The Democracy Fund + UCLA Nationscape Project found some misinformation about the coronavirus is more widespread that you might think.

Maxim Rabinovich, Aaditya Ramdas, Michael I. Jordan, Martin J. Wainwright.

Source: Bayesian Analysis, Volume 15, Number 2, 505--532.

Abstract:
Slow mixing is the central hurdle is applications of Markov chains, especially those used for Monte Carlo approximations (MCMC). In the setting of Bayesian inference, it is often only of interest to estimate the stationary expectations of a small set of functions, and so the usual definition of mixing based on total variation convergence may be too conservative. Accordingly, we introduce function-specific analogs of mixing times and spectral gaps, and use them to prove Hoeffding-like function-specific concentration inequalities. These results show that it is possible for empirical expectations of functions to concentrate long before the underlying chain has mixed in the classical sense, and we show that the concentration rates we achieve are optimal up to constants. We use our techniques to derive confidence intervals that are sharper than those implied by both classical Markov-chain Hoeffding bounds and Berry-Esseen-corrected central limit theorem (CLT) bounds. For applications that require testing, rather than point estimation, we show similar improvements over recent sequential testing results for MCMC. We conclude by applying our framework to real-data examples of MCMC, providing evidence that our theory is both accurate and relevant to practice.

Antony Overstall, James McGree.

Source: Bayesian Analysis, Volume 15, Number 1, 103--131.

Abstract:
A Bayesian design is given by maximising an expected utility over a design space. The utility is chosen to represent the aim of the experiment and its expectation is taken with respect to all unknowns: responses, parameters and/or models. Although straightforward in principle, there are several challenges to finding Bayesian designs in practice. Firstly, the utility and expected utility are rarely available in closed form and require approximation. Secondly, the design space can be of high-dimensionality. In the case of intractable likelihood models, these problems are compounded by the fact that the likelihood function, whose evaluation is required to approximate the expected utility, is not available in closed form. A strategy is proposed to find Bayesian designs for intractable likelihood models. It relies on the development of an automatic, auxiliary modelling approach, using multivariate Gaussian process emulators, to approximate the likelihood function. This is then combined with a copula-based approach to approximate the marginal likelihood (a quantity commonly required to evaluate many utility functions). These approximations are demonstrated on examples of stochastic process models involving experimental aims of both parameter estimation and model comparison.

Jeong Eun Lee, Geoff K. Nicholls, Robin J. Ryder.

Source: Bayesian Analysis, Volume 14, Number 4, 1245--1269.

Abstract:
We develop and apply two calibration procedures for checking the coverage of approximate Bayesian credible sets, including intervals estimated using Monte Carlo methods. The user has an ideal prior and likelihood, but generates a credible set for an approximate posterior based on some approximate prior and likelihood. We estimate the realised posterior coverage achieved by the approximate credible set. This is the coverage of the unknown “true” parameter if the data are a realisation of the user’s ideal observation model conditioned on the parameter, and the parameter is a draw from the user’s ideal prior. In one approach we estimate the posterior coverage at the data by making a semi-parametric logistic regression of binary coverage outcomes on simulated data against summary statistics evaluated on simulated data. In another we use Importance Sampling from the approximate posterior, windowing simulated data to fall close to the observed data. We illustrate our methods on four examples.

Julyan Arbel, Pierpaolo De Blasi, Igor Prünster.

Source: Bayesian Analysis, Volume 14, Number 3, 753--771.

Abstract:
In this paper we consider approximations to the popular Pitman–Yor process obtained by truncating the stick-breaking representation. The truncation is determined by a random stopping rule that achieves an almost sure control on the approximation error in total variation distance. We derive the asymptotic distribution of the random truncation point as the approximation error $epsilon$ goes to zero in terms of a polynomially tilted positive stable random variable. The practical usefulness and effectiveness of this theoretical result is demonstrated by devising a sampling algorithm to approximate functionals of the $epsilon$ -version of the Pitman–Yor process.

Marko Järvenpää, Michael U. Gutmann, Arijus Pleska, Aki Vehtari, Pekka Marttinen.

Source: Bayesian Analysis, Volume 14, Number 2, 595--622.

Abstract:
Approximate Bayesian computation (ABC) is a method for Bayesian inference when the likelihood is unavailable but simulating from the model is possible. However, many ABC algorithms require a large number of simulations, which can be costly. To reduce the computational cost, Bayesian optimisation (BO) and surrogate models such as Gaussian processes have been proposed. Bayesian optimisation enables one to intelligently decide where to evaluate the model next but common BO strategies are not designed for the goal of estimating the posterior distribution. Our paper addresses this gap in the literature. We propose to compute the uncertainty in the ABC posterior density, which is due to a lack of simulations to estimate this quantity accurately, and define a loss function that measures this uncertainty. We then propose to select the next evaluation location to minimise the expected loss. Experiments show that the proposed method often produces the most accurate approximations as compared to common BO strategies.

Łukasz Rajkowski.

Source: Bayesian Analysis, Volume 14, Number 2, 477--494.

Abstract:
Mixture models are a natural choice in many applications, but it can be difficult to place an a priori upper bound on the number of components. To circumvent this, investigators are turning increasingly to Dirichlet process mixture models (DPMMs). It is therefore important to develop an understanding of the strengths and weaknesses of this approach. This work considers the MAP (maximum a posteriori) clustering for the Gaussian DPMM (where the cluster means have Gaussian distribution and, for each cluster, the observations within the cluster have Gaussian distribution). Some desirable properties of the MAP partition are proved: ‘almost disjointness’ of the convex hulls of clusters (they may have at most one point in common) and (with natural assumptions) the comparability of sizes of those clusters that intersect any fixed ball with the number of observations (as the latter goes to infinity). Consequently, the number of such clusters remains bounded. Furthermore, if the data arises from independent identically distributed sampling from a given distribution with bounded support then the asymptotic MAP partition of the observation space maximises a function which has a straightforward expression, which depends only on the within-group covariance parameter. As the operator norm of this covariance parameter decreases, the number of clusters in the MAP partition becomes arbitrarily large, which may lead to the overestimation of the number of mixture components.

Ruosi Guo, Chunming Zhang, Zhengjun Zhang.

Source: Statistical Science, Volume 35, Number 1, 145--157.

Abstract:
In many scientific disciplines, finding hidden influential factors behind observational data is essential but challenging. The majority of existing approaches, such as the independent component analysis (${mathrm{ICA}}$), rely on linear transformation, that is, true signals are linear combinations of hidden components. Motivated from analyzing nonlinear temporal signals in neuroscience, genetics, and finance, this paper proposes the “maximum independent component analysis” (${mathrm{MaxICA}}$), based on max-linear combinations of components. In contrast to existing methods, ${mathrm{MaxICA}}$ benefits from focusing on significant major components while filtering out ignorable components. A major tool for parameter learning of ${mathrm{MaxICA}}$ is an augmented genetic algorithm, consisting of three schemes for the elite weighted sum selection, randomly combined crossover, and dynamic mutation. Extensive empirical evaluations demonstrate the effectiveness of ${mathrm{MaxICA}}$ in either extracting max-linearly combined essential sources in many applications or supplying a better approximation for nonlinearly combined source signals, such as $mathrm{EEG}$ recordings analyzed in this paper.

Andreas Buja, Arun Kumar Kuchibhotla, Richard Berk, Edward George, Eric Tchetgen Tchetgen, Linda Zhao.

Source: Statistical Science, Volume 34, Number 4, 606--620.

Abstract:
We respond to the discussants of our articles emphasizing the importance of inference under misspecification in the context of the reproducibility/replicability crisis. Along the way, we discuss the roles of diagnostics and model building in regression as well as connections between our well-specification framework and semiparametric theory.

Dalia Ghanem, Todd A. Kuffner.

Source: Statistical Science, Volume 34, Number 4, 604--605.

David Whitney, Ali Shojaie, Marco Carone.

Source: Statistical Science, Volume 34, Number 4, 591--598.

Anthony C. Davison, Erwan Koch, Jonathan Koh.

Source: Statistical Science, Volume 34, Number 4, 584--590.

Abstract:
This discussion focuses on areas of disagreement with the papers, particularly the target of inference and the case for using the robust ‘sandwich’ variance estimator in the presence of moderate mis-specification. We also suggest that existing procedures may be appreciably more powerful for detecting mis-specification than the authors’ RAV statistic, and comment on the use of the pairs bootstrap in balanced situations.

Roderick J. Little.

Source: Statistical Science, Volume 34, Number 4, 580--583.

Dag Tjøstheim.

Source: Statistical Science, Volume 34, Number 4, 575--579.

Nikki L. B. Freeman, Xiaotong Jiang, Owen E. Leete, Daniel J. Luckett, Teeranan Pokaprakarn, Michael R. Kosorok.

Source: Statistical Science, Volume 34, Number 4, 572--574.

Jerald F. Lawless.

Source: Statistical Science, Volume 34, Number 4, 569--571.

Abstract:
I comment on the papers Models as Approximations I and II, by A. Buja, R. Berk, L. Brown, E. George, E. Pitkin, M. Traskin, L. Zhao and K. Zhang.

Sara van de Geer.

Source: Statistical Science, Volume 34, Number 4, 566--568.

Abstract:
We discuss the papers “Models as Approximations” I & II, by A. Buja, R. Berk, L. Brown, E. George, E. Pitkin, M. Traskin, L. Zao and K. Zhang (Part I) and A. Buja, L. Brown, A. K. Kuchibhota, R. Berk, E. George and L. Zhao (Part II). We present a summary with some details for the generalized linear model.

Andreas Buja, Lawrence Brown, Arun Kumar Kuchibhotla, Richard Berk, Edward George, Linda Zhao.

Source: Statistical Science, Volume 34, Number 4, 545--565.

Abstract:
We develop a model-free theory of general types of parametric regression for i.i.d. observations. The theory replaces the parameters of parametric models with statistical functionals, to be called “regression functionals,” defined on large nonparametric classes of joint ${x extrm{-}y}$ distributions, without assuming a correct model. Parametric models are reduced to heuristics to suggest plausible objective functions. An example of a regression functional is the vector of slopes of linear equations fitted by OLS to largely arbitrary ${x extrm{-}y}$ distributions, without assuming a linear model (see Part I). More generally, regression functionals can be defined by minimizing objective functions, solving estimating equations, or with ad hoc constructions. In this framework, it is possible to achieve the following: (1) define a notion of “well-specification” for regression functionals that replaces the notion of correct specification of models, (2) propose a well-specification diagnostic for regression functionals based on reweighting distributions and data, (3) decompose sampling variability of regression functionals into two sources, one due to the conditional response distribution and another due to the regressor distribution interacting with misspecification, both of order $N^{-1/2}$, (4) exhibit plug-in/sandwich estimators of standard error as limit cases of ${x extrm{-}y}$ bootstrap estimators, and (5) provide theoretical heuristics to indicate that ${x extrm{-}y}$ bootstrap standard errors may generally be preferred over sandwich estimators.

Andreas Buja, Lawrence Brown, Richard Berk, Edward George, Emil Pitkin, Mikhail Traskin, Kai Zhang, Linda Zhao.

Source: Statistical Science, Volume 34, Number 4, 523--544.

Abstract:
In the early 1980s, Halbert White inaugurated a “model-robust” form of statistical inference based on the “sandwich estimator” of standard error. This estimator is known to be “heteroskedasticity-consistent,” but it is less well known to be “nonlinearity-consistent” as well. Nonlinearity, however, raises fundamental issues because in its presence regressors are not ancillary, hence cannot be treated as fixed. The consequences are deep: (1) population slopes need to be reinterpreted as statistical functionals obtained from OLS fits to largely arbitrary joint ${x extrm{-}y}$ distributions; (2) the meaning of slope parameters needs to be rethought; (3) the regressor distribution affects the slope parameters; (4) randomness of the regressors becomes a source of sampling variability in slope estimates of order $1/sqrt{N}$; (5) inference needs to be based on model-robust standard errors, including sandwich estimators or the ${x extrm{-}y}$ bootstrap. In theory, model-robust and model-trusting standard errors can deviate by arbitrary magnitudes either way. In practice, significant deviations between them can be detected with a diagnostic test.

Georg Lindgren.

Source: Statistical Science, Volume 34, Number 1, 100--128.

Abstract:
We describe and compare how methods based on the classical Rice’s formula for the expected number, and higher moments, of level crossings by a Gaussian process stand up to contemporary numerical methods to accurately deal with crossing related characteristics of the sample paths. We illustrate the relative merits in accuracy and computing time of the Rice moment methods and the exact numerical method, developed since the late 1990s, on three groups of distribution problems, the maximum over a finite interval and the waiting time to first crossing, the length of excursions over a level, and the joint period/amplitude of oscillations. We also treat the notoriously difficult problem of dependence between successive zero crossing distances. The exact solution has been known since at least 2000, but it has remained largely unnoticed outside the ocean science community. Extensive simulation studies illustrate the accuracy of the numerical methods. As a historical introduction an attempt is made to illustrate the relation between Rice’s original formulation and arguments and the exact numerical methods.

Christelle Peyron
Dec 1, 1998; 18:9996-10015
Articles

Peter Klivenyi
Jan 1, 2000; 20:1-7
Cellular

Lennart Mucke
Jun 1, 2000; 20:4050-4058
Cellular

French translation of the press release about the Basel Committee publishing a discussion paper on "The regulatory treatment of sovereign exposures" (7 December 2017)

French translation of "Frequently asked questions on market risk capital requirements" by the Basel Committee, March 2018.

French translation of "Pillar 3 disclosure requirements - updated framework", December 2018

Discurso del Dr. Agustín Carstens, Director General del Banco de Pagos Internacionales, en la Celebración del 25 Aniversario de la Autonomía del Banco de México, Ciudad de México, 22 de noviembre de 2019.

To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452.

Speech by Dr Agustín Carstens at the celebration of 25 years of Bank of Mexico independence, Mexico City, 22 November 2019.

Exiting low inflation traps by "consensus": nominal wages and price stability - Speech by Luiz A Pereira da Silva and Benoît Mojon, based on the keynote speech at the Eighth High-level Policy Dialogue between the Eurosystem and Latin American Central Banks, Cartagena de Indias, Colombia, 28-29 November 2019.

Knowledge about objects encompasses not only their prototypical features but also complex, atypical, semantic knowledge (e.g., "Pizza was invented in Naples"). This fMRI study of male and female human participants combines univariate and multivariate analyses to consider the cortical representation of this more complex semantic knowledge. Using the categories of food, people, and places, this study investigates whether access to spatially related geographic semantic knowledge (1) involves the same domain-selective neural representations involved in access to prototypical taste knowledge about food; and (2) elicits activation of neural representations classically linked to places when this geographic knowledge is accessed about food and people. In three experiments using word stimuli, domain-relevant and atypical conceptual access for the categories food, people, and places were assessed. Results uncover two principles of semantic representation: food-selective representations in the left insula continue to be recruited when prototypical taste knowledge is task-irrelevant and under conditions of high cognitive demand; access to geographic knowledge for food and people categories involves the additional recruitment of classically place-selective parahippocampal gyrus, retrosplenial complex, and transverse occipital sulcus. These findings underscore the importance of object category in the representation of a broad range of knowledge, while showing how the cross recruitment of specialized representations may endow the considerable flexibility of our complex semantic knowledge.

SIGNIFICANCE STATEMENT We know not only stereotypical things about objects (an apple is round, graspable, edible) but can also flexibly combine typical and atypical features to form complex concepts (the metaphorical role an apple plays in Judeo-Christian belief). In this fMRI study, we observe that, when atypical geographic knowledge is accessed about food dishes, domain-selective sensorimotor-related cortical representations continue to be recruited, but that regions classically associated with place perception are additionally engaged. This interplay between categorically driven representations, linked to the object being accessed, and the flexible recruitment of semantic stores linked to the content being accessed, provides a potential mechanism for the broad representational repertoire of our semantic system.

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression or energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.

SIGNIFICANCE STATEMENT POMC and NPY/AgRP neurons are derived from the same hypothalamic progenitors but have opposing effects on food intake. We profiled the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypothalamus to decipher the transcriptional codes behind the versus orexigenic neuron identity. Our analyses revealed 29 transcription regulators that are selectively enriched in one of the two populations. We generated new mouse genetic models to selective ablate one of POMC-neuron enriched transcription factors Prdm12 in developing and adult POMC neurons. Our studies establish a previously unrecognized role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis.

Prohibitin (PHB) is a critical protein involved in many cellular activities. In brain, PHB resides in mitochondria, where it forms a large protein complex with PHB2 in the inner TFmembrane, which serves as a scaffolding platform for proteins involved in mitochondrial structural and functional integrity. PHB overexpression at moderate levels provides neuroprotection in experimental brain injury models. In addition, PHB expression is involved in ischemic preconditioning, as its expression is enhanced in preconditioning paradigms. However, the mechanisms of PHB functional regulation are still unknown. Observations that nitric oxide (NO) plays a key role in ischemia preconditioning compelled us to postulate that the neuroprotective effect of PHB could be regulated by NO. Here, we test this hypothesis in a neuronal model of ischemia–reperfusion injury and show that NO and PHB are mutually required for neuronal resilience against oxygen and glucose deprivation stress. Further, we demonstrate that NO post-translationally modifies PHB through protein S-nitrosylation and regulates PHB neuroprotective function, in a nitric oxide synthase-dependent manner. These results uncover the mechanisms of a previously unrecognized form of molecular regulation of PHB that underlies its neuroprotective function.

SIGNIFICANCE STATEMENT Prohibitin (PHB) is a critical mitochondrial protein that exerts a potent neuroprotective effect when mildly upregulated in mice. However, how the neuroprotective function of PHB is regulated is still unknown. Here, we demonstrate a novel regulatory mechanism for PHB that involves nitric oxide (NO) and shows that PHB and NO interact directly, resulting in protein S-nitrosylation on residue Cys⁶⁹ of PHB. We further show that nitrosylation of PHB may be essential for its ability to preserve neuronal viability under hypoxic stress. Thus, our study reveals a previously unknown mechanism of functional regulation of PHB that has potential therapeutic implications for neurologic disorders.

Nitric oxide (NO) is an important signaling molecule that fulfills diverse functional roles as a neurotransmitter or diffusible second messenger in the developing and adult CNS. Although the impact of NO on different behaviors such as movement, sleep, learning, and memory has been well documented, the identity of its molecular and cellular targets is still an area of ongoing investigation. Here, we identify a novel role for NO in strengthening inhibitory GABA_A receptor-mediated transmission in molecular layer interneurons of the mouse cerebellum. NO levels are elevated by the activity of neuronal NO synthase (nNOS) following Ca²⁺ entry through extrasynaptic NMDA-type ionotropic glutamate receptors (NMDARs). NO activates protein kinase G with the subsequent production of cGMP, which prompts the stimulation of NADPH oxidase and protein kinase C (PKC). The activation of PKC promotes the selective strengthening of α3-containing GABA_ARs synapses through a GABA receptor-associated protein-dependent mechanism. Given the widespread but cell type-specific expression of the NMDAR/nNOS complex in the mammalian brain, our data suggest that NMDARs may uniquely strengthen inhibitory GABAergic transmission in these cells through a novel NO-mediated pathway.

SIGNIFICANCE STATEMENT Long-term changes in the efficacy of GABAergic transmission is mediated by multiple presynaptic and postsynaptic mechanisms. A prominent pathway involves crosstalk between excitatory and inhibitory synapses whereby Ca²⁺-entering through postsynaptic NMDARs promotes the recruitment and strengthening of GABA_A receptor synapses via Ca²⁺/calmodulin-dependent protein kinase II. Although Ca²⁺ transport by NMDARs is also tightly coupled to nNOS activity and NO production, it has yet to be determined whether this pathway affects inhibitory synapses. Here, we show that activation of NMDARs trigger a NO-dependent pathway that strengthens inhibitory GABAergic synapses of cerebellar molecular layer interneurons. Given the widespread expression of NMDARs and nNOS in the mammalian brain, we speculate that NO control of GABAergic synapse efficacy may be more widespread than has been appreciated.

Microglial cells are considered as sensors of brain pathology by detecting any sign of brain lesions, infections, or dysfunction and can influence the onset and progression of neurological diseases. They are capable of sensing their neuronal environment via many different signaling molecules, such as neurotransmitters, neurohormones and neuropeptides. The neuropeptide VGF has been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide and has been shown to signal via C3aR1 and C1qBP receptors. The effect of TLQP21 on microglial functions in health or disease is not known. Studying microglial cells in acute brain slices, we found that TLQP21 impaired metabotropic purinergic signaling. Specifically, it attenuated the ATP-induced activation of a K⁺ conductance, the UDP-stimulated phagocytic activity, and the ATP-dependent laser lesion-induced process outgrowth. These impairments were reversed by blocking C1qBP, but not C3aR1 receptors. While microglia in brain slices from male mice lack C3aR1 receptors, both receptors are expressed in primary cultured microglia. In addition to the negative impact on purinergic signaling, we found stimulating effects of TLQP21 in cultured microglia, which were mediated by C3aR1 receptors: it directly evoked membrane currents, stimulated basal phagocytic activity, evoked intracellular Ca²⁺ transient elevations, and served as a chemotactic signal. We conclude that TLQP21 has differential effects on microglia depending on C3aR1 activation or C1qBP-dependent attenuation of purinergic signaling. Thus, TLQP21 can modulate the functional phenotype of microglia, which may have an impact on their function in health and disease.

SIGNIFICANCE STATEMENT The neuropeptide VGF and its peptides have been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide that activates C1qBP receptors, which are expressed by microglia. We show here, for the first time, that TLQP21 impairs P2Y-mediated purinergic signaling and related functions. These include modulation of phagocytic activity and responses to injury. As purinergic signaling is central for microglial actions in the brain, this TLQP21-mediated mechanism might regulate microglial activity in health and disease. We furthermore show that, in addition to C1qBP, functional C3aR1 responses contribute to TLQP21 action on microglia. However, C3aR1 responses were only present in primary cultures but not in situ, suggesting that the expression of these receptors might vary between different microglial activation states.

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.

The terraced hills of the Andes, the rice paddies of southern China, the oasis systems of the Maghreb: agriculture molds landscapes and places. Agriculture also shapes livelihoods, lifestyles, food traditions and cultures. What kind of plants grow or can’t grow, how they are harvested and what people eat define people’s lives.  Because our natural resources are under great strain, we need [...]

Elvis Cortés Hernández grabs his lunch and sits down with his friends. We’re at the General Lázaro Cárdenas school in Ajalpan, deep in the heart of Mexico’s Puebla province and the ten–year–old is chatting about the school’s vegetable garden, one element of its progressive food policy. “I like to eat in the school dining room because they give me carrots, [...]

What does William Shakespeare have in common with Mexican beekeeper Francisco Lenin Bartolo Reyes? Both men understand the importance of the honey bee, a small but invaluable ally of the human race.

Scientists discover neurotoxin-producing bacteria living on the skin of rough-skinned newts

Fears around the pandemic are causing sleep patterns to change and strange dreams to linger in people’s memories

Expelled by animals as a waste product, the gas appears to play a crucial role in keeping these bizarre, burrowing rodents safe

The Catholic Church's actions during World War II have long been a matter of historical debate

Engineers around the world are tweaking drones, robots and smart tools to help prevent the spread of the virus