RESUMEN
In the first billion years after the Big Bang, sources of ultraviolet (UV) photons are believed to have ionized intergalactic hydrogen, rendering the Universe transparent to UV radiation. Galaxies brighter than the characteristic luminosity L* (refs. 1,2) do not provide enough ionizing photons to drive this cosmic reionization. Fainter galaxies are thought to dominate the photon budget; however, they are surrounded by neutral gas that prevents the escape of the Lyman-α photons, which has been the dominant way to identify them so far. JD1 was previously identified as a triply-imaged galaxy with a magnification factor of 13 provided by the foreground cluster Abell 2744 (ref. 3), and a photometric redshift of z ≈ 10. Here we report the spectroscopic confirmation of this very low luminosity (≈0.05 L*) galaxy at z = 9.79, observed 480 Myr after the Big Bang, by means of the identification of the Lyman break and redward continuum, as well as multiple â³4σ emission lines, with the Near-InfraRed Spectrograph (NIRSpec) and Near-InfraRed Camera (NIRCam) instruments. The combination of the James Webb Space Telescope (JWST) and gravitational lensing shows that this ultra-faint galaxy (MUV = -17.35)-with a luminosity typical of the sources responsible for cosmic reionization-has a compact (≈150 pc) and complex morphology, low stellar mass (107.19 Mâ) and subsolar (≈0.6 Zâ) gas-phase metallicity.
RESUMEN
Accurate, simple, and valuable analytical methods for detection of food contamination are rapidly expanding to evaluate the validity of food product quality because of ethnic considerations and food safety. Herein molecularly imprinted nanogels (MIP-NGs), capable of porcine serum albumin (PSA) recognition, were prepared as artificial molecular recognition elements. The MIP-NGs were immobilized on a quartz crystal microbalance (QCM) sensor for detection of pork contamination in real beef extract samples. The MIP-NGs-based QCM sensor showed high affinity and excellent selectivity toward PSA compared to reference serum albumins from five different animals. The high PSA specificity of MIP-NGs led to the detection of pork contamination with a detection limit of 1% (v/v) in real beef extract samples. We believe the artificial molecular recognition materials prepared by molecular imprinting are a promising candidate for halal food control.
Asunto(s)
Contaminación de Alimentos/análisis , Carne/análisis , Impresión Molecular , Nanogeles/química , Albúmina Sérica/análisis , Animales , Bovinos , Tecnicas de Microbalanza del Cristal de Cuarzo , PorcinosRESUMEN
Nanomaterials have become increasingly promising for biomedical applications owing to their specific biological characteristics. As drug delivery vehicles, nanomaterials have to circulate in the bloodstream to deliver the encapsulated components to the target tissues. Protein corona regulation is one of the promising approaches that gives stealth capability to avoid immune response. The aim of this study was to develop molecularly imprinted polymer nanogels (MIP-NGs) capable of protein corona regulation, using intrinsic human serum albumin (HSA) and with a functional monomer, dansylamide ethyl acrylamide (DAEAm), the dansylamide group serving as a ligand for HSA. The recognition capability of HSA for MIP-NGs was investigated by isothermal titration calorimetry (ITC). The affinity of the MIP-NGs prepared with DAEAm was then compared to that of the reference MIP-NGs prepared with pyrrolidyl acrylate developed in our previous study. Furthermore, we demonstrated that the concurrent use of these two different functional monomers for molecular imprinting was further effective to construct high-affinity recognition nanocavities for HSA and to form HSA-rich protein corona in the human plasma owing to the different interaction modes of the monomers. We believe that the molecular imprinting strategy developed through the use of ligand-based functional monomer is an effective strategy to create artificial molecular recognition materials.
Asunto(s)
Impresión Molecular , Corona de Proteínas , Compuestos de Dansilo , Humanos , Nanogeles , Albúmina Sérica HumanaRESUMEN
Alport syndrome-diffuse leiomyomatosis (AS-DL, OMIM: 308940) is a rare variant of the X-linked Alport syndrome that shows overgrowth of visceral smooth muscles in the gastrointestinal, respiratory and female reproductive tracts in addition to renal symptoms. AS-DL results from deletions that encompass the 5' ends of the COL4A5 and COL4A6 genes, but deletion breakpoints between COL4A5 and COL4A6 have been determined in only four cases. Here, we characterize deletion breakpoints in five AS-DL patients and show a contiguous COL4A6/COL4A5 deletion in each case. We also demonstrate that eight out of nine deletion alleles involved sequences homologous between COL4A5 and COL4A6. Most breakpoints took place in recognizable transposed elements, including long and short interspersed repeats, DNA transposons and long-terminal repeat retrotransposons. Because deletions involved the bidirectional promoter region in each case, we suggest that the occurrence of leiomyomatosis in AS-DL requires inactivation of both genes. Altogether, our study highlights the importance of homologous recombination involving multiple transposed elements for the development of this continuous gene syndrome and other atypical loss-of-function phenotypes.
Asunto(s)
Colágeno Tipo IV/genética , Eliminación de Gen , Leiomiomatosis/complicaciones , Leiomiomatosis/genética , Nefritis Hereditaria/complicaciones , Nefritis Hereditaria/genética , Secuencia de Bases , HumanosRESUMEN
Three new norlanostane-type triterpene glycosides, scillanostasides A, B, and C, and two new lanostane-type triterpene glycosides, scillanostasides D and E, were isolated from the bulbs of Scilla scilloides Druce (Liliaceae) along with one known norlanostane-type triterpene heptaglycoside, scillascilloside G-1. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.
Asunto(s)
Glicósidos/química , Scilla/química , Triterpenos/química , Glicósidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Conformación Molecular , Raíces de Plantas/químicaRESUMEN
A 7-year-old Japanese girl with conductive deafness and preauricular fistulae developed proteinuria. She had renal insufficiency, and ultrasound revealed bilateral small kidneys. These findings indicated that she had branchio-oto-renal (BOR) syndrome. In the present patient, we identified, by using multiplex ligation-dependent probe amplification (MLPA) analysis, a heterozygous EYA1 gene deletion comprising at least exons 5 to 7. In her parents, we did not detect any deletion in EYA1 by MLPA, so the deletion was a de novo mutation. PCR analysis and sequencing of patient DNA revealed a heterozygous approximately 17 kb EYA1 deletion starting from the eight last bases of exon 4 and proceeding to base 1,217 of intron 7. Furthermore, in place of this deleted region was inserted a 3756-bp-long interspersed nuclear elements-1 (LINE-1, L1). Accordingly, RT-PCR showed that exons 4-7 were not present in EYA1 mRNA expressed from the mutated allele. Although there are reports of L1 element insertion occurring in various human diseases, this is the first report of a large EYA1 deletion in combination with L1 element insertion.
Asunto(s)
Anomalías Múltiples/genética , Región Branquial/anomalías , Oído/anomalías , Eliminación de Gen , Péptidos y Proteínas de Señalización Intracelular/genética , Riñón/anomalías , Elementos de Nucleótido Esparcido Largo/genética , Mutagénesis Insercional/genética , Proteínas Nucleares/genética , Proteínas Tirosina Fosfatasas/genética , Anomalías Múltiples/patología , Niño , Femenino , Regulación del Desarrollo de la Expresión Génica , Humanos , Técnicas de Amplificación de Ácido Nucleico , ARN Mensajero/metabolismo , Insuficiencia Renal/genética , SíndromeRESUMEN
The object of this study was to determine the efficacy and safety of brain hypothermia therapy (BHT) for neonates with severe birth asphyxia in our neonatal intensive care unit (NICU). We retrospectively reviewed medical records to analyze the prognosis and the factors affecting the prognosis of 21 patients who underwent BHT at the NICU between 2001 and 2007. The prognosis of those 21 patients at the time of discharge from the NICU was as follows: good-11 patients (52.4%); disability-5 patients (23.8%); and death-5 patients (23.8%). The ten poor prognosis patients (disability: 5, death: 5) had a shorter gestational period, a lower Apgar score, and a significantly higher blood lactate level in comparison with good-prognosis newborns. In particular, a gestational period of less than 34 weeks (3 patients) and a blood lactate level of at least 200 mg/dl (6 out of 7 patients) are considered to be factors for a poor prognosis. In addition, intraventricular hemorrhage was recorded in 7 patients of the 10 poor-prognosis patients and 4 of those patients developed acute renal failure during BHT. Consequently, these disorders are considered to worsen the prognosis. This study supports the efficacy and safety of BHT for neonates with severe birth asphyxia. On the other hand, BHT for the above mentioned types of high-risk patients still requires further consideration for the adoption and methods of BHT.
Asunto(s)
Asfixia Neonatal/terapia , Encéfalo , Hipotermia Inducida/métodos , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Asfixia Neonatal/sangre , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Japón/epidemiología , Ácido Láctico/sangre , Pronóstico , Estudios Retrospectivos , Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND OBJECTIVES: Gitelman's syndrome (GS) is an autosomal recessive renal tubular disorder caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Despite meticulous sequencing of genomic DNA, approximately one-third of GS patients are negative or heterozygotes for the known mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Because blood leukocytes express NCC mRNA, we evaluate whether deep intronic mutations contribute to GS patients with uniallelic or undetectable SLC12A3 mutations. Twenty-nine patients with GS (men/women = 16/13), including eight negative and 21 uniallelic SLC12A3 mutations from 19 unrelated families, and normal controls were enrolled in an academic medical center. Analysis of cDNA from blood leukocytes, sequencing of the corresponding introns of genomic DNA for abnormal transcript, and analysis of NCC protein expression from renal biopsy were performed. RESULTS: We identified nine Taiwan aboriginal patients carrying c.1670-191CâT mutations in intron 13 and 10 nonaboriginal patients carrying c.2548+253CâT mutations in intron 21 from 14 families (14/19). These two mutations undetected in 100 healthy subjects created pseudoexons containing new premature termination codons. Haplotype analysis with markers flanking SLC12A3 revealed that both mutations did not have founder effects. Apical NCC expression in the DCT of renal tissue was markedly diminished in two patients carrying deep intronic mutations. CONCLUSIONS: Deep intronic mutations in SLC12A3 causing defective NCC expression can be identified with the RNA-based approach in patients with GS. c.1670-191CâT and c.2548+253CâT are hot spot mutations that can be screened in GS patients with uniallelic or negative SLC12A3 mutations.