Fluoride-assisted detection of glutathione by surface Ce/Ce engineered nanoceria.

Nanoceria has evolved as a promising nanomaterial due to its unique enzyme-like properties, including excellent oxidase mimetic activity, which significantly increases in the presence of fluoride ions. However, this significant increase in oxidase activity has never been utilised as a signal enhancer for the detection of biological analytes partly because of the lack of understanding of the mechanism involved in this process. In this study, we show that the surface oxidation state of cerium ions plays a very crucial role in different enzymatic activities, especially the oxidase mimetic activity by engineering nanoceria with three different surface Ce/Ce compositions.

Tuning the enzyme-like activities of cerium oxide nanoparticles using a triethyl phosphite ligand.

Cerium oxide nanoparticles (CeNPs) exhibit excellent and antioxidant properties, determined by the redox switching of surface cerium ions between their two oxidation states (Ce and Ce). It is known that ligands such as triethyl phosphite (TEP) can tune the redox behavior of CeNPs and change their biological enzyme-mimetic activities; however, the corresponding mechanism for such a behavior is completely unknown. Herein, we have studied the effect of TEP in promoting the SOD-enzyme-like activity in CeNPs with high and low Ce/Ce ratio, which were synthesized by wet chemical and thermal hydrolysis methods, respectively, and incubated with varying concentrations of TEP.

Chemical bond imaging using torsional and flexural higher eigenmodes of qPlus sensors.

Non-contact atomic force microscopy (AFM) with CO-functionalized tips allows visualization of the chemical structure of adsorbed molecules and identify individual inter- and intramolecular bonds. This technique enables in-depth studies of on-surface reactions and self-assembly processes. Herein, we analyze the suitability of qPlus sensors, which are commonly used for such studies, for the application of modern multifrequency AFM techniques.

Experimental analysis of tip vibrations at higher eigenmodes of QPlus sensors for atomic force microscopy.

QPlus sensors are non-contact atomic force microscope probes constructed from a quartz tuning fork and a tungsten wire with an electrochemically etched tip. These probes are self-sensing and offer an atomic-scale spatial resolution. Therefore, qPlus sensors are routinely used to visualize the chemical structure of adsorbed organic molecules via the so-called bond imaging technique.

Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis.

Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205.

A review of demodulation techniques for multifrequency atomic force microscopy.

This article compares the performance of traditional and recently proposed demodulators for multifrequency atomic force microscopy. The compared methods include the lock-in amplifier, coherent demodulator, Kalman filter, Lyapunov filter, and direct-design demodulator. Each method is implemented on a field-programmable gate array (FPGA) with a sampling rate of 1.

Conditional knockout of SHP2 in ErbB2 transgenic mice or inhibition in HER2-amplified breast cancer cell lines blocks oncogene expression and tumorigenesis.

Overexpression of the human epidermal growth factor receptor 2 (HER2) is the cause of HER2-positive breast cancer (BC). Although HER2-inactivating therapies have benefited BC patients, development of resistance and disease recurrence have been the major clinical problems, pointing to a need for alternative therapeutic strategies. For that to happen, proteins that play critical roles in the biology of HER2-induced tumorigenesis have to be identified and characterized.

Multimodal atomic force microscopy with optimized higher eigenmode sensitivity using on-chip piezoelectric actuation and sensing.

Atomic force microscope (AFM) cantilevers with integrated actuation and sensing provide several distinct advantages over conventional cantilever instrumentation. These include clean frequency responses, the possibility of down-scaling and parallelization to cantilever arrays as well as the absence of optical interference. While cantilever microfabrication technology has continuously advanced over the years, the overall design has remained largely unchanged; a passive rectangular shaped cantilever design has been adopted as the industry wide standard.

Lyapunov estimation for high-speed demodulation in multifrequency atomic force microscopy.

An important issue in the emerging field of multifrequency atomic force microscopy (MF-AFM) is the accurate and fast demodulation of the cantilever-tip deflection signal. As this signal consists of multiple frequency components and noise processes, a lock-in amplifier is typically employed for its narrowband response. However, this demodulator suffers inherent bandwidth limitations as high-frequency mixing products must be filtered out and several must be operated in parallel.

A review of demodulation techniques for amplitude-modulation atomic force microscopy.

In this review paper, traditional and novel demodulation methods applicable to amplitude-modulation atomic force microscopy are implemented on a widely used digital processing system. As a crucial bandwidth-limiting component in the -axis feedback loop of an atomic force microscope, the purpose of the demodulator is to obtain estimates of amplitude and phase of the cantilever deflection signal in the presence of sensor noise or additional distinct frequency components. Specifically for modern multifrequency techniques, where higher harmonic and/or higher eigenmode contributions are present in the oscillation signal, the fidelity of the estimates obtained from some demodulation techniques is not guaranteed.

Note: Guaranteed collocated multimode control of an atomic force microscope cantilever using on-chip piezoelectric actuation and sensing.

The quality (Q) factor is an important parameter of the resonance of the microcantilever as it determines both imaging bandwidth and force sensitivity. The ability to control the Q factor of multiple modes is believed to be of great benefit for atomic force microscopy techniques involving multiple eigenmodes. In this paper, we propose a novel cantilever design employing multiple piezoelectric transducers which are used for separated actuation and sensing, leading to guaranteed collocation of the first eight eigenmodes up to 3 MHz.

Multimodal cantilevers with novel piezoelectric layer topology for sensitivity enhancement.

Self-sensing techniques for atomic force microscope (AFM) cantilevers have several advantageous characteristics compared to the optical beam deflection method. The possibility of down scaling, parallelization of cantilever arrays and the absence of optical interference associated imaging artifacts have led to an increased research interest in these methods. However, for multifrequency AFM, the optimization of the transducer layout on the cantilever for higher order modes has not been addressed.

High-bandwidth multimode self-sensing in bimodal atomic force microscopy.

Using standard microelectromechanical system (MEMS) processes to coat a microcantilever with a piezoelectric layer results in a versatile transducer with inherent self-sensing capabilities. For applications in multifrequency atomic force microscopy (MF-AFM), we illustrate that a single piezoelectric layer can be simultaneously used for multimode excitation and detection of the cantilever deflection. This is achieved by a charge sensor with a bandwidth of 10 MHz and dual feedthrough cancellation to recover the resonant modes that are heavily buried in feedthrough originating from the piezoelectric capacitance.

SOX9 inhibits β-TrCP-mediated protein degradation to promote nuclear GLI1 expression and cancer stem cell properties.

The high mobility group box protein SOX9 and the GLI1 transcription factor play protumorigenic roles in pancreatic ductal adenocarcinoma (PDA). In Kras transgenic mice, each of these factors are crucial for the development of PDA precursor lesions. SOX9 transcription is directly regulated by GLI1, but how SOX9 functions downstream of GLI1 is unclear.

KAP1 promotes proliferation and metastatic progression of breast cancer cells.

KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers.

MicroRNAs 206 and 21 cooperate to promote RAS-extracellular signal-regulated kinase signaling by suppressing the translation of RASA1 and SPRED1.

Despite the low prevalence of activating point mutation of RAS or RAF genes, the RAS-extracellular signal-regulated kinase (ERK) pathway is implicated in breast cancer pathogenesis. Indeed, in triple-negative breast cancer (TNBC), there is recurrent genetic alteration of pathway components. Using short hairpin RNA (shRNA) methods, we observed that the zinc finger transcription factor Krüppel-like factor 4 (KLF4) can promote RAS-ERK signaling in TNBC cells.

A novel self-sensing technique for tapping-mode atomic force microscopy.

This work proposes a novel self-sensing tapping-mode atomic force microscopy operation utilizing charge measurement. A microcantilever coated with a single piezoelectric layer is simultaneously used for actuation and deflection sensing. The cantilever can be batch fabricated with existing micro electro mechanical system processes.

Keratinocyte-targeted expression of human laminin γ2 rescues skin blistering and early lethality of laminin γ2 deficient mice.

Laminin-332 is a heterotrimeric basement membrane component comprised of the α3, ß3, and γ2 laminin chains. Laminin-332 modulates epithelial cell processes, such as adhesion, migration, and differentiation and is prominent in many embryonic and adult tissues. In skin, laminin-332 is secreted by keratinocytes and is a key component of hemidesmosomes connecting the keratinocytes to the underlying dermis.

A KLF4-miRNA-206 autoregulatory feedback loop can promote or inhibit protein translation depending upon cell context.

Krüppel-like factor 4 (KLF4), a transcription factor that regulates cell fate in a context-dependent fashion, is normally induced upon growth arrest or differentiation. In many cancer cells there is dysregulation, with increased expression in proliferating cells. To identify sequence elements that mediate KLF4 suppression in normal epithelial cells, we utilized a luciferase reporter and RK3E cells, which undergo a proliferation-differentiation switch to form an epithelial sheet.

Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling.

The transcription factors Notch1 and KLF4 specify epithelial cell fates and confer stem cell properties. Suggesting a functional relationship, each gene can act to promote or suppress tumorigenesis in a context-dependent manner, and alteration of KLF4 or Notch pathway genes in mice gives rise to similar phenotypes. Activation of a conditional allele of KLF4 in RK3E epithelial cells rapidly induces expression of Notch1 mRNA and the active, intracellular form of Notch1.

Prevention of KLF4-mediated tumor initiation and malignant transformation by UAB30 rexinoid.

The transcription factor KLF4 acts in post-mitotic epithelial cells to promote differentiation and functions in a context-dependent fashion as an oncogene. In the skin KLF4 is co-expressed with the nuclear receptors RARgamma and RXRalpha, and formation of the skin permeability barrier is a shared function of these three proteins. We utilized a KLF4-transgenic mouse model of skin cancer in combination with cultured epithelial cells to examine functional interactions between KLF4 and retinoic acid receptors.

Lack of efficacy of the statins atorvastatin and lovastatin in rodent mammary carcinogenesis.

The statins are highly effective in lowering cholesterol by inhibiting 3-hydroxy-3-methylglutaryl CoA reductase. Recently, there has been conflicting epidemiologic data indicating that statins decrease the incidence of certain types of cancer, including breast cancer. Atorvastatin and lovastatin, statins with different lipophicilities, were administered in diet either as single agents or in combination with suboptimal doses of tamoxifen or the retinoid X receptor agonist bexarotene were evaluated for prevention of estrogen receptor-positive mammary cancers induced in the rat with methylnitrosourea.