Single-Cell Transcriptional Analysis of Neuronal Progenitors

AbstractThe extraordinary cellular heterogeneity of the mammalian nervous system has largely hindered the molecular analysis of neuronal identity and diversity. In order to uncover mechanisms involved in neuronal differentiation and diversification, we have monitored the expression profiles of individual neurons and progenitor cells collected from dissociated tissue or captured from intact slices. We demonstrate that this technique provides a sensitive and reproducible representation of the single-cell transcriptome. In the olfactory system, hundreds of transcriptional differences were identified between olfactory progenitors and mature sensory neurons, enabling us to define the large variety of signaling pathways expressed by individual progenitors at a precise developmental stage. Finally, we show that regional differences in gene expression can be predicted from transcriptional analysis of single neuronal precursors isolated by laser capture from defined areas of the developing brain

Effects of Short Term Adiponectin Receptor Agonism on Cardiac Function and Energetics in Diabetic db/db Mice.

Objective Impaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice. Methods A non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions. Results Based on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment. Conclusion AdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice

Quantitative Genetics, Pleiotropy, and Morphological Integration in the Dentition of Papio hamadryas

Variation in the mammalian dentition is highly informative of adaptations and evolutionary relationships, and consequently has been the focus of considerable research. Much of the current research exploring the genetic underpinnings of dental variation can trace its roots to Olson and Miller's 1958 book Morphological Integration. These authors explored patterns of correlation in the post-canine dentitions of the owl monkey and Hyopsodus, an extinct condylarth from the Eocene. Their results were difficult to interpret, as was even noted by the authors, due to a lack of genetic information through which to view the patterns of correlation. Following in the spirit of Olson and Miller's research, we present a quantitative genetic analysis of dental variation in a pedigreed population of baboons. We identify patterns of genetic correlations that provide insight to the genetic architecture of the baboon dentition. This genetic architecture indicates the presence of at least three modules: an incisor module that is genetically independent of the post-canine dentition, and a premolar module that demonstrates incomplete pleiotropy with the molar module. We then compare this matrix of genetic correlations to matrices of phenotypic correlations between the same measurements made on museum specimens of another baboon subspecies and the Southeast Asian colobine Presbytis. We observe moderate significant correlations between the matrices from these three primate taxa. From these observations we infer similarity in modularity and hypothesize a common pattern of genetic integration across the dental arcade in the Cercopithecoidea

Novel cis-regulatory modules control expression of the hairy and enhancer of split-1 (HES1) transcription factor in myoblasts

The expression profile of a gene is controlled by DNA sequences called cis-regulatory modules (CRMs). CRMs can function over large genomic distances and can be located many kilobases away from their target promoters. hes1 is a key developmental gene that is overexpressed in certain cancers and is a primary target of NOTCH signaling. Despite this, analysis of hes1 transcriptional control has been limited solely to its promoter. Here, we identify seven conserved DNA sequence blocks, representing the hes1 promoter and six novel CRMs, within 57 kb upstream of the mouse hes1 gene. We identify 12 binding sites for the RBP-Jκ NOTCH effector and a single M-CAT motif within these regions. We validate RBP-Jκ and TEAD family occupancy in cells in culture and test the response of each of these CRMs to active NOTCH. We show that two regions, CRM5 and CRM7, function as enhancers, and four can repress transcription. A pair of RBP-Jκ motifs arranged in a tail-tail configuration in CRM5 and the M-CAT motif in CRM7 are necessary for enhancer function. Furthermore, these enhancers are occupied by transcriptional co-activators and loop onto the hes1 promoter within the endogenous hes1 locus. This work demonstrates the power of combining computational genomics and experimental methodologies to identify novel CRMs and characterize their function. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

Please Don’t Leave Me—Separation Anxiety and Related Traits in Borderline Personality Disorder

Purpose of Review: In light of the apparent symptomatic resemblance of separation anxiety disorder (SAD) symptoms on the one hand and abandonment fears, anxiousness, and separation insecurity central to borderline personality disorder (BPD) on the other hand, a comprehensive overview of separation anxiety and related traits in BPD is provided. Recent Findings: Epidemiological, environmental, psychological, and neurobiological data connecting BPD to separation events, feelings of loneliness, insecure attachment styles, dimensional separation anxiety as well as SAD per se suggest a partly shared etiological pathway model underlying BPD and SAD. Differential diagnostic aspects and implications for treatment are discussed, highlighting separation anxiety as a promising transdiagnostic target for specific psychotherapeutic and pharmacological treatment approaches in BPD. Summary: This innovative angle on cross-disorder symptomatology might carry potential for novel preventive and therapeutic avenues in clinical practice by guiding the development of interventions specifically targeting separation anxiety and attachment-related issues in BPD

Entwicklung einer CdTe/CdS Duennschicht-Solarzelle Schlussbericht

The focus was on the development and optimisation of the close-spaced sublimation process in an inline coating plant for production of stable high-efficiency CdS/CdTe solar wafers. An inline plant was to be constructed by ANTEC GmbH and ISFH. Film layers were to be optimised, and investigations were to show whether processing of single films is possible without breaking the vacuum, e.g. for etching. The results were to be used directly by ANTEC GmbH. An efficiency of 14 percent and an idle voltage of about 850 V were to be achieved with a film thickness of 2 #mu#m. To achieve these goals, the following project stages were envisaged: 1. Replacement of the expensive window material ITO by a less costly material. 2. Higher stability of the back contact by using appropriate intermediate layers. 3. Alternative activation processes other than the conventional CdCl_2 activation. 4. Investigation of the effects of the activation step on the electric properties of the sample.Die uebergreifende Aufgabenstellung des Projektes war die Entwicklung und Optimierung des Close-spaced-Sublimation verfahrens in einer Inline-Beschichtungsanlage fuer die Herstellung stabiler und hocheffizienter CdS/CdTe Duennschichtsolarzellen. Mit dem Wissen der ANTEC GmbH sollte zusammen mit dem ISFH eine Inline-Anlage konzipiert und gebaut werden. Die fuer die Solarzelle notwendigen Einzelschichten sollten in dem Inline-Prozess optimiert werden. Es sollte ermittelt werden, ob eine Prozessierung der Einzelschichten ohne Brechen des Vakuums, z.B. fuer einen Aetzschritt, moeglich ist. Die erzielten Ergebnisse sollen direkt der ANTEC GmbH zufliessen. In dem Projekt wurde als Endziel ein Wirkungsgrad der CdTe/CdS-Duennschichtsolarzelle von 14% und eine Erhoehung der Leerlaufspannung auf Werte um 850 mV angestrebt. Gleichzeitig sollte die CdTe-Schichtdicke auf 2 #mu#m vermindert werden. Um dieses Gesamtziel zu erreichen, sollen folgende Teilaufgaben bearbeitet werden: 1) Das teuere Fenstermaterial ITO soll durch ein kostenguenstiges Material ersetzt werden. 2) Die Stabilitaet des Rueckkontaktes soll durch geeignete Rueckkontaktzwischenschichten erhoeht werden. 3) Alternative Aktivierungsprozesse zur herkoemmlichen CdCl_2-Aktivierung sollen erprobt werden. 4) Die Auswirkung des Aktivierungsschrittes auf das elektrische Verhalten der Probe soll mit geeigneten Verfahren untersucht werden. (orig.)Available from TIB Hannover: F03B576+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman