A cross-center smoothness prior for variational Bayesian brain tissue segmentation

Suppose one is faced with the challenge of tissue segmentation in MR images, without annotators at their center to provide labeled training data. One option is to go to another medical center for a trained classifier. Sadly, tissue classifiers do not generalize well across centers due to voxel intensity shifts caused by center-specific acquisition protocols. However, certain aspects of segmentations, such as spatial smoothness, remain relatively consistent and can be learned separately. Here we present a smoothness prior that is fit to segmentations produced at another medical center. This informative prior is presented to an unsupervised Bayesian model. The model clusters the voxel intensities, such that it produces segmentations that are similarly smooth to those of the other medical center. In addition, the unsupervised Bayesian model is extended to a semi-supervised variant, which needs no visual interpretation of clusters into tissues.Comment: 12 pages, 2 figures, 1 table. Accepted to the International Conference on Information Processing in Medical Imaging (2019

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Thrombus or tumor? a case of fibroelastoma as indicated during the submission process

We describe the case of a 50-year-old woman who was admitted to a pheriferal department for heart failure. The echocardiography revealed a small mass measuring about 1.3 × 1.0 cm adhering to the non-coronary cusp of the aortic valve, mild dilated cardiomiopathy and severe biventricular dysfunction. This mass had erroneously been considered a thrombotic lesion, so the patient was treated with thrombolysis and heparin e.v. Only after a transoesophageal echocardiography a tumour cardiac mass was suspected. The diagnosis of fibroelastoma was confirmed by MRI and then from the anatomic and histoligical definition after surgery

Preliminary Report: Missense mutations in the APOL gene family are associated with end stage kidney disease risk previously attributed to the MYH9 gene

MYH9 has been proposed as a major genetic risk locus for a spectrum of non-diabetic end stage kidney disease (ESKD). We use recently released sequences from the 1000 Genomes Project to identify two western African specific missense mutations (S342G and I384M) in the neighbouring APOL1 gene, and demonstrate that these are more strongly associated with ESKD than previously reported MYH9 variants. We also show that the distribution of these risk variants in African populations is consistent with the pattern of African ancestry ESKD risk previously attributed to the MYH9 gene. Additional associations were also found among other members of the APOL gene family, and we propose that ESKD risk is caused by western African variants in members of the APOL gene family, which evolved to confer protection against pathogens, such as Trypanosoma.Comment: 25 pages, 6 figure

The Teleost Retina as a Model for Developmental and Regeneration Biology

Retinal development in teleosts can broadly be divided into three epochs. The first is the specification of cellular domains in the larval forebrain that give rise to the retinal primordia and undergo early morphogenetic movements. The second is the neurogenic events within the retina proper—proliferation, cell fate determination, and pattern formation—that establish neuronal identities and form retinal laminae and cellular mosaics. The third, which is unique to teleosts and occurs in the functioning eye, is stretching of the retina and persistent neurogenesis that allows the growth of the retina to keep pace with the growth of the eye and other tissues. The first two events are rapid, complete by about 3 days postfertilization in the zebrafish embryo. The third is life-long and accounts for the bulk of retinal growth and the vast majority of adult retinal neurons. In addition, but clearly related to the retina's developmental history, lesions that kill retinal neurons elicit robust neuronal regeneration that originates from cells intrinsic to the retina. This paper reviews recent studies of retinal development in teleosts, focusing on those that shed light on the genetic and molecular regulation of retinal specification and morphogenesis in the embryo, retinal neurogenesis in larvae and adults, and injury-induced neuronal regeneration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63365/1/zeb.2004.1.257.pd

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Water quality monitoring records for estimating tap water arsenic and nitrate: a validation study

<p>Abstract</p> <p>Background</p> <p>Tap water may be an important source of exposure to arsenic and nitrate. Obtaining and analyzing samples in the context of large studies of health effects can be expensive. As an alternative, studies might estimate contaminant levels in individual homes by using publicly available water quality monitoring records, either alone or in combination with geographic information systems (GIS).</p> <p>Methods</p> <p>We examined the validity of records-based methods in Washington State, where arsenic and nitrate contamination is prevalent but generally observed at modest levels. Laboratory analysis of samples from 107 homes (median 0.6 μg/L arsenic, median 0.4 mg/L nitrate as nitrogen) served as our "gold standard." Using Spearman's rho we compared these measures to estimates obtained using only the homes' street addresses and recent and/or historical measures from publicly monitored water sources within specified distances (radii) ranging from one half mile to 10 miles.</p> <p>Results</p> <p>Agreement improved as distance decreased, but the proportion of homes for which we could estimate summary measures also decreased. When including all homes, agreement was 0.05-0.24 for arsenic (8 miles), and 0.31-0.33 for nitrate (6 miles). Focusing on the closest source yielded little improvement. Agreement was greatest among homes with private wells. For homes on a water system, agreement improved considerably if we included only sources serving the relevant system (ρ = 0.29 for arsenic, ρ = 0.60 for nitrate).</p> <p>Conclusions</p> <p>Historical water quality databases show some promise for categorizing epidemiologic study participants in terms of relative tap water nitrate levels. Nonetheless, such records-based methods must be used with caution, and their use for arsenic may be limited.</p