Multitargeting Pt(IV) Derivatives of Cisplatin or Oxaliplatin Inhibit Tumor Growth in Mice without Inducing Neuropathic Pain.

Cisplatin and oxaliplatin are Pt(II) anticancer agents that are used to treat several cancers, usually in combination with other drugs. Their efficacy is diminished by dose-limiting peripheral neuropathy (PN) that affects ∼70% of patients. PN is caused by selective accumulation of the platinum drugs in the dorsal root ganglia (DRG), which overexpress transporters for cisplatin and oxaliplatin.

Of mice and men: Dendritic architecture differentiates human from mice neuronal networks.

The organizational principles that distinguish the human brain from other species have been a long-standing enigma in neuroscience. Focusing on the uniquely evolved human cortical layers 2 and 3, we computationally reconstruct the cortical architecture for mice and humans. We show that human pyramidal cells form highly complex networks, demonstrated by the increased number and simplex dimension compared to mice.

What makes human cortical pyramidal neurons functionally complex.

Humans exhibit unique cognitive abilities within the animal kingdom, but the neural mechanisms driving these advanced capabilities remain poorly understood. Human cortical neurons differ from those of other species, such as rodents, in both their morphological and physiological characteristics. Could the distinct properties of human cortical neurons help explain the superior cognitive capabilities of humans? Understanding this relationship requires a metric to quantify how neuronal properties contribute to the functional complexity of single neurons, yet no such standardized measure currently exists.

Approximating R1 and R2: A Quantitative Approach to Clinical Weighted MRI.

Weighted MRI images are widely used in clinical as well as open-source neuroimaging databases. Weighted images such as T1-weighted, T2-weighted, and proton density-weighted (T1w, T2w, and PDw, respectively) are used for evaluating the brain's macrostructure; however, their values cannot be used for microstructural analysis, as they lack physical meaning. Quantitative MRI (qMRI) relaxation rate parameters (e.

Altered blood and keratinocyte microRNA/transfer RNA fragment profiles related to fibromyalgia syndrome and its severity.

Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls).

Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery.

Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells.

Spontaneous associative thought may facilitate scene-gist memory via implicit scene-labeling.

Spontaneous associative processes (e.g., mind wandering, spontaneous memory recollection) are prevalent in everyday life, yet their influence on perceptual scene memory is under debate.

Autism spectrum disorder variation as a computational trade-off via dynamic range of neuronal population responses.

Individuals diagnosed with autism spectrum disorder (ASD) show neural and behavioral characteristics differing from the neurotypical population. This may stem from a computational principle that relates inference and computational dynamics to the dynamic range of neuronal population responses, reflecting the signal levels for which the system is responsive. In the present study, we showed that an increased dynamic range (IDR), indicating a gradual response of a neuronal population to changes in input, accounts for neural and behavioral variations in individuals diagnosed with ASD across diverse tasks.

Inferring DNA methylation in non-skeletal tissues of ancient specimens.

Genome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing ancient DNA methylation maps focused on studying evolutionary changes in the skeletal system. Here we suggest that DNA methylation patterns in one tissue may, under certain conditions, be informative on DNA methylation patterns in other tissues of the same individual.

Untrained neural networks can demonstrate memorization-independent abstract reasoning.

The nature of abstract reasoning is a matter of debate. Modern artificial neural network (ANN) models, like large language models, demonstrate impressive success when tested on abstract reasoning problems. However, it has been argued that their success reflects some form of memorization of similar problems (data contamination) rather than a general-purpose abstract reasoning capability.

Rats synchronize predictively to metronomes.

Predictive auditory-motor synchronization, in which rhythmic movements anticipate rhythmic sounds, is at the core of the human capacity for music. Rodents show impressive capabilities in timing and motor tasks, but their ability to predictively coordinate sensation and action has not been demonstrated. Here, we reveal a clear capacity for predictive auditory-motor synchronization in rodent species using a modeling approach for the quantitative exploration of synchronization behaviors.

Computational modeling of the relationship between morphological heterogeneity and functional responses in mouse hippocampal astrocytes.

Recent studies indicate that astrocytes show heterogeneity in morphology and physiological function. They integrate synaptic signals and release calcium in reaction to active neurons. These calcium signals are not yet fully understood as they are highly dependent on the cell's morphology, which can vary across and within brain regions.

Fetal body composition reference charts and sexual dimorphism using magnetic resonance imaging.

Background: The American Academy of Pediatrics advises that the nutrition of preterm infants should target a body composition similar to that of a fetus in utero. Still, reference charts for intrauterine body composition are missing. Moreover, data on sexual differences in intrauterine body composition during pregnancy are limited.

Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding.

TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by Fanet al."Structural basis of TRPV1 inhibition by SAF312 and cholesterol" sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials.

Validation of behavioral measures of social cognition in individuals diagnosed with schizophrenia.

Schizophrenia, a complex neuropsychiatric disorder, manifests severe impairments in social cognition, notably in Theory of Mind (ToM), empathy, and emotion recognition, which significantly influence social competence and overall functioning. These aspects are crucial for prognosis in individuals diagnosed with schizophrenia (SZ). This study validates a comics strip paradigm for ToM and empathy assessment, the Montreal Affective Voices (MAV) for measuring emotion recognition, and a Go-NoGo task for inhibition control estimation in individuals diagnosed with SZ, comparing their performance with healthy controls.

High-dimensional encoding of movement by single neurons in basal ganglia output.

The substantia nigra pars reticulata (SNpr), an output structure of the basal ganglia, is hypothesized to gate movement execution. Previous studies in the eye movement system focusing mostly on saccades have reported that SNpr neurons are tonically active and either pause or increase their firing during movements, consistent with the gating role. We recorded activity in the SNpr of two monkeys during smooth pursuit and saccadic eye movements.

Spatiotemporal dynamics of locomotor decisions in .

Decision-making in animals often involves choosing actions while navigating the environment, a process markedly different from static decision paradigms commonly studied in laboratory settings. Even in decision-making assays in which animals can freely locomote, decision outcomes are often interpreted as happening at single points in space and single moments in time, a simplification that potentially glosses over important spatiotemporal dynamics. We investigated locomotor decision-making in in Y-shaped mazes, measuring the extent to which their future choices could be predicted through space and time.

The Role of Population Receptive Field Sizes in Higher-Order Visual Dysfunction.

Purpose Of Review: Population receptive field (pRF) modeling is an fMRI technique used to retinotopically map visual cortex, with pRF size characterizing the degree of spatial integration. In clinical populations, most pRF mapping research has focused on damage to visual system inputs. Herein, we highlight recent work using pRF modeling to study high-level visual dysfunctions.

Single neuron responses to perceptual difficulty in the mouse auditory cortex.

Perceptual learning leads to improvement in behavioral performance, yet how the brain supports challenging perceptual demands is unknown. We used two photon imaging in the mouse primary auditory cortex during behavior in a Go-NoGo task designed to test perceptual difficulty. Using general linear model analysis, we found a subset of neurons that increased their responses during high perceptual demands.