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Previous research on racial ingroup bias in empathy for pain focused on neural responses to a single person's suffering. It is unclear whether empathy for simultaneously perceived multiple individuals' pain (denoted as collective empathy in this study) is also sensitive to perceived racial identities of empathy targets. We addressed this issue by recording electroencephalography from Chinese adults who responded to racial identities of 2 × 2 arrays of Asian or White faces in which 4 faces, 1 face, or no face showed painful expressions. Participants reported greater feelings of others' pain and their own unpleasantness when viewing 4 compared to 1 (or no) painful faces. Behavioral responses to racial identities of faces revealed decreased speeds of information acquisition when responding to the face arrays with 4 (vs. 1 or no) painful expressions of Asian (but not White) faces. Moreover, Asian compared to White face arrays with 4 (vs. 1 or no) painful expressions elicited a larger positive neural response at 160-190 ms (P2) at the frontal/central electrodes and enhanced alpha synchronizations at 288-1,000 ms at the central electrodes. Our findings provide evidence for racial ingroup biases in collective empathy for pain and unravel its relevant neural underpinnings.
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Empatia , Racismo , Adulto , Humanos , Eletroencefalografia , Dor , EmoçõesRESUMO
Cyclic di-adenosine monophosphate (c-di-AMP) is a second messenger involved in diverse metabolic processes including osmolyte uptake, cell wall homeostasis, as well as antibiotic and heat resistance. This study investigates the role of the c-di-AMP receptor protein DarA in the osmotic stress response in Bacillus subtilis. Through a series of experiments, we demonstrate that DarA plays a central role in the cellular response to osmotic fluctuations. Our findings show that DarA becomes essential under extreme potassium limitation as well as upon salt stress, highlighting its significance in mediating osmotic stress adaptation. Suppressor screens with darA mutants reveal compensatory mechanisms involving the accumulation of osmoprotectants, particularly potassium and citrulline. Mutations affecting various metabolic pathways, including the citric acid cycle as well as glutamate and arginine biosynthesis, indicate a complex interplay between the osmotic stress response and metabolic regulation. In addition, the growth defects of the darA mutant during potassium starvation and salt stress in a strain lacking the high-affinity potassium uptake systems KimA and KtrAB can be rescued by increased affinity of the remaining potassium channel KtrCD or by increased expression of ktrD, thus resulting in increased potassium uptake. Finally, the darA mutant can respond to salt stress by the increased expression of MleN , which can export sodium ions.IMPORTANCEEnvironmental bacteria are exposed to rapidly changing osmotic conditions making an effective adaptation to these changes crucial for the survival of the cells. In Gram-positive bacteria, the second messenger cyclic di-AMP plays a key role in this adaptation by controlling (i) the influx of physiologically compatible organic osmolytes and (ii) the biosynthesis of such osmolytes. In several bacteria, cyclic di-adenosine monophosphate (c-di-AMP) can bind to a signal transduction protein, called DarA, in Bacillus subtilis. So far, no function for DarA has been discovered in any organism. We have identified osmotically challenging conditions that make DarA essential and have identified suppressor mutations that help the bacteria to adapt to those conditions. Our results indicate that DarA is a central component in the integration of osmotic stress with the synthesis of compatible amino acid osmolytes and with the homeostasis of potassium, the first response to osmotic stress.
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Aminoácidos , Bacillus subtilis , Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Homeostase , Pressão Osmótica , Potássio , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Potássio/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Aminoácidos/metabolismo , Fosfatos de Dinucleosídeos/metabolismo , MutaçãoRESUMO
In contrast to rational choice theory predicting humans to optimize expected utilities of choices, humans deviate from rational behavior in decision-making paradigms. Hewig et al. (2011) explored affective correlates of decision-making in the ultimatum game (UG) and the dictator game (DG). They found that feedback-related negativity (FRN), subjective valence ratings, and autonomic nervous system activity predicted rejection of monetary offers. This registered replication aimed to validate and extend these findings. Although behavioral patterns and results of subjective ratings closely matched the original study, not all psychophysiological effects were successfully replicated. Firstly, we could not replicate the reported effects of autonomic nervous system activity. Secondly, a quadratic instead of the originally proposed linear relation between the offer and the FRN emerged, possibly driven by the offer evaluation in economic games and the rewarding anticipation of successful punishment for low offers. Thirdly, P3 amplitudes mirrored the quadratic offer response pattern, generally peaking for the lowest offer. In contrast to the original study, P3 responses were larger in the UG compared with the DG. Finally, our findings indicate that participant-related higher midfrontal theta activation predicted lower acceptance behavior in the UG, with a systematic dampening effect for fairer offers. This highlights cognitive control as a crucial mechanism in economic decision-making to overcome behavioral defaults. Overall, our results conceptually support the original conclusion that decision-making in economic games is non-rational and dependent on the objective situation as well as emotional and neural markers, though not precisely as suggested by Hewig et al. (2011).
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Biomaterial characteristics such as surface topographies have been shown to modulate macrophage phenotypes. The standard methodologies to measure macrophage response to biomaterials are marker-based and invasive. Raman microspectroscopy (RM) is a marker-independent, noninvasive technology that allows the analysis of living cells without the need for staining or processing. In the present study, we analyzed human monocyte-derived macrophages (MDMs) using RM, revealing that macrophage activation by lipopolysaccharides (LPS), interferons (IFN), or cytokines can be identified by lipid composition, which significantly differs in M0 (resting), M1 (IFN-γ/LPS), M2a (IL-4/IL-13), and M2c (IL-10) MDMs. To identify the impact of a biomaterial on MDM phenotype and polarization, we cultured macrophages on titanium disks with varying surface topographies and analyzed the adherent MDMs with RM. We detected surface topography-induced changes in MDM biochemistry and lipid composition that were not shown by less sensitive standard methods such as cytokine expression or surface antigen analysis. Our data suggest that RM may enable a more precise classification of macrophage activation and biomaterial-macrophage interaction.
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Lipidômica/métodos , Ativação de Macrófagos/fisiologia , Macrófagos , Análise Espectral Raman/métodos , Materiais Biocompatíveis/farmacologia , Citocinas/farmacologia , Feminino , Humanos , Imunidade Inata , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , MasculinoRESUMO
Pain is a biopsychosocial phenomenon, resulting from the interplay between physiological and psychological processes and social factors. Given that humans constantly interact with others, the effect of social factors is particularly relevant. Documenting the significance of the social modulation of pain, an increasing number of studies have investigated the effect of social contact on subjective pain intensity and pain-related physiological changes. While evidence suggests that social contact can alleviate pain, contradictory findings indicate an increase in pain intensity and a deterioration of pain coping strategies. This evidence primarily stems from studies examining the effect of social contact on pain within highly controlled laboratory conditions. Moreover, pain assessments often rely on one-time subjective reports of average pain intensity across a predefined period. Ecological momentary assessments (EMAs) can circumvent these problems, as they can capture diverse aspects of behavior and experiences multiple times a day, in real time, with high resolution, and within naturalistic and ecologically valid settings. These multiple measures allow for the examination of fluctuations of pain symptoms throughout the day in relation to affective, cognitive, behavioral, and social factors. In this opinion paper, we review the current state and future relevance of EMA-based social pain research in daily life. Specifically, we examine whether everyday-life social support reduces or enhances pain. The first part of the paper provides a comprehensive overview of the use of EMA in pain research and summarizes the main findings. The review of the relatively limited number of existing EMA studies shows that the association between pain and social contact in everyday life depends on numerous factors, including pain syndromes, temporal dynamics, the nature of social interactions, and characteristics of the interaction partners. In line with laboratory research, there is evidence that everyday-life social contact can alleviate, but also intensify pain, depending on the type of social support. Everyday-life emotional support seems to reduce pain, while extensive solicitous support was found to have opposite effects. Moreover, positive short-term effects of social support can be overshadowed by other symptoms such as fatigue. Overall, gathering and integrating experiences from a patient's social environment can offer valuable insights. These insights can help interpret dynamics in pain intensity and accompanying symptoms such as depression or fatigue. We conclude that factors determining the reducing versus enhancing effects of social contact on pain need to be investigated more thoroughly. We advocate EMA as the assessment method of the future and highlight open questions that should be addressed in future EMA studies on pain and the potential of ecological momentary interventions for pain treatment.
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Dor , Humanos , Dor/psicologia , Dor/fisiopatologia , Adaptação Psicológica , Interação Social , Apoio Social , Avaliação Momentânea Ecológica , Medição da Dor/métodosRESUMO
BACKGROUND: Obstetrics and gynecology (OB/GYN) is an essential medical field that focuses on women's health. Universities aim to provide high-quality healthcare services to women through comprehensive education of medical students. In Germany, medical education is undergoing a phase of restructuring towards the implementation of competency-based learning. The objective of the current survey was to gain insights into the teaching methods, resources, and challenges at German medical universities in the field OB/GYN. This aims to document the current state of medical education and derive potential suggestions for improvements in the era of competency-based learning. The survey was conducted with teaching coordinators from the majority of OB/GYN departments at German universities. METHODS: A questionnaire was sent to the teaching coordinators in all 41 OB/GYN departments at German university hospitals. The survey was delivered via email with a link to an online survey platform. RESULTS: The study received 30 responses from 41 universities. Differences were observed in the work environment of teaching coordinators concerning release from clinical duties for teaching purposes and specialized academic training. Overall, medical education and student motivation were perceived positively, with noticeable gaps, particularly in practical gynecological training. Deficiencies in supervision and feedback mechanisms were also evident. Subfields such as urogynecology and reproductive medicine appear to be underrepresented in the curriculum, correlating with poorer student performance. E-learning was widely utilized and considered advantageous. CONCLUSION: The present study provides valuable insights into the current state of medical education in OB/GYN at German universities from the perspective of teaching experts. We highlight current deficits, discuss approaches to overcome present obstacles, and provide suggestions for improvement.
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Ginecologia , Obstetrícia , Gravidez , Feminino , Humanos , Ginecologia/educação , Educação Baseada em Competências , Obstetrícia/educação , Currículo , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study evaluates the overall treatment indicators and outcomes of patients who underwent loop electrosurgical excision procedure (LEEP) at the Department of Women's Health Tübingen and the impact of certification as a dysplasia unit on treatment quality. METHODS: Retrospective data analysis of 1596 patients from 2013 to 2018 who underwent LEEP excision at the Department of Women's Health Tübingen. Data of cytology, colposcopy, biopsy, LEEP histology, repeat LEEP histology and general characteristics were collected and analyzed descriptively. RESULTS: 85.4% (1364) of patients had CIN 2 + and 14.6% (232) had CIN 1 or normal findings on LEEP histology. The proportion of CIN 2 + excisions increased significantly from 82.4% in 2013 to 89% in 2018. The concordance of HSIL biopsy and LEEP histology was 89.1% in 2013 and 92.6% in 2018. In 2018, more biopsies and colposcopies were performed before excision. Complete resection (R0) was achieved in 88.3% of all excisions. R0 rates in patients with CIN 3 increased in 2014-2017 compared to 2013, resulting in fewer Re-LEEP excisions and hysterectomies. CONCLUSION: Certification as a dysplasia unit and the associated requirements have improved the diagnostic quality for patients with cervical dysplasia undergoing LEEP. This was demonstrated by several treatment indicators such as the number of colposcopies and biopsies and treatment outcomes such as an increased proportion of CIN 2 + excisions and R0 resections.
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Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Eletrocirurgia/métodos , Estudos Retrospectivos , Displasia do Colo do Útero/patologia , Colposcopia/métodos , CertificaçãoRESUMO
PURPOSE: Cervical cancer screening by visual inspection with acetic acid (VIA) during colposcopy can be challenging and is highly dependent on the clinical experience of the examiner. Health-care systems lack qualified physicians able to perform the examination in both industrialized and low- and middle-income countries. Previous work has shown the general potential of hyperspectral imaging (HSI) to discriminate CIN from normal tissue, but clinical translation has been limited due to the lack of medically approved HSI systems. METHODS: In this study, we evaluate the feasibility of a commercially available HSI system for CIN detection in a prospective monocentric clinical trial. RESULTS: By obtaining spectral fingerprints of 41 patients with CIN 1-3 we show that HSI-based differentiation between CIN and normal tissue is possible with high statistical significance. Major spectral differences were seen in the 555-585 wavelength area. CONCLUSION: HSI advances tissue differentiation by associating each pixel with high-dimensional spectra and thereby obtains morphological and biochemical information of the observed tissue. Currently available and medically approved HSI systems may represent a contact- and marker-free examiner-independent method for the diagnosis of CIN.
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Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Colposcopia , Detecção Precoce de Câncer , Imageamento Hiperespectral , Estudos Prospectivos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/prevenção & controleRESUMO
INTRODUCTION: Gender disparities exist in the OBGYN discipline. This study investigates, for the first time, whether gender impacts on the confidence of practical and surgical skills among OBGYN residents, and of being prepared to work as a specialist. METHODS: The gynecological societies of Austria, Germany, and Switzerland established a web-based survey of 30 questions that was sent to all registered OBGYN members-in-training from August to September 2020. Data collection, controlling and analysis were performed by the Swiss Federal Institute of Technology in Zurich (ETH). RESULTS: A total of 422 participants took part in the survey, of which 375 (88.9%) were female, 46 (10.9%) were male, and one (0.2%) was divers. The diverse participant was excluded from further analyses. The gender distribution was comparable in all three countries. Multiple regression analyses showed that gender is an independent variable significantly impacting on the confidence levels in performing standard gynaecological (p = 0.03) and obstetric (p < 0.001) procedures. Similarly, the feeling of confidence in being prepared for working as a specialist in a clinic showed to be gender-dependent (p < 0.001), however, not the feeling of being prepared for working as specialist in an outpatient setting (p = 0.37). The "female factor" significantly decreases the confidence rating for surgical and practical skills and for working in a hospital. Covariates including year of training, country, workload, receiving regular feedback, and implemented simulation training were included in all analyses. DISCUSSION: Improvements of residency programs to promote female doctors to overcome factors reducing their confidence in their own OBGYN skills are highly warranted.
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Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation.
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Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Adulto , Testes Genéticos , Estudo de Associação Genômica Ampla , Humanos , Mutação , Doenças Renais Policísticas/genética , Rim Policístico Autossômico Dominante/genéticaRESUMO
PURPOSE: The diagnosis of cervical intraepithelial neoplasia during pregnancy poses a great challenge to the treating clinician and the patient. According to the current guidelines, watchful waiting during pregnancy can be justified. Only in cases of invasion, immediate treatment may be indicated. However, few data are available on the management of cervical dysplasia during pregnancy. Further research is important for counselling affected women. METHODS: Data of pregnant patients with suspected cervical dysplasia who presented to the University Women's Hospital Tübingen between 2008 and 2018 were evaluated retrospectively. Colposcopic, cytologic, and histologic assessment was performed for diagnosis. Data on remission, persistence and progression of disease based on histologic and cytologic assessment and the mode of delivery were correlated. RESULTS: 142 patients were enrolled. Cytology at first presentation was PAPIII (-p/-g) in 7.0%, PAPIIID (IIID1/IIID2) in 38.7%, PAPIVa (-p/-g) in 50.0%, PAPIVb (-p) in 2.8%, and PAPV (-p) in 1.4%. All cases with suspected invasion were recorded at the initial presentation. Complete histological or cytological remission was observed in 24.4%, partial remission in 10.4%, persistence in 56.3%, and progression in 8.9%. In two cases (1.5%) progression to squamous cell carcinoma occurred. CONCLUSIONS: Watchful waiting for cervical intraepithelial neoplasia during pregnancy seems to be sufficient and oncologically safe. It is important to exclude invasion during pregnancy, to perform frequent colposcopic, cytologic and histologic examinations and to ensure a postpartum follow-up examination to initiate the treatment of high-grade lesions. Spontaneous delivery seems to be safe in patients with cervical dysplasia, Caesarean section is not indicated.
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Complicações Neoplásicas na Gravidez , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Gestantes , Cesárea , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Complicações Neoplásicas na Gravidez/patologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/terapia , Displasia do Colo do Útero/patologia , Colposcopia , Esfregaço VaginalRESUMO
Electrosurgery in gynecology has changed over the past few decades. The use of energy-based devices, especially in minimally invasive procedures, is extremely important for preparation, short reconvalescence and patient safety. Recently, there have been major advances in energy-based surgical devices that have further shortened OR time and increased patient safety. Although bipolar and monopolar electrosurgery is still very important, the introduction of high-frequency ultrasound in gynecologic surgery has improved cutting and coagulation by lowering thermal damage in the surrounding tissue. Furthermore, new technical inventions have fundamentally changed the treatment of specific diseases. The introduction of ablation in the therapy of uterine fibroids, for example, has made conventional myomectomy no longer necessary in some cases, as necrosis of fibroids can be induced by placing very small thermal probes into the fibroids. Robotic surgery will change the face of gynecological surgery in the near future, as the initial studies could show lower surgical morbidity and faster recovery of patients after robotic-assisted laparoscopy. In this article we provide a short overview of current technical advances, review possible indications as well as limitations, and take a look into the future of minimally invasive surgery in gynecology.
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Ginecologia , Laparoscopia , Leiomioma , Eletrocirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Laparoscopia/métodos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
PURPOSE: Functional pituitary adenomas (FPAs) cause severe neuro-endocrinopathies including Cushing's disease (CD) and acromegaly. While many are effectively cured following FPA resection, some encounter disease recurrence/progression or hormonal non-remission requiring adjuvant treatment. Identification of risk factors for suboptimal postoperative outcomes may guide initiation of adjuvant multimodal therapies. METHODS: Patients undergoing endonasal transsphenoidal resection for CD, acromegaly, and mammosomatotroph adenomas between 1992 and 2019 were identified. Good outcomes were defined as hormonal remission without imaging/biochemical evidence of disease recurrence/progression, while suboptimal outcomes were defined as hormonal non-remission or MRI evidence of recurrence/progression despite adjuvant treatment. Multivariate regression modeling and multilayered neural networks (NN) were implemented. The training sets randomly sampled 60% of all FPA patients, and validation/testing sets were 20% samples each. RESULTS: 348 patients with mean age of 41.7 years were identified. Eighty-one patients (23.3%) reported suboptimal outcomes. Variables predictive of suboptimal outcomes included: Requirement for additional surgery in patients who previously had surgery and continue to have functionally active tumor (p = 0.0069; OR = 1.51, 95%CI 1.12-2.04), Preoperative visual deficit not improved after surgery (p = 0.0033; OR = 1.12, 95%CI 1.04-1.20), Transient diabetes insipidus (p = 0.013; OR = 1.27, 95%CI 1.05-1.52), Higher MIB-1/Ki-67 labeling index (p = 0.038; OR = 1.08, 95%CI 1.01-1.15), and preoperative low cortisol axis (p = 0.040; OR = 2.72, 95%CI 1.06-7.01). The NN had overall accuracy of 87.1%, sensitivity of 89.5%, specificity of 76.9%, positive predictive value of 94.4%, and negative predictive value of 62.5%. NNs for all FPAs were more robust than for CD or acromegaly/mammosomatotroph alone. CONCLUSION: We demonstrate capability of predicting suboptimal postoperative outcomes with high accuracy. NNs may aid in stratifying patients for risk of suboptimal outcomes, thereby guiding implementation of adjuvant treatment in high-risk patients.
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Adenoma , Neoplasias Hipofisárias , Acromegalia , Adenoma/cirurgia , Adulto , Humanos , Recidiva Local de Neoplasia , Redes Neurais de Computação , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Potassium and glutamate are the major cation and anion, respectively, in every living cell. Due to the high concentrations of both ions, the cytoplasm of all cells can be regarded as a potassium glutamate solution. This implies that the concentrations of both ions need to be balanced. While the control of potassium uptake by glutamate is well established for eukaryotic cells, much less is known about the mechanisms that link potassium homeostasis to glutamate availability in bacteria. Here, we have discovered that the availability of glutamate strongly decreases the minimal external potassium concentration required for the highly abundant Bacillus subtilis potassium channel KtrCD to accumulate potassium. In contrast, the inducible KtrAB and KimA potassium uptake systems have high apparent affinities for potassium even in the absence of glutamate. Experiments with mutant strains revealed that the KtrD subunit responds to the presence of glutamate. For full activity, KtrD synergistically requires the presence of the regulatory subunit KtrC and of glutamate. The analysis of suppressor mutants of a strain that has KtrCD as the only potassium uptake system and that experiences severe potassium starvation identified a mutation in the ion selectivity filter of KtrD (Gly282 to Val) that similarly results in a strongly glutamate-independent increase of the apparent affinity for potassium. Thus, this work has identified two conditions that increase the apparent affinity of KtrCD for potassium, i.e., external glutamate and the acquisition of a single point mutation in KtrD.IMPORTANCE In each living cell, potassium is required for maintaining the intracellular pH and for the activity of essential enzymes. Like most other bacteria, Bacillus subtilis possesses multiple low- and high-affinity potassium uptake systems. Their activity is regulated by the second messenger cyclic di-AMP. Moreover, the pools of the most abundant ions potassium and glutamate must be balanced. We report two conditions under which the low-affinity potassium channel KtrCD is able to mediate potassium uptake at low external potassium concentrations: physiologically, the presence of glutamate results in a severely increased potassium uptake. Moreover, this is achieved by a mutation affecting the selectivity filter of the KtrD channel. These results highlight the integration between potassium and glutamate homeostasis in bacteria.
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Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Ácido Glutâmico/metabolismo , Canais de Potássio/metabolismo , Bacillus subtilis/química , Bacillus subtilis/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Transporte Biológico , Regulação Bacteriana da Expressão Gênica , Ácido Glutâmico/química , Cinética , Potássio/química , Potássio/metabolismo , Canais de Potássio/química , Canais de Potássio/genéticaRESUMO
The signaling nucleotide cyclic di-AMP (c-di-AMP) is the only known essential second messenger in bacteria. Recently, c-di-AMP has been identified as being essential for controlling potassium uptake in the model organism Bacillus subtilis and several other bacteria. A B. subtilis strain lacking c-di-AMP is not viable at high potassium concentrations, unless the bacteria acquire suppressor mutations. In this study, we isolated such suppressor mutants and found mutations that reduced the activities of the potassium transporters KtrCD and KimA. Although c-di-AMP-mediated control of KtrCD has previously been demonstrated, it is unknown how c-di-AMP affects KimA activity. Using the DRaCALA screening assay, we tested for any interactions of KimA and other potential target proteins in B. subtilis with c-di-AMP. This assay identified KimA, as well as the K+/H+ antiporter KhtT, the potassium exporter CpaA (YjbQ), the osmoprotectant transporter subunit OpuCA, the primary Mg2+ importer MgtE, and DarB (YkuL), a protein of unknown function, as bona fide c-di-AMP-binding proteins. Further, binding of c-di-AMP to KimA inhibited potassium uptake. Our results indicate that c-di-AMP controls KimA-mediated potassium transport at both kimA gene expression and KimA activity levels. Moreover, the discovery that potassium exporters are c-di-AMP targets indicates that this second messenger controls potassium homeostasis in B. subtilis at a global level by binding to riboswitches and to different classes of transport proteins involved in potassium uptake and export.
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Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Fosfatos de Dinucleosídeos/metabolismo , Homeostase , Potássio/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Bacillus subtilis/genética , Bacillus subtilis/crescimento & desenvolvimento , Proteínas de Bactérias/genética , MutaçãoRESUMO
A crucial aspect of social decision-making is the ability to learn from the outcomes of preceding decisions. In particular, learning might be influenced by the expectedness of feedback and its valence. Expectedness has largely been operationalized as the frequency of stimulus occurrence and not in terms of its social context. Therefore, we investigated the influence of socially unexpected feedback, i.e., smiling upon adverse events, on behavioral and neural responses. We used a modified version of the ultimatum game, a commonly used paradigm for economic decision-making, by implementing different proposer identities with a distinct reaction pattern towards accepted and rejected monetary offers. We could show that an identity, who reacted with a smile towards rejected offers, evoked lower acceptance rates compared to identities, who reward acceptance with a smile. Electrophysiological correlates indicate N170 effects for emotional identities compared to a neutral control identity. Regarding FRN and P3 brain potentials, we detected a particular function of the smiling face when used as a socially unexpected, negative feedback stimulus. Hence, individuals seek an unexpected smile despite the associated monetary loss, which is accompanied by distinct neural patterns.
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Tomada de Decisões/fisiologia , Emoções/fisiologia , Expressão Facial , Retroalimentação , Sorriso/fisiologia , Adulto , Encéfalo/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recompensa , Adulto JovemRESUMO
BACKGROUND: For decades, the nature of emotions has been at the center of psychological research, particularly regarding the underlying mechanisms that enable people to perceive, recognize, and process emotional stimuli. Research has indicated that there are interindividual differences in the processing of emotions. This includes age, which underlies neurological changes that contribute to the specific processing of emotions. Increasing age seems to be associated with a more positive evaluation of emotional information, from perception itself to attention, memory, and decision-making. METHOD: The current study aimed to investigate whether these differences can be found in highly artificial emotional faces. Since emojis are representatives of emotional faces in digital communication, we selected a subset of 13 emojis and asked 170 participants to evaluate them for their ability to represent different target emotions. RESULTS: An exploratory factor analysis revealed a two-factorial structure with positive and negative valence for most of the ratings for the evaluated emojis. Furthermore, a multilevel model analysis based on the individual factor scores indicated higher age to be associated with an increase in factor scores for negative valence compared to positive valence. CONCLUSION: In the present study, a trend for an age-specific positivity bias could only be shown in the classical smiley, while other emojis were related to negative valence with increasing age. Thus, we revealed age-related differences in emotion classification, even for highly artificial stimuli such as emojis.
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Envelhecimento/psicologia , Gráficos por Computador , Emoções , Expressão Facial , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Passenger cars in Europe have become both heavier and more powerful over the past decades. This trend has increased vehicle utility but it might have also offset technical improvements in powertrain efficiency. Here, we analyze efficiency trade-offs and CO2 emissions for three popular compact cars in Germany. We find that mass, power, and front area of model variants has increased by 66%, 147%, and 22%, respectively between 1980 and 2018. In the same period, fuel consumption decreased 14% for gasoline models but it increased 9% for diesel models. However, if vehicle mass, power, and front area had remained at 1980 levels, technical efficiency improvements would have decreased the fuel consumption of gasoline and diesel models by 23% and 24%, respectively. The related efficiency trade-offs amount to 24â¯g CO2/km or 13% of the current fuel consumption for gasoline models and 40â¯g CO2/km or 25% of the current fuel consumption for diesel models. These findings suggest that about half of the technical efficiency improvements in gasoline models and all of the technical efficiency improvements in diesel models are offset through other vehicle attributes. By accounting for the observed efficiency trade-offs, climate policy could become more effective.
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PURPOSE: The Commission for the Promotion of Young Talents of the German Society for Gynaecology and Obstetrics e.V. was founded in 2017, aiming to inspire medical students for a career in obstetrics and gynaecology by developing a concept for the first German Summer School in this field. Here, medical students shall be introduced to this multifaceted specialty and have their interest in it kindled. METHODS: This article reports about the experiences of the first gynaecological summer school which was held at the University Hospital Heidelberg for 2 days in August 2018. The programme included keynote presentations, discussion roundtables and skills-lab training. To assess students' related satisfaction, and to improve future projects, an evaluation survey with seven items and two open-comment questions was given to each participant after the event. RESULTS: Mostly female students [n (â) = 37, 93%; n (â) = 3, 7%] from 15 different medical universities from all over Germany participated. Available places were booked within 1 week. Participants were in their clinical part of their studies between the 5th and 16th semester. The average rating of the event was excellent with 1.1 points (1 = best-5 = worst), while the selection of topics scored lowest marks with an average rating of 1.7 points. CONCLUSION: Due to the great success, the high demand and the student's positive evaluation, annual summer schools in obstetrics and gynaecology are planned. Because most of the participating students have shown a high interest and have appropriate education in the domain, the information content of keynote presentations could be increased above basic level in future projects.
Assuntos
Educação Médica/organização & administração , Ginecologia/educação , Obstetrícia/educação , Estudantes de Medicina/estatística & dados numéricos , Feminino , Alemanha , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Fibroids are the most common benign tumors in women of childbearing age and can be found in almost 80-90% of all women by age 50 years. They can cause pain, excessive menstrual bleeding or infertility. The development of fibroids increases with age. Since the age of women in industrial countries who are trying to conceive is generally increasing, there has been a growing demand for minimally invasive and uterine-sparing surgical treatment of fibroids. Whereas the main focus of previous surgical techniques for the treatment of fibroids was enucleation of the tumour with subsequent closure of the uterine incision, modern devices developed over the past decade can destroy fibroids by using ultrasound or radio-frequency without incising the uterine wall. Thus, there is no uterine scar, which would impart a risk of rupture during labour or pregnancy. This article provides an overview of the latest techniques and devices used for uterine-sparing surgical treatment of fibroids. While laparoscopic myomectomy is still the gold standard, novel laparoscopic and transcervical radiofrequency ablation techniques use low-voltage and alternating current to induce heat in the uterine tissue, which triggers necrosis in fibroids. This enables the removal of multiple fibroids without the need for large incisions in the uterine wall. In addition, we address the benefits and potential risks, as well as the impact on fertility and pregnancy, of the different surgical approaches used for the treatment of uterine fibroids.