RESUMO
Two titanium-based MOFs MIL-125 and MIL-125_NH2 are synthesized and characterized using high-temperature powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), N2 sorption, Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), and electron paramagnetic resonance (EPR). Stable up to 300 °C, both compounds exhibited similar specific surface areas (SSA) values (1207 and 1099 m2 g-1 for MIL-125 and MIL-125_NH2, respectively). EPR signals of Ti3+ are observed in both, whith MIL-125_NH2 also showing âNH2 â+ signatures. Both MOFs efficiently adsorbed iodine in continuous gas flow over five days, with MIL-125 trapping 1.9 g.g-1 and MIL-125_NH2 trapping 1.6 g.g-1. MIL-125_NH2 exhibited faster adsorption kinetics due to its smaller band gap (2.5 against 3.6 eV). In situ Raman spectroscopy conducted during iodine adsorption revealed signal evolution from "free" I2 to "perturbed" I2, and I3 -. TGA and in situ Raman desorption experiments showed that âNH2 groups improved the stabilization of I3 - due to an electrostatic interaction with NH2 â+BDC radicals. The Albery model indicated longer lifetimes for iodine desorption in I2@MIL-125_NH2, attributed to a rate-limiting step due to stronger interaction between the anionic iodine species and the âNH2 â+ radicals. This study underscores how MOFs with efficient charge separation and hole-stabilizer functional groups enhance iodine stability at higher temperatures.
RESUMO
The maintenance of polymorphisms often depends on multiple selective forces, but less is known on the role of stochastic or historical processes in maintaining variation. The common wall lizard (Podarcis muralis) is a colour polymorphic species in which local colour morph frequencies are thought to be modulated by natural and sexual selection. Here, we used genome-wide single-nucleotide polymorphism data to investigate the relationships between morph composition and population biogeography at a regional scale, by comparing morph composition with patterns of genetic variation of 54 populations sampled across the Pyrenees. We found that genetic divergence was explained by geographic distance but not by environmental features. Differences in morph composition were associated with genetic and environmental differentiation, as well as differences in sex ratio. Thus, variation in colour morph frequencies could have arisen via historical events and/or differences in the permeability to gene flow, possibly shaped by the complex topography and environment. In agreement with this hypothesis, colour morph diversity was positively correlated with genetic diversity and rates of gene flow and inversely correlated with the likelihood of the occurrence of bottlenecks. Concurrently, we did not find conclusive evidence for selection in the two colour loci. As an illustration of these effects, we observed that populations with higher proportions of the rarer yellow and yellow-orange morphs had higher genetic diversity. Our results suggest that processes involving a decay in overall genetic diversity, such as reduced gene flow and/or bottleneck events have an important role in shaping population-specific morph composition via non-selective processes.
Assuntos
Fluxo Gênico , Genética Populacional , Lagartos , Polimorfismo de Nucleotídeo Único , Lagartos/genética , Lagartos/anatomia & histologia , Lagartos/classificação , Animais , Pigmentação/genética , Seleção Genética , Variação Genética , Filogeografia , MasculinoRESUMO
OBJECTIVE: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. METHODS: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis. RESULTS: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites). SIGNIFICANCE: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.
Assuntos
Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Epilepsia , Animais , Masculino , Ratos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Modelos Animais de Doenças , Epilepsia/etiologia , Epilepsia Pós-Traumática/etiologia , Epilepsia Pós-Traumática/patologia , Percussão , Fenótipo , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , ConvulsõesRESUMO
In many vertebrates, the enzymatic oxidation of dietary yellow carotenoids generates red keto-carotenoids giving color to ornaments. The oxidase CYP2J19 is here a key effector. Its purported intracellular location suggests a shared biochemical pathway between trait expression and cell functioning. This might guarantee the reliability of red colorations as individual quality signals independent of production costs. We hypothesize that the ornament type (feathers vs. bare parts) and production costs (probably CYP2J19 activity compromising vital functions) could have promoted tissue-specific gene relocation. We review current avian tissue-specific CYP2J19 expression data. Among the ten red-billed species showing CYP2J19 bill expression, only one showed strong hepatic expression. Moreover, a phylogenetically-controlled analysis of 25 red-colored species shows that those producing red bare parts are less likely to have strong hepatic CYP2J19 expression than species with only red plumages. Thus, both production costs and shared pathways might have contributed to the evolution of red signals.
Assuntos
Carotenoides , Pigmentação , Animais , Pigmentação/genética , Reprodutibilidade dos Testes , Carotenoides/metabolismo , Aves/genética , Expressão GênicaRESUMO
Birds exhibit striking variation in eye color that arises from interactions between specialized pigment cells named chromatophores. The types of chromatophores present in the avian iris are lacking from the integument of birds or mammals, but are remarkably similar to those found in the skin of ectothermic vertebrates. To investigate molecular mechanisms associated with eye coloration in birds, we took advantage of a Mendelian mutation found in domestic pigeons that alters the deposition of yellow pterin pigments in the iris. Using a combination of genome-wide association analysis and linkage information in pedigrees, we mapped variation in eye coloration in pigeons to a small genomic region of ~8.5kb. This interval contained a single gene, SLC2A11B, which has been previously implicated in skin pigmentation and chromatophore differentiation in fish. Loss of yellow pigmentation is likely caused by a point mutation that introduces a premature STOP codon and leads to lower expression of SLC2A11B through nonsense-mediated mRNA decay. There were no substantial changes in overall gene expression profiles between both iris types as well as in genes directly associated with pterin metabolism and/or chromatophore differentiation. Our findings demonstrate that SLC2A11B is required for the expression of pterin-based pigmentation in the avian iris. They further highlight common molecular mechanisms underlying the production of coloration in the iris of birds and skin of ectothermic vertebrates.
Assuntos
Columbidae/genética , Cor de Olho/genética , Iris/metabolismo , Pigmentação/genética , Pigmentação da Pele/genética , Vertebrados/genética , Animais , Cromatóforos/metabolismo , Columbidae/metabolismo , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Proteínas Facilitadoras de Transporte de Glucose/genética , Mutação , Estabilidade de RNA/genética , Vertebrados/metabolismo , Sequenciamento Completo do Genoma/métodosRESUMO
Saltatorial locomotion is a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. The molecular mechanisms that control and fine-tune the formation of this type of gait are unknown. Here, we take advantage of one strain of domesticated rabbits, the sauteur d'Alfort, that exhibits an abnormal locomotion behavior defined by the loss of the typical jumping that characterizes wild-type rabbits. Strikingly, individuals from this strain frequently adopt a bipedal gait using their front legs. Using a combination of experimental crosses and whole genome sequencing, we show that a single locus containing the RAR related orphan receptor B gene (RORB) explains the atypical gait of these rabbits. We found that a splice-site mutation in an evolutionary conserved site of RORB results in several aberrant transcript isoforms incorporating intronic sequence. This mutation leads to a drastic reduction of RORB-positive neurons in the spinal cord, as well as defects in differentiation of populations of spinal cord interneurons. Our results show that RORB function is required for the performance of saltatorial locomotion in rabbits.
Assuntos
Marcha/genética , Locomoção/genética , Mutação com Perda de Função , Membro 2 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Animais , Sequência de Bases , Mapeamento Cromossômico , Estudos de Associação Genética , Genoma , Genômica/métodos , Interneurônios/metabolismo , Fenótipo , Sítios de Splice de RNA , Coelhos , Medula Espinal/metabolismoRESUMO
Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever. Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common. Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment. The present case describes a stepwise approach to a patient with Mucha-Habermann disease with insufficient response to methotrexate.
Assuntos
Metotrexato , Pitiríase Liquenoide , Humanos , Febre/etiologia , Herpes Simples , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Pitiríase Liquenoide/patologia , Pitiríase Liquenoide/tratamento farmacológico , Úlcera Cutânea/etiologia , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/patologiaRESUMO
Oceanic islands are characterized by conditions that favour diversification into endemic lineages that can be very different from their mainland counterparts. This can be the result of fast phenotypic divergence due to drift or the result of slower adaptation to local conditions. This uniqueness can obscure their evolutionary history. Here we used morphological, stable isotope, genetic and genomic data to characterize common quails (Coturnix coturnix) in the Azores archipelago and assess the divergence from neighbouring common quail populations. Historical documents suggested that these quails could have a recent origin associated with the arrival of humans in the last centuries. Our results show that Azorean quails constitute a well-differentiated lineage with small size and dark throat pigmentation that has lost the migratory ability and that diverged from mainland quail lineages more than 0.8 mya, contrary to the notion of a recent human-mediated arrival. Even though some Azorean quails carry an inversion that affects 115 Mbp of chromosome 1 and that has been associated with the loss of the migratory behaviour in other common quail populations, half of the analysed individuals do not have that inversion and still do not migrate. The long coexistence and evolution in isolation in the Azores of two chromosomal variants (with and without the inversion) is best explained by balancing selection. Thus, a unique and long evolutionary history led to the island endemic that we know today, C. c. conturbans.
RESUMO
Most of the world's nations (around 130) have committed to reaching net-zero carbon dioxide or greenhouse gas (GHG) emissions by 2050, yet robust policies rarely underpin these ambitions. To investigate whether existing and expected national policies will allow Brazil to meet its net-zero GHG emissions pledge by 2050, we applied a detailed regional integrated assessment modelling approach. This included quantifying the role of nature-based solutions, such as the protection and restoration of ecosystems, and engineered solutions, such as bioenergy with carbon capture and storage. Our results highlight ecosystem protection as the most critical cost-effective climate mitigation measure for Brazil, whereas relying heavily on costly and not-mature-yet engineered solutions will jeopardise Brazil's chances of achieving its net-zero pledge by mid-century. We show that the full implementation of Brazil's Forest Code (FC), a key policy for emission reduction in Brazil, would be enough for the country to achieve its short-term climate targets up to 2030. However, it would reduce the gap to net-zero GHG emissions by 38% by 2050. The FC, combined with zero legal deforestation and additional large-scale ecosystem restoration, would reduce this gap by 62% by mid-century, keeping Brazil on a clear path towards net-zero GHG emissions by around 2040. While some level of deployment of negative emissions technologies will be needed for Brazil to achieve and sustain its net-zero pledge, we show that the more mitigation measures from the land-use sector, the less costly engineered solutions from the energy sector will be required. Our analysis underlines the urgent need for Brazil to go beyond existing policies to help fight climate emergency, to align its short- and long-term climate targets, and to build climate resilience while curbing biodiversity loss.
Assuntos
Efeito Estufa , Gases de Efeito Estufa , Agricultura/métodos , Ecossistema , Brasil , Gases de Efeito Estufa/análiseRESUMO
In hemophilia, the unmet needs regarding adherence to prophylaxis and lack of effective longterm prophylaxis regimens, especially in patients with inhibitors, led to the production of emicizumab, the first non-factor medicine for subcutaneous administration in patients with severe and moderate hemophilia A with or without factor VIII inhibitors. This article describes the research steps behind the development of this game-changer medication, its success for the prophylaxis of bleeding episodes as witnessed by the results of pivotal clinical trial but also by real life use in the frame of a still expanding global market. We shall also discuss potential and actual adverse events and the nuances related to clinical use such as laboratory monitoring, development of neutralizing anti-drug-antibodies, risk of thrombosis/hypercoagulability and use in the management of surgical operations. The potential of using emicizumab to prevent bleeding in other congenital and acquired coagulation disorders will also be sketched.
RESUMO
One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 µg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use.
Assuntos
Nitroglicerina , Vasodilatadores , Humanos , Artéria Radial , Resultado do Tratamento , Cateterismo Cardíaco/efeitos adversos , Espasmo/diagnóstico , Espasmo/etiologia , Espasmo/prevenção & controleRESUMO
The current investigation was conducted to test the potential effects of in ovo feeding of creatine monohydrate (CMH) on hatchability, embryonic mortality, hatching weight, and development of heart and gastrointestinal tract (main organs and regions) of breeder chick embryos. Rhode Island Red fertile eggs were randomly distributed into seven experimental treatments: untreated egg (control), a sterile buffered solution (0.50% NaCl), and five solutions containing increased levels of CMH (0.50, 1.00, 1.50, and 2.00%) + 0.50% NaCl, being separated in four groups/replicates (three with 15 eggs and one with 16 eggs), totaling 61 eggs/treatment and a total of 427 fertile eggs used. All-in ovo injected groups with CMH decreased the hatchability and increased the intermediary embryonic mortality. At hatching, all-in ovo injected groups with CMH also increased the hatching weight and stimulated the development of the heart and the total length of the gastrointestinal tract, especially important organs for digestion of nutrients (yolk sac, pro-ventricle and gizzard) and regions for nutrient absorption (jejunum + ileum and colon + rectum). Conclusively, the in ovo feeding using CMH showed positive impacts on hatching weight and the development of gastrointestinal tract of chicks. However, caused negative impacts on hatchability.
Assuntos
Creatina , Cloreto de Sódio , Embrião de Galinha , Animais , Creatina/farmacologia , Galinhas , Fertilidade , Injeções , ÓvuloRESUMO
Understanding the factors that underlie the physical exercise-induced increase in body core temperature (TCORE) is essential to developing strategies to counteract hyperthermic fatigue and reduce the risk of exertional heatstroke. This study analyzed the contribution of six factors to TCORE attained at fatigue in Wistar rats (n = 218) subjected to incremental-speed treadmill running: ambient temperature (TAMB), distance traveled, initial TCORE, body mass, measurement site, and heat loss index (HLI). First, we ran hierarchical multiple linear regression analyses with data from different studies conducted in our laboratory (n = 353 recordings). We observed that TAMB, distance traveled, initial TCORE, and measurement site were the variables with predictive power. Next, regression analyses were conducted with data for each of the following TCORE indices: abdominal (TABD), brain cortex (TBRAIN), or colonic (TCOL) temperature. Our findings indicated that TAMB, distance traveled (i.e., an exercise performance-related variable), initial TCORE, and HLI predicted the three TCORE indices at fatigue. Most intriguingly, HLI was inversely related to TABD and TBRAIN but positively associated with TCOL. Lastly, we compared the temperature values at fatigue among these TCORE indices, and the following descendent order was noticed - TCOL, TABD, and TBRAIN - irrespective of TAMB where experiments were conducted. In conclusion, TCORE in rats exercised to fatigue depends primarily on environmental conditions, performance, pre-exercise TCORE, and measurement site. Moreover, the influence of cutaneous heat loss on TCOL is qualitatively different from the influence on TABD and TBRAIN, and the temperature values at fatigue are not homogenous within the body core.
Assuntos
Regulação da Temperatura Corporal , Temperatura Corporal , Ratos , Animais , Temperatura , Ratos Wistar , FadigaRESUMO
AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.
Assuntos
Síndrome Coronariana Aguda , Influenza Humana , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Síndrome Coronariana Aguda/terapia , Influenza Humana/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Vacinação , Acidente Vascular Cerebral/prevenção & controle , Vacinas de Produtos Inativados , Resultado do TratamentoRESUMO
Traumatic brain injury (TBI) causes 10-20% of structural epilepsies and 5% of all epilepsies. The lack of prognostic biomarkers for post-traumatic epilepsy (PTE) is a major obstacle to the development of anti-epileptogenic treatments. Previous studies revealed TBI-induced alterations in blood microRNA (miRNA) levels, and patients with epilepsy exhibit dysregulation of blood miRNAs. We hypothesized that acutely altered plasma miRNAs could serve as prognostic biomarkers for brain damage severity and the development of PTE. To investigate this, epileptogenesis was induced in adult male Sprague Dawley rats by lateral fluid-percussion-induced TBI. Epilepsy was defined as the occurrence of at least one unprovoked seizure during continuous 1-month video-electroencephalography monitoring in the sixth post-TBI month. Cortical pathology was analyzed by magnetic resonance imaging on day 2 (D2), D7, and D21, and by histology 6 months post-TBI. Small RNA sequencing was performed from tail-vein plasma samples on D2 and D9 after TBI (n = 16, 7 with and 9 without epilepsy) or sham operation (n = 4). The most promising miRNA biomarker candidates were validated by droplet digital polymerase chain reaction in a validation cohort of 115 rats (8 naïve, 17 sham, and 90 TBI rats [21 with epilepsy]). These included 7 brain-enriched plasma miRNAs (miR-434-3p, miR-9a-3p, miR-136-3p, miR-323-3p, miR-124-3p, miR-212-3p, and miR-132-3p) that were upregulated on D2 post-TBI (p < 0.001 for all compared with naïve rats). The acute post-TBI plasma miRNA profile did not predict the subsequent development of PTE or PTE severity. Plasma miRNA levels, however, predicted the cortical pathology severity on D2 (Spearman ρ = 0.345-0.582, p < 0.001), D9 (ρ = 0.287-0.522, p < 0.001-0.01), D21 (ρ = 0.269-0.581, p < 0.001-0.05) and at 6 months post-TBI (ρ = 0.230-0.433, p < 0.001-0.05). We found that the levels of 6 of 7 miRNAs also reflected mild brain injury caused by the craniotomy during sham operation (ROC AUC 0.76-0.96, p < 0.001-0.05). In conclusion, our findings revealed that increased levels of neuronally enriched miRNAs in the blood circulation after TBI reflect the extent of cortical injury in the brain but do not predict PTE development.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , MicroRNA Circulante , Epilepsia , MicroRNAs , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas/complicações , MicroRNAs/genética , Epilepsia/genética , Biomarcadores , Modelos Animais de DoençasRESUMO
We tested a hypothesis that in silico-discovered compounds targeting traumatic brain injury (TBI)-induced transcriptomics dysregulations will mitigate TBI-induced molecular pathology and augment the effect of co-administered antiseizure treatment, thereby alleviating functional impairment. In silico bioinformatic analysis revealed five compounds substantially affecting TBI-induced transcriptomics regulation, including calpain inhibitor, chlorpromazine, geldanamycin, tranylcypromine, and trichostatin A (TSA). In vitro exposure of neuronal-BV2-microglial co-cultures to compounds revealed that TSA had the best overall neuroprotective, antioxidative, and anti-inflammatory effects. In vivo assessment in a rat TBI model revealed that TSA as a monotherapy (1 mg/kg/d) or in combination with the antiseizure drug levetiracetam (LEV 150 mg/kg/d) mildly mitigated the increase in plasma levels of the neurofilament subunit pNF-H and cortical lesion area. The percentage of rats with seizures during 0-72 h post-injury was reduced in the following order: TBI-vehicle 80%, TBI-TSA (1 mg/kg) 86%, TBI-LEV (54 mg/kg) 50%, TBI-LEV (150 mg/kg) 40% (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 30% (p < 0.05). Cumulative seizure duration was reduced in the following order: TBI-vehicle 727 ± 688 s, TBI-TSA 898 ± 937 s, TBI-LEV (54 mg/kg) 358 ± 715 s, TBI-LEV (150 mg/kg) 42 ± 64 (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 109 ± 282 s (p < 0.05). This first preclinical intervention study on post-TBI acute seizures shows that a combination therapy with the tissue recovery enhancer TSA and LEV was safe but exhibited no clear benefit over LEV monotherapy on antiseizure efficacy. A longer follow-up is needed to confirm the possible beneficial effects of LEV monotherapy and combination therapy with TSA on chronic post-TBI structural and functional outcomes, including epileptogenesis.
RESUMO
Long-term maintenance of colour polymorphisms often depends on the interplay of multiple selective forces. In the common wall lizard (Podarcis muralis), up to three pure and two mosaic ventral colour morphs co-exist across most of its range. Available evidence suggests that colour morphs in this species are maintained through the interaction between sexual and environment-dependent selection. In particular, colour-assortative pairing has been recorded, suggesting some degree of assortative mating. Here, we combined reduced-representation sequencing (ddRADseq) and fine-scale distribution data to explore the effects of assortative pairing on the common wall lizard. Overall, our results do not support any population structure (FST = 0 and K = 1) nor a significant effect of colour morph or geographic location on genomic differentiation. Therefore, we argue that assortative pairing may not fully translate into assortative mating and genomic differentiation between colour morphs and discuss possible explanations. Nonetheless, we find potential support for an elevated population size and/or source-sink dynamics and debate the potential contribution of other forms of selection to the maintenance of colour polymorphisms in lacertids.
Assuntos
Lagartos , Animais , Genômica , Lagartos/genética , Pigmentação/genética , Polimorfismo Genético , ReproduçãoRESUMO
OBJECTIVE: This study was undertaken to identify prognostic biomarkers for posttraumatic epileptogenesis derived from parameters related to the hippocampal position and orientation. METHODS: Data were derived from two preclinical magnetic resonance imaging (MRI) follow-up studies: EPITARGET (156 rats) and Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx; University of Eastern Finland cohort, 43 rats). Epileptogenesis was induced with lateral fluid percussion-induced traumatic brain injury (TBI) in adult male Sprague Dawley rats. In the EPITARGET cohort, T 2 ∗ -weighted MRI was performed at 2, 7, and 21 days and in the EpiBioS4Rx cohort at 2, 9, and 30 days and 5 months post-TBI. Both hippocampi were segmented using convolutional neural networks. The extracted segmentation mask was used for a geometric construction, extracting 39 parameters that described the position and orientation of the left and right hippocampus. In each cohort, we assessed the parameters as prognostic biomarkers for posttraumatic epilepsy (PTE) both individually, using repeated measures analysis of variance, and in combination, using random forest classifiers. RESULTS: The extracted parameters were highly effective in discriminating between sham-operated and TBI rats in both the EPITARGET and EpiBioS4Rx cohorts at all timepoints (t; balanced accuracy > .9). The most discriminating parameter was the inclination of the hippocampus ipsilateral to the lesion at t = 2 days and the volumes at t ≥ 7 days after TBI. Furthermore, in the EpiBioS4Rx cohort, we could effectively discriminate epileptogenic from nonepileptogenic animals with a longer MRI follow-up, at t = 150 days (area under the curve = .78, balanced accuracy = .80, p = .0050), based on the orientation of both hippocampi. We found that the ipsilateral hippocampus rotated outward on the horizontal plane, whereas the contralateral hippocampus rotated away from the vertical direction. SIGNIFICANCE: We demonstrate that assessment of TBI-induced hippocampal deformation by clinically translatable MRI methodologies detects subjects with prior TBI as well as those at high risk of PTE, paving the way toward subject stratification for antiepileptogenesis studies.
Assuntos
Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Epilepsia , Animais , Biomarcadores , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Modelos Animais de Doenças , Epilepsia/diagnóstico , Epilepsia Pós-Traumática/diagnóstico por imagem , Epilepsia Pós-Traumática/tratamento farmacológico , Epilepsia Pós-Traumática/etiologia , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Percussão , Prognóstico , Ratos , Ratos Sprague-DawleyRESUMO
Competition with invasive grasses is one of the most important drivers of tree planting failures, especially in tropical forests. A widely disseminated weeding approach has been glyphosate spraying, the most used herbicide globally in forestry and ecosystem restoration. However, glyphosate use in restoration is highly controversial and requires further studies to elucidate its effects on restoration processes and the environment. We evaluated the use of glyphosate in riparian forest restoration and its impacts on tree planting costs, weed control efficiency, planted seedling performance, herbaceous and woody species regeneration, soil bacteria, and environmental contamination, using mowing treatments as a reference and based on a controlled experiment established in the Brazilian Atlantic Forest. Glyphosate spraying reduced by one-half and one-third the accumulated aboveground biomass of, respectively, weeds in general and of the invasive grass Urochloa decumbens compared to mowing treatments, and it reduced the cost by half. The performance of planted tree seedlings was markedly favored by glyphosate spraying compared to mowing treatments, as expressed by improved seedling height (~twice higher), crown area (~5× higher), and basal area (~5× higher); the regeneration of both native woody and ruderal herbaceous plants were also enhanced. Neither glyphosate nor its metabolite Aminomethylphosphonic acid (AMPA) residues were detected in either water runoff or soil samples, but they were found at relatively high concentrations in the runoff sediments (from 1.32 to 24.75 mg/kg for glyphosate and from 1.75 to 76.13 mg/kg for AMPA). Soil bacteria communities differed before and after glyphosate spraying in comparison to mowing plots (without glyphosate). Glyphosate spraying was far more cost effective than mowing for controlling U. decumbens and greatly improved the performance of planted tree seedlings and natural regeneration, while not leaving residues in soil and water. However, the changes in the structure of bacterial communities and high concentration of glyphosate and AMPA residues in runoff sediments highlight the need for caution when using this herbicide in riparian buffers. We present alternatives for reducing glyphosate use and minimizing its risks in tree planting initiatives.
Assuntos
Ecossistema , Florestas , Glicina/análogos & derivados , Plantas Daninhas , Solo , Árvores , GlifosatoRESUMO
Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [sepiapterin reductase (SPR)] and carotenoid [beta-carotene oxygenase 2 (BCO2)] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been coopted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles, and haplotype analysis revealed abundant transspecific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.