Prodromal non-motor symptoms of Parkinson’s disease

The motor symptoms of Parkinson’s disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents

Failure to downregulate the BAF53a subunit of the SWI/SNF chromatin remodeling complex contributes to the differentiation block in rhabdomyosarcoma

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Measurements and estimation of the columnar optical depth of tropospheric aerosols in the UV spectral region

International audienceWe report values of the columnar tropospheric aerosol optical depth at UV wavelengths based on experimental measurements of the direct spectral irradiances carried out by a commercial spectroradiometer (Li1800 of Licor company) covering the range from 300?1100 nm at two stations with different climate characteristics in Spain. The first station is located in a rural site in north central Spain with continental climate. The data extend from March to the end of October of 1995. The other station is a coastal site in the Gulf of Cádiz (southwest Spain) of maritime climate type. This study is mainly focused on the capability of estimating aerosol optical depth values in the UV region based on the extracted information in the visible and near infrared ranges. A first method has been used based on the Ångström turbidity parameters. However, since this method requires detailed spectral information, a second method has also been used, based on the correlation between wavelengths. A correlation has been established between the experimental aerosol optical depth values at 350 nm and 500 nm wavelengths. Although the type of aerosol seems to be the key factor that determines the quality of these estimations, the evaluation of the associated error is necessary to know the behaviour of these estimations in each area of study

Distribución temporal del tamaño de los molariformes de Ursus spelaeus Ros.-Hein.ibérico

[Abstract] This paper deals with a metrical comparison of cheek-teeth length of Ursus spelaeus Ros.-Hein.Iberian population representatives

Detection of an optical transient following the 13 March 2000 short/hard gamma-ray burst

We imaged the error box of a gamma-ray burst of the short (0.5 s), hard type (GRB 000313), with the BOOTES-1 experiment in southern Spain, starting 4 min after the gamma-ray event, in the I-band. A bright optical transient (OT 000313) with I = 9.4 +/- 0.1 was found in the BOOTES-1 image, close to the error box (3-sigma) provided by BATSE. Late time VRIK'-band deep observations failed to reveal an underlying host galaxy. If the OT 000313 is related to the short, hard GRB 000313, this would be the first optical counterpart ever found for this kind of events (all counterparts to date have been found for bursts of the long, soft type). The fact that only prompt optical emission has been detected (but no afterglow emission at all, as supported by theoretical models) might explain why no optical counterparts have ever been found for short, hard GRBs.This fact suggests that most short bursts might occur in a low-density medium and favours the models that relate them to binary mergers in very low-density enviroments.Comment: Revised version. Accepted for publication in Astronomy and Astrophysics Letters, 5 pages, 3 figure

Stress-induced modulation of endocannabinoid signaling leads to delayed strengthening of synaptic connectivity in the amygdala

none11siopenYasmin, F.; Colangeli, R.; Morena, M.; Filipski, S.; van der Stelt, M.; Pittman, Q.J.; Hillard, C.J.; Campbell Teskey, G.; McEwen, B.S.; Hill, M.N.; Chattarji, S.Yasmin, F.; Colangeli, R.; Morena, M.; Filipski, S.; van der Stelt, M.; Pittman, Q. J.; Hillard, C. J.; Campbell Teskey, G.; Mcewen, B. S.; Hill, M. N.; Chattarji, S

Small nucleolar RNAs determine resistance to doxorubicin in human osteosarcoma

Doxorubicin (Dox) is one of the most important first-line drugs used in osteosarcoma therapy. Multiple and not fully clarified mechanisms, however, determine resistance to Dox. With the aim of identifying new markers associated with Dox-resistance, we found a global up-regulation of small nucleolar RNAs (snoRNAs) in human Dox-resistant osteosarcoma cells. We investigated if and how snoRNAs are linked to resistance. After RT-PCR validation of snoRNAs up-regulated in osteosarcoma cells with different degrees of resistance to Dox, we overexpressed them in Dox-sensitive cells. We then evaluated Dox cytotoxicity and changes in genes relevant for osteosarcoma pathogenesis by PCR arrays. SNORD3A, SNORA13 and SNORA28 reduced Dox-cytotoxicity when over-expressed in Dox-sensitive cells. In these cells, GADD45A and MYC were up-regulated, TOP2A was down-regulated. The same profile was detected in cells with acquired resistance to Dox. GADD45A/MYC-silencing and TOP2A-over-expression counteracted the resistance to Dox induced by snoRNAs. We reported for the first time that snoRNAs induce resistance to Dox in human osteosarcoma, by modulating the expression of genes involved in DNA damaging sensing, DNA repair, ribosome biogenesis, and proliferation. Targeting snoRNAs or down-stream genes may open new treatment perspectives in chemoresistant osteosarcomas

Evaluation of Bronchoscopy and Bronchoalveolar Lavage Findings in Cats With Aelurostrongylus abstrusus in Comparison to Cats With Feline Bronchial Disease

The cat lungworm Aelurostrongylus abstrusus is a cause of lower respiratory tract disease worldwide. Bronchoscopy and bronchoalveolar lavage (BAL) are important tools for diagnosing respiratory diseases in cats. Therefore, the aim of the study was to investigate the usefulness of bronchoscopy and BAL in the diagnosis of A. abstrusus. Findings from bronchoscopic examination and BAL of 24 naturally infected cats were evaluated and compared with those of 12 cats with idiopathic Feline Bronchial Diseases (FBDs). Data were analyzed using Mann-Whitney or Fisher's exact tests. No significant bronchoscopic differences were detected between cats with aelurostrongylosis and FBDs in bronchial mucus, nodular lesions, and airway collapse. On the other hand, airway hyperemia, epithelial irregularities, and bronchial stenosis were observed more frequently in cats affected by FBDs than aelurostrongylosis, while bronchiectasis was found only in cats infected by A. abstrusus. Neutrophilic, eosinophilic, lymphocytic, and mixed inflammation were recorded in both groups. Bacteria or bacterial DNA was identified regardless of the presence or absence of A. abstrusus with no significant differences between groups. Larvae of A. abstrusus were cytologically detected in 5 of the 24 cats (20.8%) with aelurostrongylosis. These results indicate that, although some findings on bronchoscopic examination (i.e., bronchiectasis) can be described more frequently in cats infected by A. abstrusus, bronchial alterations and cytological findings in aelurostrongylosis are not specific unless larvae are observed and overlap with those of other feline airway diseases

Molecular dissection of structural variations involved in antithrombin deficiency

Inherited antithrombin deficiency, the most severe form of thrombophilia, is predominantly caused by variants in SERPINC1. Few causal structural variants have been described, usually detected by multiplex ligation-dependent probe amplification or cytogenetic arrays, which only define the gain or loss and the approximate size and location. This study has done a complete dissection of the structural variants affecting SERPINC1 of 39 unrelated patients with antithrombin deficiency using multiplex ligation-dependent probe amplification, comparative genome hybridization array, long-range PCR, and whole genome nanopore sequencing. Structural variants, in all cases only affecting one allele, were deleterious and caused a severe type I deficiency. Most defects were deletions affecting exons of SERPINC1 (82.1%), but the whole cohort was heterogeneous, as tandem duplications, deletion of introns, or retrotransposon insertions were also detected. Their size was also variable, ranging from 193 bp to 8 Mb, and in 54% of the cases involved neighboring genes. All but two structural variants had repetitive elements and/or microhomologies in their breakpoints, suggesting a common mechanism of formation. This study also suggested regions recurrently involved in structural variants causing antithrombin deficiency and found three structural variants with a founder effect: the insertion of a retrotransposon, duplication of exon 6, and a 20-gene deletion. Finally, nanopore sequencing was determined to be the most appropriate method to identify and characterize all structural variants at nucleotide level, independently of their size or type.Supported by the National Institute for Health Research (NIHR) for the NIHR BioResource project (grant numbers RG65966 and RG94028), by the Instituto de Salud Carlos III grant; Fondo Europeo de Desarrollo Regional (FEDER) grant PI18/00598; and Fundación Séneca 19873/GERM/15. M.E.d.l.M.-B. has a postdoctoral contract from University of Murcia, Murcia, Spain. C.B.-P. has a Río Hortega fellowship. B.d.l.M.-B. has a postdoctoral fellowship from Fundación Séneca. J.C.-G. has a predoctoral fellowship from the Ministry of Universities FPU19/03662