Measures for the Assessment of Pain in Adults

Peer reviewedPublisher PD

Genomic data of different resolutions reveal consistent inbreeding estimates but contrasting homozygosity landscapes for the threatened Aotearoa New Zealand hihi

Inbreeding can lead to a loss of heterozygosity in a population and when combined with genetic drift may reduce the adaptive potential of a species. However, there is uncertainty about whether resequencing data can provide accurate and consistent inbreeding estimates. Here, we performed an in-depth inbreeding analysis for hihi (Notiomystis cincta), an endemic and nationally vulnerable passerine bird of Aotearoa New Zealand. We first focused on subsampling variants from a reference genome male, and found that low-density data sets tend to miss runs of homozygosity (ROH) in some places and overestimate ROH length in others, resulting in contrasting homozygosity landscapes. Low-coverage resequencing and 50 K SNP array densities can yield comparable inbreeding results to high-coverage resequencing approaches, but the results for all data sets are highly dependent on the software settings employed. Second, we extended our analysis to 10 hihi where low-coverage whole genome resequencing, RAD-seq and SNP array genotypes are available. We inferred ROH and individual inbreeding to evaluate the relative effects of sequencing depth versus SNP density on estimating inbreeding coefficients and found that high rates of missingness downwardly bias both the number and length of ROH. In summary, when using genomic data to evaluate inbreeding, studies must consider that ROH estimates are heavily dependent on analysis parameters, data set density and individual sequencing depth

Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge

Research Funding Wellcome Trust, UK. Grant Numbers: 086827, 080088 NIH. Grant Number: DE022550Peer reviewedPublisher PD

The role of environmental distractions in the experience of fibrofog in real-world settings

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (award K01‐AR‐064275; Principal Investigator, Dr. Kratz). The Michigan Institute for Clinical & Health Research (NIH award UL1‐TR‐002240) provided subject recruitment support through the UMHealthResearch.org website.Peer reviewedPublisher PD

Anti-oesophageal cancer activity in extracts of deep-water Marion Island sponges

Oesophageal cancer is one of the most common causes of cancer-related deaths in South African black males. The limited efficacy of chemotherapeutic agents to treat this disease has prompted a search for potential new chemical entities with anticancer properties. We report here on the evidence for anti-oesophageal cancer activity in the methanolic extracts of five species of sponges dredged from a depth of approximately 100 m in the vicinity of Marion Island in the Southern Ocean during the autumn of 2004

Fibrofog in daily life : An examination of ambulatory subjective and objective cognitive function in fibromyalgia

Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (award number K01AR064275; PI: Kratz). The Michigan Institute for Clinical & Health Research (MICHR: NIH award number UL1TR002240) provided subject recruitment support through the UMHealthResearch.org website. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Peer reviewedPostprin

Effect of pain on mood affective disorders in adults with cerebral palsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155961/1/dmcn14559_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155961/2/dmcn14559.pd

Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation.

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation

Characterization of Novel and Uncharacterized p53 SNPs in the Chinese Population – Intron 2 SNP Co-Segregates with the Common Codon 72 Polymorphism

Multiple single nucleotide polymorphisms (SNPs) have been identified in the tumor suppressor gene p53, though the relevance of many of them is unclear. Some of them are also differentially distributed in various ethnic populations, suggesting selective functionality. We have therefore sequenced all exons and flanking regions of p53 from the Singaporean Chinese population and report here the characterization of some novel and uncharacterized SNPs - four in intron 1 (nucleotide positions 8759/10361/10506/11130), three in intron 3 (11968/11969/11974) and two in the 3′UTR (19168/19514). Allelic frequencies were determined for all these and some known SNPs, and were compared in a limited scale to leukemia and lung cancer patient samples. Intron 2 (11827) and 7 (14181/14201) SNPs were found to have a high minor allele frequency of between 26–47%, in contrast to the lower frequencies found in the US population, but similar in trend to the codon 72 polymorphism (SNP12139) that shows a distribution pattern correlative with latitude. Several of the SNPs were linked, such as those in introns 1, 3 and 7. Most interestingly, we noticed the co-segregation of the intron 2 and the codon 72 SNPs, the latter which has been shown to be expressed in an allele-specific manner, suggesting possible regulatory cross-talk. Association analysis indicated that the T/G alleles in both the co-segregating intron 7 SNPs and a 4tagSNP haplotype was strongly associated increased susceptibility to lung cancer in non-smoker females [OR: 1.97 (1.32, 3.394)]. These data together demonstrate high SNP diversity in p53 gene between different populations, highlighting ethnicity-based differences, and their association with cancer risk

Lack of Wdr13 Gene in Mice Leads to Enhanced Pancreatic Beta Cell Proliferation, Hyperinsulinemia and Mild Obesity

WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes