Low-energy excitations in the S=(1/2) molecular nanomagnet K6[V₁₅^IVAs6O42(H2O)]·8H2O from proton NMR and µSR

Zero- and longitudinal-field muon-spin-rotation (µSR) and 1H NMR measurements on the S=(1/2) molecular nanomagnet K6[V15IVAs6O42(H2O)]·8H2O are presented. In LF experiments, the muon asymmetry P(t) was fitted by the sum of three different exponential components with fixed weights. The different muon relaxation rates lambdai (i=1,2,3) and the low-field H=0.23 T 1H NMR spin-lattice relaxation rate 1/T1 show a similar behavior for T>50 K: starting from room temperature they increase as the temperature is decreased. The increase of lambdai and 1/T1 can be attributed to the "condensation" of the system toward the lowest-lying energy levels. The gap Delta~550 K between the first and second S=(3/2) excited states was determined experimentally. For T<2 K, the muon relaxation rates lambdai stay constant, independently of the field value H<=0.15 T. The behavior for T<2 K strongly suggests that, at low T, the spin fluctuations are not thermally driven but rather originate from quasielastic intramolecular or intermolecular magnetic interactions. We suggest that the very-low-temperature relaxation rates could be driven by energy exchanges between two almost degenerate S=(1/2) ground states and/or by quantum effects

Magnetic susceptibility and spin dynamics of a polyoxovanadate cluster: A proton NMR study of a model spin tetramer

We report susceptibility and nuclear magnetic resonance (NMR) measurements in a polyoxovanadate compound with formula (NHEt)3[VIV8VV4As8O40(H2O)]H2O = (V12). The magnetic properties can be described by considering only the central square of localized V4+ ions and treated by an isotropic Heisenberg Hamiltonian of four intrinsic spins 1/2 coupled by nearest-neighbor antiferromagnetic interaction with J17.6K. In this simplified description the ground state is nonmagnetic with ST = 0. The 1H NMR linewidth (full width at half maximum) data depend on both the magnetic field and temperature, and are explained by the dipolar interaction between proton nuclei and V4+ ion spins. The behavior of the nuclear spin-lattice relaxation rate T-11 in the temperature range (4.2–300 K) is similar to that of χT vs T and it does not show any peak at low temperatures contrary to previous observations in antiferromagnetic rings with larger intrinsic spins. The results are explained by using the general features of the Moriya formula and by introducing a single T-independent broadening parameter for the electronic spin system. From the exponential T dependence of T-11 at low T(2.5K < T < 4.2K) we have obtained a field dependent gap following the linear relation ΔNMR = Δ0 “ gπBH, with the gap Δ0 17.6K in agreement with the susceptibility data. Below 2.5 K the proton T-11 deviates from the exponential decrease indicating the presence of a small, almost temperature independent, but strongly field dependent, nuclear relaxation contribution, which we will investigate in detail in the near future. © 2004 American Physical Society

Preclinical and clinical evaluation of the liver tumor irreversible electroporation by magnetic resonance imaging

Irreversible electroporation (IRE) is a relatively new technique for tumor ablation. It has shown promising results in difficult cases where surgery is not recommended and delicate anatomic structures are present near or within the tumor. Currently, liver cancer is one of the most common targets for IRE treatment. Pre-operative and post-operative imaging has a key role in IRE procedures and research studies. Although ultrasound is usually the first choice, especially for intra-operative guidance, magnetic resonance imaging (MRI) plays an important role in the visualization and characterization of tumor before and after IRE in clinical and preclinical studies. However, the appearance of liver lesions after IRE with different MRI sequences has never been systematically investigated, and the most common practice is to limit the acquisition protocol to only contrast-enhanced T1-weighted images. In this work, the role of MRI in clinical and preclinical assessment of hepatic tumors treated with IRE is reviewed and discussed

Transcriptome analysis of haploid male gametophyte development in Arabidopsis

BACKGROUND: The haploid male gametophyte generation of flowering plants consists of two- or three-celled pollen grains. This functional specialization is thought to be a key factor in the evolutionary success of flowering plants. Moreover, pollen ontogeny is also an attractive model in which to dissect cellular networks that control cell growth, asymmetric cell division and cellular differentiation. Our objective, and an essential step towards the detailed understanding of these processes, was to comprehensively define the male haploid transcriptome throughout development. RESULTS: We have developed staged spore isolation procedures for Arabidopsis and used Affymetrix ATH1 genome arrays to identify a total of 13,977 male gametophyte-expressed mRNAs, 9.7% of which were male-gametophyte-specific. The transition from bicellular to tricellular pollen was accompanied by a decline in the number of diverse mRNA species and an increase in the proportion of male gametophyte-specific transcripts. Expression profiles of regulatory proteins and distinct clusters of coexpressed genes were identified that could correspond to components of gametophytic regulatory networks. Moreover, integration of transcriptome and experimental data revealed the early synthesis of translation factors and their requirement to support pollen tube growth. CONCLUSIONS: The progression from proliferating microspores to terminally differentiated pollen is characterized by large-scale repression of early program genes and the activation of a unique late gene-expression program in maturing pollen. These data provide a quantum increase in knowledge concerning gametophytic transcription and lay the foundations for new genomic-led studies of the regulatory networks and cellular functions that operate to specify male gametophyte development

Diffusion Mri Biomarkers Predict the Outcome O Irreversible Electroporation in a Pancreatic Tumor Mouse Model

The purpose of this work is to explore the potential contribution of diffusion MRI to predict the effects of irreversible electroporation (IRE) in a pancreatic ductal adenocarcinoma (PDAC) mouse model. Thirteen mice were injected with Panc-02 PDAC cells in both flanks. One tumor was treated with IRE when it reached a diameter of about 5 mm. T2- and diffusion-weighted MRI sequences were acquired before IRE treatment and 1, 3 and 7 days later. The mice were euthanized 1 day (n = 6) or 2 weeks (n = 7) after treatment. The tumors were excised and stained with H&E, caspase-3, CD-3, F4/80. The volume and the mean and standard deviation of the apparent diffusion coefficient (ADC) were compared between treated and untreated lesions and correlated with histology-derived measures. At 1-day post-treatment, a dramatic ADC increase (+50.81%, P <0.05) was found in ablated lesions, strongly correlated with apoptosis (τ = 0.90). At later time points the ADC returned to pre-treatment values, though histopathology showed a quite different scenario compared to the untreated controls. The ADC standard deviation measured within the treated tumors 1 day after IRE treatment had a strong negative correlation with the number of tumor cells found 14 days later (τ = 0.80). There was also a strong correlation between 1-day ADC and 14-day apoptosis in untreated tumors (τ = 0.95). In conclusion, diffusion MRI is sensitive to the short-term effects of IRE in PDAC tumors, and can help predict the long-term treatment outcome

A phase I study of the nitroimidazole hypoxia marker SR4554 using 19F magnetic resonance spectroscopy

SR4554 is a fluorine-containing 2-nitroimidazole, designed as a hypoxia marker detectable with 19F magnetic resonance spectroscopy (MRS). In an initial phase I study of SR4554, nausea/vomiting was found to be dose-limiting, and 1400 mg m−2 was established as MTD. Preliminary MRS studies demonstrated some evidence of 19F retention in tumour. In this study we investigated higher doses of SR4554 and intratumoral localisation of the 19F MRS signal. Patients had tumours 3 cm in diameter and 4 cm deep. Measurements were performed using 1H/19F surface coils and localised 19F MRS acquisition. SR4554 was administered at 1400 mg m−2, with subsequent increase to 2600 mg m−2 using prophylactic metoclopramide. Spectra were obtained immediately post infusion (MRS no. 1), at 16 h (MRS no. 2) and 20 h (MRS no. 3), based on the SR4554 half-life of 3.5 h determined from a previous study. 19Fluorine retention index (%) was defined as (MRS no. 2/MRS no. 1)*100. A total of 26 patients enrolled at: 1400 (n=16), 1800 (n=1), 2200 (n=1) and 2600 mg m−2 (n=8). SR4554 was well tolerated and toxicities were all grade 1; mean plasma elimination half-life was 3.7±0.9 h. SR4554 signal was seen on both unlocalised and localised MRS no. 1 in all patients. Localised 19F signals were detected at MRS no. 2 in 5 out of 9 patients and 4 out of 5 patients at MRS no. 3. The mean retention index in tumour was 13.6 (range 0.6-43.7) compared with 4.1 (range 0.6-7.3) for plasma samples taken at the same times (P=0.001) suggesting 19F retention in tumour and, therefore, the presence of hypoxia. We have demonstrated the feasibility of using 19F MRS with SR4554 as a potential method of detecting hypoxia. Certain patients showed evidence of 19F retention in tumour, supporting further development of this technique for detection of tumour hypoxia

Molecular Foundations of Reproductive Lethality in Arabidopsis thaliana

The SeedGenes database (www.seedgenes.org) contains information on more than 400 genes required for embryo development in Arabidopsis. Many of these EMBRYO-DEFECTIVE (EMB) genes encode proteins with an essential function required throughout the life cycle. This raises a fundamental question. Why does elimination of an essential gene in Arabidopsis often result in embryo lethality rather than gametophyte lethality? In other words, how do mutant (emb) gametophytes survive and participate in fertilization when an essential cellular function is disrupted? Furthermore, why do some mutant embryos proceed further in development than others? To address these questions, we first established a curated dataset of genes required for gametophyte development in Arabidopsis based on information extracted from the literature. This provided a basis for comparison with EMB genes obtained from the SeedGenes dataset. We also identified genes that exhibited both embryo and gametophyte defects when disrupted by a loss-of-function mutation. We then evaluated the relationship between mutant phenotype, gene redundancy, mutant allele strength, gene expression pattern, protein function, and intracellular protein localization to determine what factors influence the phenotypes of lethal mutants in Arabidopsis. After removing cases where continued development potentially resulted from gene redundancy or residual function of a weak mutant allele, we identified numerous examples of viable mutant (emb) gametophytes that required further explanation. We propose that the presence of gene products derived from transcription in diploid (heterozygous) sporocytes often enables mutant gametophytes to survive the loss of an essential gene in Arabidopsis. Whether gene disruption results in embryo or gametophyte lethality therefore depends in part on the ability of residual, parental gene products to support gametophyte development. We also highlight here 70 preglobular embryo mutants with a zygotic pattern of inheritance, which provide valuable insights into the maternal-to-zygotic transition in Arabidopsis and the timing of paternal gene activation during embryo development

Penetration of the Stigma and Style Elicits a Novel Transcriptome in Pollen Tubes, Pointing to Genes Critical for Growth in a Pistil

Pollen tubes extend through pistil tissues and are guided to ovules where they release sperm for fertilization. Although pollen tubes can germinate and elongate in a synthetic medium, their trajectory is random and their growth rates are slower compared to growth in pistil tissues. Furthermore, interaction with the pistil renders pollen tubes competent to respond to guidance cues secreted by specialized cells within the ovule. The molecular basis for this potentiation of the pollen tube by the pistil remains uncharacterized. Using microarray analysis in Arabidopsis, we show that pollen tubes that have grown through stigma and style tissues of a pistil have a distinct gene expression profile and express a substantially larger fraction of the Arabidopsis genome than pollen grains or pollen tubes grown in vitro. Genes involved in signal transduction, transcription, and pollen tube growth are overrepresented in the subset of the Arabidopsis genome that is enriched in pistil-interacted pollen tubes, suggesting the possibility of a regulatory network that orchestrates gene expression as pollen tubes migrate through the pistil. Reverse genetic analysis of genes induced during pollen tube growth identified seven that had not previously been implicated in pollen tube growth. Two genes are required for pollen tube navigation through the pistil, and five genes are required for optimal pollen tube elongation in vitro. Our studies form the foundation for functional genomic analysis of the interactions between the pollen tube and the pistil, which is an excellent system for elucidation of novel modes of cell–cell interaction

Low-energy spin dynamics in the giant keplerate molecule {Mo72Fe30}: A muon spin relaxation and 1H NMR investigation

We present muon spin relaxation and H-1 NMR results on the magnetically frustrated keplerate molecule {Mo72Fe30}, aimed at studying the local spin dynamics as a function of temperature. We find that, in common with other molecular magnets, the relaxation spectrum of this material is characterized by a single dominating electronic correlation time tau. Experiments and theory show that tau has a thermally activated behavior with an activation gap of the order of the energy difference between the lowest-lying rotational bands in this material. This shows that, in the intermediate temperature range just above 1 K, the relaxation of the electronic spin system occurs via Orbach processes involving energy levels belonging to the two lowest-lying rotational bands. Our data thus provide an experimental estimate of the first interband gap