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1.
Nature ; 633(8029): 389-397, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39261618

RESUMEN

Rapa Nui (also known as Easter Island) is one of the most isolated inhabited places in the world. It has captured the imagination of many owing to its archaeological record, which includes iconic megalithic statues called moai1. Two prominent contentions have arisen from the extensive study of Rapa Nui. First, the history of the Rapanui has been presented as a warning tale of resource overexploitation that would have culminated in a major population collapse-the 'ecocide' theory2-4. Second, the possibility of trans-Pacific voyages to the Americas pre-dating European contact is still debated5-7. Here, to address these questions, we reconstructed the genomic history of the Rapanui on the basis of 15 ancient Rapanui individuals that we radiocarbon dated (1670-1950 CE) and whole-genome sequenced (0.4-25.6×). We find that these individuals are Polynesian in origin and most closely related to present-day Rapanui, a finding that will contribute to repatriation efforts. Through effective population size reconstructions and extensive population genetics simulations, we reject a scenario involving a severe population bottleneck during the 1600s, as proposed by the ecocide theory. Furthermore, the ancient and present-day Rapanui carry similar proportions of Native American admixture (about 10%). Using a Bayesian approach integrating genetic and radiocarbon dates, we estimate that this admixture event occurred about 1250-1430 CE.


Asunto(s)
Indio Americano o Nativo de Alaska , ADN Antiguo , Pueblo Europeo , Genética de Población , Genoma Humano , Migración Humana , Nativos de Hawái y Otras Islas del Pacífico , Femenino , Humanos , Masculino , Indio Americano o Nativo de Alaska/genética , Indio Americano o Nativo de Alaska/historia , Américas/etnología , Teorema de Bayes , ADN Antiguo/análisis , Europa (Continente)/etnología , Pueblo Europeo/genética , Pueblo Europeo/historia , Genoma Humano/genética , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia Antigua , Historia Medieval , Migración Humana/historia , Nativos de Hawái y Otras Islas del Pacífico/genética , Nativos de Hawái y Otras Islas del Pacífico/historia , Filogenia , Polinesia/etnología , Densidad de Población , Datación Radiométrica , Secuenciación Completa del Genoma
2.
Neuropharmacology ; 260: 110116, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39151654

RESUMEN

Congenital Myasthenic Syndromes (CMS) are a set of genetic diseases that affect the neuromuscular transmission causing muscular weakness. The standard pharmacological treatment aims at ameliorating the myasthenic symptom by acetylcholinesterase inhibitors. Most patients respond well in the short and medium term, however, over time the beneficial effects rapidly fade, and the efficacy of the treatment diminishes. Increasing evidence shows that ß2-adrenergic agonists can be a suitable choice for the treatment of neuromuscular disorders, including CMS, as they promote beneficial effects in the neuromuscular system. The exact mechanism on which they rely is not completely understood, although patients and animal models respond well to the treatment, especially over extended periods. Here, we report the use of the long-lasting specific ß2-adrenergic agonist formoterol in a myasthenic mouse model (mnVAChT-KD), featuring deletion of VAChT (Vesicular Acetylcholine Transporter) specifically in the α-motoneurons. Our findings demonstrate that formoterol treatment (300 µg/kg/day; sc) for 30 days increased the neuromuscular junction area, induced skeletal muscle hypertrophy and altered fibre type composition in myasthenic mice. Interestingly, ß2-adrenergic agonists have shown efficacy even in the absence of ACh (acetylcholine). Our data provide important evidence supporting the potential of ß2-adrenergic agonists in treating neuromuscular disorders of pre-synaptic origin and characterized by disruptions in nerve-muscle communication, through a direct and beneficial action within the motor unit.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2 , Modelos Animales de Enfermedad , Fumarato de Formoterol , Síndromes Miasténicos Congénitos , Unión Neuromuscular , Proteínas de Transporte Vesicular de Acetilcolina , Animales , Síndromes Miasténicos Congénitos/tratamiento farmacológico , Síndromes Miasténicos Congénitos/genética , Fumarato de Formoterol/farmacología , Fumarato de Formoterol/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Unión Neuromuscular/efectos de los fármacos , Ratones , Proteínas de Transporte Vesicular de Acetilcolina/metabolismo , Proteínas de Transporte Vesicular de Acetilcolina/genética , Ratones Endogámicos C57BL , Masculino
3.
Int J Mol Sci ; 25(10)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38791562

RESUMEN

We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid (GABA)ergic system, including the Ca2+-binding proteins parvalbumin (PV), calretinin (CR), calbindin (CB), and the neuropeptides somatostatin (SST) and neuropeptide Y (NPY). We also analyzed the density of cholinergic varicosities, brain-derived neurotrophic factor (BDNF), reelin (RELN), and cyclin-dependent kinase-5 (CDK-5) mRNA levels, and glial fibrillary acidic protein (GFAP) expression. The cafeteria diet reduced PV-positive neurons in the granular layer, hilus, and CA1, as well as NPY-positive neurons in the hilus, without altering other GABAergic populations or overall GABA levels. The high-sugar diet induced a decrease in the number of PV-positive cells in CA3 and an increase in CB-positive cells in the hilus and CA1. No alterations were observed in the cholinergic varicosities. The cafeteria diet also reduced the relative mRNA expression of RELN without significant changes in BDNF and CDK5 levels. The cafeteria diet increased the number but reduced the length of the astrocyte processes. These data highlight the significance of determining the mechanisms mediating the observed effects of these diets and imply that the cognitive impairments previously found might be related to both the neuroinflammation process and the reduction in PV, NPY, and RELN expression in the hippocampal formation.


Asunto(s)
Astrocitos , Quinasa 5 Dependiente de la Ciclina , Hipocampo , Neurogénesis , Proteína Reelina , Animales , Astrocitos/metabolismo , Ratas , Proteína Reelina/metabolismo , Masculino , Hipocampo/metabolismo , Quinasa 5 Dependiente de la Ciclina/metabolismo , Quinasa 5 Dependiente de la Ciclina/genética , Neuronas GABAérgicas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Neuropéptido Y/metabolismo , Neuropéptido Y/genética , Ratas Wistar , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/genética , Parvalbúminas/metabolismo
4.
Cureus ; 16(2): e53892, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38465167

RESUMEN

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity that can significantly impact a child's daily life and academic performance. Some studies have noted challenges in social cognition among children with ADHD, specifically in aspects like emotion perception and processing, empathy, Theory of Mind, and pragmatics. One of the lesser-explored aspects of ADHD is its potential impact on higher-level language skills, such as irony understanding. Our goal in this study was to compare irony comprehension in two groups: schoolchildren with normal development and schoolchildren with ADHD. METHODS: We performed a comparative cross-sectional study on a total of 35 children aged between 6 and 12 years: 17 with ADHD and 18 not neurodevelopmentally impaired. Irony comprehension was evaluated using an assessment method validated for the Portuguese population: Turtle on the Island - Battery of Assessment of Executive Functions in Children (TI-BAFEC). We also applied the EACE (Emotional Awareness and Coping in Children) scale. It is the Portuguese adaptation of the Assessment of Children's Emotion Skills and assesses children's emotional knowledge. RESULTS: We obtained two comparable groups concerning sociodemographic data. The analysis of the data, using the Mann-Whitney U Test, showed that in all parameters, the control group consistently exhibited superior performance compared to the ADHD group. However, only TI-BAFEC (p = 0.005) and emotional behavior (p = 0.007) showed a significant statistical variance between the two groups. CONCLUSION: This article shows that children with ADHD encounter challenges in grasping irony. However, the underlying cognitive processes contributing to these difficulties warrant further investigation.

5.
Sci Rep ; 14(1): 6227, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486065

RESUMEN

Low-coverage imputation is becoming ever more present in ancient DNA (aDNA) studies. Imputation pipelines commonly used for present-day genomes have been shown to yield accurate results when applied to ancient genomes. However, post-mortem damage (PMD), in the form of C-to-T substitutions at the reads termini, and contamination with DNA from closely related species can potentially affect imputation performance in aDNA. In this study, we evaluated imputation performance (i) when using a genotype caller designed for aDNA, ATLAS, compared to bcftools, and (ii) when contamination is present. We evaluated imputation performance with principal component analyses and by calculating imputation error rates. With a particular focus on differently imputed sites, we found that using ATLAS prior to imputation substantially improved imputed genotypes for a very damaged ancient genome (42% PMD). Trimming the ends of the sequencing reads led to similar improvements in imputation accuracy. For the remaining genomes, ATLAS brought limited gains. Finally, to examine the effect of contamination on imputation, we added various amounts of reads from two present-day genomes to a previously downsampled high-coverage ancient genome. We observed that imputation accuracy drastically decreased for contamination rates above 5%. In conclusion, we recommend (i) accounting for PMD by either trimming sequencing reads or using a genotype caller such as ATLAS before imputing highly damaged genomes and (ii) only imputing genomes containing up to 5% of contamination.


Asunto(s)
ADN Antiguo , Genoma , Genotipo , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple
6.
Biology (Basel) ; 13(3)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38534426

RESUMEN

The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.

8.
Nature ; 625(7994): 329-337, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38200294

RESUMEN

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.


Asunto(s)
Genoma Humano , Genómica , Migración Humana , Pueblos Nórdicos y Escandinávicos , Humanos , Dinamarca/etnología , Emigrantes e Inmigrantes/historia , Genotipo , Pueblos Nórdicos y Escandinávicos/genética , Pueblos Nórdicos y Escandinávicos/historia , Migración Humana/historia , Genoma Humano/genética , Historia Antigua , Polen , Dieta/historia , Caza/historia , Agricultores/historia , Cultura , Fenotipo , Conjuntos de Datos como Asunto
9.
Nature ; 625(7994): 301-311, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38200295

RESUMEN

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.


Asunto(s)
Genética de Población , Genoma Humano , Migración Humana , Metagenómica , Humanos , Agricultura/historia , Asia Occidental , Mar Negro , Diploidia , Europa (Continente)/etnología , Genotipo , Historia Antigua , Migración Humana/historia , Caza/historia , Cubierta de Hielo
10.
Rev. odontopediatr. latinoam ; 14: 234634, 2024. ilus
Artículo en Español | LILACS, COLNAL | ID: biblio-1552008

RESUMEN

La luxación intrusiva es el tipo más común de lesión traumática en la dentición primaria, caracterizada por el desplazamiento del diente hacia el interior del alvéolo. Requieren minucioso examen clínico, buena radiografía y seguimiento del caso, siendo el prognóstico desfavorable, principalmente por la probabilidad de daño al germen del diente permanente. Este trabajo tiene como objetivo reportar un caso clínico de luxación intrusiva en dentición primaria, desde el diagnóstico hasta el seguimiento. Se trata de un paciente masculino, de 3 años, que acudió a la Emergencia de la Clínica de Especialidades Infantiles ­ Universidad Estatal de Londrina (UEL) por traumatismo dentoalveolar en la región antero-superior ocurrido hace tres días. En el examen físico, se observó que el diente 61 presentaba intrusión de grado II con un tercio de la corona visible y el diente 62 intrusión de grado I, con más de un tercio de la corona visible. Radiográficamente se observa inclinación vestibular, sin fractura de la placa ósea, por lo que se optó por un tratamiento conservador, a la espera de la reerupción espontánea de los dientes afectados. Se informó a los padres sobre posibles consecuencias de este tipo de traumatismo y la necesidad de consultas de seguimiento clínico y radiológico. Después de ocho meses de seguimiento, los dientes erupcionaron satisfactoriamente. Es de suma importancia establecer un protocolo de observación y control del diente en el cual se ha identificado el trauma, observando signos y síntomas de los tejidos involucrados en el trauma para reducir secuelas en ambas denticiones


A luxação intrusiva é o tipo de lesão traumática mais frequente na dentição decídua, caracterizada pelo deslocamento do dente para o alvéolo. As intrusões requerem exame físico minucioso, radiografias de valor diagnóstico e acompanhamento do caso, pois o prognóstico é desfavorável, principalmente pela probabilidade de danos ao germe dentário permanente. Este trabalho tem como objetivo relatar um caso clínico de luxação intrusiva na dentição decídua, desde o diagnóstico até o acompanhamento. Trata-se de paciente do sexo masculino, 3 anos de idade, atendido no Pronto Socorro do Ambulatório de Especialidades Infantis da Universidade Estadual de Londrina (UEL) devido a trauma dento-alveolar em região ântero-superior ocorrido há três dias. Ao exame físico intraoral, observou-se que o dente 61 apresentava intrusão grau II (um terço da coroa visível) e o dente 62 apresentava intrusão grau I, com mais de um terço da coroa visível. Radiograficamente foi observada inclinação vestibular, sem fratura da tábua óssea. Assim, optou-se pelo tratamento conservador, aguardando a reerupção espontânea dos dentes envolvidos. Além disso, os pais foram informados sobre as possíveis consequências deste tipo de trauma e a necessidade de consultas de proservação clínica e radiográfica. Após oito meses de acompanhamento, os dentes erupcionaram satisfatoriamente. É de extrema importância estabelecer um protocolo de observação e controle do dente traumatizado, observando sinais e sintomas dos tecidos envolvidos no trauma para reduzir sequelas em ambas as dentições.


Intrusive dislocation is the most frequent type of traumatic injury in the primary dentition, characterized by displacement of the tooth into the alveolus. Intrusions require a thorough physical examination, radiographs of diagnostic value, and follow-up of the case, since the prognosis is unfavorable, mainly due to the probability of damage to the permanent tooth germ. This work aims to report a clinical case of intrusive dislocation in the primary dentition, from diagnosis to follow-up. This is a male patient, 3 years old, who attended in the Emergency of the Children's Specialty Clinic ­ State University of Londrina (UEL) due to dento-alveolar trauma in the antero-superior region that occurred three days ago. On clinical examination, tooth 61 had grade II intrusion (one-third of the crown visible), and tooth 62 with grade I intrusion, with more than one-third of the crown visible. Radiographically, a buccal inclination was observed, with no fracture of the bone plate. Thus, we opted for conservative treatment, waiting for the spontaneous re-eruption of the teeth involved. Furthermore, parents were informed about the possible consequences of this type of trauma and the need for clinical and radiographic follow-up consultations. After eight months of follow-up, the teeth erupted satisfactorily. It is extremely important to establish a protocol for observation and control of the traumatized tooth, observing signs and symptoms of the tissues involved in the trauma to reduce sequelae in both dentitions


Asunto(s)
Humanos , Masculino , Preescolar
11.
Inflamm Res ; 72(10-11): 2073-2088, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37837557

RESUMEN

OBJECTIVE AND DESIGN: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. MATERIAL: Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). METHODS: Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis. RESULTS: Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3. CONCLUSIONS: In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.


Asunto(s)
COVID-19 , Virus de la Hepatitis Murina , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Virus de la Hepatitis Murina/metabolismo , Citocinas/metabolismo , COVID-19/patología , Encéfalo/metabolismo
12.
Neurochem Int ; 169: 105567, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37348761

RESUMEN

COVID-19 affects primarily the lung. However, several other systemic alterations, including muscle weakness, fatigue and myalgia have been reported and may contribute to the disease outcome. We hypothesize that changes in the neuromuscular system may contribute to the latter symptoms observed in COVID-19 patients. Here, we showed that C57BL/6J mice inoculated intranasally with the murine betacoronavirus hepatitis coronavirus 3 (MHV-3), a model for studying COVID-19 in BSL-2 conditions that emulates severe COVID-19, developed robust motor alterations in muscle strength and locomotor activity. The latter changes were accompanied by degeneration and loss of motoneurons that were associated with the presence of virus-like particles inside the motoneuron. At the neuromuscular junction level, there were signs of atrophy and fragmentation in synaptic elements of MHV-3-infected mice. Furthermore, there was muscle atrophy and fiber type switch with alteration in myokines levels in muscles of MHV-3-infected mice. Collectively, our results show that acute infection with a betacoronavirus leads to robust motor impairment accompanied by neuromuscular system alteration.


Asunto(s)
COVID-19 , Virus de la Hepatitis Murina , Ratones , Animales , Ratones Endogámicos C57BL , Neuronas Motoras , Unión Neuromuscular , Virus de la Hepatitis Murina/fisiología
13.
Nat Genet ; 55(7): 1088-1090, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37386250

RESUMEN

The release of 150,119 UK Biobank sequences represents an unprecedented opportunity as a reference panel to impute low-coverage whole-genome sequencing data with high accuracy but current methods cannot cope with the size of the data. Here we introduce GLIMPSE2, a low-coverage whole-genome sequencing imputation method that scales sublinearly in both the number of samples and markers, achieving efficient whole-genome imputation from the UK Biobank reference panel while retaining high accuracy for ancient and modern genomes, particularly at rare variants and for very low-coverage samples.


Asunto(s)
Bancos de Muestras Biológicas , Polimorfismo de Nucleótido Simple , Frecuencia de los Genes , Polimorfismo de Nucleótido Simple/genética , Genoma , Reino Unido , Genotipo
14.
Nat Commun ; 14(1): 3660, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37339987

RESUMEN

Due to postmortem DNA degradation and microbial colonization, most ancient genomes have low depth of coverage, hindering genotype calling. Genotype imputation can improve genotyping accuracy for low-coverage genomes. However, it is unknown how accurate ancient DNA imputation is and whether imputation introduces bias to downstream analyses. Here we re-sequence an ancient trio (mother, father, son) and downsample and impute a total of 43 ancient genomes, including 42 high-coverage (above 10x) genomes. We assess imputation accuracy across ancestries, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. When downsampled at 1x, 36 of the 42 genomes are imputed with low error rates (below 5%) while African genomes have higher error rates. We validate imputation and phasing results using the ancient trio data and an orthogonal approach based on Mendel's rules of inheritance. We further compare the downstream analysis results between imputed and high-coverage genomes, notably principal component analysis, genetic clustering, and runs of homozygosity, observing similar results starting from 0.5x coverage, except for the African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method that can improve ancient DNA studies.


Asunto(s)
Genoma Humano , Técnicas de Genotipaje , Humanos , Técnicas de Genotipaje/métodos , Genoma Humano/genética , ADN Antiguo , Genotipo , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple
15.
Rev Col Bras Cir ; 50: e20233404, 2023.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-37222382

RESUMEN

INTRODUCTION: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. PURPOSE: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. METHODS: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. RESULTS: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. CONCLUSIONS: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.


Asunto(s)
Adenocarcinoma , Laparoscopía , Cirujanos , Humanos , Estudios Retrospectivos , Reoperación
16.
Nutrients ; 15(6)2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36986100

RESUMEN

High-caloric diets induce several deleterious alterations in the human body, including the brain. However, information on the effects of these diets on the elderly brain is scarce. Therefore, we studied the effects of 2 months of treatment with high-fat (HF) and high-fat-high-sugar (HFHS) diets on aged male Wistar rats at 18 months. Anxiety levels were analyzed using the open-field and plus-maze tests, while learning and memory processes were analyzed using the Morris water maze test. We also analyzed neurogenesis using doublecortin (DCX) and neuroinflammation using glial fibrillary acidic protein (GFAP). In aged rats, the HFHS diet impaired spatial learning, memory, and working memory and increased anxiety levels, associated with a reduction in the number of DCX cells and an increase in GFAP cells in the hippocampus. In contrast, the effects of the HF diet were lighter, impairing spatial memory and working memory, and associated with a reduction in DCX cells in the hippocampus. Thus, our results suggest that aged rats are highly susceptible to high-caloric diets, even if they only started in the elderly, with an impact on cognition and emotions. Furthermore, diets rich in saturated fats and sugar are more detrimental to aged rats than high-fat diets are.


Asunto(s)
Dieta Alta en Grasa , Azúcares , Humanos , Ratas , Masculino , Animales , Anciano , Dieta Alta en Grasa/efectos adversos , Ratas Wistar , Azúcares/metabolismo , Enfermedades Neuroinflamatorias , Hipocampo/metabolismo , Ansiedad/etiología , Memoria Espacial , Neurogénesis
17.
18.
Bioinformatics ; 39(2)2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36637197

RESUMEN

SUMMARY: We introduce mapache, a flexible, robust and scalable pipeline to map, quantify and impute ancient and present-day DNA in a reproducible way. Mapache is implemented in the workflow manager Snakemake and is optimized for low-space consumption, allowing to efficiently (re)map large datasets-such as reference panels and multiple extracts and libraries per sample - to one or several genomes. Mapache can easily be customized or combined with other Snakemake tools. AVAILABILITY AND IMPLEMENTATION: Mapache is freely available on GitHub (https://github.com/sneuensc/mapache). An extensive manual is provided at https://github.com/sneuensc/mapache/wiki. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
ADN Antiguo , Programas Informáticos , Genoma , Flujo de Trabajo
20.
Rev. Col. Bras. Cir ; 50: e20233404, 2023. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1440935

RESUMEN

ABSTRACT Introduction: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. Purpose: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. Methods: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. Results: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. Conclusions: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.


RESUMO Introdução: com o aperfeiçoamento e a ampla aceitação da laparoscopia nas operações colorretais, houve necessidade de treinamento específico dos cirurgiões em formação. Existem poucos estudos avaliando os resultados pós operatórios das colectomias videolaparoscópicas realizadas por médicos residentes e seu impacto na segurança do paciente. Objetivo: analisar os resultados cirúrgicos e oncológicos das colectomias videolaparoscópicas realizadas por residentes de coloproctologia e comparar com dados da literatura. Métodos: trata-se de uma análise retrospectiva de pacientes submetidos a cirurgias colorretais laparoscópicas, realizadas por médicos residentes do Hospital das Clínicas de Ribeirão Preto, entre 2014 e 2018. Foram estudadas as características clínicas dos pacientes bem como os principais aspectos cirúrgicos e oncológicos em um período de um ano. Resultados: analisou-se 191 operações, cuja principal indicação cirúrgica foi adenocarcinoma, a maioria estadio III. A duração média das cirurgias foi 210±58 minutos. Houve necessidade de estoma em 21,5% dos pacientes, principalmente colostomia em alça. A taxa de conversão foi 23%, sendo 79,5% por dificuldades técnicas, e os principais fatores preditores de conversão foram obesidade e acidentes intra-operatórios. A mediana do tempo de internação foi 6 dias. Anemia pré operatória associou-se a uma maior taxa de complicações (11,5%) e reoperações (12%). Houve comprometimento das margens de ressecção cirúrgica em 8,6% dos casos. A taxa de recidiva em um ano foi de 3,2%, e a taxa de mortalidade, 6,3%. Conclusões: a cirurgia colorretal videolaparoscópica realizada por residentes apresentou eficácia e segurança semelhante aos dados encontrados na literatura.

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