Prader-Willi syndrome: genetic tests and clinical findings

Here we describe the genetic studies performed in 53 patients with the suspected diagnosis of Prader-Willi syndrome (PWS). PWS is characterized by neonatal hypotonia, hypogonadism, delayed psychomotor development, hyperphagia, obesity, short stature, small hands and feet, learning disabilities, and obsessive-compulsive behavior. Through the methylation analysis of the SNRPN gene, microsatellite studies of loci mapped within and outside the PWS/AS region, and fluorescence in situ hybridization (FISH) study, we confirmed the diagnosis in 35 patients: 27 with a paternal deletion, and 8 with maternal uniparental disomy (UPD). The clinical comparisons between deleted and UPD patients indicated that there were no major phenotype differences, except for a lower birth length observed in the UPD children. Our sample was composed of more girls than boys; UPD patients were diagnosed earlier than the deleted cohort (2(10/12) s. 7(9/12) years); and, in the deleted group, the boys were diagnosed earlier than the girls (5(2/12) vs. 7(8/12) years, respectively).     

Emergent decarboxylase activity and attenuation of α/β-hydrolase activity during the evolution of methylketone biosynthesis in tomato

Specialized methylketone-containing metabolites accumulate in certain plants, in particular wild tomatoes in which they serve as toxic compounds against chewing insects. In Solanum habrochaites f. glabratum, methylketone biosynthesis occurs in the plastids of glandular trichomes and begins with intermediates of de novo fatty acid synthesis. These fatty-acyl intermediates are converted via sequential reactions catalyzed by Methylketone Synthase2 (MKS2) and MKS1 to produce the n-1 methylketone. We report crystal structures of S. habrochaites MKS1, an atypical member of the α/β-hydrolase superfamily. Sequence comparisons revealed the MKS1 catalytic triad, Ala-His-Asn, as divergent to the traditional α/β-hydrolase triad, Ser-His-Asp. Determination of the MKS1 structure points to a novel enzymatic mechanism dependent upon residues Thr-18 and His-243, confirmed by biochemical assays. Structural analysis further reveals a tunnel leading from the active site consisting mostly of hydrophobic residues, an environment well suited for fatty-acyl chain binding. We confirmed the importance of this substrate binding mode by substituting several amino acids leading to an alteration in the acyl-chain length preference of MKS1. Furthermore, we employ structure-guided mutagenesis and functional assays to demonstrate that MKS1, unlike enzymes from this hydrolase superfamily, is not an efficient hydrolase but instead catalyzes the decarboxylation of 3-keto acids.     

Next-generation education in crop genetics

Today, plant breeders are being met with new opportunities to develop superior varieties. Fruitful genetic research into populations with novel diversity using genotyping by sequencing combined with genotype-to-phenotype bioinformatics has generated much knowledge that is directly relevant to crop improvement. These advances can assist the breeders in associating genetic makeup with traits of commercial value. The greatest challenge now is to find ways to attract the best young people to work in plant breeding for its innovation, open field experience and ability to support food security. We discuss the need, opportunities and conflicts associated with revamping plant breeding teaching programs to bridge the art and science of this profession with a rapidly expanding job market.     

Extensive heterosis in growth of yeast hybrids is explained by a combination of genetic models

Heterosis, also known as hybrid vigor, is the superior performance of a heterozygous hybrid relative to its homozygous parents. Despite the scientific curiosity of this phenotypic phenomenon and its significance for food production in agriculture, its genetic basis is insufficiently understood. Studying heterosis in yeast can potentially yield insights into its genetic basis, can allow one to test the different hypotheses that have been proposed to explain the phenomenon and allows better understanding of how to take advantage of this phenomenon to enhance food production. We therefore crossed 16 parental yeast strains to form 120 yeast hybrids, and measured their growth rates under five environmental conditions. A considerable amount of dominant genetic variation was found in growth performance, and heterosis was measured in 35% of the hybrid–condition combinations. Despite previous reports of correlations between heterosis and measures of sequence divergence between parents, we detected no such relationship. We used several analyses to examine which genetic model might explain heterosis. We found that dominance complementation of recessive alleles, overdominant interactions within loci and epistatic interactions among loci each contribute to heterosis. We concluded that in yeast heterosis is a complex phenotype created by the combined contribution of different genetic interactions.     

Glycosylation at Asn211 Regulates the Activation State of the Discoidin Domain Receptor 1 (DDR1)

Discoidin domain receptor 1 (DDR1) belongs to a unique family of receptor tyrosine kinases that signal in response to collagens. DDR1 undergoes autophosphorylation in response to collagen binding with a slow and sustained kinetics that is unique among members of the receptor tyrosine kinase family. DDR1 dimerization precedes receptor activation suggesting a structural inhibitory mechanism to prevent unwarranted phosphorylation. However, the mechanism(s) that maintains the autoinhibitory state of the DDR1 dimers is unknown. Here, we report that N-glycosylation at the Asn²¹¹ residue plays a unique role in the control of DDR1 dimerization and autophosphorylation. Using site-directed mutagenesis, we found that mutations that disrupt the conserved ²¹¹NDS N-glycosylation motif, but not other N-glycosylation sites (Asn²⁶⁰, Asn³⁷¹, and Asn³⁹⁴), result in collagen I-independent constitutive phosphorylation. Mass spectrometry revealed that the N211Q mutant undergoes phosphorylation at Tyr⁴⁸⁴, Tyr⁵²⁰, Tyr⁷⁹², and Tyr⁷⁹⁷. The N211Q traffics to the cell surface, and its ectodomain displays collagen I binding with an affinity similar to that of the wild-type DDR1 ectodomain. However, unlike the wild-type receptor, the N211Q mutant exhibits enhanced receptor dimerization and sustained activation upon ligand withdrawal. Taken together, these data suggest that N-glycosylation at the highly conserved ²¹¹NDS motif evolved to act as a negative repressor of DDR1 phosphorylation in the absence of ligand. The presence of glycan moieties at that site may help to lock the collagen-binding domain in the inactive state and prevent unwarranted signaling by receptor dimers. These studies provide a novel insight into the structural mechanisms that regulate DDR activation.     

The anti-idiotypic response to the experimental administration of the inactivated or live influenza virus]

The injection of inactivated and live influenza virus into rabbits induces the formation of anti-idiotypic antibodies, appearing after anti-influenza hemagglutinins, in the blood. The presence of immune complexes antibody--anti-idiotypic antibody in the blood of the animals has been established. The booster immunization of the animals with influenza virus antigens produces a rise in the levels of both idiotypic and anti-idiotypic antibodies. The injection of autologous anti-idiotypic globulin into the primed animals ensures the induction of idiotypic and anti-idiotypic revaccinal reactions.     

Species of the genus Papio (Cercopithecidae, primates) as subjects of biomedical research: II. Quantitative characteristics of contemporary use of baboon species in medical and biological investigations

Independence of the five Papio species is evaluated. Baboons appear to be more similar to man than are other monkey species, which makes them a desirable model for use in experimental research to approximate human health conditions. They are, however, used less widely than macaques. Publications on baboons account for 10.3% of literature on the use of primates in experimental research. Baboons were most intensively used in surgery, then in hematology, cardiology, endocrinology. They were most rarely used in stomatology and in studies on infectious diseases.     

Domestic water versus imported virtual blue water for agricultural production: A comparison based on energy consumption and related greenhouse gas emissions

The supply of water, food, and energy in our global economy is highly interlinked. Virtual blue water embedded into internationally traded food crops has therefore been extensively researched in recent years. This study focuses on the often neglected energy needed to supply this blue irrigation water. It provides a globally applicable and spatially explicit approach to the watershed level for water source specific quantification of energy consumption and related greenhouse gas (GHG) emissions of irrigation water supply. The approach is applied to Israel's total domestic and imported food crop supply of 105 crops by additionally including import-related transportation energy and emissions. Total energy use and related emissions of domestic crop production were much lower (551 GWh/422 kt CO₂-equivalents [CO₂e]) than those embedded into crop imports (1639 GWh/649 kt CO₂e). Domestic energy and emissions were mainly attributable to the irrigation water supply with artificial water sources (treated domestic wastewater and desalinated water, 84%). Transport accounted for 79% and 66% of virtually imported energy and emissions, respectively. Despite transport, specific GHG emissions (CO₂e per ton of crop) were significantly lower for several crops (e.g., olives, almonds, chickpeas) compared to domestic production. This could be attributed to the high share of energy-intensive artificial water supply in combination with higher irrigation water demands in Israel. In the course of an increasing demand for artificial water supply in arid and semi-arid regions, our findings point to the importance of including “energy for water” into comparative environmental assessment of crop supply to support decision-making related to the water–energy–food nexus.