Refine
Document Type
- Article (1)
- Conference Proceeding (1)
- Working Paper (1)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- Amino acid analysis (1)
- Computer-aided drug design (1)
- Congenital anomalies (1)
- DNA sequence analysis (1)
- Embryos (1)
- Gene expression (1)
- Mutation databases (1)
- Transcriptome analysis (1)
Institute
- Biochemie und Chemie (1)
- MPI für Biophysik (1)
- Medizin (1)
Poster presentation at 1st International Workshop on Odor Spaces.
Mice are exceptional in their ability to capture their chemical environment, mapping the olfactory world into a basic sensory representation with over one thousand different types of chemical sensors, that is, olfactory sensory neurons (OSNs). OSNs of each type converge in the olfactory bulb onto exclusive distinct physiological areas called glomeruli. The glomeruli constitute the first relay station of olfactory stimulus representation in the mouse brain. Thus, the stimulus induced glomerular input pattern spatially embodies an important part of the sensory representation in the olfactory bulb. Still, topographic organization principles (chemotopy, tunotopy) are under debate. One reason might be that investigation are, due to experimental limitations, only performed on stimuli sets in the size of one hundred odors. But this represents only a tiny snapshot of the vast amount of molecules in the olfactory world and topographic relationships might be disguised in the incomplete representation of molecular receptive ranges (MRR). Therefore we investigated the problem with the MOR18-2 glomerulus as point of reference: First we determined it's MRR. Then, based on a measurement set covering this MRR, we elucidated the topographic embedding. It shows that MOR18-2 is embedded in a hierarchy of patchy tunotopic domains.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
Der starke Anstieg von nitrophytischen Flechten während der letzten 15 Jahren in landwirtschaftlich genutzten und städtischen Bereichen hat die Frage aufgeworfen, welche Stickstoffverbindung dafür verantwortlich sind, welche physiologischen Probleme diese machen, wo diese herkommen, welche Auswirkungen sie auf die Flechten haben, was mit dem Stickstoff in den Flechten passiert, wie sich Feinstaub und trockene Deposition auswirken und wieso Nitrophyten auch in unbelasteten Gebieten dominieren. Nach den Ergebnissen zahlreicher Einzelstudien, die hier mit neuen Daten ergänzt werden, ist Ammoniak die relevante Stickstoffquelle. Dieser wird als Ammoniumnitrat speziell in Form von trockener Deposition von den Flechten aufgenommen. Da Ammoniumnitrat ein Salz ist, haben Nitrophyten höhere osmotische Werte, weswegen sie in belasteten Gebieten konkurrenzkräftiger sind. Dies erlaubt Nitrophyten gleichzeitig die Existenz in Trockengebieten auch ohne Stickstoffemissionen, weswegen sie nicht unbedingt Stickstoffzeiger sondern auch Trockenzeiger sind. Der anfallende Stickstoff wird in Form von Aminosäuren in der Flechte passiv gespeichert, weswegen Nitrophyten nicht nitrophil sondern nitrotolerant, halotolerant und xerophytisch sind. Die momentane Temperaturerhöhung und die damit verbundene erhöhte Verdunstung sowie die Zunahme trockener Deposition (Feinstaubbelastung) führen zur Zeit trotz sinkender Gesamtstickstoffbelastung zu einem weiteren Anstieg der nitrophytischen Flechten.