Compromising tyrosine hydroxylase function extends and blunts the temporal profile of reinforcement by dopamine neurons in .

For a proper representation of the causal structure of the world, it is adaptive to consider both evidence for and evidence against causality. To take punishment as an example, the causality of a stimulus is unlikely if there is a temporal gap before punishment is received, but causality is credible if the stimulus immediately precedes punishment. In contrast, causality can be ruled out if the punishment occurred first.

Reliability of the OMERACT Giant cell arteritis Ultrasonography Score (OGUS): results of a patient-based exercise involving experts and non-experts in vascular ultrasonography.

Objective: To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography.

Methods: Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2.

EDENT1FI Master Protocol for screening of presymptomatic early-stage type 1 diabetes in children and adolescents.

Introduction: The identification of type 1 diabetes at an early presymptomatic stage has clinical benefits. These include a reduced risk of diabetic ketoacidosis (DKA) at the clinical manifestation of the disease and a significant reduction in clinical symptoms. The European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception (EDENT1FI) represents a pioneering effort to advance early detection of type 1 diabetes through public health screening.

Readiness of adults with type 1 diabetes and diabetes caregivers for diabetes distress monitoring using a voice-based digital health solution: insights from the PsyVoice mixed methods study.

Objectives: Diabetes distress can negatively affect the well-being of individuals with type 1 diabetes (T1D). Voice-based (VB) technology can be used to develop inexpensive and ecological tools for managing diabetes distress. This study explored the competencies to engage with digital health services, needs and preferences of individuals with T1D or caring for a child with this condition regarding VB technology to inform the tailoring of a co-designed tool for supporting diabetes distress management.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

External quality assessment (EQA) cycles are the smallest complete units within EQA programs that laboratories can use to obtain external assessments of their performance. In each cycle, several samples are distributed to the laboratories registered for participation, and ideally, EQA programs not only cover the examination procedures but also the pre- and post-examination procedures. The properties and concentration range of measurands in individual samples are selected with regard to the intended challenge for the participants so that each sample fulfils its purpose.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

External quality assessment (EQA) enhances patient safety through the evaluation of the quality of laboratory-based and point of care testing. Regulatory agencies and accreditation organizations utilize the results and the laboratory's response to them as part of assessing the laboratory's fitness to practice. In addition, where EQA samples are commutable and the assigned value has been determined using reference measurement procedures (RMPs), EQA data contributes to the verification of metrological traceability of assays as part of the post-market surveillance of diagnostic (IVD) medical devices (IVD-MDs).

Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation.

Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately optimized, both modalities lead to proteasomal degradation of the protein of interest (POI). Due to the complexity of the induced multistep degradation process, controls for degrader evaluation are critical and commonly used in the literature.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

Providers of external quality assessment (EQA) programs evaluate data or information obtained and reported by participant laboratories using their routine procedures to examine properties or measurands in samples provided for this purpose. EQA samples must offer participants an equal chance to obtain accurate results, while being designed to provide results in clinically relevant ranges. It is the responsibility of the EQA provider to meet the necessary requirements for homogeneity, stability and some other properties of the EQA items in order to offer participants a fair, reliable and technically interesting EQA experience.

Fast EEG/MEG BEM-Based Forward Problem Solution for High-Resolution Head Models.

A fast BEM (boundary element method) based approach is developed to solve an EEG/MEG forward problem for a modern high-resolution head model. The method utilizes a charge-based BEM accelerated by the fast multipole method (BEM-FMM) with an adaptive mesh pre-refinement method (called b-refinement) close to the singular dipole source(s). No costly matrix-filling or direct solution steps typical for the standard BEM are required; the method generates on-skin voltages as well as MEG magnetic fields for high-resolution head models within 90 seconds after initial model assembly using a regular workstation.

Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.

Complement factor H (CFH) common genetic variants have been associated with age-related macular degeneration (AMD). While most previous in vitro RPE studies focused on the common p.His402Tyr CFH variant, we characterized rare CFH variants that are highly penetrant for AMD using induced pluripotent stem-cell-derived retinal pigment epithelium (iPSC-RPE).

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.

Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.

4D structural biology-The 9 Murnau Conference on structural biology.

The data presented at the 9 International Murnau Conference on September 18-21, 2024, the largest recurring structural biology meeting in Central Europe, illustrated the thriving state of the structural biology community. This is largely attributed to the ground-breaking developments over the last decade, which were intensely discussed during the meeting.

Evidence that altercentric biases in a continuous false belief task depend on highlighting the agent's belief.

As social beings, we excel at understanding what other people think or believe. We even seem to be influenced by the belief of others in situations where it is irrelevant to our current tasks. Such altercentric interference has been proposed to reflect implicit belief processing.

Impact of reactive sclerosis on outcome of MR-HIFU for osteoid osteomas.

Objectives: To evaluate the influence of clinical and procedural factors, particularly the thickness of reactive sclerosis, on clinical outcome of MR-guided high-intensity focused ultrasound (MR-HIFU) for the treatment of symptomatic osteoid osteomas (OO) of the extremities.

Materials And Methods: 18 consecutive patients (median age 19.5y) with symptomatic OO of the extremities eligible for MR-HIFU were enrolled in this ongoing prospective study (German Clinical Trials Register; nr.

Preliminary findings on the association between maternal salivary and hair cortisol and the mother-infant-interaction during the early postpartum period.

Maternal capabilities to engage in sensitive caregiving are important for infant development and mother-infant-interaction, however, can be negatively affected by cortisol due to a stress response. Previous research suggested that cortisol possibly impairs cognitive functions important for caregiving behavior, which potentially leads to less maternal sensitivity. However, studies investigating the influence of cortisol using endocrine parameters on the mother-infant-interaction during the early postpartum are lacking.

Taxonomic revision of the SK 15 mandible based on bone and tooth structural organization.

The hominin mandible SK 15 was discovered in April 1949 in Swartkrans Member 2, dated to ∼1.4 Ma. Albeit distorted on the right side, the left and right corpus of SK 15 are relatively low and thick, even compared to most Early to Middle Pleistocene Homo specimens.

Local and landscape factors differently influence health and pollination services in two important pollinator groups.

Agricultural management significantly affects insects, especially pollinators, which are crucial for crop pollination and biodiversity. In agricultural landscapes, various factors spanning different spatial scales are known to affect pollinator health, which, in turn, can influence pollination services. However, the importance of these factors in driving the health and performance of different pollinator groups remains unclear.

Demystifying the art of isotope-enabled hydrological and climate modelling.

Over the last 20 years, we have dramatically improved hydrometeorological data including isotopes, but are we making the most of this data? Stable isotopes of oxygen and hydrogen in the water molecule (stable water isotopes - SWI) are well known tracers of the global hydrological cycle producing critical climate science. Despite this, stable water isotopes are not explicitly included in influential climate reports (e.g.

Contrasting effects of arsenic on mycorrhizal-mediated silicon and phosphorus uptake by rice.

Silicon (Si) and arbuscular mycorrhizal fungi (AMF) increase plant resistance to various environmental stresses, including heavy metal (and metalloid) toxicity. Although Si and AMF each independently enhance plant tolerance, the nature of their interactions and their combined impacts on nutrient uptake, especially in the context of toxic elements such as arsenic (As), remains to be elucidated. This study investigated AMF-mediated regulation of plant nutrient uptake under As stress using rice, a model Si-accumulating plant.

A whole gamma imaging prototype for higher quantitative imaging ofZr-labeled antibodies in a tumor mouse model.

PET has become an important clinical modality but is limited to imaging positron emitters. Recently, PET imaging withZr, which has a half-life of 3 days, has attracted much attention in immuno-PET to visualize immune cells and cancer cells by targeting specific antibodies on the cell surface. However,Zr emits a single gamma ray at 909 keV four times more frequently than positrons, causing image quality degradation in conventional PET.