Publications by authors named "O'Flaherty C"

Study Question: What role do sphingolipids have in mediating human sperm capacitation?

Summary Answer: Sphingosine 1-phosphate (S1P) mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1 and promoting production of reactive oxygen species such as nitric oxide and superoxide anion.

What Is Known Already: Bioactive sphingolipids, such as S1P, are fundamental for regulating numerous physiological domains and processes, such as cell membranes and signalling, cell death and proliferation, cell migration and invasiveness, inflammation, and central nervous system development.

Study Design, Size, Duration: Semen samples were obtained from a cohort of 10 healthy non-smoking volunteers (18-30 years old) to investigate the role of S1P in sperm.

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Article Synopsis
  • The study explores the role of glycerol-3-phosphate phosphatase (G3PP) in male fertility, highlighting its crucial expression in the testis and sperm, especially during spermatogenesis.
  • Researchers found that male mice lacking G3PP (cG3PP-KO) are infertile due to dysfunctional sperm with poor motility and increased oxidative stress, while a tamoxifen-inducible version (icG3PP-KO) maintained some fertility due to a small number of normal sperm.
  • The results suggest that G3PP is vital for sperm function and health, as its absence leads to abnormal sperm production and metabolism, impacting overall male fertility.
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Sperm capacitation is a complex process essential for the spermatozoon to recognize and fertilize the oocyte. For capacitation to occur, human spermatozoa require low levels of reactive oxygen species (ROS), increased protein tyrosine phosphorylation, and sufficient levels of energy metabolites such as citrate. Human spermatozoa are exposed to high concentrations of citrate from the seminal plasma, yet the role of citrate in sperm capacitation is largely unknown.

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Article Synopsis
  • * The program uses impactful visual messaging about the dangers of excess body weight and promotes healthier eating habits through TV-led campaigns.
  • * Evaluation results from 2012 to 2019 indicate significant increases in awareness of the link between obesity and chronic diseases, as well as positive shifts in intentions to consume more fruits and vegetables and reduce sugary drink intake among participants.
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Heparan sulfate (HS), an abundant component of the apical cell surface and basement membrane, belongs to the glycosaminoglycan family of carbohydrates covalently linked to proteins called heparan sulfate proteoglycans. After endocytosis, HS is degraded in the lysosome by several enzymes, including heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT), and in its absence causes Mucopolysaccharidosis III type C (Sanfilippo type C). Since endocytosis occurs in epithelial cells of the testis and epididymis, we examined the morphological effects of Hgsnat inactivation in these organs.

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The purpose of this article is to provide an explanation of the background behind a checklist that declares the laboratory methods used in a scientific study. It focuses primarily on implementing laboratory procedures to yield reliable results in basic semen examinations. While the World Health Organization (WHO) and international standards provide recommendations for basic semen examination, manuscripts submitted to Andrology frequently lack transparency regarding the specific techniques used.

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Lysophosphatidic acid (LPA) signalling is essential for maintaining germ cell viability during mouse spermatogenesis; however, its role in human spermatozoa is unknown. We previously demonstrated that peroxiredoxin 6 (PRDX6) calcium-independent phospholipase A (iPLA) releases lysophospholipids such as LPA or arachidonic acid (AA) and that inhibiting PRDX6 iPLA activity impairs sperm cell viability. The exogenous addition of LPA bypassed the inhibition of PRDX6 iPLA activity and maintained the active phosphoinositide 3-kinase (PI3K)/AKT pathway.

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Issue Addressed: This study explored trends in public support for obesity prevention policies in Western Australia (WA).

Methods: A series of cross-sectional surveys of a representative sample of WA adults aged 25-49 years (N = 11 534) were undertaken between 2012 and 2020 as part of an evaluation of the LiveLighter® mass media campaign, a component of a statewide healthy lifestyle education and promotion programme. Computer-assisted telephone interviews were used to gauge support for a range of obesity prevention initiatives that could be implemented by government.

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The spermatozoa have limited antioxidant defences, a high polyunsaturated fatty acids content and the impossibility of synthesizing proteins, thus being susceptible to oxidative stress. High levels of reactive oxygen species (ROS) harm human spermatozoa, promoting oxidative damage to sperm lipids, proteins and DNA, leading to infertility. Coenzyme A (CoA) is a key metabolic integrator in all living cells.

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The persistent exposure of coral assemblages to more variable abiotic regimes is assumed to augment their resilience to future climatic variability. Yet, while the determinants of coral population resilience across species remain unknown, we are unable to predict the winners and losers across reef ecosystems exposed to increasingly variable conditions. Using annual surveys of 3171 coral individuals across Australia and Japan (2016-2019), we explore spatial variation across the short- and long-term dynamics of competitive, stress-tolerant, and weedy assemblages to evaluate how abiotic variability mediates the structural composition of coral assemblages.

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In Brief: This review focuses on the enzymatic antioxidant mechanisms to fight oxidative stress by spermatozoa, highlighting the differences among mammalian species. We discuss recent evidence about players that promote and fight oxidative stress and the need for novel strategies to diagnose and treat cases of male infertility associated with oxidative damage of the spermatozoon.

Abstract: The spermatozoon is very sensitive to high reactive oxygen species (ROS) levels due to its limited antioxidant system.

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Background: Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention.

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Antibiotic resistance is becoming increasingly prevalent amongst bacterial pathogens and there is an urgent need to develop new types of antibiotics with novel modes of action. One promising strategy is to develop resistance-breaker compounds, which inhibit resistance mechanisms and thus resensitize bacteria to existing antibiotics. In the current study, we identify bacterial DNA double-strand break repair as a promising target for the development of resistance-breaking co-therapies.

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Article Synopsis
  • Biomedical science is improving in transparency and reproducibility, which is crucial for research involving semen analysis.
  • Two key documents have been released: the WHO Laboratory Manual and the International Standard ISO 23162:2021, both focusing on semen examination protocols.
  • It is recommended that authors adhere to these guidelines when publishing their studies, ideally using a provided checklist for proper compliance.
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Background: Axillary lymph node status remains the most powerful prognostic indicator in invasive breast cancer. Ductal carcinoma in situ (DCIS) is a non-invasive disease and does not spread to axillary lymph nodes. The presence of an invasive component to DCIS mandates nodal evaluation through sentinel lymph node biopsy (SLNB).

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Human infertility is an important health problem that affects one in six couples worldwide. Half of these cases are due to male infertility. Oxidative stress is a common culprit of male infertility, promoting lipid peroxidation and the oxidation of proteins and DNA in spermatozoa, thereby impairing motility, capacitation and fertilization.

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Proper functionality of the spermatozoa depends on the tight regulation of their redox status; at the same time these cells are highly energy demanding and in the energetic metabolism, principally in the electron transport chain in the mitochondria, reactive oxygen species are continuously produced, in addition to that observed in the Krebs cycle and during the β-oxidation of fatty acids. In addition, in glycolysis, elimination of phosphate groups from glyceraldehyde 3-phosphate and dihydroxyacetone phosphate results in the byproducts glyoxal (G) and methylglyoxal (MG); these products are 2-oxoaldehydes. The presence of adjacent carbonyl groups makes them strong electrophiles that react with nucleophiles in proteins, lipids, and DNA, forming advanced glycation end products.

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Spermatozoa are complex and compartmentalized cells that undergo capacitation, a series of biochemical and morphological changes to acquire the ability to fertilize oocytes. Reactive oxygen species (ROS) have a prominent dual role in capacitation. At physiological levels, ROS regulate numerous cellular processes, including increases of cyclic adenosine monophosphate, calcium, and activation of phosphorylation events needed for capacitation.

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Background: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR).

Aims: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival.

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Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for 50% of the cases. Currently, a physical examination, hormone profiling and the evaluation of two consecutive semen samples (to determine the sperm concentration, motility, morphology and, in very few cases, sperm DNA integrity) are the sole tools that physicians have to evaluate infertility in men.

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Human infertility affects ~15% of couples worldwide, and it is now recognized that in half of these cases, the causes of infertility can be traced to men[...

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Oxidative stress is a common culprit of several conditions associated with male fertility. High levels of reactive oxygen species (ROS) promote impairment of sperm quality mainly by decreasing motility and increasing the levels of DNA oxidation. Oxidative stress is a common feature of environmental pollutants, chemotherapy and other chemicals, smoke, toxins, radiation, and diseases that can have negative effects on fertility.

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Peroxiredoxins (PRDXs) are antioxidant enzymes that protect cells from oxidative stress and play a role in reactive oxygen species (ROS)-mediated signaling. We reported that PRDXs are critical for human fertility by maintaining sperm viability and regulating ROS levels during capacitation. Moreover, studies on Prdx6 mice revealed the essential role of PRDX6 in the viability, motility, and fertility competence of spermatozoa.

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Spermatozoa are very sensitive to high levels of reactive oxygen species (ROS) due to the limited antioxidant systems present in these terminal cells. However, tight regulation of ROS levels must be ensured to accomplish the unique goal of the spermatozoon, that is, the transfer of the paternal genome into the mature oocyte during the fertilization process. Thus, it is essential that the restricted antioxidant enzymatic systems are active for sperm function.

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In this systematic review, we examined the rigor and outcomes across 27 object play intervention studies using single-case research methodology. We focused on studies including children age 5 years or younger and examined several descriptive characteristics including materials, instructional packages, and settings. We also analyzed the facilitation and measurement of generalized play and several methodological features including quality, rigor, and visual analysis procedures.

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