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Article ; Online: Ex vivo quantification of lanthanum and gadolinium in post-mortem human tibiae with estimated barium and iodine concentrations using K x-ray fluorescence.

Nguyen, Joanna / Crawford, Daniel / Howarth, David / Sukhu, Balram / Pejović-Milić, Ana / Gräfe, James L

2019 Volume 40, Issue 8, Page(s) 85006

Abstract: Objectives: Lanthanum (La) and gadolinium (Gd) are known to deposit in bone of exposed populations, namely those who are orally administered lanthanum carbonate (LaC, La: Approach: Two calibration lines were produced for La and Gd and the minimum ... ...

Abstract	Objectives: Lanthanum (La) and gadolinium (Gd) are known to deposit in bone of exposed populations, namely those who are orally administered lanthanum carbonate (LaC, La Approach: Two calibration lines were produced for La and Gd and the minimum detection limits (MDLs) of the system were determined using a 180° irradiation-detection geometry. Main results: The MDLs of the system were 0.4 µg La g Significance: The XRF system has determined baseline concentrations of these four heavy metals in trace quantities from natural exposure pathways (with the exception of iodine in four donors). This indicates that the system can measure low levels in ex vivo tibiae samples and can potentially be further developed for in vivo studies involving live subjects who are directly exposed to these metals.
MeSH term(s)	Autopsy ; Barium/analysis ; Gadolinium/analysis ; Humans ; Iodine/analysis ; Lanthanum/analysis ; Limit of Detection ; Monte Carlo Method ; Phantoms, Imaging ; Spectrometry, X-Ray Emission ; Tibia/chemistry
Chemical Substances	Barium (24GP945V5T) ; Lanthanum (6I3K30563S) ; Iodine (9679TC07X4) ; Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2019-09-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1149545-5
ISSN	1361-6579 ; 0967-3334
ISSN (online)	1361-6579
ISSN	0967-3334
DOI	10.1088/1361-6579/ab3c0e
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Article ; Online: Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells).

Howarth, Joanna L / Lee, Youn Bok / Uney, James B

Cell biology and toxicology

2009 Volume 26, Issue 1, Page(s) 1–20

Abstract: In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary ... ...

Abstract	In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described.
MeSH term(s)	Animals ; Cell Line ; Cells, Cultured ; Enhancer Elements, Genetic ; Gene Expression ; Gene Expression Regulation ; Gene Transfer Techniques ; Genes ; Genetic Vectors ; Humans ; Mitosis ; Models, Animal ; Promoter Regions, Genetic ; Regulatory Sequences, Ribonucleic Acid ; Virion/genetics ; Viruses
Chemical Substances	Regulatory Sequences, Ribonucleic Acid
Language	English
Publishing date	2009-10-15
Publishing country	Netherlands
Document type	Introductory Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	48824-0
ISSN	1573-6822 ; 0742-2091
ISSN (online)	1573-6822
ISSN	0742-2091
DOI	10.1007/s10565-009-9139-5
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Article ; Online: HSP70 interacting protein prevents the accumulation of inclusions in polyglutamine disease.

Howarth, Joanna L / Glover, Colin P J / Uney, James B

Journal of neurochemistry

2008 Volume 108, Issue 4, Page(s) 945–951

Abstract: Heat shock proteins (HSPs) are associated with the proteinaceous inclusions that characterise many neurodegenerative diseases. This suggests they may be associated with disease aetiology and/or represents an attempt to remove abnormal protein aggregates. ...

Abstract	Heat shock proteins (HSPs) are associated with the proteinaceous inclusions that characterise many neurodegenerative diseases. This suggests they may be associated with disease aetiology and/or represents an attempt to remove abnormal protein aggregates. In this study the adenoviral mediated over-expression of HSP70 interacting protein (HIP) alone was shown to significantly reduce inclusion formation in both an in vitro model of Spinal Bulbar Muscular Atrophy and a primary neuronal model of polyglutamine disease. Experiments to determine the mechanism of action showed that: denatured luciferase activity (a measure of protein refolding) was not increased in the presence of HIP alone but was increased when HIP was co-expressed with HSP70 or Heat Shock cognate protein 70 (HSC70); the expression of polyglutamine inclusions in cortical neurons mediated an increase in the levels of HSC70 but not HSP70. Our data suggest that HIP may prevent inclusion formation by facilitating the constitutive HSC70 refolding cycle and possibly by preventing aggregation. HIP expression is not increased following stress and its over-expression may therefore reduce toxic polyglutamine aggregation events and contribute to an effective therapeutic strategy.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Animals ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Cells, Cultured ; Genetic Predisposition to Disease/genetics ; Genetic Vectors ; HSC70 Heat-Shock Proteins/metabolism ; HSP72 Heat-Shock Proteins/metabolism ; Heredodegenerative Disorders, Nervous System/genetics ; Heredodegenerative Disorders, Nervous System/metabolism ; Heredodegenerative Disorders, Nervous System/physiopathology ; Humans ; Inclusion Bodies/genetics ; Inclusion Bodies/metabolism ; Inclusion Bodies/pathology ; Mice ; Models, Biological ; Muscular Atrophy, Spinal/genetics ; Muscular Atrophy, Spinal/metabolism ; Muscular Atrophy, Spinal/physiopathology ; Neurons/metabolism ; Neurons/pathology ; Peptides/genetics ; Peptides/metabolism ; Protein Folding ; Rats ; Rats, Wistar ; Transfection
Chemical Substances	Adaptor Proteins, Signal Transducing ; Carrier Proteins ; HSC70 Heat-Shock Proteins ; HSP72 Heat-Shock Proteins ; HSPBP1 protein, human ; Hspa8 protein, mouse ; Peptides ; polyglutamine (26700-71-0)
Language	English
Publishing date	2008-08-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.0022-3042.2008.05847.x
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Article ; Online: Cue competition effects in the planarian.

Prados, Jose / Alvarez, Beatriz / Howarth, Joanna / Stewart, Katharine / Gibson, Claire L / Hutchinson, Claire V / Young, Andrew M J / Davidson, Colin

Animal cognition

2013 Volume 16, Issue 2, Page(s) 177–186

Abstract: The learning abilities of planarian worms (Dugesia tigrina) were assessed by using a number of Pavlovian conditioning paradigms. Experiment 1 showed that planaria were susceptible to basic conditioning in that they readily developed a conditioned ... ...

Abstract	The learning abilities of planarian worms (Dugesia tigrina) were assessed by using a number of Pavlovian conditioning paradigms. Experiment 1 showed that planaria were susceptible to basic conditioning in that they readily developed a conditioned response to a change in ambient luminance when it was consistently paired with an electric shock over a number of trials. In Experiment 2, the change in luminance was presented in a compound with a vibration stimulus during conditioning. Subsequent tests revealed poor conditioning of the elements compared with control groups in which the animals were conditioned in the presence of the elements alone, an instance of overshadowing. In Experiment 3, pre-training of one of the elements before compound conditioning resulted in blocking of learning about the other element. These results add to other studies that have reported cue competition effects in animal species belonging to different phyla (chordate, mollusk, arthropod), suggesting that learning in these phyla could be ruled by similar principles. The results are discussed adopting an evolutionary-comparative approach.
MeSH term(s)	Animals ; Conditioning, Classical ; Cues ; Electroshock ; Photic Stimulation ; Planarians
Language	English
Publishing date	2013-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1466332-6
ISSN	1435-9456 ; 1435-9448
ISSN (online)	1435-9456
ISSN	1435-9448
DOI	10.1007/s10071-012-0561-3
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Article: Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

Howarth, Joanna L / Lee, Youn Bok / Uney, James B

Cell biology and toxicology. 2010 Feb., v. 26, no. 1

2010

Abstract	In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described.
Language	English
Dates of publication	2010-02
Size	p. 1-20.
Publisher	Springer Netherlands
Publishing place	Dordrecht
Document type	Article
ZDB-ID	48824-0
ISSN	1573-6822 ; 0742-2091
ISSN (online)	1573-6822
ISSN	0742-2091
DOI	10.1007/s10565-009-9139-5
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Article: HSP70 interacting protein prevents the accumulation of inclusions in polyglutamine disease

Howarth, Joanna L / Glover, Colin P.J / Uney, James B

Journal of neurochemistry. 2009 Feb., v. 108, no. 4

2009

Abstract	Heat shock proteins (HSPs) are associated with the proteinaceous inclusions that characterise many neurodegenerative diseases. This suggests they may be associated with disease aetiology and/or represents an attempt to remove abnormal protein aggregates. In this study the adenoviral mediated over-expression of HSP70 interacting protein (HIP) alone was shown to significantly reduce inclusion formation in both an in vitro model of Spinal Bulbar Muscular Atrophy and a primary neuronal model of polyglutamine disease. Experiments to determine the mechanism of action showed that: denatured luciferase activity (a measure of protein refolding) was not increased in the presence of HIP alone but was increased when HIP was co-expressed with HSP70 or Heat Shock cognate protein 70 (HSC70); the expression of polyglutamine inclusions in cortical neurons mediated an increase in the levels of HSC70 but not HSP70. Our data suggest that HIP may prevent inclusion formation by facilitating the constitutive HSC70 refolding cycle and possibly by preventing aggregation. HIP expression is not increased following stress and its over-expression may therefore reduce toxic polyglutamine aggregation events and contribute to an effective therapeutic strategy.
Language	English
Dates of publication	2009-02
Size	p. 945-951.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2008.05847.x
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Article ; Online: Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic, Omalizumab, in Severe Asthma in Adults: Results of the SoMOSA Study.

Djukanović, Ratko / Brinkman, Paul / Kolmert, Johan / Gomez, Cristina / Schofield, James / Brandsma, Joost / Shapanis, Andy / Skipp, Paul J S / Postle, Anthony / Wheelock, Craig / Dahlén, Sven-Erik / Sterk, Peter J / Brown, Thomas / Jackson, David J / Mansur, Adel / Pavord, Ian / Patel, Mitesh / Brightling, Christopher / Siddiqui, Salman /

American journal of respiratory and critical care medicine

2024

Abstract: Background: The anti-IgE monoclonal, omalizumab, is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during one year of omalizumab treatment.: Methods: 1-year, open-label, : Results: 191 ... ...

Abstract	Background: The anti-IgE monoclonal, omalizumab, is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during one year of omalizumab treatment. Methods: 1-year, open-label, Results: 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ≥50%, while 57% (37/65) on mOCS reduced their dose by ≥50%. The primary outcome 2, 3-dinor-11-β-PGF2α, GETE and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five breathomics (GC-MS) and 5 plasma lipid biomarkers strongly predicted the ≥50% reduction in exacerbations (receiver operating characteristic area under the curve (AUC): 0.780 and 0.922, respectively) and early responses (AUC:0.835 and 0.949, respectively). In independent cohorts, the GC-MS biomarkers differentiated between severe and mild asthma. Conclusions This is the first discovery of omics biomarkers that predict improvement to a biologic for asthma. Their prospective validation and development for clinical use is justified. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202310-1730OC
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Article: Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA

Clinical and translational allergy

2017 Volume 7, Page(s) 3

Abstract: Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases.: Objective: We investigated the ... ...

Abstract	Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (β-coefficient -2.34; 95% confidence interval [CI] -4.09, -0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
Language	English
Publishing date	2017-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2630865-4
ISSN	2045-7022
ISSN	2045-7022
DOI	10.1186/s13601-016-0140-9
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Article ; Online: MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex.

Scott, Helen L / Tamagnini, Francesco / Narduzzo, Katherine E / Howarth, Joanna L / Lee, Youn-Bok / Wong, Liang-Fong / Brown, Malcolm W / Warburton, Elizabeth C / Bashir, Zafar I / Uney, James B

The European journal of neuroscience

2012 Volume 36, Issue 7, Page(s) 2941–2948

Abstract: Evidence suggests that the acquisition of recognition memory depends upon CREB-dependent long-lasting changes in synaptic plasticity in the perirhinal cortex.The CREB-responsive microRNA miR-132 has been shown to regulate synaptic transmission and we set ...

Abstract	Evidence suggests that the acquisition of recognition memory depends upon CREB-dependent long-lasting changes in synaptic plasticity in the perirhinal cortex.The CREB-responsive microRNA miR-132 has been shown to regulate synaptic transmission and we set out to investigate a role for this microRNA in recognition memory and its underlying plasticity mechanisms. To this end we mediated the specific overexpression of miR-132 selectively in the rat perirhinal cortex and demonstrated impairment in short-term recognition memory. This functional deficit was associated with a reduction in both long-term depression and long-term potentiation. These results confirm that microRNAs are key coordinators of the intracellular pathways that mediate experience-dependent changes in the brain. In addition, these results demonstrate a role for miR-132 in the neuronal mechanisms underlying the formation of short-term recognition memory.
MeSH term(s)	Animals ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiology ; Excitatory Postsynaptic Potentials ; Gene Expression Regulation ; HeLa Cells ; Humans ; Long-Term Potentiation/genetics ; Long-Term Potentiation/physiology ; Long-Term Synaptic Depression/physiology ; Male ; Memory, Short-Term/physiology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Rats ; Rats, Wistar ; Recognition, Psychology/physiology
Chemical Substances	MIRN132 microRNA, rat ; MicroRNAs
Language	English
Publishing date	2012-07-30
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/j.1460-9568.2012.08220.x
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Article ; Online: MiR-3120 is a mirror microRNA that targets heat shock cognate protein 70 and auxilin messenger RNAs and regulates clathrin vesicle uncoating.

Scott, Helen / Howarth, Joanna / Lee, Youn Bok / Wong, Liang-Fong / Bantounas, Ioannis / Phylactou, Leonidas / Verkade, Paul / Uney, James B

The Journal of biological chemistry

2012 Volume 287, Issue 18, Page(s) 14726–14733

Abstract: We show that a single gene locus gives rise to two fully processed and functional miRNAs, i.e. that due to imperfect base pairing, two distinct microRNAs (miRNAs) can be produced from the fully complementary DNA strands. The antisense strand encodes miR- ... ...

Abstract	We show that a single gene locus gives rise to two fully processed and functional miRNAs, i.e. that due to imperfect base pairing, two distinct microRNAs (miRNAs) can be produced from the fully complementary DNA strands. The antisense strand encodes miR-214, which is transcribed by its own promoter, whereas a novel miRNA, miR-3120, is co-expressed with its host gene mRNA. We also found that miR-3120 regulates important aspects of cellular function that are similar to that of its host gene, dynamin-3. miR-3120 was found to be located in neuronal cell bodies and to target Hsc70 and auxilin, and its lentivirus-mediated expression inhibited the uncoating of clathrin-coated vesicles. Finally, mirror miRNAs are likely to represent a new group of miRNAs with complex roles in coordinating gene expression.
MeSH term(s)	Animals ; Auxilins/biosynthesis ; Auxilins/genetics ; Clathrin-Coated Vesicles/genetics ; Clathrin-Coated Vesicles/metabolism ; Dynamin III/biosynthesis ; Dynamin III/genetics ; Gene Expression Regulation/physiology ; HSP70 Heat-Shock Proteins/biosynthesis ; HSP70 Heat-Shock Proteins/genetics ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; Neurons/cytology ; Neurons/metabolism ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Rats ; Rats, Wistar
Chemical Substances	Auxilins ; HSP70 Heat-Shock Proteins ; MicroRNAs ; RNA, Messenger ; Dynamin III (EC 3.6.5.5)
Language	English
Publishing date	2012-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M111.326041
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