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1.
Curr Biol ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38991613

RESUMO

Vision in humans and other primates enlists parallel processing streams in the dorsal and ventral visual cortex, known to support spatial and object processing, respectively. These streams are bridged, however, by a prominent white matter tract, the vertical occipital fasciculus (VOF), identified in both classical neuroanatomy and recent diffusion-weighted magnetic resonance imaging (dMRI) studies. Understanding the evolution of the VOF may shed light on its origin, function, and role in visually guided behaviors. To this end, we acquired high-resolution dMRI data from the brains of select mammalian species, including anthropoid and strepsirrhine primates, a tree shrew, rodents, and carnivores. In each species, we attempted to delineate the VOF after first locating the optic radiations in the occipital white matter. In all primate species examined, the optic radiation was flanked laterally by a prominent and coherent white matter fasciculus recognizable as the VOF. By contrast, the equivalent analysis applied to four non-primate species from the same superorder as primates (tree shrew, ground squirrel, paca, and rat) failed to reveal white matter tracts in the equivalent location. Clear evidence for a VOF was also absent in two larger carnivore species (ferret and fox). Although we cannot rule out the existence of minor or differently organized homologous fiber pathways in the non-primate species, the results suggest that the VOF has greatly expanded, or possibly emerged, in the primate lineage. This adaptation likely facilitated the evolution of unique visually guided behaviors in primates, with direct impacts on manual object manipulation, social interactions, and arboreal locomotion.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38721987

RESUMO

The COVID-19 pandemic has significantly affected the psychological well-being of individuals worldwide. Previous research has indicated that values and beliefs, particularly social axioms, are associated with psychological responses during crises. However, most of the studies have focused on specific regions; the impact of social axioms on a global scale remains unclear. We conducted a multinational study comprising stratified samples of 18,171 participants from 35 cultures. Using multilevel modeling, we examined the associations between social axioms, personal worry, normative concerns, trust, and individuals' psychological responses to the pandemic. The results showed that greater personal worry and normative concerns predicted more negative psychological responses. Furthermore, the study also identified significant buffering effects at the societal level, as cultures with higher overall levels of fate control, religiosity, or reward for application exhibited weaker associations between personal worry and negative responses. Our findings reveal the influence of social axioms on psychological responses during the pandemic, with varying effects across cultures. The buffering effects of fate control, religiosity, and reward for application underscore the importance of considering cultural differences and individual variability when examining the impact of social axioms on psychological outcomes.

3.
bioRxiv ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38496676

RESUMO

Diffusion magnetic resonance imaging (dMRI) has been widely employed to model the trajectory of myelinated fiber bundles in white matter. Increasingly, dMRI is also used to assess local tissue properties throughout the brain. In the cerebral cortex, myelin content is a critical indicator of the maturation, regional variation, and disease related degeneration of gray matter tissue. Gray matter myelination can be measured and mapped using several non-diffusion MRI strategies; however, first order diffusion statistics such as fractional anisotropy (FA) show only weak spatial correlation with cortical myelin content. Here we show that a simple higher order diffusion parameter, the mean diffusion kurtosis (MK), is strongly correlated with the laminar and regional variation of myelin in the primate cerebral cortex. We carried out ultra-high resolution, multi-shelled dMRI in ex vivo marmoset monkey brains and compared dMRI parameters from a number of higher order models (diffusion kurtosis, NODDI and MAP MRI) to the distribution of myelin obtained using histological staining, and via Magnetization Transfer Ratio MRI (MTR), a non-diffusion MRI method. In contrast to FA, MK closely matched the myelin content assessed by histology and by MTR in the same sample. The parameter maps from MAP-MRI and NODDI also showed good correspondence with cortical myelin content. The results demonstrate that dMRI can be used to assess the variation of local myelin content in the primate cortical cortex, which may be of great value for assessing tissue integrity and tracking disease in living human patients.

4.
PNAS Nexus ; 2(10): pgad318, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37841324

RESUMO

Trust plays a crucial role in implementing public health interventions against the COVID-19 pandemic. We examined the prospective associations of interpersonal, institutional, and media trust with vaccination rates and excess mortality over time in two multinational studies. In study 1, we investigated the country-level relationships between interpersonal trust, vaccination rates, and excess mortality across 54 countries. Interpersonal trust at the country level was calculated by aggregating data of 80,317 participants from the World Values Survey in 2017-20. Data on vaccination rates and excess mortality were obtained from the World Health Organization. Our findings indicated that higher levels of interpersonal trust were linked to higher vaccination rates and lower excess mortality rates in both 2020 and 2021. In study 2, we collected data from 18,171 adults in 35 countries/societies, stratified by age, gender, and region of residence. At the country/society level, interpersonal trust and trust in local healthcare facilities, local healthcare services, and healthcare professionals were associated with higher vaccination rates and lower excess mortality, whereas social media trust was associated with lower vaccination rates and higher excess mortality across three time points over 2 years. Our findings are robust when controlling for country-level covariates of the government stringency index, population density, and medical resources (i.e. critical care beds) in both studies.

5.
BMC Public Health ; 23(1): 1106, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286984

RESUMO

BACKGROUND: The COVID-19 pandemic has brought challenges to families around the world. The prolonged school closures in Hong Kong have forced young students to stay at home and adapt to remote learning for over a year, putting their mental health conditions at risk. Focusing on primary school students and their parents, the main objective of our research is to investigate the socioemotional factors and their associations with mental health conditions. METHODS: A total of 700 Hong Kong primary schoolers (mean age = 8.2) reported their emotional experiences, loneliness, and academic self-concept via a user-friendly online survey; 537 parents reported depression and anxiety, perceived child depression and anxiety, and social support. Responses from students and parents were paired to account for the family context. Structural Equation Modeling was used for correlations and regressions. RESULTS: The results of students' responses showed that positive emotional experiences were negatively associated with loneliness and positively related to academic self-concept among students. Furthermore, the paired sample results showed that, during the one-year societal lockdown and remote learning period, the socioemotional factors were associated with mental health conditions among primary school students and their parents. Among our family sample in Hong Kong, evidence supports the unique negative association between students-reported positive emotional experiences and parents-reported child depression and anxiety, as well as between social support and parents' depression and anxiety. CONCLUSIONS: These findings highlighted the associations between socioemotional factors and mental health among young primary schoolers during the societal lockdown. We thus call for more attention to the societal lockdown and remote learning context, especially since the social distancing practice could be "the new normal" for our society to handle the future pandemic crisis.


Assuntos
COVID-19 , Saúde Mental , Criança , Humanos , Pandemias , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Estudantes , Instituições Acadêmicas , Pais
6.
BMC Psychol ; 11(1): 137, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37106457

RESUMO

BACKGROUND: Students with special educational needs (SEN) often face dehumanization, which negatively impacts their mental health, daily functioning, and educational outcomes. This study seeks to address the research gap in dehumanization literature by examining the prevalence, dynamics, and consequences of self-dehumanization and other-dehumanization among SEN students. Moreover, by utilizing psychological experiments, the study aims to identify potential intervention strategies and make recommendations to minimize the negative psychological consequences derived from the dual model of dehumanization. METHODS: This two-phase, mixed-methods study incorporates cross-sectional surveys and quasi-experimental designs. Phase 1 investigates the self-dehumanization of SEN students and other-dehumanization from non-SEN peers, teachers, parents, and the public. Phase 2 involves four experimental studies to evaluate the effectiveness of interventions emphasizing human nature and uniqueness in reducing self-dehumanization and other-dehumanization of SEN students, as well as their associated negative consequences. DISCUSSION: The study fills a research gap by examining dehumanization in SEN students, applying dyadic modeling, and identifying potential solutions to ameliorate dehumanization and its negative consequences. The findings will contribute to the advancement of the dual model of dehumanization, increase public awareness and support for SEN students in inclusive education, and promote changes in school practice and family support. The 24-month study in Hong Kong schools is expected to provide significant insights into inclusive education in school and community settings.


Assuntos
Educação Inclusiva , Estudantes , Humanos , Educação Inclusiva/métodos , Prevalência , Estudos Transversais , Estudantes/psicologia , Desumanização
7.
Nat Commun ; 13(1): 6702, 2022 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335105

RESUMO

Diffusion magnetic resonance imaging (dMRI) is commonly used to assess the tissue and cellular substructure of the human brain. In the white matter, myelinated axons are the principal neural elements that shape dMRI through the restriction of water diffusion; however, in the gray matter the relative contributions of myelinated axons and other tissue features to dMRI are poorly understood. Here we investigate the determinants of diffusion in the cerebral cortex. Specifically, we ask whether myelinated axons significantly shape dMRI fractional anisotropy (dMRI-FA), a measure commonly used to characterize tissue properties in humans. We compared ultra-high resolution ex vivo dMRI data from the brain of a marmoset monkey with both myelin- and Nissl-stained histological sections obtained from the same brain after scanning. We found that the dMRI-FA did not match the spatial distribution of myelin in the gray matter. Instead dMRI-FA was more closely related to the anisotropy of stained tissue features, most prominently those revealed by Nissl staining and to a lesser extent those revealed by myelin staining. Our results suggest that unmyelinated neurites such as large caliber apical dendrites are the primary features shaping dMRI measures in the cerebral cortex.


Assuntos
Imagem de Tensor de Difusão , Substância Branca , Humanos , Anisotropia , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Córtex Cerebral/diagnóstico por imagem , Encéfalo/patologia
8.
Neuroimage ; 264: 119653, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36257490

RESUMO

The variations in cellular composition and tissue architecture measured with histology provide the biological basis for partitioning the brain into distinct cytoarchitectonic areas and for characterizing neuropathological tissue alterations. Clearly, there is an urgent need to develop whole-brain neuroradiological methods that can assess cortical cyto- and myeloarchitectonic features non-invasively. Mean apparent propagator (MAP) MRI is a clinically feasible diffusion MRI method that quantifies efficiently and comprehensively the net microscopic displacements of water molecules diffusing in tissues. We investigate the sensitivity of high-resolution MAP-MRI to detecting areal and laminar variations in cortical cytoarchitecture and compare our results with observations from corresponding histological sections in the entire brain of a rhesus macaque monkey. High-resolution images of MAP-derived parameters, in particular the propagator anisotropy (PA), non-gaussianity (NG), and the return-to-axis probability (RTAP) reveal cortical area-specific lamination patterns in good agreement with the corresponding histological stained sections. In a few regions, the MAP parameters provide superior contrast to the five histological stains used in this study, delineating more clearly boundaries and transition regions between cortical areas and laminar substructures. Throughout the cortex, various MAP parameters can be used to delineate transition regions between specific cortical areas observed with histology and to refine areal boundaries estimated using atlas registration-based cortical parcellation. Using surface-based analysis of MAP parameters we quantify the cortical depth dependence of diffusion propagators in multiple regions-of-interest in a consistent and rigorous manner that is largely independent of the cortical folding geometry. The ability to assess cortical cytoarchitectonic features efficiently and non-invasively, its clinical feasibility, and translatability make high-resolution MAP-MRI a promising 3D imaging tool for studying whole-brain cortical organization, characterizing abnormal cortical development, improving early diagnosis of neurodegenerative diseases, identifying targets for biopsies, and complementing neuropathological investigations.


Assuntos
Mapeamento Encefálico , Processamento de Imagem Assistida por Computador , Animais , Mapeamento Encefálico/métodos , Processamento de Imagem Assistida por Computador/métodos , Macaca mulatta , Imageamento por Ressonância Magnética/métodos , Encéfalo
9.
Proc Natl Acad Sci U S A ; 119(36): e2206559119, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36044550

RESUMO

The brain is a highly organized, dynamic system whose network architecture is often assessed through resting functional magnetic resonance imaging (fMRI) functional connectivity. The functional interactions between brain areas, including those observed during rest, are assumed to stem from the collective influence of action potentials carried by long-range neural projections. However, the contribution of individual neurons to brain-wide functional connectivity has not been systematically assessed. Here we developed a method to concurrently measure and compare the spiking activity of local neurons with fMRI signals measured across the brain during rest. We recorded spontaneous activity from neural populations in cortical face patches in the macaque during fMRI scanning sessions. Individual cells exhibited prominent, bilateral coupling with fMRI fluctuations in a restricted set of cortical areas inside and outside the face patch network, partially matching the pattern of known anatomical projections. Within each face patch population, a subset of neurons was positively coupled with the face patch network and another was negatively coupled. The same cells showed inverse correlations with distinct subcortical structures, most notably the lateral geniculate nucleus and brainstem neuromodulatory centers. Corresponding connectivity maps derived from fMRI seeds and local field potentials differed from the single unit maps, particularly in subcortical areas. Together, the results demonstrate that the spiking fluctuations of neurons are selectively coupled with discrete brain regions, with the coupling governed in part by anatomical network connections and in part by indirect neuromodulatory pathways.


Assuntos
Encéfalo , Conectoma , Descanso , Encéfalo/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Descanso/fisiologia
10.
Neuroimage ; 245: 118759, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34838750

RESUMO

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template "SC21" from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.


Assuntos
Tonsila do Cerebelo/anatomia & histologia , Gânglios da Base/anatomia & histologia , Tronco Encefálico/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Hipotálamo/anatomia & histologia , Tálamo/anatomia & histologia , Tonsila do Cerebelo/diagnóstico por imagem , Animais , Atlas como Assunto , Gânglios da Base/diagnóstico por imagem , Tronco Encefálico/diagnóstico por imagem , Técnicas Histológicas , Hipotálamo/diagnóstico por imagem , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Tálamo/diagnóstico por imagem
11.
Front Psychol ; 12: 691858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367018

RESUMO

In two studies, we investigated how Hong Kong university students reacted to descriptions of China as multicultural vs. assimilatory, examining effects on emotions, prejudice toward Mainland Chinese, attitudes toward Hong Kong/China culture mixing, and cultural identities. Study 1 compared a multicultural priming condition to a control condition and found that the multiculturalism prime significantly reduced desire to socially distance from Mainland Chinese. Study 2 compared multiculturalism, assimilation, or control primes' effects, and found that the multiculturalism prime, through increased positive emotions, indirectly reduced social distancing from Mainland Chinese and disgust toward culture mixing, and increased Chinese ethnic identity and multicultural identity styles; the assimilation prime had the opposite indirect effects through increasing negative emotions. Results show new evidence of the importance of emotion in how non-immigrant regional groups, who are both minority and majority culture members, react to different diversity models. Multicultural frames increased positive emotions, with downstream positive effects on both intergroup attitudes and integrated identities.

12.
Neuroimage ; 241: 118429, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311068

RESUMO

Magnetic resonance imaging (MRI) is now an essential tool in the field of neuroscience involving non-human primates (NHP). Structural MRI scanning using T1-weighted (T1w) or T2-weighted (T2w) images provides anatomical information, particularly for experiments involving deep structures such as the basal ganglia and cerebellum. However, for certain subcortical structures, T1w and T2w image contrasts are insufficient for their detection of important anatomical details. To better visualize such structures in the macaque brain, we applied a relatively new method called quantitative susceptibility mapping (QSM), which enhances tissue contrast based on the local tissue magnetic susceptibility. The QSM significantly improved the visualization of important structures, including the ventral pallidum (VP), globus pallidus external and internal segments (GPe and GPi), substantia nigra (SN), subthalamic nucleus (STN) in the basal ganglia and the dentate nucleus (DN) in the cerebellum. We quantified this the contrast enhancement by systematically comparing of contrast-to-noise ratios (CNRs) of QSM images relative to the corresponding T1w and T2w images. In addition, QSM values of some structures were correlated to the age of the macaque subjects. These results identify the QSM method as a straightforward and useful tool for clearly visualizing details of subcortical structures that are invisible with more traditional scanning sequences.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Ferro/metabolismo , Imageamento por Ressonância Magnética/métodos , Animais , Mapeamento Encefálico/normas , Processamento de Imagem Assistida por Computador/normas , Macaca mulatta , Imageamento por Ressonância Magnética/normas , Masculino , Primatas
13.
Sci Rep ; 11(1): 106, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420210

RESUMO

Magnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared-RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm3 voxel at 9.4 T. Test-retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.


Assuntos
Encéfalo/diagnóstico por imagem , Meios de Contraste/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Imageamento por Ressonância Magnética/métodos , Animais , Feminino , Imageamento por Ressonância Magnética/instrumentação , Camundongos , Camundongos Endogâmicos C57BL , Sensibilidade e Especificidade
14.
Cereb Cortex ; 31(1): 439-447, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32901254

RESUMO

Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechanisms leading to brain damage. This study aimed to characterize cortical lesions in marmosets with EAE using ultrahigh-field (7 T) MRI and histological analysis. Tissue preparation was optimized to enable the acquisition of high-spatial resolution (50-µm isotropic) T2*-weighted images. A total of 14 animals were scanned in this study, and 70% of the diseased animals presented at least one cortical lesion on postmortem imaging. Cortical lesions identified on MRI were verified with myelin proteolipid protein immunostaining. An optimized T2*-weighted sequence was developed for in vivo imaging and shown to capture 65% of cortical lesions detected postmortem. Immunostaining confirmed extensive demyelination with preserved neuronal somata in several cortical areas of EAE animals. Overall, this study demonstrates the relevance and feasibility of the marmoset EAE model to study cortical lesions, among the most important yet least understood features of MS.


Assuntos
Lesões Encefálicas/patologia , Encéfalo/patologia , Doenças Desmielinizantes/patologia , Encefalomielite Autoimune Experimental/patologia , Esclerose Múltipla/patologia , Animais , Criança , Pré-Escolar , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Técnicas Histológicas/métodos , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-35010498

RESUMO

The COVID-19 pandemic and social unrest have posed a unique set of challenges to Hong Kong. During these two social events, parents of children with special educational needs (SEN) who were already experiencing caregiving pressure, likely coped with additional stressors; they were at a higher risk of mental health problems. A pre-registered, cross-sectional survey study was carried out among 234 Hong Kong parents of children with SEN, investigating the associations of stigmatized identity, perceived discrimination, and subjective well-being under the impact of these social events. Utilizing the Bayesian modelling, we found that highly self-stigmatized parents not only perceived more daily-life discriminating behaviors against them, but also reported having higher distress, more negative emotions, and lower life satisfaction. A higher perceived impact of social events and more discrimination were also associated with lower well-being. Additionally, stigmatized identity, perceived discrimination, and perceived impact of social events demonstrated unique associations with well-being variables, indicating they were substantial stressors. The study called out for public attention to the mental health conditions among parents of children with SEN and other disadvantaged groups in society.


Assuntos
COVID-19 , Teorema de Bayes , Criança , Estudos Transversais , Hong Kong , Humanos , Pandemias , Discriminação Percebida , SARS-CoV-2
16.
Genetics ; 215(3): 609-621, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32414869

RESUMO

New anticancer therapeutics require extensive in vivo characterization to identify endogenous and exogenous factors affecting efficacy, to measure toxicity and mutagenicity, and to determine genotypes that result in therapeutic sensitivity or resistance. We used Caenorhabditis elegans as a platform with which to characterize properties of the anticancer therapeutic CX-5461. To understand the processes that respond to CX-5461-induced damage, we generated pharmacogenetic profiles for a panel of C. elegans DNA replication and repair mutants with common DNA-damaging agents for comparison with the profile of CX-5461. We found that multiple repair pathways, including homology-directed repair, microhomology-mediated end joining, nucleotide excision repair, and translesion synthesis, were needed for CX-5461 tolerance. To determine the frequency and spectrum of CX-5461-induced mutations, we used a genetic balancer to capture CX-5461-induced mutations. We found that CX-5461 is mutagenic, resulting in both large copy number variations and a high frequency of single-nucleotide variations (SNVs), which are consistent with the pharmacogenetic profile for CX-5461. Whole-genome sequencing of CX-5461-exposed animals found that CX-5461-induced SNVs exhibited a distinct mutational signature. We also phenocopied the CX-5461 photoreactivity observed in clinical trials and demonstrated that CX-5461 generates reactive oxygen species when exposed to UVA radiation. Together, the data from C. elegans demonstrate that CX-5461 is a multimodal DNA-damaging anticancer agent.


Assuntos
Antineoplásicos/toxicidade , Benzotiazóis/toxicidade , Caenorhabditis elegans/genética , Testes de Carcinogenicidade/métodos , Estudo de Associação Genômica Ampla/métodos , Mutagênicos/toxicidade , Naftiridinas/toxicidade , Variantes Farmacogenômicos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Reparo do DNA , Resistencia a Medicamentos Antineoplásicos , Genoma Helmíntico , Mutação , Polimorfismo de Nucleotídeo Único
17.
Brain Struct Funct ; 225(4): 1313-1326, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32253509

RESUMO

The primate brain contains a large number of interconnected visual areas, whose spatial organization and intracortical projections show a high level of conservation across species. One fiber pathway of recent interest is the vertical occipital fasciculus (VOF), which is thought to support communication between dorsal and ventral visual areas in the occipital lobe. A recent comparative diffusion MRI (dMRI) study reported that the VOF in the macaque brain bears a similar topology to that of the human, running superficial and roughly perpendicular to the optic radiation. The present study reports a comparative investigation of the VOF in the common marmoset, a small New World monkey whose lissencephalic brain is approximately tenfold smaller than the macaque and 150-fold smaller than the human. High-resolution ex vivo dMRI of two marmoset brains revealed an occipital white matter structure that closely resembles that of the larger primate species, with one notable difference. Namely, unlike in the macaque and the human, the VOF in the marmoset is spatially fused with other, more anterior vertical tracts, extending anteriorly between the parietal and temporal cortices. We compare several aspects of this continuous structure, which we term the VOF complex (VOF +), and neighboring fasciculi to those of macaques and humans. We hypothesize that the essential topology of the VOF+ is a conserved feature of the posterior cortex in anthropoid primates, with a clearer fragmentation into multiple named fasciculi in larger, more gyrified brains.


Assuntos
Lobo Occipital/anatomia & histologia , Substância Branca/anatomia & histologia , Animais , Callithrix , Imagem de Tensor de Difusão , Humanos , Processamento de Imagem Assistida por Computador/métodos , Especificidade da Espécie , Vias Visuais/anatomia & histologia
18.
Nat Neurosci ; 23(2): 271-280, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31932765

RESUMO

While the fundamental importance of the white matter in supporting neuronal communication is well known, existing publications of primate brains do not feature a detailed description of its complex anatomy. The main barrier to achieving this is that existing primate neuroimaging data have insufficient spatial resolution to resolve white matter pathways fully. Here we present a resource that allows detailed descriptions of white matter structures and trajectories of fiber pathways in the marmoset brain. The resource includes: (1) the highest-resolution diffusion-weighted MRI data available to date, which reveal white matter features not previously described; (2) a comprehensive three-dimensional white matter atlas depicting fiber pathways that were either omitted or misidentified in previous atlases; and (3) comprehensive fiber pathway maps of cortical connections combining diffusion-weighted MRI tractography and neuronal tracing data. The resource, which can be downloaded from marmosetbrainmapping.org, will facilitate studies of brain connectivity and the development of tractography algorithms in the primate brain.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/anatomia & histologia , Substância Branca/anatomia & histologia , Animais , Callithrix , Imageamento Tridimensional
19.
Nat Commun ; 10(1): 1975, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036814

RESUMO

The default mode network (DMN) is associated with a wide range of brain functions. In humans, the DMN is marked by strong functional connectivity among three core regions: medial prefrontal cortex (mPFC), posterior parietal cortex (PPC), and the medial parietal and posterior cingulate cortex (PCC). Neuroimaging studies have shown that the DMN also exists in non-human primates, suggesting that it may be a conserved feature of the primate brain. Here, we found that, in common marmosets, the dorsolateral prefrontal cortex (dlPFC; peak at A8aD) has robust fMRI functional connectivity and reciprocal anatomical connections with the posterior DMN core regions (PPC and PCC), while the mPFC has weak connections with the posterior DMN core regions. This strong dlPFC but weak mPFC connectivity in marmoset differs markedly from the stereotypical DMN in humans. The mPFC may be involved in brain functions that are further developed in humans than in other primates.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Callithrix , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Lobo Parietal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem
20.
Neuron ; 97(4): 940-952.e4, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29398365

RESUMO

Patterns of spontaneous brain activity, typically measured in humans at rest with fMRI, are used routinely to assess the brain's functional organization. The mechanisms that generate and coordinate the underlying neural fluctuations are largely unknown. Here we investigate the hypothesis that the nucleus basalis of Meynert (NBM), the principal source of widespread cholinergic and GABAergic projections to the cortex, contributes critically to such activity. We reversibly inactivated two distinct sites of the NBM in macaques while measuring fMRI activity across the brain. We found that inactivation led to strong, regionalized suppression of shared or "global" signal components of cortical fluctuations ipsilateral to the injection. At the same time, the commonly studied resting-state networks retained their spatial structure under this suppression. The results indicate that the NBM contributes selectively to the global component of functional connectivity but plays little if any role in the specific correlations that define resting-state networks.


Assuntos
Núcleo Basal de Meynert/fisiologia , Córtex Cerebral/fisiologia , Animais , Nível de Alerta , Mapeamento Encefálico , Feminino , Macaca mulatta , Imageamento por Ressonância Magnética , Vias Neurais/fisiologia
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