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Every organ in the body requires blood vessels for efficient delivery of oxygen and nutrients, but independent vascular beds are highly specialized to meet the individual needs of specific organs. The vasculature of the brain is tightly sealed, with blood-brain barrier (BBB) properties developing coincident with neural vascularization. G protein-coupled receptor 124 (GPR124) (tumor endothelial marker 5, TEM5), an orphan member of the adhesion family of G protein-coupled receptors, was previously identified on the basis of its overexpression in tumor vasculature. Here, we show that global deletion or endothelial-specific deletion of GPR124 in mice results in embryonic lethality associated with abnormal angiogenesis of the forebrain and spinal cord. Expression of GPR124 was found to be required for invasion and migration of blood vessels into neuroepithelium, establishment of BBB properties, and expansion of the cerebral cortex. Thus, GPR124 is an important regulator of neurovasculature development and a potential drug target for cerebrovascular diseases.

BigNeuron is an open community bench-testing platform combining the expertise of neuroscientists and computer scientists toward the goal of setting open standards for accurate and fast automatic neuron reconstruction. The project gathered a diverse set of image volumes across several species representative of the data obtained in most neuroscience laboratories interested in neuron reconstruction. Here we report generated gold standard manual annotations for a selected subset of the available imaging datasets and quantified reconstruction quality for 35 automatic reconstruction algorithms. Together with image quality features, the data were pooled in an interactive web application that allows users and developers to perform principal component analysis t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and reconstruction data, and benchmarking of automatic reconstruction algorithms in user-defined data subsets. Our results show that image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. By benchmarking automatic reconstruction algorithms, we observed that diverse algorithms can provide complementary information toward obtaining accurate results and developed a novel algorithm to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms. Finally, to aid users in predicting the most accurate automatic reconstruction results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic reconstructions. Competing Interest Statement The authors have declared no competing interest. Footnotes * https://linusmg.shinyapps.io/BigNeuron_Gold166/ * https://neuroxiv.net/bigneuron/ * https://github.com/BigNeuron/BigNeuron-Wiki/wiki * https://github.com/lmanubens/BigNeuron

Advances in the field of antiangiogenesis therapy have clearly demonstrated that this approach can augment more traditional methods of cancer treatment which aim to destroy the tumor cells directly. Although antiangiogenic agents such as neutralizing anti-VEGF antibodies have revealed clear clinical utility in certain cancer types, disease inevitably progresses, highlighting the continued need for the development of more effective therapeutic agents. The successful development of novel antiangiogenic and vascular disrupting agents that specifically target the tumor vasculature depends on a detailed knowledge of the molecular signatures of the tumor vasculature. Several laboratories have exploited recent advances in proteomics and global gene expression analysis to uncover a variety of cell surface tumor endothelial markers (TEMs) that may prove useful in the design of novel strategies for targeting tumor vasculature. A better understanding of these TEMs is key to uncovering their potential role in angiogenesis as well as their suitability as therapeutic targets.

Lt. Gov. Anthony Brown reflected back on the O'Malley-Brown administration's appointment of 4,103 women leaders, which reportedly accounted for 42 percent of all appointees since 2007, noting that gender diversity was a priority in both Cabinet and executive leadership.

Does the candidate understand the proper use of grammar? Since we typically communicate with our virtual client members via email, it's important for our employees to be able to write. [...]when evaluating resumes, I'm checking spelling as well as small details such as the organization of the resume and their email address.

[...]when your day is done and, like William, you enjoy listening to music before you fall asleep, set your timer and change the \"when timer ends\" to \"stop playing.\"

Since that path sometimes resulted in a sale of the business, the next firm I joined formed a group that valued companies, prepared them for sale and subsequently consulted with the seller on the transaction price.

Conjure up the image of \"Leave It To Beaver\" and their telephone manners. . . and dare I say what happened if I forgot to take down the telephone number or the person's first AND last name?