Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available.

Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases.

Introduction: Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) represent a spectrum of neurodegenerative disorders (NDDs). Here, we performed the first direct comparison of their transcriptomic landscapes.

Methods: We profiled the whole transcriptomes of NDD cortical tissue by snRNA-seq.

Sequence-defined phosphoestamers for selective inhibition of the KRAS/RAF1 interaction.

RAS proteins are the most frequently mutated in cancer, yet they have proved extremely difficult to target in drug discovery, largely because interfering with the interaction of RAS with its downstream effectors comes up against the challenge of protein-protein interactions (PPIs). Sequence-defined synthetic oligomers could combine the precision and customisability of synthetic molecules with the size required to address entire PPI surfaces. We have adapted the phosphoramidite chemistry of oligonucleotide synthesis to produce a library of nearly one million non-nucleosidic oligophosphoester sequences (phosphoestamers) composed of units taken from synthetic supramolecular chemistry, and used a fluorescent-activated bead sorting (FABS) process to select those that inhibit the interaction between KRAS (the most prevalent, and undrugged, RAS mutant) and RAF, a downstream effector of RAS that drives cell proliferation.

Transcriptomic Analysis of the Amygdala in Subjects with Schizophrenia, Bipolar Disorder and Major Depressive Disorder Reveals Differentially Altered Metabolic Pathways.

Background And Hypothesis: The amygdala, crucial for mood, anxiety, fear, and reward regulation, shows neuroanatomical and molecular divergence in psychiatric disorders like schizophrenia, bipolar disorder and major depression. This region is also emerging as an important regulator of metabolic and immune pathways. The goal of this study is to address the paucity of molecular studies in the human amygdala.