231 research outputs found
Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment
Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-beta- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic
Analysis of threshold voltage instabilities in semi-vertical GaN-on-Si FETs
We present a first study of threshold voltage instabilities of semi-vertical GaN-on-Si trench-MOSFETs, based on double pulsed, threshold voltage transient, and UV-Assisted C-V analysis. Under positive gate stress, small negative V th shifts (low stress) and a positive V thshifts (high stress) are observed, ascribed to trapping within the insulator and at the metal/insulator interface. Trapping effects are eliminated through exposure to UV light; wavelength-dependent analysis extracts the threshold de-Trapping energy ≈2.95 eV. UV-Assisted CV measurements describe the distribution of states at the GaN/Al2O3 interface. The described methodology provides an understanding and assessment of trapping mechanisms in vertical GaN transistors
Exploration of Gate Trench Module for Vertical GaN devices
The aim of this work is to present the optimization of the gate trench module
for use in vertical GaN devices in terms of cleaning process of the etched
surface of the gate trench, thickness of gate dielectric and magnesium
concentration of the p-GaN layer. The analysis was carried out by comparing the
main DC parameters of devices that differ in surface cleaning process of the
gate trench, gate dielectric thickness, and body layer doping. . On the basis
of experimental results, we report that: (i) a good cleaning process of the
etched GaN surface of the gate trench is a key factor to enhance the device
performance, (ii) a gate dielectric >35-nm SiO2 results in a narrow
distribution for DC characteristics, (iii) lowering the p-doping in the body
layer improves the ON-resistance (RON). Gate capacitance measurements are
performed to further confirm the results. Hypotheses on dielectric
trapping/detrapping mechanisms under positive and negative gate bias are
reported.Comment: 5 pages, 10 figures, submitted to Microelectronics Reliability
(Special Issue: 31st European Symposium on Reliability of Electron Devices,
Failure Physics and Analysis, ESREF 2020
A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals.
Synapses are often far from the soma and independently cope with proteopathic stress induced by intense neuronal activity. However, how presynaptic compartments turn over proteins is poorly understood. We show that the synapse-enriched protein EndophilinA, thus far studied for its role in endocytosis, induces macroautophagy at presynaptic terminals. We find that EndophilinA executes this unexpected function at least partly independent of its role in synaptic vesicle endocytosis. EndophilinA-induced macroautophagy is activated when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in animals where EndophilinA cannot be phosphorylated. EndophilinA-phosphorylation promotes the formation of highly curved membranes, and reconstitution experiments show these curved membranes serve as docking stations for autophagic factors, including Atg3. Functionally, deregulation of the EndophilinA phosphorylation state accelerates activity-induced neurodegeneration. Given that EndophilinA is connected to at least three Parkinson's disease genes (LRRK2, Parkin and Synaptojanin), dysfunction of EndophilinA-dependent synaptic macroautophagy may be common in this disorder
Bisphenol A shapes children’s brain and behavior: towards an integrated neurotoxicity assessment including human data
The authors gratefully acknowledge editorial assistance provided by Richard
Davies. VM is under contract within the Human Biomonitoring for Europe
Project (European Union Commission H2020-EJP-HBM4EU). The authors acknowledge the funding received from the Biomedical Research Networking
Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the Instituto
de Salud Carlos III (ISCIII) (FIS-PI16/01820 and FIS-PI16/01812). The funders
had no role in the study design, data.Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and
colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time,
associations were reported between prenatal BPA exposure and differences in children’s brain microstructure, which
appeared to mediate the association between this exposure and children’s behavioral symptoms. Findings in numerous
previous mother-child cohorts have pointed in a similar worrying direction, linking higher BPA exposure during pregnancy
to more behavioral problems throughout childhood as assessed by neuropsychological questionnaires. Notwithstanding, this
body of work has not been adequately considered in risk assessment. From a toxicological perspective, results are now
available from the CLARITY-BPA consortium, designed to reconcile academic and regulatory toxicology findings. In fact, the
brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those
considered safe by regulatory agencies such as the European Food Safety Authority (EFSA). In this Commentary, we
contextualize the results of Grohs et al. within the setting of previous epidemiologic and CLARITY-BPA data and express our
disquiet about the “all-or-nothing” criterion adopted to select human data in a recent EFSA report on the appraisal
methodology for their upcoming BPA risk assessment. We discuss the most relevant human studies, identify emerging
patterns, and highlight the need for adequate assessment and interpretation of the increasing epidemiologic literature in this
field in order to support decision-making. With the aim of avoiding a myopic or biased selection of a few studies in
traditional risk assessment procedures, we propose a future reevaluation of BPA focused on neurotoxicity and based on a
systematic and comprehensive integration of available mechanistic, animal, and human data. Taken together, the
experimental and epidemiologic evidence converge in the same direction: BPA is a probable developmental neurotoxicant
at low doses. Accordingly, the precautionary principle should be followed, progressively implementing stringent preventive
policies worldwide, including the banning of BPA in food contact materials and thermal receipts, with a focus on the
utilization of safer substitutes.European Union (EU): H2020-EJP-HBM4EUBiomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP)Instituto de Salud Carlos III
FIS-PI16/01820
FIS-PI16/0181
Triplet Exciton Generation in Bulk-Heterojunction Solar Cells based on Endohedral Fullerenes
Organic bulk-heterojunctions (BHJ) and solar cells containing the trimetallic
nitride endohedral fullerene 1-[3-(2-ethyl)hexoxy
carbonyl]propyl-1-phenyl-Lu3N@C80 (Lu3N@C80-PCBEH) show an open circuit voltage
(VOC) 0.3 V higher than similar devices with [6,6]-phenyl-C[61]-butyric acid
methyl ester (PC61BM). To fully exploit the potential of this acceptor molecule
with respect to the power conversion efficiency (PCE) of solar cells, the short
circuit current (JSC) should be improved to become competitive with the state
of the art solar cells. Here, we address factors influencing the JSC in blends
containing the high voltage absorber Lu3N@C80-PCBEH in view of both
photogeneration but also transport and extraction of charge carriers. We apply
optical, charge carrier extraction, morphology, and spin-sensitive techniques.
In blends containing Lu3N@C80-PCBEH, we found 2 times weaker photoluminescence
quenching, remainders of interchain excitons, and, most remarkably, triplet
excitons formed on the polymer chain, which were absent in the reference
P3HT:PC61BM blends. We show that electron back transfer to the triplet state
along with the lower exciton dissociation yield due to intramolecular charge
transfer in Lu3N@C80-PCBEH are responsible for the reduced photocurrent
Non-Breeding Song Rate Reflects Nutritional Condition Rather than Body Condition
Numerous studies have focused on song in songbirds as a signal involved in mate choice and intrasexual competition. It is expected that song traits such as song rate reflect individual quality by being dependent on energetic state or condition. While seasonal variation in bird song (i.e., breeding versus non-breeding song) and its neural substrate have received a fair amount of attention, the function and information content of song outside the breeding season is generally much less understood. Furthermore, typically only measures of condition involving body mass are examined with respect to song rate. Studies investigating a potential relationship between song rate and other indicators of condition, such as physiological measures of nutritional condition, are scant. In this study, we examined whether non-breeding song rate in male European starlings (Sturnus vulgaris) reflects plasma metabolite levels (high-density lipoproteins (HDL), albumin, triglycerides and cholesterol) and/or body mass. Song rate was significantly positively related to a principal component representing primarily HDL, albumin and cholesterol (and to a lesser degree plasma triglyceride levels). There was only a trend toward a significant positive correlation between song rate and body mass, and no significant correlation between body mass and the abovementioned principal component. Therefore, our results indicate that nutritional condition and body mass represent different aspects of condition, and that song rate reflects nutritional rather than body condition. Additionally, we also found that intra-individual song rate consistency (though not song rate itself) was significantly positively related to lutein levels, but not to body mass or nutritional condition. Together our results suggest that the relation between physiological measures of nutritional condition and song rate, as well as other signals, may present an interesting line of future research, both inside and outside the breeding season
Parthenogenic Blastocysts Derived from Cumulus-Free In Vitro Matured Human Oocytes
Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis..Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer
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