Glycolysis, a driving force of rheumatoid arthritis.

Resident synoviocytes and synovial microvasculature, together with immune cells from circulation, contribute to pannus formation, the main pathological feature of rheumatoid arthritis (RA), leading to destruction of adjacent cartilage and bone. Seeds, fibroblast-like synoviocytes (FLSs), macrophages, dendritic cells (DCs), B cells, T cells and endothelial cells (ECs) seeds with high metabolic demands undergo metabolic reprogramming from oxidative phosphorylation to glycolysis in response to poor soil of RA synovium with hypoxia, nutrient deficiency and inflammatory stimuli. Glycolysis provides rapid energy supply and biosynthetic precursors to support pathogenic growth of these seeds. The metabolite lactate accumulated during this process in turn condition the soil microenvironment and affect seeds growth by modulating signalling pathways and directing lactylation modifications. This review explores in depth the survival mechanism of seeds with high metabolic demands in the poor soil of RA synovium, providing useful support for elucidating the etiology of RA. In addition, we discuss the role and major post-translational modifications of proteins and enzymes linked to glycolysis to inspire the discovery of novel anti-rheumatic targets.

The scientific progress and prospects of artificial intelligence in digestive endoscopy: A comprehensive bibliometric analysis.

BACKGROUND: Artificial intelligence (AI) has been used for diagnosis and outcome prediction in clinical practice. Furthermore, AI in digestive endoscopy has attracted much attention and shown promising and stimulating results. This study aimed to determine the development trends and research hotspots of AI in digestive endoscopy by visualizing articles. Publications on AI in digestive endoscopy research were retrieved from the Web of Science Core Collection on April 25, 2022. VOSviewer and CiteSpace were used to assess and plot the research outputs. This analytical research was based on original articles and reviews. A total of 524 records of AI research in digestive endoscopy, published between 2005 and 2022, were retrieved. The number of articles has increased 27-fold from 2017 to 2021. Fifty-one countries and 994 institutions contributed to all publications. Asian countries had the highest number of publications. China, the USA, and Japan were consistently the leading driving forces and mainly contributed (26%, 21%, and 14.31%, respectively). With a solid academic reputation in this area, Japan has the highest number of citations per article. Tada Tomohiro published the most articles and received the most citations.. Gastrointestinal endoscopy published the largest number of publications, and 4 of the top 10 cited papers were published in this journal. "The Classification," "ulcerative colitis," "capsule endoscopy," "polyp detection," and "early gastric cancer" were the leading research hotspots. Our study provides systematic elaboration for researchers to better understand the development of AI in gastrointestinal endoscopy.

Geniposide inhibits SphK1 membrane targeting to restore macrophage polarization balance in collagen-induced arthritis mice.

Imbalance of macrophage polarization plays a critical role in the progression of rheumatoid arthritis (RA). Geniposide (GE) has been shown to exert anti-inflammatory effects. However, the effect of GE on macrophage polarization remains unclear. Here, we investigated the regulation of GE on the imbalance of macrophage polarization in RA and how it functions. We established a mouse model of collagen-induced arthritis (CIA) and isolated bone marrow-derived macrophages (BMDMs). The results confirmed that pro-inflammatory M1 macrophages were dominant in CIA mice, but the polarization imbalance of macrophages was restored to a certain extent after GE treatment. Furthermore, the membrane targeting of sphingosine kinase 1 (SphK1) was increased in BMDMs of CIA mice, as manifested by increased membrane and cytoplasmic expression of p-SphK1 and high secretion level of sphingosine-1-phosphate (S1P). RAW264.7 cells were stimulated with lipopolysaccharide (LPS)-interferon (IFN)-γ or interleukin (IL)-4 to induce M1 or M2 phenotype, respectively, to revalidate the results obtained in BMDMs. The results again observed SphK1 membrane targeting in LPS-IFN-γ-stimulated RAW264.7 cells. Selective inhibition of SphK1 by PF543 or inhibition of the S1P receptors by FTY720 both restored the proportion of M1 and M2 macrophages in LPS-IFN-γ-stimulated RAW264.7 cells, confirming that SphK1 membrane targeting mediated a proportional imbalance in M1 and M2 macrophage polarization. In addition, GE inhibited SphK1 membrane targeting and kinase activity. Taken together, results confirmed that the inhibition of SphK1 membrane targeting by GE was responsible for restoring the polarization balance of macrophages in CIA mice.

Global research trends in the field of liver cirrhosis from 2011 to 2020: A visualised and bibliometric study.

BACKGROUND: Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge. AIM: This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decision-making and scientific research. METHODS: Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace. RESULTS: The analytic research was based on original articles and reviews. A total of 7775 records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most (21.95%) and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles (177 articles) and was cited the most frequently. The Journal of Hepatology ranked third in the top 10 journals, which has the highest impact factor (impact factor 2019 = 20.582). Jasmohan S. Bajaj was the most productive author (72 articles). Burst keywords (e.g., sofosbuvir, burden, care, sarcopenia, chronic liver failure, human gut microbiome, and nonalcoholic fatty liver disease) and a succession of reference citation bursts have provided clues about research frontiers in recent years. CONCLUSION: This study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.

Metabonomic analysis of abnormal sphingolipid metabolism in rheumatoid arthritis synovial fibroblasts in hypoxia microenvironment and intervention of geniposide.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a joint hypoxia microenvironment. Our previous untargeted metabolomics study found that sphingolipid (SPL) metabolism was abnormal in the joint synovial fluid samples from adjuvant arthritis (AA) rats. Geniposide (GE), an iridoid glycoside component of the dried fruit of Gardenia jasminoides Ellis, is commonly used for RA treatment in many Asian countries. At present, the mechanism of GE in the treatment of RA, especially in the joint hypoxia microenvironment, is not entirely clear from the perspective of SPL metabolism. The purpose of this research was to explore the potential mechanism of abnormal SPL metabolism in RA joint hypoxia microenvironment and the intervention effect of GE, through the untargeted metabolic analysis based on the ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Arthritis index, foot swelling and histopathology were used to assess whether the AA rat model was successfully established. The SPLs extracts collected from AA rats' synovial tissue, serum and rheumatoid arthritis synovial fibroblasts (RASFs, MH7A cells, hypoxia/normoxia culture) were analyzed by metabolomics and lipdomics approach based on UPLC-Q-TOF/MS, to identify potential biomarkers associated with disorders of GE regulated RA sphingolipid metabolism. As a result, 11 sphingolipid metabolites related to RA were screened and identified. Except for galactosylceramide (d18:1/20:0), GE could recover the change levels of the above 10 sphingolipid biomarkers in varying degrees. Western blotting results showed that the changes in ceramide (Cer) level regulated by GE were related to the down-regulation of acid-sphingomyelinase (A-SMase) expression in synovial tissue of AA rats. To sum up, this research examined the mechanism of GE in the treatment of RA from the perspective of SPL metabolism and provided a new strategy for the screening of biomarkers for clinical diagnosis of RA.

Barrier Properties and Hydrophobicity of Biodegradable Poly(lactic acid) Composites Reinforced with Recycled Chinese Spirits Distiller's Grains.

Adding natural biomass to poly(lactic acid) (PLA) as a reinforcing filler is a way to change the properties of PLA. This paper is about preparing PLA/biomass composites by physically melting and blending Chinese Spirits distiller's grains (CSDG) biomass and PLA to optimize the composite performance. Composites of modified PLA (MPLA) with varying amounts of CSDG were also prepared by the melt-mixing method, and unmodified PLA/CSDG composites were used as a control group for comparative analysis. The functional groups of MPLA enhanced the compatibility between the polymer substrate and CSDG. The composite water vapor/oxygen barrier and mechanical properties were studied. It was found that the barrier and mechanical properties of MPLA/CSDG composites were significantly improved. SEM was adopted to examine the tensile section structure of the composites, and the compatibility between the filler and the matrix was analyzed. An appropriate amount of CSDG had a better dispersibility in the matrix, and it further improved the interfacial bonding force, which in turn improved the composite mechanical properties. X-ray diffraction, thermogravimetric analysis, and differential scanning calorimetry were conducted to determine the crystalline properties and to analyze the stability of the composites. It was found that the CSDG content had a significant effect on the crystallinity. Barrier and biodegradation mechanisms were also discussed.

Genome-wide identification of polar auxin transporter gene families reveals a possible new polar auxin flow in inverted cuttings of Populus yunnanensis.

Inverted cuttings of Populus yunnanensis are characterized by enlarged stems and dwarfed new shoots, and phytohormones play a crucial role in the response to inversion. The polar auxin transport (PAT) system is distinct from the transport systems of other hormones and is controlled by three major transporter gene families: pin-formed (PIN), auxin-resistant/like aux (AUX/LAX) and ATP-binding cassette transporters of the B class (ABCB). Here, we identified these three families in P. trichocarpa, P. euphratica and P. yunnanensis through a genome-wide analysis. The Populus PIN, AUX/LAX and ABCB gene families comprised 15, 8 and 31 members, respectively. Most PAT genes in Populus and Arabidopsis were identified as clear sister pairs, and some had unique motifs. Transcriptome profiling revealed that the expression of most PAT genes was unrelated to cutting inversion and that only several genes showed altered expression when cuttings were inverted. The auxin content difference at positions was opposite in upright and inverted cutting bodies during rooting, which obeyed the original plant polarity. However, during plant growth, the two direction types exhibited similar auxin movements in the cutting bodies, and the opposite auxin changes were observed in new shoots. Four PAT genes with a positive response to cutting inversion, PyuPIN10, PyuPIN11, PyuLAX6 and PyuABCB27, showed diverse expression patterns between upright and inverted cuttings during rooting and plant growth. Furthermore, PAT gene expression retained its polarity, which differs from the results found for auxin flow during plant growth. The inconformity indicated that a new downward auxin flow in addition to the old upward flow might be established during the growth of inverted cuttings. Some highly polar PAT genes were involved in the maintenance of original auxin polarity, which might cause the enlarged stems of inverted cuttings. This work lays a foundation for understanding the roles of auxin transport in plant responses to inversion.

Cu2O nanoparticles anchored on carbon for the efficient removal of propofol from operating room wastewater via peroxymonosulfate activation: efficiency, mechanism, and pathway.

Anesthetic drug wastage has increasingly become the main resource of operating room sewage, which poses a great risk to the safety of humans and other organisms. Propofol is the most widely used anesthetic drug in the world, and also occupies the largest proportion of the total anesthetic wastage in the operating room. In this work, a 2D Cu2O anchored carbon catalyst (Cu2O@NC) was prepared by the assembly-pyrolysis process and successfully applied to peroxymonosulfate (PMS) activation. We took propofol as a typical example and investigated the removal activity through heterostructure-enhanced advanced oxidation processes (AOPs). Through the degradation process, propofol can be removed from 20 ppm to ultralow levels within 5 min using the PMS/Cu2O@NC system. The degradation pathway of propofol was deduced through quantum chemical calculation and LC/GC-MS results. The final products were verified as CO2 and H2O. Moreover, sulfate radicals (SO4˙-) proved to be the dominant reactive oxidation species by radical scavenger experiments and ESR results. In addition, it has great universality for various pharmaceuticals such as tetracycline (TC), amoxicillin (AMX), cephalexin (CPX), and norfloxacin (NFX). Our work provided the possibility to treat operation room sewage in a rapid, high-efficiency, and feasible way.

Bark tissue transcriptome analyses of inverted Populus yunnanensis cuttings reveal the crucial role of plant hormones in response to inversion.

Inverted cuttings of Populus yunnanensis exhibit an interesting growth response to inversion. This response is characterized by enlargement of the stem above the shoot site, while the upright stem shows obvious outward growth below the shoot site. In this study, we examined transcriptome changes in bark tissue at four positions on upright and inverted cuttings of P. yunnanensis: position B, the upper portion of the stem; position C, the lower portion of the stem; position D, the bottom of new growth; and position E, the top of new growth. The results revealed major transcriptomic changes in the stem, especially at position B, but little alteration was observed in the bark tissue of the new shoot. The differentially expressed genes (DEGs) were mainly assigned to four pathways: plant hormone signal transduction, plant-pathogen interaction, mitogen-activated protein kinase (MAPK) signaling pathway-plant, and adenosine triphosphate-binding cassette (ABC) transporters. Most of these DEGs were involved in at least two pathways. The levels of many hormones, such as auxin (IAA), cytokinin (CTK), gibberellins (GAs), ethylene (ET), and brassinosteroids (BRs), underwent large changes in the inverted cuttings. A coexpression network showed that the top 20 hub unigenes at position B in the upright and inverted cutting groups were associated mainly with the BR and ET signaling pathways, respectively. Furthermore, brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) in the BR pathway and both ethylene response (ETR) and constitutive triple response 1 (CTR1) in the ET pathway were important hubs that interfaced with multiple pathways.

Environmental controls on soil pH in planted forest and its response to nitrogen deposition.

BACKGROUND: Soil pH is important for controlling many soil properties. The variation in soil pH can be associated with changes in climate, soil buffering system, nitrogen deposition, and plants. However, there still lacks a comprehensive study exploring the effects of all these factors on soil pH simultaneously. Here we aimed to investigate the environmental controls on the spatial variation of soil pH in planted forests across Northern China and reveal its response to different-forms of nitrogen deposition for different species of tree plantations. METHODS: We sampled 1980 soil profiles from 660 planted forest plots (3 profiles in each plot) in Northern China. We used correlation analyses and structure equation models (SEM) to explore the impacts of multiple environmental factors on soil pH. RESULTS: Climate (water balance, temperature) and soil inorganic carbon accounted for most variations of soil pH. Specifically, the concentration of hydrogen ions ([H+]) varied almost isometrically with soil inorganic carbon, which was also the major buffering system in this region. Nitrogen deposition affected both soil pH values and soil buffering system. Results from structure equation model indicated that nitrate nitrogen directly decreased soil pH, while ammonium nitrogen mostly affected soil pH indirectly through its impacts on soil inorganic carbon. The responses of soil pH to nitrogen deposition were species-specific, and conifer stands tended to have higher soil acidification rate than stands of other tree species. CONCLUSIONS: Our study provides important information for understanding mechanisms controlling the spatial pattern of soil pH in planted forests and highlights the need to develop informed policies for soil resource management under increasing threats from anthropogenic nitrogen deposition.

Physiological Analysis and Transcriptome Profiling of Inverted Cuttings of Populus yunnanensis Reveal That Cell Wall Metabolism Plays a Crucial Role in Responding to Inversion.

Inverted cuttings of Populus yunnanensis remain alive by rooting from the original morphological apex and sprouting from the base, but the lateral branches exhibit less vigorous growth than those of the upright plant. In this study, we examined the changes in hormone contents, oxidase activities, and transcriptome profiles between upright and inverted cuttings of P. yunnanensis. The results showed that the indole-3-acetic acid (IAA) and gibberellic acid (GA3) contents were significantly lower in inverted cuttings than in upright cuttings only in the late growth period (September and October), while the abscisic acid (ABA) level was always similar between the two direction types. The biosynthesis of these hormones was surprisingly unrelated to the inversion of P. yunnanensis during the vegetative growth stage (July and August). Increased levels of peroxidases (PODs) encoded by 13 differentially expressed genes (DEGs) served as lignification promoters that protected plants against oxidative stress. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that most DEGs (107) were related to carbohydrate metabolism. Furthermore, altered activities of uridine diphosphate (UDP)-sugar pyrophosphorylase (USP, 15 DEGs) for nucleotide sugars, pectin methylesterase (PME, 7 DEGs) for pectin, and POD (13 DEGs) for lignin were important factors in the response of the trees to inversion, and these enzymes are all involved cell wall metabolism.

Analyzing the phylogeny of poplars based on molecular data.

Methods for constructing trees using DNA sequences, known as molecular phylogenetics, have been applied to analyses of phylogenetic origin, evolutionary relatedness and taxonomic classification. Combining data sequenced in this study and downloaded from GenBank, we sampled 112 (chloroplast data) / 122 (ITS data) specimens belonging to 49 (chloroplast data) / 46 (ITS data) poplar species or hybrids from six (chloroplast data) / five sections (ITS data). Maximum parsimony and Bayesian inference were used to analyze phylogenetic relationships within the genus Populus based on eight chloroplast combinations and ITS regions. The results suggested that Bayesian inference might be more suitable for the phylogenetic reconstruction of Populus. All Populus species could be divided into two clades: clade 1, including subclades 1 and 2, and clade 2, including subclades 3 and 4. Species within clade 1, involving five sections except for Leuce, clustered coinciding with their two specific main geographical distribution areas: China (subclade 1) and North America (subclade 2). Clustering in subclade 3, section Leuce was confirmed to be of monophyletic origin and independent evolution. Its two subsections, namely Albidae and Trepidae, could be separated by chloroplast data but had frequent gene flow based on ITS data. Phylogeny analysis based on chloroplast data demonstrated once more that section Aigeiros was paraphyletic and further showed that the P. deltoides lineage is restricted in subclade 2 and that P. nigra lineage, located in subclade 3, originated from a hybrid of which an Albidae ancestor species was the material parent. Similarly, section Tacamahaca was found to be paraphyletic and had two lineages: a clade 1 lineage, such as P. cathayana, and a clade 2 lineage, such as P. simonii. Section Leucoides was paraphyletic and closely linked to section Tacamahaca. Their section boundaries were not conclusively delimitated by sequencing information.

Total Synthesis of the Caged Indole Alkaloid Arboridinine Enabled by aza-Prins and Metal-Mediated Cyclizations.

Although alkaloid natural products possess incredible diversity when considered broadly, certain domains are sometimes shared by several members, even from different sub-collections. Such homology can point to potential synthetic strategies. Herein, we highlight how such an analysis of the natural product arboridinine pinpointed two key elements of structural similarity that suggested the value of a metal-mediated 6-endo-dig cyclization to fashion its tetracyclic indolenine core, as well as the need to develop what could be considered a reversed polarity aza-Prins cyclization to deliver its tertiary allylic alcohol and final cage structure. The power of the latter design element is highlighted by several failures in achieving similar functional group patterning through more traditional aza-Prins and Mannich cyclization strategies. Overall, these operations fueled an inaugural 13-step racemic synthesis of the target; exploration of varied solutions for the enantioselective preparation of a key 7-membered indole-containing piece afforded a 16-step formal asymmetric solution.

Pyrone Diels-Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ(7) -Mesembrenone.

Although the Diels-Alder reaction has long been utilized for the preparation of numerous heterocycles, opportunities to extend its power remain. Herein, we detail a simple, modular, and robust approach that combines various amines regioselectively with 4,6-dichloropyrone to create substrates which, under appropriate conditions, can directly deliver varied indolines and hydroindolines through [4+2] cycloadditions with substitution patterns difficult to access otherwise. As an initial demonstration of the power of the strategy, several different natural products have been obtained either formally or by direct total synthesis, with efforts toward one of these-the complex amaryllidaceae alkaloid gracilamine-affording the shortest route to date in terms of linear step count.

Rumination and Loneliness Independently Predict Six-Month Later Depression Symptoms among Chinese Elderly in Nursing Homes.

BACKGROUND: Previous studies conducted in Western countries independently demonstrated that loneliness and rumination are remarkable risk factors of depression among the elderly in both community and nursing homes. However, knowledge on the relationship between these three constructs among the elderly in Eastern countries is scarce. The current study aims to determine the relationship between loneliness, rumination, and depression among Chinese elderly in nursing homes. METHODS: A total of 71 elderly participants with an average age of 82.49 years completed this six-month longitudinal study. Physical reports indicated that none of the participants were clinically depressed before the study. At Time 1, their loneliness and rumination were measured using UCLA-8 Loneliness Scale and Ruminative Responses Scale. Six months later, the participants completed the Center for Epidemiologic Studies Depression Scale to assess depressive symptoms (Time 2). RESULTS: Multiple regression analysis revealed that both loneliness and rumination at Time 1 were the predictors of depression symptoms at Time 2 among the Chinese elderly in nursing homes. However, in the mediation analysis using PROCESS, the indirect effect between loneliness at Time 1 and depression symptoms at Time 2 was insignificant. CONCLUSIONS: Results suggest that previous loneliness and rumination thinking are predictors of future depression symptoms among the Chinese elderly in nursing homes. However, the insignificant mediation further suggests that the differences between loneliness and rumination should be explored in future studies. Findings have important implications for mental health professionals in nursing homes in China.

Relationships among Trait Resilience, Virtues, Post-traumatic Stress Disorder, and Post-traumatic Growth.

The present study aims to examine the relationship between trait resilience and virtues in the context of trauma. A total of 537 participants who attended the preliminary investigation and completed the Life Events Checklist were screened. Of these participants, 142 suffered from personal traumatic experiences in the past year; these individuals were qualified and invited to respond to online questionnaires to assess trait resilience, virtues (i.e., Conscientiousness, Vitality, and Relationship), post-traumatic stress disorder (PTSD) symptoms, and post-traumatic growth (PTG). The following questionnaires were used: Connor-Davidson Resilience Scale-Revised, Chinese Virtues Questionnaire, PTSD Checklist-Specific, and Post-traumatic Growth Inventory-Chinese. Only 95 participants who manifested self-reported PTSD symptoms and PTG were involved in the current analyses. Trauma was positively and significantly correlated with PTSD in the current sample. Results indicated that trait resilience was positively associated with virtues and PTG; by contrast, PTSD scores were negatively but not significantly related to most of these factors. The three virtues contributed to PTG to a greater extent than trait resilience in non-PTSD and PTSD groups. However, trait resilience remained a significant predictor in the PTSD group even when the three virtues were controlled. The relationship between trait resilience and PTG was moderated by PTSD type (non-PTSD group vs. PTSD group). Our results further suggested that trait resilience and virtues were conceptually related but functionally different constructs. Trait resilience and virtues are positively related; thus, these factors contributed variances to PTG in the context of trauma; however, trait resilience is only manifested when virtues are controlled and when individuals are diagnosed as PTSD. Furthermore, implications and limitations of this study are discussed.

(E)-α,ß-unsaturated amides from tertiary amines, olefins and CO via Pd/Cu-catalyzed aerobic oxidative N-dealkylation.

A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N-dealkylation/carbonylation reaction has been developed. Tertiary amines are utilized as a "reservoir" of "active" secondary amines in this transformation, which inhibits the formation of undesired by-products and the deactivation of the catalysts. This protocol allows for an efficient and straightforward construction of synthetically useful and bioactive (E)-α,ß-unsaturated amide derivatives from easily available tertiary amines, olefins and CO.

TUBB3/ßIII-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer.

ßIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non-small cell lung cancer (NSCLC), but the basis for its pathogenic influence is not understood. Functional and differential proteomics revealed that ßIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesion-associated tumor suppressor maspin was differentially regulated by ßIII-tubulin. Functionally, ßIII-tubulin suppression altered cell morphology, reduced tumor spheroid outgrowth, and increased sensitivity to anoikis. Mechanistically, the PTEN/AKT signaling axis was defined as a critical pathway regulated by ßIII-tubulin in NSCLC cells. ßIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how ßIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of ßIII-tubulin in tumorigenesis.

Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.

Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B-Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB.

Half-integer spin heptanuclear single-molecule magnet with an unusual Mn(III)6Mn(II) exchange-coupled core.

The synthesis, X-ray crystallography, magnetic properties, and high-field electron paramagnetic resonance (HFEPR) of a new heptanuclear manganese complex [Mn(7)(heamp)(6)](ClO(4))(2)·4CH(2)Cl(2)·H(2)O (complex 2), in which heampH(3) is 2-[N,N-di(2-hydroxyethyl)aminomethyl]phenol (compound 1), is reported. Complex 2 has a hexagonal, disk-shaped topology and contains six Mn(III) ions and a central Mn(II) ion. It crystallizes in the monoclinic space group P2(1)/c with two molecular orientations. Consideration of the cluster topology, together with variable-temperature and variable-field DC magnetic susceptibility data, suggest that complex 2 exists in a half-integer, S = (19)/(2) ± 1 spin ground state, with appreciable uniaxial zero-field splitting (D = -0.16 cm(-1)). AC magnetic susceptibility measurements clearly show out-of-phase signals, which are frequency- and temperature-dependent, indicating slow magnetization relaxation behavior. An analysis of the relaxation data employing the Arrhenius formula yielded an effective relaxation barrier of 12.9 cm(-1). Simulations of HFEPR studies agree with the assignment of an S ≈ (19)/(2) spin ground state, with g = 1.96, D = -4.71 GHz (-0.16 cm(-1)), and a longitudinal fourth-order zero-field splitting parameter B(4)(0) = -2.7 × 10(-4) GHz (-9.0 × 10(-6) cm(-1)).