Low-shot learning methods for image classification support learning from sparse data. We extend these techniques to support dense semantic image segmentation. Specifically, we train a network that, given a small set of annotated images, produces parameters for a Fully Convolutional Network (FCN). We use this FCN to perform dense pixel-level prediction on a test image for the new semantic class. Our architecture shows a 25% relative meanIoU improvement compared to the best baseline methods for one-shot segmentation on unseen classes in the PASCAL VOC 2012 dataset and is at least 3× faster. The code is publicly available at: https://github.com/lzzcd001/OSLSM.

Transforming growth factor (TGF)-β family members are multifunctional cytokines that elicit their effects on cells, including endothelial and mural cells, via specific type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. Knock-out mouse models for TGF-β family signaling pathway components have revealed their critical importance in proper yolk sac angiogenesis. Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular syndromes such as hereditary hemorrhagic telangiectasia, primary pulmonary hypertension and Marfan syndrome. In this review, we present recent advances in our understanding of the role of TGF-β receptor signaling in vascular biology and disease, and discuss how this may be applied for therapy.

Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting in part due to inadequate databases used in intake estimation. A database of nine phytoestrogens in foods relevant to Western diets was developed to more accurately estimate intakes. Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data were presented on an as is (wet) basis per 100 g and per serving. Food groups with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds, soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages. Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads, legumes, fruits, vegetables, soy products, processed foods, alcoholic, and nonalcoholic beverages. The richest sources of specific phytoestrogens, including coumestrol, were identified. The database will improve phytoestrogen intake estimation in future epidemiological and clinical studies particularly in Western populations.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.

Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome. We found no significant improvement of the targeting efficiency by the HMEJ-based method in either mouse embryonic stem cells or the neuroblastoma cell line, N2a, compared to the HR-based method. However, the HMEJ-based method yielded a higher knock-in efficiency in HEK293T cells, primary astrocytes and neurons. More importantly, this approach achieved transgene integration in mouse and monkey embryos, as well as in hepatocytes and neurons in vivo, with an efficiency much greater than HR-, NHEJ- and MMEJ-based strategies. Thus, the HMEJ-based strategy may be useful for a variety of applications, including gene editing to generate animal models and for targeted gene therapies.