A community of practice approach to the management of metal resources, metalworking and hoarding in Bronze Age societies.

The burial of metals in hoards is a trademark phenomenon of prehistoric Europe that may be counterintuitive to perceptions of value nowadays. For the first time here, we establish detailed biographies of a large corpus of hoarded metal objects, providing new insights into how societies in the second millennium BC engaged with their convertible material wealth. We move beyond previous research on prehistoric hoarding commonly focussing on separate questions such as what was placed in hoards, who selected the objects, what were the origins of materials, and where and when they were buried.

A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT Technology for Assessing Total Anti-Oxidative Capacity.

Background: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility.

Structure-Activity Relationship in the Leucettine Family of Kinase Inhibitors.

The protein kinase DYRK1A is involved in Alzheimer's disease, Down syndrome, diabetes, viral infections, and leukemia. Leucettines, a family of 2-aminoimidazolin-4-ones derived from the marine sponge alkaloid Leucettamine B, have been developed as pharmacological inhibitors of DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases). We report here on the synthesis and structure-activity relationship (SAR) of 68 Leucettines.

Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes.

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS).

Collective migration during a gap closure in a two-dimensional haptotactic model.

The ability of cells to respond to substrate-bound protein gradients is crucial for many physiological processes, such as immune response, neurogenesis and cancer cell migration. However, the difficulty to produce well-controlled protein gradients has long been a limitation to our understanding of collective cell migration in response to haptotaxis. Here we use a photopatterning technique to create circular, square and linear fibronectin (FN) gradients on two-dimensional (2D) culture substrates.

Engineering slit-like channels for studying the growth of epithelial tissues in 3D-confined spaces.

The development of epithelial lumens in ducts is essential to the functioning of various organs and in organogenesis. Ductal elongation requires the collective migration of cell cohorts in three-dimensional (3D) confined spaces, while maintaining their epithelial integrity. Epithelial lumens generally adopt circular morphologies, however abnormalities in complex physiological environments can lead to the narrowing of glandular spaces that adopt elongated and slit-like morphologies.

Pelvic MRI for Endometriosis: A Diagnostic Challenge for the Inexperienced Radiologist. How Much Experience Is Enough?

Purpose: The purpose of this study was to investigate the impact of radiologist experience on diagnostic performance of pelvic magnetic resonance imaging (MRI) for the evaluation of endometriomas and different localisations of deep pelvic endometriosis (DPE).

Materials And Methods: In this prospective study all pelvic MRI examinations performed for pelvic endometriosis from December 2016 to August 2017 were evaluated by readers with different experience levels; junior resident (0-6 weeks of experience in female imaging), senior resident (7-24 weeks), fellow (6-24 months), and expert (10 years) in female imaging for the presence of endometriomas and DPE. Their evaluations were compared with surgery confirmed with pathology.

Producing Collagen Micro-stripes with Aligned Fibers for Cell Migration Assays.

Introduction: The orientation of collagen fibers in native tissues plays an important role in cell signaling and mediates the progression of tumor cells in breast cancer by a contact guidance mechanism. Understanding how migration of epithelial cells is directed by the alignment of collagen fibers requires assays with standardized orientations of collagen fibers.

Methods: To address this issue, we produced micro-stripes with aligned collagen fibers using an easy-to-use and versatile approach based on the aspiration of a collagen solution within a microchannel.

Actomyosin contractility scales with myoblast elongation and enhances differentiation through YAP nuclear export.

Skeletal muscle fibers are formed by the fusion of mononucleated myoblasts into long linear myotubes, which differentiate and reorganize into multinucleated myofibers that assemble in bundles to form skeletal muscles. This fundamental process requires the elongation of myoblasts into a bipolar shape, although a complete understanding of the mechanisms governing skeletal muscle fusion is lacking. To address this question, we consider cell aspect ratio, actomyosin contractility and the Hippo pathway member YAP as potential regulators of the fusion of myoblasts into myotubes.

Innovative Tools for Mechanobiology: Unraveling Outside-In and Inside-Out Mechanotransduction.

Cells and tissues can sense and react to the modifications of the physico-chemical properties of the extracellular environment (ECM) through integrin-based adhesion sites and adapt their physiological response in a process called mechanotransduction. Due to their critical localization at the cell-ECM interface, transmembrane integrins are mediators of bidirectional signaling, playing a key role in "outside-in" and "inside-out" signal transduction. After presenting the basic conceptual fundamentals related to cell mechanobiology, we review the current state-of-the-art technologies that facilitate the understanding of mechanotransduction signaling pathways.

Traumatic Obturator Hip Dislocation with Marginal Femoral Head Fracture in a 15-Year-Old Adolescent: A High-Energy Trauma-A Case Report and a Review of the Literature.

We report the case of a 15-year-old boy brought to the emergency department after a bike accident, complaining of an isolated left hip pain. The X-rays showed an obturator hip dislocation treated by closed reduction under general anaesthesia, followed by 6 weeks of discharge. The follow-up MRI performed 6 weeks after the trauma showed an avascular femoral head necrosis, for which we performed multiple retrograde femoral head drilling, completed by the injection of autologue stem cells from the iliaq crest.

Talus fracture in a 4-year-old child.

Fracture of the talus is uncommon in childhood. We report a case of talar neck fracture that occurred in a 4-year-old girl. We present the radiological findings, the orthopaedic follow-up and the clinical outcome.

Probing cytoskeletal pre-stress and nuclear mechanics in endothelial cells with spatiotemporally controlled (de-)adhesion kinetics on micropatterned substrates.

The mechanical properties of living cells reflect their propensity to migrate and respond to external forces. Both cellular and nuclear stiffnesses are strongly influenced by the rigidity of the extracellular matrix (ECM) through reorganization of the cyto- and nucleoskeletal protein connections. Changes in this architectural continuum affect cell mechanics and underlie many pathological conditions.

Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks.

3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties.

Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity.

Natural product extracts of the Canadian prairie plant, Thermopsis rhombifolia, have anti-cancer activity in phenotypic cell-based assays.

Many plant species within the terrestrial ecological zones of Canada have not yet been investigated for anti-cancer activity. We examined the scientific literature describing the endemic flora from the prairie ecological zone and selected the species, Thermopsis rhombifolia, locally known as the buffalo bean, for investigation of its anti-cancer potential. We tested it in cell-based assays using phenotypic screens that feature some of the hallmarks of cancer.

Ferrocifen derivatives that induce senescence in cancer cells: selected examples.

Platinum coordination complexes represent an important class of anti-tumor agents. Due to recognized drawbacks, research into other types of metallodrugs has been diversified with the aim of finding new chemical entities with alternative mechanisms of action to overcome classical chemoresistance. P5 and DP1, two closely related ferrocenyl complexes bearing a similar ferrocenyl-ene-phenyl motif and displaying marked differences in their conformations and oxidation state versatility, were assayed in cancer cell models characterized by various sensitivities to pro-apoptotic stimuli.

Growth inhibitory activity for cancer cell lines of lapachol and its natural and semi-synthetic derivatives.

A series of 17 selected natural and semisynthetic 1,4-naphthoquinones were synthesized, and their growth inhibitory activity was evaluated in vitro. The compounds were tested on six human cancer cell lines using the MTT colorimetric assay. The data revealed that of the chemicals under study only lapachol, its acetate and 3-geranyllawsone displayed the highest activity, recording mean IC50 values ranging from 15 to 22 μM.

[Corrigendum] Temozolomide-induced modification of the CXC chemokine network in experimental gliomas.

After the publication of the article, the authors noted an error. The changes are as follows: In the initial and published version of Fig. 5, the data relied on triplicates in both the control (SCR) and treated (siCXCL2)conditions.

CDK/CK1 inhibitors roscovitine and CR8 downregulate amplified MYCN in neuroblastoma cells.

To understand the mechanisms of action of (R)-roscovitine and (S)-CR8, two related pharmacological inhibitors of cyclin-dependent kinases (CDKs), we applied a variety of '-omics' techniques to the human neuroblastoma SH-SY5Y and IMR32 cell lines: (1) kinase interaction assays, (2) affinity competition on immobilized broad-spectrum kinase inhibitors, (3) affinity chromatography on immobilized (R)-roscovitine and (S)-CR8, (4) whole genome transcriptomics analysis and specific quantitative PCR studies, (5) global quantitative proteomics approach and western blot analysis of selected proteins. Altogether, the results show that the major direct targets of these two molecules belong to the CDKs (1,2,5,7,9,12), DYRKs, CLKs and CK1s families. By inhibiting CDK7, CDK9 and CDK12, these inhibitors transiently reduce RNA polymerase 2 activity, which results in downregulation of a large set of genes.

In vitro anti-proliferative effect of naturally occurring oxyprenylated chalcones.

As a continuation of our ongoing studies aimed to depict the effects and mechanism of action of naturally occurring oxyprenylated phenylpropanoids and polyketides, in this paper we describe the synthesis and in vitro anti-proliferative effects of selected compounds belonging to the above cited classes of secondary metabolites on six cancer cell lines using the MTT colorimetric assay. Our study revealed that among the natural products tested, only oxyprenylated chalcones exhibited an appreciable effect (mean IC50 = 32 - 64 microM), while substituted alcohols, phenylpropenes, naphthoquinones, and aminoacid derivatives were by far less active or inactive.

Targeting cyclin-dependent kinases in anti-neoplastic therapy.

Cell cycle progression is controlled by sequential activation of cyclin-dependent kinases (CDKs), which are often deregulated in cancer. Consequently numerous pharmacological inhibitors of CDKs have been developed with the aim of treating cancers. The article briefly reviews CDK inhibitors and their use to treat cancers, with specific focus on the use of biomarkers and drugs combination to improve their therapeutic efficacy.