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1.
JACS Au ; 4(6): 2130-2150, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38938812

RESUMEN

Monoclonal antibodies (mAbs) have gradually dominated the drug markets for various diseases. Improvement of the therapeutic activities of mAbs has become a critical issue in the pharmaceutical industry. A novel endo-ß-N-acetylglucosaminidase, EndoSz, from Streptococcus equisubsp. zooepidemicus Sz105 is discovered and applied to enhance the activities of mAbs. Our studies demonstrate that the mutant EndoSz-D234M possesses an excellent transglycosylation activity to generate diverse glycoconjugates on mAbs. We prove that EndoSz-D234M can be applied to various marketed therapeutic antibodies and those in development for antibody remodeling. The remodeled homogeneous antibodies (mAb-G2S2) produced by EndoSz-D234M increase the relative ADCC activities by 3-26-fold. We further report the high-resolution crystal structures of EndoSz-D234M in the apo-form at 2.15 Å and the complex form with a bound G2S2-oxazoline intermediate at 2.25 Å. A novel pH-jump method was utilized to obtain the complex structure with a high resolution. The detailed interactions of EndoSz-D234M and the carried G2S2-oxazoline are hence delineated. The oxazoline sits in a hole, named the oxa-hole, which stabilizes the G2S2-oxazoline in transit and catalyzes the further transglycosylation reaction while targeting Asn-GlcNAc (+1) of Fc. In the oxa-hole, the H-bonding network involved with oxazoline dominates the transglycosylation activity. A mobile loop2 (a.a. 152-159) of EndoSz-D234M reshapes the binding grooves for the accommodation of G2S2-oxazoline upon binding, at which Trp154 forms a hydrogen bond with Man (-2). The long loop4 (a.a. 236-248) followed by helix3 is capable of dominating the substrate selectivity of EndoSz-D234M. In addition, the stepwise transglycosylation behavior of EndoSz-D234M is elucidated. Based on the high-resolution structures of the apo-form and the bound form with G2S2-oxazoline as well as a systematic mutagenesis study of the relative transglycosylation activity, the transglycosylation mechanism of EndoSz-D234M is revealed.

2.
Viruses ; 16(5)2024 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-38793686

RESUMEN

Parrot bornavirus (PaBV) is an infectious disease linked with proventricular dilatation disease (PDD) with severe digestive and neurological symptoms affecting psittacine birds. Despite its detection in 2008, PaBV prevalence in Taiwan remains unexplored. Taiwan is one of the leading psittacine bird breeders; hence, understanding the distribution of PaBV aids preventive measures in controlling spread, early disease recognition, epidemiology, and transmission dynamics. Here, we aimed to detect the prevalence rate of PaBV and assess its genetic variation in Taiwan. Among 124 psittacine birds tested, fifty-seven were PaBV-positive, a prevalence rate of 45.97%. Most of the PaBV infections were adult psittacine birds, with five birds surviving the infection, resulting in a low survival rate (8.77%). A year of parrot bornavirus surveillance presented a seasonal pattern, with peak PaBV infection rates occurring in the spring season (68%) and the least in the summer season (25%), indicating the occurrence of PaBV infections linked to seasonal factors. Histopathology reveals severe meningoencephalitis in the cerebellum and dilated cardiomyopathy of the heart in psittacine birds who suffered from PDD. Three brain samples underwent X/P gene sequencing, revealing PaBV-2 and PaBV-4 viral genotypes through phylogenetic analyses. This underscores the necessity for ongoing PaBV surveillance and further investigation into its pathophysiology and transmission routes.


Asunto(s)
Enfermedades de las Aves , Bornaviridae , Infecciones por Mononegavirales , Filogenia , Psittaciformes , Animales , Taiwán/epidemiología , Bornaviridae/genética , Bornaviridae/clasificación , Bornaviridae/aislamiento & purificación , Infecciones por Mononegavirales/veterinaria , Infecciones por Mononegavirales/virología , Infecciones por Mononegavirales/epidemiología , Enfermedades de las Aves/virología , Enfermedades de las Aves/epidemiología , Prevalencia , Psittaciformes/virología , Estaciones del Año , Variación Genética , Loros/virología , Monitoreo Epidemiológico/veterinaria
3.
J Vet Med Sci ; 86(6): 670-676, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38692859

RESUMEN

Gastric ulcer is a common disease affecting pigs worldwide, with a prevalence reported as high as 93%. The cause of porcine gastric ulcer is multifactorial, with Helicobacter suis (H. suis) being considered as the primary pathogenic factor. To date, prevalence of H. suis resulting in porcine gastric ulcer in Taiwan has not been investigated. In this study, we collected 360 pig stomachs from the slaughterhouses. In addition, stomach tissues from the 88 diseased pigs submitted for necropsy were divided into symptomatic and asymptomatic groups. Gastric lesions were scored, and polymerase chain reaction was used to determine the occurrence of gastric ulcer and the prevalence of H. suis. The positive rate of H. suis in the samples from slaughtered pigs was 49.7%, and both infection of H. suis and the presence of gastric lesions were prone to occur in autumn. The positive rates of H. suis infection in the symptomatic and asymptomatic groups were 59.1% and 31.8%, respectively. Moreover, the proportion of the samples with gastroesophageal ulcer in the symptomatic group was 68.2%, predominantly observed in growing pigs. The incidence of the samples from the slaughterhouses with gastroesophageal erosion to ulceration revealed a significant difference between H. suis -infected and H. suis -uninfected pigs; however, there is no significant difference in the samples of diseased pigs. In conclusion, H. suis infection was associated with gastric ulcer in slaughtered pigs, but it was not the primary cause of gastroesophageal ulcer in diseased pigs with clinical symptoms.


Asunto(s)
Infecciones por Helicobacter , Helicobacter heilmannii , Úlcera Gástrica , Enfermedades de los Porcinos , Animales , Taiwán/epidemiología , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/microbiología , Úlcera Gástrica/veterinaria , Úlcera Gástrica/epidemiología , Úlcera Gástrica/microbiología , Úlcera Gástrica/patología , Porcinos , Infecciones por Helicobacter/veterinaria , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Prevalencia , Helicobacter heilmannii/aislamiento & purificación , Mataderos , Reacción en Cadena de la Polimerasa/veterinaria
4.
J Formos Med Assoc ; 2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38158260

RESUMEN

Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring.

5.
J Prosthet Dent ; 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38036320

RESUMEN

STATEMENT OF PROBLEM: Progressive peri-implant marginal bone loss and peri-implantitis have become a growing problem, but cross-sectional studies on their prevalence and risk factors are sparse. PURPOSE: The purpose of this cross-sectional clinical study was to investigate the prevalence of peri-implant marginal bone loss (MBL) and to identify systemic and local risk factors. MATERIAL AND METHODS: All adult patients who had received dental implants at the National Taiwan University Hospital (NTUH) during 2009 or 2010 were included. Their medical records were collected from the NTUH-integrative Medical Database. Consecutive follow-up radiographs were accessed for severity of MBL. The influence of each factor on MBL was estimated by using generalized estimating equations (GEEs). RESULTS: A total of 732 participants with 1873 implants were analyzed (mean follow-up: 5.30 years). The prevalence of MBL was 59.15% at the individual level and 49.55% at the implant level. The risk indicators identified for the presence of MBL were follow-up period of more than 2 years, diagnosis of diabetes within 12 months, radiation therapy (2 years after implant placement), implant location at maxillary canine (compared with mandibular molar), and implants from the Nobel Biocare brands (Brånemark System and NobelActive). A second multivariate GEE model confirmed the association of progressive MBL with implant location at the maxillary canine and mandibular incisor and implant brand or design. CONCLUSIONS: The identified risk indicators for MBL were longer follow-up period, diagnosis of diabetes, radiation therapy, implant location at maxillary canine, and implant brand or design.

6.
Nat Commun ; 14(1): 545, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36726015

RESUMEN

Understanding the structural diversity of honeybee-infecting viruses is critical to maintain pollinator health and manage the spread of diseases in ecology and agriculture. We determine cryo-EM structures of T = 4 and T = 3 capsids of virus-like particles (VLPs) of Lake Sinai virus (LSV) 2 and delta-N48 LSV1, belonging to tetraviruses, at resolutions of 2.3-2.6 Å in various pH environments. Structural analysis shows that the LSV2 capsid protein (CP) structural features, particularly the protruding domain and C-arm, differ from those of other tetraviruses. The anchor loop on the central ß-barrel domain interacts with the neighboring subunit to stabilize homo-trimeric capsomeres during assembly. Delta-N48 LSV1 CP interacts with ssRNA via the rigid helix α1', α1'-α1 loop, ß-barrel domain, and C-arm. Cryo-EM reconstructions, combined with X-ray crystallographic and small-angle scattering analyses, indicate that pH affects capsid conformations by regulating reversible dynamic particle motions and sizes of LSV2 VLPs. C-arms exist in all LSV2 and delta-N48 LSV1 VLPs across varied pH conditions, indicating that autoproteolysis cleavage is not required for LSV maturation. The observed linear domino-scaffold structures of various lengths, made up of trapezoid-shape capsomeres, provide a basis for icosahedral T = 4 and T = 3 architecture assemblies. These findings advance understanding of honeybee-infecting viruses that can cause Colony Collapse Disorder.


Asunto(s)
Proteínas de la Cápside , Virus ARN , Abejas , Animales , Proteínas de la Cápside/metabolismo , Cápside/metabolismo , Microscopía por Crioelectrón , Conformación Molecular , Ensamble de Virus
7.
J Formos Med Assoc ; 121(9): 1728-1738, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35168836

RESUMEN

BACKGROUND: The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored. METHODS: Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006-2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning. RESULTS: Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P < 0.05) were found in 34 (58.6%), of which 15 were caused by changes in diagnostic codes, wrong accounts, or modified orders. For the rest, the differences were related to accumulation of hospital visits over time. In the remaining 24 tables (41.4%) without significant differences, three were revised because of incorrect computer programming or wrong accounts. For the rest, the programming was correct and absolute differences were negligible. The applicability was confirmed using the data of 2,730,883 patients and 15,647,468 patient-visits transmitted during 2017-2018, in which 10 (3.5%) tables were corrected. CONCLUSION: Significant magnitude of inconsistent data does exist during the transmission of big data from diverse sources. Systematic validation is essential. Comparing the number of data tabulated using the primary keys allow us to rapidly identify and correct these scattered errors.


Asunto(s)
Macrodatos , Investigación Biomédica , Bases de Datos Factuales , Registros Electrónicos de Salud , Humanos , Sistemas Multiinstitucionales
8.
PLoS One ; 16(7): e0254028, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34197557

RESUMEN

BACKGROUND/AIMS: Hepatitis C Virus (HCV) infection is diagnosed by the presence of antibody to HCV and/or HCV RNA. This study aimed to evaluate the accuracy of anti-HCV titer (S/CO ratio) in predicting HCV viremia in patients with or without hepatitis B virus (HBV) dual infection. METHODS: Anti-HCV seropositive patients who were treatment-naïve consecutively enrolled. Anti-HCV antibodies were detected using a commercially chemiluminescent microparticle immunoassay. HCV RNA was detected by real-time PCR method. RESULTS: A total of 1321 including1196 mono-infected and 125 HBV dually infected patients were analyzed. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001). Of the entire cohort, the anti-HCV cut-off value of 10 provided the best accuracy, 96.8%, with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96.3%, 98.9%, 99.7% and 87.3% respectively. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001) and 9.36 (AUROC 1.00, P<0.0001) in patients with HCV mono-infection and HBV dual-infection respectively. Among the HBV dually infected patients, the accuracy of anti-HCV titer in predicting HCV viremia reached up to 100% with the cut-off value of 9. All the patients were HCV-viremic if their anti-HCV titer was greater than 9 (PPV 100%). On the other hand, all the patients were HCV non-viremic if their anti-HCV titer was less than 9 (NPV 100%). CONCLUSIONS: Anti-HCV titer strongly predicted HCV viremia. This excellent performance could be generalized to either HCV mono-infected or HBV dually infected patients.


Asunto(s)
Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/sangre , Anciano , Femenino , Hepacivirus/aislamiento & purificación , Hepacivirus/patogenicidad , Hepatitis B/genética , Hepatitis B/patología , Virus de la Hepatitis B/patogenicidad , Hepatitis C/patología , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Viral , Pruebas Serológicas
9.
Toxicol In Vitro ; 75: 105197, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34062233

RESUMEN

Following the global trend of reducing animal testing, various reconstructed human epidermis (RHE) models for skin irritation test (SIT) have been developed, verified, validated and included in OECD TG 439. We developed a new RHE called EPiTRI and a SIT method using EPiTRI (EPiTRI-SIT model) following the OECD guidelines. EPiTRI possesses morphological, biochemical and physiological properties similar to human epidermis with well-differentiated multilayered viable cells with barrier function. The EPiTRI-SIT model was tested for 20 reference chemicals in Performance Standard of OECD TG 439 (GD 220), showing good predictive capacity with 100% sensitivity, 70% specificity and 85% accuracy. EPiTRI had sensitivity in detecting di-n-propyl disulphate, as an irritant chemical (UN GHS Category 2), whereas most validated reference methods detected it as a non-irritant. An international validation study of EPiTRI-SIT was conducted in four laboratories to confirm the within- and between-laboratory reproducibility, as well as predictive capacity. The phase I/II within-laboratory and between-laboratory reproducibility was 100%/95% and 95%, respectively. The overall sensitivity, specificity and accuracy of EPiTRI-SIT was 96%, 70% and 83%, respectively, which fulfilled the OECD criteria. Thus, EPiTRI, meets the criteria of Performance Standards of OECD TG 439 (GD 220) and is suitable for screening irritating chemicals in vitro.


Asunto(s)
Epidermis/efectos de los fármacos , Técnicas In Vitro , Irritantes/toxicidad , Pruebas de Irritación de la Piel , Supervivencia Celular/efectos de los fármacos , Epidermis/ultraestructura , Prepucio , Humanos , Masculino , Organización para la Cooperación y el Desarrollo Económico , Reproducibilidad de los Resultados
10.
J Healthc Eng ; 2020: 8871849, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33194160

RESUMEN

There are various methods to generate nanobubbles, and in this study, we experimented using a nanobubble generator with a high-density of stainless steel mesh nozzle to deliver nanobubble water (normal water and two kinds of mouthwash) stream through a tooth tray to clean bacteria coated on the denture. It showed that with various combinations of motor speed settings and pore diameters, a clearing rate of 95% or more could be achieved, while in some combinations, a clearing rate of 100% was possible. This confirmed the plaque removing the function of the nanobubble water streams. The motor speed setting of the nanobubble generator directly influenced the flow velocity and nanobubble diameter of the water stream. However, the nanobubble dimensions were found to have a significant impact on plaque removal. The bubble diameters and plaque removal efficacy were as follows: the smaller the diameter, the slower the flow velocity and the better the plaque removal. The nanobubble formation of mouthwash was better on plaque removal, compared with the soaking method. From these results, we theorized that plaque removal is influenced by the dimension of nanobubbles; smaller bubble diameter led to improved plaque removal efficacy.


Asunto(s)
Higiene Bucal , Agua , Humanos
11.
IUCrJ ; 7(Pt 5): 934-948, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32939285

RESUMEN

In Pseudomonas aeruginosa, an important opportunistic pathogen that causes numerous acute and chronic infections, the hybrid two-component system (TCS) regulates the swarming ability and biofilm formation with a multistep phospho-relay, and consists of hybrid-sensor histidine kinase (HK), histidine-containing phospho-transfer protein (Hpt) and response regulator (RR). In this work, two crystal structures of HptB and the receiver domain of HK PA1611 (PA1611REC) of P. aeruginosa have been determined in order to elucidate their interactions for the transfer of the phospho-ryl group. The structure of HptB folds into an elongated four-helix bundle - helices α2, α3, α4 and α5, covered by the short N-terminal helix α1. The imidazole side chain of the conserved active-site histidine residue His57, located near the middle of helix α3, protrudes from the bundle and is exposed to solvent. The structure of PA1611REC possesses a conventional (ß/α)5 topology with five-stranded parallel ß-sheets folded in the central region, surrounded by five α-helices. The divalent Mg2+ ion is located in the negatively charged active-site cleft and interacts with Asp522, Asp565 and Arg567. The HptB-PA1611REC complex is further modeled to analyze the binding surface and interactions between the two proteins. The model shows a shape complementarity between the convex surface of PA1611REC and the kidney-shaped HptB with fewer residues and a different network involved in interactions compared with other TCS complexes, such as SLN1-R1/YPD1 from Saccharomyces cerevisiae and AHK5RD/AHP1 from Arabidopsis thaliana. These structural results provide a better understanding of the TCS in P. aeruginosa and could potentially lead to the discovery of a new treatment for infection.

12.
J Appl Biomater Funct Mater ; 18: 2280800020919881, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32941104

RESUMEN

An experiment was performed on oral bacteria removal using the design variables, which included the three-segment rotor speed of the testing device and three types of stainless steel meshes (with different layers). The overall hygienic results showed an effect of up to 95% bacteria removal, and some combinations had 100% hygienic effect. The study proposed that the use of nanobubble generated by a high-density stainless-steel mesh-manufactured nozzle removes dental bacteria. In addition, the device could also be used for auxiliary oral hygiene to decrease the frequency of future medical visits due to periodontal diseases or to enable the device to assist patients with severe periodontal disease more conveniently for oral hygiene.


Asunto(s)
Higiene Bucal , Acero Inoxidable , Cepillado Dental , Bacterias , Adhesión Bacteriana , Dentaduras , Desinfección , Diseño de Equipo , Humanos , Ensayo de Materiales , Enfermedades Periodontales/fisiopatología , Periodontitis/prevención & control , Factores de Tiempo
13.
Biochim Biophys Acta Proteins Proteom ; 1868(12): 140528, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32853773

RESUMEN

Mnemiopsin 2 from a luminous ctenophore with two functional EF-hand motifs is a calcium-regulated photoprotein that is responsible for emitting a bright blue bioluminescence upon reacting with coelenterazine and calcium ions in Mnemiopsis leidyi. Synchrotron radiation-based Fourier-transform infrared (SR-FTIR) spectroscopy was applied to analyze the distribution of secondary structures, the conformational changes resulting from calcium binding and the structural stabilities in wild-type mnemiopsin 2, as well as its mutant type that possesses three EF-hand motifs. The distribution of secondary structures of these proteins indicates that mutant apo-mnemiopsin 2 has a more stable secondary structure than the wild-type. Analyses of the SR-FTIR spectra revealed that the conformational changes at the secondary structures of both mnemiopsin 2 depend on the calcium concentrations, such that the most noticeable changes in structures of wild-type and mutant mnemiopsin 2 occur at optimum concentrations 6 and 2 mM of calcium chloride, respectively. The addition of calcium to both proteins increases the proportions of their secondary structures in the amide I and II regions. The major amide I bands in the IR spectra of both mnemiopsin­calcium complexes shift towards smaller wavenumbers, whereas their main amide II bands are identified at larger wavenumbers.


Asunto(s)
Calcio/química , Proteínas Luminiscentes/química , Estructura Secundaria de Proteína , Espectroscopía Infrarroja por Transformada de Fourier , Concentración de Iones de Hidrógeno , Proteínas Luminiscentes/genética , Proteínas Mutantes , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Soluciones , Relación Estructura-Actividad
14.
ACS Omega ; 5(7): 3428-3443, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-32118157

RESUMEN

The protrusion domain (P-domain; MrNVPd) of Macrobrachium rosenbergii nodavirus (MrNV) exists in two conformations, parallel and X-shaped. We have performed a theoretical study to gain insight into the nature of the dimeric interactions involving the dimeric interfaces within parallel and X-shaped conformations of MrNVPd by applying the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in the framework of the density functional theory (DFT) approach. The results reveal that the dimer-dimer interfaces of MrNVPd have hydrogen bonds of common types. Leu255-Lys287, Tyr257-Lys287, Lys287-Ser253, Met294-Cys328, Asp295-Lys327, Ser298-Ser324, Ile326-Asp295, and Cys328-Met294 are the key residue pairs of the dimer-dimer interfaces to maintain the dimer-dimer structures of MrNVPd through charge-charge, charge-dipole, dipole-dipole, hydrophobic, and hydrogen bonding interactions. The strengths of these intermolecular dimer-dimer interactions in the parallel conformation are much greater than those in the X-shaped conformation. The parallel trimeric interface is held basically by electrostatic and hydrophobic interactions. The electrostatic interactions accompanying a strong hydrogen bond of Oγ1-Hγ1···Oγ1 in the Thr276 A-Thr276 D pair maintain the intermolecular interface of two X-shaped MrNVPd dimers.

15.
Commun Biol ; 2: 72, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30820467

RESUMEN

Shrimp nodaviruses, including Penaeus vannamei (PvNV) and Macrobrachium rosenbergii nodaviruses (MrNV), cause white-tail disease in shrimps, with high mortality. The viral capsid structure determines viral assembly and host specificity during infections. Here, we show cryo-EM structures of T = 3 and T = 1 PvNV-like particles (PvNV-LPs), crystal structures of the protrusion-domains (P-domains) of PvNV and MrNV, and the crystal structure of the ∆N-ARM-PvNV shell-domain (S-domain) in T = 1 subviral particles. The capsid protein of PvNV reveals five domains: the P-domain with a new jelly-roll structure forming cuboid-like spikes; the jelly-roll S-domain with two calcium ions; the linker between the S- and P-domains exhibiting new cross and parallel conformations; the N-arm interacting with nucleotides organized along icosahedral two-fold axes; and a disordered region comprising the basic N-terminal arginine-rich motif (N-ARM) interacting with RNA. The N-ARM controls T = 3 and T = 1 assemblies. Increasing the N/C-termini flexibility leads to particle polymorphism. Linker flexibility may influence the dimeric-spike arrangement.


Asunto(s)
Proteínas de la Cápside/química , Cápside/metabolismo , Nodaviridae/fisiología , Palaemonidae/virología , Penaeidae/virología , Virión/metabolismo , Secuencia de Aminoácidos , Animales , Cápside/ultraestructura , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Microscopía por Crioelectrón , Modelos Moleculares , Nodaviridae/genética , Nodaviridae/ultraestructura , Dominios Proteicos , Multimerización de Proteína , Homología de Secuencia de Aminoácido , Virión/ultraestructura , Ensamble de Virus
16.
J Med Internet Res ; 21(2): e11016, 2019 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-30724742

RESUMEN

BACKGROUND: Adverse drug reactions (ADRs) are common and are the underlying cause of over a million serious injuries and deaths each year. The most familiar method to detect ADRs is relying on spontaneous reports. Unfortunately, the low reporting rate of spontaneous reports is a serious limitation of pharmacovigilance. OBJECTIVE: The objective of this study was to identify a method to detect potential ADRs of drugs automatically using a deep neural network (DNN). METHODS: We designed a DNN model that utilizes the chemical, biological, and biomedical information of drugs to detect ADRs. This model aimed to fulfill two main purposes: identifying the potential ADRs of drugs and predicting the possible ADRs of a new drug. For improving the detection performance, we distributed representations of the target drugs in a vector space to capture the drug relationships using the word-embedding approach to process substantial biomedical literature. Moreover, we built a mapping function to address new drugs that do not appear in the dataset. RESULTS: Using the drug information and the ADRs reported up to 2009, we predicted the ADRs of drugs recorded up to 2012. There were 746 drugs and 232 new drugs, which were only recorded in 2012 with 1325 ADRs. The experimental results showed that the overall performance of our model with mean average precision at top-10 achieved is 0.523 and the rea under the receiver operating characteristic curve (AUC) score achieved is 0.844 for ADR prediction on the dataset. CONCLUSIONS: Our model is effective in identifying the potential ADRs of a drug and the possible ADRs of a new drug. Most importantly, it can detect potential ADRs irrespective of whether they have been reported in the past.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos/normas , Redes Neurales de la Computación , Humanos , Prohibitinas
17.
Sci Rep ; 8(1): 14935, 2018 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-30297797

RESUMEN

The membrane-embedded quinol:fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain. The electron/proton-transfer pathways in QFRs remain controversial. Here we report the crystal structure of QFR from the anaerobic sulphate-reducing bacterium Desulfovibrio gigas (D. gigas) at 3.6 Å resolution. The structure of the D. gigas QFR is a homo-dimer, each protomer comprising two hydrophilic subunits, A and B, and one transmembrane subunit C, together with six redox cofactors including two b-hemes. One menaquinone molecule is bound near heme bL in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane. Armed with these structural insights, we propose electron/proton-transfer pathways in the quinol reduction of fumarate to succinate in the D. gigas QFR.


Asunto(s)
Proteínas Bacterianas/metabolismo , Desulfovibrio gigas/metabolismo , Oxidorreductasas/metabolismo , Proteínas Bacterianas/química , Cristalografía por Rayos X , Desulfovibrio gigas/química , Infecciones por Desulfovibrionaceae/microbiología , Transporte de Electrón , Humanos , Modelos Moleculares , Oxidorreductasas/química , Unión Proteica , Conformación Proteica , Protones , Especificidad por Sustrato , Vitamina K 2/metabolismo
18.
IET Nanobiotechnol ; 12(7): 973-980, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30247140

RESUMEN

Patients with serious gingivitis or periodontal diseases suffer from receding gums. Brushing teeth with a toothbrush may result in bleeding gums and new wounds, which increases the difficulty of removing facultative anaerobes from gum pockets, to decrease the damage inflicted on gums, this study proposed a cleaning device that can generate and emit oxygen microbubbles for eliminating facultative anaerobes in the mouth cavity. In this study, the authors conducted simulations with a denture to investigate the efficacy of using this method to remove facultative anaerobes. In this research for the optimal device design, several variables were manipulated including rotation speeds of the bubble generator, different nozzle diameters, and different numbers of nozzle holes. The results revealed that the device is effective in removing facultative anaerobes; moreover, of all design variables, the number of nozzle holes was the factor having the largest effect on anaerobe removal, as it influenced the flow volume and oxygen content of the discharge: the greater the number of nozzles, the greater the flow volume, oxygen content, and efficacy of anaerobe removal.


Asunto(s)
Antibacterianos/farmacología , Bacterias Anaerobias/efectos de los fármacos , Gingivitis/microbiología , Microburbujas , Higiene Bucal/instrumentación , Oxígeno/farmacología , Adulto , Diseño de Equipo , Humanos , Modelos Dentales
19.
J Nurs Res ; 26(5): 332-339, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29219940

RESUMEN

BACKGROUND: Postpartum fatigue is a very common complaint among postpartum women. Although current evidence indicates that several factors (e.g., parity, epidural analgesia, perineal trauma, perineal pain, and longer second stage of labor) are associated with postpartum, not enough is known about the relationships among these physical factors simultaneously and how they contribute to the development of postpartum fatigue. Increased awareness of the complex relationships among these factors will help nurses assess, prevent, and alleviate postpartum fatigue. PURPOSE: The aims of this study were to test a model of factors that influence postpartum fatigue and to estimate the direct and indirect effects of these factors on postpartum fatigue in vaginal-birth women. METHODS: The hypothesized model of the factors that influence postpartum fatigue after vaginal birth was developed based on previous studies. This study used a cross-sectional correlational design and convenience sampling. The Visual Analog Scale for Pain was used to measure postpartum perineal pain, and the Postpartum Fatigue Scale was used to assess postpartum fatigue via a structured, self-report questionnaire. Data analysis included descriptive statistics, Pearson's correlation coefficients, and path analysis. RESULTS: This study evaluated 326 healthy postpartum women within the first day after vaginal birth. Participants ranged from 20 to 43 years old, and 50.9% were primiparous. The model of the factors influencing postpartum fatigue after vaginal birth showed a good fit with the empirical data. Parity and the use of epidural analgesia predicted the duration of the second stage of labor, and the degree of perineal trauma predicted perineal pain. Participants who had experienced longer durations of the second stage of labor and more perineal pain reported higher levels of early postpartum fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: It is suggested that maternal nurses should better understand postpartum fatigue, take precautions to decrease perineal pain, and pay more attention to the longer duration of the second stage of labor to minimize postpartum fatigue, increase patient comfort, and improve the quality of perinatal care.


Asunto(s)
Parto Obstétrico/estadística & datos numéricos , Fatiga/epidemiología , Periodo Posparto , Adulto , Estudios Transversales , Femenino , Humanos , Enfermería Maternoinfantil , Modelos Teóricos , Embarazo , Factores de Riesgo , Adulto Joven
20.
Technol Health Care ; 25(6): 1195-1200, 2017 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-28946603

RESUMEN

OBJECTIVE: This study proposed a method of using a modified micro-bubble generator with its ejection nozzle connected to an ergonomically designed soft teeth-tray for plaque removal. The applicability of this method was verified and the influence on plaque removal efficacy of some parameters of this device was clarified. METHODS: The micro-bubble generator used in this study has 5 rotation speed settings, 5 nozzle sizes, and a soft teeth-tray ejection pore diameters. These were used as independent variables to investigate their effect on the ejected flow volume, velocity and micro-bubble dimension, and how they eventually affect the plaque removal efficacy from a denture. RESULTS: When the micro-bubble generator coupled with large (4.8 mm) ejection pore teeth-tray and the largest (1.2 mm) nozzle diameter more than 98% of plaque can be removed; its applicability on cleaning denture can be verified. In general, the larger nozzle diameter and teeth-tray ejection pore diameter will remove more plaques; while the higher the flow velocity and the smaller the micro-bubble of the ejected stream, better cleaning efficacy can be achieved. CONCLUSION: The application of micro-bubble on plaque removal seems effective, although at this moment it is applied on denture cleaning. The finding of the influence of some critical design parameters of micro-bubble generator and variables of ejected stream can be referred to further design a new micro-bubble cleaner for effective plaque removal from the teeth in human oral cavity.


Asunto(s)
Placa Dental/terapia , Microburbujas/uso terapéutico , Humanos
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