Chemo-Phosphoproteomic Profiling with ATR Inhibitors Berzosertib and Gartisertib Uncovers New Biomarkers and DNA Damage Response Regulators.

The ATR kinase protects cells against DNA damage and replication stress and represents a promising anti-cancer drug target. The ATR inhibitors (ATRi) berzosertib and gartisertib are both in clinical trials for the treatment of advanced solid tumors as monotherapy or in combination with genotoxic agents. We carried out quantitative phospho-proteomic screening for ATR biomarkers that are highly sensitive to berzosertib and gartisertib, using an optimized mass spectrometry pipeline.

Biobased de novo synthesis, upcycling, and recycling - the heartbeat toward a green and sustainable polyethylene terephthalate industry.

Polyethylene terephthalate (PET) has revolutionized the industrial sector because of its versatility, with its predominant uses in the textiles and packaging materials industries. Despite the various advantages of this polymer, its synthesis is, unfavorably, tightly intertwined with nonrenewable fossil resources. Additionally, given its widespread use, accumulating PET waste poses a significant environmental challenge.

Accuracy of Palatal Orthodontic Mini-Implants Placed Using Fully Digital Planned Insertion Guides: A Cadaver Study.

Digital workflows have become integral in orthodontic diagnosis and therapy, reducing risk factors and chair time with one-visit protocols. This study assessed the transfer accuracy of fully digital planned insertion guides for orthodontic mini-implants (OMIs) compared with freehanded insertion. Cone-beam computed tomography (CBCT) datasets and intraoral surface scans of 32 cadaver maxillae were used to place 64 miniscrews in the anterior palate.

Systems metabolic engineering upgrades Corynebacterium glutamicum for selective high-level production of the chiral drug precursor and cell-protective extremolyte L-pipecolic acid.

The nonproteinogenic cyclic metabolite l-pipecolic acid is a chiral precursor for the synthesis of various commercial drugs and functions as a cell-protective extremolyte and mediator of defense in plants, enabling high-value applications in the pharmaceutical, medical, cosmetic, and agrochemical markets. To date, the production of the compound is unfavorably fossil-based. Here, we upgraded the strain Corynebacterium glutamicum for l-pipecolic acid production using systems metabolic engineering.

Effects of wingwave on athletes' wellbeing and fluidity of gaze behavior.

Introduction: The wingwave method combining a muscular test and elements of eye movement desensitization and reprocessing has been found to successfully reduce anxiety and improve relaxation in people. However, it is still unclear how exactly its application improves individual wellbeing (though it is assumed to be related to changes in gaze patterns) and if it works for team sport athletes.

Method: To test both, team sport athletes who had reported a problem with a team sport aspect were randomly assigned to an experimental group and a control group.

Systems metabolic engineering upgrades Corynebacterium glutamicum to high-efficiency cis, cis-muconic acid production from lignin-based aromatics.

Lignin displays a highly challenging renewable. To date, massive amounts of lignin, generated in lignocellulosic processing facilities, are for the most part merely burned due to lacking value-added alternatives. Aromatic lignin monomers of recognized relevance are in particular vanillin, and to a lesser extent vanillate, because they are accessible at high yield from softwood-lignin using industrially operated alkaline oxidative depolymerization.

In vivo stress reporters as early biomarkers of the cellular changes associated with progeria.

Age-related diseases account for a high proportion of the total global burden of disease. Despite recent advances in understanding their molecular basis, there is a lack of suitable early biomarkers to test selected compounds and accelerate their translation to clinical trials. We have investigated the utility of in vivo stress reporter systems as surrogate early biomarkers of the degenerative disease progression.

Biobased PET from lignin using an engineered cis, cis-muconate-producing Pseudomonas putida strain with superior robustness, energy and redox properties.

Polyethylene terephthalate (PET), the most common synthetic polyester today, is largely produced from fossil resources, contributing to global warming. Consequently, sustainable sources must be developed to meet the increasing demand for this useful polymer. Here, we demonstrate a cascaded value chain that provides green PET from lignin, the world's most underutilized renewable, via fermentative production of cis, cis-muconate (MA) from lignin-based aromatics as a central step.

Anxiety Reduction and Improved Concentration in Schoolchildren through Wingwave Coaching.

(1) Background: For nearly 20 years, the wingwave method, which combines elements of eye movement desensitization and reprocessing (EMDR) and a muscular strength test, has been used to reduce anxiety and improve relaxation in subjects. Past studies have scientifically evaluated this method in various contexts and have found it to be effective. In this study, we investigated the effects of short-term wingwave coaching on specific anxiety parameters regarding school, concentration ability, and subjective feelings towards two self-chosen themes in schoolchildren.

Entrained Flow Gasification of Polypropylene Pyrolysis Oil.

Petrochemical products could be produced from circular feedstock, such as waste plastics. Most plants that utilize syngas in their production are today equipped with entrained flow gasifiers, as this type of gasifier generates the highest syngas quality. However, feeding of circular feedstocks to an entrained flow gasifier can be problematic.

Guiding stars to the field of dreams: Metabolically engineered pathways and microbial platforms for a sustainable lignin-based industry.

Lignin is an important structural component of terrestrial plants and is readily generated during biomass fractionation in lignocellulose processing facilities. Due to lacking alternatives the majority of technical lignins is industrially simply burned into heat and energy. However, considering its vast abundance and a chemically interesting richness in aromatics, lignin is presently regarded both as the most under-utilized and promising feedstock for value-added applications.

CDKL5 kinase controls transcription-coupled responses to DNA damage.

Mutations in the gene encoding the CDKL5 kinase are among the most common genetic causes of childhood epilepsy and can also give rise to the severe neurodevelopmental condition CDD (CDKL5 deficiency disorder). Despite its importance for human health, the phosphorylation targets and cellular roles of CDKL5 are poorly understood, especially in the cell nucleus. Here, we report that CDKL5 is recruited to sites of DNA damage in actively transcribed regions of the nucleus.

Aspects of chemical recycling of complex plastic waste via the gasification route.

Oxygen blown high-temperature gasification constitutes an opportunity for chemical recycling of plastic wastes. This article summarizes the results from comparative tests of combustion and gasification of two complex plastic wastes: a plastic reject (PR) from processing recycled paper and an automotive shredder residue (ASR). Calculated gasification efficiencies corresponded to about 80% and 60%, respectively.

Differential proteome analysis of the leaves of lead hyperaccumulator, Rhoeo discolor (L. Her.) Hance.

The present study investigated Rhoeo discolor (L. Her.) Hance for its ability to accumulate Pb, which is of relevance to phytoremediation applications.

Ovarian Blood Sampling Identifies Junction Plakoglobin as a Novel Biomarker of Early Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy. Early detection would improve survival, but an effective diagnostic test does not exist. Novel biomarkers for early ovarian cancer diagnosis are therefore warranted.

Phosphoproteomic screening identifies physiological substrates of the CDKL5 kinase.

Mutations in the gene encoding the protein kinase CDKL5 cause a debilitating neurodevelopmental disease termed CDKL5 disorder. The impact of these mutations on CDKL5 function is poorly understood because the substrates and cellular processes controlled by CDKL5 are unclear. Here, we describe a quantitative phosphoproteomic screening which identified MAP1S, CEP131 and DLG5-regulators of microtubule and centrosome function-as cellular substrates of CDKL5.

Reliability of the I-mIBG heart/mediastinum ratio: Results of a multicenter test-retest reproducibility study.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test-retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days.

Proteomic comparisons of opaque and transparent variants of Streptococcus pneumoniae by two dimensional-differential gel electrophoresis.

Streptococcus pneumoniae (the pneumococcus) is a human pathogen, accounting for massive global morbidity and mortality. Although asymptomatic colonization of the nasopharynx almost invariably precedes disease, the critical determinants enabling pneumococcal progression from this niche to cause invasive disease are poorly understood. One mechanism proposed to be central to this transition involves opacity phase variation, whereby pneumococci harvested from the nasopharynx are typically transparent, while those simultaneously harvested from the blood are opaque.

Proteome Analysis of Drosophila Mutants Identifies a Regulatory Role for 14-3-3ε in Metabolic Pathways.

The evolutionary conserved family of 14-3-3 proteins appears to have a role in integrating numerous intracellular pathways, including signal transduction, intracellular trafficking, and metabolism. However, little is known about how this interactive network might be affected by the direct abrogation of 14-3-3 function. The loss of Drosophila 14-3-3ε resulted in reduced survival of mutants during larval-to-adult transition, which is known to depend on an energy supply coming from the histolysis of fat body tissue.

Retrospective 25-year follow-up of treatment outcomes in Angle Class III patients : Success versus failure.

Objectives: Despite recommendations for early treatment of hereditary Angle Class III syndrome, late pubertal growth may cause a relapse requiring surgical intervention. This study was performed to identify predictors of successful Class III treatment.

Materials And Methods: Thirty-eight Class III patients treated with a chincup were retrospectively analyzed.

Novel IEF Peptide Fractionation Method Reveals a Detailed Profile of N-Terminal Acetylation in Chemotherapy-Responsive and -Resistant Ovarian Cancer Cells.

Although acetylation is regarded as a common protein modification, a detailed proteome-wide profile of this post-translational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimized a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 344 N-terminally acetylated proteins, 12 of which are previously unreported.

Proteomic responses to gold(iii)-toxicity in the bacterium Cupriavidus metallidurans CH34.

The metal-resistant β-proteobacterium Cupriavidus metallidurans drives gold (Au) biomineralisation and the (trans)formation of Au nuggets largely via unknown biochemical processes, ultimately leading to the reductive precipitation of mobile, toxic Au(i/iii)-complexes. In this study proteomic responses of C. metallidurans CH34 to mobile, toxic Au(iii)-chloride are investigated.

The use of MALDI-MSI in the investigation of psychiatric and neurodegenerative disorders: A review.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a mass spectrometry technique used for the analysis of macromolecules on an intact tissue of interest, thereby allowing the assessment of molecular signatures in health and disease in the anatomical context. MALDI-MSI is increasingly used to investigate neurodegenerative and psychiatric disorders at the molecular level, including Alzheimer's disease (AD), Parkinson's disease (PD), and schizophrenia (SCZ). These illnesses are characterized by complex neuropathological processes, and conventional proteomic techniques investigating brain tissue homogenates have inherent limitations in determining the precise anatomical or cellular location of proteomic findings.

The European Board of Orthodontists.

The multiplicity of nations, languages and differing ways and levels of specialized orthodontic education in Europe lead to the need for an objective review of the quality of orthodontic care. To this purpose, The European Board of Orthodontists (EBO) was introduced. This article gives an overview of the objectives of the EBO, its development and the requirements for membership.