Publications by authors named "JF Donoghue"

Background: Despite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence.

View Article and Find Full Text PDF

We argue that the well-known beta functions of quadratic gravity do not correspond to the physical dependence of scattering amplitudes on external momenta, and derive the correct physical beta functions. Asymptotic freedom turns out to be compatible with the absence of tachyons.

View Article and Find Full Text PDF

Natural variability in menstrual cycle length, coupled with rapid changes in endometrial gene expression, makes it difficult to accurately define and compare different stages of the endometrial cycle. Here we develop and validate a method for precisely determining endometrial cycle stage based on global gene expression. Our 'molecular staging model' reveals significant and remarkably synchronised daily changes in expression for over 3400 endometrial genes throughout the cycle, with the most dramatic changes occurring during the secretory phase.

View Article and Find Full Text PDF

Endometriosis, defined as the growth of hormonally responsive endometrial-like tissue outside of the uterine cavity, is an estrogen-dependent, chronic, pro-inflammatory disease that affects up to 11.4% of women of reproductive age and gender-diverse people with a uterus. At present, there is no long-term cure, and the identification of new therapies that provide a high level of efficacy and favourable long-term safety profiles with rapid clinical access are a priority.

View Article and Find Full Text PDF

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells.

View Article and Find Full Text PDF

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.

View Article and Find Full Text PDF

Endometriosis-associated pain and the mechanisms responsible for its initiation and persistence are complex and difficult to treat. Endometriosis-associated pain is experienced as dysmenorrhea, cyclical pain related to organ function including dysuria, dyschezia and dyspareunia, and persistent pelvic pain. Pain symptomatology correlates poorly with the extent of macroscopic disease.

View Article and Find Full Text PDF

Endocannabinoids mediate cellular functions and their activity is controlled by a complex system of enzymes, membrane receptors and transport molecules. Endocannabinoids are present in endometrium, a cyclical regenerative tissue requiring tightly regulated cellular mechanisms for maturation. The objective of this study was to investigate the gene expression of key elements involved in the endocannabinoid system across the menstrual cycle.

View Article and Find Full Text PDF

Synchrotron microbeam radiation therapy (MRT) is a preclinical irradiation technique which could be used to treat intracranial malignancies. The goal of this work was to discern differences in gene expression and the predicted regulation of molecular pathways in the brainstem after MRT versus synchrotron broad-beam radiation therapy (SBBR). Healthy C57BL/6 mice received whole-head irradiation with median acute toxic doses of MRT (241 Gy peak dose) or SBBR (13 Gy).

View Article and Find Full Text PDF

Purpose: γH2AX biodosimetry has been proposed as an alternative dosimetry method for microbeam radiation therapy (MRT) because conventional dosimeters, such as ionization chambers, lack the spatial resolution required to accurately measure the MRT valley dose. Here we investigated whether γH2AX biodosimetry should be used to measure the biological valley dose of MRT-irradiated mammalian cells.

Materials And Methods: We irradiated human skin fibroblasts and mouse skin flaps with synchrotron MRT and broad beam (BB) radiation.

View Article and Find Full Text PDF

Endometriosis is a complex disease, influenced by genetic factors. Genetic markers associated with endometriosis exist at chromosome 1p36.12 and lead to altered expression of the long intergenic non-coding RNA 339 (LINC00339), however, the role of LINC00339 in endometriosis pathophysiology remains unknown.

View Article and Find Full Text PDF

Epidermal growth factor (EGF) maintains intestinal stem cell (ISC) proliferation and is a key component of organoid growth media yet is dispensable for intestinal homeostasis, suggesting roles for multiple EGF family ligands in ISC function. Here, we identified neuregulin 1 (NRG1) as a key EGF family ligand that drives tissue repair following injury. NRG1, but not EGF, is upregulated upon damage and is expressed in mesenchymal stromal cells, macrophages, and Paneth cells.

View Article and Find Full Text PDF

Study Question: Are uterine natural killer (uNK) cell numbers and their distribution relative to endometrial arterioles altered in women with recurrent implantation failure (RIF) compared to women with embryo implantation success (IS)?

Summary Answer: uNK cell numbers and their distribution relative to endometrial arterioles are not significantly different in women with RIF compared to women in whom embryo implantation occurs successfully following IVF.

What Is Already Known: uNK cells are regulators of decidual angiogenesis and spiral arteriole remodelling during early pregnancy. Although some studies have shown that uNK cell numbers may be altered in women with RIF, the methods used to measure uNK cell numbers have proven inconsistent, making reproduction of these results difficult.

View Article and Find Full Text PDF

Causality in quantum field theory is defined by the vanishing of field commutators for spacelike separations. However, this does not imply a direction for causal effects. Hidden in our conventions for quantization is a connection to the definition of an arrow of causality, i.

View Article and Find Full Text PDF

Endometriotic lesions are composed in part of endometrial-like stromal cells, however, there is a shortage of immortalized human endometrial stromal cultures available for research. As genetic factors play a role in endometriosis risk, it is important that genotype is also incorporated into analysis of pathological mechanisms. Human telomerase reverse transcriptase (hTERT) immortalization (using Lenti-hTERT-green fluorescent protein virus) took place following genotype selection; 13 patients homozygous for either the risk or non-risk 'other' allele for one or more important endometriosis risk single nucleotide polymorphism on chromosome 1p36.

View Article and Find Full Text PDF

Synchrotron radiation can facilitate novel radiation therapy modalities such as microbeam radiation therapy (MRT) and high dose-rate synchrotron broad-beam radiation therapy (SBBR). Both of these modalities have unique physical properties that could be exploited for an improved therapeutic effect. While pre-clinical studies report promising normal tissue sparing phenomena, systematic toxicity data are still required.

View Article and Find Full Text PDF

Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ErbB2 Receptor Tyrosine Kinase 4 (ERBB4) is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples.

View Article and Find Full Text PDF

Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy modality that has been proposed as an alternative to conventional radiation therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a devastating pediatric tumor of the brainstem. The primary goal of this study was to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761 and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that these DIPG cell lines would exhibit differential responses to each radiation modality.

View Article and Find Full Text PDF

Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy modality that has been proposed as an alternative to conventional radiation therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a devastating pediatric tumor of the brainstem. The primary goal of this study was to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761 and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that these DIPG cell lines would exhibit differential responses to each radiation modality.

View Article and Find Full Text PDF

Coastal wetland responses to sea-level rise are greatly influenced by biogeomorphic processes that affect wetland surface elevation. Small changes in elevation relative to sea level can lead to comparatively large changes in ecosystem structure, function, and stability. The surface elevation table-marker horizon (SET-MH) approach is being used globally to quantify the relative contributions of processes affecting wetland elevation change.

View Article and Find Full Text PDF

Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines.

View Article and Find Full Text PDF

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells.

View Article and Find Full Text PDF

We consider the scattering of lightlike matter in the presence of a heavy scalar object (such as the Sun or a Schwarzschild black hole). By treating general relativity as an effective field theory we directly compute the nonanalytic components of the one-loop gravitational amplitude for the scattering of massless scalars or photons from an external massive scalar field. These results allow a semiclassical computation of the bending angle for light rays grazing the Sun, including long-range ℏ contributions.

View Article and Find Full Text PDF
Article Synopsis
  • - A mutant form of the epidermal growth factor receptor, EGFRvIII, is often found in glioma, a tough-to-treat brain cancer, and it promotes tumor growth by activating other receptor tyrosine kinases (RTKs).
  • - The study focuses on how EGFRvIII activates the MET RTK in glioma cells, revealing that this process is linked to the formation of pairs of MET and uses a scaffold protein called focal adhesion kinase (FAK).
  • - Using a combination therapy targeting both EGFRvIII and the activated RTKs significantly improved survival in a mouse model of glioma, suggesting a potentially effective treatment strategy for patients with this aggressive cancer type.
View Article and Find Full Text PDF