Assessment of selected pharmaceuticals in Riyadh wastewater treatment plants, Saudi Arabia: Mass loadings, seasonal variations, removal efficiency and environmental risk.

Despite increasing interest in pharmaceutical emissions worldwide, studies of environmental contamination with pharmaceuticals arising from wastewater discharges in Saudi Arabia are scarce. Therefore, this study examined occurrence, mass loads and removal efficiency for 15 pharmaceuticals and one metabolite (oxypurinol) from different therapeutic classes in three wastewater treatment plants (WWTPs), in Riyadh city in Saudi Arabia. A total of 144 samples were collected from the influents and effluents between March 2018 and July 2019 and analyzed using Solid Phase Extraction followed by triple quadrupole LC-MS/MS.

Ectopic expression of T in the paraxial mesoderm disrupts somite maturation in the mouse.

T is the founding member of the T-box family of transcription factors; family members are critical for cell fate decisions and tissue morphogenesis throughout the animal kingdom. T is expressed in the primitive streak and notochord with mouse mutant studies revealing its critical role in mesoderm formation in the primitive streak and notochord integrity. We previously demonstrated that misexpression of Tbx6 in the paraxial and lateral plate mesoderm results in embryos resembling Tbx15 and Tbx18 nulls.

A Multiple-Trait Bayesian Variable Selection Regression Method for Integrating Phenotypic Causal Networks in Genome-Wide Association Studies.

Bayesian regression methods that incorporate different mixture priors for marker effects are used in multi-trait genomic prediction. These methods can also be extended to genome-wide association studies (GWAS). In multiple-trait GWAS, incorporating the underlying causal structures among traits is essential for comprehensively understanding the relationship between genotypes and traits of interest.

Functionally distinct roles for T and Tbx6 during mouse development.

The mouse T-box transcription factors T and Tbx6 are co-expressed in the primitive streak and have unique domains of expression; T is expressed in the notochord, while Tbx6 is expressed in the presomitic mesoderm. T-box factors are related through a shared DNA binding domain, the T-domain, and can therefore bind to similar DNA sequences at least We investigated the functional similarities and differences of T and Tbx6 DNA binding and transcriptional activity and their interaction genetically We show that at one target, , the T-domains of T and Tbx6 have different affinities for the binding sites present in the mesoderm enhancer. We further show using assays that T and Tbx6 differentially affect transcription with Tbx6 activating expression tenfold higher than T, that T and Tbx6 can compete at target gene enhancers, and that this competition requires a functional DNA binding domain.

Capacity challenges in water quality monitoring: understanding the role of human development.

Monitoring the qualitative status of freshwaters is an important goal of the international community, as stated in the Sustainable Development Goal (SDGs) indicator 6.3.2 on good ambient water quality.

Water Quality Assessment: A Quali-Quantitative Method for Evaluation of Environmental Pressures Potentially Impacting on Groundwater, Developed under the M.I.N.O.Re. Project.

At global level, the vulnerability of aquifers is deteriorating at an alarming rate due to environmental pollution and intensive human activities. In this context, Local Health Authority ASL Lecce has launched the M.I.

Applying citizen science to monitor for the Sustainable Development Goal Indicator 6.3.2: a review.

The United Nations has called for increased public participation in scientific research, to benefit professionals, the public and the planet. Citizen science has been suggested as a cost-effective means by which this call can be met, and by which monitoring for the Sustainable Development Goals (SDGs) may be carried out. Indeed, citizen science has gained significant attention in recent years as the scale of environmental issues surpasses the monitoring resources that currently exist.

Validating citizen science monitoring of ambient water quality for the United Nations sustainable development goals.

Citizen science (CS) may be described as research carried out by members of the public with the aim of gathering scientific information for the purpose of aiding in scientific projects. It has many potential advantages, including data collection at a scale not possible by professional scientists alone. The United Nations (UN) has recently recognized citizen science as a potential source of data that may contribute to the UN Sustainable Development Goals (SDGs).

Impaired intermediate formation in mouse embryos expressing reduced levels of Tbx6.

Intermediate mesoderm (IM) is the strip of tissue lying between the paraxial mesoderm (PAM) and the lateral plate mesoderm that gives rise to the kidneys and gonads. Chick fate mapping studies suggest that IM is specified shortly after cells leave the primitive streak and that these cells do not require external signals to express IM-specific genes. Surgical manipulations of the chick embryo, however, revealed that PAM-specific signals are required for IM differentiation into pronephros-the first kidney.

TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.

Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined.

Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.

In humans, congenital spinal defects occur with an incidence of 0.5-1 per 1000 live births. One of the most severe syndromes with such defects is spondylocostal dysostosis (SCD).

Microbiological assessment of private drinking water supplies in Co. Cork, Ireland.

The microbiological quality of 75 private drinking water supply boreholes in Co. Cork, Ireland was assessed in order to determine the incidence of contamination and the potential pathways of such contamination. Microbiological analysis was carried out using the membrane filtration technique for the recovery of thermotolerant (faecal) coliforms.

The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.

Segmentation is an organizing principle of body plans. The segmentation clock, a molecular oscillator best illustrated by the cyclic expression of Notch signalling genes, controls the periodic cleavage of somites from unsegmented presomitic mesoderm during vertebrate segmentation. Wnt3a controls the spatiotemporal expression of cyclic Notch genes; however, the underlying mechanisms remain obscure.

Tbx18 and Tbx15 null-like phenotypes in mouse embryos expressing Tbx6 in somitic and lateral plate mesoderm.

Members of the T-box family of transcription factors play essential roles in cell type specification, differentiation, and proliferation during embryonic development. All T-box family members share a common DNA binding domain - the T-domain - and can therefore recognize similar sequences. Consequently, T-box proteins that are co-expressed during development have the potential to compete for binding at downstream targets.

Kinked tail mutation results in notochord defects in heterozygotes and distal visceral endoderm defects in homozygotes.

Proper formation of the anterior-posterior (AP) axis in the developing embryo is critical for the correct patterning and often survival of the organism. In the mouse, an initial step in axis establishment is the specification and migration of the distal visceral endoderm (DVE). We have identified a semi-dominant spontaneous mutation in mouse, named kinked tail (knk), which when heterozygous results in a kinky tail phenotype due to fusions and dysmorphology of the tail vertebrae.

Generation of transgenic mice expressing Cre recombinase under the control of the Dll1 mesoderm enhancer element.

To study paraxial mesoderm formation in the mouse, transgenic lines that can be used to either selectively delete or express genes of interest in the paraxial mesoderm are required. We have generated a transgenic mouse line that expresses Cre recombinase in the paraxial mesoderm (PAM) beginning at e7.5.

Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis.

The metameric structures in vertebrates are based on the periodicity of the somites that are formed one by one from the anterior end of the presomitic mesoderm (PSM). The timing and spacing of somitogenesis are regulated by the segmentation clock, which is characterized by the oscillation of several signaling pathways in mice. The temporal information needs to be translated into a spatial pattern in the so-called determination front, at which cells become responsive to the clock signal.

Clinical laboratory specimen rejection--association with the site of patient care and patients' characteristics: findings from a single health care organization.

Context: Programs to track laboratory quality have reported aggregated specimen rejection rates ranging from 0.30% to 0.83%.

3-[Substituted]-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitriles: identification of highly potent and selective metabotropic glutamate subtype 5 receptor antagonists.

Structure-activity relationship studies on the phenyl ring of 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile 2 led to the discovery that small, non-hydrogen bond donor substituents at the 3-position led to a substantial increase in in vitro potency. In particular, 3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (7) is a highly potent and selective mGlu5 receptor antagonist with good rat pharmacokinetics, brain penetration, and in vivo receptor occupancy.

Dll1 is a downstream target of Tbx6 in the paraxial mesoderm.

Tbx6 is a member of the T-box family of transcription factors. In the mouse, Tbx6 is expressed in the primitive streak, tail bud, and presomitic mesoderm and is essential for the specification of posterior paraxial mesoderm; in its absence, posterior somites are replaced by ectopic neural tubes. Analysis of embryos expressing reduced levels of Tbx6 also revealed that it is required for the correct patterning of the somites as well as their initial specification.

Regulation of Tbx6 expression by Notch signaling.

Somites are the first overt sign of segmentation in the vertebrate embryo and form from bilateral strips of paraxial mesoderm. Paraxial mesoderm arises from the primitive streak; it then migrates laterally and comes to lie on both sides of the neural tube. In the mouse, the T-box transcription factor Tbx6 is required for both somite formation and patterning.

Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice.

The metabotropic glutamate receptor subtype mGlu5 modulates central reward pathways. Many transmitter systems within reward pathways affect feeding. We examined the potential role of mGlu5 in body weight regulation using genetic and pharmacological approaches.

Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity.

Structure-activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as (10) that are devoid of cytochrome P450 inhibitory activity.

3-[3-Fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl]-4-methylpyridine: a highly potent and orally bioavailable metabotropic glutamate subtype 5 (mGlu5) receptor antagonist.

Structure-activity relationship studies performed around 3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile for the purpose of developing novel mGlu5 receptor antagonists are described. Synthesis of a series of four-ring tetrazoles led to the discovery of 3-[3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl]-4-methylpyridine, a highly potent, brain penetrant, azole-based mGlu5 receptor antagonist.