Scanning-probe spectroscopy of semiconductor donor molecules

Semiconductor devices continue to press into the nanoscale regime, and new applications have emerged for which the quantum properties of dopant atoms act as the functional part of the device, underscoring the necessity to probe the quantum structure of small numbers of dopant atoms in semiconductors[1-3]. Although dopant properties are well-understood with respect to bulk semiconductors, new questions arise in nanosystems. For example, the quantum energy levels of dopants will be affected by the proximity of nanometer-scale electrodes. Moreover, because shallow donors and acceptors are analogous to hydrogen atoms, experiments on small numbers of dopants have the potential to be a testing ground for fundamental questions of atomic and molecular physics, such as the maximum negative ionization of a molecule with a given number of positive ions[4,5]. Electron tunneling spectroscopy through isolated dopants has been observed in transport studies[6,7]. In addition, Geim and coworkers identified resonances due to two closely spaced donors, effectively forming donor molecules[8]. Here we present capacitance spectroscopy measurements of silicon donors in a gallium-arsenide heterostructure using a scanning probe technique[9,10]. In contrast to the work of Geim et al., our data show discernible peaks attributed to successive electrons entering the molecules. Hence this work represents the first addition spectrum measurement of dopant molecules. More generally, to the best of our knowledge, this study is the first example of single-electron capacitance spectroscopy performed directly with a scanning probe tip[9].Comment: In press, Nature Physics. Original manuscript posted here; 16 pages, 3 figures, 5 supplementary figure

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Coordinated grid and place cell replay during rest

Hippocampal replay has been hypothesized to underlie memory consolidation and navigational planning, yet the involvement of grid cells in replay is unknown. During replay we found grid cells to be spatially coherent with place cells, encoding locations 11 ms delayed relative to the hippocampus, with directionally modulated grid cells and forward replay exhibiting the greatest coherence with the CA1 area of the hippocampus. This suggests grid cells are engaged during the consolidation of spatial memories to the neocortex

MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1

© 2018 The Author(s). Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions. Furthermore, this process occurs independently of changes in expression of Arc/Arg3.1, a previously characterised MEF2 transcriptional target and mediator of mGluR-dependent long-term depression. These data demonstrate a novel MEF2A-dependent mechanism for the regulation of activity-dependent AMPAR trafficking

In Vivo Analysis of MEF2 Transcription Factors in Synapse Regulation and Neuronal Survival

MEF2 (A–D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain and suggest that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function

Emotional stress as a trigger of falls leading to hip or pelvic fracture. Results from the ToFa study – a case-crossover study among elderly people in Stockholm, Sweden

<p>Abstract</p> <p>Background</p> <p>Sudden emotions may interfere with mechanisms for keeping balance among the elderly. The aim of this study is to analyse if emotional stress and specifically feelings of anger, sadness, worries, anxiety or stress, can trigger falls leading to hip or pelvic fracture among autonomous older people.</p> <p>Methods</p> <p>The study applied the case-crossover design and was based on data gathered by face to face interviews carried out in Stockholm between November 2004 and January 2006 at the emergency wards of two hospitals. Cases (n = 137) were defined as persons aged 65 and older admitted for at least one night due to a fall-related hip or pelvic fracture (ICD10: S72 or S32) and meeting a series of selection criteria. Results are presented as relative risks with 95% confidence intervals.</p> <p>Results</p> <p>There was an increased risk for fall and subsequent hip or pelvic fracture for up to one hour after emotional stress. For anger there was an increased relative risk of 12.2 (95% CI 2.7–54.7), for sadness of 5.7 (95% CI 1.1–28.7), and for stress 20.6 (95% CI 4.5–93.5) compared to periods with no such feelings.</p> <p>Conclusion</p> <p>Emotional stress seems to have the potential to trigger falls and subsequent hip or pelvic fracture among autonomous older people. Further studies are needed to clarify how robust the findings are – as the number of exposed cases is small – and the mechanisms behind them – presumably balance and vision impairment in stress situation.</p

Risk alleles for chronic hepatitis B are associated with decreased mRNA expression of HLA-DPA1 and HLA-DPB1 in normal human liver

A genome-wide association study identified single nucleotide polymorphisms (SNPs) rs3077 and rs9277535 located in the 3′ untranslated regions of human leukocyte antigen (HLA) class II genes HLA-DPA1 and HLA-DPB1, respectively, as the independent variants most strongly associated with chronic hepatitis B. We examined whether these SNPs are associated with mRNA expression of HLA-DPA1 and HLA-DPB1. We identified gene expression-associated SNPs (eSNPs) in normal liver samples obtained from 651 individuals of European ancestry by integrating genotype (∼650 000 SNPs) and gene expression (>39 000 transcripts) data from each sample. We used the Kruskal–Wallis test to determine associations between gene expression and genotype. To confirm findings, we measured allelic expression imbalance (AEI) of complementary DNA compared with DNA in liver specimens from subjects who were heterozygous for rs3077 and rs9277535. On a genome-wide basis, rs3077 was the SNP most strongly associated with HLA-DPA1 expression (p=10−48), and rs9277535 was strongly associated with HLA-DPB1 expression (p=10−15). Consistent with these gene expression associations, we observed AEI for both rs3077 (p=3.0 × 10−7; 17 samples) and rs9277535 (p=0.001; 17 samples). We conclude that the variants previously associated with chronic hepatitis B are also strongly associated with mRNA expression of HLA-DPA1 and HLA-DPB1, suggesting that expression of these genes is important in control of HBV

Structural representations: causally relevant and different from detectors

This paper centers around the notion that internal, mental representations are grounded in structural similarity, i.e., that they are so-called S-representations. We show how S-representations may be causally relevant and argue that they are distinct from mere detectors. First, using the neomechanist theory of explanation and the interventionist account of causal relevance, we provide a precise interpretation of the claim that in S-representations, structural similarity serves as a ‘‘fuel of success’’, i.e., a relation that is exploitable for the representation using system. Then, we discuss crucial differences between S-representations and indicators or detectors, showing that—contrary to claims made in the literature—there is an important theoretical distinction to be drawn between the two

Prioritized memory access explains planning and hippocampal replay.

To make decisions, animals must evaluate candidate choices by accessing memories of relevant experiences. Yet little is known about which experiences are considered or ignored during deliberation, which ultimately governs choice. We propose a normative theory predicting which memories should be accessed at each moment to optimize future decisions. Using nonlocal 'replay' of spatial locations in hippocampus as a window into memory access, we simulate a spatial navigation task in which an agent accesses memories of locations sequentially, ordered by utility: how much extra reward would be earned due to better choices. This prioritization balances two desiderata: the need to evaluate imminent choices versus the gain from propagating newly encountered information to preceding locations. Our theory offers a simple explanation for numerous findings about place cells; unifies seemingly disparate proposed functions of replay including planning, learning, and consolidation; and posits a mechanism whose dysfunction may underlie pathologies like rumination and craving