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M J Higgins

Publications and source records attributed to M J Higgins.

At least 19 recordsLinked to original sources
PubMed2005

Percolation transition in the heterogeneous vortex state of NbSe2.

A percolation transition in the vortex state of a superconducting 2H-NbSe2 crystal is observed in the regime where vortices form a heterogeneous phase consisting of ordered and disordered domains. The transition is signaled by a sharp increase in critical current that occurs when the volume fraction of disordered domains reaches the value P(c) = 0.26 +/- 0.04. Measurements on different vortex states show that, while the temperature of the transition depends on history and measurement speed, the value of P(c) and the critical exponent characterizing the approach to it, r = 1.97 +/- 0.66, are universal.

Journal Article↗
PubMed2005

The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion.

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Alternative mechanisms associated with silencing of CDKN1C in Beckwith-Wiedemann syndrome.

BACKGROUND: Mutations in the imprinted gene CDKN1C account for approximately 10% of Beckwith-Wiedemann syndrome (BWS) cases. Fibroblasts from BWS patients with loss of methylation (LOM) at the imprinting control region (ICR) KvDMR1 have reduced CDKN1C expression. Another group of BWS patients with downregulated CDKN1C expression but with normal methylation at KvDMR1 has been identified. OBJECTIVE: To investigate the mechanism of CDKN1C silencing in BWS in these two classes of patients. METHODS: The CDKN1C promoter region was analysed for changes in DNA methylation using bisulphite sequencing, and for alterations in chromatin structure using the chromatin immunoprecipitation (ChIP) assay. RESULTS: There was only spurious CpG methylation of the CDKN1C promoter in fibroblast DNA from both normal individuals and patients with BWS, irrespective of the methylation status of KvDMR1. There was no detectable change in chromatin structure at the CDKN1C promoter in patients with LOM at KvDMR1. BWS patients with downregulated CDKN1C and normal methylation at KvDMR1 had depletion of dimethylated H3-K4 and enrichment of dimethylated H3-K9 and HP1gamma at the CDKN1C promoter, suggesting that in these cases gene silencing is associated with repressive chromatin changes. CONCLUSIONS: CDKN1C may be downregulated by multiple mechanisms including some that do not involve promoter methylation. In BWS patients with normal methylation at KvDMR1 and reduced expression of CDKN1C, repressive chromatin may play a role, but the absence of methylation and repressive chromatin structure at the CDKN1C promoter in BWS patients with LOM at KvDMR1 argues for a direct role of this epimutation in silencing CDKN1C.

Beckwith-Wiedemann Syndrome↗
PubMed2005

Roles of methanogens on volatile organic sulfur compound production in anaerobically digested wastewater biosolids.

Land application of wastewater biosolids is both economical and beneficial to resource recycling. However, this environmentally friendly practice can be at risk due to odor complaints. Volatile organic sulfur compounds (VOSCs) including methanethiol, dimethyl sulfide, and dimethyl disulfide, have been identified as major contributors to biosolids odor. In this study, methanogens were shown to play a key role in removing VOSCs and reducing odors, and methane production was related to reduced VOSC production. Factors influencing the growth of methanogens such as the shear during dewatering and storage temperature showed a strong impact on net odor production. Examination of the microbial communities of both bacteria and archaea indicated a simplified archaeal community in biosolids, which is susceptible to environmental perturbations. Therefore, one possible odor control strategy is the preservation and enhancement of the methanogenic population during biosolids storage.

Air Pollutants↗
PubMed2004

Comparison of demographic and donation profiles and transfusion-transmissible disease markers and risk rates in previously transfused and nontransfused blood donors.

BACKGROUND: Increasing concern about transfusion transmission of variant Creutzfeldt-Jakob disease has resulted in indefinite deferral of transfused donors in France and the UK. Little is known, however, about the impact of indefinite deferral of transfused donors on blood safety and availability in the US. STUDY DESIGN AND METHODS: Data were collected on allogeneic donations at five US blood centers during 1991 through 2000. Donation characteristics, prevalence, and incidence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were compared between transfused and nontransfused donors. Unreported deferrable risk (UDR) and reasons to donate were evaluated with data from a mail survey. RESULTS: Transfusion history was reported by 4.2 percent of donors. Prevalence and incidence of HIV and HBV were comparable between transfused and nontransfused donors. Although HCV incidence was similar in both groups, HCV prevalence was nearly three times higher in transfused than in nontransfused first-time donors. UDR and reasons to donate were similar in the two groups, except transfused donors were less likely to donate for screening test results (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). CONCLUSION: Transfused and nontransfused donors had similar viral incidence and comparable UDR, suggesting that indefinite deferral of transfused donors would unlikely improve blood safety. Until more is known about the prevalence and transfusion transmissibility of emerging agents, indefinite deferral of previously transfused donors in the US does not appear warranted.

Adult↗
PubMed2003

Prevalence of transfusion-transmissible viral infections in first-time US blood donors by donation site.

BACKGROUND: Understanding the donor base, infectious disease prevalence, and donation loss at various blood donation sites will help maximize blood collection efforts and blood availability. STUDY DESIGN AND METHODS: Using donation data collected at five US blood centers, the prevalence of HIV, HTLV, HBsAg, and HCV in first-time whole-blood donations at 10 donation sites was evaluated: military, education, religious, professional, industry, services, community, health care, government, and fixed sites. Donation loss from screening test reactivity at each donation site was also evaluated. RESULTS: During the study, 1.2 million first-time whole-blood donations were collected. Military and education sites had a low prevalence of all viral markers, except for HBsAg, which was highest at education sites. Variations in viral marker prevalence among donation sites were partially explained by donor demographic differences. Donation loss varied by donation site, ranging from 3.3 percent at education sites to 6.4 percent at industry sites, indicating differential efficiency of blood collection efforts. CONCLUSION: Different rates of positive viral test results and donation loss in first-time whole-blood donors were observed at various types of donation sites. This information may be useful in estimating the yield of usable units from specific blood drives and in allocating resources to meet blood center collection goals.

Adult↗
PubMed2003

Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome.

CONTEXT: Beckwith-Wiedemann syndrome (BWS) arises by several genetic and epigenetic mechanisms affecting the balance of imprinted gene expression in chromosome 11p15.5. The most frequent alteration associated with BWS is the absence of methylation at the maternal allele of KvDMR1, an intronic CpG island within the KCNQ1 gene. Targeted deletion of KvDMR1 suggests that this locus is an imprinting control region (ICR) that regulates multiple genes in 11p15.5. Cell culture based enhancer blocking assays indicate that KvDMR1 may function as a methylation modulated chromatin insulator and/or silencer. OBJECTIVE: To determine the potential consequence of loss of methylation (LOM) at KvDMR1 in the development of BWS. METHODS: The steady state levels of CDKN1C gene expression in fibroblast cells from normal individuals, and from persons with BWS who have LOM at KvDMR1, was determined by both real time quantitative polymerase chain reaction (qPCR) and ribonuclease protection assay (RPA). Methylation of the CDKN1C promoter region was assessed by Southern hybridisation using a methylation sensitive restriction endonuclease. RESULTS: Both qPCR and RPA clearly demonstrated a marked decrease (86-93%) in the expression level of the CDKN1C gene in cells derived from patients with BWS, who had LOM at KvDMR1. Southern analysis indicated that downregulation of CDKN1C in these patients was not associated with hypermethylation at the presumptive CDKN1C promoter. CONCLUSIONS: An epimutation at KvDMR1, the absence of maternal methylation, causes the aberrant silencing of CDKN1C, some 180 kb away on the maternal chromosome. Similar to mutations at this locus, this silencing may give rise to BWS.

Beckwith-Wiedemann Syndrome↗
PubMed2002

Driven dynamics of the vortex-phase mixture near the peak effect: the "vortex capacitor".

A phenomenological model of vortex dynamics in the vicinity of the peak effect, which considers a coexistence of two vortex phases with different critical current densities, is proposed. It provides a quantitative description of the widely reported anomalous dynamic effects in terms of "contamination" and "annealing" of the vortex matter. Scanning ac Hall microscopy in the superconductor NbSe(2) is used to obtain the first real-space visualization of pinning in the driven vortex lattice. The results are consistent with the proposed scenario.

Journal Article↗
PubMed2001

Taxol induces apoptosis in cortical neurons by a mechanism independent of Bcl-2 phosphorylation.

Bcl-2, an antiapoptotic protein, protects cells against many but not all forms of apoptosis. For example, Bcl-2 does not protect non-neuronal cells against taxol, a microtubule-stabilizing agent. The underlying mechanism for the ineffectiveness of Bcl-2 against taxol has been the subject of intense interest. Data from non-neuronal cells indicate that taxol-induced apoptosis requires activation of N-terminal c-Jun protein kinase (JNK) that phosphorylates and inactivates Bcl-2. This suggests the interesting possibility that the apoptotic activity of JNK may be caused by phosphorylation of Bcl-2 and inhibition of the antiapoptotic activity of Bcl-2. Here we report that taxol induces apoptosis in cortical neurons but by a mechanism significantly different from that in non-neuronal cells. In contrast to human embryonic kidney 293 cells, expression of wild-type Bcl-2 in cortical neurons protected against taxol-induced apoptosis, and taxol did not induce Bcl-2 phosphorylation. Furthermore, cortical neurons express high basal JNK activity, and taxol did not stimulate total JNK activity. However, taxol activated a subpool of JNK in the nucleus and stimulated c-Jun phosphorylation. JNK inhibition or expression of a dominant-negative c-Jun abrogated taxol-induced apoptosis in cortical neurons, suggesting a role for JNK and JNK-mediated transcription in taxol-stimulated apoptosis. Furthermore, taxol-induced apoptosis in cortical neurons required inhibition of phosphatidylinositol 3-kinase signaling. These data suggest that taxol induces apoptosis in neurons by a mechanism quite distinct from that of non-neuronal cell lines and emphasize the importance of elucidating apoptotic mechanisms specific for neurons in the CNS.

Animals↗
PubMed2001

Two coexisting vortex phases in the peak effect regime in a superconductor.

The critical current in the vortex phase of a type-II superconductor such as NbSe2 displays a striking anomaly in the vicinity of the superconductor-to-normal-metal transition. Instead of going to zero smoothly, it rebounds to a sharp and pronounced maximum, just before vanishing at the transition. This counter-intuitive phenomenon, known as the peak effect, has remained an unsolved problem for 40 years. Here we use a scanning a.c. Hall microscope to visualize the real-space distribution of the critical current in NbSe2. We show that in the peak-effect regime two distinct vortex-matter phases with intrinsically different pinning strengths coexist on a macroscopic scale. The composition of the two-phase mixture and the transformation of one phase into another are responsible for the history effects and anomalous voltage response commonly seen when external parameters such as temperature, magnetic field or transport current are varied. We argue that the observed phase coexistence is, in fact, the hallmark of a disorder-driven non-thermal phase transition.

Journal Article↗
PubMed2001

Knowledge of HIV/AIDS transmission and screening in United States blood donors.

BACKGROUND: Increased knowledge of HIV transmission and behavioral and test screening may encourage high-risk blood donors to self-defer. STUDY DESIGN AND METHODS: Knowledge of HIV transmission and screening and the association with demographics, screening test reactivity, and unreported deferrable risks (UDRs) was assessed by a 1998 anonymous mail survey sent to 92,581 blood donors, of whom 57 percent responded. Groups were compared by using weighted chi-square tests and logistic regression analysis. RESULTS: Four percent of the donors thought that it was very likely or somewhat likely for a person to contract HIV from donating blood, and 20 percent perceived a similar risk from blood transfusion. Only 60 percent of the donors knew that the available screening tests may not detect a recent infection. Thirty-seven percent either did not know or felt it was acceptable to donate blood to obtain HIV testing. Those most likely to answer knowledge questions incorrectly were more likely to have a higher prevalence of test reactivity or UDRs and to be <or=25 years old, members of a minority, less educated, non-US-born, or first-time donors. CONCLUSION: Innovative ways to increase donor understanding of the implications of risk behaviors and the limitations of current screening procedures should be developed. They might prevent high-risk individuals from donating blood.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The pericentromeric region of human chromosome 11: evidence for a chromosome-specific duplication.

We have identified a chromosome duplication in the pericentromeric region of human chromosome 11 located in 11p11 and 11q14. A detailed physical map of each duplicated region was generated to describe the nature of the duplication, the involvement at the centromere and to resolve the correct maps. All clones were evaluated to ensure they were representative of their genetic origin. The order of clones, based on their marker content, as well as the distance covered was determined by SEGMAP. Each duplication encompasses more than 1 Mb of DNA and appears to be chromosome 11 specific. Ten STS markers were mapped within each duplication. Comparative sequence analysis along the duplication identified 35 nucleotide changes in 2,036 bp between the two copies, suggesting the duplication occurred over 14 million years ago. A suggested organization of the pericentromeric region, including the duplications and alpha-related repetitive sequences, is presented.

Centromere↗
PubMed2001

Granulomatous appendicitis revisited: report of a case.

BACKGROUND: Isolated granulomatous appendicitis is uncommon and previously was considered to be a form of localised Crohn's disease. However more recent series have noted that relapse is rare after appendicectomy and concluded that the condition is a distinct entity unrelated to Crohn's disease. Following a case of granulomatous appendicitis at St. Vincent's University Hospital Dublin, the condition was reviewed and the results are detailed herein. METHODS: A case of granulomatous appendicitis is presented with discussion of 4 previous cases encountered in our practice and the literature is reviewed. RESULTS: The clinical presentation was sub-acute appendicitis with a mass palpable in the right iliac fossa. At operation an enlarged, inflamed appendix with a broad base was noted and appendicectomy performed. Histopathology showed numerous granulomata on microscopic examination. The yersinia serology tests were negative. Review of computerised histopathology records in the hospital for the last 7 years showed 4 additional cases of granulomatous appendicitis. This is a total of 5 of 1,615 appendectomies (an incidence of 0.31%). In all cases, the post-operative course was uneventful and the patients have had no further complaints. CONCLUSION: This small series provides further evidence that granulomatous appendicitis is a distinct clinical entity unrelated to Crohn's disease and is cured by appendicectomy. It should be suspected when there is a sub-acute onset of appendicitis and an enlarged, broad-based appendix is found at operation.

Acute Disease↗
PubMed2001

Mapping of genes and transcribed sequences in a gene rich 400-kb region on human chromosome 11p15.1-->p14.

We have identified a number of transcribed sequences within a 400-kb interval on chromosome 11p15.1--> p14. Six genes and 13 novel transcripts including ESTs, cDNAs and exons have been identified and assigned to this region. Comparison of mRNA sequence with genomic sequence has enabled us to determine the exon/intron structure of four of the genes (NUCB2, PIK3C2A, RPS13 and OR7E14P).

Base Sequence↗
PubMed2000

The application of atomic force microscopy to topographical studies and force measurements on the secreted adhesive of the green alga Enteromorpha.

Atomic force microscopy (AFM) enables the topographical structure of cells and biological materials to be resolved under natural (physiological) conditions, without fixation and dehydration artefacts associated with imaging methods in vacuo. It also provides a means of measuring interaction forces and the mechanical properties of biomaterials. In the present study, AFM has been applied for the first time to the study of the mechanical properties of a natural adhesive produced by a green plant cell. Swimming spores of the green alga Enteromorpha linza (L.) J. Ag. (7-10 microm) secrete an adhesive glycoprotein which provides firm anchorage to the substratum. Imaging of the adhesive in its hydrated state revealed a swollen gel-like pad, approximately 1 microm thick, surrounding the spore body. Force measurements revealed that freshly released adhesive has an adhesion strength of 173 +/- 1.7 mN m(-1) (mean +/- SE; n=90) with a maximum value for a single adhesion force curve of 458 mN m(-1). The adhesive had a compressibility (equivalent to Young's modulus) of 0.54 x 10(6) +/- 0.05 x 10(6) N m-2 (mean +/- SE; n=30). Within minutes of release the adhesive underwent a progressive 'curing' process with a 65% reduction in mean adhesive strength within an hour of settlement, which was also reflected in a reduction in the average length of the adhesive polymer strands (polymer extension) and a 10-fold increase in Young's modulus. Measurements on the spore surface itself revealed considerably lower adhesion-strength values but higher polymer-extension values than the adhesive pad, which may reflect the deposition of different polymers on this surface as a new cell wall is formed. The study demonstrates the value of AFM to the imaging of plant cells in the absence of fixation and dehydration artefacts and to the characterisation of the mechanical properties of plant glycoproteins that have potential utility as adhesives.

Cell Adhesion↗
PubMed2000

Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human.

Recombination between chromosome-specific low-copy repeats (duplicons) is an underlying mechanism for several genetic disorders. Recently, a chromosome 15 duplicon was discovered in the common breakpoint regions of Prader-Willi and Angelman syndrome deletions. We identified previously the large HERC2 transcript as an ancestral gene in this duplicon, with approximately 11 HERC2-containing duplicons, and demonstrated that recessive mutations in mouse Herc2 lead to a developmental syndrome, juvenile development and fertility 2 (jdf2). We have now constructed and sequenced a genomic contig of HERC2, revealing a total of 93 exons spanning approximately 250 kb and a CpG island promoter. A processed ribosomal protein L41 pseudogene occurs in intron 2 of HERC2, and putative VNTRs occur in intron 70 (28 copies, approximately 76-bp repeat) and 3' exon 40 through intron 40 (6 copies, approximately 62-bp repeat). Sequence comparisons show that HERC2-containing duplicons have undergone several deletion, inversion, and dispersion events to form complex duplicons in 15q11, 15q13, and 16p11. To further understand the developmental role of HERC2, a highly conserved Drosophila ortholog was characterized, with 70% amino acid sequence identity to human HERC2 over the carboxy-terminal 743 residues. Combined, these studies provide significant insights into the structure of complex duplicons and into the evolutionary pathways of formation, dispersal, and genomic instability of duplicons. Our results establish that some genes not only have a protein coding function but can also play a structural role in the genome.

Amino Acid Sequence↗
PubMed2000

Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a model imprinting disorder resulting from mutations or epigenetic events involving imprinted genes at chromosome 11p15.5. Thus, germline mutations in CDKN1C, uniparental disomy (UPD), and loss of imprinting of IGF2 and other imprinted genes have been implicated. Many familial BWS cases have germline CDKN1C mutations. However, most BWS cases are sporadic and UPD or putative imprinting errors predominate in this group. We have identified previously a subgroup of sporadic cases with loss of imprinting (LOI) of IGF2 and epigenetic silencing of H19 proposed to be caused by a defect in a distal 11p15.5 imprinting control element (designated BWSIC1). However, many sporadic BWS patients show biallelic IGF2 expression in the presence of normal H19 methylation and expression patterns. This and other evidence suggested the existence of a further imprinting control element (BWSIC2) at 11p15. 5. Recently, we showed that a subgroup of BWS patients have loss of methylation (LOM) at a differentially methylated region (KvDMR1) within the KCNQ1 gene centromeric to the IGF2 and H19 genes. We have now analysed a large series of sporadic cases to define the frequency and phenotypic correlates of epigenetic abnormalities in BWS. LOM at KvDMR1 was detected by Southern analysis or a novel PCR based method in 35 of 69 (51%) sporadic BWS without UPD. LOM at KvDMR1 was often, but not invariably associated with LOI of IGF2. KvDMR1 LOM was not detected in BWS patients with putative BWSIC1 defects and cases with KvDMR1 LOM (that is, putative BWSIC2 defects) invariably had a normal H19 methylation pattern. The incidence of exomphalos in putative BWSIC2 defect patients was not significantly different from that in patients with germline CDKN1C mutations (20/29 and 13/15 respectively), but was significantly greater than that in patients with putative BWSIC1 defects (0/5, p=0.007) and UPD (0/22, p<0.0001). These findings are consistent with the hypothesis that LOM of KvDMR1 (BWSIC2 defect) results in epigenetic silencing of CDKN1C and variable LOI of IGF2. BWS patients with embryonal tumours have UPD or a BWSIC1 defect but not LOM of KvDMR1. This study has further shown how (1) variations in phenotypic expression of BWS may be linked to specific molecular subgroups and (2) molecular analysis of BWS can provide insights into mechanisms of imprinting regulation.

Beckwith-Wiedemann Syndrome↗