Integration ethologischer und funktioneller Merkmale in Zuchtprogramme für die Sau von morgen

Das Projekt „FreeSow“ hatte zum Ziel, Sauen hinsichtlich ihrer Eignung für freiere Abferkelsysteme und alternative Haltungsverfahren zu charakterisieren und diese Eigenschaften in die zukünftige Zuchtplanung zu integrieren, um einen wichtigen Beitrag zur nachhaltigen Tierzucht zu leisten. Da Systeme ohne Fixierung besondere Herausforderungen mit sich bringen, wird von einer in ihnen gehaltenen Sau erwartet, dass sie sowohl eine gute Mütterlichkeit gegenüber ihren Ferkeln aufweist als auch mögliche Interaktionen mit dem Menschen toleriert. Daher wurden im Projekt verschiedene Verhaltenstests zur Beschreibung des Verhaltens der Sauen entwickelt und angewandt. Für die praktische Datenerfassung über zwei Jahre standen der Basiszuchtbetrieb Garlitz (BHZP) mit 80 Bewegungsbuchten für detaillierte Untersuchungen und die ökologische Sauenhaltung des LBZ-Echem (LWK) für die Validierung unter ökologischen Bedingungen zur Verfügung. Umfangreiche Datenerhebungen und -analysen zur Tiergesundheit und zum Wohlbefindens bildeten einen weiteren Schwerpunkt. Alle im Rahmen des Projektes entwickelten Verhaltenstests zur Toleranz gegenüber menschlichen Interaktionen erwiesen sich als geeignet, um das Verhalten der Sauen in praxi zu charakterisieren. Die geschätzten Heritabilitäten für die Merkmale, die sich mittels Test ergaben und Verhalten der Sauen gegenüber Menschen charakterisierten, lagen im Bereich von h² = 0,131 bis h² = 1.87. Diese Erblichkeitsgrade lassen eine erfolgreiche züchterische Bearbeitung zu. Zudem fanden sich bei Genom-weiten Assoziationsstudien erste Hinweise auf vielversprechende SNPs. Für die Nutzung in einem Sauenplaner wurden neue Merkmale des Tierverhaltens entwickelt und integriert, so dass eine einfache Dokumentationsmöglichkeit für den Sauenhalter geschaffen worden ist. Bereits während der Projektlaufzeit wurde die Selektion gegen unerwünschte Verhaltensweisen von Sauen in Abferkelsystemen mit größerer Bewegungsmöglichkeit umgesetzt

Untreated PKU patients without intellectual disability: SHANK gene family as a candidate modifier

Phenylketonuria (PKU) is an inborn error of metabolism caused by variants in the phenylalanine hydroxylase (PAH) gene and it is characterized by excessively high levels of phenylalanine in body fluids. PKU is a paradigm for a genetic disease that can be treated and majority of developed countries have a population-based newborn screening. Thus, the combination of early diagnosis and immediate initiation of treatment has resulted in normal intelligence for treated PKU patients. Although PKU is a monogenic disease, decades of research and clinical practice have shown that the correlation between the genotype and corresponding phenotype is not simple at all. Attempts have been made to discover modifier genes for PKU cognitive phenotype but without any success so far. We conducted whole genome sequencing of 4 subjects from unrelated non-consanguineous families who presented with pathogenic mutations in the PAH gene, high blood phenylalanine concentrations and near-normal cognitive development despite no treatment. We used cross sample analysis to select genes common for more than one patient. Thus, the SHANK gene family emerged as the only relevant gene family with variants detected in 3 of 4 analyzed patients. We detected two novel variants, p.Pro1591Ala in SHANK1 and p.Asp18Asn in SHANK2, as well as SHANK2:p.Gly46Ser, SHANK2:p.Pro1388_Phe1389insLeuPro and SHANK3:p.Pro1716Thr variants that were previously described. Computational analysis indicated that the identified variants do not abolish the function of SHANK proteins. However, changes in posttranslational modifications of SHANK proteins could influence functioning of the glutamatergic synapses, cytoskeleton regulation and contribute to maintaining optimal synaptic density and number of dendritic spines. Our findings are linking SHANK gene family and brain plasticity in PKU for the first time. We hypothesize that variant SHANK proteins maintain optimal synaptic density and number of dendritic spines under high concentrations of phenylalanine and could have protective modifying effect on cognitive development of PKU patients

Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants

Glycogen storage disease (GSD) type I is inborn metabolic disease characterized by accumulation of glycogen in multiple organs. We analyzed 38 patients with clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We identified 28 GSD Ib and 5 GSD Ia patients. In 5 patients, GSD III, VI, IX, cholesteryl-ester storage disease and Shwachman-Diamond syndrome diagnoses were set using NGS. Incidences for GSD Ia and GSD Ib were estimated at 1:172746 and 1:60461 live-births, respectively. Two variants were identified in G6PC gene: c.247C gt T (p.Arg83Cys) and c.518T gt C (p.Leu173Pro). In SLC37A4 gene, 6 variants were detected. Three previously reported variants c.81T gt A (p.Asn27Lys), c.162C gt A (p.Ser54Arg) and c.1042_1043delCT (p.Leu348Valfs*53) accounted for 87% of all analyzed alleles. Computational, transcription studies and/or clinical presentation in patients confirmed pathogenic effect of 3 novel variants: c.248G gt A (p.Gly83Glu), c.404G gt A (p.Gly135Asp) and c.785G gt A (p.Ser263Glyfs*33 or p.Gly262Asp). In the cohort, hepatomegaly, hypoglycemia and failure to thrive were the most frequent presenting signs of GSD Ia, while hepatomegaly and recurrent bacterial infections were clinical hallmarks of GSD Ib. All GSD Ib patients developed neutropenia while 20.6% developed inflammatory bowel disease. Our study revealed the highest worldwide incidence of GSD Ib. Furthermore, description of 3 novel variants will facilitate medical genetic practice.This is the peer reviewed version of the paper: Skakic, A., Djordjevic, M., Sarajlija, A., Klaassen, K., Tosic, N., Kecman, B., Ugrin, M., Spasovski, V., Pavlovic, S., & Stojiljkovic, M. (2018). Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants. Clinical Genetics, 93(2), 350–355. [https://doi.org/10.1111/cge.13093

MAST: a mass spectrometer telescope for studies of the isotopic composition of solar, anomalous, and galactic cosmic ray nuclei

The mass spectrometer telescope (MAST) on SAMPEX (Solar, Anomalous, and Magnetospheric Particle Explorer) is designed to provide high-resolution measurements of the isotopic composition of energetic nuclei from He to Ni (Z=2 to 28) over the energy range from ~10 to several hundred MeV/nucleon. During large solar flares MAST will measure the isotopic abundances of solar energetic particles to determine directly the composition of the solar corona, while during solar quiet times MAST will study the isotopic composition of galactic cosmic rays. In addition, MAST will measure the isotopic composition of both interplanetary and trapped fluxes of anomalous cosmic rays, believed to be a sample of the nearby interstellar medium

Custom Analog VLSI for the Advanced Composition Explorer (ACE)

Two custom analog VLSI chips are currently in development for scientific payloads of NASA's Advanced Composition Explorer. One chip will be fabricated in the radiation hard 1.2 um CMOS process of the United Technologies Microelectronics Center (UlMC), and will contain 16 complete discriminator/12 bit pulse-height-analysis chains for the readout of heavy ion Si strip detectors. The second chip will be fabricated by Harris Semiconductor in their dielectrically isolated bipolar VHF process. This chip will contain the active elements of a single precision pulse-height-analysis chain and several precision discriminator chains. The chips designed in this effort and the techniques employed are expected to be applicable in science payloads of future missions, especially those which place extraordinary premiums on weight, power, and/or performance

Large-Area Silicon Detectors for the Advanced Composition Explorer (ACE) Solar Isotope Spectrometer (SIS)

Extensive measurements were made of the thicknesses and dead-layers of the large-area, highpurity silicon detectors used for the Solar Isotope Spectrometer (SIS), an instrument to be launched on the Advanced Composition Explorer (ACE) spacecraft. Tests using accelerated beams of heavy nuclei were also carried out to characterize the completed instrument

The ACE-CRIS Scintillating Optical Fiber Trajectory (SOFT) Detector: Calibrations at the NSCL and GSI

The Scintillating Optical Fiber Trajectory (SOFT) detector, the hodoscope for the Cosmic Ray Isotope Spectrometer (CRIS) on the NASA Advanced Composition Explorer, was calibrated using 155 MeV/n He, Li, C, N, 0, and Ar at the Michigan State University National Superconducting Cyclotron Laboratory (NSCL), and 200 - 700 MeV/n C, Si, and Fe at the GSI facility in Darrnstadt. Germany. The flight instrument consists of three hodoscope fiber planes and one trigger plane. read out by an image intensified CCD camera system and by intensified photodiodes respectively. The spatial and angular resolution of the hodoscope is described, along with the detection efficiency of both the hodoscope and trigger plane as a function of charge

The Cosmic-Ray Isotope Spectrometer for the Advanced Composition Explorer

The Cosmic-Ray Isotope Spectrometer is designed to cover the highest decade of the Advanced Composition Explorer's energy interval, from ∼50 to ∼500 MeV nucl^(−1), with isotopic resolution for elements from Z≃2 to Z≃30. The nuclei detected in this energy interval are predominantly cosmic rays originating in our Galaxy. This sample of galactic matter can be used to investigate the nucleosynthesis of the parent material, as well as fractionation, acceleration, and transport processes that these particles undergo in the Galaxy and in the interplanetary medium. Charge and mass identification with CRIS is based on multiple measurements of dE/dx and total energy in stacks of silicon detectors, and trajectory measurements in a scintillating optical fiber trajectory (SOFT) hodoscope. The instrument has a geometrical factor of ∼r250 cm^2 sr for isotope measurements, and should accumulate ∼5×10^6 stopping heavy nuclei (Z>2) in two years of data collection under solar minimum conditions

PET: A Proton/Electron Telescope for Studies of Magnetospheric, Solar, and Galactic Particles

The proton/electron telescope (PET) on SAMPEX (Solar, Anomalous, and Magnetospheric Particle Explorer) is designed to provide measurements of energetic electrons and light nuclei from solar, Galactic, and magnetospheric sources. PET is an all solid-state system that will measure the differential energy spectra of electrons from ~1 to ~30 MeV and H and He nuclei from ~20 to ~300 MeV/nucleon, with isotope resolution of H and He extending from ~20 to ~80 MeV/nucleon. As SAMPEX scans all local times and geomagnetic cutoffs over the course of its near-polar orbit, PET will characterize precipitating relativistic electron events during periods of declining solar activity, and it will examine whether the production rate of odd nitrogen and hydrogen molecules in the middle atmosphere by precipitating electrons is sufficient to affect O_3 depletion. In addition, PET will complement studies of the elemental and isotopic composition of energetic heavy (Z>2) nuclei on SAMPEX by providing measurements of H, He, and electrons. Finally, PET has limited capability to identify energetic positrons from potential natural and man-made sources