Publications by authors named "Julia Fischer"

167 Publications

Peripartum Covid-19 Pneumonia with Severe ARDS - A Case Report.

Z Geburtshilfe Neonatol 2021 Apr 19;225(2):183-187. Epub 2021 Apr 19.

Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Introduction: SARS-CoV-2 is a novel coronavirus that was first isolated in Wuhan, China, and resulted in a rapidly spreading pandemic worldwide. Currently there is only limited evidence on the effect of COVID-19 on pregnant women.

Case: Here we present one of the first serious COVID-19 cases in pregnancy at term with subsequent delivery. Postpartum the mother required antibiotic and symptomatic treatment. She experienced acute worsening of symptoms and developed acute respiratory failure requiring endotracheal intubation and subsequently extracorporeal membrane oxygenation.

Conclusion: COVID-19 affects all medical disciplines, requiring interdisciplinary approaches and development of patient care regimes. Obstetricians should be aware and be prepared for the special needs of pregnant women with potential prenatal and postnatal issues. Ideally pregnant COVID-19 patients should be cared for at a tertiary perinatal center with experienced perinatologists and neonatologists.
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http://dx.doi.org/10.1055/a-1365-9262DOI Listing
April 2021

How Do Persons with Young and Late Onset Dementia Die?

J Alzheimers Dis 2021 Apr 3. Epub 2021 Apr 3.

Technical University of Munich, School of Medicine, Department of Psychiatry and Psychotherapy, Munich, Germany.

Background: End of life symptoms and symptom management as well as the quality of dying (QoD) of persons with advanced dementia (PWAD) have not yet been systematically studied in Germany.

Objective: 1) To investigate symptoms, treatment and care at the end of life, advance care planning, and circumstances of death of recently deceased PWAD; 2) To determine whether there are differences between young and late onset dementia (YOD and LOD).

Methods: The study was performed in the context of the project EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of Young-onset and Late-Onset dementia in Germany). Closest relatives of recently deceased patients with advanced YOD (N = 46) and LOD (N = 54) living at home or in long term care were interviewed.

Results: Circumstances of death, symptoms, and treatment appeared to be similar between YOD and LOD, except that persons with LOD had significantly more somatic comorbidities and were admitted to hospital in the last three months of life more often than persons with LOD. At end of life, 60%of PWAD appeared to be "at peace". Difficulty swallowing, gurgling, shortness of breath, and discomfort were observed most frequently. Large interindividual differences in suffering and QoD were present. Determinants of QoD were not identified.

Conclusion: Our findings suggest that low QoD was caused by inadequate recognition and/or insufficient treatment of burdensome physical and emotional symptoms. PWADs' needs should be assessed regularly, and strategies focusing on treatment and implementing support for both the patient and caregiver must be established.
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http://dx.doi.org/10.3233/JAD-210046DOI Listing
April 2021

Analysis of condom evidence in forensic science: Background survey of the human vaginal matrix using DRIFTS and pyrolysis-GC/MS.

Forensic Sci Int 2021 Apr 16;321:110724. Epub 2021 Feb 16.

Ecole des Sciences Criminelles, University of Lausanne, Switzerland. Electronic address:

Condom traces are increasingly detected from victims of sexual assault, mostly from vaginal swabs. Protocols have been developed for the analysis of silicone-based condom lubricants using DRIFTS-FTIR and py-GC/MS, but very little research is concerned with the background contribution of the vaginal matrix itself. The present contribution would be an asset for more fundamental research on condom residues in the vaginal matrix, as well as for interpretative purposes in the forensic area. This study investigated vaginal matrix residues using Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFTS-FTIR) and pyrolysis Gas-Chromatography coupled to Mass Spectrometry (py-GC/MS) to obtain fundamental information about the vaginal matrix's initial composition. Differences between women of a given population were investigated as well as the prevalence of silicone-based residues for natural purposes in the population. Apolar fractions of the samples were investigated after extraction with hexane, as it is the one targeted for silicone-based lubricants used in condoms. Infrared spectroscopy outlined the presence of various proteins and lipids in all the samples, and the spectral regions 1000-1850 cm and 2700-3600 cm were identified as the most relevant zones of the spectra. Pyrolysis-GC results confirmed the presence of lipids, more specifically the presence of cholesterol residues. Chemometrics analyses showed that it was not possible to distinguish the samples based on the qualitative nor semi-quantitative content. This suggest that the same type of compounds are extracted regardless of the donor. None of the samples were found to contain any silicones residues. These results are promising from a forensic evidence interpretation perspective. Further research is required to fully validate such models and assess their robustness and limitation in casework conditions.
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http://dx.doi.org/10.1016/j.forsciint.2021.110724DOI Listing
April 2021

Quality of Life in Advanced Dementia with Late Onset, Young Onset, and Very Young Onset.

J Alzheimers Dis 2021 ;80(1):283-297

Technical University of Munich, School of Medicine, Department of Psychiatry and Psychotherapy, Munich, Germany.

Background: Advanced stages of dementia are characterized by severe cognitive and physical impairment. It has not yet been investigated whether persons with young onset dementia (YOD) and late onset dementia (LOD) differ in advanced disease stages.

Objectives: To compare quality of life (QoL) between persons with advanced YOD and LOD; to explore the determinants of QoL; to investigate whether YOD and LOD differ with regard to symptoms and care.

Methods: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of YOD and LOD in Germany). Persons with advanced dementia (PWAD) were assessed and caregivers were interviewed. QoL was measured with the proxy rating Quality of Life in Late Stage Dementia (QUALID) scale.

Results: 93 persons with YOD and 98 with LOD were included. No significant differences in QoL were detected. Determinants of QoL were similar in YOD and LOD. Behavioral and psychological symptoms of dementia (BPSD), suffering and other distressing symptoms were associated with a lower QoL. In YOD but not in LOD antipsychotic treatment was associated with low QoL. The group of persons who were younger than 65 years at the time of the study visit experienced significantly more distressing symptoms than older PWAD.

Conclusion: Overall, persons with advanced YOD do not appear to be disadvantaged compared to old and oldest PWAD. Special attention, however, must be paid to the group of the very young persons who seem to be particularly vulnerable.
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http://dx.doi.org/10.3233/JAD-201302DOI Listing
January 2021

A refined panel of 42 microsatellite loci to universally genotype catarrhine primates.

Ecol Evol 2021 Jan 13;11(1):498-505. Epub 2020 Dec 13.

Primate Genetics Laboratory German Primate Center Leibniz Institute for Primate Research Göttingen Germany.

Microsatellite genotyping is an important genetic method for a number of research questions in biology. Given that the traditional fragment length analysis using polyacrylamide gel or capillary electrophoresis has several drawbacks, microsatellite genotyping-by-sequencing (GBS) has arisen as a promising alternative. Although GBS mitigates many of the problems of fragment length analysis, issues with allelic dropout and null alleles often remain due to mismatches in primer binding sites and unnecessarily long PCR products. This is also true for GBS in catarrhine primates where cross-species amplification of loci (often human derived) is common.We therefore redesigned primers for 45 microsatellite loci based on 17 available catarrhine reference genomes. Next, we tested them in singleplex and different multiplex settings in a panel of species representing all major lineages of Catarrhini and further validated them in wild Guinea baboons () using fecal samples.The final panel of 42 microsatellite loci can efficiently be amplified with primers distributed into three amplification pools.With our microsatellite panel, we provide a tool to universally genotype catarrhine primates via GBS from different sample sources in a cost- and time-efficient way, with higher resolution, and comparability among laboratories and species.
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http://dx.doi.org/10.1002/ece3.7069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790618PMC
January 2021

Vocal convergence in a multi-level primate society: insights into the evolution of vocal learning.

Proc Biol Sci 2020 12 16;287(1941):20202531. Epub 2020 Dec 16.

Cognitive Ethology Laboratory, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany.

The extent to which nonhuman primate vocalizations are amenable to modification through experience is relevant for understanding the substrate from which human speech evolved. We examined the vocal behaviour of Guinea baboons, , ranging in the Niokolo Koba National Park in Senegal. Guinea baboons live in a multi-level society, with units nested within parties nested within gangs. We investigated whether the acoustic structure of grunts of 27 male baboons of two gangs varied with party/gang membership and genetic relatedness. Males in this species are philopatric, resulting in increased male relatedness within gangs and parties. Grunts of males that were members of the same social levels were more similar than those of males in different social levels ( = 351 dyads for comparison within and between gangs, and = 169 dyads within and between parties), but the effect sizes were small. Yet, acoustic similarity did not correlate with genetic relatedness, suggesting that higher amounts of social interactions rather than genetic relatedness promote the observed vocal convergence. We consider this convergence a result of sensory-motor integration and suggest this to be an implicit form of vocal learning shared with humans, in contrast to the goal-directed and intentional explicit form of vocal learning unique to human speech acquisition.
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http://dx.doi.org/10.1098/rspb.2020.2531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779498PMC
December 2020

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Immunity 2020 12 26;53(6):1296-1314.e9. Epub 2020 Nov 26.

Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany. Electronic address:

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.
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http://dx.doi.org/10.1016/j.immuni.2020.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689306PMC
December 2020

On Multifaceted Definitions of Multilevel Societies: Response to Papageorgiou and Farine.

Trends Ecol Evol 2021 01 11;36(1):17-19. Epub 2020 Nov 11.

Department of Anthropology, Queens College, City University of New York, Flushing, NY, USA; New York Consortium in Evolutionary Primatology, New York, NY, USA; Anthropology, Biology and Psychology Programs, CUNY Graduate Center, 365 Fifth Avenue, New York, NY, USA; Department of Archaeology, University of Cape Town, Rondebosch, 7701, Cape Town, South Africa.

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http://dx.doi.org/10.1016/j.tree.2020.10.012DOI Listing
January 2021

Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis.

Infection 2020 Nov 2. Epub 2020 Nov 2.

Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Background: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers.

Methods: The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON-TB Gold Plus (QFT Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT Plus and IP-10 levels.

Results: Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis.

Conclusion: Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.
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http://dx.doi.org/10.1007/s15010-020-01541-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605464PMC
November 2020

Do infants and preschoolers quantify probabilities based on proportions?

R Soc Open Sci 2020 Sep 9;7(9):191751. Epub 2020 Sep 9.

Leibniz ScienceCampus Primate Cognition, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany.

Most statistical problems encountered throughout life require the ability to quantify probabilities based on proportions. Recent findings on the early ontogeny of this ability have been mixed: For example, when presented with jars containing preferred and less preferred items, 12-month-olds, but not 3- and 4-years-olds, seem to rely on the proportions of objects in the jars to predict the content of samples randomly drawn out of them. Given these contrasting findings, it remains unclear what the probabilistic reasoning abilities of young children are and how they develop. In our study, we addressed this question and tested, with identical methods across age groups and similar methods to previous studies, whether 12-month-olds and 3- and 4-years-olds rely on proportions of objects to estimate probabilities of random sampling events. Results revealed that neither infants nor preschoolers do. While preschoolers' performance is in line with previous findings, infants' performance is difficult to interpret given their failure in a control condition in which the outcomes happened with certainty rather than a graded probability. More systematic studies are needed to explain why infants succeeded in a previous study but failed in our study.
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http://dx.doi.org/10.1098/rsos.191751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540750PMC
September 2020

An unintentional complication during an intentional procedure-Sinus of Valsalva laceration during BASILICA.

Clin Res Cardiol 2020 Sep 21. Epub 2020 Sep 21.

Department of Internal Medicine and Cardiology, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstr. 76, 01307, Dresden, Germany.

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http://dx.doi.org/10.1007/s00392-020-01745-3DOI Listing
September 2020

Differential ageing trajectories in motivation, inhibitory control and cognitive flexibility in Barbary macaques ().

Philos Trans R Soc Lond B Biol Sci 2020 11 21;375(1811):20190617. Epub 2020 Sep 21.

Cognitive Ethology Laboratory, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany.

Across the lifespan, the performance in problem-solving tasks varies strongly, owing to age-related variation in cognitive abilities as well as the motivation to engage in a task. Non-human primates provide an evolutionary perspective on human cognitive and motivational ageing, as they lack an insight into their own limited lifetime, and ageing trajectories are not affected by customs and societal norms. To test age-related variation in inhibitory control, cognitive flexibility and persistence, we presented Barbary macaques (), living at La Forêt des Singes in Rocamadour (France), with three problem-solving tasks. We conducted 297 trials with 143 subjects aged 2-30 years. We found no effect of age on success and latency to succeed in the inhibitory control task. In the cognitive flexibility task, 21 out of 99 monkeys were able to switch their strategy, but there was no evidence for an effect of age. Yet, the persistence in the motivation task as well as the overall likelihood to participate in any of the tasks declined with increasing age. These results suggest that motivation declines earlier than the cognitive abilities assessed in this study, corroborating the notion that non-human primates and humans show similar changes in motivation in old age. This article is part of the theme issue 'Evolution of the primate ageing process'.
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http://dx.doi.org/10.1098/rstb.2019.0617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540953PMC
November 2020

TRIM21 Is Targeted for Chaperone-Mediated Autophagy during Typhimurium Infection.

J Immunol 2020 11 18;205(9):2456-2467. Epub 2020 Sep 18.

Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine, University Hospital Cologne, University of Cologne, 50935 Cologne, Germany;

serovar Typhimurium ( Typhimurium) is a Gram-negative bacterium that induces cell death of macrophages as a key virulence strategy. We have previously demonstrated that the induction of macrophage death is dependent on the host's type I IFN (IFN-I) response. IFN-I signaling has been shown to induce tripartite motif (TRIM) 21, an E3 ubiquitin ligase with critical functions in autoimmune disease and antiviral immunity. However, the importance and regulation of TRIM21 during bacterial infection remains poorly understood. In this study, we investigated the role of TRIM21 upon Typhimurium infection of murine bone marrow-derived macrophages. Although expression was induced in an IFN-I-dependent manner, we found that TRIM21 levels were mainly regulated posttranscriptionally. Following TLR4 activation, TRIM21 was transiently degraded via the lysosomal pathway by chaperone-mediated autophagy (CMA). However, Typhimurium-induced mTORC2 signaling led to phosphorylation of Akt at S473, which subsequently impaired TRIM21 degradation by attenuating CMA. Elevated TRIM21 levels promoted macrophage death associated with reduced transcription of NF erythroid 2-related factor 2 (NRF2)-dependent antioxidative genes. Collectively, our results identify IFN-I-inducible TRIM21 as a negative regulator of innate immune responses to Typhimurium and a previously unrecognized substrate of CMA. To our knowledge, this is the first study reporting that a member of the TRIM family is degraded by the lysosomal pathway.
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http://dx.doi.org/10.4049/jimmunol.2000048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576115PMC
November 2020

Trialling Meta-Research in Comparative Cognition: Claims and Statistical Inference in Animal Physical Cognition.

Anim Behav Cogn 2020 Aug;7(3):419-444

Institute for Globally Distributed Open Research and Education (IGDORE).

Scientific disciplines face concerns about replicability and statistical inference, and these concerns are also relevant in animal cognition research. This paper presents a first attempt to assess how researchers make and publish claims about animal physical cognition, and the statistical inferences they use to support them. We surveyed 116 published experiments from 63 papers on physical cognition, covering 43 different species. The most common tasks in our sample were trap-tube tasks (14 papers), other tool use tasks (13 papers), means-end understanding and string-pulling tasks (11 papers), object choice and object permanence tasks (9 papers) and access tasks (5 papers). This sample is not representative of the full scope of physical cognition research; however, it does provide data on the types of statistical design and publication decisions researchers have adopted. Across the 116 experiments, the median sample size was 7. Depending on the definitions we used, we estimated that between 44% and 59% of our sample of papers made positive claims about animals' physical cognitive abilities, between 24% and 46% made inconclusive claims, and between 10% and 17% made negative claims. Several failures of animals to pass physical cognition tasks were reported. Although our measures had low inter-observer reliability, these findings show that negative results can and have been published in the field. However, publication bias is still present, and consistent with this, we observed a drop in the frequency of -values above .05. This suggests that some non-significant results have not been published. More promisingly, we found that researchers are likely making many correct statistical inferences at the individual-level. The strength of evidence of statistical effects at the group-level was weaker, and its -value distribution was consistent with some effect sizes being overestimated. Studies such as ours can form part of a wider investigation into statistical reliability in comparative cognition. However, future work should focus on developing the validity and reliability of the measurements they use, and we offer some starting points.
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http://dx.doi.org/10.26451/abc.07.03.09.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115978PMC
August 2020

Macaque Gaze Responses to the Primatar: A Virtual Macaque Head for Social Cognition Research.

Front Psychol 2020 17;11:1645. Epub 2020 Jul 17.

Department of Primate Cognition, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, University of Göttingen, Göttingen, Germany.

Following the expanding use and applications of virtual reality in everyday life, realistic virtual stimuli are of increasing interest in cognitive studies. They allow for control of features such as gaze, expression, appearance, and movement, which may help to overcome limitations of using photographs or video recordings to study social responses. In using virtual stimuli however, one must be careful to avoid the uncanny valley effect, where realistic stimuli can be perceived as eerie, and induce an aversion response. At the same time, it is important to establish whether responses to virtual stimuli mirror responses to depictions of a real conspecific. In the current study, we describe the development of a new virtual monkey head with realistic facial features for experiments with nonhuman primates, the "Primatar." As a first step toward validation, we assessed how monkeys respond to facial images of a prototype of this Primatar compared to images of real monkeys (RMs), and an unrealistic model. We also compared gaze responses between original images and scrambled as well as obfuscated versions of these images. We measured looking time to images in six freely moving long-tailed macaques () and gaze exploration behavior in three rhesus macaques (). Both groups showed more signs of overt attention to original images than scrambled or obfuscated images. In addition, we found no evidence for an uncanny valley effect; since for both groups, looking times did not differ between real, realistic, or unrealistic images. These results provide important data for further development of our Primatar for use in social cognition studies and more generally for cognitive research with virtual stimuli in nonhuman primates. Future research on the absence of an uncanny valley effect in macaques is needed, to elucidate the roots of this mechanism in humans.
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http://dx.doi.org/10.3389/fpsyg.2020.01645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379899PMC
July 2020

Introduction to special issue: Frontiers in baboon research.

J Hum Evol 2020 09 1;146:102822. Epub 2020 Aug 1.

Cognitive Ethology Laboratory, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077, Göttingen, Germany; Leibniz ScienceCampus Primate Cognition, Kellnerweg 4, 37077, Göttingen, Germany; Department for Primate Cognition, Georg-August-University, Kellnerweg 4, 37077, Göttingen, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jhevol.2020.102822DOI Listing
September 2020

Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting and Typhimurium.

Microorganisms 2020 Jul 22;8(8). Epub 2020 Jul 22.

Department I of Internal Medicine, University of Cologne, 50937 Cologne, Germany.

The prevalence of bacterial pathogens being resistant to antibiotic treatment is increasing worldwide, leading to a severe global health challenge. Simultaneously, the development and approval of new antibiotics stagnated in the past decades, leading to an urgent need for novel approaches to avoid the spread of untreatable bacterial infections in the future. We developed a highly comprehensive screening platform based on quantification of pathogen driven host-cell death to detect new anti-virulence drugs targeting () and serovar Typhimurium (T), both known for their emerging antibiotic resistance. By screening over 10,000 small molecules we could identify several substances showing promising effects on and T pathogenicity in our in vitro infection model. Importantly, we could detect compounds potently inhibiting bacteria induced killing of host cells and one novel comipound with impact on the function of the type 3 secretion system (T3SS) of T. Thus, we provide proof of concept data of rapid and feasible medium- to high-throughput drug screening assays targeting virulence mechanisms of two major Gram-negative pathogens.
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http://dx.doi.org/10.3390/microorganisms8081096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463580PMC
July 2020

On the evolution of baboon greeting rituals.

Philos Trans R Soc Lond B Biol Sci 2020 08 29;375(1805):20190420. Epub 2020 Jul 29.

Cognitive Ethology Laboratory, German Primate Center, Kellnerweg 4, 37077 Goettingen, Germany.

To balance the trade-offs of male co-residence, males living in multi-male groups may exchange ritualized greetings. Although these non-aggressive signals are widespread in the animal kingdom, the repertoire described in the genus is exceptional, involving potentially harmful behaviours such as genital fondling. Such greetings are among the most striking male baboon social interactions, yet their function remains disputed. Drawing on the comprehensive analysis from our own research on wild Guinea baboons, combined with a survey of the literature into other baboon species, we review the form and function of male-male ritualized greetings and their relation to the various social systems present in this genus. These ritualized signals differ between species in their occurrence, form and function. While ritualized greetings are rare in species with the most intense contest competition, the complexity of and risk involved in greeting rituals increase with the degree of male-male tolerance and cooperation. The variety of societies found in this genus, combined with its role as a model for human socioecological evolution, sheds light on the evolution of ritualized behaviour in non-human primates and rituals in humans. This article is part of the theme issue 'Ritual renaissance: new insights into the most human of behaviours'.
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http://dx.doi.org/10.1098/rstb.2019.0420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423252PMC
August 2020

Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60.

Elife 2020 06 15;9. Epub 2020 Jun 15.

Max Planck Institute for Biology of Ageing, Cologne, Germany.

Splicing is a vital cellular process that modulates important aspects of animal physiology, yet roles in regulating innate immunity are relatively unexplored. From genetic screens in , we identified splicing factor RNP-6/PUF60 whose activity suppresses immunity, but promotes longevity, suggesting a tradeoff between these processes. Bacterial pathogen exposure affects gene expression and splicing in a dependent manner, and gain and loss-of-function activities reveal an active role in immune regulation. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. RNP-6 acts through TIR-1/PMK-1/MAPK signaling to modulate immunity. The mammalian homolog, PUF60, also displays anti-inflammatory properties, and its levels swiftly decrease after bacterial infection in mammalian cells, implying a role in the host response. Altogether our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.
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http://dx.doi.org/10.7554/eLife.57591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332298PMC
June 2020

Multilevel Organisation of Animal Sociality.

Trends Ecol Evol 2020 09 27;35(9):834-847. Epub 2020 May 27.

Department of Anthropology, Queens College, City University of New York, Flushing, NY 11367-1597, USA; New York Consortium in Evolutionary Primatology, New York, NY 11367, USA; Anthropology, Biology and Psychology Programs, CUNY Graduate Center, 365 Fifth Avenue, New York, NY 10016, USA; Department of Archaeology, University of Cape Town, Rondebosch, 7701, Cape Town, South Africa.

Multilevel societies (MLSs), stable nuclear social units within a larger collective encompassing multiple nested social levels, occur in several mammalian lineages. Their architectural complexity and size impose specific demands on their members requiring adaptive solutions in multiple domains. The functional significance of MLSs lies in their members being equipped to reap the benefits of multiple group sizes. Here, we propose a unifying terminology and operational definition of MLS. To identify new avenues for integrative research, we synthesise current literature on the selective pressures underlying the evolution of MLSs and their implications for cognition, intersexual conflict, and sexual selection. Mapping the drivers and consequences of MLS provides a reference point for the social evolution of many taxa, including our own species.
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http://dx.doi.org/10.1016/j.tree.2020.05.003DOI Listing
September 2020

What "Impact" Do NLME Publications Have Outside Our Community?

CPT Pharmacometrics Syst Pharmacol 2020 04 20;9(4):191-194. Epub 2020 Mar 20.

Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.

The number of publications applying nonlinear mixed-effect (NLME) modeling has increased yearly since its first appearance in 1979. Here, we evaluated articles that have used NLME modeling, were published in journals that attract a broader audience, and we discussed the standard of presentation of these to stimulate target audience-specific improvements for increased impact in the future.
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http://dx.doi.org/10.1002/psp4.12501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179956PMC
April 2020

Quantitative coronary computed tomography angiography for the detection of cardiac allograft vasculopathy.

Eur Radiol 2020 Aug 16;30(8):4317-4326. Epub 2020 Mar 16.

Department of Interventional and Diagnostic Radiology, University of Leipzig - Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany.

Objectives: To associate coronary wall volume and composition, derived from coronary computed tomography angiography (CTA), with cardiac allograft vasculopathy (CAV) detected on invasive coronary angiography (ICA) in heart-transplanted (HTX) patients.

Methods: We included consecutive adults who received ICA and coronary CTA for evaluation of CAV ≥ 10 months after HTX. In all coronary segments, we assessed lumen and wall volumes and segmental length, calculated volume-length ratio (VLR) (volumes indexed by segmental length; mm/mm), wall burden (WB) (wall/wall + lumen volumes; %), and assessed proportions of calcified, fibrotic, fibro-fatty, and low-attenuation tissue (%) in coronary wall. We rendered independent CTA measures associated with CAV by ICA, tested their discriminatory capacity, and assessed concordance between CTA and ICA.

Results: Among 50 patients (84% men; 53.6 ± 11.9 years), we analyzed 632 coronary segments. Mean interval between HTX and CTA was 6.7 ± 4.7 years and between ICA and CTA 1 (0-1) day. Segmental VLR, WB, and proportion of fibrotic tissue were independently associated with CAV (OR = 1.06-1.27; p ≤ 0.002), reaching a high discriminatory capacity (combination of all three: AUC = 0.84; 95%CI, 0.75-0.90). Concordance between CTA and ICA was higher in advanced CAV (88%) compared with that in none (37%) and mild (19%) CAV. Discordance was primarily driven by a large number of segments with coronary wall changes on CTA but without luminal stenoses on ICA (177/591; 25%).

Conclusion: CTA-derived coronary wall VLR, WB, and the proportion of fibrotic tissue are independent markers of CAV. Combination of these three parameters may aid the detection of early CAV not detected by ICA, the current standard of care.

Key Points: • Coronary CTA detects CAV in HTX patients. • Coronary wall volume-length ratio, wall burden, and proportion of fibrotic tissue are independently associated with CAV. • In contrast to ICA, coronary CTA may identify the early stages of CAV.
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http://dx.doi.org/10.1007/s00330-019-06653-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338811PMC
August 2020

Development and testing of an informative guide about palliative care for family caregivers of people with advanced dementia.

BMC Palliat Care 2020 Mar 12;19(1):30. Epub 2020 Mar 12.

School of Medicine, Department of Psychiatry and Psychotherapy, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Background: Since people with advanced dementia are usually not able to make complex decisions, it is usually the family caregivers, as proxies, who have to decide on treatments and their termination. However, these decisions are difficult for the caregivers to make, as they are often inadequately informed and cannot properly assess the consequences; moreover, they are concerned about harming the sick person. We aimed to first develop an informative booklet about palliative care issues for caregivers of people with advanced dementia. Secondly, we aimed to investigate a change in family caregivers' knowledge regarding palliative care issues and caregivers' involvement in medical and care decisions before and after studying this booklet.

Methods: A first version of the booklet was drafted by an experienced psychiatrist and palliative care specialist based on existing booklets and guidelines; necessary cultural adaptions were taken into consideration. A nominal group process was conducted to develop the informative guide. In order to investigate the acceptance of the booklet and the possibility to implement it, 38 patient-caregiver dyads were recruited, and caregivers were interviewed both before receiving the booklet and after 3 months of receiving the booklet.

Results: Experts from various disciplines collaborated on a German booklet for family caregivers of people with advanced dementia as an information aid regarding issues of palliative care. The subsequent test showed that all caregivers had experienced a personal benefit from the booklet. Caregivers had a significant gain of knowledge after provision of the booklet. A large proportion of caregivers who had not previously considered and/or discussed medical topics reported that they had done so within 3 months after obtaining the booklet, or planned to do so in the near future.

Conclusions: The caregivers valued the comprehensible, concise and well-structured information guide on palliative care issues in advanced dementia. They agreed it increases knowledge and prompts decision making and therefore should be developed in many languages and disseminated among family caregivers of people with dementia.

Trial Registration: clinicaltrial.gov, NCT03548142. Retrospectively registered 7 June 2018.
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http://dx.doi.org/10.1186/s12904-020-0533-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068859PMC
March 2020

Towards a new taxonomy of primate vocal production learning.

Philos Trans R Soc Lond B Biol Sci 2020 01 18;375(1789):20190045. Epub 2019 Nov 18.

Cognitive Ethology Laboratory, German Primate Center, Kellnerweg 4, Göttingen, Niedersachsen 37077, Germany.

The extent to which vocal learning can be found in nonhuman primates is key to reconstructing the evolution of speech. Regarding the adjustment of vocal output in relation to auditory experience (vocal production learning in the narrow sense), effects on the ontogenetic trajectory of vocal development as well as adjustment to group-specific call features have been found. Yet, a comparison of the vocalizations of different primate genera revealed striking similarities in the structure of calls and repertoires in different species of the same genus, indicating that the structure of nonhuman primate vocalizations is highly conserved. Thus, modifications in relation to experience only appear to be possible within relatively tight species-specific constraints. By contrast, comprehension learning may be extremely rapid and open-ended. In conjunction, these findings corroborate the idea of an ancestral independence of vocal production and auditory comprehension learning. To overcome the futile debate about whether or not vocal production learning can be found in nonhuman primates, we suggest putting the focus on the different mechanisms that may mediate the adjustment of vocal output in response to experience; these mechanisms may include auditory facilitation and learning from success. This article is part of the theme issue 'What can animal communication teach us about human language?'
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http://dx.doi.org/10.1098/rstb.2019.0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895554PMC
January 2020

Insights into the evolution of social systems and species from baboon studies.

Elife 2019 11 12;8. Epub 2019 Nov 12.

Cognitive Ethology Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, Germany.

Baboons, members of the genus comprise six closely related species distributed throughout sub-Saharan Africa and southwest Arabia. The species exhibit more ecological flexibility and a wider range of social systems than many other primates. This article summarizes our current knowledge of the natural history of baboons and highlights directions for future research. We suggest that baboons can serve as a valuable model for complex evolutionary processes, such as speciation and hybridization. The evolution of baboons has been heavily shaped by climatic changes and population expansion and fragmentation in the African savanna environment, similar to the processes that acted during human evolution. With accumulating long-term data, and new data from previously understudied species, baboons are ideally suited for investigating the links between sociality, health, longevity and reproductive success. To achieve these aims, we propose a closer integration of studies at the proximate level, including functional genomics, with behavioral and ecological studies.
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http://dx.doi.org/10.7554/eLife.50989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850771PMC
November 2019

Identification of the immunological profile in rejection-free heart transplantation.

Transpl Immunol 2020 04 6;59:101259. Epub 2019 Nov 6.

University Department for Cardiac Surgery, Heart Center Leipzig, HELIOS Clinic, Leipzig, Germany. Electronic address:

Background: Tolerance induction following organ transplantation can be achieved by adoptive cell transfer of regulatory T-cells (T) or dendritic cells (DCs). However, the target immunological profile is unknown. The present study aimed to identify an immunological profile connected to tolerance induction following heart transplantation (HTx).

Methods: Blood samples of long-term rejection-free HTx patients (LT-HTx, n = 20) and patients on the HTx waiting list (pre-HTx, n = 20) were compared. Flow cytometric and multiplex analyses of DCs, T, subsets of both cell types and serum cytokines were performed. Furthermore, principle component and cluster analysis was used to identify a target immunological profile using a multiparametric dataset.

Results: Plasmacytoid DCs expressing blood DC antigen (BDCA) 2 and BDCA4 were significantly increased in LT-HTx patients (BDCA2: 29.4 ± 10.1%, p = .022; BDCA4: 26.4 ± 9.3%, p = .008) compared to pre-HTx patients (BDCA2: 22.8 ± 7.2%; BDCA4: 18.9 ± 7.4%). The percentage of total T and of their CD62L subset was reduced in LT-HTx patients (%T: 9.1 ± 3.7%, p = .026; %CD62L: 85.1 ± 11.9%, p = .009) compared to pre-HTx patients (%T: 11.8 ± 3.6%; %CD62L: 93.3 ± 4.5%). LT-HTx patients showed different cytokine levels than pre-HTx patients. Principle component and cluster analysis revealed that the total DCs, BDCA2 and BDCA4 DCs and CD147 T had the strongest influence to distinguish among long-term rejection-free and pre-HTx patients.

Conclusion: In conclusion, we defined the immune status of pre-HTx patients and the target immunological profile of LT-HTx patients. These data may help to establish a monitoring tool that is based on a multiparametric dataset.
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http://dx.doi.org/10.1016/j.trim.2019.101259DOI Listing
April 2020

Establishing an infrastructure for collaboration in primate cognition research.

PLoS One 2019 24;14(10):e0223675. Epub 2019 Oct 24.

Georgia State University, Atlanta, Georgia, United States of America.

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223675PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812783PMC
March 2020

Long-tailed macaques extract statistical information from repeated types of events to make rational decisions under uncertainty.

Sci Rep 2019 08 20;9(1):12107. Epub 2019 Aug 20.

Cognitive Ethology Laboratory, German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany.

Human children and apes seem to be intuitive statisticians when making predictions from populations of objects to randomly drawn samples, whereas monkeys seem not to be. Statistical reasoning can also be investigated in tasks in which the probabilities of different possibilities must be inferred from relative frequencies of events, but little is known about the performance of nonhuman primates in such tasks. In the current study, we investigated whether long-tailed macaques extract statistical information from repeated types of events to make predictions under uncertainty. In each experiment, monkeys first experienced the probability of rewards associated with different factors separately. In a subsequent test trial, monkeys could then choose between the different factors presented simultaneously. In Experiment 1, we tested whether long-tailed macaques relied on probabilities and not on a comparison of absolute quantities to make predictions. In Experiment 2 and 3 we varied the nature of the predictive factors and the complexity of the covariation structure between rewards and factors. Results indicate that long-tailed macaques extract statistical information from repeated types of events to make predictions and rational decisions under uncertainty, in more or less complex scenarios. These findings suggest that the presentation format affects the monkeys' statistical reasoning abilities.
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http://dx.doi.org/10.1038/s41598-019-48543-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702217PMC
August 2019

Leptin signaling impairs macrophage defenses against Typhimurium.

Proc Natl Acad Sci U S A 2019 08 26;116(33):16551-16560. Epub 2019 Jul 26.

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany;

The dynamic interplay between metabolism and immune responses in health and disease, by which different immune cells impact on metabolic processes, are being increasingly appreciated. However, the potential of master regulators of metabolism to control innate immunity are less understood. Here, we studied the cross-talk between leptin signaling and macrophage function in the context of bacterial infections. We found that upon infection with Gram-negative pathogens, such as Typhimurium, leptin receptor (Lepr) expression increased in both mouse and human macrophages. Unexpectedly, both genetic ablation in macrophages and global pharmacologic leptin antagonization augmented lysosomal functions, reduced Typhimurium burden, and diminished inflammation in vitro and in vivo. Mechanistically, we show that leptin induction activates the mTORC2/Akt pathway and subsequently down-regulates Phlpp1 phosphatase, allowing for phosphorylated Akt to impair lysosomal-mediated pathogen clearance. These data highlight a link between leptin signaling, the mTORC2/Phlpp1/Akt axis, and lysosomal activity in macrophages and have important therapeutic implications for modulating innate immunity to combat Gram-negative bacterial infections.
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http://dx.doi.org/10.1073/pnas.1904885116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697794PMC
August 2019

[Career Prospects for Young Physicians in Infectious Diseases].

Dtsch Med Wochenschr 2019 06 4;144(11):764-769. Epub 2019 Jun 4.

Klinik I für Innere Medizin, Klinische Infektiologie, Universitätsklinikum Köln.

Infectious Diseases are a cross-sectional area connected to various medical disciplines and offer interested physicians multiple working opportunities. The spectrum of infectious diseases covers both out- and inpatient care as well as basic, clinical and epidemiological research. The need for infectious diseases specialists is increasing, thus career prospects are promising. Working conditions in infectious diseases are comparatively family-friendly. With this article we intend to arouse interest for working in the fascinating fields of infectious diseases and provide information on career opportunities. Data from a recently conducted survey among members of the German Society of Infectious Diseases deliver insight, how infectious disease specialists work today.
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http://dx.doi.org/10.1055/a-0875-7120DOI Listing
June 2019