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1.
Nature ; 626(7999): 542-548, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38109940

RESUMO

The success of colloidal semiconductor nanocrystals (NCs) in science and optoelectronics is inextricable from their surfaces. The functionalization of lead halide perovskite NCs1-5 poses a formidable challenge because of their structural lability, unlike the well-established covalent ligand capping of conventional semiconductor NCs6,7. We posited that the vast and facile molecular engineering of phospholipids as zwitterionic surfactants can deliver highly customized surface chemistries for metal halide NCs. Molecular dynamics simulations implied that ligand-NC surface affinity is primarily governed by the structure of the zwitterionic head group, particularly by the geometric fitness of the anionic and cationic moieties into the surface lattice sites, as corroborated by the nuclear magnetic resonance and Fourier-transform infrared spectroscopy data. Lattice-matched primary-ammonium phospholipids enhance the structural and colloidal integrity of hybrid organic-inorganic lead halide perovskites (FAPbBr3 and MAPbBr3 (FA, formamidinium; MA, methylammonium)) and lead-free metal halide NCs. The molecular structure of the organic ligand tail governs the long-term colloidal stability and compatibility with solvents of diverse polarity, from hydrocarbons to acetone and alcohols. These NCs exhibit photoluminescence quantum yield of more than 96% in solution and solids and minimal photoluminescence intermittency at the single particle level with an average ON fraction as high as 94%, as well as bright and high-purity (about 95%) single-photon emission.


Assuntos
Desenho de Fármacos , Ligantes , Nanopartículas Metálicas , Pontos Quânticos , Acetona/química , Álcoois/química , Ânions , Compostos de Cálcio/química , Cátions , Coloides/química , Chumbo , Medições Luminescentes , Espectroscopia de Ressonância Magnética , Nanopartículas Metálicas/química , Simulação de Dinâmica Molecular , Óxidos/química , Fosfolipídeos/química , Pontos Quânticos/química , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/química
2.
Nature ; 626(7999): 535-541, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297126

RESUMO

The brightness of an emitter is ultimately described by Fermi's golden rule, with a radiative rate proportional to its oscillator strength times the local density of photonic states. As the oscillator strength is an intrinsic material property, the quest for ever brighter emission has relied on the local density of photonic states engineering, using dielectric or plasmonic resonators1,2. By contrast, a much less explored avenue is to boost the oscillator strength, and hence the emission rate, using a collective behaviour termed superradiance. Recently, it was proposed3 that the latter can be realized using the giant oscillator-strength transitions of a weakly confined exciton in a quantum well when its coherent motion extends over many unit cells. Here we demonstrate single-photon superradiance in perovskite quantum dots with a sub-100 picosecond radiative decay time, almost as short as the reported exciton coherence time4. The characteristic dependence of radiative rates on the size, composition and temperature of the quantum dot suggests the formation of giant transition dipoles, as confirmed by effective-mass calculations. The results aid in the development of ultrabright, coherent quantum light sources and attest that quantum effects, for example, single-photon emission, persist in nanoparticles ten times larger than the exciton Bohr radius.

3.
Chem Rev ; 124(8): 4543-4678, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38564235

RESUMO

The activity and durability of the Cu/ZnO/Al2O3 (CZA) catalyst formulation for methanol synthesis from CO/CO2/H2 feeds far exceed the sum of its individual components. As such, this ternary catalytic system is a prime example of synergy in catalysis, one that has been employed for the large scale commercial production of methanol since its inception in the mid 1960s with precious little alteration to its original formulation. Methanol is a key building block of the chemical industry. It is also an attractive energy storage molecule, which can also be produced from CO2 and H2 alone, making efficient use of sequestered CO2. As such, this somewhat unusual catalyst formulation has an enormous role to play in the modern chemical industry and the world of global economics, to which the correspondingly voluminous and ongoing research, which began in the 1920s, attests. Yet, despite this commercial success, and while research aimed at understanding how this formulation functions has continued throughout the decades, a comprehensive and universally agreed upon understanding of how this material achieves what it does has yet to be realized. After nigh on a century of research into CZA catalysts, the purpose of this Review is to appraise what has been achieved to date, and to show how, and how far, the field has evolved. To do so, this Review evaluates the research regarding this catalyst formulation in a chronological order and critically assesses the validity and novelty of various hypotheses and claims that have been made over the years. Ultimately, the Review attempts to derive a holistic summary of what the current body of literature tells us about the fundamental sources of the synergies at work within the CZA catalyst and, from this, suggest ways in which the field may yet be further advanced.

4.
Pharmacol Rev ; 75(2): 380-396, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36781218

RESUMO

Studies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage binge drinking avoid the human confounds and support lifelong changes that increase risks. AIE increases adult alcohol drinking, risky decision-making, reward-seeking, and anxiety as well as reductions in executive function that all increase risks for the development of an AUD. AIE causes persistent increases in brain neuroimmune signaling high-mobility group box 1 (HMGB1), Toll-like receptor, receptor for advanced glycation end products, and innate immune genes that are also found to be increased in human AUD brain. HMGB1 is released from cells by ethanol, both free and within extracellular vesicles, that act on neurons and glia, shifting transcription and cellular phenotype. AIE-induced decreases in adult hippocampal neurogenesis and loss of basal forebrain cholinergic neurons are reviewed as examples of persistent AIE-induced pathology. Both are prevented and reversed by anti-inflammatory and epigenetic drugs. Findings suggest AIE-increased HMGB1 signaling induces the RE-1 silencing transcript blunting cholinergic gene expression, shifting neuronal phenotype. Inhibition of HMGB1 neuroimmune signaling, histone methylation enzymes, and galantamine, the cholinesterase inhibitor, both prevent and reverse AIE pathology. These findings provide new targets that may reverse AUD neuropathology as well as other brain diseases linked to neuroimmune signaling. SIGNIFICANCE STATEMENT: Adolescent underage binge drinking studies find that earlier adolescent drinking is associated with lifelong alcohol problems including high levels of lifetime alcohol use disorder (AUD). Preclinical studies find the underage binge drinking adolescent intermittent ethanol (AIE) model causes lasting changes in adults that increase risks of developing adult alcohol problems. Loss of hippocampal neurogenesis and loss of basal forebrain cholinergic neurons provide examples of how AIE-induced epigenetic and neuroimmune signaling provide novel therapeutic targets for adult AUD.


Assuntos
Alcoolismo , Consumo Excessivo de Bebidas Alcoólicas , Proteína HMGB1 , Consumo de Álcool por Menores , Adolescente , Animais , Humanos , Ratos , Consumo de Bebidas Alcoólicas , Alcoolismo/tratamento farmacológico , Alcoolismo/genética , Alcoolismo/patologia , Consumo Excessivo de Bebidas Alcoólicas/genética , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Consumo Excessivo de Bebidas Alcoólicas/patologia , Epigênese Genética , Etanol/efeitos adversos , Proteína HMGB1/genética , Proteína HMGB1/metabolismo
5.
J Neuroinflammation ; 21(1): 215, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218898

RESUMO

BACKGROUND: Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia and cognitive decline. The release of soluble amyloid (Aß) oligomers into the extracellular space is an early feature of AD pathology. This can promote excitotoxicity and microglial activation. Microglia can adopt several activation states with various functional outcomes. Protective microglial activation states have been identified in response to Aß plaque pathology in vivo. However, the role of microglia and immune mediators in neurotoxicity induced by soluble Aß oligomers is unclear. Further, there remains a need to identify druggable molecular targets that promote protective microglial states to slow or prevent the progression of AD. METHODS: Hippocampal entorhinal brain slice culture (HEBSC) was employed to study mechanisms of Aß1-42 oligomer-induced neurotoxicity as well as the role of microglia. The roles of glutamate hyperexcitation and immune signaling in Aß-induced neurotoxicity were assessed using MK801 and neutralizing antibodies to the TNF-related apoptosis-inducing ligand (TRAIL) respectively. Microglial activation state was manipulated using Gi-hM4di designer receptor exclusively activated by designer drugs (DREADDs), microglial depletion with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX3397, and microglial repopulation (PLX3397 withdrawal). Proteomic changes were assessed by LC-MS/MS in microglia isolated from control, repopulated, or Aß-treated HEBSCs. RESULTS: Neurotoxicity induced by soluble Aß1-42 oligomers involves glutamatergic hyperexcitation caused by the proinflammatory mediator and death receptor ligand TRAIL. Microglia were found to have the ability to both promote and restrain Aß-induced toxicity. Induction of microglial Gi-signaling with hM4di to prevent pro-inflammatory activation blunted Aß neurotoxicity, while microglial depletion with CSF1R antagonism worsened neurotoxicity caused by Aß as well as TRAIL. HEBSCs with repopulated microglia, however, showed a near complete resistance to Aß-induced neurotoxicity. Comparison of microglial proteomes revealed that repopulated microglia have a baseline anti-inflammatory and trophic phenotype with a predicted pathway activation that is nearly opposite that of Aß-exposed microglia. mTORC2 and IRF7 were identified as potential targets for intervention. CONCLUSION: Microglia are key mediators of both protection and neurodegeneration in response to Aß. Polarizing microglia toward a protective state could be used as a preventative strategy against Aß-induced neurotoxicity.


Assuntos
Peptídeos beta-Amiloides , Microglia , Fragmentos de Peptídeos , Ligante Indutor de Apoptose Relacionado a TNF , Microglia/metabolismo , Microglia/efeitos dos fármacos , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Animais , Fragmentos de Peptídeos/toxicidade , Fragmentos de Peptídeos/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/toxicidade , Camundongos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Córtex Entorrinal/metabolismo , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/patologia , Técnicas de Cultura de Órgãos
6.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34962259

RESUMO

The current global pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken a substantial number of lives across the world. Although few vaccines have been rolled-out, a number of vaccine candidates are still under clinical trials at various pharmaceutical companies and laboratories around the world. Considering the intrinsic nature of viruses in mutating and evolving over time, persistent efforts are needed to develop better vaccine candidates. In this study, various immuno-informatics tools and bioinformatics databases were deployed to derive consensus B-cell and T-cell epitope sequences of SARS-CoV-2 spike glycoprotein. This approach has identified four potential epitopes which have the capability to initiate both antibody and cell-mediated immune responses, are non-allergenic and do not trigger autoimmunity. These peptide sequences were also evaluated to show 99.82% of global population coverage based on the genotypic frequencies of HLA binding alleles for both MHC class-I and class-II and are unique for SARS-CoV-2 isolated from human as a host species. Epitope number 2 alone had a global population coverage of 98.2%. Therefore, we further validated binding and interaction of its constituent T-cell epitopes with their corresponding HLA proteins using molecular docking and molecular dynamics simulation experiments, followed by binding free energy calculations with molecular mechanics Poisson-Boltzmann surface area, essential dynamics analysis and free energy landscape analysis. The immuno-informatics pipeline described and the candidate epitopes discovered herein could have significant impact upon efforts to develop globally effective SARS-CoV-2 vaccines.


Assuntos
Vacinas contra COVID-19 , Epitopos de Linfócito B , Epitopos de Linfócito T , Simulação de Acoplamento Molecular , SARS-CoV-2 , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Humanos , SARS-CoV-2/química , SARS-CoV-2/imunologia , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/imunologia
7.
Epilepsia ; 65(6): 1568-1580, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38606600

RESUMO

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.


Assuntos
Epilepsia do Lobo Temporal , Hipocampo , Imageamento por Ressonância Magnética , Esclerose , Convulsões Febris , Estado Epiléptico , Humanos , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Masculino , Feminino , Esclerose/patologia , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/patologia , Estado Epiléptico/etiologia , Convulsões Febris/patologia , Convulsões Febris/diagnóstico por imagem , Lactente , Pré-Escolar , Criança , Seguimentos , Atrofia/patologia , Esclerose Hipocampal
8.
Brain ; 146(8): 3444-3454, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37143309

RESUMO

Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic brain oedema, of which megalencephalic leukoencephalopathy with subcortical cysts (MLC) is the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved in astrocyte volume regulation, are the main causes of MLC. In some patients, the genetic cause remains unknown. We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We determined subcellular localization of the related novel proteins in cells and in human brain tissue. We investigated functional consequences of the newly identified variants on volume regulation pathways using cell volume measurements, biochemical analysis and electrophysiology. We identified a novel homozygous variant in AQP4, encoding the water channel aquaporin-4, in two siblings, and two de novo heterozygous variants in GPRC5B, encoding the orphan G protein-coupled receptor GPRC5B, in three unrelated patients. The AQP4 variant disrupts membrane localization and thereby channel function. GPRC5B, like MLC1, GlialCAM and aquaporin-4, is expressed in astrocyte endfeet in human brain. Cell volume regulation is disrupted in GPRC5B patient-derived lymphoblasts. GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation. In conclusion, we identify aquaporin-4 and GPRC5B as old and new players in genetic brain oedema. Our findings shed light on the protein complex involved in astrocyte volume regulation and identify GPRC5B as novel potentially druggable target for treating brain oedema.


Assuntos
Edema Encefálico , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Humanos , Proteínas de Membrana/genética , Edema Encefálico/genética , Edema Encefálico/metabolismo , Mutação/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Encéfalo/metabolismo , Astrócitos/metabolismo , Aquaporina 4/genética , Aquaporina 4/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
9.
Dev Med Child Neurol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718250

RESUMO

Accurate determination of death is a necessary responsibility of the medical profession. Brain death, or death by neurological criteria (DNC), can be legally declared after the determination of permanent loss of clinical brain function, including the capacity for consciousness, brainstem reflexes, and the ability to breathe spontaneously. Despite longstanding debates over the exact definition of brain death or DNC and how it is determined, most middle- and high-income countries have compatible medical protocols and legal policies for brain death or DNC. This review summarizes the 2023 updated guidelines for brain death or DNC determination, which integrate adult and pediatric diagnostic criteria. We discuss the clinical challenges related to brain death or DNC determination in infants and young children. We emphasize that physicians must follow the standardized and meticulous evaluation processes outlined in these guidelines to reduce diagnostic error and ensure no false positive determinations. An essential component of the brain death or DNC evaluation is appropriate and transparent communication with families. Ongoing efforts to promote consistency and legal uniformity in the declaration of death are needed.

10.
Am J Respir Crit Care Med ; 208(12): 1305-1315, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37820359

RESUMO

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).


Assuntos
Doenças Transmissíveis , Doenças Pleurais , Sepse , Humanos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos de Viabilidade , Doenças Transmissíveis/etiologia , Sepse/tratamento farmacológico , Sepse/cirurgia , Sepse/etiologia , Terapia Enzimática
11.
Lasers Surg Med ; 56(7): 673-681, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39039622

RESUMO

OBJECTIVE: In this study, we evaluated the effectiveness of antimicrobial blue light (aBL; 410 nm wavelength) against ß-lactamase-carrying bacteria and the effect of aBL on the activity of ß-lactamases. METHODS: Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae strains carrying ß-lactamases as well as a purified ß-lactamase enzymes were studied. ß-lactamase activity was assessed using a chromogenic cephalosporin hydrolysis assay. Additionally, we evaluated the role of porphyrins in the photoreaction, as well as protein degradation by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Finally, we investigated the bactericidal effect of combined aBL-ceftazidime exposure against a metallo-ß-lactamase expressing P. aeruginosa strain. RESULTS: Our study demonstrated that aBL effectively killed ß-lactamase-producing bacteria and reduced ß-lactamase activity. After an aBL exposure of 1.52 J/cm2, a 50% reduction in enzymatic activity was observed in P. aeruginosa. Additionally, we found a 40% decrease in the photoreaction activity of porphyrins following an aBL exposure of 64.8 J/cm2. We also revealed that aBL reduced ß-lactamase activity via protein degradation (after 136.4 J/cm2). Additionally, aBL markedly improved the bactericidal effect of ceftazidime (by >4-log10) in the metallo-ß-lactamase P. aeruginosa strain. CONCLUSION: Our results provide evidence that aBL compromises bacterial ß-lactamase activity, offering a potential approach to overcome ß-lactam resistance in bacteria.


Assuntos
Luz Azul , Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Resistência beta-Lactâmica , beta-Lactamases , Antibacterianos/farmacologia , Resistência beta-Lactâmica/efeitos da radiação , beta-Lactamases/metabolismo , Ceftazidima/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/efeitos da radiação , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação
12.
J Helminthol ; 98: e9, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38247291

RESUMO

Based on an integrative approach, this study describes a new species of Urocleidoides infesting Schizodon nasutus in the Paranapanema River basin, Brazil. The new species can be distinguished from its congeners by specific morphological features, including the shape of the male copulatory organ and accessory piece, the ventral bar shape, and the shape and size of the hooks. Molecular analyses, particularly of the 28S rDNA gene, suggest a close relationship between the new species and Urocleidoides paradoxus. The phylogenetic and taxonomic arrangement of Urocleidoides is discussed, as the analyses of the 28S rDNA and COI mtDNA resolved the genus as non-monophyletic, with Diaphorocleidus, Rhinoxenus, and Cacatuocotyle nested within it. Additional morphological and molecular data of other congeneric species are required to investigate the phylogenetic position and classification of Urocleidoides. This study underscores the significance of using integrative approaches in understanding host-parasite associations and phylogenetic relationships, contributing to the description of the freshwater fish parasite biodiversity in South America, particularly in the Paranapanema river basin.


Assuntos
Caraciformes , Trematódeos , Masculino , Animais , Caraciformes/genética , Brasil , Brânquias , Filogenia , DNA Ribossômico/genética
13.
J Helminthol ; 98: e23, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462988

RESUMO

During an ecological study with a near-endangered anuran in Brazil, the Schmidt's Spinythumb frog, Crossodactylus schmidti Gallardo, 1961, we were given a chance to analyze the gastrointestinal tract of a few individuals for parasites. In this paper, we describe a new species of an allocreadiid trematode of the genus Creptotrema Travassos, Artigas & Pereira, 1928, which possesses a unique trait among allocreadiids (i.e., a bivalve shell-like muscular structure at the opening of the ventral sucker); the new species represents the fourth species of allocreadiid trematode parasitizing amphibians. Besides, the new species is distinguished from other congeners by the combination of characters such as the body size, ventral sucker size, cirrus-sac size, and by having small eggs. DNA sequences through the 28S rDNA and COI mtDNA further corroborated the distinction of the new species. Phylogenetic analyses placed the newly generated sequences in a monophyletic clade together with all other sequenced species of Creptotrema. Genetic divergences between the new species and other Creptotrema spp. varied from 2.0 to 4.2% for 28S rDNA, and 15.1 to 16.8% for COI mtDNA, providing robust validation for the recognition of the new species. Even though allocreadiids are mainly parasites of freshwater fishes, our results confirm anurans as hosts of trematodes of this family. Additionally, we propose the reallocation of Auriculostoma ocloya Liquin, Gilardoni, Cremonte, Saravia, Cristóbal & Davies, 2022 to the genus Creptotrema. This study increases the known diversity of allocreadiids and contributes to our understanding of their evolutionary relationships, host-parasite relationships, and biogeographic history.


Assuntos
Trematódeos , Infecções por Trematódeos , Humanos , Animais , Infecções por Trematódeos/veterinária , Infecções por Trematódeos/parasitologia , Filogenia , Trematódeos/genética , DNA Ribossômico/genética , DNA Ribossômico/química , Anuros , DNA Mitocondrial/genética , Brasil , RNA Ribossômico 28S/genética
14.
Dev Med Child Neurol ; 65(7): 900-907, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36732680

RESUMO

The aim of this review was to discuss bioethics in prenatal diagnosis and health care after recent legislative and judicial changes affecting reproductive rights, such as the repeal of 'Roe v. Wade' in the United States. We recognize that abortion involves particular moralities that are not universal or shared by all cultures, groups, and individuals. We reviewed the historical aspects of embryology and personhood, fetal morbidity and mortality, and parental options for prenatal diagnostic testing. We examined relevant ethical issues including informed consent, the emergence of fetal pain, reproductive autonomy, the fiduciary responsibilities of pregnant mothers, and the obligations of physicians caring for the maternal-fetal dyad. The code of medical ethics includes respect for decisional privacy and the protection of information shared in confidence. When a fetal anomaly is diagnosed, pregnant mothers must be informed about the risks, burdens, and alternatives in either continuing or terminating the pregnancy. Parental choice should include the right to refuse testing, the informed choice not to know about certain genetic test results, and the right to make informed decisions about the best interests of the future child. In the diagnosis and care of fetal anomalies, moral dilemmas arise. Before fetal viability, the mother's autonomy, sense of beneficence, and personal values should be trusted and respected. Perinatal palliative care should be available to pregnant mothers whose anomalous fetus is carried to birth.


Assuntos
Aborto Induzido , Gestantes , Gravidez , Feminino , Criança , Humanos , Estados Unidos , Diagnóstico Pré-Natal , Ética Médica , Pessoalidade , Feto
15.
Proc Natl Acad Sci U S A ; 117(26): 15182-15192, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32554494

RESUMO

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.


Assuntos
Antineoplásicos/efeitos adversos , Cromatina/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/efeitos adversos , Animais , Linhagem Celular , Doxorrubicina/análogos & derivados , Doxorrubicina/síntese química , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Cardiopatias/induzido quimicamente , Histonas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos
16.
J Helminthol ; 97: e13, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700418

RESUMO

Mexico possesses a large diversity of amphibians partly due to its complex topography and transitional position between the Nearctic and Neotropical biogeographical regions. However, its helminth parasite fauna has been relatively poorly studied. Specimens of the Vaillant's frog, Lithobates vaillanti (Brocchi) were sampled in the tropical rain forest of Nahá, in the Chiapas Highlands, and examined for parasites. Two trematode species were collected from their hosts; morphologically, specimens were allocated to the genera Langeronia Caballero and Bravo-Hollis, 1949 and Haematoloechus Looss, 1899, respectively. Individuals were sequenced for two molecular markers (the mitochondrial cytochrome c oxidase gene, and the ribosomal gene 28S), and processed for morphological analyses, including scanning electron microscopy. The new evidence was not enough to accomplish the identification at species level of Langeronia sp. due to the lack of sequence data from the type localities of Langeronia parva Christian, 1970 and Langeronia macrocirra Caballero and Bravo-Hollis, 1949. Likewise, the newly generated data were useful to properly identify the adult specimens of lung flukes as Haematoloechus complexus Seely, 1906.


Assuntos
Helmintos , Parasitos , Trematódeos , Humanos , Animais , México , Ranidae/parasitologia , Filogenia
17.
J Helminthol ; 97: e98, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095098

RESUMO

Scaphanocephalus is a small trematode genus belonging to the family Opistorchiidae. The genus currently contains only three species associated with marine fish as intermediate hosts and fish-eating birds as definitive hosts. Here, specimens of Scaphanocephalus were collected from the Osprey, Pandion haliaetus, and the White mullet, Mugil curema in the Yucatán Peninsula, Mexico. We report for the first-time DNA sequences of adult specimens of Scaphanocephalus, particularly S. expansus, as well as a sequence of a different species sampled as metacercaria. Morphological comparisons of Scaphanocephalus expansus confirmed the identity of the adult specimens, with minor morphological variations; Scanning electron photomicrographs were included, and the species was re-described. Phylogenetic analysis based on 28S rDNA sequences showed that Scaphanocephalus is monophyletic within Opisthorchiidae and consists of three independent lineages. Sequences of adults are identical to those of S. expansus. Instead, the sequence of the metacercaria sampled from the mesentery of Mugil curema nested with specimens reported as Scaphanocephalus sp. from a labrid fish in the Mediterranean Sea, herein named it as Scaphanocephalus sp. 2.


Assuntos
Falconiformes , Doenças dos Peixes , Heterophyidae , Smegmamorpha , Trematódeos , Infecções por Trematódeos , Animais , México , Filogenia , DNA de Helmintos/genética , Heterophyidae/genética , Peixes , Metacercárias , Infecções por Trematódeos/veterinária
18.
J Helminthol ; 97: e85, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37945308

RESUMO

Clinostomidae is a diverse family of digenean parasitizing fish-eating birds as adults and fishes as metacercariae. The species composition, within the genus Clinostomum has been steadily increasing in recent years. In Argentina, four named species of Clinostomum have been documented, accompanied by four metacercariae representing distinct genetic lineages whose adults have not been identified. This study focused on examining clinostomids in three fish species - Australoheros scitulus (ASI), Cichlasoma dimerus (CDIM), and Pimelodella laticeps (PLA) - at various localities in Argentina. We conducted both morphological and molecular characterizations of the Clinostomum metacercariae collected from these fish species. Molecular phylogenetic analyses using COI mtDNA were performed to determine the placement of these metacercariae within the clinostomid phylogenetic tree. Clinostomum ASC represents a distinct lineage, morphologically distinguishable from other sequenced metacercariae due to its body shape (widest anteriorly and becoming slender towards the posterior end); this lineage was found to be closely related to C. caffarae. While Clinostomum CDIM and Clinostomum PLA exhibited morphological differences, they clustered together genetically with metacercariae reported in previous studies as Clinostomum L3 and Clinostomum CVI. This outcome, coupled with a low genetic distance (0 to 3%), suggests that they are conspecific with metacercariae found in fish across Mexico, Costa Rica, and Argentina. In light of the extensive diversity of fish species in Argentine freshwater ecosystems (over 500 species), and considering the relatively constrained extent of prior investigations, the anticipation of unearthing additional Clinostomum species or lineages is plausible.


Assuntos
Ciclídeos , Doenças dos Peixes , Trematódeos , Infecções por Trematódeos , Animais , DNA Mitocondrial/genética , Infecções por Trematódeos/veterinária , Metacercárias/anatomia & histologia , Filogenia , Ecossistema , Peixes , Água Doce , América do Sul , Poliésteres
19.
J Helminthol ; 97: e68, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37612585

RESUMO

Phyllodistomum pepirense n. sp. is described from the urinary bladder of Hoplias malabaricus (Bloch, 1794), sampled in the Jacaré-Pepira River in São Paulo state, Brazil. The isolates of the new species were recovered as a monophyletic group in the phylogenetic analysis of the 28S rRNA gene, which showed the new species as the sister taxa of Phyllodistomum virmantasi Pinacho-Pinacho, Sereno-Uribe, Hernández-Orts, García-Varela & Pérez-Ponce de León, 2021, a species sampled from an eleotrid fish in Southeastern Mexico. The new species differs morphologically from P. virmantasi by having a larger body size, slightly lobed testes and ovary, a mostly intercaecal uterus, slightly diverticulated caeca, and vitelline masses irregularly shaped. The new species is also readily distinguished from other species of Phyllodistomum Braun, 1899 reported from freshwater fishes in Brazil - namely, P. rhamdiae Amato & Amato, 1993 and P. spatula Odhner, 1902. The new species is herein described based on morphological characteristics, molecular data from D1-D3 domains of the 28S rRNA gene, host association, and geographical distribution.


Assuntos
Caraciformes , Trematódeos , Animais , Feminino , Brasil , Filogenia , Trematódeos/genética , Tamanho Corporal , RNA Ribossômico 28S/genética
20.
BMC Public Health ; 22(1): 462, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35255865

RESUMO

BACKGROUND: Burkina Faso experienced an epidemic resurgence of dengue in 2016, which led to the implementation of several control strategies. In order to allow a better adaptation of these strategies, we studied the spatio-temporal distribution of dengue. METHODS: Monthly dengue cases from 2016 to 2019, aggregated at the health district level, were used to map the crude incidence, excess risk, and smoothed incidence of dengue in Burkina Faso with GeoDa software. A Kulldoff scan on Satscan software was then used to identify spatio-temporal clustering of cases. RESULTS: The results show that the distribution of dengue fever across the health districts of Burkina Faso is heterogeneous. Dengue was considered non-endemic in 9 out of the 70 health districts, minimally endemic in 45 districts (< 10 incidences), moderately endemic (10-100 incidences) in 12 districts, and highly endemic (> 100 incidences) in 4 districts. The main cluster covered the health districts of Baskuy, Nongr-massom, Sig-noghin, Boulmiougou, and Bogodogo. The months of October and November corresponded to the peak of cases and a significant temporal cluster in 2017. CONCLUSION: This study identified the spatial and temporal clustering of dengue cases in Burkina Faso. These results may help to develop better preventive strategies.


Assuntos
Dengue , Burkina Faso/epidemiologia , Análise por Conglomerados , Dengue/epidemiologia , Humanos , Incidência , Análise Espaço-Temporal
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