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A comprehensive collection of mouse major histocompatibility complex (MHC) promoter and exon 2 sequences is here presented and analysed. It covers the three best known class II genes and one class I gene, and includes new wild mouse sequences from the ‘w’ back-cross strains and from the Jackson collection. All sequences are in GenBank, and the new exon sequences largely confirm previous typing by serology and immune function. As in human leucocyte antigen (HLA), the overall nucleotide diversity is higher in the class II genes, in keeping with their more diverse function. Diversity along the promoters is highest in the region of known transcription factor binding, most notably in and around the CRE and rCAAT sequences. This distribution parallels that of maximum single nucleotide polymorphism impact previously obtained with reporter constructs. Taking into account the low nucleotide diversity of the CIITA promoter, we conclude that MHC promoters are likely to have diversified through co-evolution with their exons, while themselves also directly subject to natural selection. The H2Ebp alleles form a distinct group, associated with their lack of the recombination hot spot located between exon 2 and exon 3. The collection is expected to prove useful in guiding functional and evolutionary studies. [ABSTRACT FROM AUTHOR]

The leading political–economy–of–trade models are virtually silent on two fundamental questions raised by Rodrik in 1995. Why are trade policies systematically biased against trade? And why are tariffs rather than more efficient production subsidies adopted to redistribute income? This paper shows that systematic political grass–root support for trade–restricting and inefficient tariffs emerges when the government has a revenue goal and collecting taxes is costly. Even if no tax instrument enjoys an advantage with respect to collection costs and the factor ownership distribution is unbiased, more people support tariffs than import or production subsidies. More generally, the presence of tax–collection costs creates a grass–root support bias for taxes over subsidies as instruments to redistribute income. [ABSTRACT FROM AUTHOR]

The α2 -macroglobulin (A2M) and the complement components C3 and C4 are related proteins derived from a common ancestor. Theoretically, this derivation could have occurred either by tandem duplications of their encoding genes or by polyploidization involving chromosomal segments, a chromosome or the whole genome. In tetrapods the A2M -, C3 - and C4 -encoding genes are generally each located on a different chromosome. This observation has been interpreted as supporting their origin by polyploidization. We identified and mapped (with the help of a radiation hybrid panel of cell lines) the A2M , C3 and C4 loci in the zebrafish, Danio rerio . Each of the three types of loci is present in the zebrafish in multiple copies, but all of the identified copies of a given type map to the same region in linkage groups 1 ( C3 ) and 15 ( A2M , C4 ). The A2M and C4 loci are mapped in the same region not linked to any of the class I or class II major histocompatibility complex ( Mhc ) loci. These observations are interpreted as supporting the origin of the A2M family of genes by tandem duplications, followed by the dispersal of the copies to different chromosomes. It is also argued that the association of C4 with the class I/II loci in tetrapods is accidental and without functional significance. [ABSTRACT FROM AUTHOR]

The jawless Agnatha (lampreys and hagfishes) represent the phylogenetically oldest order of vertebrates that are believed to lack the adaptive immune system of jawed vertebrates. In order to search for molecular markers specific for cellular components of the adaptive immune system in lampreys, we used the polymerase chain reaction (PCR) to identify genes for transcription factors of the Ikaros family in genomic DNA and cDNA libraries from two species of lampreys, Petromyzon marinus and Lampetra fluviatilis . The mammalian Ikaros-like family of transcription factors consists of five members, Ikaros, Helios, Aiolos, Eos and Pegasus, of which the first three appear to be essential for lymphocyte development. Two different Ikaros -like genes, named IKLF1 and IKLF2 , were identified in lamprey. They both have the conserved exon–intron structure of seven exons and show alternative splicing like their counterparts in jawed vertebrates. The genes code for predicted proteins of 589 and 513 amino acid residues, respectively. The proteins contain six highly conserved zinc finger motifs that are 83–91% identical to the mammalian members of the Ikaros-like family. The remaining parts of the sequences are, however, mostly unalignable. Phylogenetic analysis based on the alignable segments of the sequences does not identify the orthologous gene in jawed vertebrates but rather shows equidistance of the lamprey Ikaros-like factors to each other and to Ikaros, Helios, Aiolos and Eos. Expression studies by reverse transcription (RT)–PCR and in situ hybridization (ISH), however, provide evidence for moderate expression in presumed lymphoid tissues like the gut epithelium and for high levels of expression in the gonads, especially in the ovary. [ABSTRACT FROM AUTHOR]

Background: Allogeneic 2-unit RBC apheresis is a safe procedure offering many advantages for donors and blood banks. A controlled study was performed to determine whether the recommended minimum interval of 4 months between 2-unit RBC apheresis donations is appropriate in terms of the recovery of RBCs and the regeneration of iron stores.Study Design and Methods: Twenty male subjects each donated 2 units of RBCs by apheresis. The RBC count, reticulocyte count, EPO, and measures of iron status were analyzed before and during the 4 months after donation.Results: A significant decrease in Hb (15.89 +/- 0.82 [mean +/- SD] vs. 14.08 +/- 0.97 mg/dL, baseline vs. Day 7; p<0.001) was equalized within 2 months. In contrast, ferritin values declined significantly from 54.2 +/- 33.7 to 23.42 +/- 21.94 microg per L (predonation vs. Day 30) and remained significantly below predonation values, but within the normal range, until the end of the study period.Conclusion: A donation interval of 4 months is appropriate in terms of RBC recovery, but may not be appropriate in terms of iron store regeneration. The tendency to shorten the donation interval should be reconsidered in light of the measurements of iron storage. The use of ferritin levels is recommended as a preselection criterion for allogeneic 2-unit RBC apheresis. [ABSTRACT FROM AUTHOR]

Purpose To assess the effect of EGFR Inhibitor Erlotinib and the downstream Inhibitor Erufosin ( PI3K) soaked into intraocular lenses ( IOLs) on human lensepithelialcell ( LEC) proliferation in vitro. Methods Foldable IOLs were incubated with Erufosin or Erlotinib. Intraocular lenses of the same lot served as uncoated controls. Each IOL was placed into cell cultre containing proliferating human LECs. Cell survival was tested by the XTT-dye reduction assay 5 days later. Furthermore IOLs were put into the Gotoh anterior chamber model. In addition, soaked IOLs were implanted into the human capsular bags and braught to cell-culture. The time until full cell-coverage of the capsular bag was measured. Results Erufosin (P<0.05) and Erlotinib (P<0.05) coated IOLs attenuated human LEC proliferation in all above described models. For both substances soaked hydrophilic acrylic IOLs were more effective inhibitors of human LEC proliferation than coated hydrophobic acrylic. Conclusions Results show that both substances are suitable agents for IOL-soaking without linker molecules. Soaked IOLs can inhibit human LEC proliferation in our models and might become of clinical relevance in future. [ABSTRACT FROM AUTHOR]

Purpose: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Erlotinib is an inhibitor of the epidermal growth factor-Receptor and reduces critical cellular events leading to PCO. In this in vitro study, Erlotinib-modified intraocular lenses (IOLs) employed as a drug delivery device have been evaluated for PCO prevention., Methods: The IC 50 concentration of Erlotinib was determined by using FHL-124 cells. For the human capsular bag model, 40 cadaver eyes underwent sham cataract surgery. Sixteen capsular bags were exposed to the IC 50 of Erlotinib. Intraocular lens (IOL) of three different materials was pharmacologically modified and tested in the anterior segment model and implanted into 24 capsular bags. To test for corneal toxicity, pairs of human cornea were exposed to high concentrations of Erlotinib and corneal endothelial cells (CEC) were exposed to the modified IOL. Release kinetics of Erlotinib from the IOL was measured., Results: IC 50 of Erlotinib was determined to be 10 μm. Erlotinib alone (p = 0.002) and when soaked into IOLs (p < 0.001) significantly increased the number of days needed until total cell coverage of the capsular bags in comparison with the control. Modified IOLs mitigated cell growth in the anterior segment model (p < 0.001). No short-term corneal toxicity was observed up to a concentration of 100 μm, and IOLs did not show toxicity on CEC. Erlotinib was released constantly from IOL., Conclusion: Erlotinib might be of clinical relevance in PCO prophylaxis, as its short-term application induces a long-term deceleration of cellular growth. Erlotinib can be introduced into the eye via soaked IOLs., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)