Warfare, Christianity, and the Law of Nature.

Early modern efforts to justify warfare entailed serious reflection on the relationship between Christianity and nature or natural law. Those working in a Thomist tradition could draw on a concept of natural law as an ethical system distinct from Christianity; others rejected that concept, working instead to show that warfare could form part of the duties of Christians. All sides recognized the tension between the words of Christ and the demands of human political life, especially when it came to defending military activity.

Onychodystrophy as the Presenting Sign of Steal Syndrome.

A man in his 70s presented to the dermatology nail clinic with a 1-month history of worsening onychodystrophy, leukonychia, and pain in his left fifth finger. Physical examination revealed a cool hand and absent radial pulse. Ischemia was suspected, and the patient was sent to the emergency department where the diagnosis of steal syndrome was made and his previously required arteriovenous fistula was ligated.

Distribution of Dermatologists in Wisconsin: How Are We Doing in Providing Care to Our Most Vulnerable Communities.

Background: The specialty of dermatology has not been affected by initiatives to help recruit physicians rurally, even with the rising demand for dermatology services. The geographic density of dermatologists is distributed unevenly across the nation; however, the distribution has not been analyzed at the state level for Wisconsin.

Methods: We analyzed geographic distribution information obtained from the American Academy of Dermatology.

Temperature effects on the activity, shape, and storage of platelets from 13-lined ground squirrels.

The objective of this study is to determine how a hibernating mammal avoids the formation of blood clots under periods of low blood flow. A microfluidic vascular injury model was performed to differentiate the effects of temperature and shear rate on platelet adhesion to collagen. Human and ground squirrel whole blood was incubated at 15 or 37 °C and then passed through a microfluidic chamber over a 250-µm strip of type I fibrillar collagen at that temperature and the shear rates of 50 or 300 s to simulate torpid and aroused conditions, respectively.

The effects of a skeletal muscle titin mutation on walking in mice.

Titin contributes to sarcomere assembly, muscle signaling, and mechanical properties of muscle. The mdm mouse exhibits a small deletion in the titin gene resulting in dystrophic mutants and phenotypically normal heterozygotes. We examined the effects of this mutation on locomotion to assess how, and if, changes to muscle phenotype explain observed locomotor differences.

Botanicals in Dermatology: Essential Oils, Botanical Allergens, and Current Regulatory Practices.

Largely because of their perceived safety, the use of essential oils and other botanically derived products has become increasingly popular. Recent evidence raises concern about the safety of these products, frequently found in cosmetics and sought as an alternative to standard medical treatments. Essential oils are challenging to standardize because of the variable growing conditions, genetics, and harvesting of botanicals.

HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism.

Mammalian class II major histocompatibility (MHCII) proteins bind peptide antigens in endosomal compartments of antigen-presenting cells. The nonclassical MHCII protein HLA-DM chaperones peptide-free MHCII, protecting it against inactivation, and catalyzes peptide exchange on loaded MHCII. Another nonclassical MHCII protein, HLA-DO, binds HLA-DM and influences the repertoire of peptides presented by MHCII proteins.

Mapping the HLA-DO/HLA-DM complex by FRET and mutagenesis.

HLA-DO (DO) is a nonclassic class II heterodimer that inhibits the action of the class II peptide exchange catalyst, HLA-DM (DM), and influences DM localization within late endosomes and exosomes. In addition, DM acts as a chaperone for DO and is required for its egress from the endoplasmic reticulum (ER). These reciprocal functions are based on direct DO/DM binding, but the topology of DO/DM complexes is not known, in part, because of technical limitations stemming from DO instability.

IMP dehydrogenase type 1 associates with polyribosomes translating rhodopsin mRNA.

IMP dehydrogenase (IMPDH) catalyzes the pivotal step in guanine nucleotide biosynthesis. Here we show that both IMPDH type 1 (IMPDH1) and IMPDH type 2 are associated with polyribosomes, suggesting that these housekeeping proteins have an unanticipated role in translation regulation. This interaction is mediated by the subdomain, a region of disputed function that is the site of mutations that cause retinal degeneration.

Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis.

Purpose: The purpose of this study was to determine the frequency and spectrum of inosine monophosphate dehydrogenase type I (IMPDH1) mutations associated with autosomal dominant retinitis pigmentosa (RP), to determine whether mutations in IMPDH1 cause other forms of inherited retinal degeneration, and to analyze IMPDH1 mutations for alterations in enzyme activity and nucleic acid binding.

Methods: The coding sequence and flanking intron/exon junctions of IMPDH1 were analyzed in 203 patients with autosomal dominant RP (adRP), 55 patients with autosomal recessive RP (arRP), 7 patients with isolated RP, 17 patients with macular degeneration (MD), and 24 patients with Leber congenital amaurosis (LCA). DNA samples were tested for mutations by sequencing only or by a combination of single-stranded conformational analysis and by sequencing.

Autosomal dominant retinitis pigmentosa mutations in inosine 5'-monophosphate dehydrogenase type I disrupt nucleic acid binding.

Two mutations of IMPDH1 (inosine 5'-monophosphate dehydrogenase type I), R224P and D226N, have recently been found to cause adRP (autosomal dominant retinitis pigmentosa). IMPDH1 catalyses the rate-limiting step in guanine nucleotide biosynthesis and also binds single-stranded nucleic acids. In the present paper, we report the biochemical characterization of the adRP-linked mutations, R224P and D226N, and a potentially pathogenic mutation, V268I.

Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides. In addition to the catalytic domain, IMPDH contains a subdomain of unknown function composed of two cystathione beta-synthase domains. Our results, using three different assays, show that IMPDHs from Tritrichomonas foetus, Escherichia coli, and both human isoforms bind single-stranded nucleic acids with nanomolar affinity via the subdomain.