Maria Daly - Academia.edu (original) (raw)

Papers by Maria Daly

The Journal of Immunology

The Cell Lab Quanta® SC analyzer, a unique platform with two excitation light sources; a 488 nm d... more The Cell Lab Quanta® SC analyzer, a unique platform with two excitation light sources; a 488 nm diode laser and a HBO arc lamp, can simultaneously measure Electronic Volume (EV), side scatter (SS) and three color fluorescence. This system has an innovative multiplate loader (MPL), which can undertake automatic sample preparation and high throughput analysis. We have used this instrument to analyze cells from various murine tissues with the objective to describe and identify changes in cellular volume and morphological complexity during development, activation and differentiation. Immunophenotypic analysis of cells isolated from bone marrow, peripheral blood, spleen, thymus and lymph nodes of C57 BL/6 mice was done with conventional combinations of MABs conjugated with FITC, PE and PE cy-5. The MPL was used for sample preparation in 96 well plates. EV, which is not used at present as a relevant parameter in flow cytometry, is a more precise measure of cell size than the conventional ...

Innate immunity provides the first line of defence against invading pathogens and provides import... more Innate immunity provides the first line of defence against invading pathogens and provides important cues for the development of adaptive immunity. Type-2 immunity-responsible for protective immune responses to helminth parasites1,2 and the underlying cause of the pathogenesis of allergic asthma3,4-consists of responses dominated by the cardinal type-2 cytokines interleukin (IL)-4, IL-5 and IL-13 (ref. 5). T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively elucidated. Here, through the use of novel Il13eGFP reporter mice, we present the identification and functional characterisation of a new innate type-2 immune effector leukocyte that we have named the nuocyte. Nuocytes expand in vivo in response to the type 2-inducing cytokines IL-25 and IL-33, and represent the predominant early source of IL-13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL-25 and IL-33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wildtype, but not IL-13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity. Type-2 immunity evolved to respond to parasitic helminth infections, with type-2 cytokines orchestrating eosinophilia, goblet cell hyperplasia, mucus secretion, and IgE production5-7. These highly complex host responses involve the coordination of innate and adaptive immune cell types. Of the defined innate immune cells, basophils, eosinophils and mast cells are known sources of type-2 cytokines, but it is not clear that they are essential for N. brasiliensis expulsion5,8-12. To identify new cell types that may mediate type-2 immunity we investigated the cellular sources of IL-13, a critical cytokine in the host response to helminth infection7,13 and allergy6,14. To allow live imaging of enhanced green fluorescent protein (eGFP) as a surrogate for IL-13 gene expression during the induction of type-2 responses we generated Il13eGFP mice (Supplementary Fig. 1).

Research article Factors associated with utilization of traditional Chinese medicine by white col... more Research article Factors associated with utilization of traditional Chinese medicine by white collar foreign workers living in Taiwan

Clinical and Translational Science, 2021

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc... more This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Applied Health Economics and Health Policy, 2020

Background The lidocaine 5% medicated plaster, Versatis ® , has one therapeutic indication listed... more Background The lidocaine 5% medicated plaster, Versatis ® , has one therapeutic indication listed on the Summary of Product Characteristics-symptomatic relief of post-herpetic neuralgia (PHN) in adults. Increased expenditure on Versatis ® suggests that there is considerable off-label use. To support the appropriate use of Versatis ® , the Health Service Executive's Primary Care Reimbursement Service (PCRS) introduced a reimbursement application system for Versatis ® from 1 September 2017. Objective The aim of this study was to investigate the effect of introducing a reimbursement application system on Versatis ® prescribing under the General Medical Services (GMS) scheme. Methods This study was carried out using prescription dispensing data from the PCRS pharmacy claims database. We carried out segmented linear regression to assess changes in the Versatis ® prescribing rate per 1000 GMS eligible population, before and after the introduction of the online reimbursement application system. Results The results of the segmented regression analysis show that there was a statistically significant level (− 4.91, p < 0.001) and trend change (− 0.69, p < 0.001) in the rate of Versatis ® prescribing post-introduction of the reimbursement application system. In the year prior to the introduction of the system, 2016, the annual GMS expenditure on Versatis ® lidocaine 5% patches was over €27 million, whereas the GMS expenditure in 2018 was reduced to just over €2 million. Conclusion In our study, a substantial decrease in the dispensing of Versatis ® was seen after the implementation of a reimbursement application system. Prescribing of Versatis ® should be restricted to patients with a diagnosis of PHN not only to reduce costs, but to ensure evidence-based use of this medication.

Blood, 1992

Since the translocation breakpoint t(15;17) (q22;q21) in acute promyelocytic leukemia (APL) occur... more Since the translocation breakpoint t(15;17) (q22;q21) in acute promyelocytic leukemia (APL) occurs within the retinoic acid receptor- alpha (RARA) gene, the expression of many genes normally regulated by RARA may be affected by this translocation. To identify genes that may be aberrantly expressed in APL, a subtraction cDNA library of an APL patient with t(15;17) was constructed. A cDNA, pRD1, specifically expressed in APL was identified. DNA sequence analysis of pRD1 showed that this gene is similar to the DNA sequence of annexin VIII, a gene which encodes a vascular anticoagulant. The annexin VIII gene was assigned to chromosome 10, which indicates that specific expression of this gene in APL is not directly involved in the t(15;17) breakpoint region. We have analyzed the expression of annexin VIII gene in nine t(15;17)-positive APL patients and one APL patient with a chromosome 17q-abnormality. We found that all APL samples expressed high levels of the annexin VIII gene. Expressi...

Database, 2016

Human cryptosporidiosis, caused primarily by Cryptosporidium hominis and a subset of Cryptosporid... more Human cryptosporidiosis, caused primarily by Cryptosporidium hominis and a subset of Cryptosporidium parvum, is a major cause of moderate-to-severe diarrhea in children under 5 years of age in developing countries and can lead to nutritional stunting and death. Cryptosporidiosis is particularly severe and potentially lethal in immunocompromised hosts. Biological and technical challenges have impeded traditional vaccinology approaches to identify novel targets for the development of vaccines against C. hominis, the predominant species associated with human disease. We deemed that the existence of genomic resources for multiple species in the genus, including a muchimproved genome assembly and annotation for C. hominis, makes a reverse vaccinology approach feasible. To this end, we sought to generate a searchable online resource, termed C. hominis gene catalog, which registers all C. hominis genes and their properties relevant for the identification and prioritization of candidate vaccine antigens, including physical attributes, properties related to antigenic potential and expression data.

Methods in molecular biology (Clifton, N.J.), 2016

Overexpression of mammalian membrane proteins in mammalian cells is an effective strategy to prod... more Overexpression of mammalian membrane proteins in mammalian cells is an effective strategy to produce sufficient protein for biophysical analyses and structural studies, because the cells generally express proteins in a correctly folded state. However, obtaining high levels of expression suitable for protein purification on a milligram scale can be challenging. As membrane protein overexpression often has a negative impact on cell viability, it is usual to make stable cell lines where the protein of interest is expressed from an inducible promoter. Here we describe a methodology for optimizing the inducible production of any membrane protein fused to GFP through the isolation of clonal cell lines. Flow cytometry is used to sort uninduced cells and the most fluorescent 5 % of the cell population are used to make clonal cell lines.

Biochemical Journal, 1997

Cytokine-induced expression of the endothelial cell surface adhesion molecule E-selectin is inhib... more Cytokine-induced expression of the endothelial cell surface adhesion molecule E-selectin is inhibited by glucocorticoids (GCs). To investigate possible mechanisms for steroid inhibition, a reporter gene (ESAP) was constructed, comprising the cytokine responsive region of the E-selectin gene (nt -383 to +81) coupled to alkaline phosphatase (AP). In A549 cells stably transfected with the ESAP gene, AP production was highly responsive to the cytokines interleukin 1β (IL-1β) and tumour necrosis factor α, with ED50 values of 3 pM and 1000 pM respectively. Furthermore the cytokine-induced AP responses were inhibited by GCs, indicating that both transcriptional activation and GC suppression of the E-selectin gene were mediated via regulatory elements within the same region of the promoter. The relative potencies of GC drugs as inhibitors of IL-1β (10 pM)-stimulated ESAP-gene activation were fluticasone > beclomethasone > dexamethasone, with IC50 values of 0.13, 1.1 and 2.7 nM respect...

Nature, 2012

Haematopoietic stem cells (HSCs) regenerate blood cells throughout the lifespan of an organism. W... more Haematopoietic stem cells (HSCs) regenerate blood cells throughout the lifespan of an organism. With age, the functional quality of HSCs declines, partly owing to the accumulation of damaged DNA. However, the factors that damage DNA and the protective mechanisms that operate in these cells are poorly understood. We have recently shown that the Fanconi anaemia DNA-repair pathway counteracts the genotoxic effects of reactive aldehydes. Mice with combined inactivation of aldehyde catabolism (through Aldh2 knockout) and the Fanconi anaemia DNA-repair pathway (Fancd2 knockout) display developmental defects, a predisposition to leukaemia, and are susceptible to the toxic effects of ethanol-an exogenous source of acetaldehyde. Here we report that aged Aldh2(-/-) Fancd2(-/-) mutant mice that do not develop leukaemia spontaneously develop aplastic anaemia, with the concomitant accumulation of damaged DNA within the haematopoietic stem and progenitor cell (HSPC) pool. Unexpectedly, we find that only HSPCs, and not more mature blood precursors, require Aldh2 for protection against acetaldehyde toxicity. Additionally, the aldehyde-oxidizing activity of HSPCs, as measured by Aldefluor stain, is due to Aldh2 and correlates with this protection. Finally, there is more than a 600-fold reduction in the HSC pool of mice deficient in both Fanconi anaemia pathway-mediated DNA repair and acetaldehyde detoxification. Therefore, the emergence of bone marrow failure in Fanconi anaemia is probably due to aldehyde-mediated genotoxicity restricted to the HSPC pool. These findings identify a new link between endogenous reactive metabolites and DNA damage in HSCs, and define the protective mechanisms that counteract this threat.

ATIENTS WITH acute promyelocytic leukemia (APL) P demonstrate a clonal proliferation of abnormal ... more ATIENTS WITH acute promyelocytic leukemia (APL) P demonstrate a clonal proliferation of abnormal promy- elocytes, and in virtually all instances the leukemic cells contain the nonrandom chromosomal translocation break- point t( 15;17) (q22;q21).' Chemotherapy can induce remis- sion in 60% to 80% of APL patients, and 40% to 50% of those who achieve remission are long-term survivors. Most patients with APL demonstrate bleeding, with clinical and laboratory findings of diffuse intravascular coagulation; 14% to 26% eventually die of hemorrhage.' It has been demonstrated that the t( 15;17) breakpoint occurs between the retinoic acid receptor-a (RAM) and the my1 (or PML) gene^.^.^ Hybrid mRNA species transcribed from the t(15; 17) breakpoint have been detected, suggesting that a fusion protein may be produced as a result of the translocation. Recently, the cDNA of the fusion transcripts my11 and the RARA/myllo have been cloned and charac- terized. Evidence suggests that the mylI...

The Journal of Organic Chemistry, 1961

6-Methylamino-Q-(tetrahydro-%furyl)prine. 6-Chloro-9-(tetrahydro-2-fury1)purine (I) (1.5 g.) was ... more 6-Methylamino-Q-(tetrahydro-%furyl)prine. 6-Chloro-9-(tetrahydro-2-fury1)purine (I) (1.5 g.) was added to 75 ml. of 40% aqueous methylamine and the solution heated on a steam bath for 1 hr. The solution was then reduced to an oil under vacuum and the syrupy residue recrystallized from a mixture of petroleum ether (b.p. 60-110") and ethyl acetate to yield 0.9 g. of white crystals, m.p. 103-104".

Journal of Medicinal Chemistry, 1963

(16) Also, when ammonia was used in ethanol at 1.50-160" for 4 hr.. the product was 4-amino-... more (16) Also, when ammonia was used in ethanol at 1.50-160" for 4 hr.. the product was 4-amino-6-chloro-m-benzenedisulfonamide. difficult concerning their relative reactivities. The reaction with aninionia in ethanol for 3 hr. at 100 gave, as the only iiisolable product, a ...

Genomics, 1996

Small cell lung cancer (SCLC) has been correlated al., 1987). The peak of this loss is at the loc... more Small cell lung cancer (SCLC) has been correlated al., 1987). The peak of this loss is at the locus D3F15S2 with a deletion in the short arm of chromosome 3, with located at 3p21.3 (Johnson et al., 1988). Although there the region 3p21 being lost from one homolog in almost are other regions on chromosome 3 that show nonranall cases. Two SCLC cell lines have homozygous deledom loss in lung cancer (Hibi et al., 1992), the 3p21.3 tions in 3p21, and these deletions overlap with a fragregion is deleted in nearly 100% of SCLC cases. In ment of chromosome 3 that has tumor suppression acaddition, we have found that a fragment of chromosome tivity in vivo. We have isolated some cDNA clones from 3 encompassing part of this region can suppress tumor this region that are homologous to the genes constitutformation by mouse A9 cells in nude mice (Killary et ing the semaphorin family. They represent a novel hual., 1992). Using Alu/PCR products from the fragment man semaphorin, termed sema III/F (HGMW-approved of 3p that suppresses A9 cells, we designed primers symbol SEMA3F), which is expressed as a 3.8-kb tranand identified a region that was homozygously deleted script in a variety of cell lines and tissues; it is detected in two SCLC lines (Daly et al., 1993; Kok et al., 1994). as early as Embryonic Day 10 in mouse development. A P1 contig of the region was constructed, and cDNA There is high expression in mammary gland, kidney, clones for the region common to the homozygous delefetal brain, and lung and lower expression in heart tions and the fragment of 3p21.3 that suppressed tuand liver. Although there is reduced expression of this mor formation were isolated. One of the cDNAs isolated gene in several SCLC lines, no mutations were found. is a homolog of the semaphorin gene family. This semaphorin homolog has characteristics of a secreted member of the semaphorin III family, with 52% The semaphorins are a family of proteins that are identity with mouse semaphorin E and 49% identity involved in signaling. All the family members have a with chicken collapsin/semaphorin D. ᭧ 1996 Academic secretion signal, a 500-amino-acid sema domain, and Press, Inc. 16 conserved cysteine residues (Kolodkin et al., 1993). The proteins can have a transmembrane region such as grasshopper (Kolodkin et al., 1992), Tribolium (Ko

Genes, Chromosomes and Cancer, 1989

DNA was prepared from tumour and normal tissue from 48 patients representing all common histologi... more DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall-cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13-14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall-cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13-14----3pter.

European Journal of Immunology, 2000

We have identified a novel Kruppel-type zinc finger (ZF) gene, SKAT-2, which is selectively expre... more We have identified a novel Kruppel-type zinc finger (ZF) gene, SKAT-2, which is selectively expressed by murine Th2 cells. The protein encoded by this gene has 14 C2H2-type ZF tandemly arrayed at its C terminus and N-terminal SCAN box and KRAB domains. SKAT-2 is tissue restricted in expression at the RNA level, detectable only in brain and at low levels in kidney and spleen and few hematopoietic cell lines. By in situ hybridization, SKAT-2 expression was found to peak in antigen-stimulated CD4 + T cells after 2-3 days of culture under Th2 but not Th1 biasing conditions. This pattern of expression closely mirrored that of GATA-3 in the same cells. In transient transfection experiments in phorbol 12-myristate 13-acetate/ ionomycin-stimulated EL4 cells, SKAT-2 was found to up-regulate the activity of the IL-4 but not the IL-5 promoter, contrasting with the ability of GATA-3 to activate both promoters. This result was confirmed using clones of EL4 cells stably expressing an inducible form of SKAT-2, thus SKAT-2 is a novel Th2-specific gene that may play a role in selective regulation of cytokine genes in T cells.

Cancer Research, 2010

Esophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the ge... more Esophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the genetic underpinnings of this disease remains limited. In this study, we identified the tetraspanin cell surface receptor uroplakin 1A (UPK1A) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. UPK1A downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (P < 0.05). Ectopic expression of UPK1A in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation in nude mice. Mechanistic investigations suggested that these effects may be mediated by inhibiting nuclear translocation of β-catenin and inactivation of its downstream targets, including cyclin-D1, c-jun, c-myc, and matrix metalloproteinase 7 (MMP7). Cell cycle arrest elicited by UPK1A at the G1-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent ki...

Cancer Genetics and Cytogenetics, 1994