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Article ; Online: A Powerful P-N Connection: Preparative Approaches, Reactivity, and Applications of P-Stereogenic Aminophosphines.

Huber, Tanja / Bauer, Jonathan O

Chemistry (Weinheim an der Bergstrasse, Germany)

2024 Volume 30, Issue 18, Page(s) e202303760

Abstract: For more than five decades, P-stereogenic aminophosphine chalcogenides and boranes have attracted ... auxiliaries. Enantiomerically pure compounds with N-P ...

Abstract	For more than five decades, P-stereogenic aminophosphine chalcogenides and boranes have attracted scientific attention and are still in the focus of ongoing research. In the last years, novel transition metal-based synthesis methods have been discovered, in addition to the long-known use of chiral auxiliaries. Enantiomerically pure compounds with N-P
Language	English
Publishing date	2024-01-15
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202303760
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Article ; Online: Parametric Imaging of P-Glycoprotein Function at the Blood-Brain Barrier Using k

Breuil, Louise / El Biali, Myriam / Vodovar, Dominique / Marie, Solène / Auvity, Sylvain / Bauer, Martin / Goutal, Sébastien / Rodrigo, Sebastian / Langer, Oliver / Tournier, Nicolas

Molecular imaging and biology

2023 Volume 25, Issue 6, Page(s) 1135–1141

Abstract: ... and from 20 to 60 min in humans. P-gp inhibition significantly decreased k: Conclusions: k ...

Abstract	Purpose: PET imaging using [ Procedures: k Results: The linear part of the log-transformed brain TACs occurred from 10 to 30 min after radiotracer injection in rats, from 15 to 60 min in baboons, and from 20 to 60 min in humans. P-gp inhibition significantly decreased k Conclusions: k
MeSH term(s)	Humans ; Rats ; Animals ; Blood-Brain Barrier/diagnostic imaging ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; ATP Binding Cassette Transporter, Subfamily B, Member 1/pharmacology ; Metoclopramide ; Brain/diagnostic imaging ; Brain/metabolism ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Positron-Emission Tomography/methods ; Papio/metabolism
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Metoclopramide (L4YEB44I46) ; ATP Binding Cassette Transporter, Subfamily B
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2079160-4
ISSN	1860-2002 ; 1536-1632
ISSN (online)	1860-2002
ISSN	1536-1632
DOI	10.1007/s11307-023-01864-z
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Zs.A 6468: Show issues

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Article ; Online: Novel heterozygous COL4A2 variant c.2572A > G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome.

Focke, Jan K / Veltkamp, Roland / Bauer, Peter / Kraemer, Markus

Journal of neurology

2022 Volume 269, Issue 9, Page(s) 5153–5156

MeSH term(s)	Angiomatosis ; Brain Neoplasms ; Collagen Type IV ; Humans
Chemical Substances	COL4A2 protein, human ; Collagen Type IV
Language	English
Publishing date	2022-04-14
Publishing country	Germany
Document type	Letter
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-022-11111-0
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Ui II Zs.40: Show issues

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Article ; Online: PINK1 p.Leu347Pro mutations in Malays: Prevalence and illustrative cases.

Tan, Ai Huey / Lohmann, Katja / Tay, Yi Wen / Lim, Jia Lun / Ahmad-Annuar, Azlina / Ramli, Norlisah / Chin, Yen Theng / Mawardi, Ahmad Shahir / Azmi, Khairul / Aziz, Zariah Abdul / Puvanarajah, Santhi Datuk / Bauer, Peter / Klein, Christine / Rolfs, Arndt / Lim, Shen-Yang

Parkinsonism & related disorders

2020 Volume 79, Page(s) 34–39

Abstract: ... of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been ... reported in people of Filipino or Chamorro (native Guamanian) ancestry.: Results: Homozygous p ... further supports the pathogenicity of the p. Leu347Pro variant. ...

Abstract	Background: An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK-PINK1 are also limited. Methods: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry. Results: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented. Conclusions: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.
MeSH term(s)	Adult ; Female ; Humans ; Malaysia/epidemiology ; Male ; Middle Aged ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/epidemiology ; Parkinson Disease/genetics ; Parkinson Disease/physiopathology ; Prevalence ; Protein Kinases/genetics
Chemical Substances	Protein Kinases (EC 2.7.-) ; PTEN-induced putative kinase (EC 2.7.11.1)
Language	English
Publishing date	2020-08-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2020.08.015
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Zs.A 4553: 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.MO 420: Show issues

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Article ; Online: Paraneoplastic Cerebellar Degeneration With P/Q-VGCC vs Yo Autoantibodies.

Winklehner, Michael / Bauer, Jan / Endmayr, Verena / Schwaiger, Carmen / Ricken, Gerda / Motomura, Masakatsu / Yoshimura, Shunsuke / Shintaku, Hiroshi / Ishikawa, Kinya / Tsuura, Yukio / Iizuka, Takahiro / Yokota, Takanori / Irioka, Takashi / Höftberger, Romana

Neurology(R) neuroimmunology & neuroinflammation

2022 Volume 9, Issue 4

Abstract: ... antigens such as Yo or cell surface neuronal antigens such as the P/Q-type voltage-gated calcium channel (P ... mediated pathology, the immune mechanisms in anti-P/Q-VGCC-PCD remain unclear. In this study, we compare ... neuropathologic characteristics of PCD with anti-P/Q-VGCC and anti-Yo autoantibodies in an archival autopsy cohort ...

Abstract	Background and objectives: Paraneoplastic cerebellar degeneration (PCD) is characterized by a widespread loss of Purkinje cells (PCs) and may be associated with autoantibodies against intracellular antigens such as Yo or cell surface neuronal antigens such as the P/Q-type voltage-gated calcium channel (P/Q-VGCC). Although the intracellular location of the target antigen in anti-Yo-PCD supports a T cell-mediated pathology, the immune mechanisms in anti-P/Q-VGCC-PCD remain unclear. In this study, we compare neuropathologic characteristics of PCD with anti-P/Q-VGCC and anti-Yo autoantibodies in an archival autopsy cohort. Methods: We performed neuropathology, immunohistochemistry, and multiplex immunofluorescence on formalin-fixed and paraffin-embedded brain tissue of 1 anti-P/Q-VGCC, 2 anti-Yo-PCD autopsy cases and controls. Results: Anti-Yo-PCD revealed a diffuse and widespread PC loss together with microglial nodules with pSTAT1 Discussion: Anti-Yo-PCD showed characteristic features of a T cell-mediated pathology, whereas this was not observed in 1 case of anti-P/Q-VGCC-PCD. Our findings support a pathogenic role of anti-P/Q-VGCC autoantibodies in causing neuronal dysfunction, probably due to altered synaptic transmission resulting in calcium dysregulation and subsequent PC death. Because disease progression may lead to irreversible PC loss, anti-P/Q-VGCC-PCD patients could benefit from early oncologic and immunologic therapies.
MeSH term(s)	Antibodies, Neoplasm ; Autoantibodies ; CD8-Positive T-Lymphocytes ; Calcium Channels, Q-Type ; Humans ; Immunoglobulin G ; Nerve Tissue Proteins ; Paraneoplastic Cerebellar Degeneration
Chemical Substances	Antibodies, Neoplasm ; Autoantibodies ; Calcium Channels, Q-Type ; Immunoglobulin G ; Nerve Tissue Proteins ; anti-Yo autoantibodies
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200006
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Article ; Online: St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

El Biali, Myriam / Wölfl-Duchek, Michael / Jackwerth, Matthias / Mairinger, Severin / Weber, Maria / Bamminger, Karsten / Poschner, Stefan / Rausch, Ivo / Schindler, Natalie / Lozano, Irene Hernández / Jäger, Walter / Nics, Lukas / Tournier, Nicolas / Hacker, Marcus / Zeitlinger, Markus / Bauer, Martin / Langer, Oliver

Clinical and translational science

2024 Volume 17, Issue 5, Page(s) e13804

Abstract: ... of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically ... relevant drug interactions. It is currently not known whether SJW can also induce P ... of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination ...

Abstract	St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [
MeSH term(s)	Humans ; Hypericum/chemistry ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/drug effects ; Phloroglucinol/pharmacokinetics ; Phloroglucinol/pharmacology ; Phloroglucinol/analogs & derivatives ; Phloroglucinol/administration & dosage ; Plant Extracts/pharmacology ; Plant Extracts/administration & dosage ; Plant Extracts/pharmacokinetics ; Male ; Adult ; Positron-Emission Tomography/methods ; Terpenes/pharmacology ; Terpenes/pharmacokinetics ; Terpenes/metabolism ; Female ; Young Adult ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Bridged Bicyclo Compounds/pharmacology ; Bridged Bicyclo Compounds/pharmacokinetics ; Bridged Bicyclo Compounds/administration & dosage ; Terfenadine/analogs & derivatives ; Terfenadine/pharmacokinetics ; Terfenadine/administration & dosage ; Terfenadine/pharmacology ; Cytochrome P-450 Enzyme System/metabolism ; Healthy Volunteers
Chemical Substances	hyperforin (RM741E34FP) ; Phloroglucinol (DHD7FFG6YS) ; Plant Extracts ; Terpenes ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; ATP Binding Cassette Transporter, Subfamily B ; fexofenadine (E6582LOH6V) ; ABCB1 protein, human ; Bridged Bicyclo Compounds ; Terfenadine (7BA5G9Y06Q) ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2024-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13804
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Article ; Online: Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.

Vulin, Milica / Zhong, Yu / Maloney, Bryan J / Bauer, Björn / Hartz, Anika M S

Fluids and barriers of the CNS

2023 Volume 20, Issue 1, Page(s) 70

Abstract: Background: Loss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ ... overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin ... proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting ...

Abstract	Background: Loss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer's disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin-proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade Methods: We treated hAPP mice with the proteasome inhibitor BTZ or a combination of BTZ with the P-gp inhibitor cyclosporin A (CSA) for 2 weeks. Vehicle-treated wild-type (WT) mice were used as a reference for normal P-gp protein expression and transport activity. In addition, we used the opioid receptor agonist loperamide as a P-gp substrate in tail flick assays to indirectly assess P-gp transport activity at the blood-brain barrier in vivo. We also determined P-gp protein expression by Western blotting, measured P-gp transport activity levels in isolated brain capillaries with live cell confocal imaging and assessed Aβ plasma and brain levels with ELISA. Results: We found that 2-week BTZ treatment of hAPP mice restored P-gp protein expression and transport activity in brain capillaries to levels found in WT mice. We also observed that hAPP mice displayed significant loperamide-induced central antinociception compared to WT mice indicating impaired P-gp transport activity at the blood-brain barrier of hAPP mice in vivo. Furthermore, BTZ treatment prevented loperamide-induced antinociception suggesting BTZ protected P-gp loss in hAPP mice. Further, BTZ-treated hAPP mice had lower Aβ40 and Aβ42 brain levels compared to vehicle-treated hAPP mice. Conclusions: Our data indicate that BTZ protects P-gp from proteasomal degradation in hAPP mice, which helps to reduce Aβ brain levels. Our data suggest that the proteasome system could be exploited for a novel therapeutic strategy in AD, particularly since increasing Aβ transport across the blood-brain barrier may prove an effective treatment for patients.
MeSH term(s)	Humans ; Mice ; Animals ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Blood-Brain Barrier/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Endopeptidase Complex/pharmacology ; Proteasome Endopeptidase Complex/therapeutic use ; Loperamide/metabolism ; Loperamide/pharmacology ; Loperamide/therapeutic use ; Proteasome Inhibitors/pharmacology ; Proteasome Inhibitors/therapeutic use ; Proteasome Inhibitors/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Brain/metabolism ; Mice, Transgenic ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; ATP Binding Cassette Transporter, Subfamily B/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Loperamide (6X9OC3H4II) ; Proteasome Inhibitors ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; ATP Binding Cassette Transporter, Subfamily B
Language	English
Publishing date	2023-10-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-023-00470-z
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Article ; Online: Impact of P-Glycoprotein Function on the Brain Kinetics of the Weak Substrate

Tournier, Nicolas / Bauer, Martin / Pichler, Verena / Nics, Lukas / Klebermass, Eva-Maria / Bamminger, Karsten / Matzneller, Peter / Weber, Maria / Karch, Rudolf / Caillé, Fabien / Auvity, Sylvain / Marie, Solène / Jäger, Walter / Wadsak, Wolfgang / Hacker, Marcus / Zeitlinger, Markus / Langer, Oliver

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2019 Volume 60, Issue 7, Page(s) 985–991

Abstract: PET with avid substrates of P-glycoprotein (ABCB1) provided evidence of the role of this efflux ...

Abstract	PET with avid substrates of P-glycoprotein (ABCB1) provided evidence of the role of this efflux transporter in effectively restricting the brain penetration of its substrates across the human blood-brain barrier (BBB). This may not reflect the situation for weak ABCB1 substrates including several antidepressants, antiepileptic drugs, and neuroleptics, which exert central nervous system effects despite being transported by ABCB1. We performed PET with the weak ABCB1 substrate
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Adult ; Brain/diagnostic imaging ; Brain/drug effects ; Brain/metabolism ; Carbon Radioisotopes ; Cyclosporine/pharmacology ; Female ; Humans ; Kinetics ; Male ; Metoclopramide/blood ; Metoclopramide/metabolism ; Metoclopramide/pharmacokinetics ; Positron-Emission Tomography
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Carbon Radioisotopes ; Carbon-11 ; Cyclosporine (83HN0GTJ6D) ; Metoclopramide (L4YEB44I46)
Language	English
Publishing date	2019-01-10
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.118.219972
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Conference proceedings ; Online: Assessment of GHBMC M50-P response for behind armour blunt trauma - impact loading with approximation of 3D surface of the armour back face displacement

Jenerowicz, Marcin / Matt, Patrick / Boljen, Matthias / Bauer, Steffen / Straßburger, Elmar / Hiermaier, Stefan

2023

Abstract: 594 ... 604 ... The present study investigates numerically the assessment capability of the GHBMC M50-P ...

Abstract	594 604 The present study investigates numerically the assessment capability of the GHBMC M50-P with regard to behind armour blunt trauma (BABT) by applying impact loading with approximation of 3D surface of the armour back face displacement (BFD). The body armour consists of a hard-ballistic plate (9 mm silicon carbide and 10 mm ultrahigh molecular weight polyethylene, UHMW-PE) and a soft-ballistic component consisting of a 40-layer aramid fabric vest. The finite element model of the ballistic vest was applied to the GHBMC M50-P thoraxusing a novel forming simulation. A load case from previous experiments was selected where no penetration ofthe plate occurred (7.62 mm x 51 armour piercing projectile). For the approximation of the 3D surface of the BFD,the last layer of UHMW-PE at its maximum deformation was transferred from Ansys-Autodyn into LS-DYNA. Forthe evaluation of the BABT, the Viscous Criterion, the Blunt Criterion and the maximum strains in the impact areawere used. The evaluation was performed at two locations: mid sternum ribs levels 3-4 and rib bone cartilagejunction area at level 4. In both cases, the obtained probability of AIS2-3 injury was exceeded and the maximumstrains indicate multiple fractures of the ribs or sternum.
Subject code	621
Language	English
Publishing country	de
Document type	Conference proceedings ; Online
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Article ; Online: Comment on 'A critical evaluation of the current "p-value controversy" '.

Bauer, Peter

Biometrical journal. Biometrische Zeitschrift

2017 Volume 59, Issue 5, Page(s) 873–874

Language	English
Publishing date	2017-04-21
Publishing country	Germany
Document type	Journal Article ; Comment
ZDB-ID	131640-0
ISSN	1521-4036 ; 0323-3847 ; 0006-3452
ISSN (online)	1521-4036
ISSN	0323-3847 ; 0006-3452
DOI	10.1002/bimj.201700019
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Z 1267: Show issues

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