Suchergebnisse

We report here the results obtained in surface ablation of RbTiOPO4 single crystals by femtosecond laser. We fabricated and characterized one-dimensional (1D) diffraction gratings with different lattice spacings of 15 and 20 μm, and with a sub-modulation of the period introduced in the later. The optical and electronic microscopy characterization and filling factor analysis of these diffraction gratings are reported. We also show that the roughness generated on the grooves by the ablation process can be improved by chemical etching. ; This work was partially funded by the European Commission under the Seventh Framework Program under Project Cleanspace FP7-SPACE-2010-1-GA-263044, supported by the Spanish Government under Projects PI09/90527, TEC2009-09551, AECID A/024560/09, FIS2009-09522, HOPE CSD2007-00007 and SAUUL CSD2007-00013 (Consolider-Ingenio 2010), by Catalan Government under Projects 2009SGR235 and 2009SGR549, by Junta de Castilla y León under Project GR27, and by the Research Center on Engineering of Materials and Systems (EMaS) of the URV. J.J.C. is supported by the Education and Science Ministry of Spain and European Social Fund under the Ramón y Cajal program, RYC2006-858. We also acknowledge support from the Centro de Laseres Pulsados, CLPU, Salamanca, Spain.

Objetivo: Valorar la influencia de la precariedad laboral y la exclusión social en la salud de hombres ymujeres migrantes que trabajan en el sector agrícola en Espa ̃na.Método: Se recogerán datos cualitativos y cuantitativos en cuatro comunidades autónomas (Catalu ̃na, LaRioja, Murcia y Andalucía) entre 2021 y 2022. En una primera fase se realizarán entrevistas personalessemiestructuradas, con un mínimo de 40 informantes clave profesionales o expertos (de ONG, asocia-ciones, sanidad, servicios sociales, sindicatos, cooperativas agrícolas, política y mediadores culturales).En una segunda fase se combinarán entrevistas personales con técnicas cualitativas participativas (bodymapping y photovoice), con 40 hombres y mujeres migrantes jornaleros/as. En una tercera fase se reali-zará un estudio transversal con una muestra estimada de 400-500 migrantes jornaleros/as basada en laEncuesta Nacional de Salud y la Encuesta de Condiciones de Vida. ; Objective: To assess the influence of job insecurity and social exclusion on the health of migrant men andwomen working in the agricultural sector in Spain.Method: Qualitative and quantitative data will be collected in four Spanish autonomous regions (Catalo-nia, La Rioja, Murcia, and Andalusia) between 2021 and 2022. First, semi-structured personal interviewswith at least 40 professional key informants or experts (from NGOs, associations, health, social servi-ces, trade unions, agricultural cooperatives, politics, and cultural mediators). Second, semi-structuredpersonal interviews combined with participatory techniques (body mapping and photovoice) will beconducted with 40 migrant men and women working in agriculture. Thirdly, a cross-sectional study withan estimated sample of 400–500 migrants working in agriculture, based on the National Health Surveyand the Living Conditions Survey

14 p.-5 fig. ; Glycogen synthase kinase-3 (GSK-3) is ubiquitously expressed throughout the brain and involved in vital molecular pathways such as cell survival and synaptic reorganization and has emerged as a potential drug target for brain diseases. A causal role for GSK-3, in particular the brain-enriched GSK-3β isoform, has been demonstrated in neurodegenerative diseases such as Alzheimer's and Huntington's, and in psychiatric diseases. Recent studies have also linked GSK-3 dysregulation to neuropathological outcomes in epilepsy. To date, however, there has been no genetic evidence for the involvement of GSK-3 in seizure-induced pathology. Status epilepticus (prolonged, damaging seizure) was induced via a microinjection of kainic acid into the amygdala of mice. Studies were conducted using two transgenic mouse lines: a neuron-specific GSK-3β overexpression and a neuron-specific dominant-negative GSK-3β (GSK-3β-DN) expression in order to determine the effects of increased or decreased GSK-3β activity, respectively, on seizures and attendant pathological changes in the hippocampus. GSK-3 inhibitors were also employed to support the genetic approach. Status epilepticus resulted in a spatiotemporal regulation of GSK-3 expression and activity in the hippocampus, with decreased GSK-3 activity evident in non-damaged hippocampal areas. Consistent with this, overexpression of GSK-3β exacerbated status epilepticus-induced neurodegeneration in mice. Surprisingly, decreasing GSK-3 activity, either via overexpression of GSK-3β-DN or through the use of specific GSK-3 inhibitors, also exacerbated hippocampal damage and increased seizure severity during status epilepticus. In conclusion, our results demonstrate that the brain has limited tolerance for modulation of GSK-3 activity in the setting of epileptic brain injury. These findings caution against targeting GSK-3 as a treatment strategy for epilepsy or other neurologic disorders where neuronal hyperexcitability is an underlying pathomechanism. ; This work was supported by funding from the Sixth Framework Programme (MIRG-CT-2004-014567, to D.C.H.) a IRCSET-Marie Curie International Mobility Fellowship, the Health Research Board (PD/2009/31 to T.E. and HRA_POR/ 2011/41 to D.C.H.); Science Foundation Ireland (13/SIRG/2098 and 17/CDA/ 4708 to T.E. and 16/RC/3948 to D.C.H.) and co-funded under the European Regional Development Fund and by FutureNeuro industry partners;); from the H2020 Marie Skłowdowksa-Curie Actions Individual Fellowship (753527 to E.B.); from the European Union's Horizon 2020 research and innovation programme under the Marie Sklowdowska-Cuire grant agreement (No. 766124 to T.E.); grants from Ministerio de Economía Industria y Competitividad of Spain SAF2009-08233 and SAF2015-65371-R to J.J.L., SAF2016-78603-R to M.M. and BFU2016-77885-P to F.H.; grant PI2015-2/06-3 from CIBERNED-ISCIII to J.J.L.; and institutional grants to CBMSO from Fundación Ramón Areces and Fundación Banco de Santander. ; Peer reviewed

Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immunesystem, predominantly Th17 and lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and in target organ damage. Preclinical studiesin mice have shown that systemic adminstration of IL-17A increases blood pressure, prob-ably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are alreadyelevated in patients with mild or moderate hypertension. Many studies in hypertensive mice models have detected IL-17A-producing cells in target organs such as the heart, vesselsand kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17lymphocytes and lymphocytes that express IL-17A. In addition, in experimental models ofhypertension, the blockade of IL-17A by genetic strategies or using neutralizing antibodies,disminished blood pressure, probablyby acting on the small mesenteric arteries as well as inthe regulation of tubule sodium transport. Moreover, IL-17A inhibition reduces end-organsdamage. As a whole, the data presented in this review suggest that IL-17A participates in theregulation of blood pressure and in the genesis and maintenance of arterial hypertension,and may constitute a therapeutic target of hypertension-related pathologies in the future. ; La interleuquina 17A (IL-17A) es una citoquina proinflamatoria producida por células del sis-tema inmune, sobre todo por los linfocitos Th17 y los linfocitos . En este trabajo, revisamosel papel de IL-17A en la patogenia de la hipertensión y de la lesión en órganos diana. Estu-dios en ratones han demostrado que la IL-17A aumenta la presión arterial, probablementepor acciones a varios niveles. Además, las concentraciones plasmáticas de IL-17A están yaaumentadas en pacientes con hipertensión arterial ligera o moderada. Estudios preclíni-cos sobre hipertensión arterial han detectado células productoras de IL-17A en órganosdiana, como corazón, vasos y ri ̃nón. En pacientes con nefroesclerosis hipertensiva existeinfiltración del ri ̃nón por linfocitos Th17 y linfocitos que expresan IL-17A. Además, enmodelos experimentales de hipertensión el bloqueo de IL-17A, mediante estrategias génicas,o utilizando anticuerpos neutralizantes, disminuye la presión arterial por acciones sobre lapared vascular y el transporte tubular de sodio y disminuye la lesión en órganos diana. Enconjunto, los datos presentados en esta revisión sugieren que la IL-17A participa en la reg-ulación de la presión arterial y en la génesis y mantenimiento de la hipertensión arterial,pudiendo constituir una diana terapéutica en el futuro. ; This work has been funded by the Spanish Society of Nephrology and by grants from the Carlos III Health Institute (ISCIII) and FEDER European Union Funds (PI17/00119 and PI20/00140 and Renal Research Network (REDINREN): RD16/0009, to MR-O, RS, PI17/01495 to JE), Community of Madrid («NOVELREN» B2017/BMD3751 to MR-O); the José Castillejo grant (CAS19/00133 to RRR-D); «Juan de la Cierva Incorporacion» of the Ministry of Economy, Industry and Competitiveness (MINECO) for SR-M (IJC2018-035187-I); "Call for Dynamization Europe Research 2019" MINECO (EIN2019-103294 to MR-O and SR-M); IMPROVE-PD project («Identification and Management of Patients at Risk – Outcome and Vascular Events in Peritoneal Dialysis») of Horizon 2020 MarieSkłodowska-Curie Grant Agreement No. 812699 to MRO, and Fondecyt Chile 1160465

Objectives: Social dysfunction is one of the most common signs of major neuropsychiatric disorders. The Default Mode Network (DMN) is crucially implicated in both psychopathology and social dysfunction, although the transdiagnostic properties of social dysfunction remains unknown. As part of the pan-European PRISM (Psychiatric Ratings using Intermediate Stratified Markers) project, we explored cross-disorder impact of social dysfunction on DMN connectivity. Methods: We studied DMN intrinsic functional connectivity in relation to social dysfunction by applying Independent Component Analysis and Dual Regression on resting-state fMRI data, among schizophrenia (SZ; N=48), Alzheimer disease (AD; N=47) patients and healthy controls (HC; N=55). Social dysfunction was operationalised via the Social Functioning Scale (SFS) and De Jong-Gierveld Loneliness Scale (LON). Results: Both SFS and LON were independently associated with diminished DMN connectional integrity within rostromedial prefrontal DMN subterritories (pcorrected range=0.02–0.04). The combined effect of these indicators (Mean.SFS + LON) on diminished DMN connectivity was even more pronounced (both spatially and statistically), independent of diagnostic status, and not confounded by key clinical or sociodemographic effects, comprising large sections of rostromedial and dorsomedial prefrontal cortex (pcorrected =0.01). Conclusions: These findings pinpoint DMN connectional alterations as putative transdiagnostic endophenotypes for social dysfunction and could aid personalised care initiatives grounded in social behaviour ; The project leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115916. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's views and neither the IMI 2JU nor EFPIA nor the European Commission are liable for any use that may be made of the ...

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. Methods: We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content "self-reported pain experienced at the time of the interview", with a dichotomous (yes or no) modality. Results: Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. Conclusions: Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates. ; The ATHLOS project (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 635316.

Background: Questionnaires are the current hallmark for quantifying social functioning in human clinical research. In this study, we compared self- and proxy-rated (caregiver and researcher) assessments of social functioning in Schizophrenia (SZ) and Alzheimer's disease (AD) patients and evaluated if the discrepancy between the two assessments is mediated by disease-related factors such as symptom severity. Methods: We selected five items from the WHO Disability Assessment Schedule 2.0 (WHODAS) to assess social functioning in 53 AD and 61 SZ patients. Caregiver- and researcher-rated assessments of social functioning were used to calculate the discrepancies between self-rated and proxy-rated assessments. Furthermore, we used the number of communication events via smartphones to compare the questionnaire outcomes with an objective measure of social behaviour. Results: WHODAS results revealed that both AD (p < 0.001) and SZ (p < 0.004) patients significantly overestimate their social functioning relative to the assessment of their caregivers and/or researchers. This overestimation is mediated by the severity of cognitive impairments (MMSE; p = 0.019) in AD, and negative symptoms (PANSS; p = 0.028) in SZ. Subsequently, we showed that the proxy scores correlated more strongly with the smartphone communication events of the patient when compared to the patient-rated questionnaire scores (self; p = 0.076, caregiver; p < 0.001, researcher-rated; p = 0.046). Conclusion: Here we show that the observed overestimation of WHODAS social functioning scores in AD and SZ patients is partly driven by disease-related biases such as cognitive impairments and negative symptoms, respectively. Therefore, we postulate the development and implementation of objective measures of social functioning that may be less susceptible to such biases. ; The PRISM project (www.prism-project.eu) leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115916. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the authors' views neither IMI JU nor EFPIA nor the European Commission are liable for any use that may be made of the information contained therein. Dr. Arango has also received funding support by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, "A way of making Europe", CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. Fundación Familia Alonso and Fundación Alicia Koplowitz

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents. Methods: We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors. Results: A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80). Conclusions: Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese. ; The ATHLOS project (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 635316

Based on many clinical and preclinical findings the 'vigilance regulation model of mania' postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605). ; The work was supported by a grant of the Spanish 'Ministerio de Sanidad, Politica Social e Igualdad' (Ministry of Health, Social Politics and Equality), EC10-110, EC10-297, EC10-333 and EC10-064, and by the Instituto de Salud Carlos III of Spain (CIBERSAM), grant 11INT2 which had been provided after a peer review process. The funding source had no rule in the study ...

The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on the global, randomised, double-blind, placebo-controlled Phase III TOURMALINE-MM1 study of ixazomib-Rd (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma. IRd resulted in a significant improvement in progression-free survival versus placebo-Rd (median: 20·6 vs. 14·7 months; hazard ratio 0·74). Common toxicities observed more commonly with IRd versus placebo-Rd were thrombocytopenia, nausea, vomiting, diarrhoea, constipation, rash, peripheral neuropathy, peripheral oedema and back pain; these were generally grade 1/2 in severity except for thrombocytopenia (19% vs. 9% grade 3/4), which appeared manageable and reversible, with no differences between arms in significant bleeding or dose discontinuations. No cumulative toxicities were observed, indicating the potential feasibility of long-term IRd treatment. Safety data from TOURMALINE-MM1 are reviewed and guidance for managing clinically relevant adverse events associated with IRd is provided. Most toxicities were manageable with supportive care and dose delays or reductions as needed. Clinicians should be aware of and understand these potential side effects to optimise and prolong patient benefit.

Death receptors (DRs) and their ligands are expressed in developing nervous system. However, neurons are generally resistant to death induction through DRs and rather their activation promotes neuronal outgrowth and branching. These results suppose the existence of DRs antagonists expressed in the nervous system. Fas apoptosis inhibitory molecule (FAIMS ) was first identified as a Fas antagonist in B-cells. Soon after, a longer alternative spliced isoform with unknown function was identified and named FAIML. FAIMS is widely expressed, including the nervous system, and we have shown previously that it promotes neuronal differentiation but it is not an anti-apoptotic molecule in this system. Here, we demonstrate that FAIML is expressed specifically in neurons, and its expression is regulated during the development. Expression could be induced by NGF through the extracellular regulated kinase pathway in PC12(pheochromocytoma cell line) cells. Contrary to FAIMS , FAIML does not increase the neurite outgrowth induced by neurotrophins and does not interfere with nuclear factor ĸB pathway activation as FAIMS does. Cells overexpressing FAIML are resistant to apoptotic cell death induced by DRs such as Fas or tumor necrosis factor R1. Reduction of endogenous expression by small interfering RNA shows that endogenousFAIML protects primary neurons from DR-induced cell death. The detailed analysis of this antagonism shows thatFAIML can bind to Fas receptor and prevent the activation of the initiator caspase-8 induced by Fas. In conclusion, our results indicate that FAIML could be responsible for maintaining initiator caspases inactive after receptor engagement protecting neurons from the cytotoxic action of death ligands. ; This work was supported by Spanish Government "Ministerio de Sanidad y Consumo" (contract number PI020051, PI04/2364, Redes Temáticas de Investigación Cooperativa, and CiberNed), Fundació La Caixa (Ayudas a la Investigación en Enfermedades Neurodegenerativas 02/055-00), Ministerio de Educacio´n y Ciencia (SAF-2005- 0176), and Generalitat de Catalunya (Suport als Grups de Recerca Consolidats and Distinció a Joves Investigadors). M.F.S., C.S., and M.J.P.-G. were supported by a postgraduate fellowship from the Spanish Government, Ministerio de Educación y Ciencia and Fondo de Investigación Sanitaria, respectively. R.G. holds a postgraduate fellowship from the Department d'Universitat, Recerca i Societat de la Informació (Generalitat de Catalunya) and Fons Social Europeu. N.B. is the recipient of a postgraduate fellowship from the Gobierno Vasco. V.J.Y. was under a Beatriu de Pino´s contract from Generalitat de Catalunya.

The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on the global, randomised, double-blind, placebo-controlled Phase III TOURMALINE-MM1 study of ixazomib-Rd (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma. IRd resulted in a significant improvement in progression-free survival versus placebo-Rd (median: 20·6 vs. 14·7 months; hazard ratio 0·74). Common toxicities observed more commonly with IRd versus placebo-Rd were thrombocytopenia, nausea, vomiting, diarrhoea, constipation, rash, peripheral neuropathy, peripheral oedema and back pain; these were generally grade 1/2 in severity except for thrombocytopenia (19% vs. 9% grade 3/4), which appeared manageable and reversible, with no differences between arms in significant bleeding or dose discontinuations. No cumulative toxicities were observed, indicating the potential feasibility of long-term IRd treatment. Safety data from TOURMALINE-MM1 are reviewed and guidance for managing clinically relevant adverse events associated with IRd is provided. Most toxicities were manageable with supportive care and dose delays or reductions as needed. Clinicians should be aware of and understand these potential side effects to optimise and prolong patient benefit.

MEC, Spain [BFU2011-23896]; European Union [278976]; Postdok BIOGLOBE, Czech Republic [CZ.1.07/2.3.00/30.0032]; European Social Fund; state budget of the Czech Republic; Ministerio de Educacion, Cultura y Deporte, Spain; EU [238511]This research was supported by MEC, Spain, grant BFU2011-23896 (JF), European Union FP7 ANTIGONE project number 278976 (JF) and Postdok BIOGLOBE, Czech Republic CZ.1.07/2.3.00/30.0032 co-financed by the European Social Fund and the state budget of the Czech Republic (JS). N. Ayllon was funded by Ministerio de Educacion, Cultura y Deporte, Spain. S. Weisheit was supported by the POSTICK ITN (Post-graduate training network for capacity building to control ticks and tick-borne diseases) within the FP7-PEOPLE-ITN programme (EU Grant No. 238511). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.06Public library scienceSan francisco ; Anaplasma phagocytophilum is an emerging zoonotic pathogen transmitted by Ixodes scapularis that causes human granulocytic anaplasmosis. Here, a high throughput quantitative proteomics approach was used to characterize A. phagocytophilum proteome during rickettsial multiplication and identify proteins involved in infection of the tick vector, I. scapularis. The first step in this research was focused on tick cells infected with A. phagocytophilum and sampled at two time points containing 10-15% and 65-71% infected cells, respectively to identify key bacterial proteins over-represented in high percentage infected cells. The second step was focused on adult female tick guts and salivary glands infected with A. phagocytophilum to compare in vitro results with those occurring during bacterial infection in vivo. The results showed differences in the proteome of A. phagocytophilum in infected ticks with higher impact on protein synthesis and processing than on bacterial replication in tick salivary glands. These results correlated well with the developmental cycle of A. phagocytophilum, in which cells convert from an intracellular reticulated, replicative form to the nondividing infectious dense-core form. The analysis of A. phagocytophilum differentially represented proteins identified stress response (GroEL, HSP70) and surface (MSP4) proteins that were over-represented in high percentage infected tick cells and salivary glands when compared to low percentage infected cells and guts, respectively. The results demonstrated that MSP4, GroEL and HSP70 interact and bind to tick cells, thus playing a role in rickettsia-tick interactions. The most important finding of these studies is the increase in the level of certain bacterial stress response and surface proteins in A. phagocytophilum-infected tick cells and salivary glands with functional implication in tick-pathogen interactions. These results gave a new dimension to the role of these stress response and surface proteins during A. phagocytophilum infection in ticks. Characterization of Anaplasma proteome contributes information on host-pathogen interactions and provides targets for development of novel control strategies for pathogen infection and transmission.

MEC, Spain [BFU2011-23896]; European Union [278976]; Postdok BIOGLOBE, Czech Republic [CZ.1.07/2.3.00/30.0032]; European Social Fund; state budget of the Czech Republic; Ministerio de Educacion, Cultura y Deporte, Spain; EU [238511]This research was supported by MEC, Spain, grant BFU2011-23896 (JF), European Union FP7 ANTIGONE project number 278976 (JF) and Postdok BIOGLOBE, Czech Republic CZ.1.07/2.3.00/30.0032 co-financed by the European Social Fund and the state budget of the Czech Republic (JS). N. Ayllon was funded by Ministerio de Educacion, Cultura y Deporte, Spain. S. Weisheit was supported by the POSTICK ITN (Post-graduate training network for capacity building to control ticks and tick-borne diseases) within the FP7-PEOPLE-ITN programme (EU Grant No. 238511). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.06Public library scienceSan francisco ; Anaplasma phagocytophilum is an emerging zoonotic pathogen transmitted by Ixodes scapularis that causes human granulocytic anaplasmosis. Here, a high throughput quantitative proteomics approach was used to characterize A. phagocytophilum proteome during rickettsial multiplication and identify proteins involved in infection of the tick vector, I. scapularis. The first step in this research was focused on tick cells infected with A. phagocytophilum and sampled at two time points containing 10-15% and 65-71% infected cells, respectively to identify key bacterial proteins over-represented in high percentage infected cells. The second step was focused on adult female tick guts and salivary glands infected with A. phagocytophilum to compare in vitro results with those occurring during bacterial infection in vivo. The results showed differences in the proteome of A. phagocytophilum in infected ticks with higher impact on protein synthesis and processing than on bacterial replication in tick salivary glands. These results correlated well with the developmental cycle of A. phagocytophilum, in ...

MEC, Spain [BFU2011-23896]; European Union [278976]; Postdok BIOGLOBE, Czech Republic [CZ.1.07/2.3.00/30.0032]; European Social Fund; state budget of the Czech Republic; Ministerio de Educacion, Cultura y Deporte, Spain; EU [238511]This research was supported by MEC, Spain, grant BFU2011-23896 (JF), European Union FP7 ANTIGONE project number 278976 (JF) and Postdok BIOGLOBE, Czech Republic CZ.1.07/2.3.00/30.0032 co-financed by the European Social Fund and the state budget of the Czech Republic (JS). N. Ayllon was funded by Ministerio de Educacion, Cultura y Deporte, Spain. S. Weisheit was supported by the POSTICK ITN (Post-graduate training network for capacity building to control ticks and tick-borne diseases) within the FP7-PEOPLE-ITN programme (EU Grant No. 238511). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.06Public library scienceSan francisco ; Anaplasma phagocytophilum is an emerging zoonotic pathogen transmitted by Ixodes scapularis that causes human granulocytic anaplasmosis. Here, a high throughput quantitative proteomics approach was used to characterize A. phagocytophilum proteome during rickettsial multiplication and identify proteins involved in infection of the tick vector, I. scapularis. The first step in this research was focused on tick cells infected with A. phagocytophilum and sampled at two time points containing 10-15% and 65-71% infected cells, respectively to identify key bacterial proteins over-represented in high percentage infected cells. The second step was focused on adult female tick guts and salivary glands infected with A. phagocytophilum to compare in vitro results with those occurring during bacterial infection in vivo. The results showed differences in the proteome of A. phagocytophilum in infected ticks with higher impact on protein synthesis and processing than on bacterial replication in tick salivary glands. These results correlated well with the developmental cycle of A. phagocytophilum, in which cells convert from an intracellular reticulated, replicative form to the nondividing infectious dense-core form. The analysis of A. phagocytophilum differentially represented proteins identified stress response (GroEL, HSP70) and surface (MSP4) proteins that were over-represented in high percentage infected tick cells and salivary glands when compared to low percentage infected cells and guts, respectively. The results demonstrated that MSP4, GroEL and HSP70 interact and bind to tick cells, thus playing a role in rickettsia-tick interactions. The most important finding of these studies is the increase in the level of certain bacterial stress response and surface proteins in A. phagocytophilum-infected tick cells and salivary glands with functional implication in tick-pathogen interactions. These results gave a new dimension to the role of these stress response and surface proteins during A. phagocytophilum infection in ticks. Characterization of Anaplasma proteome contributes information on host-pathogen interactions and provides targets for development of novel control strategies for pathogen infection and transmission.