Low glucose induced Alzheimer's disease-like biochemical changes in human induced pluripotent stem cell-derived neurons is due to dysregulated O-GlcNAcylation.

Introduction: Sporadic Alzheimer's disease (sAD) is the leading type of dementia. Brain glucose hypometabolism, along with decreased O-GlcNAcylation levels, occurs before the onset of symptoms and correlates with pathogenesis. Heretofore, the mechanisms involved and the roles of O-GlcNAcylation in sAD pathology largely remain unknown due to a lack of human models of sAD.

Unraveling the Entangled Brain: How Do We Go About It?

An impactful understanding of the brain will require entirely new approaches and unprecedented collaborative efforts. The next steps will require brain researchers to develop theoretical frameworks that allow them to tease apart dependencies and causality in complex dynamical systems, as well as the ability to maintain awe while not getting lost in the effort. The outstanding question is: How do we go about it?

The tricky business of defining brain functions.

Neuroscience has a long history of investigating the neural correlates of brain functions. One example is fear, which has been studied intensely in a variety of species. In parallel, unease about definitions of brain functions has existed for over 100 years.

Altered O-GlcNAcylation and mitochondrial dysfunction, a molecular link between brain glucose dysregulation and sporadic Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disease that affected over 6.5 million people in the United States in 2021, with this number expected to double in the next 40 years without any sort of treatment. Due to its heterogeneity and complexity, the etiology of Alzheimer's disease, especially sporadic Alzheimer's disease, remains largely unclear.

A call for more clarity around causality in neuroscience.

In neuroscience, the term 'causality' is used to refer to different concepts, leading to confusion. Here we illustrate some of those variations, and we suggest names for them. We then introduce four ways to enhance clarity around causality in neuroscience.

Ritalin as a causal perturbation.

Causal perturbations provide the strongest tests of the relationships between brain mechanism and brain function. In cognitive neuroscience, persuasive causal perturbations are difficult to achieve. In a recent paper, Ni et al.

Priority coding in the visual system.

Although we are continuously bombarded with visual input, only a fraction of incoming visual events is perceived, remembered or acted on. The neural underpinnings of various forms of visual priority coding, including perceptual expertise, goal-directed attention, visual salience, image memorability and preferential looking, have been studied. Here, we synthesize information from these different examples to review recent developments in our understanding of visual priority coding and its neural correlates, with a focus on the role of behaviour to evaluate candidate correlates.

Have farmers had enough of experts?

The exponential rise of information available means we can now, in theory, access knowledge on almost any question we ask. However, as the amount of unverified information increases, so too does the challenge in deciding which information to trust. Farmers, when learning about agricultural innovations, have historically relied on in-person advice from traditional 'experts', such as agricultural advisers, to inform farm management.

Remembering the Past to See the Future.

In addition to the role that our visual system plays in determining what we are seeing right now, visual computations contribute in important ways to predicting what we will see next. While the role of memory in creating future predictions is often overlooked, efficient predictive computation requires the use of information about the past to estimate future events. In this article, we introduce a framework for understanding the relationship between memory and visual prediction and review the two classes of mechanisms that the visual system relies on to create future predictions.

Pinpointing the neural signatures of single-exposure visual recognition memory.

Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys' behavior was largely contrast invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those that are of lower contrast.

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors.

Since exacerbated inflammation and microvascular leakage are hallmarks of dengue virus (DENV) infection, here we interrogated whether systemic activation of the contact/kallikrein-kinin system (KKS) might hamper endothelial function. In vitro assays showed that dextran sulfate, a potent contact activator, failed to generate appreciable levels of activated plasma kallikrein (PKa) in the large majority of samples from a dengue cohort ( = 70), irrespective of severity of clinical symptoms. Impaired formation of PKa in dengue-plasmas correlated with the presence of cleaved Factor XII and high molecular weight kininogen (HK), suggesting that the prothrombogenic contact system is frequently triggered during the course of infection.

The Citation Diversity Statement: A Practice of Transparency, A Way of Life.

Appending a Citation Diversity Statement to a paper is a simple and effective way to increase awareness about citation bias and help mitigate it. Here, we describe why reducing citation bias is important and how to include a Citation Diversity Statement in your next publication.

Understanding Image Memorability.

Why are some images easier to remember than others? Here, we review recent developments in our understanding of 'image memorability', including its behavioral characteristics, its neural correlates, and the optimization principles from which it originates. We highlight work that has used large behavioral data sets to leverage memorability scores computed for individual images. These studies demonstrate that the mapping of image content to image memorability is not only predictable, but also non-intuitive and multifaceted.

Charge exchange recombination spectroscopy at Wendelstein 7-X.

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

How to transition to reduced-meat diets that benefit people and the planet.

Overwhelming evidence shows that overconsumption of meat is bad for human and environmental health and that moving towards a more plant-based diet is more sustainable. For instance, replacing beef with beans in the US could free up 42% of US cropland and reduce greenhouse gas emissions by 334 mmt, accomplishing 75% of the 2020 carbon reduction target. We summarise the evidence on how overconsumption of meat affects social, environmental and economic sustainability.

The integration of visual and target signals in V4 and IT during visual object search.

Searching for a specific visual object requires our brain to compare the items in view with a remembered representation of the sought target to determine whether a target match is present. This comparison is thought to be implemented, in part, via the combination of top-down modulations reflecting target identity with feed-forward visual representations. However, it remains unclear whether top-down signals are integrated at a single locus within the ventral visual pathway (e.

Visual novelty, curiosity, and intrinsic reward in machine learning and the brain.

A strong preference for novelty emerges in infancy and is prevalent across the animal kingdom. When incorporated into reinforcement-based machine learning algorithms, visual novelty can act as an intrinsic reward signal that vastly increases the efficiency of exploration and expedites learning, particularly in situations where external rewards are difficult to obtain. Here we review parallels between recent developments in novelty-driven machine learning algorithms and our understanding of how visual novelty is computed and signaled in the primate brain.

Population response magnitude variation in inferotemporal cortex predicts image memorability.

Most accounts of image and object encoding in inferotemporal cortex (IT) focus on the distinct patterns of spikes that different images evoke across the IT population. By analyzing data collected from IT as monkeys performed a visual memory task, we demonstrate that variation in a complementary coding scheme, the magnitude of the population response, can largely account for how well images will be remembered. To investigate the origin of IT image memorability modulation, we probed convolutional neural network models trained to categorize objects.

Rethinking assumptions about how trial and nuisance variability impact neural task performance in a fast-processing regime.

Task performance is determined not only by the amount of task-relevant signal present in our brains but also by the presence of noise, which can arise from multiple sources. Internal noise, or "trial variability," manifests as trial-by-trial variations in neural responses under seemingly identical conditions. External factors can also translate into noise, particularly when a task requires extraction of a particular type of information from our environment amid changes in other task-irrelevant "nuisance" parameters.

Inferotemporal cortex multiplexes behaviorally-relevant target match signals and visual representations in a manner that minimizes their interference.

Finding a sought visual target object requires combining visual information about a scene with a remembered representation of the target to create a "target match" signal that indicates when a target is in view. Target match signals have been reported to exist within high-level visual brain areas including inferotemporal cortex (IT), where they are mixed with representations of image and object identity. However, these signals are not well understood, particularly in the context of the real-world challenge that the objects we search for typically appear at different positions, sizes, and within different background contexts.

Single-exposure visual memory judgments are reflected in inferotemporal cortex.

Our visual memory percepts of whether we have encountered specific objects or scenes before are hypothesized to manifest as decrements in neural responses in inferotemporal cortex (IT) with stimulus repetition. To evaluate this proposal, we recorded IT neural responses as two monkeys performed a single-exposure visual memory task designed to measure the rates of forgetting with time. We found that a weighted linear read-out of IT was a better predictor of the monkeys' forgetting rates and reaction time patterns than a strict instantiation of the repetition suppression hypothesis, expressed as a total spike count scheme.

Reach and messages of the world's largest ivory burn.

Recent increases in ivory poaching have depressed African elephant populations. Successful enforcement has led to ivory stockpiling. Stockpile destruction is becoming increasingly popular, and most destruction has occurred in the last 5 years.

Do rats see like we see?

Like primates, the rat brain areas thought to be involved in visual object recognition are arranged in a hierarchy.

Neural Quadratic Discriminant Analysis: Nonlinear Decoding with V1-Like Computation.

Linear-nonlinear (LN) models and their extensions have proven successful in describing transformations from stimuli to spiking responses of neurons in early stages of sensory hierarchies. Neural responses at later stages are highly nonlinear and have generally been better characterized in terms of their decoding performance on prespecified tasks. Here we develop a biologically plausible decoding model for classification tasks, that we refer to as neural quadratic discriminant analysis (nQDA).