The social contexts of behaviors and relationships: The relation of classroom and cyber victimization to number of classroom and cyber friends.

Behaviors and relationships exist within a variety of social contexts. More specifically for the current research, victimization and friendships occur in classrooms and, increasingly, in online virtual contexts. The current research examined how the number of classroom friends and number of cyber friends related to the extent of classroom victimization and extent of cyber victimization.

Shifting Norms in Faith Communities to Reduce Intimate Partner Violence: Results from a Cluster Randomized Controlled Trial in Nigeria.

Programs aiming to reduce intimate partner violence (IPV) increasingly seek to shift social norms. Few interventions have been rigorously evaluated for their impact on norms and incidence of IPV, particularly in sub-Saharan Africa. Shifting norms at the community level and subsequent pathways to behavior change remain poorly understood.

AKT activation because of PTEN loss upregulates xCT via GSK3β/NRF2, leading to inhibition of ferroptosis in PTEN-mutant tumor cells.

Here, we show that the tumor suppressor phosphatase and tensin homolog deleted from chromosome 10 (PTEN) sensitizes cells to ferroptosis, an iron-dependent form of cell death, by restraining the expression and activity of the cystine/glutamate antiporter system X (xCT). Loss of PTEN activates AKT kinase to inhibit GSK3β, increasing NF-E2 p45-related factor 2 (NRF2) along with transcription of one of its known target genes encoding xCT. Elevated xCT in Pten-null mouse embryonic fibroblasts increases the flux of cystine transport and synthesis of glutathione, which enhances the steady-state levels of these metabolites.

Technologies bringing young Zebrafish from a niche field to the limelight.

Fundamental life science and pharmaceutical research are continually striving to provide physiologically relevant context for their biological studies. Zebrafish present an opportunity for high-content screening (HCS) to bring a true in vivo model system to screening studies. Zebrafish embryos and young larvae are an economical, human-relevant model organism that are amenable to both genetic engineering and modification, and direct inspection via microscopy.

Do children with mathematical learning disabilities use the inversion principle to solve three-term arithmetic problems?: The impact of presentation mode.

Numerical inversion is the ability to understand that addition is the opposite of subtraction and vice versa. Three-term arithmetic problems can be solved without calculation using this conceptual shortcut. To verify that this principle is used, inverse problems (a + b - b) can be compared with standard problems (a + b - c).

Differential Requirement of and for Primitive and Definitive Myeloid Development in Zebrafish.

Germline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of the Gata2 gene as a result of an additional round of ancestral whole genome duplication.

A versatile, automated and high-throughput drug screening platform for zebrafish embryos.

Zebrafish provide a unique opportunity for drug screening in living animals, with the fast-developing, transparent embryos allowing for relatively high-throughput, microscopy-based screens. However, the limited availability of rapid, flexible imaging and analysis platforms has limited the use of zebrafish in drug screens. We have developed an easy-to-use, customisable automated screening procedure suitable for high-throughput phenotype-based screens of live zebrafish.

TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling.

Myelodysplastic syndrome (MDS) is a hematological malignancy characterized by blood cytopenias and predisposition to acute myeloid leukemia (AML). Therapies for MDS are lacking, particularly those that have an impact in the early stages of disease. We developed a model of MDS in zebrafish with knockout of Rps14, the primary mediator of the anemia associated with del(5q) MDS.

AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway-Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B.

Unlabelled: Using a panel of cancer cell lines, we characterized a novel degrader of AKT, MS21. In mutant PI3K-PTEN pathway cell lines, AKT degradation was superior to AKT kinase inhibition for reducing cell growth and sustaining lower signaling over many days. AKT degradation, but not kinase inhibition, profoundly lowered Aurora kinase B (AURKB) protein, which is known to be essential for cell division, and induced G2-M arrest and hyperploidy.

Strategies and analytical workflows to extend the dynamic range in quantitative LC-MS/MS analysis.

To evaluate alternative analytical strategies to extend the dynamic range in quantitative LC-MS/MS. Two approaches based on prior or no prior knowledge of expected exposure levels were evaluated. These approaches make use of two analytical strategies, which include the use of more than one injection volume or dilution of sample extract with solvents or solvent mixtures.

Novel non-ATP competitive small molecules targeting the CK2 α/β interface.

Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2α and CK2β at the α-β interface of the holoenzyme.

Engaging police to identify challenging school crossings and potential improvements.

This paper discusses the value of police officers as vital sources of information regarding pedestrian safety in their communities by presenting results from a survey of traffic safety police officers. The survey requested information on school crossings that the officers considered most challenging for pedestrians. Officers specified the intersections or mid-block locations with school crossings, and answered questions about elements of the locations, such as what makes the locations challenging, and what might be done to improve conditions at these locations.

Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium falciparum.

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-cross-linkable probe to investigate the targets of our diaminoquinazoline series.

Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti- activity.

HKMTs (PfHKMTs) play a key role in controlling gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent anti- activity.

Flexible nano- and microliter injections on a single liquid chromatography-mass spectrometry system: Minimizing sample preparation and maximizing linear dynamic range.

Lack of knowledge on the expected concentration range or insufficient linear dynamic range of the analytical method applied are common challenges for the analytical scientist. Samples that are above the upper limit of quantification are typically diluted and reanalyzed. The analysis of undiluted highly concentrated samples can cause contamination of the system, while the dilution step is time consuming and as the case for any sample preparation step, also potentially leads to precipitation, adsorption or degradation of the analytes.

An atmospheric pressure ionization source using a high voltage target compared to electrospray ionization for the LC/MS analysis of pharmaceutical compounds.

The type and design of an ionization source can have a significant influence on the performances of a bioanalytical method. It is, therefore, of high interest to evaluate the performances of newly introduced sources to highlight their benefits and limitations in comparison to other well established sources. In this paper, liquid chromatography - mass spectrometry (LC/MS) performances of a new atmospheric pressure ionization (API) source, commercialized as UniSpray, is evaluated.

Atmospheric Pressure Ionization Using a High Voltage Target Compared to Electrospray Ionization.

A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head comparison with electrospray ionization (ESI) on the same high-resolution MS system. The atmospheric pressure ionization source is composed of a grounded nebulizer spraying onto a high voltage, cylindrical stainless steel target.

Enhanced performance for the analysis of prostaglandins and thromboxanes by liquid chromatography-tandem mass spectrometry using a new atmospheric pressure ionization source.

Eicosanoids, including prostaglandins and thromboxanes are lipid mediators synthetized from polyunsaturated fatty acids. They play an important role in cell signaling and are often reported as inflammatory markers. LC-MS/MS is the technique of choice for the analysis of these compounds, often in combination with advanced sample preparation techniques.

XPC: Going where no DNA damage sensor has gone before.

XPC has long been considered instrumental in DNA damage recognition during global genome nucleotide excision repair (GG-NER). While this recognition is crucial for organismal health and survival, as XPC's recognition of lesions stimulates global genomic repair, more recent lines of research have uncovered many new non-canonical pathways in which XPC plays a role, such as base excision repair (BER), chromatin remodeling, cell signaling, proteolytic degradation, and cellular viability. Since the first discovery of its yeast homolog, Rad4, the involvement of XPC in cellular regulation has expanded considerably.

One drop chemical derivatization--DESI-MS analysis for metabolite structure identification.

Structural elucidation of metabolites is an important part during the discovery and development process of new pharmaceutical drugs. Liquid Chromatography (LC) in combination with Mass Spectrometry (MS) is usually the technique of choice for structural identification but cannot always provide precise structural identification of the studied metabolite (e.g.

Anterior cingulate cortex and intuitive bias detection during number conservation.

Children's number conservation is often biased by misleading intuitions but the precise nature of these conservation errors is not clear. A key question is whether children detect that their erroneous conservation judgment is unwarranted. The present study reanalyzed available fMRI data to test the implication of the anterior cingulate cortex (ACC) in this detection process.

The deubiquitinating enzyme USP24 is a regulator of the UV damage response.

Regulation of p53 by ubiquitination and deubiquitination is important for its function. In this study, we demonstrate that USP24 deubiquitinates p53 in human cells. Functional USP24 is required for p53 stabilization, and p53 destabilization in USP24-depleted cells can be corrected by the forced expression of USP24.

Sources of individual variability: miRNAs that predispose to neuropathic pain identified using genome-wide sequencing.

Background: We carried out a genome-wide study, using microRNA sequencing (miRNA-seq), aimed at identifying miRNAs in primary sensory neurons that are associated with neuropathic pain. Such scans usually yield long lists of transcripts regulated by nerve injury, but not necessarily related to pain. To overcome this we tried a novel search strategy: identification of transcripts regulated differentially by nerve injury in rat lines very similar except for a contrasting pain phenotype.

Dynamics of the anatomical changes that occur in the brains of schoolchildren as they learn to read.

Although the functional brain network involved in reading for adults and children is now well documented, a critical lack of knowledge still exists about the structural development of these brain areas. To provide a better overview of the structural dynamics of the brain that sustain reading acquisition, we acquired anatomical MRI brain images from 55 children that were divided into two groups: one prior to the formal learning of reading (n = 33, 5-6 years old) and the second a few years after formal learning (n = 22, 9-10 years old). Reading performances were collected based on the "Alouette-R" test, a standardized test for reading text in French.

A human XPC protein interactome--a resource.

Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening.