Explore the vast range of titles available.

Objectives To evaluate bone marrow changes on knee magnetic resonance imaging (MRI) in patients with 3- to 6-week-long period of unloading. Methods MRI knee examinations were performed in 30 patients (14 men, 16 women; aged 20–53 years) at baseline and 5–10 weeks after immobilisation of the ipsilateral lower extremity; subsets of patients were examined at additional time-points. Ten volunteers (4 men, 6 women; aged 20–50 years) were studied as control cohort at two time-points. Bone marrow signal abnormalities were analysed according to: (1) severity, (2) signal alteration relative to hyaline cartilage, (3) morphology, (4) increased vascularity in the knee joint and (5) T1-signal alteration. Spearman’s rank correlation test (SRC) and Kendall’s tau (KT) were used to compare individual scores. Results All 30 patients presented abnormal bone marrow findings after unloading, which reached a peak at 10–25 weeks ( P <0.001). These findings decreased within 1 year ( P  < 0.001). High scores of severity were associated with confluent and patchy patterns of bone marrow (SCR = 0.923, P  < 0.001 and KT = 0.877, P <0.001). Conclusions Signal abnormalities of the bone marrow related to unloading are consistent findings and most prominent 10–25 weeks following immobilisation when both confluent and patchy hyperintense patterns are present. Key Points • Disuse is associated with hyperintense MRI signal alteration on fluid - sensitive sequence . • Disuse findings are more prominent at the patella and femoral epiphyses . • Disuse MRI findings appear to be characterised by a specific chronological pattern .

Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To systematically profile morpho-electric properties of mammalian neurons, we established a single-cell characterization pipeline using standardized patch-clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly accessible online database, the Allen Cell Types Database, to display these datasets. Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex, morphological properties were measured from 461 reconstructed neurons, and 452 neurons had both measurements available. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We established a taxonomy of morphologically and electrophysiologically defined cell types for this region of the cortex, with 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. There was good correspondence with previously defined transcriptomic cell types and subclasses using the same transgenic mouse lines.

Glioblastoma is the most lethal form of human brain cancer. The genomic alterations and gene expression profiles characterizing this tumor type have been widely studied. Puchalski et al. created the Ivy Glioblastoma Atlas, a freely available online resource for the research community. The atlas, a collaborative effort between bioinformaticians and pathologists, maps molecular features of glioblastomas, such as transcriptional signatures, to histologically defined anatomical regions of the tumors. The relationships identified in this atlas, in conjunction with associated databases of clinical and genomic information, could provide new insights into the pathogenesis, diagnosis, and treatment of glioblastoma. Science , this issue p. 660 An online resource maps the molecular genetic features of glioblastoma, a lethal brain cancer, to its anatomic features. Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor’s molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment.

The neocortex is disproportionately expanded in human compared with mouse 1 , 2 , both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth 3 . Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer’s disease 4 , 5 . Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease. Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey ( Macaca mulatta ) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey. A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex. Gene expression in the primate brain Following the publication of the mouse and human brain gene expression atlases in recent years, Ed Lein and colleagues now present a high-resolution transcriptional atlas of pre- and post-natal brain development for the rhesus monkey — the dominant non-human primate model for human brain development and disease. The data charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders. New whole-brain mapping resources With President Barack Obama's BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative now entering year two, this issue of Nature presents two landmark papers that mobilize 'big science' resources to the cause. Hongkui Zeng and colleagues present the first brain-wide, mesoscale connectome for a mammalian species — the laboratory mouse — based on cell-type-specific tracing of axonal projections. The wiring diagram of a complete nervous system has long been available for a small roundworm, but neuronal connectivity data for larger animals has been patchy until now. The new three-dimensional Allen Mouse Brain Connectivity Atlas is a whole-brain connectivity matrix that will provide insights into how brain regions communicate. Much of the data generated in this project will be of relevance to investigations of neural networks in humans and should help to further our understanding of human brain connectivity and its involvement in brain disorders. In a separate report Ed Lein and colleagues present a transcriptional atlas of the mid-gestational human brain at high spatial resolution, based on laser microdissection and DNA microarray technology. The structure and function of the human brain is largely determined by prenatal transcriptional processes that initiate gene expression, but our understanding of the developing brain has been limited. The new data set reveals transcriptional signatures for developmental processes associated with the massive expansion of neocortex during human evolution, and suggests new cortical germinal zones or postmitotic neurons as sites of dynamic expression for many genes associated with neurological or psychiatric disorders.

With approximately 1.2 million New Yorkers poised to gain health insurance coverage as a result of federal health reform, demand for primary care services is likely to increase greatly. The Affordable Care Act includes$11 billion in funding to enhance primary care access at community health centers. Recognizing a need and an opportunity, in August 2010 the New York State Health Foundation made a grant of nearly $ 400,000 to the Community Health Care Association of New York State to work with twelve health centers to develop successful proposals for obtaining and using these federal funds. Ultimately, eleven of the twelve sites are expected to receive $25.6 million in federal grants over a five-year period-a sixty-four-fold return on the foundation's investment. This article describes the strategy for investing in community health centers; identifies key project activities, challenges, and lessons; and highlights its next steps for strengthening primary care. [PUBLICATION ABSTRACT]

The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort.

Slowing the rate of growth of health spending is as critical a goal at the state level as it is at the national level. Philanthropy can hardly address this issue alone, yet it has an obligation to take on big and seemingly intractable problems. The New York State Health Foundation is committed to stimulating innovative and replicable approaches to bending the cost curve. This article describes how the foundation recently awarded six grants to support efforts related to payment reform, hospital readmissions, medical malpractice reform, palliative care, and the quantification of other cost containment approaches that could be pursued at the state level. [PUBLICATION ABSTRACT]