Chemical Textures on Rare Earth Carbonates: An Experimental Approach to Mimic the Formation of Bastnäsite.

The interaction between multi-component rare earth element (REE) aqueous solutions and carbonate grains (dolomite, aragonite, and calcite) are studied at hydrothermal conditions (21-210 °C). The effect of ionic radii of five REEs (La, Ce, Pr, Nd, Dy) on solid formation are analyzed using two solution types: equal REE concentrations and concentrations normalized to Post Archean Australian Shale Standard (PAAS). The interaction replaces the host Ca-Mg carbonate grains with a series of REE minerals (lanthanite → kozoite → bastnäsite → cerianite).

The role of fluocerite in the genesis of bastnäsite: mechanistic insights and transformation pathways.

Fluocerite is a rare earth element (REE) fluoride found as an accessory mineral in magmatic-hydrothermal REE ore deposits, including alkaline complexes and carbonatites, where it is often associated with REE-fluorocarbonates. This study investigates the crystallisation kinetics, mechanisms and energetics of fluocerite (REEF) and its role as a precursor phase of bastnäsite, one of the key minerals used for the extraction of REE. Fluocerite was synthesized by reacting pure fluorite (CaF) with La-, Ce- and Nd-bearing solutions at temperatures ranging from ambient to low hydrothermal (30-90 °C).

Triptolide and its prodrug Minnelide target high-risk MYC-amplified medulloblastoma in preclinical models.

Most children with medulloblastoma (MB) achieve remission, but some face very aggressive metastatic tumors. Their dismal outcome highlights the critical need to advance therapeutic approaches that benefit such high-risk patients. Minnelide, a clinically relevant analog of the natural product triptolide, has oncostatic activity in both preclinical and early clinical settings.

Mechanistic insights into medulloblastoma relapse.

Pediatric brain tumors are the leading cause of cancer-related deaths in children, with medulloblastoma (MB) being the most common type. A better understanding of these malignancies has led to their classification into four major molecular subgroups. This classification not only facilitates the stratification of clinical trials, but also the development of more effective therapies.

Impact of Rare Earth Elements on CaCO Crystallization: Insights into Kinetics, Mechanisms, and Crystal Morphology.

This study investigated the crystallization kinetics and mechanisms of calcium carbonate (CaCO) in the presence of rare earth elements (REEs) including lanthanum (La), neodymium (Nd), and dysprosium (Dy). Through a comprehensive approach utilizing UV-vis spectrophotometry, powder X-ray diffraction, and high-resolution electron microscopy, we examined the effects of REEs on CaCO growth from solution at varying concentrations and combinations of REEs. Our findings highlight that even trace amounts of REEs significantly decelerate the rate of CaCO crystallization, also leading to alterations in crystal morphology and mechanisms of growth.

Endoplasmic reticulum regulation of glucose metabolism in glioma stem cells.

Glioblastoma (GBM) treatment is extremely challenging due to the high complexity of the tumor. It is one of the tumors in which a subpopulation of highly resistant glioma initiating cells (GICs) has been clearly identified. Thus, understanding the differences between GICs and tumor bulk cells is therefore essential to move to less conventional but more efficient approaches.

The role of nanocerianite (CeO) in the stability of Ce carbonates at low-hydrothermal conditions.

The formation of cerianite (CeO) was investigated at low hydrothermal conditions (35-205 °C) two experimental settings: (1) crystallisation from solution experiments, and (2) replacement of Ca-Mg carbonates (calcite, dolomite, aragonite) mediated by Ce-bearing aqueous solutions. The solid samples were studied with a combination of powder X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The results revealed a multi-step crystallisation pathway: amorphous Ce carbonate → Ce-lanthanite [Ce(CO)·8HO] → Ce-kozoite [orthorhombic CeCO(OH)] → Ce-hydroxylbastnasite [hexagonal CeCO(OH)] → cerianite [CeO].

Targeted Crystallization of Rare Earth Carbonate Polymorphs at Hydrothermal Conditions via Mineral Replacement Reactions.

The interaction between rare earth element (REE)-rich (La, Pr, Nd, Dy) aqueous solutions, dolomite (CaMg(CO)), and aragonite (CaCO) at low temperature hydrothermal conditions (25-220 °C) is studied. The experiments result in the solvent-mediated surface precipitation and subsequent pseudomorphic mineral replacement of the dolomite and aragonite seeds by newly formed REE-carbonates. The host grains are replaced from periphery inward.

Protein arginine methyltransferase 5 regulates SHH-subgroup medulloblastoma progression.

Background: Medulloblastoma (MB) is the most common pediatric brain tumor. Although standard-of-care treatment generally results in good prognosis, many patients exhibit treatment-associated lifelong disabilities. This outcome could be improved by employing therapies targeting the molecular drivers of this cancer.

Systemic protothecosis in an immunocompetent patient.

Background: Although uncommon, there is increasing interest and public health concerns of the pathogen Prototheca spp, a ubiquitous achlorophilic microalgae that can affect both humans and animals. High mortality rates have been reported in immunocompromised patients with disseminated infection, but no data is available in the immunocompetent population.

Case Presentation: We present the case of a 59-year-old man from rural area of Colombia who was admitted to the intensive care unit due to decompensated heart failure that was difficult to medically manage, with development of septic shock and isolation of Prototheca wickerhamii from blood culture.

Neuromuscular blocking agents in the intensive care unit.

Neuromuscular blocking agents (NMBA) are a controversial therapeutic option in the approach to the critically ill patient. They are not innocuous, and the available evidence does not support their routine use in the intensive care unit. If necessary, monitoring protocols should be established to avoid residual relaxation, adverse effects, and associated complications.

A Druggable UHRF1/DNMT1/GLI Complex Regulates Sonic Hedgehog-Dependent Tumor Growth.

Unlabelled: Dysregulation of Sonic hedgehog (SHH) signaling drives the growth of distinct cancer subtypes, including medulloblastoma (MB). Such cancers have been treated in the clinic with a number of clinically relevant SHH inhibitors, the majority of which target the upstream SHH regulator, Smoothened (SMO). Despite considerable efficacy, many of these patients develop resistance to these drugs, primarily due to mutations in SMO.

Noncanonical activation of GLI signaling in SOX2 cells drives medulloblastoma relapse.

SRY (sex determining region Y)-box 2 (SOX2)-labeled cells play key roles in chemoresistance and tumor relapse; thus, it is critical to elucidate the mechanisms propagating them. Single-cell transcriptomic analyses of the most common malignant pediatric brain tumor, medulloblastoma (MB), revealed the existence of astrocytic cells expressing sonic hedgehog (SHH) signaling biomarkers. Treatment with vismodegib, an SHH inhibitor that acts on Smoothened (Smo), led to increases in astrocyte-like cells.

Epigenetic pathways and plasticity in brain tumors.

Clinical studies have shown that treating many primary brain tumors is challenging due in part to the lack of safe and effective compounds that cross the blood brain barrier (BBB) (Tan et al., 2018). However, if we were to imagine that we have ideal BBB penetrant compounds that target brain tumor cells selectively, recent studies suggest that those compounds may still not be effective due to the heterogenous nature of the tumors.

Regulation of cancer cell glucose metabolism is determinant for cancer cell fate after melatonin administration.

Several oncogenic pathways plus local microenvironmental conditions, such as hypoxia, converge on the regulation of cancer cells metabolism. The major metabolic alteration consists of a shift from oxidative phosphorylation as the major glucose consumer to aerobic glycolysis, although most of cancer cells utilize both pathways to a greater or lesser extent. Aerobic glycolysis, together with the directly related metabolic pathways such as the tricarboxylic acid cycle, the pentose phosphate pathway, or gluconeogenesis are currently considered as therapeutic targets in cancer research.

Role of glucose metabolism in the differential antileukemic effect of melatonin on wild‑type and FLT3‑ITD mutant cells.

The FMS‑like tyrosine kinase 3 internal tandem duplication (FLT3‑ITD) mutation represents the most frequent genetic alteration in acute myeloid leukemia (AML) and is associated with poor prognosis. The mutation promotes cancer cell survival and proliferation, and shifts their glucose metabolism towards aerobic glycolysis, a frequent alteration in cancer. In the present study, the impact of melatonin on the viability of AML cell lines with (MV‑4‑11 and MOLM‑13) or without the FLT3‑ITD mutation (OCI‑AML3 and U‑937) was evaluated.

Time series modeling of cell cycle exit identifies Brd4 dependent regulation of cerebellar neurogenesis.

Cerebellar neuronal progenitors undergo a series of divisions before irreversibly exiting the cell cycle and differentiating into neurons. Dysfunction of this process underlies many neurological diseases including ataxia and the most common pediatric brain tumor, medulloblastoma. To better define the pathways controlling the most abundant neuronal cells in the mammalian cerebellum, cerebellar granule cell progenitors (GCPs), we performed RNA-sequencing of GCPs exiting the cell cycle.

A CK1α Activator Penetrates the Brain and Shows Efficacy Against Drug-resistant Metastatic Medulloblastoma.

Purpose: Although most children with medulloblastoma are cured of their disease, Sonic Hedgehog (SHH) subgroup medulloblastoma driven by mutations is essentially lethal. Casein kinase 1α (CK1α) phosphorylates and destabilizes GLI transcription factors, thereby inhibiting the key effectors of SHH signaling. We therefore tested a second-generation CK1α activator against -mutant, -amplified medulloblastoma.

Organic synthesis on Mars by electrochemical reduction of CO.

The sources and nature of organic carbon on Mars have been a subject of intense research. Steele (2012) showed that 10 martian meteorites contain macromolecular carbon phases contained within pyroxene- and olivine-hosted melt inclusions. Here, we show that martian meteorites Tissint, Nakhla, and NWA 1950 have an inventory of organic carbon species associated with fluid-mineral reactions that are remarkably consistent with those detected by the Mars Science Laboratory (MSL) mission.

Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma.

The SMOOTHENED inhibitor vismodegib is FDA approved for advanced basal cell carcinoma (BCC), and shows promise in clinical trials for SONIC HEDGEHOG (SHH)-subgroup medulloblastoma (MB) patients. Clinical experience with BCC patients shows that continuous exposure to vismodegib is necessary to prevent tumor recurrence, suggesting the existence of a vismodegib-resistant reservoir of tumor-propagating cells. We isolated such tumor-propagating cells from a mouse model of SHH-subgroup MB and grew them as sphere cultures.

Differential abundance of CK1α provides selectivity for pharmacological CK1α activators to target WNT-dependent tumors.

Constitutive WNT activity drives the growth of various human tumors, including nearly all colorectal cancers (CRCs). Despite this prominence in cancer, no WNT inhibitor is currently approved for use in the clinic largely due to the small number of druggable signaling components in the WNT pathway and the substantial toxicity to normal gastrointestinal tissue. We have shown that pyrvinium, which activates casein kinase 1α (CK1α), is a potent inhibitor of WNT signaling.

The role of amorphous precursors in the crystallization of La and Nd carbonates.

Crystalline La and Nd carbonates can be formed from poorly-ordered nanoparticulate precursors, termed amorphous lanthanum carbonate (ALC) and amorphous neodymium carbonate (ANC). When reacted in air or in aqueous solutions these precursors show highly variable lifetimes and crystallization pathways. We have characterized these precursors and the crystallization pathways and products with solid-state, spectroscopic and microscopic techniques to explain the differences in crystallization mechanisms between the La and Nd systems.

Biomineralisation by earthworms - an investigation into the stability and distribution of amorphous calcium carbonate.

Background: Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions.