Regulation of Stearoyl Coenzyme A Desaturase 1 Gene Promoter in Bovine Mammary Cells.

Stearoyl-Coenzyme A desaturase 1 (SCD1) belongs to the fatty acid family of desaturases. In lactating ruminants, the SCD1 protein is highly expressed in the mammary gland and is relevant for the fatty acid composition of milk and dairy products. Bovine mammary epithelial cells (BME-UV1), cultured in vitro, have been proposed as a model to reproduce the biology of the mammary gland. The present study was designed to investigate the responsiveness of bovine SCD1 promoter to serum, insulin, oleic acid, and NFY transcription factor in BME-UV1 cells. A luciferase-based reporter assay was used to monitor the transcriptional activity of the SCD1 promoter region in BME-UV1 cells treated or not with insulin and/or oleic acid. The level of endogenous SCD1 mRNA was evaluated by Real time PCR. Insulin (20 ng/mL) induced a 2.0 to 2.5-fold increase of SCD1 promoter activity. Additionally, the effect of insulin was inhibited by oleic acid, serum components, and NFY enforced expression. Serum and NFY showed no synergistic or additive effect on SCD1 promoter activity suggesting that they repress SCD1 transcription through the same responsive element.

3D structure of the Campi Flegrei caldera central sector reconstructed through short-period magnetotelluric imaging.

The Campi Flegrei caldera experienced an unrest phase dating to 2005, which primary expression is the impressive ground uplift, accompanied by increasing degassing and seismic activities. Such last two phenomena developed mainly in the caldera central sector, including the Solfatara-Pisciarelli complex. However, the inner structure of such an area is still not defined, and this originates a poor understanding of the ongoing unrest. This paper describes the results of a new magnetotelluric survey performed in the Campi Flegrei caldera central sector. Through the inversion of data collected in 47 independent soundings, a 3D model of the electrical resistivity has been retrieved, which evidenced a partition of the investigated structure. The Agnano-Astroni area seems to be associated with a liquid-dominated geothermal reservoir, whereas the Solfatara-Pisciarelli area seems to be characterized by a single mixed liquid and gasses-dominated geothermal reservoir, which supplies the main caldera fumaroles. The proposed reconstruction of the geometrical characteristics of the hydrothermal system and the primary fluid rising pathways gives substantial clues about the significance of the detected structures in the evolution of the caldera unrest.

The Pisciarelli main fumarole mechanisms reconstructed by electrical resistivity and induced polarization imaging.

Pisciarelli, together with the adjacent Solfatara maar-diatreme, represents the most active structure of the Campi Flegrei caldera (Italy) in terms of degassing and seismic activity. This paper aims to define the structure of the Pisciarelli hydrothermal system (down to a 20 m depth) through electrical resistivity and time-domain-induced polarization tomography and self-potential mapping. The retrieved 3D image of the area helps reconstruct the Pisciarelli subsurface in its area of maximum degassing, containing the main fumarole ("soffione") and the mud pool. In particular, a channel has been identified in which fluids stored in a deeper reservoir rise toward the surface. Such a structure seems to be surmounted by a clay-cap formation that could govern the circulation of fluids and the abundance of gases/vapors emitted by the soffione. Based on this new reconstruction of the Pisciarelli fumarolic field structural setting, the first conceptual model has been suggested that is capable of simultaneously explaining the mechanisms governing soffione activity and elucidating the role played by the fluid/gas of deeper origin in the shallow fluid circulation system. The proposed model can potentially help to better monitor the processes occurring throughout the Pisciarelli fumarolic field and provide an evaluation of the associated hazards.

Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study.

Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BP(ND)(t) or K(occ)(t) = a*e((-)(bt)(-d)(A) + c, where BP(ND) = tracer binding potential (nondispaceable), K(OCC) = tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.

Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease.

BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.

Levodopa-sensitive, dynamic changes in effective connectivity during simultaneous movements in Parkinson's disease.

Changes in effective connectivity during the performance of a motor task appear important for the pathogenesis of motor symptoms in Parkinson's disease (PD). One type of task that is typically difficult for individuals with PD is simultaneous or bimanual movement, and here we investigate the changes in effective connectivity as a potential mechanism. Eight PD subjects off and on l-DOPA medication and 10 age-matched healthy control subjects performed both simultaneous and unimanual motor tasks in an fMRI scanner. Changes in effective connectivity between regions of interest (ROIs) during simultaneous and unimanual task performance were determined with structural equation modeling (SEM), and changes in the temporal dynamics of task performance were determined with multivariate autoregressive modeling (MAR). PD subjects demonstrated alterations in both effective connectivity and temporal dynamics compared with control subjects during the performance of a simultaneous task. l-DOPA treatment was able to partially normalize effective connectivity and temporal patterns of activity in PD, although some connections remained altered in PD even after medication. Our results suggest that difficulty performing simultaneous movements in PD is at least in part mediated by a disruption of effective communication between widespread cortical and subcortical areas, and l-DOPA assists in normalizing this disruption. These results suggest that even when the site of neurodegeneration is relatively localized, study of how disruption in a single region affects connectivity throughout the brain can lead to important advances in the understanding of the functional deficits caused by neurodegenerative disease.

Publisher Correction: Deep Electrical Resistivity Tomography for a 3D picture of the most active sector of Campi Flegrei caldera.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Deep Electrical Resistivity Tomography for a 3D picture of the most active sector of Campi Flegrei caldera.

The central sector of the Campi Flegrei volcano, including the Solfatara maar and Pisciarelli fumarole field, is currently the most active area of the caldera as regards seismicity and gaseous emissions and it plays a significant role in the ongoing unrest. However, a general volcano-tectonic reconstruction of the entire sector is still missing. This work aims to depict, for the first time, the architecture of the area through the application of deep Electrical Resistivity Tomography. We reconstructed a three-dimensional resistivity model for the entire sector. Results provide useful elements to understand the present state of the system and the possible evolution of the volcanic activity and shed solid bases for any attempt to develop physical-mathematical models investigating the ongoing phenomena.

Neuroimaging in Parkinson's disease.

Structural imaging studies often reveal relatively limited findings in Parkinsonian disorders, as the most profound changes are neurochemical and hence better revealed by functional studies such as PET or SPECT. However, newer magnetic resonance techniques such as spectroscopy, diffusion weighted imaging, diffusion tensor imaging and magnetization transfer have shown promise in differentiating between idiopathic Parkinson's and the atypical parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy. We review here recent advances in functional imaging as well as in structural studies of basal ganglia disorders. Functional studies may give insights into mechanisms underlying disease pathogenesis, as well as neurochemical alterations.

[Interictal personality syndrome in non-dominant temporal lobe epilepsy: case report]. / Síndrome de personalidade interictal na epilepsia do lobo temporal não-dominante: relato de caso.

The syndrome of interictal personality in non-dominant temporal lobe epilepsy consists of hyposexuality, hyperreligiosity, humorlessness and hypergraphia. Its notification, in 1974, was followed by an extensive search for these traits in broad epileptic populations. Nevertheless, these statistical studies failed to match this syndrome in general temporal lobe epileptics, and its existence became then target of doubt. We report the case of a 35 year-old man presenting partial complex epilepsy, whose singularity lies in his sophisticated drawing abilities. The large amount of buildings and houses he paints expresses his hypergraphia. He also presents hyposexuality and hyperreligiosity. MRI shows right mesial temporal sclerosis. Temporal hyperconnection, caused by a basal temporal irritative focus, is the most probable pathophysiological mechanism. Epileptic fits can be controlled in the majority of cases. However, behavioural symptoms usually do not respond to pharmacological approach or psychotherapy.

[Neuroacanthocytosis. A case report]. / Neuroacantocitose. Relato de caso.

We present a 45 years old man with neuroacanthocytosis. This gentleman has complex partial seizures and generalized tonic-clonic seizures, as well as movement disorders characterized by chorea and orofacial diskinesia. Complementary examination shows acanthocytosis of 11% on peripheral blood, irritative focus on right temporal lobe on EEG, serum creatinokinase of 101 U/l and volume reduction and hypersignal on caudate nucleus and putamen bilaterally on MRI.

[Hemichorea-hemiballism associated to cryptococcal granuloma in a patient with AIDS: case report]. / Hemicoréia-hemibalismo associado a granuloma criptocócico em paciente com SIDA: relato de caso.

Movement disorders are not common in acquired immunodeficiency syndrome. Hemichorea-hemiballism (HC-HB) is the most common of them all, and it is usually related to oportunistic toxoplasmosis of the basal ganglia. We present a 28-year-old man, HIV positive with HC-HB caused by a right subthalamic granuloma, which did not respond to treatment for toxoplasmosis. Cryptoccococic antigen was positive in the cerebrospinal fluid and antifungic therapy led to clinical and radiologic improvement, thus the diagnosis of a granulomatous lesion by Cryptococcus neoformans was established. Current literature on HC-HB and its relationship with AIDS is subsequently reviewed.

Phenytoin as the first option in female epileptic patients?

OBJECTIVE: Phenytoin (PHT) is one of the first-choice drugs in several epileptic syndromes, mostly in partial epilepsies, in which case it is effective as carbamazepine and phenobarbital. However, like any other anti-epileptic drug (AED), unpleasant side-effects are not rare. The aim of this study is the evaluation of dermatological troubles related to chronic PHT usage in female patients. METHOD: Between 1990-93, 731 new patients underwent investigation for epilepsy at the Multidisciplinary Clinic for Epilepsy in our State. In this sample 283 were AED users at the time of the first assessment. Sixty one female patients taking PHT were identified. They were taking PHT in a dosage ranging from 100 to 300 mg daily, in mono or polytherapy regimen, during 1-5 previous years. RESULTS: More than 50% of the sample showed coarse facial features made by the combination of several degrees of acne, hirsutism and gingival hyperplasia. CONCLUSION: Except in emergency situations, PHT should not be prescribed as the first option to the treatment of female epileptic patients, because not uncommonly the cosmetic side-effects are more socially handicapping than the epileptic syndrome by itself.

PET demonstrates reduced dopamine transporter expression in PD with dyskinesias.

OBJECTIVE: Dyskinesias are common in Parkinson disease (PD). Prior investigations suggest that dopamine (DA) terminals compensate for abnormal DA transmission. We verified whether similar adaptations could be related to the development of treatment-related complications. METHODS: Thirty-six patients with PD with motor fluctuations were assessed with PET using [(11)C]-d-threo-methylphenidate (MP) and [(11)C]-(+/-) dihydrotetrabenazine (DTBZ). The expression of DA transporter relative to DA nerve terminal density was estimated by determining the MP/DTBZ ratio. Age, treatment, and disease severity were also taken into account in the evaluation of our data. RESULTS: Twenty-seven of the 36 patients had dyskinesias. Nine individuals had motor fluctuations without dyskinesia. The two patient groups were comparable in terms of age, disease duration and severity, medication, and striatal MP and DTBZ binding potentials. The MP/DTBZ ratio in the caudate was not different between groups (nondyskinesia 1.54 +/- 0.36, dyskinesia 1.39 +/- 0.28; mean +/- SD, p = 0.23). Putaminal MP/DTBZ was decreased in individuals with dyskinesia (1.18 +/- 0.24), compared to those who had motor fluctuations without dyskinesia (1.52 +/- 0.24, p = 0.019). The relationship between putaminal MP/DTBZ ratio and the presence of dyskinesias was not altered after correcting for age, treatment, and measures of disease severity. CONCLUSIONS: This investigation supports the role of presynaptic alterations in the appearance of dyskinesias. Dopamine (DA) transporter downregulation may minimize symptoms by contributing to increased synaptic DA levels in early Parkinson disease, but at the expense of leading to increased extracellular DA catabolism and oscillating levels of DA. Such oscillations might ultimately facilitate the appearance of dyskinesias.

Functional imaging in Tourette's syndrome.

The cause or causes of Tourette's syndrome (TS) remain unknown. Functional imaging studies have evaluated several implicated neurotransmitter systems and focused predominantly on the frequency or severity of tics. The results have been inconclusive and frequently contradictory with little light shed on pathogenetic mechanisms. However, metabolic derangements have been demonstrated within regions of the basal ganglia, limbic system and sensori-motor cortex and are in keeping with the concept of TS as both a motor and behavioral disorder. TS has long been regarded an involuntary movement disorder. However, many patients have stated that without the premonitory sensation, there would be no tics. For this reason, it has been suggested that the premonitory urge may be considered the involuntary component of TS and the performance of the tic merely a voluntary response. Future studies are needed to differentiate functional changes relating to urge from those associated with the performance of tics and tic suppression.