DNA sequence analysis suggests that cytb-nd1 PCR-RFLP may not be applicable to sandfly species identification throughout the Mediterranean region

Molecular methods are increasingly used for both species identification of sandflies and assessment of their population structure. In general, they are based on DNA sequence analysis of targets previously amplified by PCR. However, this approach requires access to DNA sequence facilities, and in some circumstances, it is time-consuming. Though DNA sequencing provides the most reliable information, other downstream PCR applications are explored to assist in species identification. Thus, it has been recently proposed that the amplification of a DNA region encompassing partially both the cytochrome-B (cytb) and the NADH dehydrogenase 1 (nd1) genes followed by RFLP analysis with the restriction enzyme Ase I allows the rapid identification of the most prevalent species of phlebotomine sandflies in the Mediterranean region. In order to confirm the suitability of this method, we collected, processed, and molecularly analyzed a total of 155 sandflies belonging to four species including Phlebotomus ariasi, P. papatasi, P. perniciosus, and Sergentomyia minuta from different regions in Spain. This data set was completed with DNA sequences available at the GenBank for species prevalent in the Mediterranean basin and the Middle East. Additionally, DNA sequences from 13 different phlebotomine species (P. ariasi, P. balcanicus, P. caucasicus, P. chabaudi, P. chadlii, P. longicuspis, P. neglectus, P. papatasi, P. perfiliewi, P. perniciosus, P. riouxi, P. sergenti, and S. minuta), from 19 countries, were added to the data set. Overall, our molecular data revealed that this PCR-RFLP method does not provide a unique and specific profile for each phlebotomine species tested. Intraspecific variability and similar RFLP patterns were frequently observed among the species tested. Our data suggest that this method may not be applicable throughout the Mediterranean region as previously proposed. Other molecular approaches like DNA barcoding or phylogenetic analyses would allow a more precise molecular species identification.This work was supported in part by Instituto de Salud Carlos III (MPY-1248/12) grant and (PI14CIII/00016) funded by AESI. Ivonne Pamela Llanes-Acevedo was granted a student fellowship by COLCIENCIAS/COLFUTURO.S

Ten lessons on the resilience of the EU common fisheries policy towards climate change and fuel efficiency - A call for adaptive, flexible and wellinformed fisheries management

To effectively future-proof the management of the European Union fishing fleets we have explored a suite of case studies encompassing the northeast and tropical Atlantic, the Mediterranean, Baltic and Black Seas. This study shows that European Union (EU) fisheries are likely resilient to climate-driven short-term stresses, but may be negatively impacted by long-term trends in climate change. However, fisheries’ long-term stock resilience can be improved (and therefore be more resilient to increasing changes in climate) by adopting robust and adaptive fisheries management, provided such measures are based on sound scientific advice which includes uncertainty. Such management requires regular updates of biological reference points. Such updates will delineate safe biological limits for exploitation, providing both high long-term yields with reduced risk of stock collapse when affected by short-term stresses, and enhanced compliance with advice to avoid higher than intended fishing mortality. However, high resilience of the exploited ecosystem does not necessarily lead to the resilience of the economy of EU fisheries from suffering shocks associated with reduced yields, neither to a reduced carbon footprint if fuel use increases from lower stock abundances. Fuel consumption is impacted by stock development, but also by changes in vessel and gear technologies, as well as fishing techniques. In this respect, energy-efficient fishing technologies already exist within the EU, though implementing them would require improving the uptake of innovations and demonstrating to stakeholders the potential for both reduced fuel costs and increased catch rates. A transition towards reducing fuel consumption and costs would need to be supported by the setup of EU regulatory instruments. Overall, to effectively manage EU fisheries within a changing climate, flexible, adaptive, well-informed and well-enforced management is needed, with incentives provided for innovations and ocean literacy to cope with the changing conditions, while also reducing the dependency of the capture fishing industry on fossil fuels. To support such management, we provide 10 lessons to characterize ‘win-win’ fishing strategies for the European Union, which develop leverages in which fishing effort deployed corresponds to Maximum Sustainable Yield targets and Common Fisheries Policy minimal effects objectives. In these strategies, higher catch is obtained in the long run, less fuel is spent to attain the catch, and the fisheries have a higher resistance and resilience to shock and long-term factors to face climate-induced stressesEn prens

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number COV20/1144 (MPY224/20) to AF-R/MJ-S). The study was also funded by CIBER - Consorcio Centro de Investigación Biomédica en Red - (CB 2021; CB21/13/00044), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea - NextGenerationEU. AF-R and MJ-S are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MJ-S). Universidad Alfonso X el Sabio, grant number 1.013.005S

Ten lessons on the resilience of the EU common fisheries policy towards climate change and fuel efficiency - A call for adaptive, flexible and well-informed fisheries management

To effectively future-proof the management of the European Union fishing fleets we have explored a suite of case studies encompassing the northeast and tropical Atlantic, the Mediterranean, Baltic and Black Seas. This study shows that European Union (EU) fisheries are likely resilient to climate-driven short-term stresses, but may be negatively impacted by long-term trends in climate change. However, fisheries' long-term stock resilience can be improved (and therefore be more resilient to increasing changes in climate) by adopting robust and adaptive fisheries management, provided such measures are based on sound scientific advice which includes uncertainty. Such management requires regular updates of biological reference points. Such updates will delineate safe biological limits for exploitation, providing both high long-term yields with reduced risk of stock collapse when affected by short-term stresses, and enhanced compliance with advice to avoid higher than intended fishing mortality. However, high resilience of the exploited ecosystem does not necessarily lead to the resilience of the economy of EU fisheries from suffering shocks associated with reduced yields, neither to a reduced carbon footprint if fuel use increases from lower stock abundances. Fuel consumption is impacted by stock development, but also by changes in vessel and gear technologies, as well as fishing techniques. In this respect, energy-efficient fishing technologies already exist within the EU, though implementing them would require improving the uptake of innovations and demonstrating to stakeholders the potential for both reduced fuel costs and increased catch rates. A transition towards reducing fuel consumption and costs would need to be supported by the setup of EU regulatory instruments. Overall, to effectively manage EU fisheries within a changing climate, flexible, adaptive, well-informed and well-enforced management is needed, with incentives provided for innovations and ocean literacy to cope with the changing conditions, while also reducing the dependency of the capture fishing industry on fossil fuels. To support such management, we provide 10 lessons to characterize 'win-win' fishing strategies for the European Union, which develop leverages in which fishing effort deployed corresponds to Maximum Sustainable Yield targets and Common Fisheries Policy minimal effects objectives. In these strategies, higher catch is obtained in the long run, less fuel is spent to attain the catch, and the fisheries have a higher resistance and resilience to shock and long-term factors to face climate-induced stresses

VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle

© 2019. Published by The Company of Biologists Ltd.Peer reviewedPublisher PD

Biodegradable drifting fish aggregating devices: Current status and future prospects

The structure, materials and designs of drifting Fish Aggregating Devices (dFADs) have generally remained rudimentary and relatively unchanged since they first came into use in the 1980 s. However, more recently, dFADs have been increasing in dimensions and the prevailing use of plastic components. Abandoned, lost or discarded dFADs can therefore contribute to the global marine litter problem. Transitioning to biodegradable and non-toxic materials that have a faster rate of decomposition, and are free of toxins and heavy metals, relative to synthetic materials, has been prescribed as an important part of the solution to reducing marine pollution from industrial tuna fisheries that rely on dFADs. This review of the current state of dFADs considers aspects related to the use of biodegradable materials in their construction, including; regulations related to dFAD materials, trials of biodegradable designs and materials and future alternatives. During the last decade, regulatory measures at tuna Regional Fishery Management Organizations (tRFMOs) have gradually moved towards the clear recommendation to use biodegradable materials in dFAD construction together with other measures limiting the number of active dFADs and the use of netting materials. However, to provide operational guidance, more clarity is needed, starting with a standardised definition of biodegradable dFADs among tRFMOs. Research involving dFAD natural and synthetic materials is required, along with improved data collection for monitoring the transition of dFAD materials against specified standards for biodegradable dFADs. In addition, alternative and complementary actions need to be explored to contribute to minimising adverse effects of dFADs on the environment. Acknowledging the current difficulties for the implementation of fully biodegradable dFADs in tuna fisheries, a stepwise process towards the implementation of commercially viable biodegradable dFADs should be considered.Peer reviewe

Afección pericárdica y miocárdica tras infección por SARS-CoV-2: estudio descriptivo transversal en trabajadores sanitarios

[EN] Introduction and objectives The cardiac sequelae of SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in healthcare workers to report evidence of pericardial and myocardial involvement after SARS-CoV-2 infection. Methods We studied 139 healthcare workers with confirmed past SARS-CoV-2 infection. Participants underwent clinical assessment, electrocardiography, and laboratory tests, including immune cell profiling and cardiac magnetic resonance (CMR). Clinically suspected pericarditis was diagnosed when classic criteria were present and clinically suspected myocarditis was based on the combination of at least 2 CMR criteria. Results Median age was 52 (41-57) years, 71.9% were women, and 16.5% were previously hospitalized for COVID-19 pneumonia. On examination (10.4 [9.3-11.0] weeks after infection-like symptoms), participants showed hemodynamic stability. Chest pain, dyspnea or palpitations were present in 41.7% participants, electrocardiographic abnormalities in 49.6%, NT-proBNP elevation in 7.9%, troponin in 0.7%, and CMR abnormalities in 60.4%. A total of 30.9% participants met criteria for either pericarditis and/or myocarditis: isolated pericarditis was diagnosed in 5.8%, myopericarditis in 7.9%, and isolated myocarditis in 17.3%. Most participants (73.2%) showed altered immune cell counts in blood, particularly decreased eosinophil (27.3%; P < .001) and increased cytotoxic T cell numbers (17.3%; P < .001). Clinically suspected pericarditis was associated (P < .005) with particularly elevated cytotoxic T cells and decreased eosinophil counts, while participants diagnosed with clinically suspected myopericarditis or myocarditis had lower (P < .05) neutrophil counts, natural killer-cells, and plasma cells. Conclusions Pericardial and myocardial involvement with clinical stability are frequent after SARS-CoV-2 infection and are associated with specific immune cell profiles.[ES] Introducción y objetivos Las secuelas cardiacas tras la infección por SARS-CoV-2 todavía están poco documentadas. Se realizó un estudio transversal en trabajadores sanitarios para estudiar la prevalencia de afección pericárdica y miocárdica tras la infección por SARS-CoV-2. Métodos Se estudió a 139 trabajadores sanitarios con infección previa confirmada por SARS-CoV-2. Los participantes se sometieron a evaluación clínica, electrocardiograma, laboratorio, incluido el perfil de células inmunitarias, y resonancia magnética cardiaca (RMC). El diagnóstico clínico de pericarditis se realizó ante la presencia de los criterios clásicos y el diagnóstico clínico de miocarditis ante la presencia de al menos 2 criterios de RMC. Resultados La mediana de edad fue de 52 (41–57) años, el 71,9% eran mujeres, y el 16.5% había sido hospitalizado previamente por neumonía por COVID-19. En la evaluación (10,4 [9,3–11,0] semanas después de los síntomas de infección), todos los participantes presentaban estabilidad hemodinámica. El 41,7% presentaba dolor torácico, disnea o palpitaciones; el 49,6%, alteraciones electrocardiográficas; el 7,9%, elevación de NT-proBNP; el 0,7%, elevación de troponina; y el 60,4%, alteraciones en la RMC. Un total de 30,9% de participantes cumplieron los criterios clínicos establecidos de pericarditis o miocarditis: pericarditis aislada en el 5,8%, miopericarditis en el 7,9% y miocarditis aislada en el 17,3%. La mayoría de los participantes (73,2%) mostraron recuentos de células inmunitarias alterados en sangre; en particular diminución de eosinófilos (27,3%; p < 0,001) y aumento del número de células T citotóxicas (17,3%; p < 0,001). La sospecha clínica de pericarditis se asoció (p < 0,005) particularmente con un elevado número de células T citotóxicas y recuento de eosinófilos disminuidos; mientras que los participantes con sospecha clínica de miopericarditis o miocarditis tenían recuentos de neutrófilos, células natural killer y células plasmáticas más bajos (p < 0,05). Conclusiones La afección pericárdica y miocárdica con estabilidad hemodinámica es frecuente después de la infección por SARS-CoV-2 y se asocia con perfiles de células inmunitarias específicas.This study was supported by CIBERCV (CB16/11/00374), CIBERONC (CB16/12/00400) and the COV20/00386 grant from the Instituto de Salud Carlos III and FEDER, Ministerio de Ciencia e Innovación, Madrid, Spain, and by GRS COVID 26/A/20 from the Gerencia Regional de Salud, Junta de Castilla y León, Spain.Peer reviewe

Pericardial and myocardial involvement after SARS-CoV-2 infection: a cross-sectional descriptive study in healthcare workers

[ES] Introducción y objetivos Las secuelas cardiacas tras la infección por SARS-CoV-2 todavía están poco documentadas. Se realizó un estudio transversal en trabajadores sanitarios para estudiar la prevalencia de afección pericárdica y miocárdica tras la infección por SARS-CoV-2. Métodos Se estudió a 139 trabajadores sanitarios con infección previa confirmada por SARS-CoV-2. Los participantes se sometieron a evaluación clínica, electrocardiograma, laboratorio, incluido el perfil de células inmunitarias, y resonancia magnética cardiaca (RMC). El diagnóstico clínico de pericarditis se realizó ante la presencia de los criterios clásicos y el diagnóstico clínico de miocarditis ante la presencia de al menos 2 criterios de RMC. Resultados La mediana de edad fue de 52 (41–57) años, el 71,9% eran mujeres, y el 16,5% había sido hospitalizado previamente por neumonía por COVID-19. En la evaluación (10,4 [9,3–11,0] semanas después de los síntomas de infección), todos los participantes presentaban estabilidad hemodinámica. El 41,7% presentaba dolor torácico, disnea o palpitaciones; el 49,6%, alteraciones electrocardiográficas; el 7,9%, elevación de NT-proBNP; el 0,7%, elevación de troponina; y el 60,4%, alteraciones en la RMC. Un total de 30,9% de participantes cumplieron los criterios clínicos establecidos de pericarditis o miocarditis: pericarditis aislada en el 5,8%, miopericarditis en el 7,9% y miocarditis aislada en el 17,3%. La mayoría de los participantes (73,2%) mostraron recuentos de células inmunitarias alterados en sangre; en particular diminución de eosinófilos (27,3%; p < 0,001) y aumento del número de células T citotóxicas (17,3%; p < 0,001). La sospecha clínica de pericarditis se asoció (p < 0,005) particularmente con un elevado número de células T citotóxicas y recuento de eosinófilos disminuidos; mientras que los participantes con sospecha clínica de miopericarditis o miocarditis tenían recuentos de neutrófilos, células natural killer y células plasmáticas más bajos (p < 0,05). Conclusiones La afección pericárdica y miocárdica con estabilidad hemodinámica es frecuente después de la infección por SARS-CoV-2 y se asocia con perfiles de células inmunitarias específicas.[EN] Introduction and objectives The cardiac sequelae of SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in healthcare workers to report evidence of pericardial and myocardial involvement after SARS-CoV-2 infection. Methods We studied 139 healthcare workers with confirmed past SARS-CoV-2 infection. Participants underwent clinical assessment, electrocardiography, and laboratory tests, including immune cell profiling and cardiac magnetic resonance (CMR). Clinically suspected pericarditis was diagnosed when classic criteria were present and clinically suspected myocarditis was based on the combination of at least 2 CMR criteria. Results Median age was 52 (41-57) years, 71.9% were women, and 16.5% were previously hospitalized for COVID-19 pneumonia. On examination (10.4 [9.3-11.0] weeks after infection-like symptoms), participants showed hemodynamic stability. Chest pain, dyspnea or palpitations were present in 41.7% participants, electrocardiographic abnormalities in 49.6%, NT-proBNP elevation in 7.9%, troponin in 0.7%, and CMR abnormalities in 60.4%. A total of 30.9% participants met criteria for either pericarditis and/or myocarditis: isolated pericarditis was diagnosed in 5.8%, myopericarditis in 7.9%, and isolated myocarditis in 17.3%. Most participants (73.2%) showed altered immune cell counts in blood, particularly decreased eosinophil (27.3%; P < .001) and increased cytotoxic T cell numbers (17.3%; P < .001). Clinically suspected pericarditis was associated (P < .005) with particularly elevated cytotoxic T cells and decreased eosinophil counts, while participants diagnosed with clinically suspected myopericarditis or myocarditis had lower (P < .05) neutrophil counts, natural killer-cells, and plasma cells. Conclusions Pericardial and myocardial involvement with clinical stability are frequent after SARS-CoV-2 infection and are associated with specific immune cell profiles.Este estudio contó con el apoyo de CIBERCV (CB16/11/00374) y CIBERONC (CB16/12/00400) y la subvención COV20/00386 del Instituto de Salud Carlos III y FEDER, Ministerio de Ciencia e Innovación, Madrid, España, y por GRS COVID 26/A/20 de la Gerencia Regional de Salud, Junta de Castilla y León, España.Peer reviewe

An archaeal compound as a driver of Parkinson’s disease pathogenesis

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD.

Immune cell kinetics and antibody response in COVID-19 patients with low-count monoclonal B-cell lymphocytosis

Low-count monoclonal B-cell lymphocytosis (MBLlo) has been associated with an underlying immunodeficiency and has recently emerged as a new risk factor for severe COVID-19. Here, we investigated the kinetics of immune cell and antibody responses in blood during COVID-19 of MBLlo versus non-MBL patients. For this study, we analyzed the kinetics of immune cells in blood of 336 COVID-19 patients (74 MBLlo and 262 non-MBL), who had not been vaccinated against SARS-CoV-2, over a period of 43 weeks since the onset of infection, using high-sensitivity flow cytometry. Plasma levels of anti-SARS-CoV-2 antibodies were measured in parallel by ELISA. Overall, early after the onset of symptoms, MBLlo COVID-19 patients showed increased neutrophil, monocyte, and particularly, plasma cell (PC) counts, whereas eosinophil, dendritic cell, basophil, and lymphocyte counts were markedly decreased in blood of a variable percentage of samples, and with a tendency toward normal levels from week +5 of infection onward. Compared with non-MBL patients, MBLlo COVID-19 patients presented higher neutrophil counts, together with decreased pre-GC B-cell, dendritic cell, and innate-like T-cell counts. Higher PC levels, together with a delayed PC peak and greater plasma levels of anti-SARS-CoV-2-specific antibodies (at week +2 to week +4) were also observed in MBLlo patients. In summary, MBLlo COVID-19 patients share immune profiles previously described for patients with severe SARS-CoV-2 infection, associated with a delayed but more pronounced PC and antibody humoral response once compared with non-MBL patients.This work was supported by “Early Cancer Research Initiative Network on MBL (ECRINM3)” ACCELERATOR award (CRUK-UK-, Fundación AECC-Spain-and Associazione Italiana per la Ricerca Sul Cancro _Italy-), by the CB16/12/00400 (CIBERONC), COV20/00386, PI17/00399, and PI22/00674, grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, (Madrid, Spain) co-funded by FONDOS FEDER, and by the SA109P20 (Consejería de Educación) and GRS-COVID-33/A/20 (Gerencia Regional de Salud, Consejería de Sanidad) grants from Junta de Castilla y León (Valladolid, Spain), by 0639-IDIAL-NET-3-3 grant (INTERREG POCTEP Spain-Portugal) from Fondo Europeo de Desarrollo Regional. G. Oliva-Ariza is supported by a grant (PR-2019 487971) from the Consejería de Educación, Junta de Castilla y León (Valladolid, Spain), B. Fuentes-Herrero is supported by the 0639-IDIAL-NET-3-3, and ECRIN-M3 grants, and Ó. González-López is supported by a grant (FI20/00116) from Instituto de Salud Carlos III co-funded by Fondo Social Europeo Plus (FSE+).Peer reviewe