Teratogen-Induced Oxidative Stress Targets Glyceraldehyde-3-Phosphate Dehydrogenase in the Organogenesis Stage Mouse Embryo

Exposure during the organogenesis stage of the mouse embryo to the model teratogen, hydroxyurea (HU), induces curly tail and limb malformations. Oxidative stress contributes to the developmental toxicity of HU. Reactive oxygen species (ROS) interact with polyunsaturated bilipid membranes to form α,β-unsaturated reactive aldehydes; 4-hydroxy-2-nonenal (4-HNE), one of the most cytotoxic of these aldehydes, covalently adducts with proteins, lipids, and nucleic acids. The goal of the current study is to determine if HU exposure of CD1 mice on gestation day 9 generates region-specific 4-HNE-protein adducts in the embryo and to identify the proteins targeted. The formation of 4-HNE-protein adducts was elevated in the caudal region of control embryos; HU exposure further increased 4-HNE-protein adduct formation in this area. Interestingly, three of the 4-HNE–modified proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamate oxaloacetate transaminase 2, and aldolase 1, A isoform, are involved in energy metabolism. The formation of 4-HNE-GAPDH protein adducts reduced GAPDH enzymatic activity by 20% and attenuated lactate production by 40%. Furthermore, HU exposure induced the nuclear translocation of GAPDH in the caudal region of exposed embryos; this nuclear translocation may be associated with the reactivation of oxidized proteins involved in DNA repair, such as apurinic/apyrimidinic endonuclease-1, and the stimulation of E1A-associated P300 protein/creb-binding protein (p300/CBP) activity, initiating cell death in a p53-dependent pathway. We propose that GAPDH is a redox-sensitive target in the embryo and may play a role in a stress response during development

Kozier and Erb's Fundamentals of Nursing [3rd Australian edition]

Kozier and Erb's Fundamentals of Nursing prepares students for practice in a range of diverse clinical settings and help them understand what it means to be a competent professional nurse in the twenty-first century. This third Australian edition has once again undergone a rigorous review and writing process. Contemporary changes in the regulation of nursing are reflected in the chapters and the third edition continues to focus on the three core philosophies: Person-centred care, critical thinking and clinical reasoning and cultural safety. Students will develop the knowledge, critical thinking and clinical reasoning skills to deliver care for their patients in ways that signify respect, acceptance, empathy, connectedness, cultural sensitivity and genuine concern

Observations of gas flows inside a protoplanetary gap

Gaseous giant planet formation is thought to occur in the first few million years following stellar birth. Models predict that giant planet formation carves a deep gap in the dust component (shallower in the gas). Infrared observations of the disk around the young star HD142527, at ~140pc, found an inner disk ~10AU in radius, surrounded by a particularly large gap, with a disrupted outer disk beyond 140AU, indicative of a perturbing planetary-mass body at ~90 AU. From radio observations, the bulk mass is molecular and lies in the outer disk, whose continuum emission has a horseshoe morphology. The vigorous stellar accretion rate would deplete the inner disk in less than a year, so in order to sustain the observed accretion, matter must flow from the outer-disk into the cavity and cross the gap. In dynamical models, the putative protoplanets channel outer-disk material into gap-crossing bridges that feed stellar accretion through the inner disk. Here we report observations with the Atacama Large Millimetre Array (ALMA) that reveal diffuse CO gas inside the gap, with denser HCO+ gas along gap-crossing filaments, and that confirm the horseshoe morphology of the outer disk. The estimated flow rate of the gas is in the range 7E-9 to 2E-7 Msun/yr, which is sufficient to maintain accretion onto the star at the present rate

Erratum: A Case-Control Study of Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Cryptorchidism in Canadian Populations

[This corrects the article DOI: 10.1289/EHP522.]

The Activation of DNA Damage Detection and Repair Responses in Cleavage-Stage Rat Embryos by a Damaged Paternal Genome

Male germ cell DNA damage, after exposure to radiation, exogenous chemicals, or chemotherapeutic agents, is a major cause of male infertility. DNA-damaged spermatozoa can fertilize oocytes; this is of concern because there is limited information on the capacity of early embryos to repair a damaged male genome or on the fate of these embryos if repair is inadequate. We hypothesized that the early activation of DNA damage response in the early embryo is a critical determinant of its fate. The objective of this study was to assess the DNA damage response and mitochondrial function as a measure of the energy supply for DNA repair and general health in cleavage-stage embryos sired by males chronically exposed to an anticancer alkylating agent, cyclophosphamide. Male rats were treated with saline or cyclophosphamide (6 mg/kg/day) for 4 weeks and mated to naturally cycling females. Pronuclear two- and eight-cell embryos were collected for immunofluorescence analysis of mitochondrial function and biomarkers of the DNA damage response: γH2AX foci, 53BP1 reactivity, and poly(ADP-ribose) polymer formation. Mitochondrial activities did not differ between embryos sired by control- and cyclophosphamide-exposed males. At the two-cell stage, there was no treatment-related increase in DNA double-strand breaks; by the eight-cell stage, a significant increase was noted, as indicated by increased medium and large γH2AX foci. This was accompanied by a dampened DNA repair response, detected as a decrease in the nuclear intensity of poly(ADP-ribose) polymers. The micronuclei formed in cyclophosphamide-sired embryos contained large γH2AX foci and enhanced poly(ADP-ribose) polymer and 53BP1 reactivity compared with their nuclear counterparts. Thus, paternal cyclophosphamide exposure activated a DNA damage response in cleavage-stage embryos. Furthermore, this damage response may be useful in assessing embryo quality and developmental competence

Kozier and Erb's Fundamentals of Nursing [4th Australian edition]

[Extract] Contemporary nursing in Australia and internationally is challenging, complex, dynamic and very rewarding. Many of the people we care for, both in the community and in hospitals, are older and sicker than they were a decade ago, oftern with complex health and psychosocial needs. This means that nurses today must be clinically competent, empathic, flexible and kowledgeable. They need a broad and deep understanding of physiology, pathophysiology, pharmacology, epidemiology, therapeutics, culture, ethics and law, as well as a commitment toevidence-based practice. Today's nurses have many roles and functions - clinician, educator, leader, researcher, to name just a few. They require highly developed skills in problem solving, critical thinking and clinical reasoning. Today's nurses must be lifelong learners who are confident in the use of information and communication technology, and able to communicate effectively with their patients and with all members of the health care team. Above all, they must care for people in ways that signify respect, acceptance, empathy, connectedness, cultural sensitivity ad genuine concern. This fourth Australian edition of Kozier and Erb's Fundamentals of Nursing has one again undergone a rigorous review and writing process. Contemporary changes in the regulation of nursing are reflected in the chapters, and this edition continues to focus on the three core philosophies: (1) person-centred care, (2) critical thinking and clinical reasoning, (3) cultural safety. These three philosophical foundations are interwoven in a meaningful way through each chapter

Mind the gap: reconciling tropical forest carbon flux estimates from earth observation and national reporting requires transparency

Background: The application of different approaches calculating the anthropogenic carbon net flux from land, leads to estimates that vary considerably. One reason for these variations is the extent to which approaches consider forest land to be “managed” by humans, and thus contributing to the net anthropogenic flux. Global Earth Observation (EO) datasets characterising spatio-temporal changes in land cover and carbon stocks provide an independent and consistent approach to estimate forest carbon fluxes. These can be compared against results reported in National Greenhouse Gas Inventories (NGHGIs) to support accurate and timely measuring, reporting and verification (MRV). Using Brazil as a primary case study, with additional analysis in Indonesia and Malaysia, we compare a Global EO-based dataset of forest carbon fluxes to results reported in NGHGIs. Results: Between 2001 and 2020, the EO-derived estimates of all forest-related emissions and removals indicate that Brazil was a net sink of carbon (− 0.2 GtCO2yr−1), while Brazil’s NGHGI reported a net carbon source (+ 0.8 GtCO2yr−1). After adjusting the EO estimate to use the Brazilian NGHGI definition of managed forest and other assumptions used in the inventory’s methodology, the EO net flux became a source of + 0.6 GtCO2yr−1, comparable to the NGHGI. Remaining discrepancies are due largely to differing carbon removal factors and forest types applied in the two datasets. In Indonesia, the EO and NGHGI net flux estimates were similar (+ 0.6 GtCO2 yr−1), but in Malaysia, they differed in both magnitude and sign (NGHGI: -0.2 GtCO2 yr−1; Global EO: + 0.2 GtCO2 yr−1). Spatially explicit datasets on forest types were not publicly available for analysis from either NGHGI, limiting the possibility of detailed adjustments. Conclusions: By adjusting the EO dataset to improve comparability with carbon fluxes estimated for managed forests in the Brazilian NGHGI, initially diverging estimates were largely reconciled and remaining differences can be explained. Despite limited spatial data available for Indonesia and Malaysia, our comparison indicated specific aspects where differing approaches may explain divergence, including uncertainties and inaccuracies. Our study highlights the importance of enhanced transparency, as set out by the Paris Agreement, to enable alignment between different approaches for independent measuring and verification