scholarly journals Hominini-Specific Regulation of CBLN2 Increases Prefrontal Synaptogenesis

2019 ◽  
Author(s):  
Mikihito Shibata ◽  
Kartik Pattabiraman ◽  
Sydney K. Muchnik ◽  
Nenad Sestan
Keyword(s):  
Binding Sites ◽  
Developmental Constraints ◽  
Gene Encoding ◽  
Synaptic Density ◽  
Spatio Temporal ◽  
Specific Regulation ◽  
Cerebral Neocortex ◽  
Anterior Posterior ◽  
Human Specific

AbstractThe similarities and differences between nervous systems of various species result from developmental constraints and specific adaptations 1-4. Comparative analyses of the prefrontal cortex (PFC), a region of the cerebral cortex involved in higher-order cognition and complex social behaviors, have identified confirmed and putative human-specific structural and molecular changes 4-8. For example, one crucial specialization involves the anterior-posterior gradient in synaptic density, with a disproportionately higher number of dendritic spines specifically in the human PFC compared to other analyzed primates 5. These changes are likely mediated by divergence in spatio-temporal patterns of gene expression 9-17, which are prominent in the mid-fetal human cerebral neocortex 15,18-20. Analyzing developmental human and macaque brain transcriptomic data 15,20, we identified a transient PFC- and laminar-specific upregulation of the gene encoding cerebellin 2 (CBLN2), a neurexin (NRXN) and glutamate receptor delta (GRID/GluD)-associated synaptic organizer 21-27, in human mid-fetal development coinciding with the initiation of synaptogenesis. Moreover, we show that this difference in expression level and laminar distribution of CBLN2, is due to Hominini-specific deletions affecting SOX5 binding sites within a retinoic acid-responsive CBLN2 enhancer. In situ genetic humanization of the mouse Cbln2 enhancer drives increased and ectopic laminar Cbln2 expression and promotes glutamatergic and GABAergic synaptogenesis specifically in the PFC. These findings identify a putative genetic and molecular basis for the disproportionately increased connectivity in the Hominini PFC and suggest a developmental mechanism linking dysfunction of the NRXN-GRID-CBLN2 complex, to the pathogenesis of neuropsychiatric disorders.

scholarly journals Human-Specific Regulation of Neurotrophic Factors MANF and CDNF by microRNAs

2021 ◽  
Vol 22 (18) ◽  
pp. 9691
Author(s):  
Julia Konovalova ◽  
Dmytro Gerasymchuk ◽  
Sergio Navarette Arroyo ◽  
Sven Kluske ◽  
Francesca Mastroianni ◽  
...  
Keyword(s):  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Binding Sites ◽  
Trophic Factors ◽  
Cytoprotective Activity ◽  
Bioinformatic Tools ◽  
Specific Regulation ◽  
First Time ◽  
Direct Regulation ◽  
Human Specific

Mesencephalic astrocyte derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are novel evolutionary conserved trophic factors, which exhibit cytoprotective activity via negative regulation of unfolded protein response (UPR) and inflammation. Despite multiple reports demonstrating detrimental effect of MANF/CDNF downregulation, little is known about the control of their expression. miRNAs—small non-coding RNAs—are important regulators of gene expression. Their dysregulation was demonstrated in multiple pathological processes and their ability to modulate levels of other neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), was previously reported. Here, for the first time we demonstrated direct regulation of MANF and CDNF by miRNAs. Using bioinformatic tools, reporter assay and analysis of endogenous MANF and CDNF, we identified that miR-144 controls MANF expression, and miR-134 and miR-141 downregulate CDNF levels. We also demonstrated that this effect is human-specific and is executed via predicted binding sites of corresponding miRNAs. Finally, we found that miR-382 suppressed hCDNF expression indirectly. In conclusion, we demonstrate for the first time direct regulation of MANF and CDNF expression by specific miRNAs, despite the fact their binding sites are not strongly evolutionary conserved. Furthermore, we demonstrate a functional effect of miR-144 mediated regulation of MANF on ER stress response markers. These findings emphasize that (1) prediction of miRNA targets based on evolutionary conservation may miss biologically meaningful regulatory pairs; and (2) interpretation of miRNA regulatory effects in animal models should be cautiously validated.

Electron Probe Analysis of Muscle

1982 ◽  
Vol 40 ◽  
pp. 398-401
Author(s):  
A. V. Somlyo ◽  
H. Shuman ◽  
A. P. Somlyo
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Resting State ◽  
Binding Sites ◽  
Electron Probe ◽  
Frog Skeletal Muscle ◽  
Electron Probe Analysis ◽  
Probe Analysis

Electron probe analysis of frozen dried cryosections of frog skeletal muscle, rabbit vascular smooth muscle and of isolated, hyperpermeab1 e rabbit cardiac myocytes has been used to determine the composition of the cytoplasm and organelles in the resting state as well as during contraction. The concentration of elements within the organelles reflects the permeabilities of the organelle membranes to the cytoplasmic ions as well as binding sites. The measurements of [Ca] in the sarcoplasmic reticulum (SR) and mitochondria at rest and during contraction, have direct bearing on their role as release and/or storage sites for Ca in situ.

scholarly journals Controlling the spatio-temporal dose distribution during STEM imaging by subsampled acquisition: In-situ observations of kinetic processes in liquids

2019 ◽  
Vol 115 (6) ◽  
pp. 063102 ◽  
Author(s):  
B. L. Mehdi ◽  
A. Stevens ◽  
L. Kovarik ◽  
N. Jiang ◽  
H. Mehta ◽  
...  
Keyword(s):  
Dose Distribution ◽  
In Situ Observations ◽  
Kinetic Processes ◽  
Spatio Temporal

Untersuchungen zur Ableitung von Windböen aus Doppler-Lidar-Messungen

2021 ◽  
Author(s):  
Carola Detring ◽  
Eileen Päschke ◽  
Julian Steinheuer ◽  
Ronny Leinweber ◽  
Markus Kayser ◽  
...  
Keyword(s):  
Field Experiment ◽  
Temporal Variability ◽  
Surface Wind ◽  
Doppler Lidar ◽  
Signal To Noise ◽  
Observation Volume ◽  
Wind Gusts ◽  
Die Profile ◽  
Spatio Temporal

<p>Mit Hilfe von Doppler-Lidar-Systemen, lassen sich die Profile von Windgeschwindigkeit und -richtung in der Atmosphärischen Grenzschicht (AGS) auf der Basis klassischer Messstrategien wie einem VAD-24 Scan (Velocity Azimuth Display mit 24 Strahlrichtungen) zuverlässig bestimmen (Päschke et al., 2015). Für praktische Anwendungen von großem Interesse sind jedoch neben dem mittleren Windprofil auch kurzzeitige Fluktuationen des Windes, wie sie zum Beispiel in Verbindung mit Windböen auftreten. Untersuchungen zu Windböen waren ein wesentlicher Aspekt der Messkampagne FESSTVaL (Field Experiment on Sub-Mesoscale Spatio-Temporal Variability in Lindenberg, www.fesstval.de).</p><p>Eine Studie von Suomi et al. (2017) hat gezeigt, dass eine Ableitung von Windböen aus Doppler Lidar Messungen prinzipiell möglich ist. Allerdings wird mit üblichen Messstrategien die hierfür erforderliche hohe zeitliche Auflösung in der Ermittlung des Windvektors nicht erreicht, so dass mit Skalierungsansätzen unter Verwendung von in-situ Windmessungen eine Korrektur der aus den Lidar-Daten abgeleiteten Böenwerte erfolgen muss.</p><p>Im Rahmen der vorliegenden Arbeit wurde eine alternative Messstrategie für Doppler-Lidar-Systeme vom Typ „Streamline“ (Halo Photonics) entwickelt und über mehrere Monate in den Jahren 2020/21 auf dem Grenzschichtmessfeld Falkenberg des DWD erprobt. Die Böenableitung basiert auf einem sog. Continous Scan Mode (CSM); dabei werden die während einer vollständigen Rotation des Lidar-Scan-Kopfes kontinuierlich durchgeführten Messungen 10-11 Strahlrichtungen zugeordnet und die Radialwindgeschwindigkeiten wiederum mit dem VAD-Verfahren ermittelt. Die Dauer eines Scans beträgt etwa 3.4s, damit kann eine Zeitauflösung erreicht werden, die der heute weit verbreiteten Definition einer Windbö entspricht (3s gleitendes Mittel; WMO (2018)).</p><p>Diese neue Konfiguration bringt Herausforderungen an die Datenverarbeitung mit sich. Im CSM muss mit vergleichsweise wenigen Lidar-Pulsen pro Messstrahl gearbeitet werden, so dass klassische Ansätze der Datenfilterung (Signal-to-Noise Schwellwert, Consensus Filterung) nicht verwendet werden können. Es wird ein alternatives Verfahren für die Prozessierung der Lidar-Rohdaten vorgeschlagen. Die Ergebnisse der Ableitung sowohl des mittleren Windvektors als auch der jeweiligen maximalen Windbö in einem 10-Minuten-Mittelungsintervall werden mit Sonic-Messungen in 90m Höhe verglichen. </p><p>Im Rahmen des FESSTVaL Experimentes wurde diese neue Messkonfiguration an drei Standorten, die ein annähernd gleichseitiges Dreieck mit einer Kantenlänge von etwa 5 km bildeten, genutzt. Es werden Fallbeispiele aus der FESSTVaL Kampagne für die Variabilität im Auftreten von Windböen gezeigt.</p><p><strong>Referenzen</strong></p><p>Päschke, E., Leinweber, R., and Lehmann, V. (2015): An assessment of the performance of a 1.5 μm Doppler lidar for operational vertical wind profiling based on a 1-year trial, Atmos. Meas. Tech., 8, 2251–2266, https://doi.org/10.5194/amt-8-2251-2015</p><p>Suomi, I., Gryning, S.‐E., O'Connor, E.J. and Vihma, T. (2017): Methodology for obtaining wind gusts using Doppler lidar. Q.J.R. Meteorol. Soc., 143: 2061-2072. https://doi.org/10.1002/qj.3059</p><p>World Meteorological Organization (WMO) (2018): Measurement of surface wind. In Guide to Meteorological Instruments and Methods of Observation, Volume I -Measurement of Meteorological Variables, No.8: 196–213, URL: https://library.wmo.int/doc_num.php?explnum_id=10616 (accessed November 2021)</p>

scholarly journals Temporal Variation of Chlorophyll-a Concentrations in Highly Dynamic Waters from Unattended Sensors and Remote Sensing Observations

Sensors ◽  
2018 ◽  
Vol 18 (8) ◽  
pp. 2699 ◽  
Author(s):  
Jian Li ◽  
Liqiao Tian ◽  
Qingjun Song ◽  
Zhaohua Sun ◽  
Hongjing Yu ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Water Quality ◽  
Chlorophyll Fluorescence ◽  
Chlorophyll A ◽  
Temporal Variations ◽  
Lake Area ◽  
Short Term ◽  
Chl A ◽  
Spatio Temporal

Monitoring of water quality changes in highly dynamic inland lakes is frequently impeded by insufficient spatial and temporal coverage, for both field surveys and remote sensing methods. To track short-term variations of chlorophyll fluorescence and chlorophyll-a concentrations in Poyang Lake, the largest freshwater lake in China, high-frequency, in-situ, measurements were collected from two fixed stations. The K-mean clustering method was also applied to identify clusters with similar spatio-temporal variations, using remote sensing Chl-a data products from the MERIS satellite, taken from 2003 to 2012. Four lake area classes were obtained with distinct spatio-temporal patterns, two of which were selected for in situ measurement. Distinct daily periodic variations were observed, with peaks at approximately 3:00 PM and troughs at night or early morning. Short-term variations of chlorophyll fluorescence and Chl-a levels were revealed, with a maximum intra-diurnal ratio of 5.1 and inter-diurnal ratio of 7.4, respectively. Using geostatistical analysis, the temporal range of chlorophyll fluorescence and corresponding Chl-a variations was determined to be 9.6 h, which indicates that there is a temporal discrepancy between Chl-a variations and the sampling frequency of current satellite missions. An analysis of the optimal sampling strategies demonstrated that the influence of the sampling time on the mean Chl-a concentrations observed was higher than 25%, and the uncertainty of any single Terra/MODIS or Aqua/MODIS observation was approximately 15%. Therefore, sampling twice a day is essential to resolve Chl-a variations with a bias level of 10% or less. The results highlight short-term variations of critical water quality parameters in freshwater, and they help identify specific design requirements for geostationary earth observation missions, so that they can better address the challenges of monitoring complex coastal and inland environments around the world.

RyR1 exhibits lower gain of CICR activity than RyR3 in the SR: evidence for selective stabilization of RyR1 channel

2004 ◽  
Vol 287 (1) ◽  
pp. C36-C45 ◽  
Author(s):  
Takashi Murayama ◽  
Yasuo Ogawa
Keyword(s):  
Binding Sites ◽  
Skeletal Muscles ◽  
Specific Activity ◽  
Adenine Nucleotides ◽  
Minor Effect ◽  
Mammalian Skeletal Muscle ◽  
Selective Stabilization ◽  
Underlying Mechanisms ◽  
A Minor

We showed that frog α-ryanodine receptor (α-RyR) had a lower gain of Ca2+-induced Ca2+ release (CICR) activity than β-RyR in sarcoplasmic reticulum (SR) vesicles, indicating selective “stabilization” of the former isoform (Murayama T and Ogawa Y. J Biol Chem 276: 2953–2960, 2001). To know whether this is also the case with mammalian RyR1, we determined [3H]ryanodine binding of RyR1 and RyR3 in bovine diaphragm SR vesicles. The value of [3H]ryanodine binding (B) was normalized by the number of maximal binding sites (Bmax), whereby the specific activity of each isoform was expressed. This B/Bmax expression demonstrated that ryanodine binding of individual channels for RyR1 was <15% that for RyR3. Responses to Ca2+, Mg2+, adenine nucleotides, and caffeine were not substantially different between in situ and purified isoforms. These results suggest that the gain of CICR activity of RyR1 is markedly lower than that of RyR3 in mammalian skeletal muscle, indicating selective stabilization of RyR1 as is true of frog α-RyR. The stabilization was partly eliminated by FK506 and partly by solubilization of the vesicles with CHAPS, each of which was additive to the other. In contrast, high salt, which greatly enhances [3H]ryanodine binding, caused only a minor effect on the stabilization of RyR1. None of the T-tubule components, coexisting RyR3, or calmodulin was the cause. The CHAPS-sensitive intra- and intermolecular interactions that are common between mammalian and frog skeletal muscles and the isoform-specific inhibition by FKBP12, which is characteristic of mammals, are likely to be the underlying mechanisms.

scholarly journals Predicting land deformation by integrating InSAR data and cone penetration testing through machine learning techniques

2020 ◽  
Vol 382 ◽  
pp. 525-529
Author(s):  
Melika Sajadian ◽  
Ana Teixeira ◽  
Faraz S. Tehrani ◽  
Mathias Lemmens
Keyword(s):  
Machine Learning ◽  
Soil Mechanics ◽  
Machine Learning Techniques ◽  
Cone Penetration ◽  
Penetration Testing ◽  
Cone Penetration Testing ◽  
Learning Techniques ◽  
Land Deformation ◽  
Spatio Temporal

Abstract. Built environments developed on compressible soils are susceptible to land deformation. The spatio-temporal monitoring and analysis of these deformations are necessary for sustainable development of cities. Techniques such as Interferometric Synthetic Aperture Radar (InSAR) or predictions based on soil mechanics using in situ characterization, such as Cone Penetration Testing (CPT) can be used for assessing such land deformations. Despite the combined advantages of these two methods, the relationship between them has not yet been investigated. Therefore, the major objective of this study is to reconcile InSAR measurements and CPT measurements using machine learning techniques in an attempt to better predict land deformation.

scholarly journals The interplay between DNA methylation and sequence divergence in recent human evolution

2015 ◽  
Author(s):  
Irene Hernando-Herraez ◽  
Holger Heyn ◽  
Marcos Fernandez-Callejo ◽  
Enrique Vidal ◽  
Hugo Fernandez-Bellon ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Binding Sites ◽  
Incomplete Lineage Sorting ◽  
Epigenetic Modification ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Methylation Patterns ◽  
Human Specific

DNA methylation is a key regulatory mechanism in mammalian genomes. Despite the increasing knowledge about this epigenetic modification, the understanding of human epigenome evolution is in its infancy. We used whole genome bisulfite sequencing to study DNA methylation and nucleotide divergence between human and great apes. We identified 360 and 210 differentially hypo- and hypermethylated regions (DMRs) in humans compared to non-human primates and estimated that 20% and 36% of these regions, respectively, were detectable throughout several human tissues. Human DMRs were enriched for specific histone modifications and contrary to expectations, the majority were located distal to transcription start sites, highlighting the importance of regions outside the direct regulatory context. We also found a significant excess of endogenous retrovirus elements in human-specific hypomethylated regions suggesting their association with local epigenetic changes. We also reported for the first time a close interplay between inter-species genetic and epigenetic variation in regions of incomplete lineage sorting, transcription factor binding sites and human differentially hypermethylated regions. Specifically, we observed an excess of human-specific substitutions in transcription factor binding sites located within human DMRs, suggesting that alteration of regulatory motifs underlies some human-specific methylation patterns. We also found that the acquisition of DNA hypermethylation in the human lineage is frequently coupled with a rapid evolution at nucleotide level in the neighborhood of these CpG sites. Taken together, our results reveal new insights into the mechanistic basis of human-specific DNA methylation patterns and the interpretation of inter-species non-coding variation.

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