Bis{tris­[3-(2-pyrid­yl)-1H-pyrazole]manganese(II)} dodeca­molybdo(V,VI)phosphate hexa­hydrate

The asymmetric unit of the title compound, [Mn(C8H7N3)3]2[PMo12O40]·6H2O, consists of a complex [Mn(C8H7N3)3]2+ cation, half of a mixed-valent MoV,VI α-Keggin-type [PMo12O40]4− heteropolyanion, and three uncoordinated water mol­ecules. The Mn2+ cation is surrounded by six N atoms from three chelating 3-(2-pyrid­yl)-1H-pyrazole ligands in a distorted octa­hedral coordination. In the heteropolyanion, two O atoms of the central PO4 group ( symmetry) are equally disordered about an inversion centre. N—H⋯O and O—H⋯O hydrogen bonding between the cations, anions and the uncoordinated water mol­ecules leads to a consolidation of the structure

Bis{tris­[3-(2-pyrid­yl)-1H-pyrazole]iron(II)} dodeca­molybdo(V,VI)phosphate hexa­hydrate

Crystals of the title compound, [Fe(C8H7N3)3]2[PMo12O40]·6H2O, prepared under hydro­thermal conditions, are isotypic with the Mn2+ and Cd2+ analogues. The Fe2+ cation is in a distorted octa­hedral coordination by six N atoms from three chelating 3-(2-pyrid­yl)-1H-pyrazole ligands. The heteropoly­anion [PMo12O40]4− is a one-electron reduced species in which two O atoms of the central PO4 group ( symmetry) are equally disordered about an inversion centre. N—H⋯O and O—H⋯O hydrogen bonds make a contribution to the crystal packing. The Fe—N bond lengths [2.085 (19)—2.15 (2) Å] are somewhat shorter than the Mn—N and Cd—N bond lengths [2.224 (6)–2.283 (5) and 2.316 (7)–2.334 (6) Å, respectively]. All other bond lengths and angles and the hydrogen-bonding motifs are very similar in the isotypic structures

Deletion of Glut1 in early postnatal cartilage reprograms chondrocytes toward enhanced glutamine oxidation

Abstract Glucose metabolism is fundamental for the functions of all tissues, including cartilage. Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development, little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis. We show here that genetic deletion of the glucose transporter Glut1 in postnatal cartilage impairs cell proliferation and matrix production in growth plate (GPs) but paradoxically increases cartilage remnants in the metaphysis, resulting in shortening of long bones. On the other hand, articular cartilage (AC) with Glut1 deficiency presents diminished cellularity and loss of proteoglycans, which ultimately progress to cartilage fibrosis. Moreover, predisposition to Glut1 deficiency severely exacerbates injury-induced osteoarthritis. Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions, both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability. However, uncontrolled glutamine flux causes collagen overmodification, thus affecting extracellular matrix remodeling in both cartilage compartments. These results uncover the pivotal and distinct roles of Glut1-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism

Bis{tris­[3-(2-pyrid­yl)-1H-pyrazole]cadmium(II)} dodeca­molybdo(V,VI)phosphate hexa­hydrate

The hydro­thermally prepared title compound, [Cd(C8H7N3)3]2[PMo12O40]·6H2O, is isotypic with its MnII analogue [Hao et al. (2010 ▶). Acta Cryst. E66, m231–m232]. The CdII cation is in a distorted octa­hedral environment, coordinated by six N atoms from three chelating 3-(2-pyrid­yl)-1H-pyrazole ligands. In the reduced heteropolyanion, two O atoms of the central PO4 group ( symmetry) are equally disordered about an inversion centre. N—H⋯O and O—H⋯O hydrogen bonds contribute to the crystal packing. Compared with the MnII analogue, the Cd—N bond lengths are longer at 2.316 (7)–2.334 (6) Å, versus 2.224 (6)–2.283 (5) Å for Mn—N, whereas all other bond lengths and angles and the hydrogen-bonding motifs are very similar in the two structures

Bis{tris­[3-(2-pyrid­yl)-1H-pyrazole]nickel(II)} dodeca­molybdo(V,VI)phosphate hexa­hydrate

The hydro­thermally prepared title compound, [Ni(C8H7N3)3]2[PMo12O40]·6H2O, is a member of the isotypic series [(M(C8H7N3)3]2[PMo12O40]·6H2O where M is Mn, Cd, and Fe. The Ni2+ cation is in a distorted octa­hedral environment, coordinated by six N atoms from three chelating 3-(2-pyrid­yl)-1H-pyrazole ligands. In the one-electron reduced heteropolyanion, two O atoms of the central PO4 group ( symmetry) are equally disordered about an inversion centre. N—H⋯O and O—H⋯O hydrogen bonds contribute to the crystal packing. Compared with the isotypic structures, the main difference is related with the M—N bond lengths, whereas all other bond lengths, angles and the hydrogen-bonding motifs are very similar

Effects of facet joint degeneration on stress alterations in cervical spine C5–C6: A finite element analysis

It has been demonstrated that articular facet degeneration can cause local strain alterations and induce neck pain. This study aims to quantify the biomechanical effects of normal and degenerated C5–C6 articular facets, and evaluate the correlation of mechanical strain between healthy and degenerated spine. A 3-dimensional finite element (FE) model of the C5–C6 cervical spine was developed [Model 0 (M0)]. The asymmetric models of C5–C6 bilateral articular facet joint were established separately to mimic articular facet joint degeneration. The capsule ligament stiffness of C5–C6 unilateral facet joint was altered with minimum and maximum threshold to simulate capsule ligaments' lesion and calcification [Model 1 (M1) and Model 2 (M2), respectively]. Besides, the cervical C5–C6 unilateral articular facet joint direction was changed by 5° and 10° forward to imitate the moderate joint hyperplasia and severe osteophyte (Model 3 and Model 4 respectively). M1 increased the rotation range of ipsilateral side (left), while M2 reduced, and both had limited effect on the contralateral side (right). The angle increased in Model 3 (M3) (61°) and Model 4 (M4) (55°) comparing to M0 during the axial rotation, and the angle of M4 was larger. M3 and M4 increased the nucleus pulposus pressure with and without controlled angular displacement during axial rotation. The pressure of nucleus pulpous increased during M1 rotating to the abnormal side but decreased when rotating to the other side, but the results of M2 were opposite. The capsule ligament stiffness made an impact on segmental mobility and vertebral spatial position, and the sagittal angle of articular facet joint exerted an influence on disc pressure distribution

Transcranial Direct Current Stimulation of the Right Lateral Prefrontal Cortex Changes a priori Normative Beliefs in Voluntary Cooperation

A priori normative beliefs, the precondition of social norm compliance that reflects culture and values, are considered unique to human social behavior. Previous studies related to the ultimatum game revealed that right lateral prefrontal cortex (rLPFC) has no stimulation effects on normative beliefs. However, no research has focused on the effects of a priori belief on the rLPFC in voluntary cooperation attached to the public good (PG) game. In this study, we used a linear asymmetric PG to confirm the influence of the rLPFC on a priori normative beliefs without threats of external punishment through transcranial direct current stimulation (tDCS). Participants engaged via computer terminals in groups of four (i.e., two high-endowment players with 35G$and two low-endowment players with 23G$). They were anonymous and had no communication during the entire process. They were randomly assigned to receive 15 min of either anodal, cathodal, or sham stimulation and then asked to answer questions concerning a priori normative beliefs (norm.belief and pg.belief). Results suggested that anodal/cathodal tDCS significantly (P < 0.001) shifted the participants’ a priori normative beliefs in opposite directions compared to the shift in the sham group. In addition, different identities exhibited varying degrees of change (28.80–54.43%). These outcomes provide neural evidence of the rLPFC mechanism’s effect on the normative beliefs in voluntary cooperation based on the PG framework

Phase I study of MLN8237—investigational Aurora A kinase inhibitor—in relapsed/refractory multiple myeloma, Non-Hodgkin lymphoma and chronic lymphocytic leukemia

Purpose Amplification or over-expression of the mitotic Aurora A kinase (AAK) has been reported in several heme-lymphatic malignancies. MLN8237 (alisertib) is a novel inhibitor of AAK that is being developed for the treatment of advanced malignancies. The objectives of this phase I study were to establish the safety, tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in patients with relapsed or refractory heme-lymphatic malignancies. Methods Sequential cohorts of patients received MLN8237 orally as either a powder-in-capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received MLN8237 PIC 25–90 mg for 14 or 21 consecutive days plus 14 or 7 days’ rest, respectively, or MLN8237 ECT, at a starting dose of 40 mg/day once-daily (QD) for 14 days plus 14 days’ rest, all in 28-day cycles. Subsequent cohorts received MLN8237 ECT 30–50 mg twice-daily (BID) for 7 days plus 14 days’ rest in 21-day cycles. Results Fifty-eight patients were enrolled (PIC n = 28, ECT n = 30). The most frequent grade ≥3 drug-related toxicities were neutropenia (45 %), thrombocytopenia (28 %), anemia (19 %), and leukopenia (19 %). The maximum tolerated dose on the ECT 7-day schedule was 50 mg BID. The terminal half-life of MLN8237 was approximately 19 h. Six (13 %) patients achieved partial responses and 13 (28 %) stable disease. Conclusion The recommended phase II dose of MLN8237 ECT is 50 mg BID for 7 days in 21-day cycles, which is currently being evaluated as a single agent in phase II/III trials in patients with peripheral T-cell lymphoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10637-013-0050-9) contains supplementary material, which is available to authorized users

Transcriptomic profiling suggests candidate molecular responses to waterlogging in cassava

Owing to climate change impacts, waterlogging is a serious abiotic stress that affects crops, resulting in stunted growth and loss of productivity. Cassava (Manihot esculenta Grantz) is usually grown in areas that experience high amounts of rainfall; however, little research has been done on the waterlogging tolerance mechanism of this species. Therefore, we investigated the physiological responses of cassava plants to waterlogging stress and analyzed global gene transcription responses in the leaves and roots of waterlogged cassava plants. The results showed that waterlogging stress significantly decreased the leaf chlorophyll content, caused premature senescence, and increased the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in the leaves and roots. In total, 2538 differentially expressed genes (DEGs) were detected in the leaves and 13364 in the roots, with 1523 genes shared between the two tissues. Comparative analysis revealed that the DEGs were related mainly to photosynthesis, amino metabolism, RNA transport and degradation. We also summarized the functions of the pathways that respond to waterlogging and are involved in photosynthesis, glycolysis and galactose metabolism. Additionally, many transcription factors (TFs), such as MYBs, AP2/ERFs, WRKYs and NACs, were identified, suggesting that they potentially function in the waterlogging response in cassava. The expression of 12 randomly selected genes evaluated via both quantitative real-time PCR (qRT-PCR) and RNA sequencing (RNA-seq) was highly correlated (R2 = 0.9077), validating the reliability of the RNA-seq results. The potential waterlogging stress-related transcripts identified in this study are representatives of candidate genes and molecular resources for further understanding the molecular mechanisms underlying the waterlogging response in cassava