Modulation sidebands spectra within inhomogeneous CW-EPR line detected by double modulation EPR spectroscopy.

Conventional modulation spectrum, MS, in continuous wave electron paramagnetic resonance, CW-EPR, is produced by applying longitudinal radiofrequency (RF) fields with the frequencies, ωrf, which exceeds the linewidth, 2πδ, of a single spectral line given in frequency units. The second longitudinal RF field with frequency, ωrf2, is employed to produce double modulation spectrum, DMS. In this work DMS are presented as a specific type of MS which can be produced from an ordinary homogenous line. The numerical simulations of DMS in the limit of low power saturation relied on the recently introduced multi-photon transitions formalism which includes one microwave photon in combination with an arbitrary number of radiofrequency photons. It is shown that DMS of an inhomogeneous line exhibits similar basic structure as MS and exhibits sideband peaks at multiples of basic radiofrequencies. Linewidths of these peaks are significantly narrower (cca. two - three orders of magnitude) than the inhomogeneous linewidth and can be correlated with the underlying homogeneous linewidth components on the basis of characteristic spin-lattice, T1, and spin-spin, T2, relaxation times. The capability to extract T1 and T2 from DMS was tested on the well-known E' defect in irradiated vitreous SiO2. The obtained results revealed the impact of "rapid passage" effect on DMS in improving the detection sensitivity of DMS in the study of paramagnetic centers with long relaxation times. Therefore, double modulation method can be considered as a complementary method for studying inhomegeneous broadening in the EPR spectra.

Enhanced accuracy of the microwave field strength measurement in a CW-EPR by pulsed modulation technique.

The microwave magnetic field strength, B1, in the cavity of a conventional continuous wave electron paramagnetic resonance, CW-EPR, spectrometer was measured by employing modulation sidebands, MS, in the EPR spectrum. MS spectrum in CW-EPR is produced by applying the modulation frequency, ωrf, which exceeds the linewidth, δB, given in frequency units. An amplitude-modulated CW-EPR, AM-CW-EPR, was selected as detection method. Theoretical description of AM-CW-EPR spectrum was modified by adding Bloch-Siegert-like shift obtained by taking into account the cumulative effect of the non-resonant interactions between the driving fields and the spin system. This approach enables to enhance the precision of B1 measurement. In order to increase the sensitivity of the method when saturation effects, due to higher intensity of B1, decrease the resolution of AM-CW-EPR spectrum, detection at the second harmonic of CW-EPR has been employed.

Prevalence of metabolic syndrome and related metabolic traits in an island population of the Adriatic.

BACKGROUND: Metabolic syndrome, a constellation of risk factors associated with cardiovascular disease and Type 2 diabetes, has reached epidemic proportions worldwide. Epidemiological studies in transitional societies will provide insight into the underlying factors that interact in its manifestation. AIMS: To estimate the prevalence of metabolic syndrome, provide a comparative analysis of two metabolic syndrome definitions and assess clustering and association of metabolic traits and cardiovascular diseases in an Adriatic island population. SUBJECTS AND METHODS: In a cross-sectional study, data on four anthropometric, blood pressure and 11 biochemical traits were obtained from 1430 adults from the island of Hvar. RESULTS: Prevalence of metabolic syndrome was 25% and 38.5% based on Adult Treatment Panel III and International Diabetes Federation definitions, respectively. Rates of abdominal obesity, elevated blood glucose and hypertension were high. Among the traits not included in the definitions, levels of LDL, total cholesterol and fibrinogen were markedly elevated. The majority of the phenotypes were significantly associated with the syndrome, the strongest being waist circumference. CONCLUSION: The Croatian islanders are characterized by a high prevalence of metabolic abnormalities. Central obesity is the strongest contributor of the syndrome. With a high prevalence of dyslipidemia and pro-inflammatory factors, the population is at substantial risk for cardiovascular diseases.

EGFRs mediate chemotactic migration in the developing telencephalon.

Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFalpha. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.

The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex.

The cerebral cortex develops from the dorsal telencephalon, at the anterior end of the neural tube. Neurons are generated by cell division at the inner surface of the telencephalic wall (in the ventricular zone) and migrate towards its outer surface, where they complete their differentiation. Recent studies have suggested that the transcription factor Pax6 is important for regulation of cell proliferation, migration and differentiation at various sites in the CNS. This gene is widely expressed from neural plate stage in the developing CNS, including the embryonic cerebral cortex, where it is required for radial glial cell development and neuronal migration. We report new findings indicating that, in the absence of Pax6, proliferative rates in the early embryonic cortex are increased and the differentiation of many cortical cells is defective. A major question concerns the degree to which cortical defects in the absence of Pax6 are a direct consequence of losing the gene function from defective cells themselves, rather than being secondary to abnormalities in other cells. Cortical defects in the absence of Pax6 become much more pronounced later in cortical development, and we propose that many result from a compounding of abnormalities in proliferation and differentiation that first appear at the onset of corticogenesis.

Evidence that the lateral geniculate nucleus regulates the normal development of visual corticocortical projections in the cat.

The aim of this work was to examine the influence of subcortical afferents on the development of corticocortical projections in the cat's visual cortex. In the adult, corticocortical axons project with precision to link retinotopically corresponding points in visual areas 17 and 18. In the newborn kitten, an excess of corticocortical connections is generated, leading to a degree of imprecision in the early pathways. During the first postnatal month, the loss of some of these early connections lowers their densities and increases the accuracy with which they project. These processes occur in an environment already influenced by afferents from the lateral geniculate nucleus and we tested the extent to which these existing inputs are required for corticocortical development. We lesioned the lateral geniculate nucleus with ibotenic acid in newborn kittens and studied connections from area 17 to area 18, and vice versa, after 1 month. In lesioned kittens, there were fewer corticocortical projections than normal in these reciprocal pathways and those that were present retained an immature, widespread pattern of projection. These results suggest that geniculate afferents are crucial for generating sufficient numbers of corticocortical projections and for creating the precision in their mapping.

Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6.

The cerebral cortex forms by the orderly migration and subsequent differentiation of neuronal precursors generated in the proliferative ventricular zone. We studied the role of the transcription factor Pax-6, which is expressed in the ventricular zone, in cortical development. Embryos homozygous for a mutation of Pax-6 (Small eye; Sey) had abnormalities suggesting defective migration of late-born cortical precursors. When late-born Sey/Sey precursors were transplanted into wild-type embryonic rat cortex, they showed similar integrative, migrational and differentiative abilities to those of transplanted wild-type mouse precursors. These results suggest that postmitotic cortical cells do not need Pax-6 to acquire the capacity to migrate and differentiate, but that Pax-6 generates a cortical environment that permits later-born precursors to express their full developmental potential.

The organization of visual corticocortical connections in early postnatal kittens.

We tested the hypothesis that, in newborn kittens, superficial layers of the extrastriate cortex receive more specific patterns of corticocortical innervation from the striate cortex than deep layers. First, we injected retrogradely transported tract-tracers at a range of depths in area 18 to label area 17. All injections were of similar tangential diameter and were in the same region of rostral area 18, where the visual field 10-20 degrees below the horizontal meridian is represented. Injections that involved only the superficial layers of area 18 labelled cells mainly in the superficial layers (future layers 2-4) of area 17, across a region that was 2-3 mm wider than the diameter of the injection site in the rostrocaudal direction. Injections that involved all layers of area 18 labelled cells in both superficial and deep layers (5 and 6) of area 17, across a region that was 6-9 mm wider than the diameter of the injection site in the rostrocaudal direction. These values demonstrate that, in neonates, the convergence of projections from area 17 to the superficial layers of area 18 is less than that to the deep layers of area 18. The lower values for convergence obtained by injecting only the superficial layers of area 18 in kittens were similar to those obtained by injecting all layers of area 18 in adult cats; the values obtained by injecting all layers of area 18 in kittens were much higher. Second, we injected the full depth of area 17 in newborn kittens with labels that travel anterogradely and retrogradely. Confirming the conclusions from the use of retrograde tracers, these focal injections produced very widespread labelling of the deep layers of area 18, but much more localized and topographically organized labelling of its superficial layers. These results indicate that there is a considerable postnatal improvement in the accuracy with which corticocortical cells in striate visual cortex target appropriate regions in extrastriate cortex, in agreement with previous findings. They also demonstrate that this change occurs mainly among those striate cortical neurons that innervate a wide region of the deep layers of extrastriate cortex at birth. The innervation of the superficial layers of extrastriate cortex is much more accurate from the outset.

Coughing can relieve or exacerbate symptoms in asthmatic patients.

From about 1190 to the present day opposing views have been expressed about the effects of coughing in patients with asthma. Some accounts have stated that it brought relief and others that it exacerbated asthma, whereas others thought that it could have both effects. In the present investigation, 187 patients with a clinical diagnosis of asthma were asked whether coughing relieved or exacerbated their asthma. In 41.7% coughing caused exacerbation, in 29.9% it brought relief, in 9.9% it had no effect, and in the remaining 18.7% it sometimes exacerbated their symptoms and sometimes brought relief. When asthma was exacerbated, the most common symptom induced was breathlessness, and then wheezing; chest tightness was the least frequent. When coughing brought relief it was mainly through the expectoration of sputum. However, a small proportion of patients found relief even if there was no expectoration. If coughing exacerbates asthma and persists in the face of treatment with standard medication, then treatment specifically directed at its diminution could reduce morbity considerably.

Glottic closure and high flows are not essential for productive cough.

For about 150 years, there has been emphasis on the importance of glottic closure and high flows in coughing. During voluntary coughing in normal subjects, the main expiratory flow usually begins as thoracic and abdominal pressures are rising. However, sometimes it starts at peak pressure whereas at other times flow and pressure rise together. Plateau flow in single coughs remains relatively constant in the face of large changes in pressure. In a group of coughs following a single inspiration, the fall in pressure is less during plateau flow. Consequently, for the same oral flows, it is likely that the mean linear velocity in the intrathoracic airways will be greater than in a single cough. Recordings have also been made of early morning involuntary coughing in patients with obstructive airways disease. Flow, volume and sound were recorded and sputum expectoration was noted. Sputum expectoration usually occurs after groups of coughs following single inspirations. Hence the movement of the equal pressure point peripherally may be important. These patients have very low flows and yet their coughs are productive. Sound often occurs during the whole of the low flow period immediately before the main expulsive phase. This could only occur if the glottis was open. Thus productive cough can occur without glottic closure and with low airflows.