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: incretin hormone glucagon-like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage-dependent potassium channel.; The gut hormone called glucagon-like peptide 1 (GLP-1) is a strong moderator of energy homeostasis and communication between the peripheral organs and the brain. GLP-1 signalling occurs in the brain; using a newly developed genetic reporter line of mice, we have discovered GLP-synthesizing cells in the olfactory bulb. GLP-1 increases the firing frequency of neurons (mitral cells) that encode olfactory information by decreasing activity of voltage-dependent K channels (Kv1.3). Modifying GLP-1 levels, either therapeutically or following the ingestion of food, could alter the excitability of neurons in the olfactory bulb in a nutrition or energy state-dependent manner to influence olfactory detection or metabolic sensing. The results of the present study uncover a new function for an olfactory bulb neuron (deep short axon cells, Cajal cells) that could be capable of modifying mitral cell activity through the release of GLP-1. This might be of relevance for the action of GLP-1 mimetics now widely used in the treatment of diabetes. The olfactory system is intricately linked with the endocrine system where it may serve as a detector of the internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU-yellow fluorescent protein mice that express a genetic reporter under the control of the preproglucagon reporter suggested the presence of the gut hormone, glucagon-like peptide (GLP-1), in deep short axon cells (Cajal cells) of the olfactory bulb and its neuromodulatory effect on mitral cell (MC) first-order neurons. A MC target for the peptide was determined using GLP-1 receptor binding assays, immunocytochemistry for the receptor and injection of fluorescence-labelled GLP-1 analogue exendin-4. Using patch clamp recording of olfactory bulb slices in the whole-cell configuration, we report that GLP-1 and its stable analogue exendin-4 increase the action potential firing frequency of MCs by decreasing the interburst interval rather than modifying the action potential shape, train length or interspike interval. GLP-1 decreases Kv1.3 channel contribution to outward currents in voltage clamp recordings as determined by pharmacological blockade of Kv1.3 or utilizing mice with Kv1.3 gene-targeted deletion as a negative control. Because fluctuations in GLP-1 concentrations monitored by the olfactory bulb can modify the firing frequency of MCs, olfactory coding could change depending upon nutritional or physiological state. As a regulator of neuronal activity, GLP-1 or its analogue may comprise a new metabolic factor with a potential therapeutic target in the olfactory bulb (i.e. via intranasal delivery) for controlling an imbalance in energy homeostasis., Grant Number: MC_UU_12012/3, R01 DC013080, MR/J013293/2, MR/J013293/1, R03 DC013988,, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865572.

: mA pathway facilitates sex determination in Drosophila.; The conserved modification N-methyladenosine (mA) modulates mRNA processing and activity. Here, we establish the Drosophila system to study the mA pathway. We first apply miCLIP to map mA across embryogenesis, characterize its mA 'writer' complex, validate its YTH 'readers' CG6422 and YT521-B, and generate mutants in five mA factors. While mA factors with additional roles in splicing are lethal, mA-specific mutants are viable but present certain developmental and behavioural defects. Notably, mA facilitates the master female determinant Sxl, since multiple mA components enhance female lethality in Sxl sensitized backgrounds. The mA pathway regulates Sxl processing directly, since miCLIP data reveal Sxl as a major intronic mA target, and female-specific Sxl splicing is compromised in multiple mA pathway mutants. YT521-B is a dominant mA effector for Sxl regulation, and YT521-B overexpression can induce female-specific Sxl splicing. Overall, our transcriptomic and genetic toolkit reveals in vivo biologic function for the Drosophila mA pathway., Grant Number: R01 ES017010, R01 GM072562, P30 CA008748, P30 ES002109, R01 DA037150, R21 ES022858, R01 NS083833, R01 NS074037, R01 GM083300, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500889.

: native cistrome and sequence motif families of the maize ear; Elucidating the transcriptional regulatory networks that underlie growth and development requires robust ways to define the complete set of transcription factor (TF) binding sites. Although TF-binding sites are known to be generally located within accessible chromatin regions (ACRs), pinpointing these DNA regulatory elements globally remains challenging. Current approaches primarily identify binding sites for a single TF (e.g. ChIP-seq), or globally detect ACRs but lack the resolution to consistently define TF-binding sites (e.g. DNAse-seq, ATAC-seq). To address this challenge, we developed MNase-defined cistrome-Occupancy Analysis (MOA-seq), a high-resolution (< 30 bp), high-throughput, and genome-wide strategy to globally identify putative TF-binding sites within ACRs. We used MOA-seq on developing maize ears as a proof of concept, able to define a cistrome of 145,000 MOA footprints (MFs). While a substantial majority (76%) of the known ATAC-seq ACRs intersected with the MFs, only a minority of MFs overlapped with the ATAC peaks, indicating that the majority of MFs were novel and not detected by ATAC-seq. MFs were associated with promoters and significantly enriched for TF-binding and long-range chromatin interaction sites, including for the well-characterized FASCIATED EAR4, KNOTTED1, and TEOSINTE BRANCHED1. Importantly, the MOA-seq strategy improved the spatial resolution of TF-binding prediction and allowed us to identify 215 motif families collectively distributed over more than 100,000 non-overlapping, putatively-occupied binding sites across the genome. Our study presents a simple, efficient, and high-resolution approach to identify putative TF footprints and binding motifs genome-wide, to ultimately define a native cistrome atlas., maize, transcription factor, cistrome, gene, Data Availability: Raw sequences from the MOA-seq and control DNA and RNA-seq libraries were deposited to the NCBI Sequence Reads Archive (https://www.ncbi.nlm.nih.gov/sra) under the Project ID PRJNA477338. https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA477338 All other relevant data are within the manuscript and its Supporting Information (https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009689#sec018) files.

: spatial dynamics of female choice in an exploded lek generate benefits of aggregation for experienced males; The spatial distribution of prospective mates can dramatically affect the process and outcome of mate choice. In a variety of species, spacing between males influences the likelihood that females visit particular individuals or respond to competing signals. Discrimination by females is expected to be highest among neighbouring males, yet males of some species aggregate in ways that apparently facilitate such comparisons. To better understand the selective pressures affecting male aggregation, we investigated how spatial organization of male territories related to female mate sampling tactics and male mating success in the lance-tailed manakin, Chiroxiphia lanceolata. This species displays in a dispersed lek of alpha males, each of which usually has a subordinate beta partner that participates in displays but does not mate with females attracted by their cooperative courtship. We video-recorded courtship activity at display perches of 12 alpha–beta pairs for 42 days in 2013, and documented 478 visits by 82 banded females. We further quantified the relationship of aggregation with genetic mating success for 49 alphas displaying at georeferenced locations in 5 years. Males with close neighbouring alphas were visited by more females, but geographic centrality was unrelated to female visit frequency. Females moved shorter distances between consecutive courtship visits than expected at random, but only 20.5% of 73 females visiting males with video-monitored nearest neighbours visited both neighbouring alpha males. Effects of aggregation on annual genetic reproductive success were only evident after accounting for the stronger effects of alpha age and experience, and only experienced alphas benefited from having close neighbours. Selection for aggregation more likely influences social behaviour of older alphas than settlement decisions by younger males. Benefits of aggregation for experienced alphas mitigate declines in old age, and may generate selective pressure favouring the long-term social alliances that are a key characteristic of this mating system., Chiroxiphia lanceolata, cooperation, cooperative display, exploded lek, female preference, hotshot, hotspot, manakin, mate choice, sampling tactic, NSF 1453408, NSF 0843334, NSF DDIG 1501660

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