RESUMO
The chirality of nanoparticles (NPs) and their assemblies has been investigated predominantly for noble metals and II-VI semiconductors. However, ceramic NPs represent the majority of nanoscale materials in nature. The robustness and other innate properties of ceramics offer technological opportunities in catalysis, biomedical sciences, and optics. Here we report the preparation of chiral ceramic NPs, as represented by tungsten oxide hydrate, WO3-x·H2O, dispersed in ethanol. The chirality of the metal oxide core, with an average size of ca. 1.6 nm, is imparted by proline (Pro) and aspartic acid (Asp) ligands via bio-to-nano chirality transfer. The amino acids are attached to the NP surface through C-O-W linkages formed from dissociated carboxyl groups and through amino groups weakly coordinated to the NP surface. Surprisingly, the dominant circular dichroism bands for NPs coated by Pro and Asp are different despite the similarity in the geometry of the NPs; they are positioned at 400-700 nm and 500-1100 nm for Pro- and Asp-modified NPs, respectively. The differences in the spectral positions of the main chiroptical band for the two types of NPs are associated with the molecular binding of the two amino acids to the NP surface; Asp has one additional C-O-W linkage compared to Pro, resulting in stronger distortion of the inorganic crystal lattice and greater intensity of CD bands associated with the chirality of the inorganic core. The chirality of WO3-x·H2O atomic structure is confirmed by atomistic molecular dynamics simulations. The proximity of the amino acids to the mineral surface is associated with the catalytic abilities of WO3-x·H2O NPs. We found that NPs facilitate formation of peptide bonds, leading to Asp-Asp and Asp-Pro dipeptides. The chiroptical activity, chemical reactivity, and biocompatibility of tungsten oxide create a unique combination of properties relevant to chiral optics, chemical technologies, and biomedicine.
Assuntos
Cerâmica/química , Nanopartículas/química , Peptídeos/química , Catálise , Tamanho da PartículaRESUMO
Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
Assuntos
Modelos Animais de Doenças , Síndrome de Job/imunologia , Mutação/imunologia , Fator de Transcrição STAT3/imunologia , Animais , Transplante de Medula Óssea , Células Cultivadas , Citrobacter rodentium/imunologia , Citrobacter rodentium/fisiologia , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Citometria de Fluxo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Síndrome de Job/genética , Síndrome de Job/cirurgia , Lipopolissacarídeos , Camundongos , Camundongos Transgênicos , Mutação/genética , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/genética , Choque Séptico/induzido quimicamente , Choque Séptico/genética , Choque Séptico/imunologia , Análise de Sobrevida , Transcriptoma/genética , Transcriptoma/imunologiaRESUMO
Intracytoplasmic sperm injection (ICSI) was originally designed to overcome barriers due to male factor infertility. However, a surveillance study found that ICSI use in non-male factor infertility increased from 15.4% to 66.9% between 1996 and 2012. Numerous studies have investigated fertilization rate, total fertilization failure, and live birth rate per cycle (LBR), comparing the use of ICSI versus conventional in vitro fertilization (IVF) for non-male factor infertility. The overwhelming conclusion shows no increase in fertilization rate or LBR per cycle with the use of ICSI for non-male factor infertility. The overuse of ICSI is likely related to the desire to avoid a higher rate of total fertilization failure in IVF. However, data supporting the benefit of using ICSI for non-male factor infertility is lacking, and 33 couples would need to be treated with ICSI unnecessarily to avoid one case of total fertilization failure. Such practice increases the cost to the patient, increases the burden on embryologist's time, and is a misapplication of resources. Additionally, there remains conflicting data regarding the safety of offspring conceived by ICSI and potential damage to the oocyte. Thus, the use of ICSI should be limited to those with male factor infertility or a history of total fertilization factor infertility due to uncertainties of potential adverse impact and lack of proven benefit in non-male factor infertility.
RESUMO
OBJECT: Intracranial monitoring for epilepsy has been proven to enhance diagnostic accuracy and provide localizing information for surgical treatment of intractable seizures. The authors investigated the usefulness of hippocampal depth electrodes in the era of more advanced imaging techniques. METHODS: Between 1988 and 2010, 100 patients underwent occipitotemporal hippocampal depth electrode (OHDE) implantation as part of invasive seizure monitoring, and their charts were retrospectively reviewed. The authors' technique involved the stereotactically guided (using the Leksell model G frame) implantation of a 12-contact depth electrode directed along the long axis of the hippocampus, through an occipital twist drill hole. RESULTS: Of the 100 patients (mean age 35.0 years [range 13-58 years], 51% male) who underwent intracranial investigation, 84 underwent resection of the seizure focus. Magnetic resonance imaging revealed mesial temporal sclerosis (MTS) in 27% of patients, showed abnormal findings without MTS in 55% of patients, and showed normal findings in 18% of patients. One patient developed a small asymptomatic occipital hemorrhage around the electrode tract. The use of OHDEs enabled epilepsy resection in 45.7% of patients who eventually underwent standard or selective temporal lobe resection. The hippocampal formation was spared during surgery because data obtained from the depth electrodes showed no or only secondary involvement in 14% of patients with preoperative temporal localization. The use of OHDEs prevented resections in 12% of patients with radiographic evidence of MTS. Eighty-three percent of patients who underwent resection had Engel Class I (68%) or II (15%) outcome at 2 years of follow-up. CONCLUSIONS: The use of OHDEs for intracranial epilepsy monitoring has a favorable risk profile, and in the authors' experience it proved to be a valuable component of intracranial investigation. The use of OHDEs can provide the sole evidence for resection of some epileptogenic foci and can also result in hippocampal sparing or prevent likely unsuccessful resection in other patients.