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1.
PLOS Glob Public Health ; 4(6): e0003332, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913605

RESUMO

Homelessness poses complex health obstacles for individuals and communities. Peer and lay health worker programs aim to increase access to health care and improve health outcomes for PEH by building trust and empowering community-based workers. The scope and breadth of peer and lay health worker programs among PEH has not been synthesized. The primary objective of this scoping review is to understand the context (setting, community, condition or disease) encompassing peer and lay health worker programs within the homelessness sector. The secondary objective is to examine the factors that either facilitate or hinder the effectiveness of peer and lay health worker programs when applied to people experiencing homelessness (PEH). We searched CINHAL, Cochrane, Web of Science Core Collection, PsycINFO, Google Scholar and MEDLINE. We conducted independent and duplicate screening of titles and abstracts, and extracted information from eligible studies including study and intervention characteristics, peer personnel characteristics, outcome measures, and the inhibitors and enablers of effective programs. We discuss how peer and lay health work programs have successfully been implemented in various contexts including substance use, chronic disease management, harm reduction, and mental health among people experiencing homelessness. These programs reported four themes of enablers (shared experiences, trust and rapport, strong knowledge base, and flexibility of role) and five themes of barriers and inhibitors (lack of support and clear scope of role, poor attendance, precarious work and high turnover, safety, and mental well-being and relational boundaries). Organizations seeking to implement these interventions should anticipate and plan around the enablers and barriers to promote program success. Further investigation is needed to understand how peer and lay health work programs are implemented, the mechanisms and processes that drive effective peer and lay health work among PEH, and to establish best practices for these programs.

2.
Am J Biol Anthropol ; 184(2): e24921, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38426243

RESUMO

OBJECTIVES: To investigate the association between the anthropometric status at birth and brain and bone growth during the first year of life. According to the brain-sparing hypothesis, we expect catch-up to be faster in head circumference (HC) than in body length. METHODS: This is a longitudinal design that included Argentinian infants under 12 months of age with at least three anthropometric records. We classified study participants into four growth status categories according to z-scores for HC (HCZ) and length (LAZ) at birth, with z-score = -2 as a threshold. We used the Count model to describe growth trajectories in HC and length in the first year of life according to the growth status at birth. Recovery indicator for HC and length was taken as the time until the predicted growth trajectory surpassed the threshold curve predicted by z-score = -2 for age. RESULTS: Growth models included 3399 infants. There were significant differences in the growth parameters between groups in all cases (p < 0.05). Within the group with a low HCZ and a low LAZ at birth, HC recovery was faster than length. In the case of a low z-score for only one of the variables, newborns with a low HCZ recovered faster than individuals born with a low LAZ. CONCLUSIONS: The postnatal growth pattern in HC and length is associated with the growth status of HC and length at birth. As we hypothesized, the fastest postnatal recovery occurs for HC in cases of intrauterine delayed growth.


Assuntos
Cefalometria , Cabeça , Humanos , Argentina , Recém-Nascido , Feminino , Cabeça/crescimento & desenvolvimento , Cabeça/anatomia & histologia , Masculino , Lactente , Estudos Longitudinais , Desenvolvimento Infantil/fisiologia , Estatura/fisiologia , Antropologia Física
3.
Eur Arch Psychiatry Clin Neurosci ; 274(4): 837-847, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38243018

RESUMO

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.


Assuntos
Eletroencefalografia , Esquizofrenia , Estimulação Magnética Transcraniana , Humanos , Esquizofrenia/fisiopatologia , Masculino , Feminino , Adulto , Projetos Piloto , Adulto Jovem , Inibição Psicológica , Pessoa de Meia-Idade , Córtex Pré-Frontal Dorsolateral/fisiopatologia , Córtex Pré-Frontal Dorsolateral/fisiologia , Inibição Neural/fisiologia , Córtex Cerebral/fisiopatologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-38036032

RESUMO

BACKGROUND: The study of the cortical functional network properties in schizophrenia (SZ) may benefit from the use of graph theory parameters applied to high-density electroencephalography (EEG). Connectivity Strength (CS) assesses global synchrony of the network, and Shannon Graph Complexity (SGC) summarizes the network distribution of link weights and allows distinguishing between primary and secondary pathways. Their joint use may help in understanding the underpinnings of the functional network hyperactivation and task-related hypomodulation previously described in psychoses. METHODS: We used 64-sensor EEG recordings during a P300 oddball task in 128 SZ patients (96 chronic, CR, and 32 first episodes, FE), as well as 46 bipolar disorder (BD) patients, and 92 healthy controls (HC). Pre-stimulus and modulation (task-response minus pre-stimulus windows values) of CS and SGC were assessed in the theta band (4-8 Hz) and the broadband (4-70 Hz). RESULTS: Compared to HC, SZ patients (CR and FE) showed significantly higher pre-stimulus CS values in the broadband, and both SZ and BD patients showed lower theta-band CS modulation. SGC modulation values, both theta-band and broadband, were also abnormally reduced in CR patients. Statistically significant relationships were found in the theta band between SGC modulation and both CS pre-stimulus and modulation values in patients. CS altered measures in patients were additionally related to their cognitive outcome and negative symptoms. A primary role of antipsychotics in these results was ruled out. CONCLUSIONS: Our results linking SGC and CS alterations in psychotic patients supported a hyperactive and hypomodulatory network mainly involving connections in secondary pathways.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Humanos , Encéfalo , Eletroencefalografia/métodos
5.
New Phytol ; 241(1): 197-208, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921581

RESUMO

Mutations affecting crossover (CO) frequency and distribution lead to the presence of univalents during meiosis, giving rise to aneuploid gametes and sterility. These mutations may have a different effect after chromosome doubling. The combination of altered ploidy and mutations could be potentially useful to gain new insights into the mechanisms and regulation of meiotic recombination; however, studies using autopolyploid meiotic mutants are scarce. Here, we have analyzed the cytogenetic consequences in colchicine-induced autotetraploids (colchiploids) from different Arabidopsis mutants with an altered CO frequency. We have found that there are three types of mutants: mutants in which chiasma frequency is doubled after chromosome duplication (zip4, mus81), as in the control; mutants in which polyploidy leads to a higher-than-expected increase in chiasma frequency (asy1, mer3, hei10, and mlh3); and mutants in which the rise in chiasma frequency produced by the presence of two extrachromosomal sets is less than doubled (msh5, fancm). In addition, the proportion of class I/class II COs varies after chromosome duplication in the control. The results obtained reveal the potential of colchiploid meiotic mutants for better understanding of the function of key proteins during plant meiosis. This is especially relevant considering that most crops are polyploids.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Duplicação Cromossômica , Cromossomos de Plantas/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Mutação/genética , Poliploidia , Meiose/genética , Troca Genética
7.
Neuroimage ; 280: 120332, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619796

RESUMO

The majority of electroencephalographic (EEG) and magnetoencephalographic (MEG) studies filter and analyse neural signals in specific frequency ranges, known as "canonical" frequency bands. However, this segmentation, is not exempt from limitations, mainly due to the lack of adaptation to the neural idiosyncrasies of each individual. In this study, we introduce a new data-driven method to automatically identify frequency ranges based on the topological similarity of the frequency-dependent functional neural network. The resting-state neural activity of 195 cognitively healthy subjects from three different databases (MEG: 123 subjects; EEG1: 27 subjects; EEG2: 45 subjects) was analysed. In a first step, MEG and EEG signals were filtered with a narrow-band filter bank (1 Hz bandwidth) from 1 to 70 Hz with a 0.5 Hz step. Next, the connectivity in each of these filtered signals was estimated using the orthogonalized version of the amplitude envelope correlation to obtain the frequency-dependent functional neural network. Finally, a community detection algorithm was used to identify communities in the frequency domain showing a similar network topology. We have called this approach the "Connectivity-based Meta-Bands" (CMB) algorithm. Additionally, two types of synthetic signals were used to configure the hyper-parameters of the CMB algorithm. We observed that the classical approaches to band segmentation are partially aligned with the underlying network topologies at group level for the MEG signals, but they are missing individual idiosyncrasies that may be biasing previous studies, as revealed by our methodology. On the other hand, the sensitivity of EEG signals to reflect this underlying frequency-dependent network structure is limited, revealing a simpler frequency parcellation, not aligned with that defined by the "canonical" frequency bands. To the best of our knowledge, this is the first study that proposes an unsupervised band segmentation method based on the topological similarity of functional neural network across frequencies. This methodology fully accounts for subject-specific patterns, providing more robust and personalized analyses, and paving the way for new studies focused on exploring the frequency-dependent structure of brain connectivity.


Assuntos
Eletroencefalografia , Magnetoencefalografia , Humanos , Algoritmos , Encéfalo , Bases de Dados Factuais
8.
Proc Natl Acad Sci U S A ; 120(33): e2305002120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549263

RESUMO

Polyploids, which arise from whole-genome duplication events, have contributed to genome evolution throughout eukaryotes. Among plants, novel features of neopolyploids include traits that can be evolutionarily or agriculturally beneficial, such as increased abiotic stress tolerance. Thus, in addition to being interesting from an evolutionary perspective, genome duplication is also increasingly recognized as a promising crop improvement tool. However, newly formed (neo)polyploids commonly suffer from fertility problems, which have been attributed to abnormal associations among the multiple homologous chromosome copies during meiosis (multivalents). Here, we test the long-standing hypothesis that reducing meiotic cross-over number may be sufficient to limit multivalent formation, favoring diploid-like bivalent associations (cytological diploidization). To do so, we developed Arabidopsis thaliana lines with low cross-over rates by combining mutations for HEI10 and TAF4b. Double mutants showed a reduction of ~33% in cross-over numbers in diploids without compromising meiotic stability. Neopolyploids derived from the double mutant show a cross-over rate reduction of about 40% relative to wild-type neotetraploids, and groups of four homologs indeed formed fewer multivalents and more bivalents. However, we also show that the reduction in multivalents comes with the cost of a slightly increased frequency of univalents and that it does not rescue neopolyploid fertility. Thus, while our results do show that reducing cross-over rates can reduce multivalent frequency in neopolyploids, they also emphasize that there are additional factors affecting both meiotic stability and neopolyploid fertility that will need to be considered in solving the neopolyploid fertility challenge.


Assuntos
Meiose , Poliploidia , Arabidopsis/citologia , Arabidopsis/genética , Recombinação Genética , Cromossomos de Plantas , Genótipo
9.
J Cogn Neurosci ; 35(9): 1410-1422, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37255451

RESUMO

Out-of-body experiences (OBEs) are subjective experiences of seeing one's own body and the environment from a location outside the physical body. They can arise spontaneously or in specific conditions, such as during the intake of dissociative drug. Given its unpredictable occurrence, one way to empirically study it is to induce subjective experiences resembling an OBE using technology such as virtual reality. We employed a complex multisensory method of virtual embodiment in a virtual reality scenario with seven healthy participants to induce virtual OBE-like experiences. Participants performed two conditions in a randomly determined order. For both conditions, the participant's viewpoint was lifted out of the virtual body toward the ceiling of the virtual room, and real body movements were (visuo-tactile ON condition) or were not (visuo-tactile OFF condition) translated into movements on the virtual body below-the latter aiming to maintain a feeling of connection with the virtual body. A continuous 128-electrode EEG was recorded. Participants reported subjective experiences of floating in the air and of feeling high up in the virtual room at a strong intensity, but a weak to moderate feeling of being "out of their body" in both conditions. The EEG analysis revealed that this subjective experience was associated with a power shift that manifested in an increase of delta and a decrease of alpha relative power. A reduction of theta complexity and an increase of beta-2 connectivity were also found. This supports the growing body of evidence revealing a prominent role of delta activity during particular conscious states.


Assuntos
Eletroencefalografia , Realidade Virtual , Humanos , Emoções , Tato
10.
Neurocirugía (Soc. Luso-Esp. Neurocir.) ; 33(5): 258-260, sept.-oct. 2022. ilus
Artigo em Espanhol | IBECS | ID: ibc-208218

RESUMO

La lesión aislada del nervio axilar asociada a la posición quirúrgica del paciente es una complicación muy poco frecuente, y en la mayoría de los casos está asociada al prono durante una cirugía de columna. La presentación de esta patología en relación con cirugías de otra índole es excepcional, existiendo solo unos pocos casos en la literatura científica.Presentamos el caso de una paciente que desarrolló clínica de parálisis aislada del nervio axilar izquierdo tras someterse a una lipoabdominoplastia y reducción mamaria, en la que se alternaron la posición en prono y en supino. La utilización de una solución de infiltración con lidocaína y adrenalina pudo contribuir a la aparición de la lesión en este caso único. Finalmente, el cuadro clínico se resolvió en su totalidad gracias al tratamiento conservador (AU)


Isolated injury to the axillary nerve associated with the patient́s surgical position is a very rare complication, and in most cases it is associated with the prone during spinal surgery. The presentation of this pathology in relation to surgeries of another nature is exceptional, with only a few cases in the scientific literature.We present the case of a patient who developed symptoms of isolated left axillary nerve palsy after undergoing lipoabdominoplasty and breast reduction, in which the prone and supine positions were alternated. The use of an infiltration solution with lidocaine and epinephrine could have contributed to the appearance of the lesion in this unique case. Finally, the clinical picture was fully resolved thanks to conservative treatment (AU)


Assuntos
Humanos , Feminino , Adulto , Lipoabdominoplastia/efeitos adversos , Paralisia/etiologia , Axila/inervação , Tratamento Conservador
11.
Viruses ; 14(7)2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35891361

RESUMO

Xanthomonas arboricola pv. juglandis (hereafter X. juglandis) is the etiological agent of walnut blight, the most important bacterial disease affecting walnut production worldwide. Currently, the disease is treated mainly with copper-derived compounds (e.g., CuSO4) despite the evidence of genetic resistance in these strains. Regarding the effectiveness and sustainability, the use of a bacteriophage appears to be a biocontrol alternative to reduce X. juglandis load and symptomatology of walnut blight. Here, the phages f20-Xaj, f29-Xaj, and f30-Xaj were characterized, and their effectiveness in walnut orchards against walnut blight was determined. These bacteriophages showed a specific lytic infection in X. juglandis strains isolated from Chile and France. Phylogenetic analysis of the complete genome of f20-Xaj and f30-Xaj indicates that these phages belong to the Pradovirus genus. In the field, the cocktail of these bacteriophages showed similar effectivity to CuSO4 in the reduction of incidence and severity in walnut tissue. Moreover, the bacterial load of X. juglandis was significantly reduced in the presence of bacteriophages in contrast to a CuSO4 treatment. These results show that the use of bacteriophages can be an alternative to combat the symptoms of walnut blight caused by X. juglandis.


Assuntos
Bacteriófagos , Juglans , Xanthomonas , Bacteriófagos/genética , Juglans/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
12.
Neurocirugia (Astur : Engl Ed) ; 33(5): 258-260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35241408

RESUMO

Isolated injury to the axillary nerve associated with the patient's surgical position is a very rare complication, and in most cases it is associated with the prone during spinal surgery. The presentation of this pathology in relation to surgeries of another nature is exceptional, with only a few cases in the scientific literature. We present the case of a patient who developed symptoms of isolated left axillary nerve palsy after undergoing lipoabdominoplasty and breast reduction, in which the prone and supine positions were alternated. The use of an infiltration solution with lidocaine and epinephrine could have contributed to the appearance of the lesion in this unique case. Finally, the clinical picture was fully resolved thanks to conservative treatment.


Assuntos
Plexo Braquial , Lipectomia , Humanos , Lipectomia/efeitos adversos , Paralisia/etiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-35218880

RESUMO

There is some consistency in previous EEG findings that patients with schizophrenia have increased resting-state cortical activity. Furthermore, in previous work, we have provided evidence that there is a deficit in the modulation of bioelectrical activity during the performance of a P300 task in schizophrenia. Our hypothesis here is that a basal hyperactivation would be related with altered ability to change or modulate cortical activity during a cognitive task. However, no study so far, to the best of our knowledge, has studied the association between resting-state activity and task-related modulation. With this aim, we used a dual EEG paradigm (resting state and oddball task for elicitation of the P300 evoked potential) in a sample of patients with schizophrenia (n = 100), which included a subgroup of patients with first episode psychosis (n = 30), as well as a group of healthy controls (n = 93). The study measures were absolute power for resting-state; and spectral entropy (SE) and connectivity strength (CS) for P300-task data, whose modulation had been previously found to be altered in schizophrenia. Following the literature on P300, we focused our study on the theta frequency band. As expected, our results showed an increase in resting state activity and altered task-related modulation. Moreover, we found an inverse relationship between the amount of resting-state activity and modulation of task-related activity. Our results confirm our hypothesis and support the idea that a greater amount of resting theta-band synchrony could hamper the modulation of signal regularity (quantified by SE) and activity density (measured by CS) during the P300 task performance. This association was found in both patients and controls, suggesting the existence of a common mechanism and a possible ceiling effect in schizophrenia patients in relation to a decreased inhibitory function that limits their cortical reactivity to the task.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Eletroencefalografia , Entropia , Humanos , Descanso/fisiologia
14.
J Neural Eng ; 19(1)2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35108688

RESUMO

Objective.Schizophrenia is a psychiatric disorder that has been shown to disturb the dynamic top-down processing of sensory information. Various imaging techniques have revealed abnormalities in brain activity associated with this disorder, both locally and between cerebral regions. However, there is increasing interest in investigating dynamic network response to novel and relevant events at the network level during an attention-demanding task with high-temporal-resolution techniques. The aim of the work was: (i) to test the capacity of a novel algorithm to detect recurrent brain meta-states from auditory oddball task recordings; and (ii) to evaluate how the dynamic activation and behavior of the aforementioned meta-states were altered in schizophrenia, since it has been shown to impair top-down processing of sensory information.Approach.A novel unsupervised method for the detection of brain meta-states based on recurrence plots and community detection algorithms, previously tested on resting-state data, was used on auditory oddball task recordings. Brain meta-states and several properties related to their activation during target trials in the task were extracted from electroencephalography data from patients with schizophrenia and cognitively healthy controls.Main results.The methodology successfully detected meta-states during an auditory oddball task, and they appeared to show both frequency-dependent time-locked and non-time-locked activity with respect to the stimulus onset. Moreover, patients with schizophrenia displayed higher network diversity, and showed more sluggish meta-state transitions, reflected in increased dwell times, less complex meta-state sequences, decreased meta-state space speed, and abnormal ratio of negative meta-state correlations.Significance.Abnormal cognition in schizophrenia is also reflected in decreased brain flexibility at the dynamic network level, which may hamper top-down processing, possibly indicating impaired decision-making linked to dysfunctional predictive coding. Moreover, the results showed the ability of the methodology to find meaningful and task-relevant changes in dynamic connectivity and pathology-related group differences.


Assuntos
Esquizofrenia , Encéfalo , Mapeamento Encefálico , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética/métodos
15.
Mol Plant Microbe Interact ; 35(1): 94-95, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34086484

RESUMO

The complete genome sequence of Xanthomonas arboricola pv. corylina A7 was obtained by a hybrid approach combining PacBio and Illumina HiSeq sequence data. A single circular chromosome of 5.1 mb with 65.47% G + C content was obtained, including 4,344 coding sequences identified as well as some genes involved in copper resistance. The information obtained corresponds to the first report of a high-quality whole genome of X. arboricola pv. corylina, isolated from infected hazelnut trees in southern Chile.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Xanthomonas , Chile , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Xanthomonas/genética
16.
Eur J Plast Surg ; 45(4): 671-674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34785865

RESUMO

The SARS-CoV-2 pandemic is giving rise to a wide range of clinical manifestations, which can affect all organs and systems. Due to the enormous and constantly growing number of infected people, even the rarest complications will be observed in a very high number of patients. Late periprosthetic seroma of the breast has gained importance since the description of Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), but this entity is not the  only cause. Among the causes of non-BIA-ALCL late seroma, we can include those of mechanical origin and those of non-mechanical origin. Within the latter, the common denominator is the triggering of an aberrant immune reaction that generates an inflammatory exudate from the periprosthetic capsule that gives rise to the seroma. We present two cases of late breast seroma as a manifestation of SARS-CoV-2 infection. Level of evidence: Level V, diagnostic study.

17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 315-318, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34891299

RESUMO

The main objective of this study was to examine the influence that recording length, sampling frequency, and imaging modality have on the estimation and characterization of spontaneous brain meta-states during rest. To this end, a recently developed method of meta-state extraction and characterization was applied to a subset of 16 healthy elderly subjects from two independent electroencephalographic and magnetoencephalographic (EEG/MEG) databases. The recordings were segmented into the first 5, 10, 15, 20, 25, 30, 60 and 90-s of artifact-free activity and meta-states were extracted. Temporal activation sequence (TAS) complexity, which characterizes the complexity of the metastateactivation sequences during rest, was calculated. Then, its stability as a function of segment length, sampling frequency, and imaging modality was assessed. The results showed that, in general, the minimum segment length needed to fully characterize resting-state meta-state activation complexity ranged from 15 to 25 seconds. Moreover, it was found that the sampling frequency has a slight influence on the complexity measure, and that results were similar across EEG and MEG. The findings indicate that the proposed methodology can be applied to both EEG and MEG recordings and displays stable behavior with relatively short segments. However, methodological choices, such as sampling frequency, should be carefully considered.


Assuntos
Eletroencefalografia , Magnetoencefalografia , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Descanso
18.
Plants (Basel) ; 10(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34961037

RESUMO

DNA topoisomerase II (TOPII) plays a very important role in DNA topology and in different biological processes such as DNA replication, transcription, repair, and chromosome condensation in higher eukaryotes. TOPII has been found to interact directly with a protein called topoisomerase II binding protein 1 (TopBP1) which also seems to have important roles in DNA replication and repair. In this study, we conducted different experiments to assess the roles of TopBP1 in DNA repair, mitosis, and meiosis, exploring the relationship between TOPII activity and TopBP1. We found that topbp1 mutant seedlings of Arabidopsis thaliana were hypersensitive to cisplatin treatment and the inhibition of TOPII with etoposide produced similar hypersensitivity levels. Furthermore, we recognised that there were no significant differences between the WT and topbp1 seedlings treated with cisplatin and etoposide together, suggesting that the hypersensitivity to cisplatin in the topbp1 mutant could be related to the functional interaction between TOPII and TopBP1. Somatic and meiotic anaphase bridges appeared in the topbp1 mutant at similar frequencies to those when TOPII was inhibited with merbarone, etoposide, or ICFR-187. The effects on meiosis of TOPII inhibition were produced at S phase/G2 stage, suggesting that catenanes could be produced at the onset of meiosis. Thus, if the processing of the catenanes is impaired, some anaphase bridges can be formed. Also, the appearance of anaphase bridges at first and second division is discussed.

19.
Brain Behav ; 11(12): e2415, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34758203

RESUMO

INTRODUCTION: Recent studies support the identification of valid subtypes within schizophrenia and bipolar disorder using cluster analysis. Our aim was to identify meaningful biotypes of psychosis based on network properties of the electroencephalogram. We hypothesized that these parameters would be more altered in a subgroup of patients also characterized by more severe deficits in other clinical, cognitive, and biological measurements. METHODS: A clustering analysis was performed using the electroencephalogram-based network parameters derived from graph-theory obtained during a P300 task of 137 schizophrenia (of them, 35 first episodes) and 46 bipolar patients. Both prestimulus and modulation of the electroencephalogram were included in the analysis. Demographic, clinical, cognitive, structural cerebral data, and the modulation of the spectral entropy of the electroencephalogram were compared between clusters. Data from 158 healthy controls were included for further comparisons. RESULTS: We identified two clusters of patients. One cluster presented higher prestimulus connectivity strength, clustering coefficient, path-length, and lower small-world index compared to controls. The modulation of clustering coefficient and path-length parameters was smaller in the former cluster, which also showed an altered structural connectivity network and a widespread cortical thinning. The other cluster of patients did not show significant differences with controls in the functional network properties. No significant differences were found between patients´ clusters in first episodes and bipolar proportions, symptoms scores, cognitive performance, or spectral entropy modulation. CONCLUSION: These data support the existence of a subgroup within psychosis with altered global properties of functional and structural connectivity.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Entropia , Humanos , Imageamento por Ressonância Magnética , Transtornos Psicóticos/psicologia
20.
NPJ Precis Oncol ; 5(1): 78, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404896

RESUMO

Despite advances in its treatment, lung cancer still represents the most common and lethal tumor. Because of that, efforts to decipher the pathophysiological actors that may promote lung tumor generation/progression are being made, with the final aim of establishing new therapeutic options. Using a transgenic mouse model, we formerly demonstrated that the sole activation of the MEK5/ERK5 MAPK route had a pathophysiological role in the onset of lung adenocarcinomas. Given the prevalence of that disease and its frequent dismal prognosis, our findings opened the possibility of targeting the MEK5/ERK5 route with therapeutic purposes. Here we have explored such possibility. We found that increased levels of MEK5/ERK5 correlated with poor patient prognosis in lung cancer. Moreover, using genetic as well as pharmacological tools, we show that targeting the MEK5/ERK5 route is therapeutically effective in lung cancer. Not only genetic disruption of ERK5 by CRISPR/Cas9 caused a relevant inhibition of tumor growth in vitro and in vivo; such ERK5 deficit augmented the antitumoral effect of agents normally used in the lung cancer clinic. The clinical correlation studies together with the pharmacological and genetic results establish the basis for considering the targeting of the MEK5/ERK5 route in the therapy for lung cancer.

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