GO-CRISPR: A highly controlled workflow to discover gene essentiality in loss-of-function screens.

Genome-wide CRISPR screens are an effective discovery tool for genes that underlie diverse cellular mechanisms that can be scored through cell fitness. Loss-of-function screens are particularly challenging compared to gain-of-function because of the limited dynamic range of decreased sgRNA sequence detection. Here we describe Guide-Only control CRISPR (GO-CRISPR), an improved loss-of-function screening workflow, and its companion software package, Toolset for the Ranked Analysis of GO-CRISPR Screens (TRACS).

Sustained EEG responses to rapidly unfolding stochastic sounds reflect Bayesian inferred reliability tracking.

How does the brain track and process rapidly changing sensory information? Current computational accounts suggest that our sensations and decisions arise from the intricate interplay between bottom-up sensory signals and constantly changing expectations regarding the statistics of the surrounding world. A significant focus of recent research is determining which statistical properties are tracked by the brain as it monitors the rapid progression of sensory information. Here, by combining EEG (three experiments N ≥ 22 each) and computational modelling, we examined how the brain processes rapid and stochastic sound sequences that simulate key aspects of dynamic sensory environments.

Spatially resolved gene expression profiles of fibrosing interstitial lung diseases.

Fibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP).

Systematic changes in neural selectivity reflect the acquired salience of category-diagnostic dimensions.

Humans and other animals develop remarkable behavioral specializations for identifying, differentiating, and acting on classes of ecologically important signals. Ultimately, this expertise is flexible enough to support diverse perceptual judgments: a voice, for example, simultaneously conveys what a talker says as well as myriad cues about her identity and state. Mature perception across complex signals thus involves both discovering and learning regularities that best inform diverse perceptual judgments, and weighting this information flexibly as task demands change.

Distributional learning drives statistical suppression and deafening.

Unlabelled: Humans and other animals use information about how likely it is for something to happen. The absolute and relative probability of an event influences a remarkable breadth of behaviors, from foraging for food to comprehending linguistic constructions -- even when these probabilities are learned implicitly. It is less clear how, and under what circumstances, statistical learning of simple probabilities might drive changes in perception and cognition.

A Genome Wide CRISPR Screen Reveals That HOXA9 Promotes Enzalutamide Resistance in Prostate Cancer.

Androgen receptor inhibitors are commonly used for prostate cancer treatment, but acquired resistance is a significant problem. Codeletion of RB and p53 is common in castration resistant prostate cancers, however they are difficult to target pharmacologically. To comprehensively identify gene loss events that contribute to enzalutamide response, we performed a genome-wide CRISPR knockout screen in LNCaP prostate cancer cells.

Development of a high-throughput UHPLC-MS/MS method for the analysis of Fusarium and Alternaria toxins in cereals and cereal-based food.

A QuEChERS (quick, easy, cheap, effective, rugged, and safe)-based multi-mycotoxin method was developed, analyzing 24 (17 free and 7 modified) Alternaria and Fusarium toxins in cereals via ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A modified QuEChERS approach was optimized for sample preparation. Quantification was conducted using a combination of stable isotope dilution analysis (SIDA) for nine toxins and matrix-matched calibration for ten toxins.

Brain Proteome Profiling Reveals Common and Divergent Signatures in Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

The molecular pathogenesis of degenerative parkinsonisms, including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and Multiple system atrophy (MSA), remains largely unknown. To gain novel insight into molecular processes associated with these diseases, we conducted a proteome-wide expression study in prefrontal cortex tissue from a cohort of 181 individuals, comprising PD (N = 73), PSP (N = 18), MSA (N = 17) and healthy control (N = 73). Using marker gene profiles, we first assess the cellular composition of the samples and, subsequently, identify distinct protein signatures for each disease, while correcting for cell composition.

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells.

Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context.

Editor's Choice - Peri-operative Mortality and Morbidity of Complex Abdominal Aortic Aneurysm Repair in Switzerland: A Swissvasc Report.

Objective: Complex abdominal aortic aneurysms (cAAA) pose a clinical challenge. The aim of this study was to assess the 30 day mortality and morbidity rates for open aneurysm repair (OAR) and fenestrated or branched endovascular aortic repair (F/B-EVAR), and the effect of hospital volume in patients with asymptomatic cAAA in Switzerland.

Methods: Retrospective, cohort study using data from Switzerland's national registry for vascular surgery, Swissvasc, including patients treated from 1 January 2019 to 31 December 2022.

A one-man bilingual cocktail party: linguistic and non-linguistic effects on bilinguals' speech recognition in Mandarin and English.

Multilingual speakers can find speech recognition in everyday environments like restaurants and open-plan offices particularly challenging. In a world where speaking multiple languages is increasingly common, effective clinical and educational interventions will require a better understanding of how factors like multilingual contexts and listeners' language proficiency interact with adverse listening environments. For example, word and phrase recognition is facilitated when competing voices speak different languages.

Development of a team-specific research strategy using a modified Delphi method in a regional public hospital dietetics department.

Objective: Evaluate research capacity and culture among regional hospital dietitians, develop a team specific research strategy, and build research skills of novice researchers.

Methods: The Research Capacity in Context Tool was used to assess current research capacity and culture at organisational, team and individual levels. Results were analysed using descriptive statistics and content analysis of free text responses.

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

Objective: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy.

Methods: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated.

Generalization of auditory expertise in audio engineers and instrumental musicians.

From auditory perception to general cognition, the ability to play a musical instrument has been associated with skills both related and unrelated to music. However, it is unclear if these effects are bound to the specific characteristics of musical instrument training, as little attention has been paid to other populations such as audio engineers and designers whose auditory expertise may match or surpass that of musicians in specific auditory tasks or more naturalistic acoustic scenarios. We explored this possibility by comparing students of audio engineering (n = 20) to matched conservatory-trained instrumentalists (n = 24) and to naive controls (n = 20) on measures of auditory discrimination, auditory scene analysis, and speech in noise perception.

EZH2 inhibition stimulates repetitive element expression and viral mimicry in resting splenic B cells.

Mammalian cells repress expression of repetitive genomic sequences by forming heterochromatin. However, the consequences of ectopic repeat expression remain unclear. Here we demonstrate that inhibitors of EZH2, the catalytic subunit of the Polycomb repressive complex 2 (PRC2), stimulate repeat misexpression and cell death in resting splenic B cells.

Auditory attention influences trajectories of symbol-speech sound learning in children with and without dyslexia.

The acquisition of letter-speech sound correspondences is a fundamental process underlying reading development, one that could be influenced by several linguistic and domain-general cognitive factors. In the current study, we mimicked the first steps of this process by examining behavioral trajectories of audiovisual associative learning in 110 7- to 12-year-old children with and without dyslexia. Children were asked to learn the associations between eight novel symbols and native speech sounds in a brief training and subsequently read words and pseudowords written in the artificial orthography.

Salient sounds distort time perception and production.

The auditory world is often cacophonous, with some sounds capturing attention and distracting us from our goals. Despite the universality of this experience, many questions remain about how and why sound captures attention, how rapidly behavior is disrupted, and how long this interference lasts. Here, we use a novel measure of behavioral disruption to test predictions made by models of auditory salience.

Attentional modulation of neural sound tracking in children with and without dyslexia.

Auditory selective attention forms an important foundation of children's learning by enabling the prioritisation and encoding of relevant stimuli. It may also influence reading development, which relies on metalinguistic skills including the awareness of the sound structure of spoken language. Reports of attentional impairments and speech perception difficulties in noisy environments in dyslexic readers are also suggestive of the putative contribution of auditory attention to reading development.

Auditory category learning is robust across training regimes.

Multiple lines of research have developed training approaches that foster category learning, with important translational implications for education. Increasing exemplar variability, blocking or interleaving by category-relevant dimension, and providing explicit instructions about diagnostic dimensions each have been shown to facilitate category learning and/or generalization. However, laboratory research often must distill the character of natural input regularities that define real-world categories.