Alterations in ether lipid metabolism and the consequences for the mouse lipidome.

Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types.

Psychosocial and bioethical challenges and developments for the future of vascularized composite allotransplantation: A scoping review and viewpoint of recent developments and clinical experiences in the field of vascularized composite allotransplantation.

Vascularized Composite Allotransplantation (VCA) has evolved in recent years, encompassing hand, face, uterus, penile, and lower extremity transplantation. Accordingly, without centralized oversight by United States Organ Procurement and Transplantation Network (OPTN) or European Programs, centers have developed their own practices and procedures that likely vary, and accordingly, present different levels of rigor to the evaluation process, internationally. The importance of psychosocial factors in the selection process and treatment course has been widely recognized, and therefore, several approaches have been developed to standardize and guide care of VCA candidates and recipients.

Adaptations of the 3T3-L1 adipocyte lipidome to defective ether lipid catabolism upon Agmo knockdown.

Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), the only enzyme capable of cleaving the 1-O-alkyl ether bond of ether lipids. Expression and enzymatic activity of this enzyme can be detected in a variety of tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as a cofactor, and mice with reduced tetrahydrobiopterin levels have alterations in body fat distribution and blood lipid concentrations.

Essential role of a conserved aspartate for the enzymatic activity of plasmanylethanolamine desaturase.

Plasmalogens are an abundant class of glycerophospholipids in the mammalian body, with special occurrence in the brain and in immune cell membranes. Plasmanylethanolamine desaturase (PEDS1) is the final enzyme of plasmalogen biosynthesis, which introduces the characteristic 1-O-alk-1'-enyl double bond. The recent sequence identification of PEDS1 as transmembrane protein 189 showed that its protein sequence is related to a special class of plant desaturases (FAD4), with whom it shares a motif of 8 conserved histidines, which are essential for the enzymatic activity.

When the genome bluffs: a tandem duplication event during generation of a novel Agmo knockout mouse model fools routine genotyping.

Background: Genome editing in mice using either classical approaches like homologous recombination or CRISPR/Cas9 has been reported to harbor off target effects (insertion/deletion, frame shifts or gene segment duplications) that lead to mutations not only in close proximity to the target site but also outside. Only the genomes of few engineered mouse strains have been sequenced. Since the role of the ether-lipid cleaving enzyme alkylglycerol monooxygenase (AGMO) in physiology and pathophysiology remains enigmatic, we created a knockout mouse model for AGMO using EUCOMM stem cells but unforeseen genotyping issues that did not agree with Mendelian distribution and enzyme activity data prompted an in-depth genomic validation of the mouse model.

The gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens.

A significant fraction of the glycerophospholipids in the human body is composed of plasmalogens, particularly in the brain, cardiac, and immune cell membranes. A decline in these lipids has been observed in such diseases as Alzheimer's and chronic obstructive pulmonary disease. Plasmalogens contain a characteristic 1--alk-1'-enyl ether (vinyl ether) double bond that confers special biophysical, biochemical, and chemical properties to these lipids.

Geneva Statement on Heritable Human Genome Editing: The Need for Course Correction.

As public interest advocates, policy experts, bioethicists, and scientists, we call for a course correction in public discussions about heritable human genome editing. Clarifying misrepresentations, centering societal consequences and concerns, and fostering public empowerment will support robust, global public engagement and meaningful deliberation about altering the genes of future generations.

European Electronic Personal Health Records initiatives and vulnerable migrants: A need for greater ethical, legal and social safeguards.

The effective collection and management of personal data of rapidly migrating populations is important for ensuring adequate healthcare and monitoring of a displaced peoples' health status. With developments in ICT data sharing capabilities, electronic personal health records (ePHRs) are increasingly replacing less transportable paper records. ePHRs offer further advantages of improving accuracy and completeness of information and seem tailored for rapidly displaced and mobile populations.

Integrative Biology and Big-Data-Centrism: Mapping out a Bioscience Ethics Perspective with a S.W.O.T. Matrix.

In current biomedicine, omics technologies drive systems-oriented modes of research to achieve a more holistic and personalized view of health and disease. This shift in scientific approach co-occurs with an era of biocapitalism characterized by markets for biomaterial (e.g.

A novel assay for the introduction of the vinyl ether double bond into plasmalogens using pyrene-labeled substrates.

Plasmanylethanolamine desaturase (PEDS) (EC 1.14.99.

An Ethical Analysis of Assisted Reproduction Providers' Websites in Pakistan.

Assisted reproductive technologies (ARTs) and reproductive genetic technologies (RGTs) are intertwined and coevolving. These technologies are increasingly used to fulfill socially and culturally framed requests, for example, "family balancing," or to enable postmenopausal women or homosexual couples to have genetically linked children. The areas of ART and RGT are replete with ethical issues, because different social practices and legal regulations, as well as economic inequalities within and among countries, create vulnerable groups and, therefore, the potential for exploitation.

The Physarum polycephalum Genome Reveals Extensive Use of Prokaryotic Two-Component and Metazoan-Type Tyrosine Kinase Signaling.

Physarum polycephalum is a well-studied microbial eukaryote with unique experimental attributes relative to other experimental model organisms. It has a sophisticated life cycle with several distinct stages including amoebal, flagellated, and plasmodial cells. It is unusual in switching between open and closed mitosis according to specific life-cycle stages.

Cuticle integrity and biogenic amine synthesis in Caenorhabditis elegans require the cofactor tetrahydrobiopterin (BH4).

Tetrahydrobiopterin (BH4) is the natural cofactor of several enzymes widely distributed among eukaryotes, including aromatic amino acid hydroxylases (AAAHs), nitric oxide synthases (NOSs), and alkylglycerol monooxygenase (AGMO). We show here that the nematode Caenorhabditis elegans, which has three AAAH genes and one AGMO gene, contains BH4 and has genes that function in BH4 synthesis and regeneration. Knockout mutants for putative BH4 synthetic enzyme genes lack the predicted enzymatic activities, synthesize no BH4, and have indistinguishable behavioral and neurotransmitter phenotypes, including serotonin and dopamine deficiency.

Tetrahydrobiopterin and alkylglycerol monooxygenase substantially alter the murine macrophage lipidome.

Tetrahydrobiopterin is a cofactor synthesized from GTP with well-known roles in enzymatic nitric oxide synthesis and aromatic amino acid hydroxylation. It is used to treat mild forms of phenylketonuria. Less is known about the role of tetrahydrobiopterin in lipid metabolism, although it is essential for irreversible ether lipid cleavage by alkylglycerol monooxygenase.

Patterns of globalized reproduction: Egg cells regulation in Israel and Austria.

Since the successful introduction of in vitro fertilization in 1978, medically assisted reproduction (MAR) has proliferated in multiple clinical innovations. Consequently, egg cells have become an object of demand for both infertility treatment and stem cell research, and this raises complex legal, ethical, social and economic issues.In this paper we compare how the procurement and use of human egg cells is regulated in two countries: Israel and Austria.

Studying fatty aldehyde metabolism in living cells with pyrene-labeled compounds.

The lack of fatty aldehyde dehydrogenase function in Sjögren Larsson Syndrome (SLS) patient cells not only impairs the conversion of fatty aldehydes into their corresponding fatty acid but also has an effect on connected pathways. Alteration of the lipid profile in these cells is thought to be responsible for severe symptoms such as ichtyosis, mental retardation, and spasticity. Here we present a novel approach to examine fatty aldehyde metabolism in a time-dependent manner by measuring pyrene-labeled fatty aldehyde, fatty alcohol, fatty acid, and alkylglycerol in the culture medium of living cells using HPLC separation and fluorescence detection.

Catalytic residues and a predicted structure of tetrahydrobiopterin-dependent alkylglycerol mono-oxygenase.

Alkylglycerol mono-oxygenase (EC 1.14.16.

Rethinking the meaning of being a scientist--the role of scientific integrity boards and some thoughts about scientific culture.

Biomedicine is a fast moving and often challenging research field. To this extent, it seems that preserving one's integrity is becoming more and more complex and occasionally stressful for individual researchers. Highly competitive funding and publication, the commercialization of biomedicine in general, the media hype about some scientific fields, the politicization of research and higher education, and, last but not least, the increasing specialization necessary to deal with increasingly sophisticated experimental systems and technologies are aspects of this complexity.

Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymes.

Alkylglycerol monooxygenase (glyceryl-ether monooxygenase, EC 1.14.16.

Monitoring of fatty aldehyde dehydrogenase by formation of pyrenedecanoic acid from pyrenedecanal.

Fatty aldehyde dehydrogenase (EC 1.2.1.

Proteomic profiling of acute cardiac allograft rejection.

Background: Proteome analysis has emerged as a valuable tool for the study of large-scale protein expression profiles. Here, we applied this novel technology to identify specific biomarkers for acute cardiac allograft rejection.

Methods: Hearts of C57BL/10 mice were placed in fully major histocompatibility complex-mismatched C3H/He recipients.

Physarum nitric oxide synthases: genomic structures and enzymology of recombinant proteins.

Physarum polycephalum expresses two closely related, calcium-independent NOSs (nitric oxide synthases). In our previous work, we showed that both NOSs are induced during starvation and apparently play a functional role in sporulation. In the present study, we characterized the genomic structures of both Physarum NOSs, expressed both enzymes recombinantly in bacteria and characterized their biochemical properties.