Molecular basis of evolutionary loss of the α1,3-galactosyltransferase gene in higher primates

Galactose-α1,3-galactose (αGal) epitopes, the synthesis of which requires the enzyme product of α1,3-galactosyltransferase (α1,3GT), are sugar chains on the cell surface of most mammalian species. Notable exceptions are higher primates including Old World monkeys, apes, and humans. The αGal-negative species as well as mice with deletion of the α1,3GT gene produce abundant anti-αGal antibodies. The evolutionary loss of αGal epitopes has been attributed to point mutations in the coding region of the gene. Because no transcripts could be found in the higher primate species with Northern blot analysis, a potential alternative explanation has been loss of upstream regulation of the gene. Here, we have demonstrated that the rhesus promoter is functional. More importantly, a variety of full-length transcripts were detected with sensitive PCR-based methods in the tissues of rhesus monkeys, orangutans, and humans. Five crucial mutations were delineated in the coding region of the human and rhesus and three in the orangutan, any one of which could be responsible for inactivation of the α1,3GT gene. Two of the mutations were shared by all three higher primates. These findings, which elucidate the molecular basis for the evolutionary loss of αGal expression, may have implications in medical research

Deconstructing Gendered vumilia (perseverance) Theology in times of the Gender-based Violence Pandemic

During the COVID-19 pandemic, cases of gender-based violence (GBV) dramatically increased. While the Kenyan governmental bodies are held responsible for their inadequate response to this “national disaster of GBV”, the role of the Kenyan churches is hardly criticized. The churches neither spoke out against this prevalent injustice, nor did they openly support the victims of GBV. Furthermore, it could be argued that churches, through their patriarchal structures and cultural and doctrinal teachings, have contributed to this disaster. This article is written from a woman’s perspective and focused on the notion of vumilia, or perseverance, an important notion in the lived faith of women. Vumilia is the Kiswahili word for “persevere” or “endure.” It appears that a gendered vumilia theology applied to gender relations, prevents churches from adequately addressing gender-based violence. Unless and until this vumilia theology is deconstructed and balanced with a liberation theology, the church’s response to gender-based violence will be superficial and insufficient. In this article, the narrative method is used to bring about the ideas and experiences of women in two Kenyan churches, the Reformed Church of East Africa (RCEA) and the African Israel Nineveh Church (AINC), related to vumilia and its cultural and theological underpinnings. The article discusses the teachings of vumilia theology in these churches and their effects on women who suffer from gender-based violence. The paper also traces the resistance of church women, indicating the contours of a woman-affirming Christ-centered theology and spirituality

Isolation of the regulatory regions and genomic organization of the porcine α1,3-galactosyltransferase gene¹

Background. α1,3-galactosyltransferase (α1,3GT) is an enzyme that produces carbohydrate chains termed αGal epitopes found in most mammals, although some species of higher primates, including human, are notable exceptions. The evolutionary origin of the lost α1,3GT enzyme activity is not yet known, although it has been suggested that the promoter activity of this gene in the ancestors of higher primates was inactivated. Methods. We used 5'-or 3'-RACE, GenomeWalking, reverse transcriptase polymerase chain reaction (RT-PCR) and dual Luciferase reporter assay for identification of the full-length cDNA, which includes the transcription initiation site and the promoter region of porcine α1,3GT gene. Results. The region around exon 1 is guanine and cytosine (GC)-rich (about 70%), comprising a CpG island spanning more than 1.5 kbp. The 5'-flanking region of exon 1 contains multiple transcription factor consensus motifs, including GC-box, SP1, AP2, and GATA-box sites, in the absence of TATA or CAAT-box sequences. The entire gene consists of three 5' noncoding and six coding region exons spanning more than 52 kbp. Detailed analysis of α1,3GT transcripts revealed two major alternative splicing patterns in the 5'-untranslated region (5'-UTR) and evidence for minor splicing activity that occurs in a tissue-specific manner. Interspecies comparison of 5'-UTR shows minimal homology between porcine and routine sequences except for exon 2, which suggests that the regulatory regions differ among species. Conclusions. These observations have important implications for experiments involving genetic manipulation of the α1,3GT gene in transgenic animals in terms of promoter utilization, and particularly in genetically engineering cells for the animal cloning technology by nuclear transfer

Humans Lack iGb3 Due to the Absence of Functional iGb3-Synthase: Implications for NKT Cell Development and Transplantation

The glycosphingolipid isoglobotrihexosylceramide, or isogloboside 3 (iGb3), is believed to be critical for natural killer T (NKT) cell development and self-recognition in mice and humans. Furthermore, iGb3 may represent an important obstacle in xenotransplantation, in which this lipid represents the only other form of the major xenoepitope Galα(1,3)Gal. The role of iGb3 in NKT cell development is controversial, particularly with one study that suggested that NKT cell development is normal in mice that were rendered deficient for the enzyme iGb3 synthase (iGb3S). We demonstrate that spliced iGb3S mRNA was not detected after extensive analysis of human tissues, and furthermore, the iGb3S gene contains several mutations that render this product nonfunctional. We directly tested the potential functional activity of human iGb3S by expressing chimeric molecules containing the catalytic domain of human iGb3S. These hybrid molecules were unable to synthesize iGb3, due to at least one amino acid substitution. We also demonstrate that purified normal human anti-Gal immunoglobulin G can bind iGb3 lipid and mediate complement lysis of transfected human cells expressing iGb3. Collectively, our data suggest that iGb3S is not expressed in humans, and even if it were expressed, this enzyme would be inactive. Consequently, iGb3 is unlikely to represent a primary natural ligand for NKT cells in humans. Furthermore, the absence of iGb3 in humans implies that it is another source of foreign Galα(1,3)Gal xenoantigen, with obvious significance in the field of xenotransplantation

Functional factor VIII made with von Willebrand factor at high levels in transgenic milk

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88017/1/j.1538-7836.2011.04505.x.pd

Gestión del diseño de producto y capacidad de aprendizaje organizativo en varios tipos de empresas del sector cerámico

[ES] Este trabajo estudia la relación entre la gestión del diseño de producto y la capacidad de aprendizaje organizativo en el sector cerámico español. A partir de un estudio de casos comparativo en cuatro empresas del mencionado sector, se determina qué factores facilitadores del aprendizaje organizativo son esenciales para cada una de las fases de la gestión del diseño de producto: la fase analítico conceptual y la fase técnico creativa. El estudio de casos evidencia una relación directa y positiva entre dichos factores facilitadores de aprendizaje organizativo y la gestión del diseño de producto. En concreto, cuatro de ellos están asociados a la obtención de conocimiento del mercado, la empresa y la tecnología, lo cual está vinculado a la fase analítica-conceptual del proceso de diseño de producto. Otros diez factores estarían asociados a la divulgación y uso del conocimiento, lo cual estaría vinculado a la fase técnica-creativa o la dirección integral del proceso de diseño.[EN] The main contribution of this paper is the formulation of an alternative to experimental determination of loss factor and, consequently, to improve the predictions of airborne sound insulation for any type of monolithic or laminated glass. In addition, a review of the standards related to measurement of mechanical parameters of glass is carried out, with particular interest in laminated glass Indeed, one of the problems that arise in the current context of building acoustics is to meet the requirements of facades airborne sound insulation of existing Building Technical Code (BTC). It is known that the blind and the hollow part of the facade should be distinguished. The weakest part regarding to airborne sound insulation is the empty one (consisting of glass, woodwork and other elements). Choosing an adequate woodwork makes the glass surface become the limiting factor. The Constructive Elements Catalog (CEC) of the BTC, the UNE-EN 12758:2011 standard, as well as some, increasingly, data vendors provide information about airborne sound insulation for monolithic glass, laminated glass and double glazing. In the case of laminated glass, these data are limited only to those with a single intermediate layer, and also nonacoustic. Can therefore be said that there is a gap of knowledge in this regard. To obtain reliable predictions of airborne sound insulation of multilayer partitions, such as laminated glass, mechanical characteristics must be known, being loss factor one of the most important.Chiva, R.; Lapiedra, R.; Devece Carañana, CA.; Gil Pechuán, I. (2012). Gestión del diseño de producto y capacidad de aprendizaje organizativo en varios tipos de empresas del sector cerámico. Boletín de la Sociedad Española de Cerámica y Vidrio. 51(4):231-238. doi:10.3989/cyv.332012S23123851