Mapping common and distinct brain correlates among cognitive flexibility tasks: concordant evidence from meta-analyses.

Cognitive flexibility allows individuals to switch between different tasks, strategies, or ideas; an ability that is important for everyday life. The Wisconsin card sorting test (WCST) and task switching paradigm (TSP) are popular measures of cognitive flexibility. Although both tasks require switching, the TSP requires participants to memorize switching rules and retrieve them when they view a cue (rule-retrieval), whereas the classic WCST requires participants to discover the switching rule via trial-and-error (rule-discovery).

Protocol for NT-CRISPR: A Method for Efficient Genome Engineering in Vibrio natriegens.

Vibrio natriegens is a gram-negative bacterium, which has received increasing attention due to its very fast growth with a doubling time of under 10 min under optimal conditions. To enable a wide range of projects spanning from basic research to biotechnological applications, we developed NT-CRISPR as a new method for genome engineering. This book chapter provides a step-by-step protocol for the use of this previously published tool.

The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.

There is a significant sex bias in lung cancer, with males showing increased mortality compared with females. A better mechanistic understanding of these differences could help identify therapeutic targets to personalize cancer therapies to each sex. After observing a clear sex bias in humanized mice, with male patient-derived xenograft lung tumors being more progressive and deadlier than female patient-derived xenograft lung tumors, we identified mouse tumor models of lung cancer with the same sex bias.

Clinical application of phage immunoprecipitation sequencing to diagnose enterovirus D68 as the underlying etiology in a case of Gullain-Barré syndrome.

Gullain-Barré syndrome (GBS) is an acute peripheral neuropathy often preceded by respiratory or gastrointestinal infections, though molecular testing of cerebrospinal fluid (CSF) is often inconclusive. In a recent case of severe pediatric GBS in British Columbia, Canada, we detected CSF antibodies against enterovirus D (EV-D) to link GBS with prior EV-D68 respiratory infection.

Graded-CRISPRi, a Tool for Tuning the Strengths of CRISPRi-Mediated Knockdowns in Using gRNA Libraries.

In recent years, the fast-growing bacterium has gained increasing attention as it has the potential to become a next-generation chassis for synthetic biology. A wide range of genetic parts and genome engineering methods have already been developed. However, there is still a need for a well-characterized tool to effectively and gradually reduce the expression levels of native genes.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981.

Effects of a multicomponent communication training to involve older people in decisions to DEPRESCRIBE cardiometabolic medication in primary care (CO-DEPRESCRIBE): protocol for a cluster randomized controlled trial with embedded process and economic evaluation.

Background: Deprescribing of medication for cardiovascular risk factors and diabetes has been incorporated in clinical guidelines but proves to be difficult to implement in primary care. Training of healthcare providers is needed to enhance deprescribing in eligible patients. This study will examine the effects of a blended training program aimed at initiating and conducting constructive deprescribing consultations with patients.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis.

Measured leaf dark respiratory CO -release is not controlled by stomatal conductance.

Leaf dark respiratory CO -release (R ) is, according to some literature, dependent on the rate of leaf transpiration. If this is true, then at a given vapor pressure deficit, the leaf stomatal conductance (g ) will be expected to be a controlling factor of measured R at any given time. We artificially lowered leaf g by applying abscisic acid (ABA).

Application of the thermal death time model in predicting thermal damage accumulation in plants.

The thermal death time (TDT) model suggests that the duration for which an organism can tolerate thermal stress decreases exponentially as the intensity of the temperature becomes more extreme. This model has been used to predict damage accumulation in ectothermic animals and plants under fluctuating thermal conditions. However, the critical assumption of the TDT model, which is additive damage accumulation, remains unverified for plants.

[Systemic sclerosis].

Background: Systemic sclerosis (SSc) is a very heterogeneous, chronic, rare, but socioeconomically important disease with a severe disease course and severe impairment of the quality of life of affected patients.

Objectives: Overview of the current state of research on the pathogenesis, diagnosis and therapy of SSc.

Methods: A literature search was performed.

Tumor Spheroid Fabrication and Encapsulation in Polyethylene Glycol Hydrogels for Studying Spheroid-Matrix Interactions.

Three-dimensional (3D) encapsulation of spheroids is crucial to adequately replicate the tumor microenvironment for optimal cell growth. Here, we designed an in vitro 3D glioblastoma model for spheroid encapsulation to mimic the tumor extracellular microenvironment. First, we formed square pyramidal microwell molds using polydimethylsiloxane.

Seek and you shall find-news on the quest for novel PET-degrading enzymes.

Plastic-degrading enzymes hold immense potential for eco-friendly recycling methods. However, the catalytic rates of current enzymes do not stack up against the mammoth task of degrading millions of tons of plastic waste per year. In the quest for more efficient polyethylene terephthalate (PET)-degrading enzymes, Zhang et al.

Targeting Oncogenic Mutant p53 and BCL-2 for Small Cell Lung Cancer Treatment.

Through a unique genomics and drug screening platform with ~800 solid tumor cell lines, we have found a subset of SCLC cell lines are hypersensitive to venetoclax, an FDA-approved inhibitor of BCL-2. SCLC-A (ASCL1 positive) and SCLC-P (POU2F3 positive), which make up almost 80% of SCLC, frequently express high levels of BCL-2. We found that a subset of SCLC-A and SCLC-P showed high BCL-2 expression but were venetoclax-resistant.

Effects of high pressure and temperature conditions on the chemical fate of flowback water related chemicals.

Environmental risk assessment is generally based on atmospheric conditions for the modelling of chemical fate after entering the environment. However, during hydraulic fracturing, chemicals may be released deep underground. This study therefore focuses on the effects of high pressure and high temperature conditions on chemicals in flowback water to determine whether current environmental fate models need to be adapted in the context of downhole activities.

A ring-like accretion structure in M87 connecting its black hole and jet.

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole.

Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation.

Facilitating pharmacy staff's conversations about non-medical medication switches: Development and testing of a communication training.

Background: Non-medical medication switches, a change to another medicine or medication label not motivated by medical reasons, occur frequently. Switches often lead to negative patient emotions, such as confusion and anger. Pharmacy staff's communication, i.

Estimation of Bedtimes of Reddit Users: Integrated Analysis of Time Stamps and Surveys.

Background: Individuals with later bedtimes have an increased risk of difficulties with mood and substances. To investigate the causes and consequences of late bedtimes and other sleep patterns, researchers are exploring social media as a data source. Pioneering studies inferred sleep patterns directly from social media data.

Atmosphere-Snow Exchange Explains Surface Snow Isotope Variability.

The climate signal imprinted in the snow isotopic composition allows to infer past climate variability from ice core stable water isotope records. The concurrent evolution of vapor and surface snow isotopic composition between precipitation events indicates that post-depositional atmosphere-snow humidity exchange influences the snow and hence the ice core isotope signal. To date, however, this is not accounted for in paeleoclimate reconstructions from isotope records.

Pharmacologic Inhibition of SHP2 Blocks Both PI3K and MEK Signaling in Low-epiregulin HNSCC via GAB1.

Preclinical and clinical studies have evidenced that effective targeted therapy treatment against receptor tyrosine kinases (RTKs) in different solid tumor paradigms is predicated on simultaneous inhibition of both the PI3K and MEK intracellular signaling pathways. Indeed, re-activation of either pathway results in resistance to these therapies. Recently, oncogenic phosphatase SHP2 inhibitors have been developed with some now reaching clinical trials.

High-risk neuroblastoma with NF1 loss of function is targetable using SHP2 inhibition.

Reoccurring/high-risk neuroblastoma (NB) tumors have the enrichment of non-RAS/RAF mutations along the mitogen-activated protein kinase (MAPK) signaling pathway, suggesting that activation of MEK/ERK is critical for their survival. However, based on preclinical data, MEK inhibitors are unlikely to be active in NB and have demonstrated dose-limiting toxicities that limit their use. Here, we explore an alternative way to target the MAPK pathway in high-risk NB.