Edinburgh : printed by J. Stark, [1836?]

[Spain?], An. 1817.

Jessica K. Hargreaves, Marina I. Knight, Jon W. Pitchford, Rachael J. Oakenfull, Sangeeta Chawla, Jack Munns, Seth J. Davis.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1817--1846.

Abstract:
Rhythmic data are ubiquitous in the life sciences. Biologists need reliable statistical tests to identify whether a particular experimental treatment has caused a significant change in a rhythmic signal. When these signals display nonstationary behaviour, as is common in many biological systems, the established methodologies may be misleading. Therefore, there is a real need for new methodology that enables the formal comparison of nonstationary processes. As circadian behaviour is best understood in the spectral domain, here we develop novel hypothesis testing procedures in the (wavelet) spectral domain, embedding replicate information when available. The data are modelled as realisations of locally stationary wavelet processes, allowing us to define and rigorously estimate their evolutionary wavelet spectra. Motivated by three complementary applications in circadian biology, our new methodology allows the identification of three specific types of spectral difference. We demonstrate the advantages of our methodology over alternative approaches, by means of a comprehensive simulation study and real data applications, using both published and newly generated circadian datasets. In contrast to the current standard methodologies, our method successfully identifies differences within the motivating circadian datasets, and facilitates wider ranging analyses of rhythmic biological data in general.

Sreenivasa Rao Jammalamadaka, Simos Meintanis, Thomas Verdebout.

Source: Bernoulli, Volume 26, Number 3, 2226--2252.

Abstract:
Circular and spherical data arise in many applications, especially in biology, Earth sciences and astronomy. In dealing with such data, one of the preliminary steps before any further inference, is to test if such data is isotropic, that is, uniformly distributed around the circle or the sphere. In view of its importance, there is a considerable literature on the topic. In the present work, we provide new tests of uniformity on the circle based on original asymptotic results. Our tests are motivated by the shape of locally and asymptotically maximin tests of uniformity against generalized von Mises distributions. We show that they are uniformly consistent. Empirical power comparisons with several competing procedures are presented via simulations. The new tests detect particularly well multimodal alternatives such as mixtures of von Mises distributions. A practically-oriented combination of the new tests with already existing Sobolev tests is proposed. An extension to testing uniformity on the sphere, along with some simulations, is included. The procedures are illustrated on a real dataset.

Brian Zingg
Apr 15, 2020; 40:3250-3267
Systems/Circuits

Sebastian Onasch
Apr 15, 2020; 40:3186-3202
Systems/Circuits

M Chalfie
Apr 1, 1985; 5:956-964
Articles

Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however, the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Here, using anatomic, functional, and molecular approaches, we provide evidence for the preferential transport of AAV1 to postsynaptically connected neurons and reveal its spread is strongly dependent on synaptic transmitter release. In addition to glutamatergic pathways, AAV1 also spreads through GABAergic synapses to both excitatory and inhibitory cell types. We observed little or no transport, however, through neuromodulatory projections (e.g., serotonergic, cholinergic, and noradrenergic). In addition, we found that AAV1 can be transported through long-distance descending projections from various brain regions to effectively transduce spinal cord neurons. Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be applied within a wide variety of pathways to categorize neurons according to their input sources, morphology, and molecular identities. These properties make AAV1 a promising anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain, although its capacity for retrograde transport currently limits its use to unidirectional circuits.

SIGNIFICANCE STATEMENT The discovery of anterograde transneuronal spread of AAV1 generates great promise for its application as a unique tool for manipulating input-defined cell populations and mapping their outputs. However, several outstanding questions remain for anterograde transsynaptic approaches in the field: (1) whether AAV1 spreads exclusively or specifically to synaptically connected neurons, and (2) how broad its application could be in various types of neural circuits in the brain. This study provides several lines of evidence in terms of anatomy, functional innervation, and underlying mechanisms, to strongly support that AAV1 anterograde transneuronal spread is highly synapse specific. In addition, several potentially important applications of transsynaptic AAV1 in probing neural circuits are described.

Neurons and circuits each with a distinct balance of intrinsic and synaptic conductances can generate similar behavior but sometimes respond very differently to perturbation. Examining a large family of circuit models with non-identical neurons and synapses underlying rhythmic behavior, we analyzed the circuits' response to modifications in single and multiple intrinsic conductances in the individual neurons. To summarize these changes over the entire range of perturbed parameters, we quantified circuit output by defining a global stability measure. Using this measure, we identified specific subsets of conductances that when perturbed generate similar behavior in diverse individuals of the population. Our unbiased clustering analysis enabled us to quantify circuit stability when simultaneously perturbing multiple conductances as a nonlinear combination of single conductance perturbations. This revealed surprising conductance combinations that can predict the response to specific perturbations, even when the remaining intrinsic and synaptic conductances are unknown. Therefore, our approach can expose hidden variability in the balance of intrinsic and synaptic conductances of the same neurons across different versions of the same circuit solely from the circuit response to perturbations. Developed for a specific family of model circuits, our quantitative approach to characterizing high-dimensional degenerate systems provides a conceptual and analytic framework to guide future theoretical and experimental studies on degeneracy and robustness.

SIGNIFICANCE STATEMENT Neural circuits can generate nearly identical behavior despite neuronal and synaptic parameters varying several-fold between individual instantiations. Yet, when these parameters are perturbed through channel deletions and mutations or environmental disturbances, seemingly identical circuits can respond very differently. What distinguishes inconsequential perturbations that barely alter circuit behavior from disruptive perturbations that drastically disturb circuit output remains unclear. Focusing on a family of rhythmic circuits, we propose a computational approach to reveal hidden variability in the intrinsic and synaptic conductances in seemingly identical circuits based solely on circuit output to different perturbations. We uncover specific conductance combinations that work similarly to maintain stability and predict the effect of changing multiple conductances simultaneously, which often results from neuromodulation or injury.

We consider the question of how sensory networks enable the detection of sensory stimuli in a combinatorial coding space. We are specifically interested in the olfactory system, wherein recent experimental studies have reported the existence of rich, enigmatic response patterns associated with stimulus onset and offset. This study aims to identify the functional relevance of such response patterns (i.e., what benefits does such neural activity provide in the context of detecting stimuli in a natural environment). We study this problem through the lens of normative, optimization-based modeling. Here, we define the notion of a low-dimensional latent representation of stimulus identity, which is generated through action of the sensory network. The objective of our optimization framework is to ensure high-fidelity tracking of a nominal representation in this latent space in an energy-efficient manner. It turns out that the optimal motifs emerging from this framework possess morphologic similarity with prototypical onset and offset responses observed in vivo in locusts (Schistocerca americana) of either sex. Furthermore, this objective can be exactly achieved by a network with reciprocal excitatory–inhibitory competitive dynamics, similar to interactions between projection neurons and local neurons in the early olfactory system of insects. The derived model also makes several predictions regarding maintenance of robust latent representations in the presence of confounding background information and trade-offs between the energy of sensory activity and resultant behavioral measures such as speed and accuracy of stimulus detection.

SIGNIFICANCE STATEMENT A key area of study in olfactory coding involves understanding the transformation from high-dimensional sensory stimulus to low-dimensional decoded representation. Here, we examine not only the dimensionality reduction of this mapping but also its temporal dynamics, with specific focus on stimuli that are temporally continuous. Through optimization-based synthesis, we examine how sensory networks can track representations without prior assumption of discrete trial structure. We show that such tracking can be achieved by canonical network architectures and dynamics, and that the resulting responses resemble observations from neurons in the insect olfactory system. Thus, our results provide hypotheses regarding the functional role of olfactory circuit activity at both single neuronal and population scales.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.

SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

What would have been Cape Breton University's largest convocation to date is being replaced by an online offering this year because of COVID-19. Some graduating students say it just won't be the same as a traditional ceremony.

The CFL and CFL Players' Association have halted discussions on potential contingency plans for the 2020 campaign due to the COVID-19 pandemic.

The only fiscal thing to fear is deficit fear itself.

This helpful #TechTip is brought to you by our Training Manager John Setzer, and covers using the smart dimension tool when sketching arcs and circles. Find more options available to you, when you want to create a dimension and don’t

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Behind the glow of city lights, a group of people easily go unnoticed—lost sheep in desperate need of the hope of the gospel.

Male circumcision reduces risk of HIV acquisition in men by 60% and is associated with other health benefits. Compared with adult circumcision, infant male circumcision is safer, less expensive, and represents a cost-saving intervention for HIV prevention in many settings.

IMC is little known in East Africa and is not routinely practiced. This is the first study to assess acceptability and uptake of IMC in East Africa among parents who were actually offered the procedure. (Read the full article)

Head circumference (HC) at birth reflects brain development in utero. However, HC charts used in Canada are either dated, mixed-gender, nonrepresentative of lower gestational ages, or reflective of other populations in the world.

We developed recent and gender-specific reference curves for HC at birth for singletons of 23 to 41 completed weeks’ gestational age, which included a large number of very prematurely born infants, reflecting the current geotemporal Canadian population and advances in obstetric care. (Read the full article)

The demand for donor kidneys for transplantation exceeds supply. En bloc kidney transplantation and donation after determination of circulatory death from pediatric donors increases the potential donor pool.

Newborn infants undergoing elective withdrawal of life support in the NICU are a previously unrecognized source of potential kidney donors. (Read the full article)

Neonatal circumcision in the United States has been estimated to be performed in ~58% of all neonates, and varies by US geographic region.

This study estimates neonatal and postneonatal circumcision rates among commercially insured males aged 0 to 18 years that were performed in both inpatient and outpatient settings. This study also estimates indications and payments for the procedure. (Read the full article)

Systemic responses occur after burn injury that lead to widespread changes to the body, including the heart. Elevated levels of catecholamines and stress hormones have been found up to 3 years after severe burns. Little is known about the longer-term effects.

Children with burns had 1.3 times as many admissions and 2.3 times the number of days in hospital for circulatory diseases compared with uninjured children. Children with minor burns had an increased risk of incident admissions for circulatory diseases. (Read the full article)

A drill focused on improving movement, teamwork and making the most of scoring chances.

D. Brooks Smith, Chief Judge of the United States Court of Appeals for the Third Circuit, will deliver the Penn State Law in University Park 2020 commencement address on May 16 in Eisenhower Auditorium.

On Netflix's social-media-based reality show, contestants live in the same building but in separate apartments, communicating via an Alexa-like voice assistant and chat system.

Wilmington, Del. (October 25, 2017) – Owing to Circumstances is a participatory site specific installation that will be on view in the Mezzanine Gallery from November 3-22, 2017. An opening reception to meet the artist will be held on Friday, November 3 from 5-7 p.m. Borders received a 2017 Emerging Fellowship in Sculpture. Borders designed […]

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