CRISPR/Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA.

A hexanucleotide GGGGCC repeat expansion in the non-coding region of the C9orf72 gene is the most common genetic mutation identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The resulting repeat RNA and dipeptide repeat proteins from non-conventional repeat translation have been recognized as important markers associated with the diseases. CRISPR/Cas13d, a powerful RNA-targeting tool, has faced challenges in effectively targeting RNA with stable secondary structures.

Anxiety sensitivity mediates relations between anxiety (but not depression) and problematic smartphone use severity, adjusting for age and sex, in Chinese adolescents early in the COVID-19 pandemic.

Risk factors for problematic smartphone use (PSU) have rapidly become an important area of research due to the prevalence of smartphones and functional impairment associated with PSU. Our aim was to examine relations between established predictors of PSU (depression and anxiety) and a potential mediator of PSU (anxiety sensitivity; AS). Participants ( = 4752) from junior and senior high schools in Tianjin, China completed a web-based survey with measures of depression, anxiety, AS, and PSU.

Anxiety and stress severity are related to greater fear of missing out on rewarding experiences: A latent profile analysis.

The fear of missing out on rewarding social experiences (FOMO) is an increasingly studied psychological construct, related to negative affectivity and increased online social engagement. Yet the heterogeneity of FOMO across individuals is not known. We conducted a latent profile analysis (LPA) of FOMO self-report ratings to determine sample heterogeneity and uncover underlying subgroups (profiles) of participants.

A Helicase Unwinds Hexanucleotide Repeat RNA G-Quadruplexes and Facilitates Repeat-Associated Non-AUG Translation.

The expansion of a hexanucleotide repeat GGGGCC (G4C2) in the gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 expansion leads to repeat-associated non-AUG (RAN) translation and the production of toxic dipeptide repeat (DPR) proteins, but the mechanisms of RAN translation remain enigmatic. Here, we report that the RNA helicase DHX36 is a robust positive regulator of RAN translation.

Modeling anxiety and fear of COVID-19 using machine learning in a sample of Chinese adults: associations with psychopathology, sociodemographic, and exposure variables.

Objectives: Research during prior virus outbreaks has examined vulnerability factors associated with increased anxiety and fear.

Design: We explored numerous psychopathology, sociodemographic, and virus exposure-related variables associated with anxiety and perceived threat of death regarding COVID-19.

Method: We recruited 908 adults from Eastern China for a cross-sectional web survey, from 24 February to 15 March 2020, when social distancing was heavily enforced in China.

Health anxiety related to problematic smartphone use and gaming disorder severity during COVID-19: Fear of missing out as a mediator.

Health anxiety has been linked with fear and anxiety regarding COVID-19. Higher levels of health anxiety likely increased social distancing and self-isolating during the pandemic. We investigated relations among health anxiety, fear of missing out (FOMO) on rewarding social experiences from social distancing, and consequential levels of problematic smartphone use (PSU) and gaming disorder (GD).

Cognitive Fatigue Predicts Cognitive Failure in Multiple Sclerosis Patients and Healthy Controls: A Case-Control Study.

Objective: Fatigue and cognitive deficits are frequent symptoms of multiple sclerosis (MS). However, the exact nature of their co-occurrence is not fully understood. We sought to determine the impact of cognitive and physical fatigue on subjective cognitive deficits in MS patients and healthy controls.

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.

An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo.

Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.

Background: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.

Methods: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months.

Molecular genetics in psychology and personality neuroscience: On candidate genes, genome wide scans, and new research strategies.

Despite the substantial heritability estimates for psychological traits, their precise genetic foundation from a molecular perspective remains elusive. We summarize findings and advances from more than twenty years of research into the molecular genetics of personality and other psychological traits. We describe how the candidate gene approach has - despite its appealing theoretical foundations - often (but not always) failed to point towards replicable associations between genetic polymorphisms and behavioral traits.

The compatibility of theoretical frameworks with machine learning analyses in psychological research.

Supervised machine learning has been increasingly used in psychology and psychiatry research. Machine learning offers an important advantage over traditional statistical analyses: statistical model training in example data to enhance predictions in external test data. Additional advantages include advanced, improved statistical algorithms, and empirical methods to select a smaller set of predictor variables.

How to overcome taxonomical problems in the study of Internet use disorders and what to do with "smartphone addiction"?

Aims: The present theoretical paper introduces the smartphone technology as a challenge for diagnostics in the study of Internet use disorders and reflects on the term "smartphone addiction."

Methods: Such a reflection is carried out against the background of a literature review and the inclusion of Gaming Disorder in ICD-11.

Results: We believe that it is necessary to divide research on Internet use disorder (IUD) into a mobile and non-mobile IUD branch.

CRISPR-Cas9 Screens Identify the RNA Helicase DDX3X as a Repressor of C9ORF72 (GGGGCC)n Repeat-Associated Non-AUG Translation.

Hexanucleotide GGGGCC repeat expansion in C9ORF72 is the most prevalent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the aberrant accumulation of dipeptide repeat (DPR) proteins produced by the unconventional translation of expanded RNA repeats. Here, we performed genome-wide CRISPR-Cas9 screens for modifiers of DPR protein production in human cells.

Human Extinction Learning Is Accelerated by an Angiotensin Antagonist via Ventromedial Prefrontal Cortex and Its Connections With Basolateral Amygdala.

Background: Deficient extinction learning and threat adaptation in the ventromedial prefrontal cortex (vmPFC)-amygdala circuitry strongly impede the efficacy of exposure-based interventions in anxiety disorders. Recent animal models suggest a regulatory role of the renin-angiotensin system in both these processes. Against this background, the present randomized placebo-controlled pharmacologic functional magnetic resonance imaging experiment aimed at determining the extinction enhancing potential of the angiotensin II type 1 receptor antagonist losartan (LT) in humans.

Association of Childhood Maltreatment With Interpersonal Distance and Social Touch Preferences in Adulthood.

Objective: Childhood maltreatment is a major risk factor for psychopathology associated with interpersonal problems in adulthood, but the etiological pathways involved are still unclear. The authors propose that childhood maltreatment confers risk for dysfunctional behavior in social interactions by altering interpersonal distance preference and the processing of social touch.

Methods: Ninety-two medication-free adults (64 of them female) with low, medium, and high levels of childhood maltreatment were tested with an interpersonal distance paradigm and subsequently underwent a social touch functional MRI task during which they rated the perceived comfort of slow touch (C-tactile [CT] optimal speed; 5 cm/s) and fast touch (non-CT-optimal speed; 20 cm/s).

The relationship between Internet Use Disorder, depression and burnout among Chinese and German college students.

In the present study, we investigated the relationship between depression and Internet Use Disorder (IUD) and between burnout and IUD among German as well as Chinese college students. Due to cultural differences and their implications for the individual's psychological health, we expected Chinese college students to have in particular higher IUD than German college students. We further expected to find positive relationships between depression and IUD and between burnout and IUD.

C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation.

Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we demonstrate that the repeat-associated non-AUG (RAN) translation of (GGGGCC) -containing RNAs into poly-dipeptides can initiate in vivo without a 5'-cap. The primary RNA substrate for RAN translation of C9ORF72 sense repeats is shown to be the spliced first intron, following its excision from the initial pre-mRNA and transport to the cytoplasm.

Edaravone: A new drug approved for ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive, adult onset neurodegenerative disease that is always fatal. The history of ALS drug discovery is fraught with many stops and starts. It took 22 years after the FDA approval of the anti-excitotoxic drug Riluzole before another drug was found to be effective in altering ALS progression: the anti-oxidant Edaravone.

Distinct Laterality in Forelimb-Movement Representations of Rat Primary and Secondary Motor Cortical Neurons with Intratelencephalic and Pyramidal Tract Projections.

Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb.

Poly(GP) proteins are a useful pharmacodynamic marker for -associated amyotrophic lateral sclerosis.

There is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. However, discovery of a GC repeat expansion in the gene as the most common genetic cause of ALS has opened up new avenues for therapeutic intervention for this form of ALS. GC repeat expansion RNAs and proteins of repeating dipeptides synthesized from these transcripts are believed to play a key role in -associated ALS (c9ALS).

Rodent Models of Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%).