Magnetoelastic Coupling and Delta-E Effect in Magnetoelectric Torsion Mode Resonators.

Magnetoelectric resonators have been studied for the detection of small amplitude and low frequency magnetic fields via the delta-E effect, mainly in fundamental bending or bulk resonance modes. Here, we present an experimental and theoretical investigation of magnetoelectric thin-film cantilevers that can be operated in bending modes (BMs) and torsion modes (TMs) as a magnetic field sensor. A magnetoelastic macrospin model is combined with an electromechanical finite element model and a general description of the delta-E effect of all stiffness tensor components Cij is derived. Simulations confirm quantitatively that the delta-E effect of the C66 component has the promising potential of significantly increasing the magnetic sensitivity and the maximum normalized frequency change Δfr. However, the electrical excitation of TMs remains challenging and is found to significantly diminish the gain in sensitivity. Experiments reveal the dependency of the sensitivity and Δfr of TMs on the mode number, which differs fundamentally from BMs and is well explained by our model. Because the contribution of C11 to the TMs increases with the mode number, the first-order TM yields the highest magnetic sensitivity. Overall, general insights are gained for the design of high-sensitivity delta-E effect sensors, as well as for frequency tunable devices based on the delta-E effect.

A single cytochrome P450 oxidase from Solanum habrochaites sequentially oxidizes 7-epi-zingiberene to derivatives toxic to whiteflies and various microorganisms.

Secretions from glandular trichomes potentially protect plants against a variety of aggressors. In the tomato clade of the Solanum genus, glandular trichomes of wild species produce a rich source of chemical diversity at the leaf surface. Previously, 7-epi-zingiberene produced in several accessions of Solanum habrochaites was found to confer resistance to whiteflies (Bemisia tabaci) and other insect pests. Here, we report the identification and characterisation of 9-hydroxy-zingiberene (9HZ) and 9-hydroxy-10,11-epoxyzingiberene (9H10epoZ), two derivatives of 7-epi-zingiberene produced in glandular trichomes of S. habrochaites LA2167. Using a combination of transcriptomics and genetics, we identified a gene coding for a cytochrome P450 oxygenase, ShCYP71D184, that is highly expressed in trichomes and co-segregates with the presence of the zingiberene derivatives. Transient expression assays in Nicotiana benthamiana showed that ShCYP71D184 carries out two successive oxidations to generate 9HZ and 9H10epoZ. Bioactivity assays showed that 9-hydroxy-10,11-epoxyzingiberene in particular exhibits substantial toxicity against B. tabaci and various microorganisms including Phytophthora infestans and Botrytis cinerea. Our work shows that trichome secretions from wild tomato species can provide protection against a wide variety of organisms. In addition, the availability of the genes encoding the enzymes for the pathway of 7-epi-zingiberene derivatives makes it possible to introduce this trait in cultivated tomato by precision breeding.

Spreading of Isolated Ptch Mutant Basal Cell Carcinoma Precursors Is Physiologically Suppressed and Counteracts Tumor Formation in Mice.

Basal cell carcinoma (BCC) originate from Hedgehog/Patched signaling-activated epidermal stem cells. However, the chemically induced tumorigenesis of mice with a CD4Cre-mediated biallelic loss of the Hedgehog signaling repressor Patched also induces BCC formation. Here, we identified the cellular origin of CD4Cre-targeted BCC progenitors as rare Keratin 5+ epidermal cells and show that wildtype Patched offspring of these cells spread over the hair follicle/skin complex with increasing mouse age. Intriguingly, Patched mutant counterparts are undetectable in age-matched untreated skin but are getting traceable upon applying the chemical tumorigenesis protocol. Together, our data show that biallelic Patched depletion in rare Keratin 5+ epidermal cells is not sufficient to drive BCC development, because the spread of these cells is physiologically suppressed. However, bypassing the repression of Patched mutant cells, e.g., by exogenous stimuli, leads to an accumulation of BCC precursor cells and, finally, to tumor development.

Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin tumor in humans. Although current therapies are sufficient to clear the tumor in many cases, the overall risk of cSCC metastasis is still 5%. Alternative treatment options could help to overcome this situation. Here we focused on the role of the Hedgehog (HH) signaling pathway and its interplay with epidermal growth factor receptor (EGFR) signaling in cSCC. The analyses revealed that, despite lack of Sonic HH (SHH) expression, a subset of human cSCC can express GLI1, a marker for active HH signaling, within distinct tumor areas. In contrast, all tumors strongly express EGFR and the hair follicle stem cell marker SOX9 at the highly proliferative tumor-stroma interface, whereas central tumor regions with a more differentiated stratum spinosum cell type lack both EGFR and SOX9 expression. In vitro experiments indicate that activation of EGFR signaling in the human cSCC cell lines SCL-1, MET-1, and MET-4 leads to GLI1 inhibition via the MEK/ERK axis without affecting cellular proliferation. Of note, EGFR activation also inhibits cellular migration of SCL-1 and MET-4 cells. Because proliferation and migration of the cells is also not altered by a GLI1 knockdown, GLI1 is apparently not involved in processes of aggressiveness in established cSCC tumors. In contrast, our data rather suggest a negative correlation between Gli1 expression level and cSCC formation because skin of Ptch +/- mice with slightly elevated Gli1 expression levels is significantly less susceptible to chemically-induced cSCC formation compared to murine wildtype skin. Although not yet formally validated, these data open the possibility that GLI1 (and thus HH signaling) may antagonize cSCC initiation and is not involved in cSCC aggressiveness, at least in a subset of cSCC.

Magnetic particle mapping using magnetoelectric sensors as an imaging modality.

Magnetic nanoparticles (MNPs) are a hot topic in the field of medical life sciences, as they are highly relevant in diagnostic applications. In this regard, a large variety of novel imaging methods for MNP in biological systems have been invented. In this proof-of-concept study, a new and novel technique is explored, called Magnetic Particle Mapping (MPM), using resonant magnetoelectric (ME) sensors for the detection of MNPs that could prove to be a cheap and efficient way to localize the magnetic nanoparticles. The simple and straightforward setup and measurement procedure includes the detection of higher harmonic excitations of MNP ensembles. We show the feasibility of this approach by building a measurement setup particularly suited to exploit the inherent sensor properties. We measure the magnetic response from 2D MNP distributions and reconstruct the distribution by solving the inverse problem. Furthermore, biological samples with magnetically labeled cells were measured and reconstruction of the distribution was compared with light microscope images. Measurement results suggest that the approach presented here is promising for MNP localization.

Wide Band Low Noise Love Wave Magnetic Field Sensor System.

We present a comprehensive study of a magnetic sensor system that benefits from a new technique to substantially increase the magnetoelastic coupling of surface acoustic waves (SAW). The device uses shear horizontal acoustic surface waves that are guided by a fused silica layer with an amorphous magnetostrictive FeCoSiB thin film on top. The velocity of these so-called Love waves follows the magnetoelastically-induced changes of the shear modulus according to the magnetic field present. The SAW sensor is operated in a delay line configuration at approximately 150 MHz and translates the magnetic field to a time delay and a related phase shift. The fundamentals of this sensor concept are motivated by magnetic and mechanical simulations. They are experimentally verified using customized low-noise readout electronics. With an extremely low magnetic noise level of ≈100 pT/[Formula: see text], a bandwidth of 50 kHz and a dynamic range of 120 dB, this magnetic field sensor system shows outstanding characteristics. A range of additional measures to further increase the sensitivity are investigated with simulations.

Isoprenoid and metabolite profiling of plant trichomes.

Plant glandular trichomes are specialized secretory structures located on the surface of the aerial parts of plants with large biosynthetic capacity, often with terpenoids as output molecules. The collection of plant trichomes requires a method to separate trichomes from leaf epidermal tissues. For metabolite profiling, trichome tissue needs to be rapidly quenched in order to maintain the indigenous state of intracellular intermediates. Appropriate extraction and chromatographic separation methods must be available, which address the wide-ranging polarity of metabolites. In this chapter, a protocol for trichome harvest using a frozen paint brush is presented. A work flow for broad-range metabolite profiling using LC-MS(2) analysis is described, which is applicable to assess very hydrophilic isoprenoid precursors as well as more hydrophobic metabolites from trichomes and other plant tissues.

DMBA/TPA treatment is necessary for BCC formation from patched deficient epidermal cells in Ptch(flox/flox)CD4Cre(+/-) mice.

The development of basal cell carcinoma (BCC), the most frequently diagnosed tumor among persons with European ancestry, is closely linked to mutations in the Hedgehog (Hh) receptor and tumor suppressor Patched1 (Ptch). Using Ptch(flox/flox)CD4Cre(+/-) mice, in which Ptch was ablated in CD4Cre-expressing cells, we demonstrate that the targeted cells can give rise to BCC after treatment with DMBA (7,12-dimethylbenz(a)anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate), but not after wounding of the skin. In addition, in this model, BCC are not caused by malfunctioning of Ptch-deficient T cells, as BCC did not develop when bone marrow (BM) of Ptch(flox/flox)CD4Cre(+/-) mice was transplanted into Ptch wild-type mice. Instead, lineage-tracing experiments and flow cytometric analyses suggest that the tumors are initiated from rare Ptch-deficient stem cell-like cells of the epidermis that express CD4. As DMBA/TPA is a prerequisite for BCC development in this model, the initiated cells need a second stimulus for expansion and tumor formation. However, in contrast to papilloma, this stimulus seems to be unrelated to alterations in the Ras signaling cascade. Together, these data suggest that biallelic loss of Ptch in CD4(+) cells does not suffice for BCC formation and that BCC formation requires a second so far unknown event, at least in the Ptch(flox/flox)CD4Cre(+/-) BCC mouse model.

An iron 13S-lipoxygenase with an α-linolenic acid specific hydroperoxidase activity from Fusarium oxysporum.

Jasmonates constitute a family of lipid-derived signaling molecules that are abundant in higher plants. The biosynthetic pathway leading to plant jasmonates is initiated by 13-lipoxygenase-catalyzed oxygenation of α-linolenic acid into its 13-hydroperoxide derivative. A number of plant pathogenic fungi (e.g. Fusarium oxysporum) are also capable of producing jasmonates, however, by a yet unknown biosynthetic pathway. In a search for lipoxygenase in F. oxysporum, a reverse genetic approach was used and one of two from the genome predicted lipoxygenases (FoxLOX) was cloned. The enzyme was heterologously expressed in E. coli, purified via affinity chromatography, and its reaction mechanism characterized. FoxLOX was found to be a non-heme iron lipoxygenase, which oxidizes C18-polyunsaturated fatty acids to 13S-hydroperoxy derivatives by an antarafacial reaction mechanism where the bis-allylic hydrogen abstraction is the rate-limiting step. With α-linolenic acid as substrate FoxLOX was found to exhibit a multifunctional activity, because the hydroperoxy derivatives formed are further converted to dihydroxy-, keto-, and epoxy alcohol derivatives.