Disordered aldosterone-volume relationship in end-stage kidney disease

Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship

Interaction proteomics of synapse protein complexes

The brain integrates complex types of information, and executes a wide range of physiological and behavioral processes. Trillions of tiny organelles, the synapses, are central to neuronal communication and information processing in the brain. Synaptic transmission involves an intricate network of synaptic proteins that forms the molecular machinery underlying transmitter release, activation, and modulation of transmitter receptors and signal transduction cascades. These processes are dynamically regulated and underlie neuroplasticity, crucial to learning and memory formation. In recent years, interaction proteomics has increasingly been used to elucidate the constituents of synaptic protein complexes. Unlike classic hypothesis-based assays, interaction proteomics detects both known and novel interactors without bias. In this trend article, we focus on the technical aspects of recent proteomics to identify synapse protein complexes, and the complementary methods used to verify the protein–protein interaction. Moreover, we discuss the experimental feasibility of performing global analysis of the synapse protein interactome

Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time

What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals

Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila

<p>Abstract</p> <p>Background</p> <p>In male <it>Drosophila melanogaster</it>, the male specific lethal (MSL) complex is somehow responsible for a two-fold increase in transcription of most X-linked genes, which are enriched for histone H4 acetylated at lysine 16 (H4K16ac). This acetylation requires MOF, a histone acetyltransferase that is a component of the MSL complex. MOF also associates with the non-specific lethal or NSL complex. The MSL complex is bound within active genes on the male X chromosome with a 3' bias. In contrast, the NSL complex is enriched at promoter regions of many autosomal and X-linked genes in both sexes. In this study we have investigated the role of MOF as a transcriptional activator.</p> <p>Results</p> <p>MOF was fused to the DNA binding domain of Gal4 and targeted to the promoter region of UAS-reporter genes in <it>Drosophila</it>. We found that expression of a UAS-red fluorescent protein (DsRed) reporter gene was strongly induced by Gal4-MOF. However, DsRed RNA levels were about seven times higher in female than male larvae. Immunostaining of polytene chromosomes showed that Gal4-MOF co-localized with MSL1 to many sites on the X chromosome in male but not female nuclei. However, in female nuclei that express MSL2, Gal4-MOF co-localized with MSL1 to many sites on polytene chromosomes but DsRed expression was reduced. Mutation of conserved active site residues in MOF (Glu714 and Cys680) reduced HAT activity <it>in vitro </it>and UAS-DsRed activation in <it>Drosophila</it>. In the presence of Gal4-MOF, H4K16ac levels were enriched over UAS-<it>lacZ </it>and UAS-<it>arm-lacZ </it>reporter genes. The latter utilizes the constitutive promoter from the <it>arm </it>gene to drive <it>lacZ </it>expression. In contrast to the strong induction of UAS-DsRed expression, UAS-<it>arm-lacZ </it>expression increased by about 2-fold in both sexes.</p> <p>Conclusions</p> <p>Targeting MOF to reporter genes led to transcription enhancement and acetylation of histone H4 at lysine 16. Histone acetyltransferase activity was required for the full transcriptional response. Incorporation of Gal4-MOF into the MSL complex in males led to a lower transcription enhancement of UAS-<it>DsRed </it>but not UAS-<it>arm-lacZ </it>genes. We discuss how association of Gal4-MOF with the MSL or NSL proteins could explain our results.</p

Uncertainty Compensation in Human Attention: Evidence from Response Times and Fixation Durations

BACKGROUND: Uncertainty and predictability have remained at the center of the study of human attention. Yet, studies have only examined whether response times (RT) or fixations were longer or shorter under levels of stimulus uncertainty. To date, no study has examined patterns of stimuli and responses through a unifying framework of uncertainty. METHODOLOGY/PRINCIPAL FINDINGS: We asked 29 college students to generate repeated responses to a continuous series of visual stimuli presented on a computer monitor. Subjects produced these responses by pressing on a keypad as soon a target was detected (regardless of position) while the durations of their visual fixations were recorded. We manipulated the level of stimulus uncertainty in space and time by changing the number of potential stimulus locations and time intervals between stimulus presentations. To allow the analyses to be conducted using uncertainty as common description of stimulus and response we calculated the entropy of the RT and fixation durations. We tested the hypothesis of uncertainty compensation across space and time by fitting the RT and fixation duration entropy values to a quadratic surface. The quadratic surface accounted for 80% of the variance in the entropy values of both RT and fixation durations. RT entropy increased as a function of spatial and temporal uncertainty of the stimulus, alongside a symmetric, compensatory decrease in the entropy of fixation durations as the level of spatial and temporal uncertainty of the stimuli was increased. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that greater uncertainty in the stimulus leads to greater uncertainty in the response, and that the effects of spatial and temporal uncertainties are compensatory. We also observed compensatory relationship across the entropies of fixation duration and RT, suggesting that a more predictable visual search strategy leads to more uncertain response patterns and vice versa

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18