months. RESULTS: All the patients tolerated the infusion, except for having transient hypocalcemia at the first infusion. Decreases in irritability and improvements in feeding were observed 2-3 months after the first infusion. All patients showed a rapid increase in bone mineral density over the first 2 years. Fractures occurred at a rate of 0.6/year. At a mean age of 6.4 years, five patients with no interruption in treatment had normal ambulatory function, but they were short in height. CONCLUSION: Patients with neonatal OI can have a favorable outcome when treated with cyclic pamidronate infusions early in life.