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Article ; Online: DCTN1 p.K56R in progressive supranuclear palsy.

Gustavsson, Emil K / Trinh, Joanne / Guella, Ilaria / Szu-Tu, Chelsea / Khinda, Jaskaran / Lin, Chin-Hsien / Wu, Ruey-Meei / Stoessl, Jon / Appel-Cresswell, Silke / McKeown, Martin / Rajput, Alex / Rajput, Ali H / Petersen, Maria Skaalum / Jeon, Beom S / Aasly, Jan O / Farrer, Matthew J

Parkinsonism & related disorders

2016 Volume 28, Page(s) 56–61

Abstract: ... in both cases and controls and the remaining nine in cases only. One of the variants, DCTN1 p.K56R, was present ... frontoparietal lobes. In HEK293 cells mutant p150(glued) (p.K56R) shows less affinity for microtubules than wild-type ... with a more diffuse cytoplasmic distribution.: Conclusions: We have identified DCTN1 p.K56R in patients ...

Abstract	Introduction: Mutations in dynactin DCTN1 (p150(glued)) have previously been linked to familial motor neuron disease or Perry syndrome (PS) consisting of depression, parkinsonism and hypoventilation. Methods: We sequenced DCTN1 in 636 Caucasian patients with parkinsonism (Parkinson's disease and Parkinson-plus syndromes) and 508 healthy controls. Variants (MAF < 0.01) were subsequently genotyped in Caucasian (1360 cases and 1009 controls) and Asian cohorts (1046 cases and 830 controls), and the functional implications of pathogenic variants were assessed. Results: We identified 17 rare variants leading to non-synonymous amino-acid substitutions. Four of the variants were only observed in control subjects, four in both cases and controls and the remaining nine in cases only. One of the variants, DCTN1 p.K56R, was present in two patients with progressive supranuclear palsy (PSP) with a shared minimal 2.2 Mb haplotype. Both subjects have parkinsonism as the most prominent symptom with abnormal ocular movements, moderate cognitive impairment and little to no l-dopa response. Neither subject presents with depression, central hypoventilation or weight loss. For one of the subjects MRI shows symmetrical atrophy of temporal and frontoparietal lobes. In HEK293 cells mutant p150(glued) (p.K56R) shows less affinity for microtubules than wild-type, with a more diffuse cytoplasmic distribution. Conclusions: We have identified DCTN1 p.K56R in patients with PSP. This variant is immediately adjacent to the N-terminal p150(glued) 'CAP-Gly' domain, affects a highly conserved amino acid and alters the protein's affinity to microtubules and its cytoplasmic distribution.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Dynactin Complex/genetics ; Female ; HEK293 Cells ; Humans ; Male ; Middle Aged ; Mutation ; Parkinson Disease/genetics ; Parkinsonian Disorders/genetics ; Phenotype ; Supranuclear Palsy, Progressive/genetics ; Supranuclear Palsy, Progressive/physiopathology ; Young Adult
Chemical Substances	DCTN1 protein, human ; Dynactin Complex
Language	English
Publishing date	2016-04-23
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.2016.04.025
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Zs.MO 420: Show issues

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Article ; Online: MHC class II-restricted presentation of the major house dust mite allergen Der p 1 Is GILT-dependent: implications for allergic asthma.

West, Laura Ciaccia / Grotzke, Jeff E / Cresswell, Peter

PloS one

2013 Volume 8, Issue 1, Page(s) e51343

Abstract: ... processing and presentation of immunodominant epitopes from the major house dust mite allergen Der p 1 ... In the absence of GILT, CD4-positive T cell responses to Der p 1 are significantly reduced, resulting ... in mitigated allergic airway inflammation in response to Der p 1 and house dust mite extracts in a murine model ...

Abstract	Gamma-interferon-inducible lysosomal thiol reductase (GILT) is known to reduce disulfide bonds present in proteins internalized by antigen presenting cells, facilitating optimal processing and presentation of peptides on Major Histocompatibility Complex class II molecules, as well as the subsequent activation of CD4-positive T lymphocytes. Here, we show that GILT is required for class II-restricted processing and presentation of immunodominant epitopes from the major house dust mite allergen Der p 1. In the absence of GILT, CD4-positive T cell responses to Der p 1 are significantly reduced, resulting in mitigated allergic airway inflammation in response to Der p 1 and house dust mite extracts in a murine model of asthma.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; Antigens, Dermatophagoides/immunology ; Arthropod Proteins/immunology ; Aspartic Acid Endopeptidases/immunology ; Asthma/immunology ; Bronchoalveolar Lavage Fluid/cytology ; Bronchoalveolar Lavage Fluid/immunology ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cell Proliferation ; Cells, Cultured ; Cockroaches/immunology ; Coculture Techniques ; Cysteine Endopeptidases/immunology ; Cytokines/genetics ; Cytokines/immunology ; Cytokines/metabolism ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Histocompatibility Antigens Class II/immunology ; Lung/immunology ; Lung/metabolism ; Lung/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidoreductases/genetics ; Oxidoreductases/immunology ; Oxidoreductases/metabolism ; Oxidoreductases Acting on Sulfur Group Donors ; Pyroglyphidae/immunology ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Antigens, Dermatophagoides ; Arthropod Proteins ; Cytokines ; Histocompatibility Antigens Class II ; Oxidoreductases (EC 1.-) ; Ifi30 protein, mouse (EC 1.8.-) ; Oxidoreductases Acting on Sulfur Group Donors (EC 1.8.-) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Dermatophagoides pteronyssinus antigen p 1 (EC 3.4.22.-) ; Aspartic Acid Endopeptidases (EC 3.4.23.-) ; allergen Bla g 2 (EC 3.4.23.-)
Language	English
Publishing date	2013-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0051343
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Article ; Online: Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease.

Mattijssen, Sandy / Hinson, Ella R / Onnekink, Carla / Hermanns, Pia / Zabel, Bernhard / Cresswell, Peter / Pruijn, Ger J M

Cellular and molecular life sciences : CMLS

2010 Volume 68, Issue 14, Page(s) 2469–2480

Abstract: ... we analyzed the effects of RNase MRP (and the structurally related RNase P) depletion on mRNAs using DNA ... this appeared to be independent of the interferon response. We detected two cleavage sites for RNase MRP/RNase P ... of a mRNA by RNase MRP/RNase P in human cells. Implications for the involvement in the pathophysiology ...

Abstract	RNase MRP is a conserved endoribonuclease, in humans consisting of a 267-nucleotide RNA associated with 7-10 proteins. Mutations in its RNA component lead to several autosomal recessive skeletal dysplasias, including cartilage-hair hypoplasia (CHH). Because the known substrates of mammalian RNase MRP, pre-ribosomal RNA, and RNA involved in mitochondrial DNA replication are not likely involved in CHH, we analyzed the effects of RNase MRP (and the structurally related RNase P) depletion on mRNAs using DNA microarrays. We confirmed the upregulation of the interferon-inducible viperin mRNA by RNAi experiments and this appeared to be independent of the interferon response. We detected two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. This is the first study providing direct evidence for the cleavage of a mRNA by RNase MRP/RNase P in human cells. Implications for the involvement in the pathophysiology of CHH are discussed.
MeSH term(s)	Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism ; Binding Sites/genetics ; Blotting, Northern ; Cell Line, Tumor ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Hair/abnormalities ; Hair/metabolism ; HeLa Cells ; Hirschsprung Disease/genetics ; Hirschsprung Disease/metabolism ; Humans ; Immunoblotting ; Immunologic Deficiency Syndromes/genetics ; Immunologic Deficiency Syndromes/metabolism ; Interferon-alpha/pharmacology ; Oligonucleotide Array Sequence Analysis ; Osteochondrodysplasias/congenital ; Osteochondrodysplasias/genetics ; Osteochondrodysplasias/metabolism ; Primary Immunodeficiency Diseases ; Proteins/genetics ; RNA Interference ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ribonuclease P/genetics ; Ribonuclease P/metabolism ; Ribonucleoproteins/genetics ; Ribonucleoproteins/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; Interferon-alpha ; POP1 protein, human ; Proteins ; RNA, Messenger ; Ribonucleoproteins ; RSAD2 protein, human (EC 1.3.-) ; Endoribonucleases (EC 3.1.-) ; mitochondrial RNA-processing endoribonuclease (EC 3.1.-) ; RPP40 protein, human (EC 3.1.26.5) ; Ribonuclease P (EC 3.1.26.5)
Language	English
Publishing date	2010-10-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-010-0568-3
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Zs.A 195: Show issues

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Article ; Online: Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism.

Appel-Cresswell, Silke / Rajput, Ali H / Sossi, Vesna / Thompson, Christina / Silva, Vanessa / McKenzie, Jessamyn / Dinelle, Katherine / McCormick, Siobhan E / Vilariño-Güell, Carles / Stoessl, A Jon / Dickson, Dennis W / Robinson, Chris A / Farrer, Matthew J / Rajput, Alex

Movement disorders : official journal of the Movement Disorder Society

2014 Volume 29, Issue 13, Page(s) 1684–1687

Abstract: ... have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and ... with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive ...

Abstract	Background: Families of Dutch-German-Russian Mennonite descent with multi-incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization. Methods: Family members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy. Results: Of the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40-85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology. Conclusion: PD associated with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical PD.
MeSH term(s)	Aged ; Aged, 80 and over ; Brain/diagnostic imaging ; Brain/drug effects ; Carbon Isotopes/pharmacokinetics ; Dopamine Agents/pharmacokinetics ; Family Health ; Fluorodeoxyglucose F18 ; Humans ; Levodopa/pharmacokinetics ; Middle Aged ; Molecular Chaperones/genetics ; Mutation/genetics ; Parkinsonian Disorders/diagnosis ; Parkinsonian Disorders/genetics ; Positron-Emission Tomography ; Tetrabenazine/analogs & derivatives ; Tetrabenazine/pharmacokinetics
Chemical Substances	Carbon Isotopes ; DNAJC13 protein, human ; Dopamine Agents ; Molecular Chaperones ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; dihydrotetrabenazine (3466-75-9) ; Levodopa (46627O600J) ; Tetrabenazine (Z9O08YRN8O)
Language	English
Publishing date	2014-09-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.26019
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Zs.A 2555: 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 238: Show issues

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Article ; Online: Nilabh Shastri (1952-2021).

Cresswell, Peter

Immunity

2021 Volume 54, Issue 3, Page(s) 389–390

MeSH term(s)	Allergy and Immunology/history ; Antigen Presentation ; Autoimmunity ; History, 20th Century ; History, 21st Century ; Humans ; Immunologic Surveillance ; India ; Male ; Neoplasms/immunology ; T-Lymphocytes/immunology ; United States
Language	English
Publishing date	2021-03-09
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article ; Portrait
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2021.02.006
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Zs.A 4227: 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 69: Show issues

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Article ; Online: Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease.

Appel-Cresswell, Silke / Vilarino-Guell, Carles / Encarnacion, Mary / Sherman, Holly / Yu, Irene / Shah, Brinda / Weir, David / Thompson, Christina / Szu-Tu, Chelsea / Trinh, Joanne / Aasly, Jan O / Rajput, Alex / Rajput, Ali H / Jon Stoessl, A / Farrer, Matthew J

Movement disorders : official journal of the Movement Disorder Society

2013 Volume 28, Issue 6, Page(s) 811–813

Abstract: Background: Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal- ... ...

Abstract	Background: Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal-dominantly inherited Parkinsonism. Methods: Here, we describe a novel missense mutation in exon 4 of SNCA encoding a H50Q substitution in a patient with dopa-responsive Parkinson's disease with a family history of parkinsonism and dementia. Results: The variant was not observed in public databases or identified in unrelated subjects. Conclusions: The substitution's evolutionary conservation and protein modeling provide additional support for pathogenicity as the amino acid perturbs the same amphipathic alpha helical structure as the previously described pathogenic mutations.
MeSH term(s)	Glutamine/genetics ; Histidine/genetics ; Humans ; Male ; Middle Aged ; Mutation/genetics ; Parkinson Disease/genetics ; Pedigree ; alpha-Synuclein/genetics
Chemical Substances	alpha-Synuclein ; Glutamine (0RH81L854J) ; Histidine (4QD397987E)
Language	English
Publishing date	2013-06
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.25421
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Zs.MO 238: Show issues

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Article ; Online: MHC class II-restricted presentation of the major house dust mite allergen Der p 1 Is GILT-dependent

Laura Ciaccia West / Jeff E Grotzke / Peter Cresswell

PLoS ONE, Vol 8, Iss 1, p e

implications for allergic asthma.

2013 Volume 51343

Abstract	Gamma-interferon-inducible lysosomal thiol reductase (GILT) is known to reduce disulfide bonds present in proteins internalized by antigen presenting cells, facilitating optimal processing and presentation of peptides on Major Histocompatibility Complex class II molecules, as well as the subsequent activation of CD4-positive T lymphocytes. Here, we show that GILT is required for class II-restricted processing and presentation of immunodominant epitopes from the major house dust mite allergen Der p 1. In the absence of GILT, CD4-positive T cell responses to Der p 1 are significantly reduced, resulting in mitigated allergic airway inflammation in response to Der p 1 and house dust mite extracts in a murine model of asthma.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: A personal retrospective on the mechanisms of antigen processing.

Cresswell, Peter

Immunogenetics

2019 Volume 71, Issue 3, Page(s) 141–160

Abstract: My intention here is to describe the history of the molecular aspects of the antigen processing field from a personal perspective, beginning with the early identification of the species that we now know as MHC class I and MHC class II molecules, to the ... ...

Abstract	My intention here is to describe the history of the molecular aspects of the antigen processing field from a personal perspective, beginning with the early identification of the species that we now know as MHC class I and MHC class II molecules, to the recognition that their stable surface expression and detection by T cells depends on peptide association, and to the unraveling of the biochemical and cell biological mechanisms that regulate peptide binding. One goal is to highlight the role that serendipity or, more colloquially, pure blind luck can play in advancing the research enterprise when it is combined with an appropriately receptive mind. This is not intended to be an overarching review, and because of my own work I focus primarily on studies of the human MHC. This means that I neglect the work of many other individuals who made advances in other species, particularly those who produced the many knockout mouse strains used to demonstrate the importance of the antigen processing machinery for initiating immune responses. I apologize in advance to colleagues around the globe whose contributions I deal with inadequately for these reasons, and to those whose foundational work is now firmly established in text books and therefore not cited. So many individuals have worked to advance the field that giving all of them the credit they deserve is almost impossible. I have attempted, while focusing on work from my own laboratory, to point out contemporaneous or sometimes earlier advances made by others. Much of the success of my own laboratory came because we simultaneously worked on both the MHC class I and class II systems and used the findings in one area to inform the other, but mainly it depended on the extraordinary group of students and fellows who have worked on these projects over the years. To those who worked in other areas who are not mentioned here, rest assured that I appreciate your efforts just as much.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Humans ; Major Histocompatibility Complex/immunology ; Molecular Chaperones/immunology ; T-Lymphocytes/immunology
Chemical Substances	Molecular Chaperones
Language	English
Publishing date	2019-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	186560-2
ISSN	1432-1211 ; 0093-7711
ISSN (online)	1432-1211
ISSN	0093-7711
DOI	10.1007/s00251-018-01098-2
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Article ; Online: Interprofessional research teams in radiography - where the magic happens.

Hogg, P / Cresswell, J

Radiography (London, England : 1995)

2021 Volume 27 Suppl 1, Page(s) S9–S13

Abstract: Based on publications and professional experiences, this article, intended for academic and clinical therapy/diagnostic radiographers, considers conducting research in interprofessional teams, including its values and how to go about achieving it. Whilst ...

Abstract	Based on publications and professional experiences, this article, intended for academic and clinical therapy/diagnostic radiographers, considers conducting research in interprofessional teams, including its values and how to go about achieving it. Whilst there is a growing number of journal papers published by interprofessional teams, almost nothing is published about how best to build interprofessional research relationships or harness the potential of the different professional experience to deliver novel research within the radiography literature. Thus, this article draws heavily on our experiences of creating, working within and leading interprofessional teams which have a specific focus on conducting radiography-related research. Suggestions are proposed about how to create an interprofessional research team and how to get the best out of it. Values of working within an interprofessional research team, to self, to research quality and to the end users of the research are considered.
MeSH term(s)	Allied Health Personnel ; Humans ; Interprofessional Relations ; Patient Care Team ; Radiography
Language	English
Publishing date	2021-06-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1289102-2
ISSN	1532-2831 ; 1078-8174
ISSN (online)	1532-2831
ISSN	1078-8174
DOI	10.1016/j.radi.2021.05.005
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Article: Effects of increased deposition of atmospheric nitrogen on an upland Calluna moor: N and P transformations.

Pilkington, M G / Caporn, S J M / Carroll, J A / Cresswell, N / Lee, J A / Emmett, B A / Johnson, D

Environmental pollution (Barking, Essex : 1987)

2005 Volume 135, Issue 3, Page(s) 469–480

Abstract: This study determined the effects of increased N deposition on rates of N and P transformations ...

Abstract	This study determined the effects of increased N deposition on rates of N and P transformations in an upland moor. The litter layer and the surface of the organic Oh horizon were taken from plots that had received long-term additions of ammonium nitrate at rates of 40, 80 and 120 kg N ha(-1) yr(-1). Net mineralisation processes were measured in both field and laboratory incubations. Soil phosphomonoesterase (PME) activity and rates of N(2)O release were measured in laboratory incubations and root-surface PME activity measured in laboratory microcosms using Calluna vulgaris bioassay seedlings. Net mineralisation rates were relatively slow, with net ammonification consistently stimulated by N addition. Net nitrification was marginally stimulated by N addition in the laboratory incubation. N additions also increased soil and root-surface (PME) activity and rates of N(2)O release. Linear correlations were found between litter C:N ratio and all the above processes except net nitrification in field incubations. When compared with data from a survey of European forest sites, values of litter C:N ratio were greater than a threshold below which substantial, N input-related increases in net nitrification rates occurred. The maintenance of high C:N ratios with negligible rates of net nitrification was associated with the common presence of ericaceous litter and a mor humus layer in both this moorland as well as the forest sites.
MeSH term(s)	Air Pollutants/analysis ; Atmosphere ; Calluna/chemistry ; Climate ; Ecosystem ; Environmental Monitoring/methods ; Minerals ; Nitrogen/analysis ; Nitrogen/chemistry ; Nitrous Oxide/chemistry ; Phosphoric Monoester Hydrolases/chemistry ; Phosphorus/chemistry ; Soil ; Soil Pollutants/analysis ; Wales
Chemical Substances	Air Pollutants ; Minerals ; Soil ; Soil Pollutants ; Phosphorus (27YLU75U4W) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; Nitrous Oxide (K50XQU1029) ; Nitrogen (N762921K75)
Language	English
Publishing date	2005-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280652-6
ISSN	1873-6424 ; 0269-7491 ; 0013-9327
ISSN (online)	1873-6424
ISSN	0269-7491 ; 0013-9327
DOI	10.1016/j.envpol.2004.11.022
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