Publications by authors named "Gaetano Perrotta"

48 Publications

Paramagnetic Rim Lesions are Specific to Multiple Sclerosis: An International Multicenter 3T MRI Study.

Ann Neurol 2020 11 9;88(5):1034-1042. Epub 2020 Sep 9.

Department of Neurology, Johns Hopkins University, Baltimore, MD.

In multiple sclerosis (MS), a subset of chronic active white matter lesions are identifiable on magnetic resonance imaging by their paramagnetic rims, and increasing evidence supports their association with severity of clinical disease. We studied their potential role in differential diagnosis, screening an international multicenter clinical research-based sample of 438 individuals affected by different neurological conditions (MS, other inflammatory, infectious, and non-inflammatory conditions). Paramagnetic rim lesions, rare in other neurological conditions (52% of MS vs 7% of non-MS cases), yielded high specificity (93%) in differentiating MS from non-MS. Future prospective multicenter studies should validate their role as a diagnostic biomarker. ANN NEUROL 2020;88:1034-1042.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25877DOI Listing
November 2020

The central vein sign in multiple sclerosis patients with vascular comorbidities.

Mult Scler 2020 Aug 4:1352458520943785. Epub 2020 Aug 4.

Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium/Department of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland/Department of Neurology, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium.

Background: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS) lesions in MS has never been evaluated.

Objective: To investigate the association between different VRFs and the percentage of CVS lesions in MS.

Methods: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS.

Results: The median frequency of CVS lesions was 71% (range: 35%-100%). In univariate analysis, age ( < 0.0001), hypertension ( < 0.001), diabetes ( < 0.01), obesity ( < 0.01), smoking ( < 0.05), and the presence of enlarged-perivascular-spaces on MRI ( < 0.005) were all associated with a lower percentage of CVS lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS lesions in MS (adjusted  = 0.46;  < 0.0001 and  = 0.01, respectively).

Conclusion: The proportion of CVS lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520943785DOI Listing
August 2020

Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis.

Can J Neurol Sci 2020 03;47(2):189-196

Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Objective: In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.

Methods: Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.

Results: Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.

Conclusion: In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/cjn.2019.329DOI Listing
March 2020

The "central vein sign" in patients with diagnostic "red flags" for multiple sclerosis: A prospective multicenter 3T study.

Mult Scler 2020 04 19;26(4):421-432. Epub 2019 Sep 19.

Department of Neurology, Center of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland.

Background: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective.

Objectives: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases.

Methods: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory "red flags" (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed.

Results: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%;  < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value.

Conclusion: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458519876031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080603PMC
April 2020

Identification of miRNAs involved in fruit ripening by deep sequencing of Olea europaea L. transcriptome.

PLoS One 2019 22;14(8):e0221460. Epub 2019 Aug 22.

Research Centre for Olive, Citrus and Tree Fruit-Council for Agricultural Research and Economics, Rende (CS) IT.

Background: The ripening process of olive fruits is associated with chemical and/or enzymatic specific transformations, making them particularly attractive to animals and humans. In olive drupes, including 'Cassanese' ones, ripening is usually accompanied by progressive chromatic change, resulting in a final red-brown colourization of both epidermis and mesocarp. This event has an exception in the 'Leucocarpa', in which we observed the destabilization in the equilibrium between the chlorophyll metabolism and that of the other pigments, particularly the anthocyanins, whose switch-off during maturation promotes the white colouration of the fruits. Recently, transcription profiling of 'Leucocarpa' and 'Cassanese' olives along ripening, performed through an Illumina RNA-seq approach, has provided useful insights on genes functions involved in fruit maturation such as those related to the biosynthesis of flavonoids and anthocyanins.

Methodology: To assess expression alterations of genes involved in flavonoids and anthocyanins biosynthetic pathways during ripening, possibly caused by small nuclear RNA (snRNA) in olive drupes, snRNA libraries from 'Leucocarpa' and 'Cassanese' were constructed with RNAs extracted at 100 and 130 Days After Flowering (DAF) and sequenced by an Illumina approach. 130 conserved microRNAs (miRNA) in the Viridiplantae belonging to 14 miRNA families were identified. Regarding the 130 conserved miRNAs, approximately the 48% were identified in all libraries, 5 and 18 miRNAs were shared between the "Cassanese" (C100, C130) and "Leucocarpa" (L100, L130) libraries, respectively.

Conclusion: For the remaining reads not-matching with known miRNAs in the Viridiplantae, we combined secondary structure and minimum free energy to discover novel olive miRNAs. Based on these analyses, 492 sequences were considered as putative novel miRNAs. The putative target genes of identified miRNA were computationally predicted by alignment with the olive drupe transcripts obtained from the same samples. A total of 218 transcripts were predicted as targets of 130 known and 492 putative novel miRNAs. Interestingly, some identified target genes are involved in negative regulation of anthocyanin metabolic process. Quantification of the expression pattern of three miRNA and their target transcripts by qRT-PCR assay confirmed the results of Illumina sequencing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221460PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705801PMC
March 2020

The role of the cerebellum in reconstructing social action sequences: a pilot study.

Soc Cogn Affect Neurosci 2019 05;14(5):549-558

Vrije Universiteit Brussel, Department of Psychology, Brussels, Belgium.

Recent research has revealed that the cerebellum plays a critical role in social reasoning and in particular in understanding false beliefs and making trait attributions. One hypothesis is that the cerebellum is responsible for the understanding of sequences of motions and actions, which may be a prerequisite for social understanding. To investigate the role of action sequencing in mentalizing, we tested patients with generalized cerebellar degenerative lesions on tests of social understanding and compared their performance with matched healthy volunteers. The tests involved understanding violations of social norms making trait and causal attributions on the basis of short behavioral sentences and generating the correct chronological order of social actions depicted in cartoons (picture sequencing task). Cerebellar patients showed clear deficits only on the picture sequencing task when generating the correct order of cartoons depicting false belief stories and showed at or close to normal performance for mechanical stories and overlearned social scripts. In addition, they performed marginally worse on trait attributions inferred from verbal behavioral descriptions. We conclude that inferring the mental state of others through understanding the correct sequences of their actions requires the support of the cerebellum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/scan/nsz032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545532PMC
May 2019

Pivotal Roles of Cryptochromes 1a and 2 in Tomato Development and Physiology.

Plant Physiol 2019 02 12;179(2):732-748. Epub 2018 Dec 12.

Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Trisaia Research Center, 75026 Rotondella (Matera), Italy

Cryptochromes are flavin-containing blue/UVA light photoreceptors that regulate various plant light-induced physiological processes. In Arabidopsis (), cryptochromes mediate de-etiolation, photoperiodic control of flowering, entrainment of the circadian clock, cotyledon opening and expansion, anthocyanin accumulation, and root growth. In tomato (), cryptochromes are encoded by a multigene family, comprising , , , and We have previously reported the phenotypes of tomato mutants and overexpressing plants. Here, we report the isolation by targeting induced local lesions in genomes, of a tomato knock-out mutant, its introgression in the indeterminate Moneymaker background, and the phenotypes of / single and double mutants. The / mutant showed phenotypes similar to its Arabidopsis counterpart (long hypocotyls in white and blue light), but also several additional features such as increased seed weight and internode length, enhanced hypocotyl length in red light, inhibited primary root growth under different light conditions, anticipation of flowering under long-day conditions, and alteration of the phase of circadian leaf movements. Both cry1a and cry2 control the levels of photosynthetic pigments in leaves, but cry2 has a predominant role in fruit pigmentation. Metabolites of the sterol, tocopherol, quinone, and sugar classes are differentially accumulated in and leaves and fruits. These results demonstrate a pivotal role of cryptochromes in controlling tomato development and physiology. The manipulation of these photoreceptors represents a powerful tool to influence important agronomic traits such as flowering time and fruit quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1104/pp.18.00793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426409PMC
February 2019

Comparative transcriptomics between high and low rubber producing Taraxacum kok-saghyz R. plants.

BMC Genomics 2018 Dec 4;19(1):875. Epub 2018 Dec 4.

Trisaia Research Center, ENEA, Italian National Agency for New Technologies Energy and Sustainable Economic Development, MT, 75026, Rotondella, Italy.

Background: Taraxacum kok-saghyz R. (Tks) is a promising alternative species to Hevea brasiliensis for production of high quality natural rubber (NR). A comparative transcriptome analysis of plants with differential production of NR will contribute to elucidate which genes are involved in the synthesis, regulation and accumulation of this natural polymer and could help to develop Tks into a rubber crop.

Results: We measured rubber content in the latex of 90 individual Tks plants from 9 accessions, observing a high degree of variability. We carried out de novo root transcriptome sequencing, assembly, annotation and comparison of gene expression of plants with the lower (LR plants) and the higher rubber content (HR plants). The transcriptome analysis also included one plant that did not expel latex, in principle depleted of latex transcripts. Moreover, the transcription of some genes well known to play a major role in rubber biosynthesis, was probed by qRT-PCR. Our analysis showed a high modulation of genes involved in the synthesis of NR between LR and HR plants, and evidenced that genes involved in sesquiterpenoids, monoterpenoids and phenylpropanoid biosynthesis are upregulated in LR plants.

Conclusions: Our results show that a higher amount of rubber in the latex in HR plants is positively correlated with high expression levels of a number of genes directly involved in rubber synthesis showing that NR production is highly controlled at transcriptional level. On the other hand, lower amounts of rubber in LR plants is related with higher expression of genes involved in the synthesis of other secondary metabolites that, we hypothesize, may compete towards NR biosynthesis. This dataset represents a fundamental genomic resource for the study of Tks and the comprehension of the synthesis of NR and other biochemically and pharmacologically relevant compounds in the Taraxacum genus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-018-5287-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280347PMC
December 2018

Toxic-induced cerebellar syndrome: from the fetal period to the elderly.

Handb Clin Neurol 2018 ;155:333-352

Neurology Service, Hôpital Erasme, Brussels, Belgium.

The cerebellum is a brain region which is particularly susceptible to intoxication. Clinical presentation is heterogeneous. It is often considered that elderly patients and patients presenting pre-existing structural lesions of the posterior fossa are particularly at risk of developing a toxic-induced cerebellar syndrome (TOICS). However, TOICS may occur at any age, including in utero. Indeed, the cerebellum is highly vulnerable during neurodevelopment. Amongst cerebellotoxic agents, ethanol is the most commonly implicated. The vermis is a privileged target. Ethanol exerts toxic effects upon neurons, glia (especially astrocytes and oligodendrocytes), and myelin sheaths. Prenatal alcohol exposure causes teratogenic effects on the developing cerebellum, impeding neuronal migration and differentiation. In adults, cerebellar ataxia is a major feature of both acute and chronic ethanol intoxication. Wernicke encephalopathy is a medical emergency characterized by a triad of ophthalmoplegia, ataxia, and impaired mental status. It requires the immediate administration of high doses of thiamine by the intravenous route. The following drugs may induce a permanent cerebellar syndrome: phenytoin, lithium salts, antineoplastics, and heroin. In addition to ethanol and drugs, environmental agents are also a source of TOICS. In particular, the cerebellum is susceptible to metal intoxication. The recently described deposits of gadolinium in cerebellar nuclei in patients who had received multiple intravenous administrations are a matter of concern on a worldwide scale but we still lack the demonstration of clinically relevant effects upon motor, oculomotor, or cognitive function. Because cerebellar symptoms may be subtle or immersed in a complex encephalopathy with combined involvement of the peripheral nervous system, the diagnosis of TOICS is often overlooked. The life-threatening risk of edema of the posterior fossa with compression of the brainstem should be kept in mind, including in cases of posterior reversible encephalopathy syndrome, and requires posterior fossa decompression when acute hydrocephalus occurs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/B978-0-444-64189-2.00022-6DOI Listing
October 2018

Into the Moment: Does Mindfulness Affect Biological Pathways in Multiple Sclerosis?

Front Behav Neurosci 2018 22;12:103. Epub 2018 May 22.

Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

Mindfulness was introduced in the Western world by Jon Kabat-Zinn in 1979. He defined it as "awareness that arises through paying attention, on purpose, in the present moment, non-judgmentally." Since then, research on mindfulness-based interventions (MBIs) has increased exponentially both in health and disease, including in patients with neurodegenerative diseases such as dementia and Parkinson's disease. Research on the effect of mindfulness and multiple sclerosis (MS) only recently gained interest. Several studies completed since 2010 provided evidence that mindfulness improves quality of life (QoL), depression and fatigue in MS patients. In addition to patient-reported outcome measures, potential effects on cognitive function have been investigated only to a very limited extent. However, research on laboratory biomarkers and neuroimaging, capable to deliver proof-of-concept of this behavioral treatment in MS, is mainly lacking. In this perspective, we illustrate possible neurobiological mechanisms, including the tripartite interaction between the brain, the immune system and neuroendocrine regulation, through which this treatment might affect multiple sclerosis symptoms. We propose to (1) include immunological and/or neuroimaging biomarkers as standard outcome measures in future research dedicated to mindfulness and MS to help explain the clinical improvements seen in fatigue and depression; (2) to investigate effects on enhancing cognitive reserve and cognitive function; and (3) to investigate the effects of mindfulness on the disease course in MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2018.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972188PMC
May 2018

A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis.

Acta Neurol Belg 2018 Jun 13;118(2):161-168. Epub 2018 Mar 13.

Department of Hematology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium.

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-018-0905-0DOI Listing
June 2018

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

Ann Neurol 2018 02 15;83(2):283-294. Epub 2018 Feb 15.

Department of Neuroscience, Drug and Child Health, University of Florence, Florence, Italy.

Objectives: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS).

Methods: In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed.

Results: MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%.

Interpretation: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901412PMC
February 2018

Rivastigmine decreases brain damage in HIV patients with mild cognitive deficits.

Ann Clin Transl Neurol 2017 12 7;4(12):915-920. Epub 2017 Nov 7.

Department of Clinical Neurosciences, Service of Neurology, Neuroimmunology Unit Lausanne University Hospital and University of Lausanne Lausanne Vaud Switzerland.

Rivastigmine has been shown to improve cognition in HIV+ patients with minor neurocognitive disorders; however, the mechanisms underlying such beneficial effect are currently unknown. To assess whether rivastigmine therapy is associated with decreased brain inflammation and damage, we performed T1/T2* relaxometry and magnetization transfer imaging in 17 aviremic HIV+ patients with minor neurocognitive disorders enrolled on a crossed over randomized rivastigmine trial. Rivastigmine therapy was associated with changes in MRI metrics indicating a decrease in brain water content (i.e., edema reabsorption) and/or reduced demyelination/axonal damage. Furthermore, MRI changes correlated with cognitive improvement on rivastigmine therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740253PMC
December 2017

The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic Research to Neurological Practice and from Pregnancy to Adulthood.

Cerebellum 2018 Jun;17(3):247-251

Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Gadolinium (Gd)-based contrast agents (GBCAs) are used in magnetic resonance imaging (MRI) to increase the diagnostic yield. Current reports using animal models or human subjects have shown that GBCAs may be deposited in brain including the cerebellum. Although further studies may be required to clarify the toxicity of GBCAs, we should be more cautious to use these agents particularly in patients who more likely to have repeated enhanced MRI along their lifespan. In this editorial, current studies to clarify the toxicity of GBCAs in the cerebellum are introduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12311-017-0903-4DOI Listing
June 2018

Absence of clinical cerebellar syndrome after serial injections of more than 20 doses of gadoterate, a macrocyclic GBCA: a monocenter retrospective study.

J Neurol 2017 Nov 27;264(11):2277-2283. Epub 2017 Sep 27.

FNRS, ULB-Hôpital Erasme, Route de Lennik 808, 1070, Brussels, Belgium.

Sound evidence of gadolinium accumulation in brain has been recently provided after repeated administrations of linear gadolinium-based contrast agents (GBCAs), especially at the cerebellum level. Although data regarding brain accumulation of macrocyclic GBCAs are more reassuring, there is now a genuine concern ("gadolinium-phobia") about possible long-term consequences of gadolinium deposits, especially in terms of cerebellar sequelae. We, therefore, questioned about the clinical impact of serial administration of gadoterate meglumine, a macrocyclic GBCA. In this retrospective study (2000-2016) of medical files of patients who received more than 20 administrations of gadoterate, we searched for cerebellar symptoms and signs developing during the regular follow-up. We reviewed medical files of ten patients (mean age 34.4 ± 20.8 years; 4 males, 6 females) who received 28.2 ± 5.3 doses of gadoterate (average total dose of GBCA 518 ± 226 ml; range 185-785 ml). Patients were examined by at least two medical specialists depending on initial diagnosis, and at least once by a neurosurgeon. Mean follow-up time was 91 months (range 49-168) and six out of ten patients experienced new symptoms or signs. No clinician reported the appearance of a rising cerebellar syndrome, nor newly appeared symptoms or signs suggested cerebellar toxicity. This retrospective clinical study shows no de novo clinical cerebellar syndrome following repeated administrations of gadoterate. Our results argue against a cerebellar toxicity of this macrocyclic agent. Still, confirmation in a larger number of subjects is required, as well as clinical studies concerning linear GBCAs whose structure and in vivo stability are distinct.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-017-8631-8DOI Listing
November 2017

The transcriptional response to the olive fruit fly (Bactrocera oleae) reveals extended differences between tolerant and susceptible olive (Olea europaea L.) varieties.

PLoS One 2017 10;12(8):e0183050. Epub 2017 Aug 10.

Dipartimento di Agraria, Università degli Studi di Napoli "Federico II", Portici (NA), Italy.

The olive fruit fly Bactrocera oleae (Diptera: Tephritidae) is the most devastating pest of cultivated olive (Olea europaea L.). Intraspecific variation in plant resistance to B. oleae has been described only at phenotypic level. In this work, we used a transcriptomic approach to study the molecular response to the olive fruit fly in two olive cultivars with contrasting level of susceptibility. Using next-generation pyrosequencing, we first generated a catalogue of more than 80,000 sequences expressed in drupes from approximately 700k reads. The assembled sequences were used to develop a microarray layout with over 60,000 olive-specific probes. The differential gene expression analysis between infested (i.e. with II or III instar larvae) and control drupes indicated a significant intraspecific variation between the more tolerant and susceptible cultivar. Around 2500 genes were differentially regulated in infested drupes of the tolerant variety. The GO annotation of the differentially expressed genes implies that the inducible resistance to the olive fruit fly involves a number of biological functions, cellular processes and metabolic pathways, including those with a known role in defence, oxidative stress responses, cellular structure, hormone signalling, and primary and secondary metabolism. The difference in the induced transcriptional changes between the cultivars suggests a strong genetic role in the olive inducible defence, which can ultimately lead to the discovery of factors associated with a higher level of tolerance to B. oleae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183050PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552259PMC
October 2017

Omics approaches on fresh-cut lettuce reveal global molecular responses to sodium hypochlorite and peracetic acid treatment.

J Sci Food Agric 2018 Jan 11;98(2):737-750. Epub 2017 Aug 11.

Department of Sustainability and Productivity of Territorial Systems, Biotechnology and Agro-Industry Division, ENEA Casaccia Research Center, Rome, Italy.

Background: Lettuce is a leafy vegetable that is extensively commercialized as a ready-to-eat product because of its widespread use in human nutrition as salad. It is well known that washing treatments can severely affect the quality and shelf-life of ready-to-eat vegetables. The study presented here evaluated the effect of two washing procedures on fresh-cut lettuce during storage.

Results: An omics approach was applied to reveal global changes at molecular level induced by peracetic acid washing in comparison with sodium hypochlorite treatment. Microbiological analyses were also performed to quantify total bacterial abundance and composition. The study revealed wide metabolic alterations induced by the two sanitizers. In particular, transcriptomic and proteomic analyses pointed out a number of transcripts and proteins differentially accumulated in response to peracetic acid washing, mainly occurring on the first day of storage. In parallel, different microbiota composition and significant reduction in total bacterial load following washing were also observed.

Conclusion: The results provide useful information for the fresh-cut industry to select an appropriate washing procedure preserving fresh-like attributes as much as possible during storage of the end product. Molecular evidence indicated peracetic acid to be a valid alternative to sodium hypochlorite as sanitizer solution. © 2017 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsfa.8521DOI Listing
January 2018

Cryptochrome 2 extensively regulates transcription of the chloroplast genome in tomato.

FEBS Open Bio 2017 Apr 1;7(4):456-471. Epub 2017 Mar 1.

ENEA Trisaia Research Center Rotondella (MT) Italy.

Light plays a key role in the regulation of many physiological processes required for plant and chloroplast development. Plant cryptochromes (crys) play an important role in monitoring, capturing, and transmitting the light stimuli. In this study, we analyzed the effects of CRY2 overexpression on transcription of tomato chloroplast genome by a tiling array, containing about 90 000 overlapping probes (5-nucleotide resolution). We profiled transcription in leaves of wild-type and CRY2-overexpressing plants grown in a diurnal cycle, to generate a comprehensive map of chloroplast transcription and to monitor potential specific modulations of the chloroplast transcriptome induced by the overexpression of CRY2. Our results demonstrate that CRY2 is a master gene of transcriptional regulation in the tomato chloroplast. In fact, it modulates the day/night mRNA abundance of about 58% of the 114 ORFs. The effect of CRY2 includes a differential extension of some transcripts at their 5'-end, according to the period of the day. We observed that the influence of CRY2 on chloroplast transcription is not limited to coding RNA; a great number of putative noncoding micro RNA also showed differential accumulation pattern. To our knowledge, this is the first study that highlights how a photoreceptor affects the day/night transcription of the chloroplast genome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/2211-5463.12082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377390PMC
April 2017

Distinct gene networks drive differential response to abrupt or gradual water deficit in potato.

Gene 2017 Jan 19;597:30-39. Epub 2016 Oct 19.

National Research Council of Italy, Institute of Biosciences and BioResources, Research Division Portici (CNR-IBBR), Portici (NA), Italy. Electronic address:

Water-limiting conditions affect dramatically plant growth and development and, ultimately, yield of potato plants (Solanum tuberosum L.). Therefore, understanding the mechanisms underlying the response to water deficit is of paramount interest to obtain drought tolerant potato varieties. Herein, potato 10K cDNA array slides were used to profile transcriptomic changes of two potato cell populations under abrupt (shocked cells) or gradual exposure (adapted cells) to polyethylene glycol (PEG)-mediated water stress. Data analysis identified >1000 differentially expressed genes (DEGs) in our experimental conditions. Noteworthy, our microarray study also suggests that distinct gene networks underlie the cellular response to shock or gradual water stress. On the basis of our experimental findings, it is possible to speculate that DEGs identified in shocked cells participate in early protective and sensing mechanisms to environmental insults, while the genes whose expression was modulated in adapted cells are directly involved in the acquisition of a new cellular homeostasis to cope with water stress conditions. To validate microarray data obtained for potato cells, the expression analysis of 21 selected genes of interest was performed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Intriguingly, the expression levels of these transcripts in 4-week old potato plants exposed to long-term water-deficit. qRT-PCR analysis showed that several genes were regulated similarly in potato cells cultures and tissues exposed to drought, thus confirming the efficacy of our simple experimental system to capture important genes involved in osmotic stress response. Highlighting the differences in gene expression between shock-like and adaptive response, our findings could contribute to the discussion on the biological function of distinct gene networks involved in the response to abrupt and gradual adaptation to water deficit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2016.10.024DOI Listing
January 2017

Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline.

PLoS One 2016 29;11(6):e0156807. Epub 2016 Jun 29.

Department of Biology, University of Florence, Florence, Italy.

Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156807PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927098PMC
July 2017

Transcript Analysis and Regulative Events during Flower Development in Olive (Olea europaea L.).

PLoS One 2016 14;11(4):e0152943. Epub 2016 Apr 14.

Italian National Agency for New Technologies, Energy and Sustainable Economic Development, TRISAIA Research Center, Rotondella (MT), Italy.

The identification and characterization of transcripts involved in flower organ development, plant reproduction and metabolism represent key steps in plant phenotypic and physiological pathways, and may generate high-quality transcript variants useful for the development of functional markers. This study was aimed at obtaining an extensive characterization of the olive flower transcripts, by providing sound information on the candidate MADS-box genes related to the ABC model of flower development and on the putative genetic and molecular determinants of ovary abortion and pollen-pistil interaction. The overall sequence data, obtained by pyrosequencing of four cDNA libraries from flowers at different developmental stages of three olive varieties with distinct reproductive features (Leccino, Frantoio and Dolce Agogia), included approximately 465,000 ESTs, which gave rise to more than 14,600 contigs and approximately 92,000 singletons. As many as 56,700 unigenes were successfully annotated and provided gene ontology insights into the structural organization and putative molecular function of sequenced transcripts and deduced proteins in the context of their corresponding biological processes. Differentially expressed genes with potential regulatory roles in biosynthetic pathways and metabolic networks during flower development were identified. The gene expression studies allowed us to select the candidate genes that play well-known molecular functions in a number of biosynthetic pathways and specific biological processes that affect olive reproduction. A sound understanding of gene functions and regulatory networks that characterize the olive flower is provided.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152943PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831748PMC
August 2016

The VZV/IE63-specific T cell response prevents herpes zoster in fingolimod-treated patients.

Neurol Neuroimmunol Neuroinflamm 2016 Apr 10;3(2):e209. Epub 2016 Feb 10.

Laboratory of Neuroimmunology, Center of Research in Neurosciences (A.M., G. Perriard, M.C., F.V., R.D.P.), and Service of Neurology (G. Perrotta, M.S., R.D.P.), Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.

Objective: To assess longitudinally the antiviral immune response of T cells from patients with multiple sclerosis (MS) treated with fingolimod (FTY) vs other disease-modifying treatments (DMTs).

Methods: We assessed cellular immune responses specific to influenza virus (FLU), JC virus (JCV), and varicella-zoster virus (VZV) using quantification of interferon-γ secretion by enzyme-linked immunospot in patients with MS on FTY (n = 31), including 2 with herpes zoster (HZ), natalizumab (n = 11), and other DMTs (n = 11). We used viral lysates for FLU and VZV and a pool of peptides for FLU, JCV (VP-1), and VZV (IE63).

Results: Besides an expected drop of T cells, we found that, proportionally to the number of CD3(+) T cells, only FTY-treated patients with MS exhibited an increased VZV/IE63-specific T cell response peaking 6 months into treatment, a response that returned to baseline after 12 and 24 months. Two FTY-treated patients developed an HZ 6 months into treatment, coinciding with an absent VZV/IE63-specific T cell response. However, cellular immune responses specific to VZV lysate, JCV, and FLU (lysate and pool of peptide epitopes) were similar between all 3 categories (FTY, natalizumab, and other DMTs) of study patients.

Conclusions: FTY-treated patients with MS exhibit an increased VZV/IE63-specific cellular immune response after 6 months of treatment. FTY-treated patients who develop an HZ are not able to mount such a response, suggesting that a T cell response directed against this viral protein may be key in preventing the occurrence of HZ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751153PMC
April 2016

Impact of hyponatremia on nerve conduction and muscle strength.

Eur J Clin Invest 2016 Apr 23;46(4):328-33. Epub 2016 Feb 23.

Internal Medicine, Erasme University Hospital, Université Libre de Bruxelles, Brussel, Belgium.

Background: Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies.

Design: In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to-moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (< 125 mmol/L) before and after the normalization of natremia.

Results: No significant change in muscle strength was observed when natremia was corrected from 127·7 ± 2·5 to 136·1 ± 1·8 mmol/L, contrary to a significant improvement in TUG from 14·9 ± 5·1 to 12·5 ± 4·7 s (P = 0·006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121·9 ± 2·4 to 135·5 ± 3·4 mmol/L (e.g. mean increase of 14·3% for motor nerve conduction and mean decrease of 21·6% for F-wave latency of left peroneal nerve).

Conclusion: Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.12597DOI Listing
April 2016

Bacterial community and proteome analysis of fresh-cut lettuce as affected by packaging.

FEMS Microbiol Lett 2016 Jan 27;363(1):fnv209. Epub 2015 Oct 27.

Sustainable Territorial and Production Systems Department, Biotechnologies and Agro-Industry Division, ENEA Casaccia Research Center, 00123, Rome, Italy

With the growing demand of fresh-cut vegetables, a variety of packaging films are produced specifically to improve safety and quality of the fresh vegetables over the storage period. The aim of our work was to evaluate the influence of different packaging films on the quality of fresh-cut lettuce analyzing changes in bacterial community composition and modifications at the proteome level, by means of culture-dependent/culture-independent methods and differential gel electrophoresis combined with mass spectrometry analysis. Total viable counts indicated the presence of a highly variable and complex microbial flora, around a mean value of 6.26 log10 CFU g(-1). Analysis of terminal-restriction fragment length polymorphism data indicated that bacterial communities changed with packaging films and time, showing differences in community composition and diversity indices between the commercially available package (F) and the new packages (A and C), in the first days after packaging. Also proteomic analysis revealed significant changes, involving proteins related to energy metabolism, photosynthesis, plant defense and oxidative stress processes, between F and A/C packages. In conclusion, microbiological and proteomic analysis have proved to be powerful tools to provide new insights into both the composition of leaf-associated bacterial communities and protein content of fresh-cut lettuce during the shelf-life storage process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/femsle/fnv209DOI Listing
January 2016

Purification of intact chloroplasts from marine plant Posidonia oceanica suitable for organelle proteomics.

Proteomics 2015 Dec;15(23-24):4159-74

Laboratory of Plant Biology and Plant Proteomics (Lab.Bio.Pro.Ve), Department of Chemistry and Chemical Technologies, Università della Calabria, Rende, Italy.

Posidonia oceanica is a marine angiosperm, or seagrass, adapted to grow to the underwater life from shallow waters to 50 m depth. This raises questions of how their photosynthesis adapted to the attenuation of light through the water column and leads to the assumption that biochemistry and metabolism of the chloroplast are the basis of adaptive capacity. In the present study, we described a protocol that was adapted from those optimized for terrestrial plants, to extract chloroplasts from as minimal tissue as possible. We obtained the best balance between tissue amount/intact chloroplasts yield using one leaf from one plant. After isopynic separations, the chloroplasts purity and integrity were evaluated by biochemical assay and using a proteomic approach. Chloroplast proteins were extracted from highly purified organelles and resolved by 1DE SDS-PAGE. Proteins were sequenced by nLC-ESI-IT-MS/MS of 1DE gel bands and identified against NCBInr green plant databases, Dr. Zompo database for seagrasses in a local customized dataset. The curated localization of proteins in sub-plastidial compartments (i.e. envelope, stroma and thylakoids) was retrieved in the AT_CHLORO database. This purification protocol and the validation of compartment markers may serve as basis for sub-cellular proteomics in P. oceanica and other seagrasses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmic.201500246DOI Listing
December 2015

Methodologies and perspectives of proteomics applied to filamentous fungi: from sample preparation to secretome analysis.

Int J Mol Sci 2015 Mar 12;16(3):5803-29. Epub 2015 Mar 12.

UTTRI-GENER Genetics and Genomics for Energy and Environment Laboratory-ENEA TRISAIA Research Center, 75025 Rotondella (Matera), Italy.

Filamentous fungi possess the extraordinary ability to digest complex biomasses and mineralize numerous xenobiotics, as consequence of their aptitude to sensing the environment and regulating their intra and extra cellular proteins, producing drastic changes in proteome and secretome composition. Recent advancement in proteomic technologies offers an exciting opportunity to reveal the fluctuations of fungal proteins and enzymes, responsible for their metabolic adaptation to a large variety of environmental conditions. Here, an overview of the most commonly used proteomic strategies will be provided; this paper will range from sample preparation to gel-free and gel-based proteomics, discussing pros and cons of each mentioned state-of-the-art technique. The main focus will be kept on filamentous fungi. Due to the biotechnological relevance of lignocellulose degrading fungi, special attention will be finally given to their extracellular proteome, or secretome. Secreted proteins and enzymes will be discussed in relation to their involvement in bio-based processes, such as biomass deconstruction and mycoremediation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms16035803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394507PMC
March 2015

The coffee genome provides insight into the convergent evolution of caffeine biosynthesis.

Science 2014 Sep 4;345(6201):1181-4. Epub 2014 Sep 4.

Institut de Recherche pour le Développement (IRD), UMR Résistance des Plantes aux Bioagresseurs (RPB) [Centre de Coopération Internationale en Recherche Agronomique pour le Développement (CIRAD), IRD, UM2)], BP 64501, 34394 Montpellier Cedex 5, France.

Coffee is a valuable beverage crop due to its characteristic flavor, aroma, and the stimulating effects of caffeine. We generated a high-quality draft genome of the species Coffea canephora, which displays a conserved chromosomal gene order among asterid angiosperms. Although it shows no sign of the whole-genome triplication identified in Solanaceae species such as tomato, the genome includes several species-specific gene family expansions, among them N-methyltransferases (NMTs) involved in caffeine production, defense-related genes, and alkaloid and flavonoid enzymes involved in secondary compound synthesis. Comparative analyses of caffeine NMTs demonstrate that these genes expanded through sequential tandem duplications independently of genes from cacao and tea, suggesting that caffeine in eudicots is of polyphyletic origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1255274DOI Listing
September 2014

Proteome regulation during Olea europaea fruit development.

PLoS One 2013 17;8(1):e53563. Epub 2013 Jan 17.

Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), TRISAIA Research Center, Rotondella (Matera), Italy.

Background: Widespread in the Mediterranean basin, Olea europaea trees are gaining worldwide popularity for the nutritional and cancer-protective properties of the oil, mechanically extracted from ripe fruits. Fruit development is a physiological process with remarkable impact on the modulation of the biosynthesis of compounds affecting the quality of the drupes as well as the final composition of the olive oil. Proteomics offers the possibility to dig deeper into the major changes during fruit development, including the important phase of ripening, and to classify temporal patterns of protein accumulation occurring during these complex physiological processes.

Methodology/principal Findings: In this work, we started monitoring the proteome variations associated with olive fruit development by using comparative proteomics coupled to mass spectrometry. Proteins extracted from drupes at three different developmental stages were separated on 2-DE and subjected to image analysis. 247 protein spots were revealed as differentially accumulated. Proteins were identified from a total of 121 spots and discussed in relation to olive drupe metabolic changes occurring during fruit development. In order to evaluate if changes observed at the protein level were consistent with changes of mRNAs, proteomic data produced in the present work were compared with transcriptomic data elaborated during previous studies.

Conclusions/significance: This study identifies a number of proteins responsible for quality traits of cv. Coratina, with particular regard to proteins associated to the metabolism of fatty acids, phenolic and aroma compounds. Proteins involved in fruit photosynthesis have been also identified and their pivotal contribution in oleogenesis has been discussed. To date, this study represents the first characterization of the olive fruit proteome during development, providing new insights into fruit metabolism and oil accumulation process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053563PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547947PMC
July 2013