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Article: Inhibition of Survivin Homodimerization Decreases Neuroblastoma Cell Growth.

Dorneburg, Carmen / Galiger, Celimene / Stadler, Giovanna L / Westhoff, Mike-Andrew / Rasche, Volker / Barth, Thomas F E / Debatin, Klaus-Michael / Beltinger, Christian

Cancers

2023 Volume 15, Issue 24

Abstract: Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been ... ...

Abstract	Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are emerging. We compared genetic inhibition of survivin transcription with the inhibition of survivin homodimerization by S12 and LQZ-7I, chosen from a larger panel of survivin dimerization inhibitors with activity against NB cells. Mice hemizygous for
Language	English
Publishing date	2023-12-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15245775
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Article ; Online: Species comparison: human and minipig PBMC reactivity under the influence of immunomodulating compounds

Pernold, Clara P S / Lagumdzic, Emil / Stadler, Maria / Dolezal, Marlies / Jäckel, Sven / Schmitt, Michael W / Mair, Kerstin H / Saalmüller, Armin

Frontiers in immunology

2024 Volume 14, Page(s) 1327776

Abstract: Considering the similarities between swine and humans, it is a logical consequence to use swine as a translational model in research and drug development, including non-clinical safety. Here, we compared the reactivity of peripheral blood mononuclear ... ...

Abstract	Considering the similarities between swine and humans, it is a logical consequence to use swine as a translational model in research and drug development, including non-clinical safety. Here, we compared the reactivity of peripheral blood mononuclear cells (PBMCs) from humans and minipigs under the influence of different compounds
MeSH term(s)	Humans ; Swine ; Animals ; Swine, Miniature ; Abatacept ; Leukocytes, Mononuclear ; CD8-Positive T-Lymphocytes ; Immunosuppressive Agents ; Sirolimus ; Receptors, Antigen, T-Cell
Chemical Substances	Abatacept (7D0YB67S97) ; Immunosuppressive Agents ; Sirolimus (W36ZG6FT64) ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-01-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1327776
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Article ; Online: Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early

Stadler, Michael R / Haines, Jenna E / Eisen, Michael B

eLife

2017 Volume 6

Abstract: High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their ... ...

Abstract	High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early
MeSH term(s)	Animals ; Chromatin/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/embryology ; Histones/metabolism ; Insulator Elements ; Polytene Chromosomes/metabolism
Chemical Substances	Chromatin ; Drosophila Proteins ; Histones
Language	English
Publishing date	2017-11-17
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.29550
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Article: Taking identity-by-descent analysis into the wild: Estimating realized relatedness in free-ranging macaques.

Freudiger, Annika / Jovanovic, Vladimir M / Huang, Yilei / Snyder-Mackler, Noah / Conrad, Donald F / Miller, Brian / Montague, Michael J / Westphal, Hendrikje / Stadler, Peter F / Bley, Stefanie / Horvath, Julie E / Brent, Lauren J N / Platt, Michael L / Ruiz-Lambides, Angelina / Tung, Jenny / Nowick, Katja / Ringbauer, Harald / Widdig, Anja

bioRxiv : the preprint server for biology

2024

Abstract: Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by- ... ...

Abstract	Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by-descent (IBD) yield the most precise estimates of relatedness. Here, we leverage novel methods for estimating locus-specific IBD from low coverage whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4-6× coverage data from a rhesus macaque (
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.09.574911
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Article ; Online: Effect of Implementing a Commercial Electronic Early Warning System on Outcomes of Hospitalized Patients.

Singh, Siddhartha / Laud, Purushottam W / Crotty, Bradley H / Nanchal, Rahul S / Hanson, Ryan / Penlesky, Annie C / Fletcher, Kathlyn E / Stadler, Michael E / Dong, Yilu / Nattinger, Ann B

American journal of medical quality : the official journal of the American College of Medical Quality

2023 Volume 38, Issue 5, Page(s) 229–237

Abstract: Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700- ... ...

Abstract	Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700-bed academic medical center. The EWS risk scores were visible in the electronic medical record by bedside clinicians. The EWS risk scores were also monitored remotely 24/7 by critical care trained nurses who actively contacted bedside nurses when a patient's risk levels increased. The primary outcome was inpatient mortality. Secondary outcomes were rapid response team calls and activation of cardiopulmonary arrest (code-4) response teams. The study team conducted a regression discontinuity analysis adjusting for age, gender, insurance, severity of illness, risk of mortality, and hospital occupancy at admission. The analysis included 53,229 hospitalizations. Adjusted analysis showed no significant change in inpatient mortality, rapid response team call, or code-4 activations after implementing the EWS. This study confirms the continued uncertainty in the effectiveness of EWSs and the need for further rigorous examinations of EWSs.
MeSH term(s)	Humans ; Hospitalization ; Critical Care ; Heart Arrest/therapy ; Hospital Rapid Response Team ; Vital Signs
Language	English
Publishing date	2023-09-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1131772-3
ISSN	1555-824X ; 1062-8606
ISSN (online)	1555-824X
ISSN	1062-8606
DOI	10.1097/JMQ.0000000000000147
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Article ; Online: Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression.

Gaskill, Marissa M / Soluri, Isabella V / Branks, Annemarie E / Boka, Alan P / Stadler, Michael R / Vietor, Katherine / Huang, Hao-Yu S / Gibson, Tyler J / Mukherjee, Apratim / Mir, Mustafa / Blythe, Shelby A / Harrison, Melissa M

Developmental cell

2023 Volume 58, Issue 17, Page(s) 1610–1624.e8

Abstract: The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic ...

Abstract	The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.
MeSH term(s)	Animals ; DNA/metabolism ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Gene Expression Regulation, Developmental ; Genome ; Transcription Factors/metabolism ; Zygote/metabolism
Chemical Substances	DNA (9007-49-2) ; Drosophila Proteins ; Transcription Factors ; Trl protein, Drosophila
Language	English
Publishing date	2023-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2023.06.010
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 76: Show issues

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Article ; Online: An Emerging Paradigm for Germline Testing in Pancreatic Ductal Adenocarcinoma and Immediate Implications for Clinical Practice: A Review.

Rainone, Michael / Singh, Isha / Salo-Mullen, Erin E / Stadler, Zsofia K / O'Reilly, Eileen M

JAMA oncology

2020 Volume 6, Issue 5, Page(s) 764–771

Abstract: Importance: Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm with a rising incidence and is a leading public health challenge. Pancreatic ductal adenocarcinoma has been well characterized genomically, with findings of therapeutic ... ...

Abstract	Importance: Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm with a rising incidence and is a leading public health challenge. Pancreatic ductal adenocarcinoma has been well characterized genomically, with findings of therapeutic actionability that have substantive implications for clinical practice based on recent high-level evidence. Observations: Pathogenic germline alterations (PGAs) are relatively common in individuals with PDAC, as evidenced in multiple recent data sets, with a frequency of approximately 10%. The most common PGAs are in BRCA1, BRCA2, and ATM and more rarely in PALB2, MLH1, MSH2, MSH6, PMS2, CDKN2A, and TP53, among others, with an aggregate frequency of 3.8% to 9.7%. These PGAs are of key interest owing to therapeutic actionability and the downstream identification of at-risk family members and possible hereditary cancer syndromes. Approximately 3% to 7% of individuals with PDAC harbor a BRCA1 or BRCA2 mutation, which are among the most frequently mutated genes in PDAC. Recent updates to the American Society of Clinical Oncology and the National Comprehensive Cancer Network guidelines recommend risk assessment for all individuals with PDAC irrespective of personal or family history or ethnicity. Treatment implications include the use of checkpoint inhibitor therapy for mismatch repair-deficient PDAC and the validation of poly-ADP (adenosine diphosphate)-ribose polymerase inhibitor (PARPi) therapy as a maintenance strategy in platinum-sensitive PDAC. Conclusions and relevance: With increasing evidence and slow improvement of outcomes, PDAC has entered the era of precision medicine. Germline mutations have been identified in key genes with an aggregate frequency of 3.8% to 9.7%, several of which are therapeutically actionable with platinum, PARPi, and checkpoint inhibitor therapy. Potential therapeutic targets need to be actively sought and identified.
MeSH term(s)	Adenocarcinoma/genetics ; Carcinoma, Pancreatic Ductal/genetics ; Genetic Predisposition to Disease/genetics ; Germ Cells ; Germ-Line Mutation/genetics ; Humans
Language	English
Publishing date	2020-02-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2019.5963
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Article ; Online: The Monocle Sign on 18F-FDG PET Indicates Contralateral Peripheral Facial Nerve Palsy.

Dana, Fatemeh / Maurer, Alexander / Muehlematter, Urs J / Husmann, Lars / Schaab, Jan / Mader, Cäcilia E / Beintner-Skawran, Stephan / Messerli, Michael / Sah, Bert-Ram / Dana, Masih / Dana, Mohsen / Duhnsen, Sjunne H / Mueller, Simon A / Stadler, Thomas / Morand, Grégoire B / Meerwein, Christian / Orita, Erika / Kaufmann, Philipp A / Huellner, Martin W

Clinical nuclear medicine

2024

Abstract: Background: The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign.: Patients and methods: A total of 85 patients with unilateral FNP were included into our ... ...

Abstract	Background: The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign. Patients and methods: A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUVmax, SUVmean, total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUVmax ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUVmax ratio for the prevalence of contralateral peripheral FNP. Results: The SUVmax ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUVmax ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630-0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%). Conclusions: Asymmetrically increased FDG uptake of the OOM (the "monocle sign") indicates contralateral peripheral FNP. A nearly 2-fold higher SUVmax represents a practically useful cutoff.
Language	English
Publishing date	2024-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	197628-x
ISSN	1536-0229 ; 0363-9762
ISSN (online)	1536-0229
ISSN	0363-9762
DOI	10.1097/RLU.0000000000005238
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Zs.A 1276: Show issues

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Article ; Online: Building a genome-based understanding of bacterial pH preferences.

Ramoneda, Josep / Stallard-Olivera, Elias / Hoffert, Michael / Winfrey, Claire C / Stadler, Masumi / Niño-García, Juan Pablo / Fierer, Noah

Science advances

2023 Volume 9, Issue 17, Page(s) eadf8998

Abstract: The environmental preferences of many microbes remain undetermined. This is the case for bacterial pH preferences, which can be difficult to predict a priori despite the importance of pH as a factor structuring bacterial communities in many systems. We ... ...

Abstract	The environmental preferences of many microbes remain undetermined. This is the case for bacterial pH preferences, which can be difficult to predict a priori despite the importance of pH as a factor structuring bacterial communities in many systems. We compiled data on bacterial distributions from five datasets spanning pH gradients in soil and freshwater systems (1470 samples), quantified the pH preferences of bacterial taxa across these datasets, and compiled genomic data from representative bacterial taxa. While taxonomic and phylogenetic information were generally poor predictors of bacterial pH preferences, we identified genes consistently associated with pH preference across environments. We then developed and validated a machine learning model to estimate bacterial pH preferences from genomic information alone, a model that could aid in the selection of microbial inoculants, improve species distribution models, or help design effective cultivation strategies. More generally, we demonstrate the value of combining biogeographic and genomic data to infer and predict the environmental preferences of diverse bacterial taxa.
MeSH term(s)	Phylogeny ; Soil Microbiology ; Bacteria/genetics ; Soil ; Hydrogen-Ion Concentration
Chemical Substances	Soil
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adf8998
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Article ; Online: A fully automated FAIMS-DIA mass spectrometry-based proteomic pipeline.

Reilly, Luke / Lara, Erika / Ramos, Daniel / Li, Ziyi / Pantazis, Caroline B / Stadler, Julia / Santiana, Marianita / Roberts, Jessica / Faghri, Faraz / Hao, Ying / Nalls, Mike A / Narayan, Priyanka / Liu, Yansheng / Singleton, Andrew B / Cookson, Mark R / Ward, Michael E / Qi, Yue A

Cell reports methods

2023 Volume 3, Issue 10, Page(s) 100593

Abstract: Here, we present a standardized, "off-the-shelf" proteomics pipeline working in a single 96-well plate to achieve deep coverage of cellular proteomes with high throughput and scalability. This integrated pipeline streamlines a fully automated sample ... ...

Abstract	Here, we present a standardized, "off-the-shelf" proteomics pipeline working in a single 96-well plate to achieve deep coverage of cellular proteomes with high throughput and scalability. This integrated pipeline streamlines a fully automated sample preparation platform, a data-independent acquisition (DIA) coupled with high-field asymmetric waveform ion mobility spectrometer (FAIMS) interface, and an optimized library-free DIA database search strategy. Our systematic evaluation of FAIMS-DIA showing single compensation voltage (CV) at -35 V not only yields the deepest proteome coverage but also best correlates with DIA without FAIMS. Our in-depth comparison of direct-DIA database search engines shows that Spectronaut outperforms others, providing the highest quantifiable proteins. Next, we apply three common DIA strategies in characterizing human induced pluripotent stem cell (iPSC)-derived neurons and show single-shot mass spectrometry (MS) using single-CV (-35 V)-FAIMS-DIA results in >9,000 quantifiable proteins with <10% missing values, as well as superior reproducibility and accuracy compared with other existing DIA methods.
MeSH term(s)	Humans ; Proteomics/methods ; Tandem Mass Spectrometry/methods ; Reproducibility of Results ; Induced Pluripotent Stem Cells/chemistry ; Proteome/analysis
Chemical Substances	Proteome
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article
ISSN	2667-2375
ISSN (online)	2667-2375
DOI	10.1016/j.crmeth.2023.100593
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