ABSTRACT
Diamond is a semiconductor material with remarkable structural, thermal, and electronic properties that has garnered significant interest in the field of electronics. Although hydrogen (H) and oxygen (O) terminations are conventionally favored in transistor designs, alternative options, such as silicon (Si) and germanium (Ge), are being explored because of their resilience to harsh processing conditions during fabrication. Density-functional theory was used to examine the non-oxidized and oxidized group-IV (Si and Ge)-terminated diamond (100) surfaces. The (3 × 1) reconstructed surfaces feature an ether configuration and show relative stability compared with the bare surface. Hybrid-functional calculations of the electronic properties revealed reduced fundamental bandgaps (<1 eV) and lower negative electron affinities (NEAs) than those of H-terminated diamond surfaces, which is attributed to the introduction of unoccupied Si (Ge) states and the depletion of negative charges. Furthermore, oxidation of these surfaces enhanced the stability of the diamond surfaces but resulted in two structural configurations: ether and ketone. Oxidized ether configurations displayed insulating properties with energy gaps of â¼4.3 ± 0.3 eV, similar to H-terminated diamond (100) surfaces, whereas bridged ether configurations exhibited metallic properties. Oxidization of the metallic ketone configurations leads to the opening of relatively smaller gaps in the range of 1.1-1.7 eV. Overall, oxidation induced a shift from NEAs to positive electron affinities, except for the reverse-ordered ketone surface with an NEA of -0.94 eV, a value comparable to the H-terminated diamond (100) surfaces. In conclusion, oxidized group-IV-terminated diamond surfaces offer enhanced stability compared to H-terminated surfaces and display unique structural and electronic properties that are influenced by surface bonding.
ABSTRACT
The Mediterranean region is distinguished by its gastronomic diversity and a wide variety of indigenous nut crops. In line with changing global food consumers' preferences, a noteworthy aspect is the increasing demand to the use of local varieties in recipe formulation. The aim of the present study was to incorporate the Terra Fria chestnut (Portugal) and Negreta hazelnut from Reus (Spain) in traditional Mediterranean recipes. The sensory, technofunctional, nutritional, and shelf-life characterization were investigated in hazelnut omelette (gluten and gluten-free) and chestnut pudding (sugar and sugar-free) formulations. Results conducted by trained assessors using the free choice profiling (FCP) showed that hazelnut omelette samples were described as "creamy," "smooth," and "handmade." In addition, the texture obtained with the hazelnut omelette gluten-free version showed the softest textural profile analysis attributes, with lower values for hardness (2.43 ± 0.36 N), adhesiveness (-0.38 ± 0.00 g s) and gumminess (2.12 ± 0.14). Furthermore, the shelf-life studies revealed a more golden color (>14.43 of a* CIELAB coordinate) and a lower moisture content (25.36%-43.59%) in the hazelnut flour formulation, in addition to the enrichment in terms of protein (8.36 g/100 g), fiber, and healthy fats. In the case of chestnut pudding, it was observed that the study parameters did not differ significantly from its sweetened analogue with positive attributes in FCP ("toasted," "fluffy," and "sweet"), positioning it as a viable alternative to sugar in this application. Therefore, both hazelnut flour in hazelnut omelette and oligofructose in chestnut pudding proved to be promising ingredients in the formulation of gluten-free and sugar-free developed products, offering attractive organoleptic and textural characteristics.
ABSTRACT
Meiosis, a reductional cell division, relies on precise initiation, maturation, and resolution of crossovers (COs) during prophase I to ensure the accurate segregation of homologous chromosomes during metaphase I. This process is regulated by the interplay of RING-E3 ligases such as RNF212 and HEI10 in mammals. In this study, we functionally characterized a recently identified RING-E3 ligase, RNF212B. RNF212B colocalizes and interacts with RNF212, forming foci along chromosomes from zygonema onward in a synapsis-dependent and DSB-independent manner. These consolidate into larger foci at maturing COs, colocalizing with HEI10, CNTD1, and MLH1 by late pachynema. Genetically, RNF212B foci formation depends on Rnf212 but not on Msh4, Hei10, and Cntd1, while the unloading of RNF212B at the end of pachynema is dependent on Hei10 and Cntd1. Mice lacking RNF212B, or expressing an inactive RNF212B protein, exhibit modest synapsis defects, a reduction in the localization of pro-CO factors (MSH4, TEX11, RPA, MZIP2) and absence of late CO-intermediates (MLH1). This loss of most COs by diakinesis results in mostly univalent chromosomes. Double mutants for Rnf212b and Rnf212 exhibit an identical phenotype to that of Rnf212b single mutants, while double heterozygous demonstrate a dosage-dependent reduction in CO number, indicating a functional interplay between paralogs. SUMOylome analysis of testes from Rnf212b mutants and pull-down analysis of Sumo- and Ubiquitin-tagged HeLa cells, suggest that RNF212B is an E3-ligase with Ubiquitin activity, serving as a crucial factor for CO maturation. Thus, RNF212 and RNF212B play vital, yet overlapping roles, in ensuring CO homeostasis through their distinct E3 ligase activities.
Subject(s)
Chromosome Pairing , Crossing Over, Genetic , Meiosis , Ubiquitin-Protein Ligases , Animals , Mice , Male , Female , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , Poly-ADP-Ribose Binding Proteins/genetics , Mice, Knockout , Humans , LigasesABSTRACT
INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Humans , HIV Infections/genetics , Acquired Immunodeficiency Syndrome/genetics , Interleukin-6/genetics , Interleukin-10/genetics , Cross-Sectional Studies , Gene Frequency , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Receptors, CCR5/geneticsABSTRACT
To determine their transfer factors, activity concentrations of natural radionuclides were measured in the leaves and acorns of holm oak (Quercus ilex L.) trees collected from seven locations with different soil properties and radionuclide activity concentrations. The chemical and mineralogical compositions of the soils were also analysed to investigate the effect these had on radionuclide absorption by the trees. Soil chemistry showed significant effects on radionuclide incorporation into Quercus ilex L. tissues. A significant relationship was established between activity concentrations and soil content of Ca and P with 238U and 226Ra in the leaves and acorns of Quercus ilex L. Differentiated transfer was found for 40K, which showed greater transfer to the leaves than the other radionuclides. The activity concentration of U and 226Ra was higher in the fruits than in the leaves, with the opposite effect being observed for 40K. The risk of U and 226Ra transfer into the food chain through acorn consumption by livestock is predicted to increase in soils poor in Ca and rich in P.
Subject(s)
Quercus , Radiation Monitoring , Fruit , Quercus/metabolism , Lead/analysis , Soil/chemistry , Plant Leaves/chemistry , TreesABSTRACT
Mechanotherapy is a groundbreaking approach to impact carcinogenesis. Cells sense and respond to mechanical stimuli, translating them into biochemical signals in a process known as mechanotransduction. The impact of stress on tumor growth has been studied in the last three decades, and many papers highlight the role of mechanics as a critical self-inducer of tumor fate at the in vitro and in vivo biological levels. Meanwhile, mathematical models attempt to determine laws to reproduce tumor dynamics. This review discusses biological mechanotransduction mechanisms and mathematical-biomechanical models together. The aim is to provide a common framework for the different approaches that have emerged in the literature from the perspective of tumor avascularity and to provide insight into emerging mechanotherapies that have attracted interest in recent years.
Subject(s)
Mechanotransduction, Cellular , Neoplasms , Humans , Mechanotransduction, Cellular/physiologyABSTRACT
La aparición de complicaciones graves, como el neumotórax o las cavitaciones pulmonares, en pacientes con infecciones recientes por el SARS-CoV-2 aumenta la morbi-mortalidad, y supone un reto diseñar la estrategia terapéutica más adecuada que permita mejorar su pronóstico. Las cavitaciones pulmonares se suelen asociar a complicaciones secundarias como la hemoptisis y el neumotórax, y confieren mal pronóstico. Se presenta el caso de dos pacientes con enfermedad COVID-19 confirmada por PCR nasofaríngea y que, tras evolución inicialmente satisfactoria, reingresaron con afectación pulmonar compatible con cavitaciones pulmonares y con insuficiencia respiratoria. Las lesiones cavitadas pulmonares en pacientes que hayan sufrido COVID-19 deben identificarse de forma precoz y realizar las determinaciones y cultivos necesarios para descartar sobreinfecciones añadidas que puedan empeorar el pronóstico.(AU)
Patients who have recently suffered from SARS-CoV-2 infections may suffer serious complications, such as pneumothorax or pulmonary cavitations that increase morbi-mortality and imply a challenge for the design of the most appropriate therapeutic strategy to improve their prognosis. Pulmonary cavities are usually associated with secondary complications such as hemoptysis and pneumothorax, and so offer a poor prognosis. We present the case of two patients with COVID-19 disease confirmed by nasopharyngeal PCR who showed satisfactory evolution before readmission with pulmonary involvement compatible with pulmonary cavitation and respiratory failure. Cavitated lesions in the lungs of patients who recently suffered COVID-19 must be identified early in order to discard additional superinfections that may worsen the prognosis.(AU)
Subject(s)
Humans , Health Sciences , Coronavirus , Cavitation , Severe acute respiratory syndrome-related coronavirus , Superinfection , PneumothoraxABSTRACT
Childhood lead poisoning is an issue that continues to plague major U.S. cities. Despite efforts by the Philadelphia Department of Public Health to curtail systemic childhood lead poisoning, children continue to be identified with elevated blood lead levels. The persistence of elevated blood lead levels in children is concerning because lead poisoning has been linked to decreases in academic achievement and IQ, with associated repercussions for entire communities. This paper reports the results of an analysis of the spatial distribution of houses with lead paint (i.e., pre-1978), demolitions, and occurrence of historic smelters, in West and North Philadelphia, relative to elevated blood lead level data, to determine which lead sources act as primary lead-risk factors. The presence of lead paint in homes and the number of demolitions of older properties were found to have the highest correlations to elevated blood lead levels for children in Philadelphia. Using lead-risk factors including lead paint, housing code violations, demolitions, and owner-occupied housing units, a lead-risk assessment was performed at the census tract level to identify future soil sampling sites and high-risk neighborhoods in Philadelphia. These sites of high risk for lead exposure, and in particular the census tracts 175 and 172, should be prioritized for lead poisoning prevention initiatives.
ABSTRACT
INTRODUCTION AND AIMS: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Many risk factors are involved, and current evidence links the gut microbiota and colorectal carcinogenesis. Fusobacterium nucleatum (F. nucleatum) is proposed as one of the risk factors at the onset and during the progression of CRC, due to immune system and inflammatory modulation. MATERIALS AND METHODS: Ninety samples from three different regions of the colon were collected through colonoscopy in patients with CRC, and qPCR TagMan® was conducted to detect F. nucleatum and cytokines (IL-17, IL-23, and IL-10) in tumor, peritumor, and normal samples. The differences between them were analyzed and correlated. RESULTS: The abundance of F. nucleatum determined through the 2-ΔΔCt method in CRC (7.750 [5.790-10.469]) was significantly higher than in the normal control (0.409 [0.251-0.817]) (p < 0.05). There was no significant association between F. nucleatum and the cytokines (p > 0.05). CONCLUSIONS: CRC is a heterogeneous disease that presents and progresses in a complex microenvironment, partially due to gut microbiome imbalance. F. nucleatum was enriched in CRC tissue, but whether that is a cause of the pathology or a consequence, has not yet been clearly defined.
Subject(s)
Colorectal Neoplasms , Fusobacterium Infections , Carcinogenesis , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Cytokines , Fusobacterium Infections/complications , Fusobacterium Infections/epidemiology , Fusobacterium nucleatum , Humans , Tumor MicroenvironmentABSTRACT
Patients who have recently suffered from SARS-CoV-2 infections may suffer serious complications, such as pneumothorax or pulmonary cavitations that increase morbi-mortality and imply a challenge for the design of the most appropriate therapeutic strategy to improve their prognosis. Pulmonary cavities are usually associated with secondary complications such as hemoptysis and pneumothorax, and so offer a poor prognosis. We present the case of two patients with COVID-19 disease confirmed by nasopharyngeal PCR who showed satisfactory evolution before readmission with pulmonary involvement compatible with pulmonary cavitation and respiratory failure. Cavitated lesions in the lungs of patients who recently suffered COVID-19 must be identified early in order to discard additional superinfections that may worsen the prognosis.
Subject(s)
COVID-19 , Pneumothorax , COVID-19/complications , Humans , Lung , Pneumothorax/etiology , SARS-CoV-2ABSTRACT
Introducción. La hipertensión pulmonar en pediatríasuele presentarse con una clínica inespecífica que hace difícilsu sospecha diagnóstica, siendo hasta en el 30% de los casosde etiología multifactorial.Caso clínico. Presentamos el caso de una lactante de2 meses de edad que comienza con clínica inespecífica(vómitos, rechazo de tomas, irritabilidad), presentando unempeoramiento progresivo que termina en varias paradascardiorrespiratorias abortadas. En el estudio diagnósticoúnicamente se encuentra una hipertensión pulmonar grave que no responde a tratamiento vasodilatador agresivo.Además, muestra hiperecogenicidad periventricular condesarrollo de edema cerebral progresivo, que termina conla vida de la paciente. El estudio metabólico muestra elevación de glicina en líquidos biológicos; y el estudio genético confirma una variante patogénica en homocigosis en elgen NFU1 (NM_001002755.3:c.622G>T, p.Gly208Cys), por loque se diagnostica de síndrome de disfunción mitocondrialmúltiple tipo 1.Conclusiones. El síndrome de disfunción mitocondrialmúltiple tipo 1 es una enfermedad autosómica recesiva conuna prevalencia <1/1.000.000, que afecta al metabolismomitocondrial por alteración del gen NFU1. La clínica comienza en las primeras etapas de la vida por síntomas inespecíficos, neurológicos e hipertensión pulmonar, con un cursomortal a los pocos meses de edad. Destaca un aumento deglicina y lactato en líquidos biológicos; una leucoencefalopatía periventricular con degeneración quística, cavitacionesy/o necrosis. El diagnóstico de las enfermedades metabólicasprecisa de una alta sospecha clínica. El curso rápidamenteprogresivo y refractario al tratamiento de una hipertensiónpulmonar que asocia clínica encefalopática, debe hacernossospechar una alteración en el metabolismo mitocondrial. (AU)
Introduction. Pulmonary hypertension in children usually presents with non-specific symptoms that makes thesuspicion difficult, being up to 30% of cases of multifactorialetiology.Clinical case. We present the case of a 2-month-old infantwho began with nonspecific symptoms, presenting a progressive worsening that results in aborted cardiorespiratoryarrest. The diagnostic work-up only shows a severe pulmonary hypertension that does not respond to aggressivevasodilator therapy. In addition, the patient has periventricular hyperechogenicity with progressive cerebral edema,causing the patients death. The metabolic study shows elevation of glycine in biological fluids; and the genetic study confirmed a homozygous pathogenic variant in the NFU1gene (NM_001002755.3:c.622G>T, p.Gly208Cys), leading tothe diagnosis of type 1 multiple mitochondrial dysfunctionsyndrome.Conclusion. Multiple mitochondrial dysfunction syndrome type 1 is an autosomal recessive disease with a prevalence <1/1,000,000, which affects mitochondrial metabolismdue to alterations in the NFU1 gene. The clinic begins in theearly stages of life presenting with nonspecific symptoms,neurological symptoms and pulmonary hypertension; witha fatal course in all cases. An increase in glycine and lactate in biological fluids is characteristic; it is also typical tofind a periventricular leukoencephalopathy with chemicaldegeneration, cavitations and/or necrosis. The diagnosisof metabolic disorders requires a high clinical suspicion. Asevere pulmonary hypertension associated with encephalopathy should lead us to suspect an alteration in mitochondrial metabolism (AU)
Subject(s)
Humans , Female , Infant , Hypertension, Pulmonary/diagnosis , Mitochondria, Heart/genetics , Mitochondrial Proteins/genetics , Mutation/genetics , SyndromeABSTRACT
Resumen Introducción: Las segundas resecciones anatómicas son cada vez más frecuentes en el tratamiento de carcinomas pulmonares sincrónicos, metacrónicos y de metástasis pulmonares de origen extrapulmonar. Objetivo: Determinar si las segundas resecciones anatómicas pulmonares se asocian con un mayor riesgo de complicaciones posoperatorias comparadas con la primera intervención. Materiales y Método: Hemos analizado todos los pacientes sometidos a una segunda resección anatómica en nuestro centro entre octubre de 2000 y febrero de 2019. Las complicaciones fueron clasificadas en mayores y menores según la clasificación estandarizada de morbilidad posoperatoria de Clavien-Dindo. Se compararon las características clínicas y demográficas de los pacientes y la ocurrencia de complicaciones mayores tras la primera y la segunda intervención quirúrgica mediante la prueba T para muestras relacionadas y la prueba exacta de McNemar para las variables cuantitativas y categóricas, respectivamente. Resultados: Setenta y cinco pacientes fueron sometidos a una segunda resección anatómica. La prevalencia de complicaciones globales y mayores tras la primera intervención fue del 26,7% y el 4% frente al 34,7% y al 6,7% tras la segunda intervención (p = 0,362 y p = 0,727, respectivamente). Las segundas resecciones pulmonares ipsilaterales se asociaron con un 16,7% de complicaciones mayores y los procedimientos consistentes en completar la neumonectomía con un 25%. Conclusión: Las segundas resecciones anatómicas pulmonares no se asocian con un mayor riesgo de complicaciones posoperatorias comparadas con la primera intervención. Sin embargo, las segundas resecciones ipsilaterales y las resecciones que impliquen completar la neumonectomía se asocian con riesgo significativamente superior de complicaciones mayores posoperatorias.
Introduction: Second anatomical resections are becoming more frequent in the treatment of synchronous, metachronous and pulmonary metastases of extrapulmonary origin. Aim: The objective of this study is to determine whether second pulmonary anatomical resections are associated with an increased risk of postoperative complications compared to the first intervention. Materials and Method: We have analyzed all patients undergoing a second anatomical resection in our center between October 2000 and February 2019. Complications were classified in major and minor according to the standardized Clavien-Dindo postoperative morbidity classification. The clinical and demographic characteristics of the patients and the occurrence of major complications after the first and second surgical intervention were compared using the T test for related samples and the McNemar exact test for quantitative and categorical variables, respectively. Results: Seventy-five patients underwent a second anatomic resection. The prevalence of global and major complications after the first intervention was 26.7% and 4% compared to 34.7% and 6.7% after the second intervention (p = 0.362 and p = 0.727, respectively). Second ipsilateral lung resections were associated with 16.7% of major complications and procedures consisting of completing pneumonectomy with 25%. Conclusion: Second lung anatomical resections are not associated with an increased risk of postoperative complications compared to the first intervention. However, second ipsilateral resections and resections that involve completing pneumonectomy are associated with a significantly higher risk of major postoperative complications.
Subject(s)
Humans , Male , Female , Neoplasms, Second Primary/surgery , Neoplasms, Second Primary/complications , Lung Neoplasms/surgery , Retrospective Studies , Risk Factors , Treatment Outcome , Risk Assessment , Lung Neoplasms/pathologyABSTRACT
INTRODUCTION AND AIMS: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Many risk factors are involved, and current evidence links the gut microbiota and colorectal carcinogenesis. Fusobacterium nucleatum is proposed as one of the risk factors at the onset and during the progression of CRC, due to immune system and inflammatory modulation. MATERIALS AND METHODS: Ninety samples from three different regions of the colon were collected through colonoscopy in patients with CRC, and qPCR TagMan® was conducted to detect F. nucleatum and cytokines (IL-17, IL-23, and IL-10) in tumor, peritumor, and normal samples. The differences between them were analyzed and correlated. RESULTS: The abundance of F. nucleatum determined through the 2-ΔΔCt method in CRC (7.750 [5.790-10.469]) was significantly higher than in the normal control (0.409 [0.251-0.817]) (p<0.05). There was no significant association between F. nucleatum and the cytokines (p>0.05). CONCLUSIONS: CRC is a heterogeneous disease that presents and progresses in a complex microenvironment, partially due to gut microbiome imbalance. F. nucleatum was enriched in CRC tissue, but whether that is a cause of the pathology or a consequence, has not yet been clearly defined.
ABSTRACT
Optic nerve drusen are acellular concretions of calcium located in the parenchyma of the optical nerve head described as the most common cause of pseudo-papilloedema, which makes it difficult to differentiate from a true optical disc oedema. Despite it being rare, the drusen of the optic nerve and the papilloedema secondary to idiopathic intracranial hypertension can coexist in the same patient. The case is presented of a 34 year-old woman referred to the Ophthalmology Department with visual discomfort, headaches, and pulsatile tinnitus of two months onset. In the physical examination there was bilateral blurring of the optic disc margin with absence of spontaneous venous pulsation. The diagnosis of idiopathic intracranial hypertension was made by lumbar puncture with the measurement of the opening pressure, and due to the findings of the magnetic resonance scan of the brain and the eye sockets. The optic nerve drusen was an incidental finding in an optical coherence tomography angiography, which would later be confirmed with an eye ultrasound. To our knowledge, this the first case reported in Latin America of the coexistence of optic nerve drusen and papilloedema secondary to idiopathic intracranial hypertension.
Subject(s)
Optic Disk Drusen , Optic Disk , Papilledema , Pseudotumor Cerebri , Adult , Female , Humans , Latin America , Optic Disk Drusen/complications , Papilledema/diagnosis , Pseudotumor Cerebri/complicationsABSTRACT
Las drusas del nervio óptico son concreciones acelulares de calcio localizadas en el parénquima de la cabeza del nervio óptico, descritas como la causa más frecuente de pseudopapiledema, lo cual las hace difícil de diferenciar de un verdadero edema del disco óptico. A pesar de su poca frecuencia, las drusas del nervio óptico y el papiledema secundario a una hipertensión intracraneal idiopática pueden coexistir en el mismo paciente. Reportamos el caso de una mujer de 34 años de vida remitida al servicio de oftalmología con molestias visuales, cefalea, y tinnitus pulsátil de dos meses de evolución; al examen físico se encontró borramiento del margen del disco óptico de manera bilateral sin pulsación venosa espontánea. El diagnóstico de hipertensión intracraneal idiopática se realizó por una punción lumbar con medición de la presión de apertura, y por los hallazgos de resonancia magnética cerebral y de órbitas. Se observó incidentalmente las drusas del nervio óptico en una tomografía de coherencia óptica con angiografía, que luego se confirmarían con una ecografía ocular. Este es el primer caso reportado en América Latina de la coexistencia de drusas del nervio óptico y papiledema secundario a hipertensión intracraneal idiopática para nuestro conocimiento (AU)
Optic nerve drusen are acellular concretions of calcium located in the parenchyma of the optic nerve head described as the most common cause of pseudo-papilloedema, which makes it difficult to differentiate from a true optical disc oedema. Despite it being rare optic nerve drusen and the papilloedema secondary to idiopathic intracranial hypertension can coexist in the same patient. We present a case of a 34-year-old woman referred to the Ophthalmology Department with visual discomfort, headaches, and pulsatile tinnitus of two months onset. In the physical examination there was bilateral blurring of the optic disc margin with absence of spontaneous venous pulsation. The diagnosis of idiopathic intracranial hypertension was made by lumbar puncture with the measurement of the opening pressure, and due to the findings of the magnetic resonance scan of the brain and orbits. The optic nerve drusen was an incidental finding in an optical coherence tomography angiography, which would later be confirmed with an eye ultrasound. To our knowledge, this the first case reported in Latin America of the coexistence of optic nerve drusen and papilloedema secondary to idiopathic intracranial hypertension (AU)
Subject(s)
Humans , Female , Young Adult , Intracranial Hypertension/complications , Optic Disk Drusen/complications , Papilledema/complications , Magnetic Resonance Imaging , Intracranial Hypertension/diagnostic imaging , Optic Disk Drusen/diagnostic imaging , Papilledema/diagnostic imagingABSTRACT
Meiotic reductional division depends on the synaptonemal complex (SC), a supramolecular protein assembly that mediates homologous chromosomes synapsis and promotes crossover formation. The mammalian SC has eight structural components, including SYCE1, the only central element protein with known causative mutations in human infertility. We combine mouse genetics, cellular, and biochemical studies to reveal that SYCE1 undergoes multivalent interactions with SC component SIX6OS1. The N terminus of SIX6OS1 binds and disrupts SYCE1's core dimeric structure to form a 1:1 complex, while their downstream sequences provide a distinct second interface. These interfaces are separately disrupted by SYCE1 mutations associated with nonobstructive azoospermia and premature ovarian failure (POF), respectively. Mice harboring SYCE1's POF mutation and a targeted deletion within SIX6OS1's N terminus are infertile with failure of chromosome synapsis. We conclude that both SYCE1-SIX6OS1 binding interfaces are essential for SC assembly, thus explaining how SYCE1's reported clinical mutations give rise to human infertility.
Subject(s)
Azoospermia , DNA-Binding Proteins , Animals , Azoospermia/genetics , Chromosome Pairing , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Mammals/genetics , Mice , Mutation , Synaptonemal Complex/genetics , Synaptonemal Complex/metabolismABSTRACT
Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model. Hsf2bpS167L/S167L females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the BRME1/HSF2BP protein complex co-immunoprecipitates with BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L variant showed a strongly decreased staining of both HSF2BP and BRME1 at the recombination nodules and a reduced number of the foci formed by the recombinases RAD51/DMC1, thus leading to a lower frequency of crossovers. Our results provide insights into the molecular mechanism of HSF2BP-S167L in human ovarian insufficiency and sub(in)fertility.
Subject(s)
Carrier Proteins , Heat-Shock Proteins , Meiosis/genetics , Mutation, Missense/genetics , Primary Ovarian Insufficiency/genetics , Recombination, Genetic/genetics , Animals , Carrier Proteins/genetics , Carrier Proteins/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Mice , Mice, Knockout , Rad51 Recombinase/genetics , Rad51 Recombinase/metabolism , Exome SequencingABSTRACT
We report the case of a 22 year-old male with a clinical picture of 4 months onset of headaches, deafness, and a decrease of vision in the left eye. His mother mentioned he also had changes in behaviour and mood. The magnetic resonance scan of the brain showed multiple hyper-intense lesions in the knee of the corpus callosum. The hearing test reported a neurosensory deafness. In the ophthalmoscopy, a retinal infarction was observed in the nerve fibre layer in the left eye, which was confirmed using optical coherence tomography. The fluorescein angiography showed multiple foci of hyperfluorescence of the arteriole walls, arteriole filling defects, and regional ischaemia foci of the choroid. These findings confirmed the presumed diagnosis of a Susac syndrome. This is one of the few cases reported in the literature of a Susac syndrome in a young man with the complete diagnostic triad, and the first in Colombia.
Subject(s)
Susac Syndrome/diagnosis , Colombia , Humans , Male , Young AdultABSTRACT
Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin1-3. Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin1. In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions4,5. Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma6,7, is turned into a separase inhibitor upon association with SAC-activated MAD2. SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin8,9, SGO2 is a competitive inhibitor that uses a pseudo-substrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31comet liberate separase from SGO2-MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC.
Subject(s)
Cell Cycle Checkpoints/physiology , Cell Cycle Proteins/metabolism , Mad2 Proteins/metabolism , Securin , Separase/antagonists & inhibitors , ATPases Associated with Diverse Cellular Activities/metabolism , Anaphase-Promoting Complex-Cyclosome/metabolism , Cdc20 Proteins/metabolism , Cell Line , Chromatids/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Humans , Protein Binding , Securin/metabolism , Separase/metabolism , CohesinsABSTRACT
Genotypes of bananas and plantains have been studied for biofortification purposes, mainly due to content of resistant starch (RS) and polyphenols. This study aims to identify banana and plantain genotypes with a high content of resistant starch, phenolic compounds and minerals, and to evaluate the impact of the ripening stage and domestic thermal processing to select superior genotypes with high levels of functional compounds. In this study, it was used bunches of bananas and plantain genotypes. The phenolic compounds profiles were determined by HPLC-DAD in pulps and peels. The resistant starch and the minerals (K, Na, Zn, Cu and Fe) were evaluated in pulps and peels of unripe fruit. The results of phenolic compounds were studied in three ripening stages, and after thermal processing (ripe stage) of two genotypes, which were most promising for biofortification studies. Resistant starch and minerals were analysed in the unripe fruits. The peel biomass showed the highest values of phenolic compounds and minerals. The total starch content in the pulp varied from 42.3% ('FC06-02') to 80.6% ('Pelipita'). Plantains and cooking bananas presented the highest contents of starch and resistant starch (stage 2 - green with yellow traces). The pulps of the dessert genotypes 'Khai' and 'Ouro da Mata', and cooking genotype 'Pacha Nadam' stood out due to their minerals high contents (P, K and Fe; Zn and Fe; Ca, Mg and Zn, respectively). The dessert bananas (e.g., 'Ney Poovan') and cooking bananas (e.g., 'Tiparot') had the highest concentrations of phenolic compounds, mainly in ripe fruit (stage 5 - yellow with green). In addition, the thermal processing of Musa spp. fruit led to increasing these secondary metabolites, mainly the cooking of fruit with peel by boiling, which should be preferred in domestic preparations.