Dopamine regulates decision thresholds in human reinforcement learning in males.

Dopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation of response vigour. Here, we examine dopaminergic mechanisms underlying human reinforcement learning and action selection via a combined pharmacological neuroimaging approach in male human volunteers (n = 31, within-subjects; Placebo, 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist Haloperidol). We found little credible evidence for previously reported beneficial effects of L-dopa vs.

Tools for Genetic Engineering and Gene Expression Control in and .

Alphaproteobacteria have a variety of cellular and metabolic features that provide important insights into biological systems and enable biotechnologies. For example, some species are capable of converting plant biomass into valuable biofuels and bioproducts have the potential to form the backbone of the sustainable bioeconomy. Among the Alphaproteobacteria, , , and , show particular promise as organisms that can be engineered to convert extracted plant lignin or sugars into bioproducts and biofuels.

The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients.

Background: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease.

Methods: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate.

Consistency is key: influence of skull density ratio distribution on the formation of clinically effective lesions and long-term tremor suppression following treatment with MR-guided focused ultrasound.

Objective: Skull density ratio (SDR) influences the permeability of the skull to the ultrasound waves used in magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor. SDR values vary across the skull and the mean value is known to be predictive of sonication thermal increase. The aim of this investigation was to explore the effects of the SDR distribution on clinical outcomes following treatment with MRgFUS.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months.

Electron counting detectors in scanning transmission electron microscopy via hardware signal processing.

Transmission electron microscopy is a pivotal instrument in materials and biological sciences due to its ability to provide local structural and spectroscopic information on a wide range of materials. However, the electron detectors used in scanning transmission electron microscopy are often unable to provide quantified information, that is the number of electrons impacting the detector, without exhaustive calibration and processing. This results in arbitrary signal values with slow response times that cannot be used for quantification or comparison to simulations.

Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in Transgenic Mice.

Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both -null and -humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, -null, and -humanized mice treated with and without the potent agonist GW7647.

Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions.

Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-N-NAM and 1-N nicotinic acid and hyperpolarized them with dDNP, reaching (13.

A Quantitative Description for Optical Mass Measurement of Single Biomolecules.

Label-free detection of single biomolecules in solution has been achieved using a variety of experimental approaches over the past decade. Yet, our understanding of the magnitude of the optical contrast and its relationship with the underlying atomic structure as well as the achievable measurement sensitivity and precision remain poorly defined. Here, we use a Fourier optics approach combined with an atomic structure-based molecular polarizability model to simulate mass photometry experiments from first principles.

Prediction accuracy of regulatory elements from sequence varies by functional sequencing technique.

Introduction: Various sequencing based approaches are used to identify and characterize the activities of -regulatory elements in a genome-wide fashion. Some of these techniques rely on indirect markers such as histone modifications (ChIP-seq with histone antibodies) or chromatin accessibility (ATAC-seq, DNase-seq, FAIRE-seq), while other techniques use direct measures such as episomal assays measuring the enhancer properties of DNA sequences (STARR-seq) and direct measurement of the binding of transcription factors (ChIP-seq with transcription factor-specific antibodies). The activities of -regulatory elements such as enhancers, promoters, and repressors are determined by their sequence and secondary processes such as chromatin accessibility, DNA methylation, and bound histone markers.

A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.

Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study.

PAC-Bayes Bounds for Bandit Problems: A Survey and Experimental Comparison.

PAC-Bayes has recently re-emerged as an effective theory with which one can derive principled learning algorithms with tight performance guarantees. However, applications of PAC-Bayes to bandit problems are relatively rare, which is a great misfortune. Many decision-making problems in healthcare, finance and natural sciences can be modelled as bandit problems.

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms.

Cohesin connects CTCF-binding sites and other genomic loci in cis to form chromatin loops and replicated DNA molecules in trans to mediate sister chromatid cohesion. Whether cohesin uses distinct or related mechanisms to perform these functions is unknown. Here, we describe a cohesin hinge mutant that can extrude DNA into loops but is unable to mediate cohesion in human cells.

Essential Gene Knockdowns Reveal Genetic Vulnerabilities and Antibiotic Sensitivities in .

The emergence of multidrug-resistant Gram-negative bacteria underscores the need to define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative pathogen, , is considered an urgent threat due to its propensity to evade antibiotic treatments. Essential cellular processes are the target of existing antibiotics and a likely source of new vulnerabilities.

Perceptions of High-Intensity Interval Training Among People With Spinal Cord Injury: A Mixed-Methods Analysis.

This mixed-method project investigated how people with spinal cord injury perceive high-intensity interval training (HIIT). Using a recumbent hand cycle, 11 active men and 9 active women with spinal cord injury or related disease participated in a single HIIT and moderate-intensity continuous training (MICT) session. Following exercise, participants completed surveys assessing enjoyment, self-efficacy, and outcome expectations.

Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.

Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans).

Improving rigor through gender inclusivity in reproductive psychiatric science.

Accurately defining the individuals that research involves and generalizes to is critical for rigorous and reproducible science. In reproductive psychiatry, which historically focuses on the impact of the menstrual cycle, pregnancy, and menopause on mental health, this means moving beyond characterizing samples and relevant populations as "women" in favor of language that precisely identifies the physiological characteristics pertinent to the research being conducted and accurately reflects the varied genders represented in those populations. Concrete recommendations are provided for precise use of sex and gender terminology and gender inclusivity throughout the scientific process, including study conceptualization, etiquette in research environments, recruitment, methods, and dissemination.

A systematic review of demographic and background factors associated with the development of children's aquatic competence.

Background: Globally, drowning is a leading cause of unintentional injury and death among children. Teaching aquatic competencies (swimming skills and water safety knowledge) to children has been proposed as a prevention strategy. In Australia, however, many children are not meeting standard aquatic competency benchmarks.

Associations between long-term aircraft noise exposure, cardiovascular disease, and mortality in US cohorts of female nurses.

Unlabelled: There is limited research examining aircraft noise and cardiovascular disease (CVD) risk. The objective of this study was to investigate associations of aircraft noise with CVD among two US cohorts, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII).

Methods: Between 1994 and 2014, we followed 57,306 NHS and 60,058 NHSII participants surrounding 90 airports.

Die Neustrukturierung der Notaufnahme gemäß dem G-BA-Beschluss zu einem gestuften System von Notfallstrukturen.

Background: There is no assessment of the effects regarding the decision of the Federal Joint Committee from April 19th, 2018 which demands a central and interdisciplinary emergency room system under the control of a professionally and organizationally independent administration. The aim of this study was to solicit the current opinion of leading orthopedic surgeons regarding the above-mentioned decision.

Material And Methods: An online questionnaire was sent to all 731 members of the Verband Leitender Orthopäden und Unfallchirurgen (www.