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1.
Nature ; 557(7703): 96-100, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29720636

RESUMO

The skull of living birds is greatly modified from the condition found in their dinosaurian antecedents. Bird skulls have an enlarged, toothless premaxillary beak and an intricate kinetic system that includes a mobile palate and jaw suspensorium. The expanded avian neurocranium protects an enlarged brain and is flanked by reduced jaw adductor muscles. However, the order of appearance of these features and the nature of their earliest manifestations remain unknown. The Late Cretaceous toothed bird Ichthyornis dispar sits in a pivotal phylogenetic position outside living groups: it is close to the extant avian radiation but retains numerous ancestral characters1-3. Although its evolutionary importance continues to be affirmed3-8, no substantial new cranial material of I. dispar has been described beyond incomplete remains recovered in the 1870s. Jurassic and Cretaceous Lagerstätten have yielded important avialan fossils, but their skulls are typically crushed and distorted 9 . Here we report four three-dimensionally preserved specimens of I. dispar-including an unusually complete skull-as well as two previously overlooked elements from the Yale Peabody Museum holotype, YPM 1450. We used these specimens to generate a nearly complete three-dimensional reconstruction of the I. dispar skull using high-resolution computed tomography. Our study reveals that I. dispar had a transitional beak-small, lacking a palatal shelf and restricted to the tips of the jaws-coupled with a kinetic system similar to that of living birds. The feeding apparatus of extant birds therefore evolved earlier than previously thought and its components were functionally and developmentally coordinated. The brain was relatively modern, but the temporal region was unexpectedly dinosaurian: it retained a large adductor chamber bounded dorsally by substantial bony remnants of the ancestral reptilian upper temporal fenestra. This combination of features documents that important attributes of the avian brain and palate evolved before the reduction of jaw musculature and the full transformation of the beak.


Assuntos
Aves/anatomia & histologia , Dinossauros/anatomia & histologia , Fósseis , Filogenia , Crânio/anatomia & histologia , Animais , Bico/anatomia & histologia , Aves/classificação , Cabeça/anatomia & histologia , Arcada Osseodentária/anatomia & histologia
2.
Exp Eye Res ; 210: 108722, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370978

RESUMO

Keratoconus (KC), a progressive, degenerative corneal disease, represents the second leading indication for corneal transplantation globally. We have previously demonstrated that components of the Integrated Stress Response (ISR) are upregulated in human keratoconic donor tissue, and treatment of normal tissue with ISR agonists attenuates collagen production. With no consistently accepted animal models available for translational KC research, we sought to establish an in vivo model based on ISR activation to elucidate its role in the development of the KC phenotype. Four-week-old female SD rats were treated with topical SAL003 formulated as a nanosuspension or vehicle every 48 h for four doses. Animals were subject to monitoring for ocular inflammation and discomfort before being euthanized at 1, 14, or 28 days after treatment was withdrawn. Schirmer's tear test, intraocular pressure, and body weight measurements were obtained at baseline and prior to euthanasia. Globes were subject to routine histopathology, immunohistochemistry for ATF4, and qPCR for Col1a1 expression. ANOVAs and Student's t tests were used to assess statistical significance (α = 0.05). SAL003 treatment did not produce any adverse ocular or systemic phenotype but did result in decreased keratocyte density. Col1a1 transcripts were reduced, corresponding to nuclear ATF4 expression within the axial cornea. In vivo topical treatment with a gel-formulated ISR agonist recapitulates key features of the activated ISR including nuclear ATF4 expression and decreased extracellular matrix (ECM) production. Exogenous ISR agonists may present one approach to establishing a rodent model for keratoconus, a charge essential for future evaluations of pathogenesis and therapeutic interventions.


Assuntos
Cinamatos/farmacologia , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Ceratocone/induzido quimicamente , Tioureia/análogos & derivados , Fator 4 Ativador da Transcrição/metabolismo , Animais , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Córnea/metabolismo , Córnea/patologia , Ceratócitos da Córnea/patologia , Proteínas da Matriz Extracelular/metabolismo , Feminino , Ceratocone/metabolismo , Ceratocone/patologia , Ratos , Ratos Sprague-Dawley , Tioureia/farmacologia
3.
Nucleic Acids Res ; 45(2): 875-885, 2017 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-27574118

RESUMO

MicroRNAs originate from primary transcripts containing hairpin structures. The levels of mature miR156 influence the leaf number prior to flowering in the life cycle of plants. To understand the molecular mechanism of biogenesis of primary miR156a (pri-miR156a) to mature miR156, a base-pair opening dynamics study was performed using model RNAs mimicking the cleavage site of wild type and B5 bulge-stabilizing mutant pri-miR156a constructs. We also determined the mature miR156 levels and measured leaf numbers at flowering of plants overexpressing the wild type and mutant constructs. Our results suggest that the stabilities and/or opening dynamics of the C15·G98 and U16·A97 base-pairs at the cleavage site are essential for formation of the active conformation and for efficient processing of pri-miR156a, and that mutations of the B5 bulge can modulate mature miR156 levels as well as miR156-driven leaf number phenotypes via changes in the base-pair stability of the cleavage site.


Assuntos
Arabidopsis/genética , Pareamento de Bases , MicroRNAs/química , MicroRNAs/genética , Conformação de Ácido Nucleico , Fenótipo , Folhas de Planta , Termodinâmica , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Estudos de Associação Genética , Hidrogênio/metabolismo , Espectroscopia de Ressonância Magnética , Mutação , Plantas Geneticamente Modificadas
4.
Sensors (Basel) ; 18(12)2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30563181

RESUMO

This study presents wind observations from an airborne Doppler Wind Lidar (ADWL) in 2016 tropical cyclones (TC). A description of ADWL measurement collection and quality control methods is introduced for the use in a TC environment. Validation against different instrumentation on-board the National Oceanographic and Atmospheric Administration's WP-3D aircraft shows good agreement of the retrieved ADWL measured wind speed and direction. Measurements taken from instruments such as the global positioning system dropsonde, flight-level wind probe, tail Doppler radar, and Stepped Frequency Microwave Radiometer are compared to ADWL observations by creating paired datasets. These paired observations represent independent measurements of the same observation space through a variety of mapping techniques that account for differences in measurement procedure. Despite high correlation values, outliers are identified and discussed in detail. The errors between paired observations appear to be caused by differences in the ability to capture various length scales, which directly relate to certain regions in a TC regime. In validating these datasets and providing evidence that shows the mitigation of gaps in 3-dimensional wind representation, the unique wind observations collected via ADWL have significant potential to impact numerical weather prediction of TCs.

5.
Biochem Biophys Res Commun ; 484(4): 839-844, 2017 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-28161630

RESUMO

Internal and environmental cues, including ambient temperature changes, regulate the timing of flowering in plants. Arabidopsis miR156 represses flowering and plays an important role in the regulation of temperature-responsive flowering. However, the molecular basis of miR156 processing at lower temperatures remains largely unknown. Here, we performed nuclear magnetic resonance studies to investigate the base-pair opening dynamics of model RNAs at 16 °C and investigated the in vivo effects of the mutant RNAs on temperature-responsive flowering. The A9C and A10CG mutations in the B5 bulge of the lower stem of pri-miR156a stabilized the C15∙G98 and U16∙A97 base-pairs at the cleavage site of pri-miR156a at 16 °C. Consistent with this, production of mature miR156 was severely affected in plants overexpressing the A9C and A10CG constructs and these plants exhibited almost no delay in flowering at 16 °C. The A10G and A9AC mutations did not strongly affect C15∙G98 and U16∙A97 base-pairs at 16 °C, and plants overexpressing A10G and A9AC mutants of miR156 produced more mature miR156 than plants overexpressing the A9C and A10CG mutants and showed a strong delay in flowering at 16 °C. Interestingly, the A9AC mutation had distinct effects on the opening dynamics of the C15∙G98 and U16∙A97 base-pairs between 16 °C and 23 °C, and plants expressing the A9AC mutant miR156 showed only a moderate delay in flowering at 16 °C. Based on these results, we propose that fine-tuning of the base-pair stability at the cleavage site is essential for efficient processing of pri-miR156a at a low temperature and for reduced flowering sensitivity to ambient temperature changes.


Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Pareamento Incorreto de Bases/genética , Pareamento de Bases/genética , Flores/genética , MicroRNAs/genética , Sensação Térmica/genética , Sequência de Bases , Dados de Sequência Molecular , Mutação , Temperatura
7.
J Exp Bot ; 67(15): 4659-70, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27335452

RESUMO

MicroRNAs originate from primary transcripts (pri-miRNAs) containing hairpin structures. Plant pri-miRNAs have highly variable structures and little is known about the information encoded in their secondary structures. Arabidopsis miR156 is an ambient temperature-responsive miRNA and plays an important role in regulating flowering time. To identify the structural determinants for miR156 processing, we analyzed the effects of mutations introduced in the upper stem of pri-miR156a on its temperature-dependent processing and flowering time. The levels of pri-miR156a and mature miR156 were opposite at different temperatures. Mutations in the upper stem, especially the region closer to the miR156a/miR156a* duplex, reduced miR156 processing at 23 °C and 16 °C and caused a less severe phenotype compared with the un-mutated construct. Mutation in the second stem near the first cleavage site of pri-miR156a affected miR156 processing at 23 °C, but not at 16 °C. This was also seen in pri-miR172a, another ambient temperature-responsive miRNA. Replacement of the upper stem of pri-miR156a with that of pri-miR172a severely affected miR156 processing and flowering time. These results suggested that the upper stem of pri-miR156a is important for miR156 processing at different temperatures. In particular, the second stem adjacent to the first cleavage site plays a role in the regulation of ambient temperature-responsive flowering.


Assuntos
Arabidopsis/metabolismo , Flores/metabolismo , MicroRNAs/metabolismo , Northern Blotting , Conformação de Ácido Nucleico , Caules de Planta/metabolismo , Reação em Cadeia da Polimerase , Temperatura
8.
J Enzyme Inhib Med Chem ; 30(4): 607-14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25431146

RESUMO

Synthesis of a new series of quinolinylaminopyrimidines 1a-k and quinazolinylmethylaminopyrimidines 2a-i containing aminoquinoline and aminoquinazoline as hinge regions is described. Their in vitro antiproliferative activities against A375P human melanoma cell line were tested. Among them, compounds 1h and 1k exhibited the highest antiproliferative activities against A375P cell line with IC50 values in sub-micromolar scale. Compounds 1i, 2b and 2g showed similar potency against A375P to Sorafenib as a reference compound. The representative compound 1h showed high, dose-dependent inhibition of MEK and ERK kinases.


Assuntos
Proliferação de Células/efeitos dos fármacos , Melanoma/patologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Linhagem Celular Tumoral , Humanos , Pirimidinas/química
9.
BMC Public Health ; 14: 907, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25182027

RESUMO

BACKGROUND: Hypertension, stroke and coronary heart disease (CHD) are common diseases that impose a heavy burden on patients and their families, particularly on those living in poor areas. This study examined catastrophic medical payments faced by patients with these diseases and the effectiveness of the new rural cooperative medical system (NRCMS) at alleviating the impact of the said diseases in fourth-class rural areas (i.e. those with annual income of less than RMB 1500/$240.2 per capita) of China. METHODS: Data on medical payments, including out-of-pocket and NRCMS-reimbursed expenses were collected through self-administered questionnaires. The pre- and post-reimbursement (via the NRCMS) prevalence of household poverty, catastrophic medical payment (CMP) incidence (H cat), mean CMP gap (Gcat), mean positive CMP gap (MPG cat) and other determinants of CMP incidence were identified. RESULTS: Out-of-pocket payments for treatment of hypertension, stroke and CHD averaged RMB 580.1/$92.9, RMB 3028.4/$484.8 and RMB 1561.4/$250.0 per capita, respectively, in 2008. H cat, Gcat and MPG cat due to the three diseases were 17.0%, 16.6% and 97.6%, respectively, and reimbursement through the NRCMS reduced them to 13.5%, 11.8% and 87.4%, respectively. The difference between pre- and post-reimbursement H cat was not statistically significant. After adjusting the covariates for age [OR = 1.87, 95% confidence interval (CI) = 1.19-2.95], education (OR = 1.56, 95% CI = 1.07-2.27), marital status (OR = 1.67, 95% CI = 1.11-2.51), occupation (OR = 1.96, 95% CI = 1.34-2.85), annual income (OR = 4.95, 95% CI = 3.28-7.48), the multiple logistic regression analysis revealed that patients with stroke (OR = 3.94, 95% CI = 2.38-6.51) or CHD (OR = 2.25, 95% CI = 1.38-3.65) were more susceptible to CMP compared with patients with hypertension only. CONCLUSIONS: Out-of-pocket medical spending on hypertension, stroke and CHD imposes a heavy financial burden on the residents of fourth-class rural areas of China. The NRCMS has some impact on reducing catastrophic medical payments associated with these diseases, but improvement of the reimbursement rate is necessary to further improve its effectiveness.


Assuntos
Doença das Coronárias/economia , Organização do Financiamento/métodos , Hipertensão/economia , Seguro Médico Ampliado/economia , Serviços de Saúde Rural/organização & administração , Acidente Vascular Cerebral/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Efeitos Psicossociais da Doença , Características da Família , Feminino , Organização do Financiamento/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Áreas de Pobreza , Avaliação de Programas e Projetos de Saúde/métodos , Serviços de Saúde Rural/economia , População Rural/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
10.
ISME Commun ; 4(1): ycae051, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38699060

RESUMO

Soil carbon loss is likely to increase due to climate warming, but microbiomes and microenvironments may dampen this effect. In a 30-year warming experiment, physical protection within soil aggregates affected the thermal responses of soil microbiomes and carbon dynamics. In this study, we combined metagenomic analysis with physical characterization of soil aggregates to explore mechanisms by which microbial communities respond to climate warming across different soil microenvironments. Long-term warming decreased the relative abundances of genes involved in degrading labile compounds (e.g. cellulose), but increased those genes involved in degrading recalcitrant compounds (e.g. lignin) across aggregate sizes. These changes were observed in most phyla of bacteria, especially for Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, and Planctomycetes. Microbial community composition was considerably altered by warming, leading to declined diversity for bacteria and fungi but not for archaea. Microbial functional genes, diversity, and community composition differed between macroaggregates and microaggregates, indicating the essential role of physical protection in controlling microbial community dynamics. Our findings suggest that microbes have the capacity to employ various strategies to acclimate or adapt to climate change (e.g. warming, heat stress) by shifting functional gene abundances and community structures in varying microenvironments, as regulated by soil physical protection.

11.
Nat Commun ; 15(1): 1178, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331994

RESUMO

Unravelling biosphere feedback mechanisms is crucial for predicting the impacts of global warming. Soil priming, an effect of fresh plant-derived carbon (C) on native soil organic carbon (SOC) decomposition, is a key feedback mechanism that could release large amounts of soil C into the atmosphere. However, the impacts of climate warming on soil priming remain elusive. Here, we show that experimental warming accelerates soil priming by 12.7% in a temperate grassland. Warming alters bacterial communities, with 38% of unique active phylotypes detected under warming. The functional genes essential for soil C decomposition are also stimulated, which could be linked to priming effects. We incorporate lab-derived information into an ecosystem model showing that model parameter uncertainty can be reduced by 32-37%. Model simulations from 2010 to 2016 indicate an increase in soil C decomposition under warming, with a 9.1% rise in priming-induced CO2 emissions. If our findings can be generalized to other ecosystems over an extended period of time, soil priming could play an important role in terrestrial C cycle feedbacks and climate change.


Assuntos
Ecossistema , Pradaria , Solo , Carbono , Mudança Climática
12.
J Exp Bot ; 64(6): 1715-29, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23404901

RESUMO

The FLOWERING LOCUS T (FT)/TERMINAL FLOWER 1 (TFL1) family proteins play an important role in the regulation of flowering time. In the Arabidopsis thaliana genome, there are six genes in the FT/TFL1 family. To determine how these FT/TFL1 family genes contribute to the regulation of flowering time, this study generated a comprehensive set of mutants (sixty-three multiple mutants in all combinations) of the FT/TFL1 family genes and analysed their flowering times at 23 and 16°C under long-day conditions. The analysis confirmed that FT and TFL1 are major determinants of flowering time under long-day conditions. At 23 °C, ft-10 tsf-1 mft-2 showed the latest flowering, whereas tfl1-20 atc-2 bft-2 showed the earliest flowering. Flowering occurred in the sextuple mutants. Introduction of tsf-1 led to reduced sensitivity to ambient temperature change. Introduction of tfl1-20 caused a stronger effect in accelerating flowering time at 16 °C than at 23 °C. Overexpression of miR156 did not block flowering of sextuple mutants, suggesting that there is a pathway to induce flowering independent of the FT/TFL1 pathway and miR156 pathway. This study proposes that this mutant population will be useful in further investigation of the functions of the FT/TFL1 family genes in plant development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Flores/fisiologia , Genes de Plantas , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Genótipo , MicroRNAs/genética , MicroRNAs/metabolismo , Família Multigênica , Mutação , Proteína de Ligação a Fosfatidiletanolamina/genética , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Fotoperíodo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , RNA de Plantas/genética , RNA de Plantas/metabolismo , Temperatura , Fatores de Tempo
13.
PeerJ ; 11: e15142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37070096

RESUMO

The Atlantic Sharpnose Shark, Rhizoprionodon terraenovae (Richardson, 1836), is the most common small coastal requiem shark in the north-central Gulf of Mexico, USA. Despite this fact, little is known about the dental variation within this taxon. To help rectify this shortcoming, we examined 126 male and female R. terraenovae jaws sets across all maturity stages to document the various types of heterodonty occurring in the dentition of this taxon. Quantitative data gathered from a subset of our sample allowed for us to place teeth within the dentition of R. terraenovae into standardized upper and lower parasymphyseal/symphyseal, anterior lateral, and posterior tooth groups. As with all carcharhinid sharks, the dentition of R. terraenovae exhibits monognathic and dignathic heterodonty. We also observed significant ontogenetic heterodonty in the species, as the teeth and dentition progress through five generalized developmental stages as the shark matures. The ontogenetic development of serrations on the teeth appears to be closely related to documented dietary changes as the shark matures. Initial diets are comprised of high percentages of invertebrate prey like shrimp, crabs, and squid, but this transitions through ontogeny to a diet that is more reliant on fishes. We also provide the first documentation of gynandric heterodonty in mature male R. terraenovae, with development of these seasonal teeth likely enabling a male to grasp female sharks during copulation. Our analysis revealed a tremendous amount of variation in the dentition of R. terraenovae, which has direct implications on the taxonomy of fossil Rhizoprionodon. A comparison of the jaws in our sample to those of the extant species of Rhizoprionodon and the morphologically similar Loxodon, Scoliodon, and Sphyrna allowed us to formulate a list of generic-level characteristics to assist with the identification of isolated teeth. When applied to the fossil record, it is shown that some species previously assigned to Rhizoprionodon likely belong to one of the other aforementioned genera. The earliest occurrence of unequivocal Rhizoprionodon teeth in the fossil record are those of the Eocene †R. ganntourensis (Arambourg, 1952), the oldest records of which occur in early Ypresian deposits in Alabama and Mississippi, USA. The early Eocene occurrence of unequivocal fossil Rhizoprionodon teeth in Alabama predates the first occurrence of Negaprion, Galeocerdo, and Carcharhinus teeth in the state, supporting published molecular and morphological phylogenies positing a basal position for Rhizoprionodon within the Carcharhinidae.


Assuntos
Tubarões , Dente , Animais , Masculino , Feminino , Golfo do México , Dentição , Fósseis , Dente/anatomia & histologia
14.
ChemMedChem ; 18(21): e202300348, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37704578

RESUMO

Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been utilized for genome editing and anti-gene experiments for over thirty years. However, the research on Ps-TFOs employing artificial nucleotides is still limited, and their photo-crosslinking properties have not been thoroughly investigated in relation to biological activities. In this study, we extensively examined the photo-crosslinking properties of Ps-TFOs to provide fundamental insights for future Ps-TFO design. We developed novel Ps-TFOs containing 2'-O,4'-C-methylene-bridged nucleic acids (Ps-LNA-mixmer) and investigated their photo-crosslinking properties using stable cell lines that express firefly luciferase constitutively to evaluate the anti-gene activities of Ps-LNA-mixmer. As a result, Ps-LNA-mixmer successfully demonstrated suppression activity, and we presented the first-ever correlation between photo-crosslinking properties and their activities. Our findings also indicate that the photo-crosslinking process is insufficient under cell irradiation conditions (365 nm, 2 mW/cm2 , 60 min). Therefore, our results highlight the need to develop new psoralen derivatives that are more reactive under cell irradiation conditions.


Assuntos
Ácidos Nucleicos , Oligonucleotídeos , Oligonucleotídeos/farmacologia , Ficusina/farmacologia , DNA/metabolismo , Linhagem Celular
15.
ISME J ; 17(4): 611-619, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36732614

RESUMO

Study of life history strategies may help predict the performance of microorganisms in nature by organizing the complexity of microbial communities into groups of organisms with similar strategies. Here, we tested the extent that one common application of life history theory, the copiotroph-oligotroph framework, could predict the relative population growth rate of bacterial taxa in soils from four different ecosystems. We measured the change of in situ relative growth rate to added glucose and ammonium using both 18O-H2O and 13C quantitative stable isotope probing to test whether bacterial taxa sorted into copiotrophic and oligotrophic groups. We saw considerable overlap in nutrient responses across most bacteria regardless of phyla, with many taxa growing slowly and few taxa that grew quickly. To define plausible life history boundaries based on in situ relative growth rates, we applied Gaussian mixture models to organisms' joint 18O-13C signatures and found that across experimental replicates, few taxa could consistently be assigned as copiotrophs, despite their potential for fast growth. When life history classifications were assigned based on average relative growth rate at varying taxonomic levels, finer resolutions (e.g., genus level) were significantly more effective in capturing changes in nutrient response than broad taxonomic resolution (e.g., phylum level). Our results demonstrate the difficulty in generalizing bacterial life history strategies to broad lineages, and even to single organisms across a range of soils and experimental conditions. We conclude that there is a continued need for the direct measurement of microbial communities in soil to advance ecologically realistic frameworks.


Assuntos
Características de História de Vida , Solo , Ecossistema , Microbiologia do Solo , Bactérias
16.
Bioorg Med Chem ; 20(10): 3287-91, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22507207

RESUMO

An artificial antigen forming the C34 trimeric structure targeting membrane-fusion mechanism of HIV-1 has been evaluated as an HIV vaccine. The C34 trimeric molecule was previously designed and synthesized using a novel template with C3-symmetric linkers by us. The antiserum produced by immunization of the C34 trimeric form antigen showed 23-fold higher binding affinity for the C34 trimer than for the C34 monomer and showed significant neutralizing activity. The present results suggest effective strategies of the design of HIV vaccines and anti-HIV agents based on the native structure mimic of proteins targeting dynamic supramolecular mechanisms in HIV fusion.


Assuntos
Vacinas contra a AIDS/química , Anticorpos Anti-HIV/imunologia , Proteína gp41 do Envelope de HIV/imunologia , Fragmentos de Peptídeos/imunologia , Vacinas contra a AIDS/genética , Sequência de Aminoácidos , Animais , Fármacos Anti-HIV/química , Linhagem Celular , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Antígenos HIV/química , Antígenos HIV/imunologia , Proteína gp41 do Envelope de HIV/síntese química , Humanos , Imunização , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Testes de Neutralização , Fragmentos de Peptídeos/síntese química
17.
Sci Rep ; 12(1): 11056, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773459

RESUMO

This study investigates the atmospheric boundary layer structure based on multiple-level tower observations with a height of 350 m during the landfall of Super Typhoon Mangkhut (2018). Results show a layer of log wind profile outside of the radius of maximum wind speed with a height of 100 m or larger. The log layer height increases with the wind speed. The height of the constant flux layer reaches ~ 300 m for 10-m wind speeds less than 13 m s-1 while this height decreases with the wind speed. Momentum fluxes and turbulent kinetic energy increase with the wind speed at all vertical levels. The drag coefficient and surface roughness length estimated at the tower location have values of 7.3 × 10-3 and 0.09 m, respectively, which are independent of wind speed. The estimated vertical eddy diffusivity and mixing length increase with height up to ~ 160 m and then slowly decrease with height. The vertical eddy diffusivity increases with the wind speed while the vertical mixing length has no dependence on the wind speed. Comparing our results with previous work indicates that the vertical eddy diffusivity is larger over land than over ocean at a given wind speed range.

18.
Mov Disord ; 26(13): 2418-22, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22109851

RESUMO

BACKGROUND: In Parkinson's disease, sleep disturbance is a common occurrence. METHODS: We evaluated sleep in 10 patients with Parkinson's disease (age, 57.5 ± 9.8 years; disease duration, 12.3 ± 2.7 years) before and after subthalamic nucleus deep brain stimulation using the Parkinson's disease sleep scale and polysomnography. RESULTS: Their total sleep scale scores and daytime sleepiness subscale scores significantly improved after subthalamic nucleus-deep brain stimulation. The novel findings from this study significantly increased normal rapid eye movement sleep, and decreased abnormal rapid eye movement sleep without atonia after deep brain stimulation in patients with Parkinson's disease. The improved total sleep scale score correlated with decreased wakefulness after sleep onset. Moreover, improved daytime sleepiness correlated with increased normal rapid eye movement sleep time. Sleep improvement did not significantly correlate with resolution of motor complication or reduced dopaminergic dosages. CONCLUSIONS: Subthalamic nucleus-deep brain stimulation may have beneficial effects on sleep disturbance in advanced Parkinson's disease by restoring sleep architecture and normal rapid eye movement sleep.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Parassonias do Sono REM/terapia , Núcleo Subtalâmico/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Polissonografia , Parassonias do Sono REM/fisiopatologia , Índice de Gravidade de Doença , Núcleo Subtalâmico/cirurgia , Resultado do Tratamento
19.
Int J Clin Oncol ; 16(1): 27-32, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20830603

RESUMO

BACKGROUND: Little information is available about long-term outcomes of hypofractionated stereotactic radiotherapy (hypo-FSRT) for acoustic neuromas. In this study, the safety and effectiveness of hypo-FSRT for unilateral acoustic neuroma were reviewed over 8 years of experience at our institution. METHODS: Between May 1998 and October 2006, 27 patients were consecutively treated by linear accelerator-based hypo-FSRT. Two patients were excluded from this study because they were lost to follow-up within 12 months. The median follow-up period for the rest was 59 (range 24-133) months. Two types of treatment schedules were adopted. Thirteen patients received 30-39 Gy, given in 10-13 fractions (regimen A), whereas after July 2003, 12 patients received 20-24 Gy, given in 5-6 fractions at the tumor periphery (regimen B). These treatments were scheduled to be delivered in three fractions per week (Monday, Wednesday, Friday). The median planning target volume was 2.0, with 1.7 ml (range 0.7-10.6) in regimen A and 5.2 ml (range 0.9-9.3) in regimen B. In the pretreatment audiogram, seven patients (two in regimen A and five in regimen B) had serviceable hearing (Gardner-Robertson Class I-II). RESULTS: Local control rates were 100% with regimen A and 92% with regimen B. Serviceable hearing was preserved in four of five patients in regimen B but no patients in regimen A at the last follow-up. No permanent facial or trigeminal nerve morbidity was observed following treatment, and no salvage surgery was needed. CONCLUSIONS: Hypo-FSRT for acoustic neuromas achieved a high local control rate with minimal facial and trigeminal nerve morbidity.


Assuntos
Neuroma Acústico/radioterapia , Radiocirurgia/métodos , Adulto , Idoso , Fracionamento da Dose de Radiação , Feminino , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/fisiopatologia , Radiocirurgia/efeitos adversos , Resultado do Tratamento
20.
Sci Rep ; 11(1): 18771, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548533

RESUMO

Helical rolls are known to play a significant role in modulating both the mean and turbulence structure of the atmospheric boundary layer in tropical cyclones. However, in-situ measurements of these rolls have been limited due to safety restrictions. This study presents analyses of data collected by an aircraft operated by the Hong Kong Observatory in Typhoon Kalmaegi (1415) and Typhoon Nida (1604). Examination of the flight-level data at ~ 600 m altitude confirmed the existence of sub-kilometer-scale rolls. These rolls were mostly observed in the outer-core region. Turbulent momentum fluxes were computed using the eddy correlation method. The averaged momentum flux of flight legs with rolls was found to be ~ 2.5 times that of legs without rolls at a similar wind speed range. This result suggests that rolls could significantly modulate turbulent transfer in the tropical cyclone boundary layer. This roll effect on turbulent fluxes should be considered in the planetary boundary layer parameterization schemes of numerical models simulating and forecasting tropical cyclones.

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