Prognostic scores in patients with severe tricuspid regurgitation: An external validation study.

Background: Four scores have been published in 2022 for assessing mortality risk of patients with tricuspid regurgitation (TR): the TRI-SCORE, those reported by Hochstadt and Wang and the TRIO score. Our objective was to perform an external validation of available scores for predicting mortality and the combined endpoint of mortality and heart failure (HF) admission, in an independent cohort of patients with severe TR and to compare their discriminative ability.

Methods: Discriminative ability of the scores for predicting events was assessed by means of receiver operating characteristics (ROC) curves.

Sleep microstructure organizes memory replay.

Recently acquired memories are reactivated in the hippocampus during sleep, an initial step for their consolidation. This process is concomitant with the hippocampal reactivation of previous memories, posing the problem of how to prevent interference between older and recent, initially labile, memory traces. Theoretical work has suggested that consolidating multiple memories while minimizing interference can be achieved by randomly interleaving their reactivation.

Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.

Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high ERK activation triggers oncogene-induced senescence, which halts tumor progression. Here we report that low-grade pancreatic intraepithelial neoplasia displays very high levels of phospho-ERK consistent with a senescence response.

Associative and predictive hippocampal codes support memory-guided behaviors.

Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal models of the world that enable predictions to be made. The mechanisms that support these associative and predictive aspects of memory are not yet understood.

Interictal epileptiform discharges affect memory in an Alzheimer's disease mouse model.

Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological diseases, such as Alzheimer's disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multilayer hippocampal silicon probes.

Hippocampo-cortical circuits for selective memory encoding, routing, and replay.

Traditionally considered a homogeneous cell type, hippocampal pyramidal cells have been recently shown to be highly diverse. However, how this cellular diversity relates to the different hippocampal network computations that support memory-guided behavior is not yet known. We show that the anatomical identity of pyramidal cells is a major organizing principle of CA1 assembly dynamics, the emergence of memory replay, and cortical projection patterns in rats.

Over and above frequency: Gamma oscillations as units of neural circuit operations.

Gamma oscillations (∼30-150 Hz) are widespread correlates of neural circuit functions. These network activity patterns have been described across multiple animal species, brain structures, and behaviors, and are usually identified based on their spectral peak frequency. Yet, despite intensive investigation, whether gamma oscillations implement causal mechanisms of specific brain functions or represent a general dynamic mode of neural circuit operation remains unclear.

Interictal epileptiform discharges affect memory in an Alzheimer's Disease mouse model.

Unlabelled: Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological disease, such as Alzheimer's Disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multi-layer hippocampal silicon probes.

CA2 orchestrates hippocampal network dynamics.

The hippocampus is composed of various subregions: CA1, CA2, CA3, and the dentate gyrus (DG). Despite the abundant hippocampal research literature, until recently, CA2 received little attention. The development of new genetic and physiological tools allowed recent studies characterizing the unique properties and functional roles of this hippocampal subregion.

High-resolution optogenetics in space and time.

To understand the neural mechanisms of behavior, it is necessary to both monitor and perturb the activity of ensembles of neurons with high specificity. While neural ensemble recordings have been available for decades, progress in high-resolution manipulation techniques has lagged behind. Optogenetics has enabled the manipulation of genetically defined cell types in behaving animals, and recent developments, including multipoint nanofabricated light sources, provide spatiotemporal resolution on a par with that of physiological recordings.

HectoSTAR μLED Optoelectrodes for Large-Scale, High-Precision In Vivo Opto-Electrophysiology.

Dynamic interactions within and across brain areas underlie behavioral and cognitive functions. To understand the basis of these processes, the activities of distributed local circuits inside the brain of a behaving animal must be synchronously recorded while the inputs to these circuits are precisely manipulated. Even though recent technological advances have enabled such large-scale recording capabilities, the development of the high-spatiotemporal-resolution and large-scale modulation techniques to accompany those recordings has lagged.

Extrinsic control and intrinsic computation in the hippocampal CA1 circuit.

In understanding circuit operations, a key problem is the extent to which neuronal spiking reflects local computation or responses to upstream inputs. We addressed this issue in the hippocampus by performing combined optogenetic and pharmacogenetic local and upstream inactivation. Silencing the medial entorhinal cortex (mEC) largely abolished extracellular theta and gamma currents in CA1 while only moderately affecting firing rates.

A hydride transfer complex reprograms NAD metabolism and bypasses senescence.

Metabolic rewiring and redox balance play pivotal roles in cancer. Cellular senescence is a barrier for tumorigenesis circumvented in cancer cells by poorly understood mechanisms. We report a multi-enzymatic complex that reprograms NAD metabolism by transferring reducing equivalents from NADH to NADP.

The continued need for animals to advance brain research.

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised.

Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease.

Objective: The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63 basal cells reportedly do not exist in the normal pancreas.

Design: We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC.

Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib.

The most frequent -p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine-kinase inhibitor (TKI) used to treat CML. Some studies suggest that transcript types confer different responses to IM.

The chromosome-scale assembly of the Canary Islands endemic spider Dysdera silvatica (Arachnida, Araneae) sheds light on the origin and genome structure of chemoreceptor gene families in chelicerates.

Here, we present the chromosome-level genome assembly of Dysdera silvatica Schmidt, 1981, a nocturnal ground-dwelling spider endemic from the Canary Islands. The genus Dysdera has undergone a remarkable diversification in this archipelago mostly associated with shifts in the level of trophic specialization, becoming an excellent model to study the genomic drivers of adaptive radiations. The new assembly (1.

Oxidative stress-induced senescence mediates inflammatory and fibrotic phenotypes in fibroblasts from systemic sclerosis patients.

Objective: SSc is an autoimmune connective tissue disorder characterized by inflammation and fibrosis. Although constitutive activation of fibroblasts is proposed to be responsible for the fibrotic and inflammatory features of the disease, the underlying mechanism remains elusive, and effective therapeutic targets are still lacking. The aim of this study was to evaluate the role of oxidative stress-induced senescence and its contribution to the pro-fibrotic and pro-inflammatory phenotypes of fibroblasts from SSc patients.

Phenylethynylbenzyl-modified biguanides inhibit pancreatic cancer tumor growth.

We present the design and synthesis of a small library of substituted biguanidium salts and their capacity to inhibit the growth of pancreatic cancer cells. We first present their in vitro and membrane activity, before we address their mechanism of action in living cells and in vivo activity. We show that phenylethynyl biguanidium salts possess higher ability to cross hydrophobic barriers, improve mitochondrial accumulation and anticancer activity.

Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies.

Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner.

Subcircuits of Deep and Superficial CA1 Place Cells Support Efficient Spatial Coding across Heterogeneous Environments.

The hippocampus is thought to guide navigation by forming a cognitive map of space. Different environments differ in geometry and the availability of cues that can be used for navigation. Although several spatial coding mechanisms are known to coexist in the hippocampus, how they are influenced by various environmental features is not well understood.

Hippocampal CA2 sharp-wave ripples reactivate and promote social memory.

The consolidation of spatial memory depends on the reactivation ('replay') of hippocampal place cells that were active during recent behaviour. Such reactivation is observed during sharp-wave ripples (SWRs)-synchronous oscillatory electrical events that occur during non-rapid-eye-movement (non-REM) sleep and whose disruption impairs spatial memory. Although the hippocampus also encodes a wide range of non-spatial forms of declarative memory, it is not yet known whether SWRs are necessary for such memories.