Complex regulatory interactions at shape joint morphology and osteoarthritis disease risk.

Our ability to pinpoint causal variants using GWAS is dependent on understanding the dynamic epigenomic and epistatic context of each associated locus. Being the best studied skeletal locus, associates with many diseases and has a complex cis-regulatory architecture. We interrogate regulatory interactions and model disease variants and .

Genetics, emotion and care: Navigating future reproductive decisions in families of children with rare genetic conditions.

Little is known regarding the future reproductive decision-making of parents of children with rare genetic conditions. Our research draws on data from an online survey and qualitative photo-elicitation interviews with families living with Noonan Syndrome. We demonstrate how genetic knowledge and prenatal genetic testing become embedded in reproductive practices.

Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice.

Background: The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of parents of reproductive age consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father's poor nutritional status has been shown to have negative consequences on foetal growth and development and ultimately impact the long-term adult health of the offspring.

The representation of medical risks and incentives concerning egg donation: an analysis of the websites of fertility clinics of Belgium, Spain and the UK.

Considering the growing demand for egg donation (ED) and the scarcity of women coming forward as donors to meet this demand, scholars have expressed concerns that clinics may (initially) misrepresent risks to recruit more donors. Additionally, (non-)monetary incentives might be used to try to influence potential donors, which may pressure these women or cause them to dismiss their concerns. Since the internet is often the first source of information and first impressions influence individuals' choices, we examined the websites of fertility clinics to explore how they present medical risks, incentives and emotional appeals.

Phonon screening and dissociation of excitons at finite temperatures from first principles.

The properties of excitons, or correlated electron-hole pairs, are of paramount importance to optoelectronic applications of materials. A central component of exciton physics is the electron-hole interaction, which is commonly treated as screened solely by electrons within a material. However, nuclear motion can screen this Coulomb interaction as well, with several recent studies developing model approaches for approximating the phonon screening of excitonic properties.

Probing the Mechanism of Action of Bis(phenolato) Amine (ONO Donor Set) Titanium(IV) Anticancer Agents.

The need for anticancer therapies that overcome metallodrug resistance while minimizing adverse toxicities is targeted, herein, using titanium coordination complexes. Octahedral titanium(IV) ,-[Ti{RN(CH-2-MeO-4-R-CH)}] [R = Et, allyl, -Pr, CHO, F, CH(morpholino), the latter from the formyl derivative; R = Me, Et; not all combinations] are attained from Mannich reactions of commercial 2-methoxyphenols (27-74% overall yield, 2 steps). These crystalline (four X-ray structures) Ti(IV)-complexes are active against MCF-7, HCT-116, HT-29, PANC-1, and MDA-MB-468 cancer cell lines (GI = 0.

A Regularized Second-Order Correlation Method from Green's Function Theory.

We present a scalable single-particle framework to treat electronic correlation in molecules and materials motivated by Green's function theory. We derive a size-extensive Brillouin-Wigner perturbation theory from the single-particle Green's function by introducing the Goldstone self-energy. This new ground state correlation energy, referred to as Quasi-Particle MP2 theory (QPMP2), avoids the characteristic divergences present in both second-order Møller-Plesset perturbation theory and Coupled Cluster Singles and Doubles within the strongly correlated regime.

Small extracellular vesicles released from germinated kiwi pollen (pollensomes) present characteristics similar to mammalian exosomes and carry a plant homolog of ALIX.

Introduction: In the last decade, it has been discovered that allergen-bearing extracellular nanovesicles, termed "pollensomes", are released by pollen during germination. These extracellular vesicles (EVs) may play an important role in pollen-pistil interaction during fertilization, stabilizing the secreted bioactive molecules and allowing long-distance signaling. However, the molecular composition and the biological role of these EVs are still unclear.

Techniques for Visualization and Quantification of Primary Cilia in Chondrocytes.

Primary cilia regulate and coordinate a variety of cell signaling pathways important in chondrocyte physiology and cartilage development, health, and disease. Despite this, the chondrocyte primary cilium and its associated role in cartilage biology remains poorly understood. Key to elucidating primary cilia structure and function in chondrocytes is the ability to visualize this unique structure.

Aerobic or Resistance Exercise for Improved Glycaemic Control and Pregnancy Outcomes in Women with Gestational Diabetes Mellitus: A Systematic Review.

Exercise is often recommended in addition to diet and medication in the management of gestational diabetes mellitus (GDM). Our aim was to determine if strength training compared with aerobic exercise had an impact on glycaemic control, maternal and neonatal outcomes. The Cochrane library, Embase, PubMed, CINAHL, Medline, Google Scholar, and OpenGrey were searched.

Multi-Omic Analysis of Two Common P53 Mutations: Proteins Regulated by Mutated P53 as Potential Targets for Immunotherapy.

The p53 protein is mutated in more than 50% of human cancers. Mutated p53 proteins not only lose their normal function but often acquire novel oncogenic functions, a phenomenon termed mutant p53 gain-of-function. Mutant p53 has been shown to affect the transcription of a range of genes, as well as protein-protein interactions with transcription factors and other effectors; however, no one has intensively investigated and identified these proteins, or their MHC presented epitopes, from the viewpoint of their ability to act as targets for immunotherapeutic interventions.

Cystic Fibrosis-Related Diabetes Mellitus and Pregnancy: A Retrospective Study.

Introduction: Cystic fibrosis-related diabetes mellitus (CFRDM) is becoming a more common issue in pregnancy care as the life expectancy of females living with cystic fibrosis has improved, with an increasing number of pregnancies in this population. Despite the Republic of Ireland having the highest incidence of cystic fibrosis globally, there is limited Irish data on pregnancy outcomes for those with CFRDM. This study aimed to retrospectively review maternal and foetal outcomes of pregnancies affected by maternal CFRDM.

Clinical Outcomes Following a Change in Gestational Diabetes Mellitus Diagnostic Criteria Due to the COVID-19 Pandemic: A Case-Control Study.

Background: Due to COVID-19, many centres adopted a change to the diagnosis of GDM.

Methods: A case-control study of antenatal patients between 1 April and 30 June in 2019 and 2020 looking at detection rates of GDM, use of medication, obstetric, and fetal outcomes.

Results: During COVID-19, the rate of positive GDM tests approximately halved (20% (42/210) in 2020 vs.

From scarcity to sisterhood: The framing of egg donation on fertility clinic websites in the UK, Belgium and Spain.

The use of third-party eggs now forms an integral part of a global reproductive bioeconomy. In order to meet clinics' growing need for donors, they employ a range of recruitment strategies including adverts for donors via their publicly facing websites. Such websites are also key sites for the articulation and popularisation of culturally specific narratives about egg donation and are therefore a rich source of data regarding the social, cultural and economic framing of bodily donation.

Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces.

Compared with our understanding of endochondral ossification, much less is known about the coordinated arrest of growth defined by the narrowing and fusion of the cartilaginous growth plate. Throughout the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. It remains unclear how mechanical cues are integrated into many biological programs, including those coordinating the ossification of the adolescent growth plate at the cessation of growth.

Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress.

Type 2 diabetes is characterised by failure to control glucose homeostasis, with numerous diabetic complications attributable to the resulting exposure of cells and tissues to chronic elevated concentrations of glucose and fatty acids. This, in part, results from formation of advanced glycation and advanced lipidation end-products that are able to modify protein, lipid, or DNA structure, and disrupt normal cellular function. Herein we used mass spectrometry to identify proteins modified by two such adduction events in serum of individuals with obesity, type 2 diabetes, and gestational diabetes, along with similar analyses of human and mouse skeletal muscle cells and mouse pancreatic islets exposed to glucolipotoxic stress.

Homocitrullination of lysine residues mediated by myeloid-derived suppressor cells in the tumor environment is a target for cancer immunotherapy.

Background: Homocitrullination is the post-translational modification of lysine that is recognized by T cells.

Methods: This study identified homocitrullinated peptides from aldolase, enolase, cytokeratin and binding immunoglobulin protein and used human leukocyte antigen (HLA) transgenic mice to assess immunogenicity by enzyme-linked immunosorbent spot assay. Vaccine efficacy was assessed in tumor therapy studies using HLA-matched B16 melanoma expressing constitutive or interferon γ (IFNγ)-inducible major histocompatibility complex class II (MHC-II) as represented by most human tumors.

Desynchronised times? Chronobiology, (bio)medicalisation and the rhythms of life itself.

This paper takes a critical look at the role of chronobiology in society today, with particular reference to its entanglements with health and medicine and whether or not this amounts to the (bio)medicalisation of our bodily rhythms. What we have here, we show, is a complex unfolding storyline, within and beyond medicine. On the one hand, the promises and problems of these circadian, infradian and ultradian rhythms for our health and well-being are now increasingly emphasised.

Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention.

Innate immunology in COVID-19-a living review. Part I: viral entry, sensing and evasion.

The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer a chance to treat disease, prophylactic and anti-viral treatments are still of vital importance, especially in context of the mutative ability of this group of viruses. Therefore, it is essential to elucidate the molecular mechanisms of viral entry, innate sensing and immune evasion of SARS-CoV-2, which control the triggers of the subsequent excessive inflammatory response.

Role of Ciliary Protein Intraflagellar Transport Protein 88 in the Regulation of Cartilage Thickness and Osteoarthritis Development in Mice.

Objective: Mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO).