po Wintrust Financial Corporation to Present at RBC Capital Markets Global Financial Institutions Conference on March 10, 2020 By www.snl.com Published On :: Thu, 27 Feb 2020 23:49:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Announces Precautionary Decision to Help Achieve Community Health Objectives By Temporarily Closing Selected Branches By www.snl.com Published On :: Tue, 17 Mar 2020 11:00:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Announces Further Actions To Help Achieve Community Health Objectives By www.snl.com Published On :: Fri, 20 Mar 2020 11:00:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Working Tirelessly To Support Strong Community Interest in the Paycheck Protection Program By www.snl.com Published On :: Fri, 10 Apr 2020 20:42:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Announces First Quarter 2020 Earnings Release Schedule By www.snl.com Published On :: Thu, 16 Apr 2020 22:51:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation to Make Loans to Approximately 8,900 Small Businesses Through the Paycheck Protection Program By www.snl.com Published On :: Fri, 17 Apr 2020 22:27:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Reports First Quarter 2020 Net Income of $62.8 million By www.snl.com Published On :: Tue, 21 Apr 2020 22:15:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Announces Cash Dividends By www.snl.com Published On :: Thu, 23 Apr 2020 20:23:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Wintrust Financial Corporation Announces Pricing of $250 Million Preferred Stock Offering By www.snl.com Published On :: Wed, 06 May 2020 22:37:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
po Academy responds to novel coronavirus and calls for ideas By www.raeng.org.uk Published On :: Thu, 26 Mar 2020 17:03:57 +00:00 Full Article
po Academy President comments on postponement of COP26 By www.raeng.org.uk Published On :: Thu, 02 Apr 2020 16:30:00 +01:00 Full Article
po Academy comments on government support for entrepreneurs By www.raeng.org.uk Published On :: Wed, 22 Apr 2020 09:15:34 +01:00 Full Article
po New Engineering X Pandemic Preparedness programme to support global innovation and knowledge sharing By www.raeng.org.uk Published On :: Mon, 04 May 2020 13:00:00 +01:00 Full Article
po National Engineering Policy Centre to provide advice to government on reaching net zero emissions By www.raeng.org.uk Published On :: Wed, 06 May 2020 00:01:54 +01:00 Full Article
po HP's COVID-19 Response: There Should Be an Award for This By www.technewsworld.com Published On :: 2020-04-27T11:16:34-07:00 Some of the troubling reports of corporate responses to COVID-19 include forced work in unsafe areas, not enough -- or any -- protection gear, massive layoffs and furloughs, and the sense that a critical mass of well-paid CEOs and politicians don't get that many people live paycheck to paycheck. There are exceptions though, and HP stands out, thanks to HR VP Tracy Keogh and CEO Enrique Lores. Full Article
po EndeavourOS 2020: Possibly the Best Arch Linux Option By www.technewsworld.com Published On :: 2020-05-01T06:00:00-07:00 EndeavourOS is a rolling release Arch Linux-based distribution with some handy new features that improve the user experience. This latest version comes with graphical install options and preconfigured desktop environments. Several new in-house utilities improve package management and error reporting. There are lots of installation tips with the Calamares installer, which has a new look and feel. Full Article
po A 6-Point Plan to Leapfrog to CX Leadership By www.crmbuyer.com Published On :: 2020-04-08T11:58:09-07:00 Customer experience as a boardroom topic is more relevant than ever. Enterprises are investing significant digital transformation budgets and commissioning large projects to elevate CX. Yet more than 70 percent of digital transformation projects fail to move the needle at scale. One topic that has a substantial impact on CX is the transformation of customer service operations using digital tools. Full Article
po The lawyer who laundered political contributions By www.mcclatchydc.com Published On :: Full Article
po SHI to sponsor lecture on totem parks of Southeast Alaska By www.sealaskaheritage.org Published On :: Full Article
po Monetary policy: 10 years after the financial crisis By www.bis.org Published On :: 2019-09-05T16:20:00Z Speech by Mr Agustín Carstens, General Manager of the BIS, to the Basler Bankenforum, Basel, 5 September 2019. Full Article
po Wise fiscal policy is not about helicopter money By www.bis.org Published On :: 2019-11-08T12:15:00Z Op-ed by Mr Claudio Borio, Head of the Monetary and Economic Department of the BIS, published in Il Sole 24 Ore, 8 November 2019. Full Article
po Data, technology and policy coordination By www.bis.org Published On :: 2019-11-14T01:00:00Z Keynote speech by Mr Agustín Carstens, General Manager of the BIS, at the 55th SEACEN Governors' Conference and High-level Seminar on "Data and technology: embracing innovation", Singapore, 14 November 2019. Full Article
po [~21.8 MB mp3] A Leading Figure In The New Apostolic Reformation By podcastdownload.npr.org Published On :: Story: Several apostles affiliated with the movement helped organize or spoke at Rick Perry's recent prayer rally. A leading apostle, C. Peter Wagner, talks about the movement and its missions, which include acquiring leadership positions in government, the media, and arts and entertainment. Full Article
po The Right Temporoparietal Junction Is Causally Associated with Embodied Perspective-taking By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning. SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner. Full Article
po Ultra-high-resolution fMRI of Human Ventral Temporal Cortex Reveals Differential Representation of Categories and Domains By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans. SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale. Full Article
po Noncoding Microdeletion in Mouse Hgf Disrupts Neural Crest Migration into the Stria Vascularis, Reduces the Endocochlear Potential, and Suggests the Neuropathology for Human Nonsyndromic Deafness DFNB39 By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness. SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic. Full Article
po Interneuron NMDA Receptor Ablation Induces Hippocampus-Prefrontal Cortex Functional Hypoconnectivity after Adolescence in a Mouse Model of Schizophrenia By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 Although the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although schizophrenia's pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical interneurons as a central element. It has been suggested that alterations in parvalbumin-positive interneurons in schizophrenia are the consequence of a deficient signaling through NMDARs. Animal studies demonstrated that early postnatal ablation of the NMDAR in corticolimbic interneurons induces neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably, the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are absent if the NMDAR is deleted during adulthood. This suggests that interneuron dysfunction must interact with development to impact on behavior. Here, we assess in vivo how an early NMDAR ablation in corticolimbic interneurons impacts on mPFC and ventral hippocampus functional connectivity before and after adolescence. In juvenile male mice, NMDAR ablation results in several pathophysiological traits, including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta rhythms. In addition, adult male KO mice showed reduced ventral hippocampus-mPFC-evoked potentials and an augmented low-frequency stimulation LTD of the pathway, suggesting that there is a functional disconnection between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in interneurons can interact with postnatal development during adolescence, triggering pathophysiological mechanisms related to schizophrenia that exceed those caused by NMDAR interneuron hypofunction alone. SIGNIFICANCE STATEMENT NMDAR hypofunction in cortical interneurons has been linked to schizophrenia pathophysiology. How a dysfunction of GABAergic cortical interneurons interacts with maturation during adolescence has not been clarified yet. Here, we demonstrate in vivo that early postnatal ablation of the NMDAR in corticolimbic interneurons results in an overactive but desynchronized PFC before adolescence. Final postnatal maturation during this stage outspreads the impact of the genetic manipulation toward a functional disconnection of the ventral hippocampal-prefrontal pathway, probably as a consequence of an exacerbated propensity toward hippocampal-evoked depotentiation plasticity. Our results demonstrate a complex interaction between genetic and developmental factors affecting cortical interneurons and PFC function. Full Article
po Resolving the Spatial Profile of Figure Enhancement in Human V1 through Population Receptive Field Modeling By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 The detection and segmentation of meaningful figures from their background is one of the primary functions of vision. While work in nonhuman primates has implicated early visual mechanisms in this figure–ground modulation, neuroimaging in humans has instead largely ascribed the processing of figures and objects to higher stages of the visual hierarchy. Here, we used high-field fMRI at 7 Tesla to measure BOLD responses to task-irrelevant orientation-defined figures in human early visual cortex (N = 6, four females). We used a novel population receptive field mapping-based approach to resolve the spatial profiles of two constituent mechanisms of figure–ground modulation: a local boundary response, and a further enhancement spanning the full extent of the figure region that is driven by global differences in features. Reconstructing the distinct spatial profiles of these effects reveals that figure enhancement modulates responses in human early visual cortex in a manner consistent with a mechanism of automatic, contextually driven feedback from higher visual areas. SIGNIFICANCE STATEMENT A core function of the visual system is to parse complex 2D input into meaningful figures. We do so constantly and seamlessly, both by processing information about visible edges and by analyzing large-scale differences between figure and background. While influential neurophysiology work has characterized an intriguing mechanism that enhances V1 responses to perceptual figures, we have a poor understanding of how the early visual system contributes to figure–ground processing in humans. Here, we use advanced computational analysis methods and high-field human fMRI data to resolve the distinct spatial profiles of local edge and global figure enhancement in the early visual system (V1 and LGN); the latter is distinct and consistent with a mechanism of automatic, stimulus-driven feedback from higher-level visual areas. Full Article
po Ventral Hippocampal Input to the Prelimbic Cortex Dissociates the Context from the Cue Association in Trace Fear Memory By www.jneurosci.org Published On :: 2020-04-15T09:30:18-07:00 The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations. SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning. Full Article
po Sustained Visual Priming Effects Can Emerge from Attentional Oscillation and Temporal Expectation By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 Priming refers to the influence that a previously encountered object exerts on future responses to similar objects. For many years, visual priming has been known as a facilitation and sometimes an inhibition effect that lasts for an extended period of time. It contrasts with the recent finding of an oscillated priming effect where facilitation and inhibition alternate over time periodically. Here we developed a computational model of visual priming that combines rhythmic sampling of the environment (attentional oscillation) with active preparation for future events (temporal expectation). Counterintuitively, it shows that both the sustained and oscillated priming effects can emerge from an interaction between attentional oscillation and temporal expectation. The interaction also leads to novel predictions, such as the change of visual priming effects with temporal expectation and attentional oscillation. Reanalysis of two published datasets and the results of two new experiments of visual priming tasks with male and female human participants provide support for the model's relevance to human behavior. More generally, our model offers a new perspective that may unify the increasing findings of behavioral and neural oscillations with the classic findings in visual perception and attention. SIGNIFICANCE STATEMENT There is increasing behavioral and neural evidence that visual attention is a periodic process that sequentially samples different alternatives in the theta frequency range. It contrasts with the classic findings of sustained facilitatory or inhibitory attention effects. How can an oscillatory perceptual process give rise to sustained attention effects? Here we make this connection by proposing a computational model for a "fruit fly" visual priming task and showing both the sustained and oscillated priming effects can have the same origin: an interaction between rhythmic sampling of the environment and active preparation for future events. One unique contribution of our model is to predict how temporal contexts affects priming. It also opens up the possibility of reinterpreting other attention-related classic phenomena. Full Article
po The Firing of Theta State-Related Septal Cholinergic Neurons Disrupt Hippocampal Ripple Oscillations via Muscarinic Receptors By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate. SIGNIFICANCE STATEMENT The major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to speculation that the septo-hippocampal cholinergic projection contributing to theta oscillation. In this article, by long-term recording of MS cholinergic neurons, we found that they show a theta state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during slow-wave sleep could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M2 and M4 receptors. Full Article
po Neurog2 Acts as a Classical Proneural Gene in the Ventromedial Hypothalamus and Is Required for the Early Phase of Neurogenesis By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 The tuberal hypothalamus is comprised of the dorsomedial, ventromedial, and arcuate nuclei, as well as parts of the lateral hypothalamic area, and it governs a wide range of physiologies. During neurogenesis, tuberal hypothalamic neurons are thought to be born in a dorsal-to-ventral and outside-in pattern, although the accuracy of this description has been questioned over the years. Moreover, the intrinsic factors that control the timing of neurogenesis in this region are poorly characterized. Proneural genes, including Achate-scute-like 1 (Ascl1) and Neurogenin 3 (Neurog3) are widely expressed in hypothalamic progenitors and contribute to lineage commitment and subtype-specific neuronal identifies, but the potential role of Neurogenin 2 (Neurog2) remains unexplored. Birthdating in male and female mice showed that tuberal hypothalamic neurogenesis begins as early as E9.5 in the lateral hypothalamic and arcuate and rapidly expands to dorsomedial and ventromedial neurons by E10.5, peaking throughout the region by E11.5. We confirmed an outside-in trend, except for neurons born at E9.5, and uncovered a rostrocaudal progression but did not confirm a dorsal-ventral patterning to tuberal hypothalamic neuronal birth. In the absence of Neurog2, neurogenesis stalls, with a significant reduction in early-born BrdU+ cells but no change at later time points. Further, the loss of Ascl1 yielded a similar delay in neuronal birth, suggesting that Ascl1 cannot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypothalamus. Together, our findings show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of tuberal hypothalamic neurogenesis. SIGNIFICANCE STATEMENT Here, we investigated the general timing and pattern of neurogenesis within the tuberal hypothalamus. Our results confirmed an outside-in trend of neurogenesis and uncovered a rostrocaudal progression. We also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the birth of early-born neurons within the ventromedial hypothalamus, acting independently of Ascl1. In addition, we revealed a role for Neurog2 in cell fate specification and differentiation of ventromedial -specific neurons. Last, Neurog2 does not have cross-inhibitory effects on Neurog1, Neurog3, and Ascl1. These findings are the first to reveal a role for Neurog2 in hypothalamic development. Full Article
po Carbon Monoxide, a Retrograde Messenger Generated in Postsynaptic Mushroom Body Neurons, Evokes Noncanonical Dopamine Release By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca2+ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling. SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation. Full Article
po The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ. SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies. Full Article
po Uncharacteristic Task-Evoked Pupillary Responses Implicate Atypical Locus Ceruleus Activity in Autism By www.jneurosci.org Published On :: 2020-05-06T09:30:22-07:00 Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD. SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD. Full Article
po M-Current Inhibition in Hippocampal Excitatory Neurons Triggers Intrinsic and Synaptic Homeostatic Responses at Different Temporal Scales By www.jneurosci.org Published On :: 2020-05-06T09:30:22-07:00 Persistent alterations in neuronal activity elicit homeostatic plastic changes in synaptic transmission and/or intrinsic excitability. However, it is unknown whether these homeostatic processes operate in concert or at different temporal scales to maintain network activity around a set-point value. Here we show that chronic neuronal hyperactivity, induced by M-channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in cultured hippocampal pyramidal neurons from mice of either sex. Homeostatic changes of intrinsic excitability occurred at a fast timescale (1–4 h) and depended on ongoing spiking activity. This fast intrinsic adaptation included plastic changes in the threshold current and a distal relocation of FGF14, a protein physically bridging Nav1.6 and Kv7.2 channels along the axon initial segment. In contrast, synaptic adaptations occurred at a slower timescale (~2 d) and involved decreases in miniature EPSC amplitude. To examine how these temporally distinct homeostatic responses influenced hippocampal network activity, we quantified the rate of spontaneous spiking measured by multielectrode arrays at extended timescales. M-Channel blockade triggered slow homeostatic renormalization of the mean firing rate (MFR), concomitantly accompanied by a slow synaptic adaptation. Thus, the fast intrinsic adaptation of excitatory neurons is not sufficient to account for the homeostatic normalization of the MFR. In striking contrast, homeostatic adaptations of intrinsic excitability and spontaneous MFR failed in hippocampal GABAergic inhibitory neurons, which remained hyperexcitable following chronic M-channel blockage. Our results indicate that a single perturbation such as M-channel inhibition triggers multiple homeostatic mechanisms that operate at different timescales to maintain network mean firing rate. SIGNIFICANCE STATEMENT Persistent alterations in synaptic input elicit homeostatic plastic changes in neuronal activity. Here we show that chronic neuronal hyperexcitability, induced by M-type potassium channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in hippocampal excitatory neurons. The data indicate that the fast adaptation of intrinsic excitability depends on ongoing spiking activity but is not sufficient to provide homeostasis of the mean firing rate. Our results show that a single perturbation such as M-channel inhibition can trigger multiple homeostatic processes that operate at different timescales to maintain network mean firing rate. Full Article
po Report: eradicate hunger and malnutrition By www.fao.org Published On :: Wed, 05 Jun 2013 01:00:00 GMT Eradicating hunger must be accompanied by strenuous efforts to end malnutrition and its devastating effects. That was a pivotal message at the launch of FAO’s key publication The State of Food and Agriculture, which this year focuses on Food systems for better nutrition. “FAO’s message is that we must strive for nothing less than the eradication of hunger and malnutrition,” said Director-General [...] Full Article
po Zero Hunger is possible ‘within our lifetimes' By www.fao.org Published On :: Tue, 24 Sep 2013 00:00:00 GMT FAO Director-General José Graziano da Silva underlined his firm belief that a hunger-free world is possible "within our lifetimes," during high-level talks in New York. "The Zero Hunger Challenge calls for something new – something bold, but long overdue," he said. It was a "decisive global commitment to end hunger, eliminate childhood stunting, make all food systems sustainable, eradicate rural poverty, [...] Full Article
po Empowerment is key to eradicating hunger By www.fao.org Published On :: Wed, 05 Mar 2014 00:00:00 GMT Global food security largely depends on smallholder family farms where in many regions of the world women play a crucial role as both producers and providers of food. Studies show that when women and other rural poor have better access to resources, the benefits are far-reaching. Families are healthier, more children attend school, agricultural productivity improves, incomes increase, and rural communities [...] Full Article
po 5 critical things we learned from the latest IPCC report on climate change By www.fao.org Published On :: Wed, 02 Apr 2014 00:00:00 GMT Today leading international experts on climate change, the IPCC, presented their latest report on the impacts of climate change on humanity, and what we can do about it. It’s a lengthy report, so we’ve shrunk it down to Oxfam's five key takeaways on climate change and hunger. 1. Climate change: the impacts on crops are worse than we thought Climate change has [...] Full Article
po 7 things you should know about FAO and the Post-2015 development agenda By www.fao.org Published On :: Thu, 03 Apr 2014 00:00:00 GMT As FAO launches dedicated webpages on post-2015, here are seven things to know about the process and how FAO is playing its part. 7 - Post-2015 development agenda - The name refers to the process through which Member States agree on a new global development framework to succeed the Millennium Development Goals (MDGs), eight goals that followed the UN Millennium Declaration [...] Full Article
po Blue growth - unlocking the potential of seas and oceans By www.fao.org Published On :: Wed, 02 Jul 2014 00:00:00 GMT Today’s fisheries sector hosts a multibillion dollar industry that is a vital source of food and nutrition, employment, trade, economic wellbeing and recreation. What is blue growth? The concept of a "blue economy" came out of the 2012 Rio+20 Conference and emphasizes conservation and sustainable management, based on the premise that healthy ocean ecosystems are more productive and a must for sustainable [...] Full Article
po Food waste & loss – the blind spot in the fight against hunger By www.fao.org Published On :: Wed, 13 May 2015 00:00:00 GMT Whether we categorize uneaten food as “lost” or “wasted” depends on where it goes out of the food supply chain. Imagine how everything we eat travels across a food supply chain, a complex journey that stretches from farm to table. Studies show that an astounding 1/3 of all the food we produce for human consumption never actually reaches our plates. Most [...] Full Article
po 7 rules-of-thumb to follow in aquaponics By www.fao.org Published On :: Wed, 19 Aug 2015 00:00:00 GMT From a media bed unit start-up in Bangkok to a fully developed 120 households deep water culture (DWC) unit in Ethiopia, aquaponics is showcasing its true potential to produce sustainable food anytime, anywhere. A marriage between aquaculture (raising aquatic animals such as fish, snails or prawns in tanks) and hydroponics (cultivating plants in water), aquaponics is a ‘clean and green’ [...] Full Article
po Spotlight: Seven bee-friendly fruits and veggies By www.fao.org Published On :: Wed, 16 Sep 2015 00:00:00 GMT Bees pollinate a third of what we eat and play a vital role in sustaining the planet’s ecosystems. Some 84% of the crops grown for human consumption need bees or other insects to pollinate them to increase their yields and quality. Bee pollination not only results in a higher number of fruits, berries or seeds, it may also give a [...] Full Article
po Spotlight: How do pulses contribute to a sustainable world? By www.fao.org Published On :: Wed, 27 Apr 2016 00:00:00 GMT Pulses are being celebrated in 2016 all over the world since they are nutritious, suited for use in a variety of dishes, easy on the budget and good for the health of the soil. From food security and nutrition to ensuring biodiversity and mitigating the effects of climate change, pulses contribute to sustainable development. Here is how. 1. Nutritional benefits of pulses Pulses [...] Full Article
po Introducing TARGET: #ZeroHunger, FAO's new podcast series on global food issues By www.fao.org Published On :: Wed, 15 Jun 2016 00:00:00 GMT Radio culture is gaining more and more ground as millions of listeners take to audio podcasts as a convenient and accessible way to learn new information. Which is why FAO is stepping up into the medium to bring you insights into some of the issues concerning food and agriculture worldwide. Here are the first seven audio offerings of FAO’s new podcast [...] Full Article
po The power of pollinators: why more bees means better food By www.fao.org Published On :: Wed, 24 Aug 2016 00:00:00 GMT What do cucumbers, mustard, almonds and alfalfa have in common? On the surface it appears to be very little. However, there is one thing they do share: They all owe their existence to the service of bees. There is more to the tiny striped helper than sweet honey and a painful sting. For millennia, it has carried out its service [...] Full Article
po State of the World: Ten reports you need in your library By www.fao.org Published On :: Wed, 01 Feb 2017 00:00:00 GMT Every year, FAO publishes a number of major ‘State of the World’ reports containing balanced, science-based reviews of issues related to food, agriculture, forestry, fisheries and natural resources. The reports also cover vital areas such as food production and hunger alleviation, which are at the heart of FAO’s work. With close to 800 million people currently chronically undernourished and an extra [...] Full Article