Evolution of mitogenomic gene order in Orthoptera.

Mitochondrial gene order has contributed to the elucidation of evolutionary relationships in several animal groups. It generally has found its application as a phylogenetic marker for deep nodes. Yet, in Orthoptera limited research has been performed on the gene order, although the group represents one of the oldest insect orders. We performed a comprehensive study on mitochondrial genome rearrangements (MTRs) within Orthoptera in the context of mitogenomic sequence-based phylogeny. We used 280 published mitogenome sequences from 256 species, including three outgroup species, to reconstruct a molecular phylogeny. Using a heuristic approach, we assigned MTR scenarios to the edges of the phylogenetic tree and reconstructed ancestral gene orders to identify possible synapomorphies in Orthoptera. We found all types of MTRs in our dataset: inversions, transpositions, inverse transpositions, and tandem-duplication/random loss events (TDRL). Most of the suggested MTRs were in single and unrelated species. Out of five MTRs which were unique in subgroups of Orthoptera, we suggest four of them to be synapomorphies; those were in the infraorder Acrididea, in the tribe Holochlorini, in the subfamily Pseudophyllinae, and in the two families Phalangopsidae and Gryllidae or their common ancestor (leading to the relationship ((Phalangopsidae + Gryllidae) + Trigonidiidae)). However, similar MTRs have been found in distant insect lineages. Our findings suggest convergent evolution of specific mitochondrial gene orders in several species, deviant from the evolution of the mitogenome DNA sequence. As most MTRs were detected at terminal nodes, a phylogenetic inference of deeper nodes based on MTRs is not supported. Hence, the marker does not seem to aid resolving the phylogeny of Orthoptera, but adds further evidence for the complex evolution of the whole group, especially at the genetic and genomic levels. The results indicate a high demand for more research on patterns and underlying mechanisms of MTR events in Orthoptera.

[Transition-oriented patient education program for adolescents and young adults with ADHD]. / Transitionsorientierte Patientenschulung bei Adoleszenten und jungen Erwachsenen mit ADHS.

Transition-oriented patient education program for adolescents and young adults with ADHD Abstract. Background: The transition from child- to adult-centered treatment includes numerous challenges in the treatment of chronic disorders. This process can be further complicated by disease-specific characteristics of attention-deficit/hyperactivity disorders (ADHD). This secondary analysis evaluated a transition workshop in individuals with ADHD. Methods: In total, 56 adolescents and young adults with ADHD (age M = 17.3 years, SD = 1.1; 17.9 % female) and their parents were quasi-randomly assigned to a control group (CG, n = 28) or an intervention group (IG, n = 28). The CG received regular medical care, whereas the IG additionally participated in a one-and-a-half-day transition workshop (ModuS-T). Before and 4 weeks after the intervention, transition competence was assessed with the Transition Competence Scale (TKS), patient activation with the Patient Activation Measure 13 for Adolescents (PAM® 13), and satisfaction with care with the Patient Satisfaction Questionnaire (ZUF-8). Results: The IG showed significantly improved transition competence (p ≤ .001) compared to the CG. There was no significant intervention effect in terms of patient activation (p = .194). Overall, the IG was highly satisfied with the workshop. Discussion: To date, transition workshops have been evaluated predominantly in individuals with chronic somatic disorders. This secondary analysis indicates that a generic workshop is also associated with improved transition competence and high satisfaction in individuals with chronic mental disorders. The integration of such approaches into routine care needs to be discussed.

Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.

BACKGROUND: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP. METHODS: We analyzed all 8 CELA3B exons in 550 German non-alcoholic CP (NACP) patients and in 241 German controls by targeted DNA sequencing. In addition, we analyzed exons 6 and 7 by Sanger sequencing and the c.129+1G>A variant by melting curve analysis in 1078 further German controls. As replication cohort, we investigated up to 243 non-German European NACP patients and up to 1665 controls originating from Poland, Hungary, and Sweden. We assessed the cellular secretion and the elastase activity of recombinant CELA3B variants. RESULTS: In the German discovery cohort, we detected a splice-site variant in intron 2, c.129+1G>A, in 9/550 (1.64%) CP patients and in 5/1319 (0.38%) controls (P=0.007, OR=4.4, 95% CI=1.5-13.0). In the European replication cohort, this variant was also enriched in patients (9/178 [5.06%]) versus controls (13/1247 [1.04%]) (P=0.001, OR=5.1, 95% CI=2.1-12.0). We did not find the two previously reported codon 90 variants, p.R90C and p.R90L. CONCLUSIONS: Our data indicate that CELA3B is a susceptibility gene for CP. In contrast to previous reports suggesting that increased CELA3B activity is associated with CP risk, the splice-site variant identified here is predicted to cause diminished CELA3B expression. How reduced CELA3B function predisposes to pancreatitis remains to be elucidated.

Variants in the pancreatic CUB and zona pellucida-like domains 1 (CUZD1) gene in early-onset chronic pancreatitis - A possible new susceptibility gene.

OBJECTIVE: Non-alcoholic chronic pancreatitis (NACP) frequently develops in the setting of genetic susceptibility associated with alterations in genes that are highly expressed in the pancreas. However, the genetic basis of NACP remains unresolved in a significant number of patients warranting a search for further risk genes. DESIGN: We analyzed CUZD1, which encodes the CUB and zona pellucida-like domains 1 protein that is found in high levels in pancreatic acinar cells. We sequenced the coding region in 1163 European patients and 2018 European controls. In addition, we analyzed 297 patients and 1070 controls from Japan. We analyzed secretion of wild-type and mutant CUZD1 from transfected cells using Western blotting. RESULTS: In the European cohort, we detected 30 non-synonymous variants. Using different prediction tools (SIFT, CADD, PROVEAN, PredictSNP) or the combination of these tools, we found accumulation of predicted deleterious variants in patients (p-value range 0.002-0.013; OR range 3.1-5.2). No association was found in the Japanese cohort, in which 13 non-synonymous variants were detected. Functional studies revealed >50% reduced secretion of 7 variants, however, these variants were not significantly enriched in European CP patients. CONCLUSION: Our data indicate that CUZD1 might be a novel susceptibility gene for NACP. How these variants predispose to pancreatitis remains to be elucidated.

Comparison of individual and common wavelength-operation for 785 nm Y-branch DBR ridge waveguide diode lasers with adjustable spectral distance.

An experimental comparison between individual and common wavelength-operation of a Y-branch distributed Bragg reflector (DBR) ridge waveguide (RW) laser at 785 nm with an electrically adjustable spectral distance is presented. The dual-wavelength Y-branch laser combines two laser cavities via a Y-section to a common output section. DBR gratings with different grating periods are associated with the two cavities, which set the emission wavelengths of the two branches. Implemented resistive heater elements allow separate wavelength tuning of the two branches, which can be operated individually for alternating emission wavelengths in applications such as differential absorption spectroscopy or shifted excitation Raman difference spectroscopy. Common wavelength operation simultaneously generates two emission lines suitable for the generation of THz radiation using difference frequency mixing. Hereby, the devices could potentially be used as single-chip light sources for a combination of Raman and THz applications. For the wavelength-operation comparison presented, the devices were operated up to optical output powers of about 105 and 185 mW in individual and common wavelength-operation mode, respectively. In individual operation mode, the devices show spectral single-mode emission over the whole operation range. In common operation mode, the spectral emission is predominantly single mode up to an optical output power of 65 mW. In both operation modes, mode hops typical for DBR lasers occur. At an optical output power of 50 mW, tuning of the spectral distance between the two wavelengths using the implemented resistor heaters is demonstrated. In both modes of wavelength operation, a flexible frequency difference between 0 and 0.8 THz (0 and 1.6 nm) with predominantly single-mode spectral emission is obtained.

Improved Detectability of Brain Stem Ischemia by Combining Axial and Coronal Diffusion-Weighted Imaging.

BACKGROUND AND PURPOSE: To evaluate the benefit of a coronal diffusion-weighted imaging (DWI) in addition to standard axial DWI for the detection of brain stem infarctions. METHODS: A retrospective analysis of patients with symptoms consistent with acute and subacute brain stem infarction who received magnetic resonance imaging, including axial and coronal DWI. Diffusion restrictions were identified by 2 independent raters blinded for the final clinical diagnosis in 3 separate reading steps: axial DWI, coronal DWI, and combined axial and coronal DWI. Lesion location and certainty level were both documented for each reading step. In cases of reader disagreement, an additional consensus reading was performed. RESULTS: Two hundred thirty-nine patients were included. Of these, 124 patients (51.9%) were clinically diagnosed with brain stem infarction. Sensitivity, specificity, positive, and negative predictive values were best for combined DWI assessment (90.3%, 99.1%, 99.1%, and 90.5%) compared with axial (85.5%, 94.9%, 94.6%, and 85.8%) and coronal DWI alone (87.9%, 96.5%, 96.5%, and 88.1%). Diffusion restriction on combined DWI was diagnosed in 112/124 patients compared with 106/124 on axial DWI and 109/124 on coronal DWI. Interobserver agreement for the detection of brain stem lesions was the highest in the combined rating step (Cohen κ coefficient=0.94). CONCLUSIONS: Coronal DWI sequences might improve the detection rate of brain stem infarction compared with standard axial DWI. The combined coronal and axial DWI provides the best detection rate while minimally increasing scan times.

783 nm wavelength stabilized DBR tapered diode lasers with a 7 W output power.

Wavelength stabilized distributed Bragg reflector (DBR) tapered diode lasers at 783 nm will be presented. The devices are based on GaAsP single quantum wells embedded in a large optical cavity leading to a vertical far field angle of about 29° (full width at half maximum). The 3-inch (7.62 cm) wafers are grown using metalorganic vapor phase epitaxy. In a full wafer process, 4 mm long DBR tapered lasers are manufactured. The devices consist of a 500 µm long 10th order surface DBR grating that acts as rear side mirror. After that, a 1 mm long ridge waveguide section is realized for lateral confinement, which is connected to a 2.5 mm long flared section having a full taper angle of 6°. At an injection current of 8 A, a maximum output power of about 7 W is measured. At output powers up to 6 W, the measured emission width limited by the resolution of the spectrometer is smaller than 19 pm. Measured at 1/e2 level at this output power, the lateral beam waist width is 11.5 µm, the lateral far field angle 12.5°, and the lateral beam parameter M2 2.5. The respective parameters measured using the second moments are 31 µm, 15.2°, and 8.3. 70% of the emitted power is originated from the central lobe.

Universal CAR 2.0 to overcome current limitations in CAR therapy.

Chimeric antigen receptor (CAR) T cell therapy has effectively complemented the treatment of advanced relapsed and refractory hematological cancers. The remarkable achievements of CD19- and BCMA-CAR T therapies have raised high expectations within the fields of hematology and oncology. These groundbreaking successes are propelling a collective aspiration to extend the reach of CAR therapies beyond B-lineage malignancies. Advanced CAR technologies have created a momentum to surmount the limitations of conventional CAR concepts. Most importantly, innovations that enable combinatorial targeting to address target antigen heterogeneity, using versatile adapter CAR concepts in conjunction with recent transformative next-generation CAR design, offer the promise to overcome both the bottleneck associated with CAR manufacturing and patient-individualized treatment regimens. In this comprehensive review, we delineate the fundamental prerequisites, navigate through pivotal challenges, and elucidate strategic approaches, all aimed at paving the way for the future establishment of multitargeted immunotherapies using universal CAR technologies.

Barcoding Fails to Delimit Species in Mongolian Oedipodinae (Orthoptera, Acrididae).

Mongolia, a country in central Asia, with its vast grassland areas represents a hotspot for Orthoptera diversity, especially for the Acrididae. For Mongolia, 128 Acrididae species have been documented so far, of which 41 belong to the subfamily Oedipodinae (band-winged grasshoppers). Yet, few studies concerning the distribution and diversity of Oedipodinae have been conducted in this country. Molecular genetic data is almost completely absent, despite its value for species identification and discovery. Even, the simplest and most used data, DNA barcodes, so far have not been generated for the local fauna. Therefore, we generated the first DNA barcode data for Mongolian band-winged grasshoppers and investigated the resolution of this marker for species delimitation. We were able to assemble 105 DNA barcode (COI) sequences of 35 Oedipodinae species from Mongolia and adjacent countries. Based on this data, we reconstructed maximum likelihood and Bayesian inference phylogenies. We, furthermore, conducted automatic barcode gap discovery and used the Poisson tree process (PTP) for species delimitation. Some resolution was achieved at the tribe and genus level, but all delimitation methods failed to differentiate species by using the COI region. This lack of resolution may have multiple possible reasons, which likely differ between taxa: the lack of resolution in the Bryodemini may be partially explained by their massive genomes, implying the potential presence of large numbers of pseudogenes, while within the Sphingonotini incomplete lineage sorting and incorrect taxonomy are more likely explanations for the lack of signal. Further studies based on a larger number of gene fragments, including nuclear DNA, are needed to distinguish the species also at the molecular level.

Type catalogue of Oedipodinae (Orthoptera: Acrididae) present in Naturalis Biodiversity Center Leiden (Netherlands).

A type catalogue of Oedipodinae in the collection of Naturalis Biodiversity Center is presented altogether 82 type specimens including 13 primary types and 5 junior synonyms: holotypes (4 species), neotype (1 species), lectotypes (2 species, 1 subspecies), and syntypes (5 species). Furthermore 50 additional secondary type specimens were recorded. Here, we present the full type material catalogue including a locality map of all species and pictures of the 15 primary type species.

Machine Learning for Medical Data Integration.

Making health data available for secondary use enables innovative data-driven medical research. Since modern machine learning (ML) methods and precision medicine require extensive amounts of data covering most of the standard and edge cases, it is essential to initially acquire large datasets. This can typically only be achieved by integrating different datasets from various sources and sharing data across sites. To obtain a unified dataset from heterogeneous sources, standard representations and Common Data Models (CDM) are needed. The process of mapping data into these standardized representations is usually very tedious and requires many manual configuration and refinement steps. A potential way to reduce these efforts is to use ML methods not only for data analysis, but also for the integration of health data on the syntactic, structural, and semantic level. However, research on ML-based medical data integration is still in its infancy. In this article, we describe the current state of the literature and present selected methods that appear to have a particularly high potential to improve medical data integration. Moreover, we discuss open issues and possible future research directions.

Characterization of the Antibacterial Activity of Quinone-Based Compounds Originating from the Alnumycin Biosynthetic Gene Cluster of a Streptomyces Isolate.

Bacteria of the genus Streptomyces produce various specialized metabolites. Single biosynthetic gene clusters (BGCs) can give rise to different products that can vary in terms of their biological activities. For example, for alnumycin and the shunt product K115, antimicrobial activity was described, while no antimicrobial activity was detected for the shunt product 1,6-dihydro 8-propylanthraquinone. To investigate the antibacterial activity of 1,6-dihydro 8-propylanthraquinone, we produced alnumycin and 1,6-dihydro 8-propylanthraquinone from a Streptomyces isolate containing the alnumycin BGC. The strain was cultivated in liquid glycerol-nitrate-casein medium (GN), and both compounds were isolated using an activity and mass spectrometry-guided purification. The structures were validated via nuclear magnetic resonance (NMR) spectroscopy. A minimal inhibitory concentration (MIC) test revealed that 1,6-dihydro 8-propylanthraquinone exhibits antimicrobial activity against E. coli ΔtolC, B. subtilis, an S. aureus type strain, and a vancomycin intermediate-resistance S. aureus strain (VISA). Activity of 1,6-dihydro 8-propylanthraquinone against E. coli ΔtolC was approximately 10-fold higher than that of alnumycin. We were unable to confirm gyrase inhibition for either compound and believe that the modes of action of both compounds are worth reinvestigating.

New estimates of genome size in Orthoptera and their evolutionary implications.

Animal genomes vary widely in size, and much of their architecture and content remains poorly understood. Even among related groups, such as orders of insects, genomes may vary in size by orders of magnitude-for reasons unknown. The largest known insect genomes were repeatedly found in Orthoptera, e.g., Podisma pedestris (1C = 16.93 pg), Stethophyma grossum (1C = 18.48 pg) and Bryodemella holdereri (1C = 18.64 pg). While all these species belong to the suborder of Caelifera, the ensiferan Deracantha onos (1C = 19.60 pg) was recently found to have the largest genome. Here, we present new genome size estimates of 50 further species of Ensifera (superfamilies Gryllidea, Tettigoniidea) and Caelifera (Acrididae, Tetrigidae) based on flow cytometric measurements. We found that Bryodemella tuberculata (Caelifera: Acrididae) has the so far largest measured genome of all insects with 1C = 21.96 pg (21.48 gBp). Species of Orthoptera with 2n = 16 and 2n = 22 chromosomes have significantly larger genomes than species with other chromosome counts. Gryllidea genomes vary between 1C = 0.95 and 2.88 pg, and Tetrigidae between 1C = 2.18 and 2.41, while the genomes of all other studied Orthoptera range in size from 1C = 1.37 to 21.96 pg. Reconstructing ancestral genome sizes based on a phylogenetic tree of mitochondrial genomic data, we found genome size values of >15.84 pg only for the nodes of Bryodemella holdereri / B. tuberculata and Chrysochraon dispar / Euthystira brachyptera. The predicted values of ancestral genome sizes are 6.19 pg for Orthoptera, 5.37 pg for Ensifera, and 7.28 pg for Caelifera. The reasons for the large genomes in Orthoptera remain largely unknown, but a duplication or polyploidization seems unlikely as chromosome numbers do not differ much. Sequence-based genomic studies may shed light on the underlying evolutionary mechanisms.

The Genomics of Isolated Populations of Gampsocleis glabra (Orthoptera: Tettigoniidae) in Central and Western Europe.

Habitat destruction and fragmentation are among the major current threats to global biodiversity. Fragmentation may also affect species with good dispersal abilities. We study the heath bushcricket Gampsocleis glabra, a specialist of steppe-like habitats across Europe that are highly fragmented, investigating if these isolated populations can be distinguished using population genomics and if there are any traces of admixture or dispersal among them. We try to answer these questions using genome-wide SNP data generated with ddRAD sequencing. We calculated F-statistics and visualized differentiation using STRUCTURE plots. While limited by the difficulty of sampling this threatened species, our results show that all populations except one that was represented by a singleton were clearly distinct, with pairwise FST values between 0.010 and 0.181. STRUCTURE indicated limited but visible admixture across most populations and probably also an exchange of individuals between populations of Germany and The Netherlands. We conclude that in G. glabra, a certain amount of gene flow has persisted, at least in the past, also among populations that are isolated today. We also detect a possibly more recent dispersal event between a population in The Netherlands and one in Germany, which may be human aided. We suggest that the conservation of larger populations should be maintained, that efforts should be taken to restore abandoned habitat, that the preservation even of small habitat fragments may be beneficial for the conservation of this species, and that these habitats should be regularly monitored for possible (re-)colonization.

Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research.

Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.

Taxonomic review of the genus Thalpomena Saussure, 1884 with new synonyms.

The genus Thalpomena Saussure, 1884 is distributed in North Africa, Somalia and Ethiopia. It currently contains nine species, including one species with four subspecies; Seven of them (including one with four subspecies) are distributed in the Atlas Mountains, one in Libya and one (originally described in the genus Vosseleria) in the Somali Highlands. In this study, we propose taxonomic changes based on morphological, genetic, ecological and morphometric data from a previous study. The following species remain valid: Thalpomena algeriana (Lucas, 1849); Thalpomena azureipennis Uvarov, 1927; Thalpomena coerulescens Uvarov, 1923; Thalpomena dernensis (Werner, 1908); and Thalpomena viridipennis Uvarov, 1927. The following names are proposed here as junior synonyms of T. algeriana: Thalpomena algeriana intermedia Dirsh, 1949 (new synonym), Thalpomena algeriana montana Dirsh, 1949 (new synonym), Thalpomena coeruleipennis Finot, 1895 (new synonym), Thalpomena deserta Dirsh, 1949 (new synonym). Thalpomena rungsi Dirsh, 1949 is a new synonym of T. azureipennis; Thalpomena algeriana maroccana Dirsh, 1949 is a new synonym of T. viridipennis. The only East African representative of the genus, Thalpomena schulthessi (Uvarov, 1923), is transferred to the genus Vosseleriana (new combination).

Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus.

The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remains unknown. Using murine leukemia virus (MuLV), we found that some commensal bacteria promoted the development of leukemia induced by this retrovirus. The promotion of leukemia development by commensals is due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators include Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b is mediated by sensing of bacteria by the NOD1/NOD2/RIPK2 pathway. This work describes a mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential targets for cancer therapy.

A Novel Method for Digital Reconstruction of the Mucogingival Borderline in Optical Scans of Dental Plaster Casts.

Adequate soft-tissue dimensions have been shown to be crucial for the long-term success of dental implants. To date, there is evidence that placement of dental implants should only be conducted in an area covered with attached gingiva. Modern implant planning software does not visualize soft-tissue dimensions. This study aims to calculate the course of the mucogingival borderline (MG-BL) using statistical shape models (SSM). Visualization of the MG-BL allows the practitioner to consider the soft tissue supply during implant planning. To deploy an SSM of the MG-BL, healthy individuals were examined and the intra-oral anatomy was captured using an intra-oral scanner (IOS). The empirical anatomical data was superimposed and analyzed by principal component analysis. Using a Leave-One-Out Cross Validation (LOOCV), the prediction of the SSM was compared with the original anatomy extracted from IOS. The median error for MG-BL reconstruction was 1.06 mm (0.49-2.15 mm) and 0.81 mm (0.38-1.54 mm) for the maxilla and mandible, respectively. While this method forgoes any technical work or additional patient examination, it represents an effective and digital method for the depiction of soft-tissue dimensions. To achieve clinical applicability, a higher number of datasets has to be implemented in the SSM.

Miro1 R272Q disrupts mitochondrial calcium handling and neurotransmitter uptake in dopaminergic neurons.

The Rho GTPase Miro1, located at the mitochondrial outer membrane is known to properly distribute mitochondria to synapses, aid calcium buffering and initiate PINK1-Parkin mediated mitophagy. Several heterozygous RHOT1/Miro1 variants were identified in sporadic Parkinson's disease patients. Miro1 R272Q is located within a calcium binding domain, but the functional outcome of this point mutation and its contribution to the development of disease are unclear. To address this, we introduced a heterozygous RHOT1/Miro1 R272Q point mutation in healthy induced pluripotent stem cells. In dopaminergic neurons, Miro1 R272Q does not affect Miro1 protein levels, CCCP-induced mitophagy, nor mitochondrial movement yet causes the fragmentation of mitochondria with reduction of cristae and ATP5A. Inhibition of the mitochondrial calcium uniporter phenocopied Miro1 R272Q cytosolic calcium response to Thapsigargin in active neurons, a similar effect was observed during the calcium buffering phase in Miro1 knockdown neuroblastoma cells. Altered mitochondrial calcium regulation is associated with reduced mitochondrial respiration and reduced catecholamine neurotransmitter uptake. Synaptic changes are not coupled to dopamine distribution or dopamine transporters but are linked to Miro1 R272Q-related calcium handling via the mitochondria concomitant with defective dopamine regulation at the mitochondrial surface by monoamine oxidase. We conclude that the Miro1 R272Q heterozygous point mutation dampens mitochondrial-calcium regulation and mitochondrial capacity via events at the outer membrane that are sufficient to disrupt dopaminergic function.

Perceptual latencies of object recognition and affect measured with the rotating spot method: Chronometric evidence for semantic primacy.

According to the semantic primacy hypothesis of emotion generation, stimuli must be semantically categorized to evoke emotions. This hypothesis was tested in two chronometric studies, using the rotating spot method of timing subjective events. Participants saw pleasant and unpleasant pictures while a spot rotated around the edge of the picture. In different blocks of trials, they indicated when they experienced the pleasant or unpleasant feeling evoked by the pictures, or recognized the depicted objects, by reporting the position of the spot at the time when these mental events occurred. In both experiments, the latency of object recognition was found to be shorter than the latency of affect for nearly all participants and pictures, and the two latencies were positively correlated across participants. Experiment 2 replicated these findings and additionally showed that an experimental manipulation that delayed object recognition, blurring the pictures, also delayed the onset of affect. A mediation analysis suggested that this effect was at least partly mediated by the delayed recognition of the objects. The findings support the semantic primacy hypothesis. (PsycInfo Database Record (c) 2022 APA, all rights reserved).