
아동기 및 청소년기의 복잡한 구조적, 기능적 변화로 인해 정신병리 발달 위험을 이해하기 위해서는 다차원적 접근이 필요하다. 이 연구는 청소년 뇌 인지 발달 데이터셋에서 정신병리 차원과 관련된 구조적 및 기능적 뇌 네트워크 패턴을 동시에 조사하였다.


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Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology ( p ) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.

### Competing Interest Statement

The authors have declared no competing interest.

Multimodal neural correlates of childhood psychopathology

아동-정신병리의-다중-양상-신경-상관관계


아동 정신병리의 다중 양상 신경 상관관계


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고도 장액성 난소암 세포의 휴면 상태에서 Netrin 신호 전달 경로가 세포 생존에 필수적인 역할을 한다.


Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context. In combination with RNA-seq, we discovered the Netrin signaling pathway as critical to dormant HGSOC cell survival. We demonstrate that Netrin-1, -3, and its receptors are essential for low level ERK activation to promote survival, and that Netrin activation of ERK is unable to induce proliferation. Deletion of all UNC5 family receptors blocks Netrin signaling in HGSOC cells and compromises viability during the dormancy step of dissemination in xenograft assays. Furthermore, we demonstrate that Netrin-1 and -3 overexpression in HGSOC correlates with poor outcome. Specifically, our experiments reveal that Netrin overexpression elevates cell survival in dormant culture conditions and contributes to greater spread of disease in a xenograft model of abdominal dissemination. This study highlights Netrin signaling as a key mediator HGSOC cancer cell dormancy and metastasis.

### Competing Interest Statement

P. Mehlen is the founder and CEO of Netris Pharma and has an ownership interest including stocks and patents. The other authors have declared that no conflict of interest exists.

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells

고도-장액성-난소암-세포의-휴면-상태에서-생존을-유지하는-netrin-신호-전달


고도 장액성 난소암 세포의 휴면 상태에서 생존을 유지하는 Netrin 신호 전달



확산 가중 자기공명분광법(dMRS)을 통해 신생아 흰쥐의 소뇌와 시상에서 세포 특이적 발달 궤적을 비침습적으로 추적할 수 있다.


It is currently impossible to non-invasively assess cerebellar cell structure during early development. Here we propose a novel approach to non-invasively and longitudinally track cell-specific development using diffusion-weighted magnetic resonance spectroscopy in combination with microstructural modelling. Tracking metabolite diffusion allows us to probe cell-specific developmental trajectories in the cerebellum and thalamus of healthy rat neonates from post-natal day (P) 5 to P30. Additionally, by comparing different analytical and biophysical microstructural models we can follow the differential contribution of cell bodies and neurites during development. The thalamus serves as a control region to assess the sensitivity of our method to microstructural differences between the regions. We found significant differences between cerebellar and thalamic metabolites diffusion properties. For most metabolites, the signal attenuation is stronger in the thalamus, suggesting less restricted diffusion compared to the cerebellum. There is also a trend for lower signal attenuation and lower ADCs with increasing age, suggesting increasing restriction of metabolite diffusion. This is particularly striking for taurine in the thalamus. We use biophysical modelling to interpret these differences. We report a decreased sphere fraction (or an increased neurite fraction) with age for taurine and total creatine in the cerebellum, marking dendritic growth. Surprisingly, we also report a U-shape trend for segment length (the distance between two embranchments in a dendritic tree) in the cerebellum agreeing with age-matching morphometry of openly available 3D-Purkinje reconstructions. Results demonstrate that diffusion-weighted MRS probes early cerebellar neuronal development non-invasively.

### Competing Interest Statement

The authors have declared no competing interest.

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates

신생아-흰쥐의-소뇌와-시상에서-신경-발달의-다양한-궤적을-추적하는-확산-mrs


신생아 흰쥐의 소뇌와 시상에서 신경 발달의 다양한 궤적을 추적하는 확산 MRS
