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1.
Biomed Opt Express ; 15(3): 1474-1485, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38495699

RESUMO

The kidney is an important organ for excreting metabolic waste and maintaining the stability of the body's internal environment. The renal function involves multiple complex and fine structures in the whole kidney, and any change in these structures may cause impaired nephric function. Consequently, achieving three-dimensional (3D) reconstruction of the entire kidney at a single-cell resolution is of significant importance for understanding the kidney's structural characteristics and exploring the pathogenesis of kidney diseases. In this paper, we propose a pipeline from sample preparation to optical microscopic imaging of the entire kidney, followed by data processing for 3D reconstruction of the whole mouse kidney. We employed transgenic fluorescent labeling and propidium iodide (PI) labeling to obtain detailed information about the vascular structure and cytoarchitecture of the kidney. Subsequently, the entire mouse kidney was imaged at submicron-resolution using high-definition fluorescent micro-optical sectioning tomography (HD-fMOST). Finally, we reconstructed the structures of interest through various data processing methods on the original images. This included detecting glomeruli throughout the entire kidney, as well as the segmentation and visualization of the renal arteries, veins, and three different types of nephrons. Our method provides a powerful tool for studying the renal microstructure and its spatial relationships throughout the entire kidney.

2.
Science ; 383(6682): eadj9198, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38300992

RESUMO

Mapping single-neuron projections is essential for understanding brain-wide connectivity and diverse functions of the hippocampus (HIP). Here, we reconstructed 10,100 single-neuron projectomes of mouse HIP and classified 43 projectome subtypes with distinct projection patterns. The number of projection targets and axon-tip distribution depended on the soma location along HIP longitudinal and transverse axes. Many projectome subtypes were enriched in specific HIP subdomains defined by spatial transcriptomic profiles. Furthermore, we delineated comprehensive wiring diagrams for HIP neurons projecting exclusively within the HIP formation (HPF) and for those projecting to both intra- and extra-HPF targets. Bihemispheric projecting neurons generally projected to one pair of homologous targets with ipsilateral preference. These organization principles of single-neuron projectomes provide a structural basis for understanding the function of HIP neurons.


Assuntos
Axônios , Mapeamento Encefálico , Hipocampo , Neurônios , Animais , Camundongos , Axônios/fisiologia , Axônios/ultraestrutura , Hipocampo/ultraestrutura , Neurônios/classificação , Neurônios/ultraestrutura , Análise de Célula Única/métodos , Rede Nervosa , Masculino , Camundongos Endogâmicos C57BL
3.
Comput Biol Med ; 171: 108102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350398

RESUMO

The morphological analysis of cells from optical images is vital for interpreting brain function in disease states. Extracting comprehensive cell morphology from intricate backgrounds, common in neural and some medical images, poses a significant challenge. Due to the huge workload of manual recognition, automated neuron cell segmentation using deep learning algorithms with labeled data is integral to neural image analysis tools. To combat the high cost of acquiring labeled data, we propose a novel semi-supervised cell segmentation algorithm for immunofluorescence-stained cell image datasets (ISC), utilizing a mean-teacher semi-supervised learning framework. We include a "cross comparison representation learning block" to enhance the teacher-student model comparison on high-dimensional channels, thereby improving feature compactness and separability, which results in the extraction of higher-dimensional features from unlabeled data. We also suggest a new network, the Multi Pooling Layer Attention Dense Network (MPAD-Net), serving as the backbone of the student model to augment segmentation accuracy. Evaluations on the immunofluorescence staining datasets and the public CRAG dataset illustrate our method surpasses other top semi-supervised learning methods, achieving average Jaccard, Dice and Normalized Surface Dice (NSD) indicators of 83.22%, 90.95% and 81.90% with only 20% labeled data. The datasets and code are available on the website at https://github.com/Brainsmatics/CCRL.


Assuntos
Algoritmos , Núcleo Celular , Humanos , Processamento de Imagem Assistida por Computador , Coloração e Rotulagem , Aprendizado de Máquina Supervisionado
4.
bioRxiv ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-37745492

RESUMO

Proteotoxic stress impairs cellular homeostasis and underlies the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The proteasomal and autophagic degradation of proteins are two major pathways for protein quality control in the cell. Here, we report a genome-wide CRISPR screen uncovering a major regulator of cytotoxicity resulting from the inhibition of the proteasome. Dihydrolipoamide branched chain transacylase E2 (DBT) was found to be a robust suppressor, the loss of which protects against proteasome inhibition-associated cell death through promoting clearance of ubiquitinated proteins. Loss of DBT altered the metabolic and energetic status of the cell and resulted in activation of autophagy in an AMP-activated protein kinase (AMPK)-dependent mechanism in the presence of proteasomal inhibition. Loss of DBT protected against proteotoxicity induced by ALS-linked mutant TDP-43 in Drosophila and mammalian neurons. DBT is upregulated in the tissues from ALS patients. These results demonstrate that DBT is a master switch in the metabolic control of protein quality control with implications in neurodegenerative diseases.

5.
J Biol Chem ; 299(11): 105329, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37805139

RESUMO

Prion diseases are a group of transmissible neurodegenerative diseases primarily caused by the conformational conversion of prion protein (PrP) from α-helix-dominant cellular prion protein (PrPC) to ß-sheet-rich pathological aggregated form of PrPSc in many mammalian species. Dogs exhibit resistance to prion diseases, but the mechanism behind the phenomenon remains poorly understood. Compared with human PrP and mouse PrP, dog PrP has two unique amino acid residues, Arg177 and Asp159. Because PrPC contains a low-complexity and intrinsically disordered region in its N-terminal domain, it undergoes liquid-liquid phase separation (LLPS) in vitro and forms protein condensates. However, little is known about whether these two unique residues modulate the formation of PrPC condensates. Here, using confocal microscopy, fluorescence recovery after photobleaching assays, thioflavin T binding assays, and transmission electron microscopy, we report that Arg177 and Asp159 from the dog PrP slow the LLPS of full-length human PrPC, shifting the equilibrium phase boundary to higher protein concentrations and inhibit amyloid formation of the human protein. In sharp contrast, His177 and Asn159 from the human PrP enhance the LLPS of full-length dog PrPC, shifting the equilibrium phase boundary to lower protein concentrations, and promote fibril formation of the canid protein. Collectively, these results demonstrate how LLPS and amyloid formation of PrP are inhibited by a single residue Arg177 or Asp159 associated with prion disease resistance, and how LLPS and fibril formation of PrP are promoted by a single residue His177 or Asn159. Therefore, Arg177/His177 and Asp159/Asn159 are key residues in modulating PrPC liquid-phase condensation.


Assuntos
Doenças Priônicas , Príons , Camundongos , Cães , Humanos , Animais , Proteínas Priônicas/metabolismo , Príons/metabolismo , Amiloide/química , Proteínas Amiloidogênicas , Mamíferos/metabolismo
6.
Front Cell Neurosci ; 17: 1259360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854514

RESUMO

Understanding the developmental changes that affect neurons is a key step in exploring the assembly and maturation of neural circuits in the brain. For decades, researchers have used a number of labeling techniques to visualize neuronal morphology at different stages of development. However, the efficiency and accuracy of neuronal labeling technologies are limited by the complexity and fragility of neonatal brains. In this review, we illustrate the various labeling techniques utilized for examining the neurogenesis and morphological changes occurring during the early stages of development. We compare the advantages and limitations of each technique from different aspects. Then, we highlight the gaps remaining in our understanding of the structure of neurons in the neonatal mouse brain.

7.
Biomed Opt Express ; 14(9): 4800-4813, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37791250

RESUMO

Optical microscopy is a powerful tool for exploring the structure and function of organisms. However, the three-dimensional (3D) imaging of large volume samples is time-consuming and difficult. In this manuscript, we described an on-line clearing and staining method for efficient imaging of large volume samples at the cellular resolution. The optimized cocktail can increase staining and imaging depth to reduce the sectioning and scanning time, more than doubling the operational efficiency of the system. Using this method, we demonstrated the rapid acquisition of Aß plaques in whole mouse brain and obtained a complete set of cytoarchitecture images of an adult porcine hemisphere at 1.625 × 1.625 × 10 µm3 voxel resolution for about 49 hours.

8.
Int J Mol Sci ; 24(18)2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37762204

RESUMO

Organoids can recapitulate human-specific phenotypes and functions in vivo and have great potential for research in development, disease modeling, and drug screening. Due to the inherent variability among organoids, experiments often require a large sample size. Embedding, staining, and imaging each organoid individually require a lot of reagents and time. Hence, there is an urgent need for fast and efficient methods for analyzing the phenotypic changes in organoids in batches. Here, we provide a comprehensive strategy for array embedding, staining, and imaging of cerebral organoids in both agarose sections and in 3D to analyze the spatial distribution of biomarkers in organoids in situ. We constructed several disease models, particularly an aging model, as examples to demonstrate our strategy for the investigation of the phenotypic analysis of organoids. We fabricated an array mold to produce agarose support with microwells, which hold organoids in place for live/dead imaging. We performed staining and imaging of sectioned organoids embedded in agarose and 3D imaging to examine phenotypic changes in organoids using fluorescence micro-optical sectioning tomography (fMOST) and whole-mount immunostaining. Parallel studies of organoids in arrays using the same staining and imaging parameters enabled easy and reliable comparison among different groups. We were able to track all the data points obtained from every organoid in an embedded array. This strategy could help us study the phenotypic changes in organoids in disease models and drug screening.


Assuntos
Organoides , Humanos , Sefarose , Biomarcadores , Avaliação Pré-Clínica de Medicamentos , Fenótipo
9.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628974

RESUMO

Compared to young people and adults, there are differences in the ability of elderly people to resist diseases or injuries, with some noticeable features being gender-dependent. However, gender differences in age-related viscera alterations are not clear. To evaluate a potential possibility of gender differences during the natural aging process, we used three age groups to investigate the impact on spleens, kidneys, and adrenal glands. The immunofluorescence results showed that male-specific p21 proteins were concentrated in the renal tubule epithelial cells of the kidney. Histological staining revealed an increase in the frequencies of fat vacuoles located in the renal tubule epithelial cells of the cortex, under the renal capsule in the kidneys of male mice with age. In female mice, we found that the width of the globular zone in the adrenal gland cortex was unchanged with age. On the contrary, the male displayed a reduction in width. Compared to females, the content of epinephrine in adrenal gland tissue according to ELISA analysis was higher in adults, and a greater decline was observed in aged males particularly. These data confirmed the age-dependent differences between female and male mice; therefore, gender should be considered one of the major factors for personalized treatment in clinical diagnosis and treatment.


Assuntos
Córtex Suprarrenal , Glândulas Suprarrenais , Feminino , Masculino , Animais , Camundongos , Rim , Córtex Cerebral , Envelhecimento
10.
BMC Psychiatry ; 23(1): 636, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648996

RESUMO

BACKGROUND: Type 2 Diabetes mellitus (T2DM) has become a major lifestyle disease endangering human health worldwide. Patients with T2DM face varying degrees of loneliness, which adversely affects their family and the larger society. This study investigates the serial multiple mediating roles of depression and self-perceived burden between family function and loneliness in the T2DM population of China. METHODS: In total, 260 T2DM patients were included. They rated themselves based on UCLA Loneliness Scale, Self-Rating Depression Scale, Self-Rating Anxiety Scale, Family Care Index, and Self-Perceived Burden Scale. Pearson and Spearman correlation analyses were conducted to clarify the association among variables. The SPSS macro-PROCESS program was used for a series of multiple mediation analyses. RESULTS: Family function, depression, self-perceived burden, and loneliness were significantly correlated (P < 0.01). Family function not only has a direct negative impact (effect = -2.809; SE = 0.213; 95%CI: LL = -3.228, UL = -2.390) on loneliness, but also has an indirect impact on loneliness through the independent mediating role of depression (effect = -0.862; SE = 0.165; 95%CI: LL = -1.202, UL = -0.567) and self-perceived burden (effect = -0.288; SE = 0.107; 95%CI: LL = -0.525, UL = -0.114) and the chain mediating role of depression and self-perceived burden (effect = -0.202; SE = 0.066; 95%CI: LL = -0.342, UL = -0.088). CONCLUSIONS: Diversified interventions aimed at improving family function of T2DM patients would help in reducing the level of depression and self-perceived burden, and ultimately reducing loneliness.


Assuntos
Depressão , Diabetes Mellitus Tipo 2 , Humanos , Solidão , China , Estilo de Vida
11.
Nat Neurosci ; 26(8): 1394-1406, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37474638

RESUMO

The brain generates predictive motor commands to control the spatiotemporal precision of high-velocity movements. Yet, how the brain organizes automated internal feedback to coordinate the kinematics of such fast movements is unclear. Here we unveil a unique nucleo-olivary loop in the cerebellum and its involvement in coordinating high-velocity movements. Activating the excitatory nucleo-olivary pathway induces well-timed internal feedback complex spike signals in Purkinje cells to shape cerebellar outputs. Anatomical tracing reveals extensive axonal collaterals from the excitatory nucleo-olivary neurons to downstream motor regions, supporting integration of motor output and internal feedback signals within the cerebellum. This pathway directly drives saccades and head movements with a converging direction, while curtailing their amplitude and velocity via the powerful internal feedback mechanism. Our finding challenges the long-standing dogma that the cerebellum inhibits the inferior olivary pathway and provides a new circuit mechanism for the cerebellar control of high-velocity movements.


Assuntos
Cerebelo , Núcleo Olivar , Núcleo Olivar/fisiologia , Cerebelo/fisiologia , Neurônios/fisiologia , Células de Purkinje/fisiologia , Axônios
12.
Cell Rep ; 42(7): 112799, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37453056

RESUMO

The dorsal bed nucleus of stria terminalis (dBNST) is a pivotal hub for stress response modulation. Dysfunction of dopamine (DA) network is associated with chronic stress, but the roles of DA network of dBNST in chronic stress-induced emotional disorders remain unclear. We examine the role of dBNST Drd1+ and Drd2+ neurons in post-weaning social isolation (PWSI)-induced behavior deficits. We find that male, but not female, PWSI rats exhibit negative emotional phenotypes and the increase of excitability and E-I balance of dBNST Drd2+ neurons. More importantly, hypofunction of dBNST Drd2 receptor underlies PWSI-stress-induced male-specific neuronal plasticity change of dBNST Drd2+ neurons. Furthermore, chemogenetic activation of dBNST Drd2+ neurons is sufficient to induce anxiogenic effects, while Kir4.1-mediated chronic inhibition of dBNST Drd2+ neurons ameliorate PWSI-induced anxiety-like behaviors. Our findings reveal an important neural mechanism underlying PWSI-induced sex-specific behavioral abnormalities and potentially provide a target for the treatment of social stress-related emotional disorder.


Assuntos
Ansiedade , Núcleos Septais , Feminino , Masculino , Ratos , Animais , Neurônios , Núcleos Septais/fisiologia , Estresse Psicológico , Isolamento Social , Receptores de Dopamina D2
13.
BMC Biol ; 21(1): 135, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280580

RESUMO

BACKGROUND: Based on their anatomical location, rostral projections of nuclei are classified as ascending circuits, while caudal projections are classified as descending circuits. Upper brainstem neurons participate in complex information processing and specific sub-populations preferentially project to participating ascending or descending circuits. Cholinergic neurons in the upper brainstem have extensive collateralizations in both ascending and descending circuits; however, their single-cell projection patterns remain unclear because of the lack of comprehensive characterization of individual neurons. RESULTS: By combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired a high-resolution whole-brain dataset of pontine-tegmental cholinergic neurons (PTCNs) and reconstructed their detailed morphology using semi-automatic reconstruction methods. As the main source of acetylcholine in some subcortical areas, individual PTCNs had abundant axons with lengths up to 60 cm and 5000 terminals and innervated multiple brain regions from the spinal cord to the cortex in both hemispheres. Based on various collaterals in the ascending and descending circuits, individual PTCNs were grouped into four subtypes. The morphology of cholinergic neurons in the pedunculopontine nucleus was more divergent, whereas the laterodorsal tegmental nucleus neurons contained richer axonal branches and dendrites. In the ascending circuits, individual PTCNs innervated the thalamus in three different patterns and projected to the cortex via two separate pathways. Moreover, PTCNs targeting the ventral tegmental area and substantia nigra had abundant collaterals in the pontine reticular nuclei, and these two circuits contributed oppositely to locomotion. CONCLUSIONS: Our results suggest that individual PTCNs have abundant axons, and most project to various collaterals in the ascending and descending circuits simultaneously. They target regions with multiple patterns, such as the thalamus and cortex. These results provide a detailed organizational characterization of cholinergic neurons to understand the connexional logic of the upper brainstem.


Assuntos
Axônios , Tronco Encefálico , Tronco Encefálico/fisiologia , Axônios/fisiologia , Ponte/anatomia & histologia , Ponte/fisiologia , Encéfalo , Neurônios Colinérgicos
14.
Scand J Psychol ; 64(6): 802-809, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37345676

RESUMO

Social avoidance and distress are the primary aspects of social anxiety. Nonautistic people with high levels of autistic traits are more likely to exhibit social avoidance and distress. However, research has yet to reveal how autistic traits induce social avoidance and distress. To fill this gap, the present study recruited 708 participants to complete the 25-item Autism Spectrum Quotient, Social Avoidance and Distress Scale, Chinese Perceived Stress Scale, and Interpersonal Alienation Subscale. The results indicated that autistic traits significantly predicted social avoidance and distress in nonautistic people. In addition, autistic traits induced social avoidance and distress through perceived stress and interpersonal alienation, respectively. Importantly, perceived stress and interpersonal alienation (including the subdimensions of interpersonal alienation: sense of loneliness, sense of social isolation, and alienation between family members) partially mediated the relationships between autistic traits and social avoidance and distress. Overall, autistic traits predict social avoidance and distress via perceived stress and interpersonal alienation. This finding extends the hypothetical model of clinical anxiety in autism spectrum disorders. Furthermore, reducing perceived stress and interpersonal alienation in nonautistic people with high levels of autistic traits may be a valid intervention method to prevent and eliminate their social avoidance and distress.


Assuntos
Transtorno Autístico , Testes Psicológicos , Humanos , Comportamento Social , Autorrelato , Estresse Psicológico
15.
Acta Diabetol ; 60(10): 1405-1415, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37380727

RESUMO

AIMS: To examined the relationship between fear of hypoglycemia and certain variables in people with type 2 diabetes mellitus (T2DM) based on the Capability, Opportunity, Motivation, and Behavior model, combined with the context unique to people with diabetes to provide a basis for developing targeted nursing interventions. METHODS: In this cross-sectional study, 212 people with T2DM were recruited from February 2021 to July 2021. Data were collected using the Hypoglycaemia Fear Survey, Gold score, Patient Assessment of Chronic Illness Care (PACIC) scale and Diabetic Self-Management Attitudes Scale. Multiple linear regression analysis was performed to determine the predictors of fear of hypoglycemia using SPSS 26.0. RESULTS: The mean fear of hypoglycemia score was 74.88 ± 18.28 (range: 37.00-132.00). In people with T2DM, the frequency of blood glucose monitoring, the frequency of hypoglycemia in the past half-year, degree of understanding of hypoglycemia, impaired awareness of hypoglycemia, PACIC, and self-management attitude of diabetes were the influencing factors of fear of hypoglycemia (adjusted R2 = 0.560, F[21,190] = 13.800, P < 0.001). These variables explained 56.0% of the variance in the fear of hypoglycemia. CONCLUSIONS: The level of fear of hypoglycemia in people with T2DM was relatively high. In addition to paying attention to the disease characteristics of people with T2DM, medical staff should also pay attention to patients' own perception and handling ability of disease and hypoglycemia, attitude toward self-management behavior and external environment support, all of which have a positive effect on improving the fear of hypoglycemia in people with T2DM, optimizing the self-management level and improving quality of life.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Estudos Transversais , Qualidade de Vida , Motivação , Automonitorização da Glicemia , Glicemia , Medo
16.
iScience ; 26(5): 106705, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37216109

RESUMO

Resin embedding combined with ultra-thin sectioning has been widely used in microscopic and electron imaging to acquire precise structural information of biological tissues. However, the existing embedding method was detrimental to quenchable fluorescent signals of precise structures and pH-insensitive fluorescent dyes. Here, we developed a low-temperature chemical polymerization method named HM20-T to maintain weak signals of various precise structures and to decrease background fluorescence. The fluorescence preservation ratio of green fluorescent protein (GFP) tagged presynaptic elements and tdTomato labeled axons doubled. The HM20-T method was suitable for a variety of fluorescent dyes, such as DyLight 488 conjugated Lycopersicon esculentum lectin. Moreover, the brains also retained immunoreactivity after embedding. In summary, the HM20-T method was suitable for the characterization of multi-color labeled precise structures, which would contribute to the acquisition of complete morphology of various biological tissues and to the investigation of composition and circuit connection in the whole brain.

17.
Acta Diabetol ; 60(9): 1155-1169, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37199797

RESUMO

AIMS: To conduct a systematic review to summarize the definition, measurement tools, prevalence, and contributing factors of impaired awareness of hypoglycemia (IAH) in type 2 diabetes mellitus (T2DM). METHODS: A reproducible search strategy was used to identify factors affecting IAH in T2DM in PubMed, MEDLINE, EMBASE, Cochrane, PsycINFO, and CINAHL from inception until 2022. Literature screening, quality evaluation, and information extraction were performed independently by 2 investigators. A meta-analysis of prevalence was performed using Stata 17.0. RESULTS: The pooled prevalence of IAH in patients with T2DM was 22% (95%CI:14-29%). Measurement tools included the Gold score, Clarke's questionnaire, and the Pedersen-Bjergaard scale. IAH in T2DM was associated with sociodemographic factors (age, BMI, ethnicity, marital status, education level, and type of pharmacy patients visited), clinical disease factors (disease duration, HbAlc, complications, insulin therapy regimen, sulfonylureas use, and the frequency and severity of hypoglycemia), and behavior and lifestyle (smoking and medication adherence). CONCLUSION: The study found a high prevalence of IAH in T2DM, with an increased risk of severe hypoglycemia, suggesting that medical workers should take targeted measures to address sociodemographic factors, clinical disease, and behavior and lifestyle to reduce IAH in T2DM and thus reduce hypoglycemia in patients.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Prevalência , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Hipoglicemia/diagnóstico , Insulina/uso terapêutico , Hipoglicemiantes/efeitos adversos
18.
J Biomol Tech ; 34(1)2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37089871

RESUMO

The National Institutes of Health (NIH) offers many types of funding programs and opportunities to support biomedical research. The best known of these programs, the NIH Research Project Grant Program, or R01, supports investigator-initiated research projects. Another well-known funding mechanism is the NIH Shared Instrumentation Grant Program, also known as SIG or S10. This year marks the S10's 40th anniversary. To commemorate this triumphant milestone and a successful 40 years, let's first review how this legendary and highly impactful program started.


Assuntos
Pesquisa Biomédica , National Institutes of Health (U.S.) , Estados Unidos , Humanos , Pesquisadores
19.
Bioinformatics ; 39(4)2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36946294

RESUMO

MOTIVATION: Reconstructing and analyzing all blood vessels throughout the brain is significant for understanding brain function, revealing the mechanisms of brain disease, and mapping the whole-brain vascular atlas. Vessel segmentation is a fundamental step in reconstruction and analysis. The whole-brain optical microscopic imaging method enables the acquisition of whole-brain vessel images at the capillary resolution. Due to the massive amount of data and the complex vascular features generated by high-resolution whole-brain imaging, achieving rapid and accurate segmentation of whole-brain vasculature becomes a challenge. RESULTS: We introduce HP-VSP, a high-performance vessel segmentation pipeline based on deep learning. The pipeline consists of three processes: data blocking, block prediction, and block fusion. We used parallel computing to parallelize this pipeline to improve the efficiency of whole-brain vessel segmentation. We also designed a lightweight deep neural network based on multi-resolution vessel feature extraction to segment vessels at different scales throughout the brain accurately. We validated our approach on whole-brain vascular data from three transgenic mice collected by HD-fMOST. The results show that our proposed segmentation network achieves the state-of-the-art level under various evaluation metrics. In contrast, the parameters of the network are only 1% of those of similar networks. The established segmentation pipeline could be used on various computing platforms and complete the whole-brain vessel segmentation in 3 h. We also demonstrated that our pipeline could be applied to the vascular analysis. AVAILABILITY AND IMPLEMENTATION: The dataset is available at http://atlas.brainsmatics.org/a/li2301. The source code is freely available at https://github.com/visionlyx/HP-VSP.


Assuntos
Aprendizado Profundo , Camundongos , Animais , Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos , Redes Neurais de Computação , Software , Processamento de Imagem Assistida por Computador/métodos
20.
iScience ; 26(4): 106316, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36968064

RESUMO

The neocortex mediates information processing through highly organized circuitry that contains various neuron types. Distinct populations of projection neurons in different cortical regions and layers make specific connections and participate in distinct physiological functions. Herein, with the fluorescence micro-optical sectioning tomography (fMOST) and transgenetic mice that targeted intratelencephalic (IT) and pyramidal tract (PT) neurons at specific layers, we dissected the long-range connectome of pyramidal neurons in six subregions of the sensorimtor cortex. The distribution of the input neurons indicated that IT and PT neurons in the same region received information from similar regions, while the neurons in different subregions received from the preferred neuron populations. Both the input and projection areas of these six subregions showed the transverse and longitudinal correspondence in the cortico-cortical, cortico-thalamic, and cortico-striatal circuits, which indicated that the connections were topologically organized. This study provides a comprehensive resource on the anatomical connections of cortical circuits.

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