Comparative evolutionary analyses of eight whitefly Bemisia tabaci sensu lato genomes: cryptic species, agricultural pests and plant-virus vectors.

BACKGROUND: The group of > 40 cryptic whitefly species called Bemisia tabaci sensu lato are amongst the world's worst agricultural pests and plant-virus vectors. Outbreaks of B. tabaci s.l. and the associated plant-virus diseases continue to contribute to global food insecurity and social instability, particularly in sub-Saharan Africa and Asia. Published B. tabaci s.l. genomes have limited use for studying African cassava B. tabaci SSA1 species, due to the high genetic divergences between them. Genomic annotations presented here were performed using the 'Ensembl gene annotation system', to ensure that comparative analyses and conclusions reflect biological differences, as opposed to arising from different methodologies underpinning transcript model identification. RESULTS: We present here six new B. tabaci s.l. genomes from Africa and Asia, and two re-annotated previously published genomes, to provide evolutionary insights into these globally distributed pests. Genome sizes ranged between 616-658 Mb and exhibited some of the highest coverage of transposable elements reported within Arthropoda. Many fewer total protein coding genes (PCG) were recovered compared to the previously published B. tabaci s.l. genomes and structural annotations generated via the uniform methodology strongly supported a repertoire of between 12.8-13.2 × 103 PCG. An integrative systematics approach incorporating phylogenomic analysis of nuclear and mitochondrial markers supported a monophyletic Aleyrodidae and the basal positioning of B. tabaci Uganda-1 to the sub-Saharan group of species. Reciprocal cross-mating data and the co-cladogenesis pattern of the primary obligate endosymbiont 'Candidatus Portiera aleyrodidarum' from 11 Bemisia genomes further supported the phylogenetic reconstruction to show that African cassava B. tabaci populations consist of just three biological species. We include comparative analyses of gene families related to detoxification, sugar metabolism, vector competency and evaluate the presence and function of horizontally transferred genes, essential for understanding the evolution and unique biology of constituent B. tabaci. s.l species. CONCLUSIONS: These genomic resources have provided new and critical insights into the genetics underlying B. tabaci s.l. biology. They also provide a rich foundation for post-genomic research, including the selection of candidate gene-targets for innovative whitefly and virus-control strategies.

Suicidal ideation among people with Parkinson's disease and comparison with a control group.

BACKGROUND: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. METHODS: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI. RESULTS: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041). CONCLUSION: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.

Glucosylation prevents plant defense activation in phloem-feeding insects.

The metabolic adaptations by which phloem-feeding insects counteract plant defense compounds are poorly known. Two-component plant defenses, such as glucosinolates, consist of a glucosylated protoxin that is activated by a glycoside hydrolase upon plant damage. Phloem-feeding herbivores are not generally believed to be negatively impacted by two-component defenses due to their slender piercing-sucking mouthparts, which minimize plant damage. However, here we document that glucosinolates are indeed activated during feeding by the whitefly Bemisia tabaci. This phloem feeder was also found to detoxify the majority of the glucosinolates it ingests by the stereoselective addition of glucose moieties, which prevents hydrolytic activation of these defense compounds. Glucosylation of glucosinolates in B. tabaci was accomplished via a transglucosidation mechanism, and two glycoside hydrolase family 13 (GH13) enzymes were shown to catalyze these reactions. This detoxification reaction was also found in a range of other phloem-feeding herbivores.

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. METHODS: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. RESULTS: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (ß = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. CONCLUSION: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.

Predictors of the change in burden, strain, mood, and quality of life among caregivers of Parkinson's disease patients.

BACKGROUND AND OBJECTIVE: Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes. PATIENTS AND METHODS: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied. RESULTS: Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; ß = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (ß = 0.416; p < 0.0001), CSI (ß = 0.277; p = 0.001), and EUROHIS-QOL (ß = 0.397; p = 0.002). CONCLUSION: Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase.

Safinamide improves sleep and daytime sleepiness in Parkinson's disease: results from the SAFINONMOTOR study.

BACKGROUND AND OBJECTIVE: Some studies observed a benefit of PD patients after treatment with safinamide in some non-motor symptoms. Our aim was to analyze the effectiveness of safinamide on sleep and daytime sleepiness in Parkinson's disease (PD) patients. MATERIAL AND METHODS: SAFINONMOTOR is a prospective open-label single-arm study conducted in 5 centers from Spain. In this analysis, a secondary objective of the study, the score in the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) at V1 (baseline) and V4 (6 months ± 1 month) were compared. RESULTS: Fifty patients were included between May/2019 and February/2020 (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The PSQI total score was reduced by 19.8% (from 10.43 ± 4.02 at V1 to 8.36 ± 4.41 at V4; p = 0.001). By domains, improvement was observed in subjective sleep quality (PSQI-C1; - 23.9%; p = 0.009), sleep latency (PSQI-C2; - 25%; p = 0.025), sleep duration (PSQI-C3; - 40%; p = 0.001), and habitual sleep efficiency (PSQI-C4; - 25.9%; p = 0.023). A significant reduction (- 24.7%) in the ESS total score from V1 to V4 was observed as well (from 9.20 ± 5.64 to 6.93 ± 5.11; p = 0.012). Specifically, the improvement in daytime sleepiness was observed in sitting and reading (p = 0.024) and sitting inactive in a public space (p = 0.027). A total of 21 adverse events in 11 patients (22%) were reported, 5 of which were severe (not related to safinamide). CONCLUSION: Safinamide was well-tolerated and improved sleep and daytime sleepiness in PD patients at 6 months.

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.

Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson's Disease.

INTRODUCTION: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. METHODS: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson's disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. RESULTS: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015-1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009-1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. CONCLUSION: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

Impact of Coronavirus Disease 2019 Pandemic on Parkinson's Disease: A Cross-Sectional Survey of 568 Spanish Patients.

BACKGROUND: The aim of this study was to know the impact of the coronavirus disease 2019 (COVID-19) pandemic on Spanish patients with Parkinson's disease (PD). METHODS: This is a descriptive, observational, cross-sectional study. An anonymous online survey with 95 questions was distributed among patients. Responses were collected from 11 May 2020 to 20 July 2020. RESULTS: Of a total of 570 questionnaires received, 568 (99.6%) were considered valid for the analysis (mean age, 63.5 ± 12.5 years; 53% females). A total of 553 patients (97.4%) were aware of the COVID-19 pandemic and 68.8% were concerned about it; 95.6% took preventive measures. A total of 484 patients (85.2%) had no contact with cases of COVID-19, and only 15 (2.6%) had confirmed COVID-19. Although up to 72.7% remained active during confinement, 65.7% perceived a worsening of their symptoms. CONCLUSIONS: Spanish patients with PD perceived the COVID-19 pandemic with concern and responsibility. More than half experienced worsening of their symptoms during confinement. © 2020 International Parkinson and Movement Disorder Society.

The impact of freezing of gait on functional dependency in Parkinson's disease with regard to motor phenotype.

BACKGROUND AND OBJECTIVE: Freezing of gait (FOG) is a disabling symptom more frequent in Parkinson's disease (PD) patients with postural instability gait difficulty (PIGD) phenotype. The aim of this study was to determine the prevalence of self-reported FOG in a large group of PD patients as well as assess its relationship with functional dependency with regard to motor phenotype. METHODS: The data correspond to the baseline evaluation of the COPPADIS-2015 study. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the freezing of gait questionnaire (FOG-Q). Functional dependency was defined as a Schwab and England (S&E) ADL scale score less than 80%. PIGD and non-PIGD (tremor dominant + indeterminate) groups were considered regarding to motor phenotype. RESULTS: Among the 689 PD patients (62.6 ± 8.9 years old, 59.8% males), 240 reported FOG (34.8%), whereas 63 presented functional dependency (9.1%). A total of 22.1% of patients with FOG presented functional dependency vs. only 2.2% of those without FOG (p < 0.0001). FOG was related to functional dependency (OR = 3.470; 95%CI 1.411-8.530; p = 0.007) after adjustment to age, gender, disease duration, daily equivalent levodopa dose, comorbidity (number of non-antiparkinsonian drugs/day), motor status (UPDRS-III), PIGD phenotype, motor complications (UPDRS-IV), NMS burden (NMSS total score), cognition (PD-CRS), and mood (BDI-II). However, according to motor phenotype, FOG was related to functional dependency only in PIGD patients (OR = 7.163; 95%CI 1.206-42.564; p = 0.030). CONCLUSIONS: Self-reported FOG is associated with functional dependency in PIGD but not in non-PIGD motor phenotype patients.

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Frateuria defendens sp. nov., bacterium isolated from the yellows grapevine's disease vector Hyalesthes obsoletus.

A Dyella-like bacterium was previously isolated from the planthopper Hyalesthes obsoletus (Hemiptera). Based on its 16S rRNA gene sequence, strain DHoT was assigned to the family Rhodanobacteraceae with Dyella and Frateuria as its closest relatives. The closest 16S rRNA gene sequences were Frateuria aurantia DSM 6220T (98.2 %), Dyella thiooxydans ATSB10T (98 %), Dyella terrae JS14-6T (97.8 %) and Dyella marensis CS5-B2T (97.8 %). Strain DHoT is a Gram-negative, aerobic, motile, yellow-pigmented, rod-shaped bacterium. Strain DHoT cells grew well at 28-30 °C and at pH 6.5-7.5 on a nutrient agar plate. DNA-DNA hybridization showed that the relatedness between strain DHoT and D. jiangningensis strain SBZ3-12T, and F. aurantia DSM 6220T was 42.7 and 42.6 %, respectively. Ubiquinone Q-8 was the predominant respiratory quinone, and the major fatty acids (>10 %) were iso-C15 : 0, iso-C16 : 0 and iso-C17 : 0. In silico analysis based on phylogenetics and sequence identity at the nucleotide and protein levels suggests that Frateuria is the closest known relative of strain DHoT. Based on the phenotypic, chemotaxonomic and phylogenetic data, strain DHoT was designated as a novel species of the genus Frateuria, for which the name Frateuria defendens sp. nov. is proposed. The type strain is DHoT (=NCCB 100648T; =DLBT=DSM 106169T).

Modeling trophic dependencies and exchanges among insects' bacterial symbionts in a host-simulated environment.

BACKGROUND: Individual organisms are linked to their communities and ecosystems via metabolic activities. Metabolic exchanges and co-dependencies have long been suggested to have a pivotal role in determining community structure. In phloem-feeding insects such metabolic interactions with bacteria enable complementation of their deprived nutrition. The phloem-feeding whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) harbors an obligatory symbiotic bacterium, as well as varying combinations of facultative symbionts. This well-defined bacterial community in B. tabaci serves here as a case study for a comprehensive and systematic survey of metabolic interactions within the bacterial community and their associations with documented occurrences of bacterial combinations. We first reconstructed the metabolic networks of five common B. tabaci symbionts genera (Portiera, Rickettsia, Hamiltonella, Cardinium and Wolbachia), and then used network analysis approaches to predict: (1) species-specific metabolic capacities in a simulated bacteriocyte-like environment; (2) metabolic capacities of the corresponding species' combinations, and (3) dependencies of each species on different media components. RESULTS: The predictions for metabolic capacities of the symbionts in the host environment were in general agreement with previously reported genome analyses, each focused on the single-species level. The analysis suggests several previously un-reported routes for complementary interactions and estimated the dependency of each symbiont in specific host metabolites. No clear association was detected between metabolic co-dependencies and co-occurrence patterns. CONCLUSIONS: The analysis generated predictions for testable hypotheses of metabolic exchanges and co-dependencies in bacterial communities and by crossing them with co-occurrence profiles, contextualized interaction patterns into a wider ecological perspective.

Species-complex diversification and host-plant associations in Bemisia tabaci: A plant-defence, detoxification perspective revealed by RNA-Seq analyses.

Insect-plant associations and their role in diversification are mostly studied in specialists. Here, we aimed to identify macroevolution patterns in the relationships between generalists and their host plants that have the potential to promote diversification. We focused on the Bemisia tabaci species complex containing more than 35 cryptic species. Mechanisms for explaining this impressive diversification have focused so far on allopatric forces that assume a common, broad, host range. We conducted a literature survey which indicated that species in the complex differ in their host range, with only few showing a truly broad one. We then selected six species, representing different phylogenetic groups and documented host ranges. We tested whether differences in the species expression profiles of detoxification genes are shaped more by their phylogenetic relationships or by their ability to successfully utilize multiple hosts, including novel ones. Performance assays divided the six species into two groups of three, one showing higher performance on various hosts than the other (the lower performance group). The same grouping pattern appeared when the species were clustered according to their expression profiles. Only species placed in the lower performance group showed a tendency to lower the expression of multiple genes. Taken together, these findings bring evidence for the existence of a common detoxification "machinery," shared between species that can perform well on multiple hosts. We raise the possibility that this "machinery" might have played a passive role in the diversification of the complex, by allowing successful migration to new/novel environments, leading, in some cases, to fragmentation and speciation.

Nature lessons: The whitefly bacterial endosymbiont is a minimal amino acid factory with unusual energetics.

Reductive genome evolution is a universal phenomenon observed in endosymbiotic bacteria in insects. As the genome reduces its size and irreversibly losses coding genes, the functionalities of the cell system, including the energetics processes, are more restricted. Several energetic pathways can also be lost. How do these reduced metabolic networks sustain the energy needs of the system? Among the bacteria with reduced genomes Candidatus Portiera aleyrodidarum, obligate endosymbiont of whiteflies, represents an extreme case since lacks several key mechanisms for ATP generation. Thus, to analyze the cell energetics in this system, a genome-scale metabolic model of this endosymbiont was constructed, and its energy production capabilities dissected using stoichiometric analysis. Our results suggest that energy generation is coupled to the synthesis of essential amino acids and carotenoids, crucial metabolites in the symbiotic association. A deeper insight showed that ATP production via carotenoid synthesis is also connected with amino acid production. This unusual association of energy production with anabolism suggests that, although minimized, endosymbiont metabolic networks maintain a remarkable biosynthetic potential.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progression.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression. METHODS/DESIGN: Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. STUDY POPULATION: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. FUNDING: Public/Private. DISCUSSION: COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Genome reduction and potential metabolic complementation of the dual endosymbionts in the whitefly Bemisia tabaci.

BACKGROUND: The whitefly Bemisia tabaci is an important agricultural pest with global distribution. This phloem-sap feeder harbors a primary symbiont, "Candidatus Portiera aleyrodidarum", which compensates for the deficient nutritional composition of its food sources, and a variety of secondary symbionts. Interestingly, all of these secondary symbionts are found in co-localization with the primary symbiont within the same bacteriocytes, which should favor the evolution of strong interactions between symbionts. RESULTS: In this paper, we analyzed the genome sequences of the primary symbiont Portiera and of the secondary symbiont Hamiltonella in the B. tabaci Mediterranean (MED) species in order to gain insight into the metabolic role of each symbiont in the biology of their host. The genome sequences of the uncultured symbionts Portiera and Hamiltonella were obtained from one single bacteriocyte of MED B. tabaci. As already reported, the genome of Portiera is highly reduced (357 kb), but has kept a number of genes encoding most essential amino-acids and carotenoids. On the other hand, Portiera lacks almost all the genes involved in the synthesis of vitamins and cofactors. Moreover, some pathways are incomplete, notably those involved in the synthesis of some essential amino-acids. Interestingly, the genome of Hamiltonella revealed that this secondary symbiont can not only provide vitamins and cofactors, but also complete the missing steps of some of the pathways of Portiera. In addition, some critical amino-acid biosynthetic genes are missing in the two symbiotic genomes, but analysis of whitefly transcriptome suggests that the missing steps may be performed by the whitefly itself or its microbiota. CONCLUSIONS: These data suggest that Portiera and Hamiltonella are not only complementary but could also be mutually dependent to provide a full complement of nutrients to their host. Altogether, these results illustrate how functional redundancies can lead to gene losses in the genomes of the different symbiotic partners, reinforcing their inter-dependency.

Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.