Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation

Cell division requires the precise coordination of chromosome segregation and cytokinesis. This coordination is achieved by the recruitment of an actomyosin regulator, Ect2, to overlapping microtubules at the centre of the elongating anaphase spindle. Ect2 then signals to the overlying cortex to promote the assembly and constriction of an actomyosin ring between segregating chromosomes. Here, by studying division in proliferating Drosophila and human cells, we demonstrate the existence of a second, parallel signalling pathway, which triggers the relaxation of the polar cell cortex at mid anaphase. This is independent of furrow formation, centrosomes and microtubules and, instead, depends on PP1 phosphatase and its regulatory subunit Sds22 (refs 2, 3). As separating chromosomes move towards the polar cortex at mid anaphase, kinetochore-localized PP1-Sds22 helps to break cortical symmetry by inducing the dephosphorylation and inactivation of ezrin/radixin/moesin proteins at cell poles. This promotes local softening of the cortex, facilitating anaphase elongation and orderly cell division. In summary, this identifies a conserved kinetochore-based phosphatase signal and substrate, which function together to link anaphase chromosome movements to cortical polarization, thereby coupling chromosome segregation to cell division

Universality class of the special adsorption point of two-dimensional lattice polymers.

In recent work [Rodrigues et al., Phys. Rev. E 100, 022121 (2019)10.1103/PhysRevE.100.022121], evidence was found that the surface adsorption transition of interacting self-avoiding trails (ISATs) placed on the square lattice displays a nonuniversal behavior at the special adsorption point (SAP) where the collapsing polymers adsorb. In fact, different surface exponents ϕ^{(s)} and 1/δ^{(s)} were found at the SAP depending on whether the surface orientation is horizontal (HS) or diagonal (DS). Here, we revisit these systems and study other ones, through extensive Monte Carlo simulations, considering much longer trails than previous works. Importantly, we demonstrate that the different exponents observed in the reference above are due to the presence of a surface-attached-globule (SAG) phase in the DS system, which changes the multicritical nature of the SAP and is absent in the HS case. By considering a modified horizontal surface (mHS), on which the trails are forbidden from having two consecutive steps, resembling the DS situation, a stable SAG phase is found in the phase diagram, and both DS and mHS systems present similar 1/δ^{(s)} exponents at the SAP, namely, 1/δ^{(s)}≈0.44, whereas 1/δ^{(s)}≈0.34 in the HS case. Intriguingly, while ϕ^{(s)}≈1/δ^{(s)} is found for the DS and HS scenarios, as expected, in the mHS case ϕ^{(s)} is about 10% smaller than 1/δ^{(s)}. These results strongly indicate that at least two universality classes exist for the SAPs of adsorbing ISATs on the square lattice

Moesin orchestrates the reorganisation of the actin cortex and shape changes during mitotic progression in an epithelium

Animal cells endure dramatic actin-dependent changes in shape as they progress through mitosis – they round up at mitotic entry, elongate at anaphase and split into two at cytokinesis. In this thesis I explore the role of Moesin, an actin-membrane crosslinker and the sole ERM protein expressed in Drosophila, in orchestrating rearrangements of the actin cortex and morphological changes in epithelial cells undergoing mitosis. To perform my studies I used the fly notum and sensory organ precursor (SOP) cells therein as a model system. In this thesis I show that Moesin is required for the stabilisation of the actomyosin cortex at metaphase. This mechanism is dependent upon phosphorylation of Moesin by the Slik kinase, which activates the ERM protein. Reduced levels of Moesin or Slik lead to myosin-II-driven cortical instabilities. Cortical stabilisation in mitotic SOP cells ensures the efficient accumulation of fate determinants at the plasma membrane. At mitotic exit, a pool of active, phosphorylated Moesin is lost from the cell poles, thereby triggering polar relaxation and initiating anaphase cell elongation. These two events precede furrow formation, are independent of centrosome or astral microtubules-derived signals, and are induced by proximity of the segregating chromosomes to the cell poles. I show that a pool of kinetochore-localised PP1-87B phosphatase and its regulatory subunit Sds22 inactivate cortical Moesin and elicit the dismantling of the actomyosin cortex at mid-anaphase. Cells with reduced amounts of PP1-87B or Sds22 fail to clear Moesin and actin from the anaphase poles. Importantly, these defects in polar relaxation are mimicked by the expression of a constitutively active form of Moesin in fly tissues. Finally, I demonstrate that delocalisation of PP1/Sds22 from the kinetochores via KNL1 depletion abolishes polar blebbing at anaphase and impairs cell elongation. My work shows how the dynamic regulation of Moesin activation and localisation controls shape changes in cells undergoing mitosis. Moreover, it sheds light on a novel mechanism of polar relaxation at anaphase, in which a kinetochore-derived signal instructs the cell cortex to become polarised, thereby initiating cytokinesis

Adsorption of interacting self-avoiding trails in two dimensions

We investigate the surface adsorption transition of interacting self-avoiding square lattice trails onto a straight boundary line. The character of this adsorption transition depends on the strength of the bulk interaction, which induces a collapse transition of the trails from a swollen to a collapsed phase, separated by a critical state. If the trail is in the critical state, the universality class of the adsorption transition changes; this is known as the special adsorption point. Using flatPERM, a stochastic growth Monte Carlo algorithm, we simulate the adsorption of self-avoiding interacting trails on the square lattice using three different boundary scenarios which differ with respect to the orientation of the boundary and the type of surface interaction. We confirm the expected phase diagram, showing swollen, collapsed, and adsorbed phases in all three scenarios, and confirm universality of the normal adsorption transition at low values of the bulk interaction strength. Intriguingly, we cannot confirm universality of the special adsorption transition. We find different values for the exponents; the most likely explanation is that this is due to the presence of strong corrections to scaling at this point.Comment: 10 pages, 8 figure

Multi-level Autonomic Business Process Management

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-38484-4_14Nowadays, business processes are becoming increasingly complex and heterogeneous. Autonomic Computing principles can reduce this complexity by autonomously managing the software systems and the running processes, their states and evolution. Business Processes that are able to be self-managed are referred to as Autonomic Business Processes (ABP). However, a key challenge is to keep the models of such ABP understandable and expressive in increasingly complex scenarios. This paper discusses the design aspects of an autonomic business process management system able to self-manage processes based on operational adaptation. The goal is to minimize human intervention during the process definition and execution phases. This novel approach, named MABUP, provides four well-defined levels of abstraction to express business and operational knowledge and to guide the management activity; namely, Organizational Level, Technological Level, Operational Level and Service Level. A real example is used to illustrate our proposal.Research supported by CAPES, CNPQ and Spanish Ministry of Science and Innovation.Oliveira, K.; Castro, J.; España Cubillo, S.; Pastor López, O. (2013). Multi-level Autonomic Business Process Management. En Enterprise, Business-Process and Information Systems Modeling. Springer. 184-198. doi:10.1007/978-3-642-38484-4_14S184198España, S., González, A., Pastor, Ó.: Communication Analysis: A Requirements Engineering Method for Information Systems. In: van Eck, P., Gordijn, J., Wieringa, R. (eds.) CAiSE 2009. LNCS, vol. 5565, pp. 530–545. Springer, Heidelberg (2009)Ganek, A.G., Corbi, T.A.: The dawning of the autonomic computing era. IBM Systems Journal 42(1), 5–18 (2003)Gonzalez, A., et al.: Unity criteria for Business Process Modelling. In: Third International Conference on Research Challenges in Information Science, RCIS 2009, pp. 155–164 (2009)Greenwood, D., Rimassa, G.: Autonomic Goal-Oriented Business Process Management. Management, 43 (2007)Haupt, T., et al.: Autonomic execution of computational workflows. In: 2011 Federated Conference on Computer Science and Information Systems, FedCSIS, pp. 965–972 (2011)Kephart, J.O., Chess, D.M.: The vision of autonomic computing. IEEE (2003)Lee, K., et al.: Workflow adaptation as an autonomic computing problem. In: Proceedings of the 2nd Workshop on Workflows in Support of Large-Scale Science, New York, NY, USA, pp. 29–34 (2007)Mosincat, A., Binder, W.: Transparent Runtime Adaptability for BPEL Processes. In: Bouguettaya, A., Krueger, I., Margaria, T. (eds.) ICSOC 2008. LNCS, vol. 5364, pp. 241–255. Springer, Heidelberg (2008)Oliveira, K., et al.: Towards Autonomic Business Process Models. In: International Conference on Software Engineering and Knowledge, SEKE 2012, San Francisco, California, USA (2012)Rahman, M., et al.: A taxonomy and survey on autonomic management of applications in grid computing environments. Concurr. Comput.: Pract. Exper. 23(16), 1990–2019 (2011)Reijers, H.A., Mendling, J.: Modularity in process models: Review and effects. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 20–35. Springer, Heidelberg (2008)Rodrigues Nt., J.A., Monteiro Jr., P.C.L., de O. Sampaio, J., de Souza, J.M., Zimbrão, G.: Autonomic Business Processes Scalable Architecture. In: ter Hofstede, A.H.M., Benatallah, B., Paik, H.-Y. (eds.) BPM Workshops 2007. LNCS, vol. 4928, pp. 78–83. Springer, Heidelberg (2008)Strohmaier, M., Yu, E.: Towards autonomic workflow management systems. ACM Press (2006)Terres, L.D., et al.: Selection of Business Process for Autonomic Automation. In: 2010 14th IEEE International Enterprise Distributed Object Computing Conference, pp. 237–246 (October 2010)Tretola, G., Zimeo, E.: Autonomic internet-scale workflows. In: Proceedings of the 3rd International Workshop on Monitoring, Adaptation and Beyond, New York, NY, USA, pp. 48–56 (2010)Vedam, H., Venkatasubramanian, V.: A wavelet theory-based adaptive trend analysis system for process monitoring and diagnosis. In: Proceedings of the 1997 American Control Conference, vol. 1, pp. 309–313 (June 1997)Wang, Y., Mylopoulos, J.: Self-Repair through Reconfiguration: A Requirements Engineering Approach. In: 2009 IEEE/ACM International Conference on Automated Software Engineering, pp. 257–268 (November 2009)Yu, T., Lin, K.: Adaptive algorithms for finding replacement services in autonomic distributed business processes. In: Proceedings Autonomous Decentralized Systems, ISADS 2005, pp. 427–434 (2005

Differential Scanning Fluorimetry provides high throughput data on silk protein transitions

Here we present a set of measurements using Differential Scanning Fluorimetry (DSF) as an inexpensive, high throughput screening method to investigate the folding of silk protein molecules as they abandon their first native melt conformation, dehydrate and denature into their final solid filament conformation. Our first data and analyses comparing silks from spiders, mulberry and wild silkworms as well as reconstituted ‘silk’ fibroin show that DSF can provide valuable insights into details of silk denaturation processes that might be active during spinning. We conclude that this technique and technology offers a powerful and novel tool to analyse silk protein transitions in detail by allowing many changes to the silk solutions to be tested rapidly with microliter scale sample sizes. Such transition mechanisms will lead to important generic insights into the folding patterns not only of silks but also of other fibrous protein (bio)polymers

Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans

Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes. hemotin mutants accumulate undigested phagocytic material inside enlarged endo-lysosomes and as a result, hemotin mutants have reduced ability to fight bacteria, and hence, have severely reduced life span and resistance to infections. We identify Stannin, a peptide involved in organometallic toxicity, as the Hemotin functional homologue in vertebrates, showing that this novel regulator of phagocytic processing is widely conserved, emphasizing the significance of smORF peptides in cell biology and disease

Coffee resistance to the main diseases : leaf rust and coffee berry disease

Sucesso considerável tem sido obtido no uso do melhoramento clássico para o controle de doenças de plantas economicamente importantes, tais como a ferrugem alaranjada das folhas e a antracnose dos frutos do cafeeiro (CBD). Há um grande consenso de que o uso de plantas geneticamente resistentes é o meio mais apropriado e eficaz em termos de custos do controle das doenças das plantas, sendo também um dos elementos chave do melhoramento da produção agrícola. Tem sido também reconhecido que um melhor conhecimento do agente patogênico e dos mecanismos de defesa das plantas permitirá o desenvolvimento de novas abordagens no sentido de aumentar a durabilidade da resistência. Após uma breve descrição de conceitos na área da resistência das plantas às doenças, nesta revisão tentou-se dar uma idéia do progresso na investigação da ferrugem alaranjada do cafeeiro e do CBD relativamente ao processo de infecção e variabilidade dos agentes patogênicos, melhoramento do cafeeiro para a resistência e mecanismos de resistência do cafeeiro

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Coupling changes in cell shape to chromosome segregation

Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance