Development and characterization of an implantable biosensor for telemetric monitoring of ethanol in the brain of freely moving rats

Ethanol is one of the most widespread psychotropic agents in western society. While its psychoactive effects are mainly associated with GABAergic and glutamatergic systems, the positive reinforcing properties of ethanol are related to activation of mesolimbic dopaminergic pathways resulting in a release of dopamine in the nucleus accumbens. Given these neurobiological implications, the detection of ethanol in brain extracellular fluid (ECF) is of great importance. In this study, we describe the development and characterization of an implantable biosensor for the amperometric detection of brain ethanol in real time. Ten different designs were characterized in vitro in terms of Michaelis-Menten kinetics (V(MAX) and K(M)), sensitivity (linear region slope, limit of detection (LOD), and limit of quantification (LOQ)), and electroactive interference blocking. The same parameters were monitored in selected designs up to 28 days after fabrication in order to quantify their stability. Finally, the best performing biosensor design was selected for implantation in the nucleus accumbens and coupled with a previously developed telemetric device for the real-time monitoring of ethanol in freely moving, untethered rats. Ethanol was then administered systemically to animals, either alone or in combination with ranitidine (an alcohol dehydrogenase inhibitor) while the biosensor signal was continuously recorded. The implanted biosensor, integrated in the low-cost telemetry system, was demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in brain ECF and represents a new generation of analytical tools for studying ethanol toxicokinetics and the effect of drugs on brain ethanol levels.     

Quantifying the dielectric constant of thick insulators by electrostatic force microscopy: effects of the microscopic parts of the probe

We present a systematic analysis of the effects that the microscopic parts of electrostatic force microscopy probes (the cone and cantilever) have on the electrostatic interaction between the tip apex and thick insulating substrates (thickness > 100 μm). We discuss how these effects can influence the measurement and quantification of the local dielectric constant of the substrates. We propose and experimentally validate a general methodology that takes into account the influence of the cone and the cantilever, thus enabling us to obtain very accurate values of the dielectric constants of thick insulators.     

Label-free identification of single dielectric nanoparticles and viruses with ultraweak polarization forces

Label-free detection of the material composition of nanoparticles could be enabled by the quantification of the nanoparticles' inherent dielectric response to an applied electric field. However, the sensitivity of dielectric nanoscale objects to geometric and non-local effects makes the dielectric response extremely weak. Here we show that electrostatic force microscopy with sub-piconewton resolution can resolve the dielectric constants of single dielectric nanoparticles without the need for any reference material, as well as distinguish nanoparticles that have an identical surface but different inner composition. We unambiguously identified unlabelled ~10 nm nanoparticles of similar morphology but different low-polarizable materials, and discriminated empty from DNA-containing virus capsids. Our approach should make the in situ characterization of nanoscale dielectrics and biological macromolecules possible.     

Evaluation of Epigenetic and Radiomodifying Effects during Radiotherapy Treatments in Zebrafish

Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful for some patients may be relatively ineffective for others. Based on this, radiobiological research is focusing on the ability of some reagents to make cancer cells more responsive to ionizing radiation, as well as to protect the surrounding healthy tissues from possible side effects. In this scenario, zebrafish emerged as an effective model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. The adoption of this experimental organism is fully justified and supported by the high similarity between fish and humans in both their genome sequences and the effects provoked in them by ionizing radiation. This review aims to provide the literature state of the art of zebrafish in vivo model for radiobiological studies, particularly focusing on the epigenetic and radiomodifying effects produced during fish embryos’ and larvae’s exposure to radiotherapy treatments.     

The multi-hop multi-rate wavelength division multiplexing ring

Transparency of the optical layer offers the possibility to design a network that operates at varying transmission bit rates. While variable bit rate interfaces are being tested and will soon provide the possibility to optimally select the transmission rate for each optical channel, the potential advantages of relying upon multiple transmission rates in the optical network have yet to be fully explored. In this paper, we define the concept of multi-hop and multi-rate (M&M for short) network in which the tributary signal is transmitted over a concatenation of optical channels, with each optical channel operating at its own transmission rate. The optimal rate of each optical channel is determined by a number of factors including the end node's interface, amount of multiplexed traffic and cost of the network components. The potential advantages provided by the M&M network when compared to first generation optical networks (i.e., SONET/SDH), to single- and multi-hop (constant bit rate) optical networks, are discussed in general and demonstrated numerically in a WDM ring. Presented results show that the network cost reduction achieved by the M&M design is a function of the cost ratio between the optical bandwidth (wavelengths) and the optical terminals     

Light‐Induced Surface Modification of Natural Plant Microparticles: Toward Colloidal Science and Cellular Adhesion Applications

Playing an instrumental role in the life of plants, pollen microparticles are one of the most fascinating biological materials in existence, with abundant and renewable supply, ultrahigh durability, and unique, species‐specific architectural features. Aside from their biological role, pollen microparticles also demonstrate broad utility as functional materials for drug delivery and microencapsulation, and increasingly for emulsion‐type applications. As natural pollen microparticles are predominantly hydrophobic, developing robust surface functionalization strategies to increase surface hydrophilicity would increase the range of colloidal science applications, including opening the door to interfacing microparticles with biological cells. This research investigates the extraction and light‐induced surface modification of discrete pollen microparticles from bee‐collected pollen granules toward achieving functional control over the responses elicited from discrete particles in colloidal science and cellular applications. Ultraviolet–ozone treatment is shown to increase the proportion of surface elemental oxygen and ketones, leading to increased surface hydrophilicity, enhanced particle dispersibility, tunable control over Pickering emulsion characteristics, and enhanced cellular adhesion. In summary, the findings demonstrate that light‐induced surface modification improves the functional properties of pollen microparticles, and such insights also have broad implications across materials science and environmental science applications.     

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways’ genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells’ differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells’ phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future.