Sensory History Drives Adaptive Neural Geometry in LP/Pulvinar-Prefrontal Cortex Circuits.

Prior expectations guide attention and support perceptual filtering for efficient processing during decision-making. Here we show that during a visual discrimination task, mice adaptively use prior stimulus history to guide ongoing choices by estimating differences in evidence between consecutive trials (| Δ Dir |). The thalamic lateral posterior (LP)/pulvinar nucleus provides robust inputs to the Anterior Cingulate Cortex (ACC), which has been implicated in selective attention and predictive processing, but the function of the LP-ACC projection is unknown.

Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing.

Astrocytes, which are increasingly recognized as pivotal constituents of brain circuits governing a wide range of functions, express GABA transporter 3 (Gat3), an astrocyte-specific GABA transporter responsible for maintenance of extra-synaptic GABA levels. Here, we examined the functional role of Gat3 in astrocyte-mediated modulation of neuronal activity and information encoding. First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice.

Changes Over Time in Masseter Muscle Activity, Symptoms of Discomfort, Stress Level and Salivary Flow Rate Following Intra-Oesophageal Acid Infusion.

Background: Intra-oesophageal acid stimulation increases masseter muscle activity. However, the infusion speeds used in previous studies are significantly slow, with minimal acid volume (30 mL over 30 min). Additionally, it is unclear how masseter muscle activity, symptoms of discomfort, stress levels and saliva quantity change over time.

Cortical norepinephrine-astrocyte signaling critically mediates learned behavior.

Updating behavior based on feedback from the environment is a crucial means by which organisms learn and develop optimal behavioral strategies. Norepinephrine (NE) release from the locus coeruleus (LC) has been shown to mediate learned behaviors such that in a task with graded stimulus uncertainty and performance, a high level of NE released after an unexpected outcome causes improvement in subsequent behavior. Yet, how the transient activity of LC-NE neurons, lasting tens of milliseconds, influences behavior several seconds later, is unclear.

Prefrontal Cortex subregions provide distinct visual and behavioral feedback modulation to the Primary Visual Cortex.

The mammalian Prefrontal Cortex (PFC) has been suggested to modulate sensory information processing across multiple cortical regions via long-range axonal projections. These axonal projections arise from PFC subregions with unique brain-wide connectivity and functional repertoires, which may provide the architecture for modular feedback intended to shape sensory processing. Here, we used axonal tracing, axonal and somatic 2-photon calcium imaging, and chemogenetic manipulations in mice to delineate how projections from the Anterior Cingulate Cortex (ACA) and ventrolateral Orbitofrontal Cortex (ORB) of the PFC modulate sensory processing in the primary Visual Cortex (VISp) across behavioral states.

Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids.

Human cerebral organoids derived from induced pluripotent stem cells can recapture early developmental processes and reveal changes involving neurodevelopmental disorders. Mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene are associated with Rett syndrome, and disease severity varies depending on the location and type of mutation. Here, we focused on neuronal activity in Rett syndrome patient-derived organoids, analyzing two types of MeCP2 mutations - a missense mutation (R306C) and a truncating mutation (V247X) - using calcium imaging with three-photon microscopy.

Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study.

Background: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods.

Methods: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed.

An intra-oral flavor detection task in freely moving mice.

Flavor plays a critical role in the pleasure of food. Flavor research has mainly focused on human subjects and revealed that many brain regions are involved in flavor perception. However, animal models for elucidating the mechanisms of neural circuits are lacking.

Low dose tacrolimus exposure and early steroid withdrawal with strict body weight control can improve post kidney transplant glucose tolerance in Japanese patients.

The development of diabetes mellitus (DM) after living donor kidney transplantation (KT) is a risk factor for worsening transplant kidney function, cardiac disease, and cerebrovascular disease, which may affect prognosis after KT. At our institution, all patients' glucose tolerance is evaluated perioperatively by oral glucose tolerance tests (OGTTs) at pre-KT, and 3, 6, and 12 month (mo.) after KT.

Characterization and treatment of gemcitabine- and cisplatin-resistant bladder cancer cells with a pan-RAS inhibitor.

Combination chemotherapy with gemcitabine and cisplatin (GC) is recommended as the primary treatment for advanced bladder cancer (BC). However, the benefits of this approach are limited owing to the acquisition of drug resistance. Here, we found that gemcitabine-resistant and cisplatin-resistant BCs do not exhibit cross-resistance, and that these BCs exhibit different mRNA patterns, as revealed using RNA sequence analysis.

Differential brain expression pattern of Sez6 alternative splicing isoform with deleted transmembrane domain.

Seizure-related gene 6 (Sez6) is a transmembrane protein specifically localized on neuronal dendrites and responsible for dendritic branching and synapse formation. Alternative splicing produces three isoforms of Sez6 mRNAs: the dominant isoform encodes a transmembrane-type protein, whereas the two recessive isoforms encode transmembrane and secretory proteins. In the present study, to clarify the differential functions of these isoforms, the expression patterns resulting from Sez6 splicing isoforms were investigated in the mouse brain as well as in cultured neurons.

H3K4me3 plays a key role in establishing permissive chromatin states during bud dormancy and bud break in apple.

Bud dormancy helps woody perennials survive winter and activate robust plant development in the spring. For apple (Malus × domestica), short-term chilling induces bud dormancy in autumn, then prolonged chilling leads to dormancy release and a shift to a quiescent state in winter, with subsequent warm periods promoting bud break in spring. Epigenetic regulation contributes to seasonal responses such as vernalization.

Conversion surgery for microsatellite instability-high gastric cancer with a complete pathological response to pembrolizumab: a case report.

Background: Immune checkpoint inhibitors are reportedly effective in treating microsatellite instability (MSI)-high gastric cancer. There are a few case reports of conversion surgery (CS) with nivolumab but none with pembrolizumab. Herein, we describe a patient with MSI-high gastric cancer who was successfully treated with pembrolizumab and underwent CS with a pathological complete response.

Auditory Cortex Neurons Show Task-Related and Learning-Dependent Selectivity toward Sensory Input and Reward during the Learning Process of an Associative Memory Task.

The activity of primary auditory cortex (A1) neurons is modulated not only by sensory inputs but also by other task-related variables in associative learning. However, it is unclear how A1 neural activity changes dynamically in response to these variables during the learning process of associative memory tasks. Therefore, we developed an associative memory task using auditory stimuli in rats.

microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1.

Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine-resistant cells were established and resistance confirmed in vitro and in vivo.

Separation from a bonded partner alters neural response to inflammatory pain in monogamous rodents.

Pain experience is known to be modified by social factors, but the brain mechanisms remain unspecified. We recently established an animal model of social stress-induced hyperalgesia (SSIH) using a socially monogamous rodent, the prairie vole, in which males separated from their female partners (loss males) became anxious and displayed exacerbated inflammatory pain behaviors compared to males with partners (paired males). In the present study, to explore the neural pathways involved in SSIH, a difference in neuronal activation in pain-related brain regions, or "pain matrix", during inflammatory pain between paired and loss males was detected using Fos immunoreactivity (Fos-ir).

Hippocampal CA1 Neurons Represent Positive Feedback During the Learning Process of an Associative Memory Task.

The hippocampus is crucial for forming associations between environmental stimuli. However, it is unclear how neural activities of hippocampal neurons dynamically change during the learning process. To address this question, we developed an associative memory task for rats with auditory stimuli.

Over-representation of fundamental decision variables in the prefrontal cortex underlies decision bias.

The brain is organized into anatomically distinct structures consisting of a variety of projection neurons. While such evolutionarily conserved neural circuit organization underlies the innate ability of animals to swiftly adapt to environments, they can cause biased cognition and behavior. Although recent studies have begun to address the causal importance of projection-neuron types as distinct computational units, it remains unclear how projection types are functionally organized in encoding variables during cognitive tasks.

Contribution of non-sensory neurons in visual cortical areas to visually guided decisions in the rat.

It is widely assumed that trial-by-trial variability in visual detection performance is explained by the fidelity of visual responses in visual cortical areas influenced by fluctuations of internal states, such as vigilance and behavioral history. However, it is not clear which neuronal ensembles represent such different internal states. Here, we utilized a visual detection task, which distinguishes internal states in response to identical stimuli, while recording neurons simultaneously from the primary visual cortex (V1) and the posterior parietal cortex (PPC).

Quantitative analysis of auxin metabolites in lychee flowers.

To investigate the modulation of endogenous indole-3-acetic acid (IAA) level by biosynthesis and inactivation during floral development, IAA and its metabolites were analyzed by LC-ESI/MS/MS in Lychee (Litchi chinensis Sonn.) flowers. In the bloomed flowers, the level of free IAA was higher in males than in females.

EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer.

Background: Cisplatin-based chemotherapy is recommended as the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, the benefits are limited due to the acquisition of drug resistance. The mechanisms of resistance remain unclear.

Clinical Outcomes of Fully Covered Self-expanding Metallic Stent Placement for Palliation of Incurable Esophageal Cancer With or Without Radiotherapy.

Background/aim: A combination therapy of esophageal stent and chemoradiotherapy (CRT) is currently considered risky for severe complications. The aim of this study was to assess the safety and efficacy of a fully covered self-expandable metallic stent (FCSEMS) placement in palliating incurable esophageal cancer before and/or after CRT.

Patients And Methods: We retrospectively reviewed clinical outcomes of 64 incurable advanced esophageal cancer patients with FCSEMS placement.