Multifunctional Magnetic-fluorescent Nanocomposites for Biomedical Applications

Nanotechnology is a fast-growing area, involving the fabrication and use of nano-sized materials and devices. Various nanocomposite materials play a number of important roles in modern science and technology. Magnetic and fluorescent inorganic nanoparticles are of particular importance due to their broad range of potential applications. It is expected that the combination of magnetic and fluorescent properties in one nanocomposite would enable the engineering of unique multifunctional nanoscale devices, which could be manipulated using external magnetic fields. The aim of this review is to present an overview of bimodal “two-in-one” magnetic-fluorescent nanocomposite materials which combine both magnetic and fluorescent properties in one entity, in particular those with potential applications in biotechnology and nanomedicine. There is a great necessity for the development of these multifunctional nanocomposites, but there are some difficulties and challenges to overcome in their fabrication such as quenching of the fluorescent entity by the magnetic core. Fluorescent-magnetic nanocomposites include a variety of materials including silica-based, dye-functionalised magnetic nanoparticles and quantum dots-magnetic nanoparticle composites. The classification and main synthesis strategies, along with approaches for the fabrication of fluorescent-magnetic nanocomposites, are considered. The current and potential biomedical uses, including biological imaging, cell tracking, magnetic bioseparation, nanomedicine and bio- and chemo-sensoring, of magnetic-fluorescent nanocomposites are also discussed

Turbiditic trench deposits at the South-Chilean active margin: A PleistoceneHolocene record of climate and tectonics

The active plate margin of South America is characterized by a frequent occurrence of large and devastating subduction earthquakes. Here we focus on marine sedimentary records off Southern Chile that are archiving the regional paleoseismic history over the Holocene and Late Pleistocene. The investigated records - Ocean Drilling Program (ODP) Site 1232 and SONNE core 50SL - are located at similar to 40 degrees S and similar to 38 degrees S, within the Peru-Chilc trench, and are characterized by frequent interbedded strata of turbiditic and hemipelagic origin. On the basis of the sedimentological characteristics and the association with the active margin of Southern Chile, we assume that the turbidites are mainly scismically triggered, and may be considered as paleo-megaearthquake indicators. However, the long-term changes in turbidite recurrence times appear to be strongly influenced by climate and sea level changes as well. During sea level highstands in the Holocene and Marine Isotope Stage (MIS) 5, recurrence times of turbiditic layers are substantially higher, primarily reflecting a climate-induced reduction of sediment availability and enhanced slope stability. In addition, segmented tectonic uplift changes and related drainage inversions likely influenced the postglacial decrease in turbidite frequencies. Glacial turbidite recurrence times (including MIS 2, MIS 3, cold substages of MIS 5, and MIS 6), on the other hand, are within the same order of magnitude as earthquake recurrence times derived from the historical record and other terrestrial paleoseismic archives of the region. Only during these cold stages sediment availability and slope instability were high enough to enable recording of the complete sequence of large earthquakes in Southern Chile. Our data thus suggest that earthquake recurrence times on the order of 100 to 200 years are a persistent feature at least during the last glacial period

Smad4 expression in gastric adenoma and adenocarcinoma: Frequent loss of expression in diffuse type of gastric adenocarcinoma

Smads are signal transducers for the members of the TGF-ß superfamily. Of these Smads, Smad4 is essential for TGF-ß signaling. The purpose of this study was to elucidate Smad4 expression and localization in 65 gastric adenomas, 49 intestinal-type and 39 diffuse type of gastric adenocarcinomas (including 12 cases of fresh frozen tissue) using Realtime RT-PCR and immunohistochemistry. Real-time RTPCR showed that intestinal type gastric adenocarcinomas have higher Smad4 mRNA expression than diffuse type gastric adenocarcinomas. Immunohistochemical stain for Smad4 revealed that expression of Smad4 was significantly lower in diffusetype gastric adenocarcinoma than intestinal-type gastric adenocarcinomas. Also, higher Smad4 protein expression in intestinal type gastric adenocarcinomas than overall gastric adenoma was noted. The rate of reduced Smad4 expression was higher in advanced gastric cancer than early gastric cancer. These results suggest that Smad4 might play different roles in human gastric carcinogenesis, especially between intestinal type and diffuse type of gastric adenocarcinoma

Expression of beta-catenin and its mechanism of delocalization in intestinal-type early gastric cancer based on mucin expression

The biological characteristics of intestinaltype early gastric cancers (ICs) differ based on mucin phenotypes. Beta-catenin delocalization is a predictive marker of aggressive biological behavior (submucosal invasion and lymph node metastasis) of ICs. The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes. Therefore, in the current study, the expression and mechanisms of delocalization of betacatenin were elucidated on the basis of mucin phenotypes in 109 cases of ICs. There was increased cytoplasmic and nuclear beta-catenin expression (delocalization) in ICs with a predominant intestinal mucin phenotype (ICIP; 46.3% [25/54 cases]) compared to ICs with a predominant gastric mucin phenotype (ICGP; 20% [11/55 cases]). There were no beta-catenin or APC mutations in ICs. APC promoter hypermethylation was present in 49 of 105 (46.7%) cases of ICs. There was a significant relationship between APC promoter hypermethylation and betacatenin delocalization in ICs, especially in ICIPs. There was no relationship between beta-catenin delocalization and APC gene loss of heterozygosity in ICs. In conclusion, we showed that beta-catenin delocalization was more evident in ICIPs, and APC promoter hypermethylation might play a role in delocalization of beta-catenin, especially in ICIPs

Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction

OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy. METHODS: We performed behavioral analyses on Cyfip2+/- mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses on Cyfip2+/- prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with viral injections. RESULTS: Adult Cyfip2+/- mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2+/- PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2+/- mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability of Cyfip2+/- L5 neurons. RNA-sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2+/- PFC. Viral-mediated CYFIP2 reduction in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior. INTERPRETATION: These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and lithium-mediated amelioration of neurobehavioral phenotypes in adult Cyfip2+/- mice, which can be implicated in CYFIP2-associated brain disorders. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.11Nsciescopu