Correction: Regulation of the DNA Damage Response and Gene Expression by the Dot1L Histone Methyltransferase and the 53Bp1 Tumour Suppressor.

[This corrects the article DOI: 10.1371/journal.pone.

Temporal Characterization of the Amyloidogenic APPswe/PS1dE9;hAPOE4 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating disorder with a global prevalence estimated at 55 million people. In clinical studies administering certain anti-beta-amyloid (Aβ) antibodies, amyloid-related imaging abnormalities (ARIAs) have emerged as major adverse events. The frequency of these events is higher among apolipoprotein ε4 allele carriers () compared to non-carriers.

Toxicity and risk management of oil-spiked sediments by diluted bitumen for two freshwater benthic invertebrates.

Diluted bitumen (dilbit) is an unconventional oil produced by the oil sands industry in Canada. Despite the knowledge available on hydrocarbon toxicity, the effects of diluted bitumen on benthic organisms are still largely unknown. Moreover, in Quebec there are only provisional threshold values of 164 mg/kg C-C for chronic effects and 832 mg/kg for acute effects.

The effects of dissolved petroleum hydrocarbons on benthic organisms: Chironomids and amphipods.

The oil sands industry in Canada, produces heavy unconventional oils, diluted for transport and called diluted bitumen. However, despite advances in our knowledge of the ecotoxicological risk that these products represent, their effects on benthic organisms following a spill are still largely unknown. In order to fill these gaps, this study aims to determine the lethal and sublethal effects of two diluted bitumens (Bluesky and Cold Lake) and one conventional oil (Lloydminster) for two freshwater benthic invertebrates: Chironomus riparius and Hyalella azteca.

PTSD in French Adolescent Victims Following the London Attack in March 2017: Data From the First Step of the AVAL Study.

Background: The terrorist attack at Westminster Bridge on March 22, 2017 impacted on French high school students on a school trip in London. This terrorist attack was claimed by the Islamic State. The aim of the study was to assess the mental health consequences of the attack on the French adolescents who were directly exposed (criteria A for , PTSD).

Socioeconomic and racial/ethnic differences in use of endocrine-disrupting chemical-associated personal care product categories among pregnant women.

Personal care products (PCPs) are important and modifiable sources of exposure to endocrine disrupting chemicals (EDCs). Research is limited on how EDC-associated PCP use differs by race/ethnicity and socioeconomic status (SES), particularly during the sensitive period of pregnancy. We investigated differences in PCP use by race/ethnicity and SES among 497 participants in the LIFECODES pregnancy cohort (Boston, Massachusetts).

Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139.

There remains an insufficient number of P2X7 receptor antagonists with adequate rodent potency, CNS permeability, and pharmacokinetic properties from which to evaluate CNS disease hypotheses preclinically. Herein, we describe the molecular pharmacology, safety, pharmacokinetics, and functional CNS target engagement of Lu AF27139, a novel rodent-active and CNS-penetrant P2X7 receptor antagonist. Lu AF27139 is highly selective and potent against rat, mouse, and human forms of the receptors.

The Cupola: an additional layer of protection for providers working in the oropharyngeal region.

Objectives: To reduce the spread of the infection, especially during aerosol generating procedures, we invented "The Cupola", a shield that creates a mechanical barrier around the patient's head and body. With this pilot study we aimed to assess the effectiveness of an additional layer of protection (The Cupola) developed for providers working in the oropharyngeal region.

Results: The mean number of 0.

Impact of a Terrorist Attack on the Mental Health of Directly Exposed French Adolescents: Study Protocol for the First Step of the AVAL Cohort Study.

Several terrorist attacks have recently taken place in France and Europe. Various studies have shown a high prevalence of Post-Traumatic Stress Disorder (PTSD) and other psychiatric disorders among the victims of these attacks. Nevertheless, research in this field is scarce and no cohort study has been conducted yet to evaluate the impact of a terrorist attack on teenagers directly exposed to this type of events.

Selective Activation of Cholecystokinin-Expressing GABA (CCK-GABA) Neurons Enhances Memory and Cognition.

Cholecystokinin-expressing GABAergic (CCK-GABA) neurons are perisomatic inhibitory cells that have been argued to regulate emotion and sculpt the network oscillations associated with cognition. However, no study has selectively manipulated CCK-GABA neuron activity during behavior in freely-moving animals. To explore the behavioral effects of activating CCK-GABA neurons on emotion and cognition, we utilized a novel intersectional genetic mouse model coupled with a chemogenetic approach.

ING3 is required for ATM signaling and DNA repair in response to DNA double strand breaks.

Inhibitor of Growth 3 (ING3) is a candidate tumor suppressor gene whose expression is lost in tumors such as hepatocellular carcinoma, head and neck squamous cell carcinoma and melanoma. In the present study, we show that ING3-depleted human cells and yeast cells deleted for its ortholog YNG2 are sensitive to DNA damage suggesting a conserved role in response to such stress. In human cells, ING3 is recruited to DNA double strand breaks and is required for ATM activation.

Researchers: share your passion for science!

The promotion of the public understanding of science has many positive impacts on society, including expanding the reach of science to a broader range of individuals and having a favourable impact on the economy. It also results in many benefits for researchers involved, including the development of their communication skills and improvement in the quality of their research. Despite increased awareness of the importance of public engagement (PE), the involvement of researchers has only slightly increased in the last 10 years.

Titanium diffusion in shinbone of rats with osseointegrated implants.

Dental implants are composed of commercially pure Ti (which is actually an alloy of titanium, and minor or trace components such as aluminium and vanadium). When the implant is inserted, its surface undergoes a number of chemical and mechanical processes, releasing particles of titanium to the medium. The metabolism of free ions of titanium is uncertain; the uptaking processes in the body are not well known, nor their toxic dose.

Effect of Bisphosphonates on the Levels of Rankl and Opg in Gingival Crevicular Fluid of Patients With Periodontal Disease and Post-menopausal Osteoporosis.

The Receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/Osteoprotegerine (OPG) system has been proposed as essential for osteoclast biology and identified as key part in regulating the physiology and pathology of the skeletal system. The study of the RANKL/RANK/OPG system has increased the understanding of the mechanisms involved in the bone remodeling process, especially in postmenopausal osteoporosis and periodontal disease. Bisphosphonates have become the mainstay of the treatment and prevention of post-menopausal osteoporosis.

Ferumoxytol-enhanced magnetic resonance angiography is a feasible method for the clinical evaluation of lower extremity arterial disease.

Background: Renal toxicity from conventional, iodinated, intravenous contrast agents is a common complication in patients with peripheral artery disease (PAD). Similarly, the potential for serious side effects prevents the use of gadolinium-based agents in many patients with depressed renal function. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a novel technique that uses an intravenous, ultrasmall, superparamagnetic, iron oxide preparation, currently approved by the Food and Drug Administration for the treatment of iron deficiency anemia in adults with chronic kidney disease.

Fused thiazolyl alkynes as potent mGlu5 receptor positive allosteric modulators.

A new series of potent fused thiazole mGlu5 receptor positive allosteric modulators (PAMs) (10, 11 and 27-31) are disclosed and details of the SAR and optimization are described. Optimization of alkynyl thiazole 9 (Lu AF11205) led to the identification of potent fused thiazole analogs 10b, 27a, 28j and 31d. In general, substituted cycloalkyl, aryl and heteroaryl carboxamides, and carbamate analogs are mGlu5PAMs, whereas smaller alkyl carboxamide, sulfonamide and sulfamide analogs tend to be mGlu5 negative allosteric modulators (NAMs).

Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1.

The mediators of the DNA damage response (DDR) are highly phosphorylated by kinases that control cell proliferation, but little is known about the role of this regulation. Here we show that cell cycle phosphorylation of the prototypical DDR mediator Saccharomyces cerevisiae Rad9 depends on cyclin-dependent kinase (CDK) complexes. We find that a specific G2/M form of Cdc28 can phosphorylate in vitro the N-terminal region of Rad9 on nine consensus CDK phosphorylation sites.

Qualitative microanalysis of calcium local structure in tooth layers by means of micro-RRS.

The Resonant inelastic X-ray scattering or resonant Raman scattering is an inelastic process of second order that becomes important when the energy of the excitation radiation is below but close to an absorption edge. In this process, the emitted photons have a continuous energy distribution with a high energy cut-off limit. In the last few years, experiments of resonant Raman scattering has become a very powerful technique to investigate excitations of electrons in solids.

Discovery and structure-activity relationship of 1,3-cyclohexyl amide derivatives as novel mGluR5 negative allosteric modulators.

A novel series of trans-1,3-cyclohexyl diamides was discovered and characterized as mGluR5 negative allosteric modulators (NAMs) lacking an alkyne moiety. Conformational constraint of one of the amide bonds in the diamide template led to a spirooxazoline template. A representative compound (24d) showed good in vitro potency, high CNS penetration and, upon subcutaneous dosing, demonstrated efficacy in the mouse marble burying test, generally used as indicative of potential anxiolytic activity.

Eukaryotic DNA damage checkpoint activation in response to double-strand breaks.

Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures the rapid detection and repair of DSBs in order to maintain genome integrity.

Regulation of the DNA damage response and gene expression by the Dot1L histone methyltransferase and the 53Bp1 tumour suppressor.

Background: Dot1L, a histone methyltransferase that targets histone H3 lysine 79 (H3K79), has been implicated in gene regulation and the DNA damage response although its functions in these processes remain poorly defined.

Methodology/principal Findings: Using the chicken DT40 model system, we generated cells in which the Dot1L gene is disrupted to examine the function and focal recruitment of the 53Bp1 DNA damage response protein. Detailed kinetic and dose response assays demonstrate that, despite the absence of H3K79 methylation demonstrated by mass spectrometry, 53Bp1 focal recruitment is not compromised in these cells.

A crystallinity study of dental tissues and tartar by infrared spectroscopy.

In this paper we report a study of an important property of biomineralized phases, crystallinity, on the basis of previous results for synthetic apatite. Crystallinity is not only important for understanding biomineralization, it is also related to the maturation and mechanisms of growth of calcium phosphates in biological surroundings. We studied two kinds of sample, teeth as an example of biomineralized tissues and dental calculi (adhering) as an example of mineralization without participation of biological agents, except possibly bacteria.

Dynamics of Rad9 chromatin binding and checkpoint function are mediated by its dimerization and are cell cycle-regulated by CDK1 activity.

Saccharomyces cerevisiae Rad9 is required for an effective DNA damage response throughout the cell cycle. Assembly of Rad9 on chromatin after DNA damage is promoted by histone modifications that create docking sites for Rad9 recruitment, allowing checkpoint activation. Rad53 phosphorylation is also dependent upon BRCT-directed Rad9 oligomerization; however, the crosstalk between these molecular determinants and their functional significance are poorly understood.

MRN and the race to the break.

In all living cells, DNA is constantly threatened by both endogenous and exogenous agents. In order to protect genetic information, all cells have developed a sophisticated network of proteins, which constantly monitor genomic integrity. This network, termed the DNA damage response, senses and signals the presence of DNA damage to effect numerous biological responses, including DNA repair, transient cell cycle arrests ("checkpoints") and apoptosis.