Comparison of Mouse Ly5a and Ly5b Leucocyte Common Antigen Alleles

The family of leucocyte common antigen (LCA) transmembrane glycoproteins is expressed in most hematopoietic cells. Molecular isoforms of the LCA molecule are generated by alternative splicing of a single gene encoded on the murine chromosome 1. Three LCA alleles with different antigenic reactivities have been identified in inbred mouse strains. To investigate the divergence between alleles, cDNA clones to the SJA (Ly5a) LCA gene have been isolated and sequenced. A comparison of this information to the Ly5b allele sequence identifies 12 allele-specific nucleotide changes. These base substitutions correspond to five amino-acid changes within the extracellular domain of the LCA molecule. These amino-acid differences are clustered in a region that also contains the greatest divergence between mouse and rat LCA sequences. Thus, these two mouse LCA alleles exhibit a pattern of sequence conservation that mimics that found over a much broader scale of evolution. Analysis of antigenicity profiles for each of the allelic sequence changes reveals three molecular domains of altered antigenicity that could account for observed serological differences between the two alleles. Sequence information from the 5' end of the Ly5a LCA gene, generated using polymerase chain-reaction techniques on genomic DNA, reveals eight additional nucleotide differences between the Ly5a and Ly5b alleles

Generating a high-resolution global magnetic model for oil and mineral exploration

This is the final contribution to the trilogy of articles on global potential-field data compilations. Getech's continental and national magnetic data compilations commenced in 1989 and were designed specifically for use in petroleum and mineral exploration. These studies complemented the continental-scale gravity-compilation studies that were the subject of the TLE “Meter Reader” contributions in March and May of this year. The success of these projects resulted from strategic partnerships, especially with Paterson, Grant and Watson Ltd. (PGW), and links to a wide range of national organizations. Early compilations covering the whole of Africa, South America, and China were followed by large-scale, small-scale, and national compilations and continue to this day with compilations of U. S. surveys. The projects spawned a range of technical developments, including approaches to remove survey-line noise, the integration of survey grids and disparate ship-track data, and the preservation of the longest-wavelength anomalies associated with the crustal magnetic field. The resulting global gravity and magnetic grids now form an invaluable resource for resource exploration

Letter: are opioid prescriptions associated with hepatic encephalopathy in patients with compensated cirrhosis? Authors’ reply

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/1/apt15669.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/2/apt15669_am.pd

Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA

The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother–child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site). On average, each individual carried one heteroplasmy, and one in eight individuals carried a disease-associated heteroplasmy, with minor allele frequency ≥1%. We observed frequent drastic heteroplasmy frequency shifts between generations and estimated the effective size of the germ-line mtDNA bottleneck at only ∼30–35 (interquartile range from 9 to 141). Accounting for heteroplasmies, we estimated the mtDNA germ-line mutation rate at 1.3 × 10−8 (interquartile range from 4.2 × 10−9 to 4.1 × 10−8) mutations per site per year, an order of magnitude higher than for nuclear DNA. Notably, we found a positive association between the number of heteroplasmies in a child and maternal age at fertilization, likely attributable to oocyte aging. This study also took advantage of droplet digital PCR (ddPCR) to validate heteroplasmies and confirm a de novo mutation. Our results can be used to predict the transmission of disease-causing mtDNA variants and illuminate evolutionary dynamics of the mitochondrial genome

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/1/apt15639_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/2/apt15639.pd

Declining liver graft quality threatens the future of liver transplantation in the United States

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of "opt-out" organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level

Antigenic and structural differences among six proteins II expressed by a single strain of Neisseria gonorrhoeae.

Gonococci express a family of related outer membrane proteins designated protein II (P.II), which undergo both phase and antigenic variation. Six P.II proteins have been identified in strain FA1090. We developed monoclonal antibodies specific for each P.II protein. Using these antibodies as probes, we purified the six different P.II proteins of this strain. Despite the relatedness of the proteins, we could not purify all of them by a single purification scheme. Four P.II proteins were purified by chromatofocusing, and the remaining two proteins were purified by hydrophobic interaction chromatography on phenyl-Sepharose. The N-terminal amino acid sequence of the proteins showed a high degree of sequence conservation. However, there was variability at specific amino acid residues, giving each P.II protein a unique N-terminal amino acid sequence. Thus P.II proteins of one strain differ among themselves not only in antigenic determinants and primary structure, but also in other characteristics affecting their properties in different chromatographic systems

Decreasing Mortality Among Patients Hospitalized With Cirrhosis in the United States From 2002 Through 2010

It is not clear whether evidence-based recommendations for inpatient care of patients with cirrhosis are implemented widely or are effective in the community. We investigated changes in inpatient outcomes and associated features over time

Declining liver utilization for transplantation in the United States and the impact of donation after cardiac death

Worsening donor liver quality resulting in decreased organ utilization may be contributing to the recent decline in liver transplants nationally. We sought to examine trends in donor liver utilization and the relationship between donor characteristics and non-use. We used the United Network for Organ Sharing database to review all deceased adult organ donors in the United States who had at least one solid organ transplanted into a recipient. Trends in donor characteristics were examined. Multivariate logistic regression was used to evaluate the association between donor characteristics and liver non-use between 2004 and 2010. Population attributable risk proportions were determined for donor factors associated with non-use. 107,259 organ donors were analyzed. The number of unused livers decreased steadily from 1,958 (66% of donors) in 1988 to 841 (15%) in 2004, but then gradually increased to 1,345 (21%) in 2010. Donor age, body mass index (BMI), and the prevalence of diabetes and donation after cardiac death (DCD) all increased over time, and all four were independently associated with liver non-use. DCD had the highest adjusted odds ratio (OR) for non-use, and the odds increased nearly four-fold between 2004 (OR 5.53; 95% CI, 4.57–6.70) and 2010 (OR 21.31; 95% CI, 18.30–24.81). The proportion of non-use attributable to DCD increased from 9% in 2004 to 28% in 2010. The proportion of donor livers not used has increased since 2004. Older donor age, greater BMI, diabetes, and DCD are all independently associated with non-use and are on the rise nationally. Current trends may lead to significant declines in liver transplant availability