Genetic connectivity between Atlantic bluefin tuna (ABFT) Larvae Spawned in the GOM and MED

Highly migratory Atlantic bluefin tuna (ABFT) is managed as two stocks, Western and Eastern. Western ABFT spawn mainly in the Gulf of Mexico (GOM) and Eastern ABFT in the Mediterranean Sea (MED) (1). Understanding connectivity between ABFT populations is important for conservation and management of this valuable fishery resource that has been exploited for centuries. ABFT are highly mixed, with multiple disciplines supporting weak structuring between Western and Eastern stocks (1). Concerning genetics, subtle structuring of ABFT populations across the Atlantic Ocean has been the conclusion of studies describing genetic tools for traceability (2,3). Larval fish provide the genetic signal of successful breeders and have occasionally been genetically characterized with juveniles (young-of-the-year, YOY) collected in nursery areas. For the first time, cooperative field collection of tuna larvae during 2014 in the main spawning area for each stock enabled us to assess the structuring of ABFT genetic diversity in a precise temporal and spatial frame exclusively through larvae (5). Partitioning of genetic diversity at nuclear microsatellite loci and in the mitochondrial control region resulted in low significant fixation indices. Individual-based clustering analysis of larval ABFT genetic diversity indicate apparent connectivity between the GOM and MED spawning grounds that could support the hypothesis of mixing of breeders belonging to different stocks.This collaborative study was supported by "ECOLATUN" PROJECT CTM2015-68473-R (MINECO/FEDER) funded by Spanish Ministry of Economy and Competitiveness; "TUNAGEN" project funded by IEO; and "BLUEFIN" project financed by IEO and Balearic Island Observing and Forecasting System (SOCIB). This research was funded by NASA (NNX11AP76G S07), the NOAA National Marine Fisheries Science Service through the Southeast Fisheries Science Center, as well as by Cooperative Institute for Marine and Atmospheric Studies under Cooperative Agreement NA15OAR43200064 at the University of Miami. There was no additional external funding received for this study. The scientific results and conclusions, as well as any views or opinions expressed herein, are those of the author(s) and do not necessarily reflect those of NOAA or the Department of Commerce

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr −/−). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m), diabetes mellitus and ALT werefound to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears.The research leading to these results has received funding from the Consejería de Salud de la Junta de Andalucía under grant agreement PC-0148-2016-0148 and PE-0451-2018 and Instituto de Salud Carlos III under grant agreements CD21/00095, PI16/01842, PI19/01404, PI19/00589, IFI18/00041, FI20/00201, CD18/00126 and EHD18PI04/2021. Rocío Gallego-Durán has received the Andrew K Burroughs Fellowship from European Association for the Study of the Liver (EASL), Aprendizaje de Nuevas Tecnologías fellowship from Asociación Española para el Estudio del Hígado (AEEH) and CIBERehd Grant to support researcher’s mobility

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study

Background and objectivesIntermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson’s disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity.MethodsA total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.DiscussionThe findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD

How binomial (traditional rainfed olive grove-Crocus sativus) crops impact the soil bacterial community and enhance microbial capacities

Intercropping can favour the yield of the main crop. However, because of the potential competition among woody crops, this system is rarely used by farmers. To increase knowledge about the intercropping system, we have explored three different combinations of alley cropping in rainfed olive groves compared to conventional management (CP): (i) Crocus sativus (D-S); (ii) Vicia sativa/Avena sativa in annual rotation (D-O); and (iii) Lavandula x intermedia (D-L). Different soil chemical properties were analyzed to evaluate the effects of alley cropping, while 16S rRNA amplification and enzymatic activities were determined to study the changes that occurred in soil microbial communities and activity. In addition, the influence of intercropping on the potential functionality of the soil microbial community was measuredThis research was funded by the European Commission Horizon 2020 project Diverfarming (Crop diversification and low-input farming across Europe: From practitioners' engagement and ecosystems services to increased revenues and value chain organisation), grant agreement 728003Peer reviewe

Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

Antiviral signaling, immune response and cell metabolism in human body are dysregulated by SARS-CoV-2, the causative agent of the COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While all four ORFs caused mitochondrial fragmentation and altered mitochondrial function, only ORF3a and ORF9c induced a marked structural alteration in mitochondrial cristae. ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes. In contrast, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes for proteins with critical mitochondrial functions and morphology. Genome-Scale Metabolic Models predicted common and private metabolic flux reprogramming, notably a depressed amino acid metabolism, and an enhanced metabolism of specific lipids distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.This research work was funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI+ Salud Global) (COVID-19-117 and SGL2103015), Junta de Andalucía (CV20-20089), Spanish Ministry of Science project (PID2021-123399OB-I00), the Agency for Management of University and Research Grants from Generalitat de Catalunya-AGAUR (2020PANDE00048 and 2021SGR00350) and ICREA foundation (ICREA-Academia-2021 to MC) of Generalitat de Catalunya, and an AESi grant of the Instituto de Salud Carlos III (PI20CIII-00014). TGG is recipient of a Ramón y Cajal contract funded by MCIN/AEU/10.13039/501100011033 and NextGeneration EU/PRTR.N

Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

1 p.Antiviral signaling, immune response and cell metabolism in human body are dysregulated by SARS-CoV-2, the causative agent of COVID-19. However, the impacts of individual accessory proteins on host cell metabolic pathways are unknown.Here, SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 were individually transduced into A549 lung carcinoma cells. Furthermore, by combining transcriptomic analysis with functional and metabolic data in accessory protein-specific GSMMs, several alterations were identified that may point to a putative target for investigating novel therapies. In this study, we showed that these accessory proteins induced a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes. In contrast, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical role in mitochondria function and morphology. On the other hand, while all four ORFs altered mitochondrial dynamics and function, only ORF3a and ORF9c induced a marked structural alteration in mitochondrial cristae. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features shared across all accessory proteins and specific ones for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. Next, qMTA identified gene knock downs (KDs) that would have the potential to revert the metabolic reprogramming induced by each individual accessory protein, especially in ORF3a and ORF10. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.Peer reviewe

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil =4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology

Historia de la RAMSA. 50º aniversario (1971-2021)

Libro conmemorativo de los 50 años de existencia de la Real Academia de Medicina de Salamanca, donde se recogen todas las actividades llevadas a cabo durante ese tiempo, los premios concedidos, los miembros elegidos, etc., así como se gestó su nacimiento en el contexto de la existencia de otras academias médicas.Universidad de Salamanc

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality