High-Throughput Omics Technologies: Potential Tools for the Investigation of Influences of EMF on Biological Systems

The mode of action of a huge amount of agents on biological systems is still unknown. One example where more questions than answers exist is covered by the term electromagnetic fields (EMF). Use of wireless communication, e.g. mobile phones, has been escalated in the last few years. Due to this fact, a lot of discussions dealt with health consequences of EMF emitted by these devices and led to an increased investigation of their effects to biological systems, mainly by using traditional methods. Omics technologies have the advantage to contain methods for investigations on DNA-, RNA- and protein level as well as changes in the metabolism

Fragmentation and systematics of the Pygmy Dipole Resonance in the stable N=82 isotones

The low-lying electric dipole (E1) strength in the semi-magic nucleus 136Xe has been measured which finalizes the systematic survey to investigate the so-called pygmy dipole resonance (PDR) in all stable even N=82 isotones with the method of nuclear resonance fluorescence using real photons in the entrance channel. In all cases, a fragmented resonance-like structure of E1 strength is observed in the energy region 5 MeV to 8 MeV. An analysis of the fragmentation of the strength reveals that the degree of fragmentation decreases towards the proton-deficient isotones while the total integrated strength increases indicating a dependence of the total strength on the neutron-to-proton ratio. The experimental results are compared to microscopic calculations within the quasi-particle phonon model (QPM). The calculation includes complex configurations of up to three phonons and is able to reproduce also the fragmentation of the E1 strength which allows to draw conclusions on the damping of the PDR. Calculations and experimental data are in good agreement in the degree of fragmentation and also in the integrated strength if the sensitivity limit of the experiments is taken into account

Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: data from a cohort study

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Since the introduction of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency in population newborn bloodspot screening (NBS) programs, subjects have been identified with variant <it>ACADM</it> (gene encoding MCAD enzyme) genotypes that have never been identified in clinically ascertained patients. It could be hypothesised that residual MCAD enzyme activity can contribute in risk stratification of subjects with variant <it>ACADM</it> genotypes.</p> <p><b>Methods</b></p> <p>We performed a retrospective cohort study of all patients identified upon population NBS for MCAD deficiency in the Netherlands between 2007–2010. Clinical, molecular, and enzymatic data were integrated.</p> <p><b>Results</b></p> <p>Eighty-four patients from 76 families were identified. Twenty-two percent of the subjects had a variant <it>ACADM</it> genotype. In patients with classical <it>ACADM</it> genotypes, residual MCAD enzyme activity was significantly lower (median 0%, range 0-8%) when compared to subjects with variant <it>ACADM</it> genotypes (range 0-63%; 4 cases with 0%, remainder 20-63%). Patients with (fatal) neonatal presentations before diagnosis displayed residual MCAD enzyme activities <1%. After diagnosis and initiation of treatment, residual MCAD enzyme activities <10% were associated with an increased risk of hypoglycaemia and carnitine supplementation. The prevalence of MCAD deficiency upon screening was 1/8,750 (95% CI 1/7,210–1/11,130).</p> <p><b>Conclusions</b></p> <p>Determination of residual MCAD enzyme activity improves our understanding of variant <it>ACADM</it> genotypes and may contribute to risk stratification. Subjects with variant <it>ACADM</it> genotypes and residual MCAD enzyme activities <10% should be considered to have the same risks as patients with classical <it>ACADM</it> genotypes. Parental instructions and an emergency regimen will remain principles of the treatment in any type of MCAD deficiency, as the effect of intercurrent illness on residual MCAD enzyme activity remains uncertain. There are, however, arguments in favour of abandoning the general advice to avoid prolonged fasting in subjects with variant <it>ACADM</it> genotypes and >10% residual MCAD enzyme activity.</p

Evolution of collectivity near mid-shell from excited-state lifetime measurements in rare earth nuclei

The B(E2) excitation strength of the first excited 2+ state in even-even nuclei should directly correlate with the size of the valence space and maximize at mid-shell. A previously found saturation of B(E2) strengths in well-deformed rotors at mid-shell is tested through high-precision measurements of the lifetimes of the lowest-lying 2+ states of the Hf168 and W174 rare earth isotopes. Measurements were performed using fast LaBr3 scintillation detectors. Combined with the recently remeasured B(E2;2+1→0+1) values for Hf and W isotopes the new data remove discrepancies observed in the differentials of B(E2) values for these isotope

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

Precise γ-ray intensity measurements in 10B

Precise electromagnetic transition matrix elements in 10Be and 10C have provided surprisingly stringent tests of modern ab initio calculations using realistic nuclear forces. The analog transition in 10B can further constrain these new calculations and probe the symmetry of the wave functions across the A=10 multiplet. We report on a careful measurement of the γ-ray intensities from states populated in the 10B(p,p) reaction at 10 MeV, including a determination of the key E2 branch from the J=2 T=1 state at 5164keV to the J=0 T=1 state at 1740keV of 0.16(4)%. \ua9 2012 American Physical Society

Identification of a Key Amino Acid of LuxS Involved in AI-2 Production in Campylobacter jejuni

Autoinducer-2 (AI-2) mediated quorum sensing has been associated with the expression of virulence factors in a number of pathogenic organisms and has been demonstrated to play a role in motility and cytolethal distending toxin (cdt) production in Campylobacter jejuni. We have initiated the work to determine the molecular basis of AI-2 synthesis and the biological functions of quorum sensing in C. jejuni. In this work, two naturally occurring variants of C. jejuni 81116 were identified, one producing high-levels of AI-2 while the other is defective in AI-2 synthesis. Sequence analysis revealed a G92D mutation in the luxS gene of the defective variant. Complementation of the AI-2− variant with a plasmid encoded copy of the wild-type luxS gene or reversion of the G92D mutation by site-directed mutagenesis fully restored AI-2 production by the variant. These results indicate that the G92D mutation alone is responsible for the loss of AI-2 activity in C. jejuni. Kinetic analyses showed that the G92D LuxS has a ∼100-fold reduced catalytic activity relative to the wild-type enzyme. Findings from this study identify a previously undescribed amino acid that is essential for AI-2 production by LuxS and provide a unique isogenic pair of naturally occurring variants for us to dissect the functions of AI-2 mediated quorum sensing in Campylobacter