Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.

Circulating tumor cells (CTCs) disseminated into peripheral blood from a primary, or metastatic, tumor can be used for early detection, diagnosis and monitoring of solid malignancies. CTC isolation by size exclusion techniques have long interested researchers as a simple broad based approach, which is methodologically diverse for use in both genomic and protein detection platforms. Though a variety of these microfiltration systems are employed academically and commercially, the limited ability to easily alter microfilter designs has hindered the optimization for CTC capture. To overcome this problem, we studied a unique photo-definable material with a scalable and mass producible photolithographic fabrication method. We use this fabrication method to systematically study and optimize the parameters necessary for CTC isolation using a microfiltration approach, followed by a comparison to a “standard” filtration membrane. We demonstrate that properly designed microfilters can capture MCF-7 cancer cells at rate of 98 ± 2% if they consist of uniform patterned distributions, ≥160 000 pores, and 7 μm pore diameters.

Silica "nanobubbles" are hollow spheres of silica that can be used as nanometer-sized containers for probe molecules. A method for the encapsulation of a fluorescent molecule into silica "nanobubbles" is reported. Fluorescein isothiocyanate (FITC) dye molecules were coadsorbed onto the surface of gold nanoparticles with 3-aminopropyltrimethoxysilane. Following silica condensation, and dissolution of the gold core, the fluorescent molecules remain inside the water-filled, but sealed, silica nanoparticle. The plasmon band of the gold particles and the absorption and fluorescence spectra of the dye are affected by adsorption of the molecule on the gold particle. Encapsulation in the silica nanobubble insulates the dye molecule from the external environment. Analogous methods can be applied to a wide range of probes.

The effects of surface modification of nanocrystalline titanium dioxide (TiO 2 ) with specific chelating agents on photocatalytic degradation of nitrobenzene (NB) was investigated in order to design a selective and effective catalyst for removal of nitroaromatic compounds from contaminated waste streams. Mechanisms of NB adsorption and photodecomposition were investigated using infrared absorption and electron paramagnetic resonance spectroscopy. Liquid chromatography and gas chromatography/mass spectrometry were used for byproduct analyses. Arginine, lauryl sulfate, and salicylic acid were found to bind to TiO 2 via their oxygen-containing functional groups. Modification of the TiO 2 surface with arginine resulted in enhanced NB adsorption and photodecomposition, and compared to unmodified TiO 2 . The initial quantum yield for photodegradation of NB in this system was found to be Φ init ) 0.31 as compared to the one obtained for Degussa P25 of Φ init ) 0.18. NB degradation followed a reductive pathway over arginine-modified TiO 2 and was enhanced upon addition of methanol. No degradation of arginine was detected under the experimental conditions. Arginine improved the coupling between NB and TiO 2 and facilitated the transfer of photogenerated electrons from the TiO 2 conduction band to the adsorbed NB. These results indicate that surface modification of nanocrystalline TiO 2 with electron-donating chelating agents is an effective route to enhance photodecomposition of nitroaromatic compounds.

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Enumeration of circulating tumor cells (CTCs) from cancer patient blood is an established diagnostic assay used to evaluate patient status as a singleplex test. However, in the coming age of personalized medicine, multiplex analysis of patient CTCs, including proteomic and genomic techniques, will have to be integrated with CTC isolation platform technologies. Advancements in microfabrication have demonstrated that CTCs can be isolated and analyzed using microfluidic lab-on-a-chip devices. However, to date, most microfluidic devices are either still in the development phase, not applicable to all clinical tests, or are not commercially available. To overcome these discrepancies, we describe an all-in-one device for the isolation and multiplexing of clinically applicable CTC assays. Microfilters present an ideal lab-on-a-chip platform for analysis of CTCs as non-toxic and inert materials allow for a multitude of tests from cell growth through clinical staining techniques, all without background interference. Lithographically fabricated microfilters, can be made with high porosity, precise pore dimensions, arrayed pore distribution, and optimized for CTC size-based isolation. In this study we describe microfilter use in isolation and in situ analysis of CTCs using multiple sequential techniques including culture, FISH, histopathological analysis, H&E staining, photobleaching and re-staining. Further, as a proof of principle, we then describe the ability to quantitatively release patient derived CTCS from the microfilters for potential use in downstream genomic/proteomic analysis.

Adsorption and photocatalytic degradation of nitrobenzene (NB) in the presence and absence of phenol (Ph) over UV-illuminated arginine-modified TiO2 colloids have been investigated by infrared absorption, electron paramagnetic resonance spectroscopy, and X-ray absorption spectroscopy. High performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry were used for monitoring degradation conversion rates and byproduct identification. It was found that photodegradation of NB and Ph strongly depends on the nature of the TiO2 surface. Through the use of the HPLC peak area ratio before and after illumination, the photocatalytic decomposition rate of NB and Ph individually using bare TiO2 is nearly identical (1.7 and 1.5, respectively) and occurs via oxidative mechanism. Through the use of arginine-modified TiO2 nanoparticles, a three-fold increase in the NB decomposition rate is observed while no Ph decomposition is observed. Furthermore, the degradation pathway using the arginine-modified photocatalyst is completely altered to a reductive mechanism, providing a more efficient means to degrade nitrocompounds that are already in a highly oxidized state and limiting the number of byproduct. These results indicate that a critical parameter in the photocatalytic decomposition of NB and Ph is their specific adsorption and coupling to the TiO2 surface. Modification of the TiO2 particle surface with chelating agents demonstrates enhanced interaction with the desired target contaminant to impart selectivity to photocatalysis.

Rituximab, an anti CD20 monoclonal antibody, is widely used in the treatment of B-cell malignancies in adults and increasingly in pediatric patients. By depleting B-cells, rituximab interferes with humoral immunity. This review provides a comprehensive overview of immune reconstitution and infectious complications after rituximab treatment in children and adolescents. Immune reconstitution starts usually after six months with recovery to normal between nine to twelve months. Extended rituximab treatment results in a prolonged recovery of B-cells without an increase of clinically relevant infections. The kinetic of B-cell recovery is influenced by the concomitant chemotherapy and the underlying disease. Intensive B-NHL treatment such as high-dose chemotherapy followed by rituximab bears a risk for prolonged hypogammaglobulinemia. Overall transient alteration of immune reconstitution and infections after rituximab treatment are acceptable for children and adolescent without significant differences compared to adults. However, age related disparities in the kinetic of immune reconstitution and the definitive role of rituximab in the treatment for children and adolescents with B-cell malignancies need to be evaluated in prospective controlled clinical trials.