Ipl1/aurora kinase suppresses S-CDK-driven spindle formation during prophase I to ensure chromosome integrity during meiosis

Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK) during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics

New light on plant ash glass found in Africa: evidence for Indian Ocean Silk Road trade using major, minor, trace element and lead isotope analysis of glass from the 15th—16th century AD from Malindi and Mambrui, Kenya

Seventeen glass vessels and twenty glass beads recovered from the excavations at the ancient city of Malindi and the archaeological site of Mambrui in Kenya, east Africa were analysed using electron probe microanalysis (EPMA) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The results show that all of the glass samples are soda-lime-silica glass. They belong to the high alumina -plant ash glass type, characterised by high alumina and relatively low calcium contents, widely distributed in eastern (10th- 16th centuries AD) and southern Africa (13th - 15th centuries AD), Central Asia (9th- 14th centuries AD) and southeast Asia (12th- 13th centuries AD), made with plant ashes and sands. This is an understudied glass type for which previous research has indicated there were three types. When compared with published research on such glasses using Zr, Ti, Ba, Cr, La, Li, Cs, Na2O, MgO and CaO we have identified at least four different compositional groups of v-Na-Al glass: Types A, B, C and D. By comparing the results with contemporary v-Na-Al glass vessels and beads from Central Asia, Africa, and southeast Asia we show that most of the Malindi and Mambrui glass share similar characteristics to the compositions of Mapungubwe Oblate and some of the Madagascar glass beads from southern Africa. They belong to Type A v-Na-Al glass which is characterised by an elevated level of Ti and Ba and a relatively high ratios of Cr/La, relatively low Zr concentrations and low ratios of Zr/ Ti. Differences in Zr, Li, MgO and Na2O concentrations in Type A glass indicates that there are subgroups which might derive from different glass workshop(s) specialising in Type A v- Na-Al glass production. Comparison with the chemical compositions of glass from Ghazni, Afghanistan and Termez, Uzbekistan, and by using lead isotope analysis, we suggest v-Na- Al glass was manufactured in Central Asia and possibly worked into vessels and beads there. Copyright: © 2020 Siu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Digit-only sauropod pes trackways from China - evidence of swimming or a preservational phenomenon?

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all

Eigenvalues of higher order Sturm-Liouville boundary value problems with derivatives in nonlinear terms

We shall consider the Sturm-Liouville boundary value problem y(m)(t)+λF(t,y(t),y′(t),…,y(q)(t))=0, t∈(0,1), y(k)(0)=0, 0≤k≤m−3, ζy(m−2)(0)−θy(m−1)(0)=0, ρy(m−2)(1)+δy(m−1)(1)=0 where m≥3, 1≤q≤m−2, and λ>0. It is noted that the boundary value problem considered has a derivative-dependent nonlinear term, which makes the investigation much more challenging. In this paper we shall develop a new technique to characterize the eigenvalues λ so that the boundary value problem has a positive solution. Explicit eigenvalue intervals are also established. Some examples are included to dwell upon the usefulness of the results obtained.Published versio

Increased blood product use among coronary artery bypass patients prescribed preoperative aspirin and clopidogrel

BACKGROUND: The administration of antiplatelet drugs before coronary artery bypass graft surgery (CABG) is associated with an increased risk of major hemorrhage and related surgical reexploration. Little is known about the relative effect of combined clopidogrel and aspirin on blood product use around the time of CABG. We evaluated the associated risk between the combined use of aspirin and clopidogrel and the transfusion of blood products perioperatively. METHODS: We retrospectively studied a cohort of 659 individuals who underwent a first CABG, without concomitant valvular or aortic surgery, at a single large Canadian cardiac surgical centre between January 2000 and April 2002. The four study exposure groups were those prescribed aspirin (n = 105), clopidogrel (n = 11), the combination of both (n = 46), or neither drug (n = 497), within 7 days prior to CABG. The primary study outcome was the excessive transfusion of blood products during CABG and up to the second post-operative day, defined as ≥ 2 units of packed red blood cells (PRBC), ≥ 2 units of fresh frozen plasma, ≥ 5 units of cryoprecipitate or ≥ 5 units of platelets. Secondary outcomes included the mean number of transfused units of each type of blood product. RESULTS: A greater mean number of units of PRBC were transfused among those who received clopidogrel alone (2.9) or in combination with aspirin (2.4), compared to those on aspirin alone (1.9) or neither antiplatelet drug (1.4) (P = 0.001). A similar trend was seen for the respective mean number of transfused units of platelets (3.6, 3.7, 1.3 and 1.0; P < 0.001) and fresh frozen plasma (2.5, 3.1, 2.3, 1.6; P = 0.01). Compared to non-users, the associated risk of excessive blood product transfusion was highest among recipients of aspirin and clopidogrel together (adjusted OR 2.2, 95% CI 1.1–4.3). No significant association was seen among lone users of aspirin (adjusted OR 1.0, 95% CI 0.6–1.6) or clopidogrel (adjusted OR 0.7, 95% CI 0.2–2.5), compared to non-users. CONCLUSIONS: While combined use of aspirin and clopidogrel shortly before CABG surgery may increase the associated risk of excess transfusion of blood products perioperatively, several study limitations prevent any confident conclusions from being drawn. Beyond challenging these findings, future research might focus on the value of both intraoperative monitoring of platelet function, and the effectiveness of antifibrinolytic agents, at reducing the risk of postoperative bleeding

C. elegans Nucleostemin Is Required for Larval Growth and Germline Stem Cell Division

The nucleolus has shown to be integral for many processes related to cell growth and proliferation. Stem cells in particular are likely to depend upon nucleolus-based processes to remain in a proliferative state. A highly conserved nucleolar factor named nucleostemin is proposed to be a critical link between nucleolar function and stem-cell–specific processes. Currently, it is unclear whether nucleostemin modulates proliferation by affecting ribosome biogenesis or by another nucleolus-based activity that is specific to stem cells and/or highly proliferating cells. Here, we investigate nucleostemin (nst-1) in the nematode C. elegans, which enables us to examine nst-1 function during both proliferation and differentiation in vivo. Like mammalian nucleostemin, the NST-1 protein is localized to the nucleolus and the nucleoplasm; however, its expression is found in both differentiated and proliferating cells. Global loss of C. elegans nucleostemin (nst-1) leads to a larval arrest phenotype due to a growth defect in the soma, while loss of nst-1 specifically in the germ line causes germline stem cells to undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of rRNAs, suggesting defects in ribosome biogenesis. However, NST-1 is generally not present in regions of the nucleolus where rRNA transcription and processing occurs, so this reduction is likely secondary to a different defect in ribosome biogenesis. Transgenic studies indicate that NST-1 requires its N-terminal domain for stable expression and both its G1 GTPase and intermediate domains for proper germ line function. Our data support a role for C. elegans nucleostemin in cell growth and proliferation by promoting ribosome biogenesis

Fluorescence activated cell sorting followed by small RNA sequencing reveals stable microRNA expression during cell cycle progression.

BACKGROUND: Previously, drug-based synchronization procedures were used for characterizing the cell cycle dependent transcriptional program. However, these synchronization methods result in growth imbalance and alteration of the cell cycle machinery. DNA content-based fluorescence activated cell sorting (FACS) is able to sort the different cell cycle phases without perturbing the cell cycle. MiRNAs are key transcriptional regulators of the cell cycle, however, their expression dynamics during cell cycle has not been explored. METHODS: Following an optimized FACS, a complex initiative of high throughput platforms (microarray, Taqman Low Density Array, small RNA sequencing) were performed to study gene and miRNA expression profiles of cell cycle sorted human cells originating from different tissues. Validation of high throughput data was performed using quantitative real time PCR. Protein expression was detected by Western blot. Complex statistics and pathway analysis were also applied. RESULTS: Beyond confirming the previously described cell cycle transcriptional program, cell cycle dependently expressed genes showed a higher expression independently from the cell cycle phase and a lower amplitude of dynamic changes in cancer cells as compared to untransformed fibroblasts. Contrary to mRNA changes, miRNA expression was stable throughout the cell cycle. CONCLUSIONS: Cell cycle sorting is a synchronization-free method for the proper analysis of cell cycle dynamics. Altered dynamic expression of universal cell cycle genes in cancer cells reflects the transformed cell cycle machinery. Stable miRNA expression during cell cycle progression may suggest that dynamical miRNA-dependent regulation may be of less importance in short term regulations during the cell cycle

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Human Embryonic Stem Cells Differentiated to Lung Lineage-Specific Cells Ameliorate Pulmonary Fibrosis in a Xenograft Transplant Mouse Model

Our aim was to differentiate human (h) embryonic stem (ES) cells into lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI) and type II (AEII) cells and Clara cells] as the first step in the development of cell-based strategies to repair lung injury in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF). A heterogeneous population of non-ciliated lung lineage-specific cells was derived by a novel method of embryoid body (EB) differentiation. This differentiated human cell population was used to modulate the profibrotic phenotype in transplanted animals.Omission or inclusion of one or more components in the differentiation medium skewed differentiation of H7 hES cells into varying proportions of AEI, AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/β-catenin/Creb-binding protein (CBP) transcription, changed marker expression of the differentiated ES cells from an AEII-like phenotype to a predominantly AEI-like phenotype. The differentiated cells were used in xenograft transplantation studies in bleomycin-treated Rag2γC(-/-) mice. Human cells were detected in lungs of the transplanted groups receiving differentiated ES cells treated with or without ICG-001. The increased lung collagen content found in bleomycin-treated mice receiving saline was significantly reduced by transplantation with the lung-lineage specific epithelial cells differentiated from ES cells. A significant increase in progenitor number was observed in the airways of bleomycin-treated mice after transplantation of differentiated hES cells.This study indicates that ES cell-based therapy may be a powerful novel approach to ameliorate lung fibrosis