Cycle Restart Research Articles

Biotransformation of Cacumen platycladi Extract by Lactiplantibacillus plantarum CCFM1348 Promotes Hair Growth in Mice.

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/β-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated β-catenin, a major factor of the Wnt/β-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/β-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.

Music Between Work and Leisure: The Case of a Collective from Fortaleza, Brazil

Lado B is a collective of musicians from Fortaleza, Brazil, that holds monthly festivals in a public cultural center. Aiming at some self-sufficiency, Lado B organizes its festivals according to a kind of adiabatic circuit, which works as follows: at a given festival, each member of the collective is in charge of a function that is necessary for the realization of that particular event. At each new festival, each member of the group performs a task different from the role played at the previous festival; that is to say, members alternate themselves in the many roles as the festivals go on, until each individual has gone through each duty at a given festival. Once everyone has done everything, the cycle restarts. Music is not the main activity of any of those artists, so they all need to keep a day job. This situation creates a divergence on Lado B: while some see the collective as a second job, others face it as a leisure activity. In other words, one segment creates a relation of continuity between life and art, submitting music to the logic of routine, and the other faction establishes a rupture between life and art, as if culture was the ordinary world upside down. Based on interviews with members of Lado B, I ask: is music a job or a leisure activity? I intend to inscribe this question within the broader debate about the relationship between life and art, everyday life and culture, routine and spirit, asceticism and pleasure, functionalism and rebellion, pragmatism and madness. Thus, in a broad sense, I question: what is the relation between life and art? Are they irreconcilable or interdependent? Equal or opposed? Do they struggle against or reinforce each other?

Vegetation patch dynamics in rangelands: How feedbacks between large herbivores, vegetation and soil fauna alter patches over space and through time

AbstractAimLarge herbivore grazing is a popular conservation management tool to promote vegetation structural diversity of rangelands. However, vegetation patch dynamics, that is, how patches of grazing‐defended tall vegetation and grazer‐preferred short lawns shift over space and time, is poorly understood. Here, we describe a new conceptual framework for patch dynamics within rangelands, combining theories of classical cyclical succession, self‐organization and multitrophic feedbacks between grazers, vegetation and bioturbating soil fauna.LocationWe use the cattle‐grazed salt marsh of the island Schiermonnikoog, The Netherlands, as a model system. The grazed salt marsh is characterized by distinct tall vegetation patches dominated by the grazing‐defended rush Juncus maritimus and grazing‐intolerant grass Elytrigia atherica, surrounded by a matrix of grazing lawn (dominated by Festuca rubra).The FrameworkBased on previous observational and experimental studies, we propose a cyclical patch dynamic where plant species composition and structure transitions through four phases: patch initiation (a) occurs when the grazing‐defended rush J. maritimus establishes in the grazed lawn. Patch establishment (b) follows when the grazing‐intolerant grass E. atherica establishes in the patch due to associational defence by J. maritimus and produces a large amount of litter that attracts the key bioturbating amphipod Orchestia gammarellus. Patch expansion (c) occurs when O. gammarellus activities improve soil properties of the patch, which favours E. atherica growth, leading to E. atherica competitively displacing J. maritimus in the centre of the patch. Patch degeneration (d) follows when cattle enter the enlarged patch to consume E. atherica in the centre, trample the soil, displace O. gammarellus and decrease vegetation cover, opening space for grazing‐lawn species to invade. The cycle restarts when remnants of the rush J. maritimus in the degenerated patches (or individuals recently established from seed dispersal) initiate new patches in the grazing lawn.SynthesisOur proposed patch‐dynamic model provides a means to describe the mechanisms driving vegetation patch dynamics and serves as a foundation for further experimental and observational exploration, not only for this specific system, but more generally for grazed systems worldwide that show patches of typical grazing‐defended and grazer‐preferred vegetation.

The game: Description and analysis of how street vendors keep working on the streets of Bogotá despite state intervention

Day-to-day management of street vending is much more a matter of starting negotiations, mediating between the interests of distinct groups, and making agreements, than it is about enforcing confusing and at times contradictory legal mechanisms with limited effectiveness. Based on the results of extended fieldwork in a low-income outer locality of Bogotá (Ciudad Bolívar), I will argue that street vendors and state representatives interact around a four-step dynamic known as the ‘ game’, which provides them with ‘working stability’ or high degrees of legitimacy, despite frequent arbitrary – and not just discretionary – interventions from the police and other state representatives. In short, the game works as follows: complaints against vendors build-up and interventions take place. Street vendors use different resistance strategies, but tension intensifies, then crisis is reached. As both parties have strong incentives to negotiate, they reach basic coexistence agreements. Vendors fail to comply with the agreements because regulations made to sanitize poverty and to hide the face of misery are rarely applicable. The cycle restarts. I conclude by arguing that efforts to eliminate or limit street vending will not be successful or sustainable until the state makes the political and fiscal commitment to offer substantial employment programs and/or guarantee a minimum income to vulnerable families.

A new secure 2PL real-time concurrency control algorithm (ES2PL)

A secure concurrency control algorithms must be devoid of covert channels originating from data conflicts between transactions, in addition to ensuring database integrity. Current secure concurrency control algorithms mistreat transactions with higher access classes. Because it better solves the priority inversion problem. A widely used concurrency control algorithm is the two-phase locking with high priority (2 PL-HP). The inclusion of cyclic restart, deadlock, unnecessary abort, pseudo-priority inversion, and starvation, on the other hand, may reduce its performance. In this paper, a new enhanced of secure two-phase locking protocol with multilevel secure distributed database systems is presented, the idea of enhanced secure Two-Phase locking protocol by adding the security level to assign the priority to the transaction. The enhanced add a secure manager to decide the level of the security and give the instruction to process the transaction in real lock with data x/virtual lock with version data x0 or decided to Abort the transaction based on the security level. The suggested study intends to reduce transaction miss rate by addressing the following issues: deadlock by splitting the execution stage into locking and processing phases, it reduces unnecessary cycle restart, transaction aborts by checking the security priority level (high, medium, low), and generating virtual lock and versions data. Finally, simulation performance confirms that improvement in transactions miss's percent and reduction in transactions' rollbacks compared to other secure concurrency control.

Reconciling conflicting predictions about transience and persistence of management concepts in management fashion theory and new institutionalism

PurposeAlthough drawing from neoinstitutional theoretical apparatus and ontology, management fashion theory is understood as a theory that explains the transitory nature of popular ideas and practices while institutional theory explains their stabilization, persistence and further institutionalization. In a nutshell, it seems that being opposed to each other, these two theories describe and predict different, incommensurable diffusion trajectories and organizational behaviour patterns. The purpose of this paper is to unify these two competing perspectives.Design/methodology/approachThis paper makes an attempt toward further unification of management fashion theory with new institutionalism by offering an alternative understanding and conceptualization of institutional change and deinstitutionalization and by distinguishing emerging concepts from already popular fashions.FindingsMost emerging concepts never achieve popularity and disappear while few of them achieve massive media attention and diffuse widely becoming new management fashions. Once these concepts have achieved a wide popularity institutional forces would favor them and lead to further institutionalization. Institutional change is understood not as a deinstitutionalization of existing management fashion in terms of erosion, discontinuity or disappearance but as a decline in its media coverage while media attention focuses on new fashionable concept. The former management fashion gets institutionalized, institutional change occurs in terms of shifting attention toward new fashion and diffusion and institutionalization cycle restarts. Institutional prediction of isomorphism and institutionalization as irreversible tendencies thus can be unified with MF prediction about the bell-shaped curves in fashions’ popularity. Therefore, postulates and predictions of management fashion theory can be derived from new institutionalism and vice versa.Practical implicationsThe paper aims to cover, generalize and explain different trajectories of various management and organizational concepts, deducing theoretical propositions from both institutional theory and management fashion theory. Theoretical and methodological ideas offered in this paper can be helpful in future research on management fashions and diffusion. Studies on the evolution of management concept can benefit from proposed categorization and causal relationships between different stages of the life cycle.Originality/valueUnifying seemingly conflicting and disparate perspectives and views allows making organization theory more coherent in terms of both explanatory power and ontological commensurability. Following other mature sciences, we share the same notion of progress, namely, the aim of achieving unification and demonstrating that different organizational theories still describe the same reality.

A hydrophobic low-complexity region regulates aggregation of the yeast pyruvate kinase Cdc19 into amyloid-like aggregates in vitro

Cells form stress granules (SGs) upon stress stimuli to protect sensitive proteins and RNA from degradation. In the yeast Saccharomyces cerevisiae, specific stresses such as nutrient starvation and heat-shock trigger recruitment of the yeast pyruvate kinase Cdc19 into SGs. This RNA-binding protein was shown to form amyloid-like aggregates that are physiologically reversible and essential for cell cycle restart after stress. Cellular Cdc19 exists in an equilibrium between a homotetramer and monomer state. Here, we show that Cdc19 aggregation in vitro is governed by protein quaternary structure, and we investigate the physical-chemical basis of Cdc19's assembly properties. Equilibrium shift toward the monomer state exposes a hydrophobic low-complexity region (LCR), which is prone to induce intermolecular interactions with surrounding proteins. We further demonstrate that hydrophobic/hydrophilic interfaces can trigger Cdc19 aggregation in vitro Moreover, we performed in vitro biophysical analyses to compare Cdc19 aggregates with fibrils produced by two known dysfunctional amyloidogenic peptides. We show that the Cdc19 aggregates share several structural features with pathological amyloids formed by human insulin and the Alzheimer's disease-associated Aβ42 peptide, particularly secondary β-sheet structure, thermodynamic stability, and staining by the thioflavin T dye. However, Cdc19 aggregates could not seed aggregation. These results indicate that Cdc19 adopts an amyloid-like structure in vitro that is regulated by the exposure of a hydrophobic LCR in its monomeric form. Together, our results highlight striking structural similarities between functional and dysfunctional amyloids and reveal the crucial role of hydrophobic/hydrophilic interfaces in regulating Cdc19 aggregation.

Reversible protein aggregation is a protective mechanism to ensure cell cycle restart after stress.

Protein aggregation is mostly viewed as deleterious and irreversible causing several pathologies. However, reversible protein aggregation has recently emerged as a novel concept for cellular regulation. Here, we characterize stress-induced, reversible aggregation of yeast pyruvate kinase, Cdc19. Aggregation of Cdc19 is regulated by oligomerization and binding to allosteric regulators. We identify a region of low compositional complexity (LCR) within Cdc19 as necessary and sufficient for reversible aggregation. During exponential growth, shielding the LCR within tetrameric Cdc19 or phosphorylation of the LCR prevents unscheduled aggregation, while its dephosphorylation is necessary for reversible aggregation during stress. Cdc19 aggregation triggers its localization to stress granules and modulates their formation and dissolution. Reversible aggregation protects Cdc19 from stress-induced degradation, thereby allowing cell cycle restart after stress. Several other enzymes necessary for G1 progression also contain LCRs and aggregate reversibly during stress, implying that reversible aggregation represents a conserved mechanism regulating cell growth and survival.

ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration.

After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation. These phosphorylations are rapidly counteracted by the chromatin-bound phosphatase Wip1, allowing cell cycle restart despite persistent ATM activity present at DNA lesions. Combining experimental data and mathematical modeling, we propose a model for how the minimal duration of cell cycle arrest is controlled. Our model shows how cell cycle restart can occur before completion of DNA repair and suggests a mechanism for checkpoint adaptation in human cells.

Triolein from Coix Lacryma-Jobi Induces Cell Cycle Arrest through P53/P21Signaling Pathway

p53, a tumor suppressor protein, has important roles in DNA repair, cell cycle and apoptosis, is a one of the key events in cancer development. Coix lacryma-jobi seed has been used as a food and traditional medicine plant with anti-oxidant, anti-cancer and anti-diabetic effects. In currently research, we identified the most potent p53-increasing compound among 4 compounds (1-4) found in Coix lacryma-jobi and demonstrated its molecular mechanism in MCF-7 cells. Among the four isolated compounds (1-4), triolein most increased p53. Triolein treatment induced p53, p21, p27 and Bax in MCF-7 cells. Moreover, triolein caused S phase arrest through suppression of CDK1, phopho-Rb and E2F1 in dose-dependent manner. We also observed the decreasing of DNA synthesis by triolein. These data suggest that triolein may induced cell cycle restart involve DNA synthesis and apoptosis pathway in MCF-7 cells. (Less)

Abstract 946: SGN-CD70A, a pyrrolobenzodiazepine (PBD) dimer linked ADC, mediates DNA damage pathway activation and G2 cell cycle arrest leading to cell death

Abstract Seattle Genetics is utilizing the highly potent DNA cross-linking molecule, pyrrolobenzodiazepine (PBD) dimer, as the payload across multiple antibody drug conjugate (ADC) platforms. Previous studies have demonstrated that PBD dimers bind to the minor groove of DNA causing an interstrand crosslink; however, it is poorly understood how the cells recognize and respond to this insult. The DNA damage pathway exists to ensure genomic fidelity by either repairing damaged DNA or forcing programmed cell death if the damage is too extensive. Cells do this in an orchestrated manner that involves sensing the damage and eliciting a signaling cascade to induce repair and cell cycle arrest and ultimately either cell cycle re-start, death, or senescence. Using SGN-CD70A, an ADC consisting of a CD70-directed engineered cysteine antibody linked to two PBD dimers, we have examined the DNA damage response and cell death kinetics in a panel of renal cell carcinoma (RCC) and non-Hodgkin lymphoma (NHL) cell lines after treatment with free PBD and SGN-CD70A. We examined the central DNA damage sensing protein kinases, ATM, ATR, and DNA-PK and find that all three are phosphorylated on activation residues within 24 hours at EC50 doses in both RCC and NHL cell lines. Similarly, the downstream checkpoint kinases, Chk1 and Chk2 are also activated, within 24 hours after treatment with SGN-CD70A. The kinetics of pChk2 activation mirror Caspase 3/7 activation, with both peaking 48-72 hours after treatment. To confirm the involvement of the DNA damage pathway in the PBD mechanism, we used small molecules to inhibit ATM (KU-60019), ATR (VE-821), DNA-PK (NU-7441), and Chk1/2 (AZD7762, LY2603618) and found that all were synergistic with SGN-CD70A and accelerated cell death kinetics. We also conducted a small molecule screen to identify other processes involved in SGN-CD70A's activity. The Mps1 inhibitor (AZ 3146), which shortens mitosis and abrogates the mitotic checkpoint, was strongly synergistic. Conversely, molecules that cause mitotic arrest, such as microtubule inhibitors and Plk1 inhibitors did not show the same degree of synergy. To follow up on this finding we looked at cell cycle kinetics. We found that SGN-CD70A treatment alone causes a G2 arrest and a modest increase in polyploid cells whereas synergistic combinations with SGN-CD70A and DNA damage kinase and Mps1 inhibitors decrease the number of cells in G2 while markedly increasing polyploid cells. These data suggest induction of mitotic catastrophe may be part of the cellular response to SGN-CD70A treatment. Based on these results, we are currently testing whether sequencing SGN-CD70A and various mitotic inhibitors can increase synergy. Citation Format: Sharsti L. Sandall, Renee McCormick, Jamie Miyamoto, Travis Biechele, Che-Leung Law, Timothy S. Lewis. SGN-CD70A, a pyrrolobenzodiazepine (PBD) dimer linked ADC, mediates DNA damage pathway activation and G2 cell cycle arrest leading to cell death. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 946. doi:10.1158/1538-7445.AM2015-946

A new approach for assimilation of 2D radar precipitation in a high‐resolution NWP model

ABSTRACTA new approach for assimilation of 2D precipitation in numerical weather prediction models is presented and tested in a case with convective, heavy precipitation. In the scheme a nudging term is added to the horizontal velocity divergence tendency equation. In case of underproduction of precipitation, the strength of the nudging is proportional to the offset between observed and modelled precipitation, leading to increased moisture convergence. If the model over‐predicts precipitation, the low level moisture source is reduced, and in‐cloud moisture is nudged towards environmental values. The method was implemented in the Danish Meteorological Institute numerical weather prediction (DMI NWP) nowcasting system, running with hourly cycles, performing a surface analysis and 3D variational analysis for upper air assimilation at each cycle restart, followed by nudging assimilation of precipitation and then a free forecast. The precipitation fields are based on a 2D composite CAPPI (constant altitude plan position indicator) field made from observations with the DMI weather radars, and have a 10 min time resolution. The results obtained in this study indicate that the new method implies fast adjustment of the dynamical state of the model to facilitate precipitation release when the model precipitation intensity is too low. Removal of precipitation is shown to be of importance and the position of the model precipitation cells becomes skilful even at the smallest scales (∼3 km). Bias is reduced for low and extreme precipitation rates. In this meteorological case, the usage of the nudging procedure has been shown to improve the prediction of heavy precipitation substantially.

Evolução das organizações por meio das abordagens institucional, ecologia das organizações e equilíbrio pontuado

DOI: 10.5902/198346592700 Within the functionalist paradigm, characterized by the philosophical objectivism and the sociology of status quo maintenance, the institutional theory and the ecology of organizations theory are thoroughly studied to explain why the organizations can be, paradoxically, so different and so similar. The theory of organizations ecology defends that there is a big difference among organizations and, as time goes by, those most adapt are selected by the environment. This makes the companies more alike, simply by natural selection or by the intention of aligning with the successful ones. This is the core idea of the institutional theory, where the existence of coercive, mimetic, and normative isomorphism standardizes organizations. When an important change occurs in the environment, the cycle restarts, a new selection takes place, and consequently we have the search for isomorphism. Finally, we can observe that one theory complements the other, generating a cycle for the organizations existence, and therefore they can not be considered as exclusive.

Cycles of Distrust: An Economic Model

We propose a model of cycles of distrust and conflict. Overlapping generations of agents from two groups sequentially play coordination games under incomplete information about whether the other side consists of extremists who will never take the good/trusting action. Good actions may be mistakenly perceived as bad/distrusting actions. We also assume that there is limited information about the history of past actions, so that an agent is unable to ascertain exactly when and how a sequence of bad actions originated. Assuming that both sides are not extremists, spirals of distrust and conflict get started as a result of a misperception, and continue because the other side interprets the bad action as evidence that it is facing extremists. However, such spirals contain the seeds of their own dissolution: after a while, Bayesian agents correctly conclude that the probability of a spiral having started by mistake is sufficiently high, and bad actions are no longer interpreted as evidence of extremism. At this point, one party experiments with a good action, and the cycle restarts. We show how this mechanism can be useful in interpreting cycles of ethnic conflict and international war, and how it also emerges in models of political participation, dynamic inter-group trade, and communication - leading to cycles of political polarization, breakdown of trade, and breakdown of communication.

An appraisal of Miscanthus x giganteus cultivation for fly ash revegetation and soil restoration

The objective of this study was to investigate the potential of Miscanthus x giganteus (MxG) for fly ash (FA) revegetation and soil restoration. To evaluate its growth ability on FA, plant development during pot experiments was compared to that obtain in a reference soil. Several physico-chemical parameters (pH, conductivity, dissolved organic carbon, ammonium, nitrite, nitrate, phosphate and potassium contents) and microbiological parameters (enumeration of total, ammonia oxidising and nitrite oxidising culturable bacteria and community diversity analysis) were investigated after plant growth. Plants demonstrated an adaptation to the FA substrate, with an average stem length and biomass production that was half of that observed in the reference soil. Lower chlorophyll contents were measured but the absence of necrosis symptom and hydration rates of aerial parts above 70% suggested physiological adaptation of plants to the FA substrate. Moreover, significant organic carbon inputs could be measured in FA leachates after 17 weeks of laboratory cultivation, which could be related to the establishment of MxG rhizosphere. Besides, the emergence of specific bacterial phylotype could be reported at the FA–root interface. Analysis of FA leachates in planted pots also showed marked decreases of nitrate but increases of nitrite contents, indicating a nitrogen cycle restart. Field trials confirmed the growth potential of MxG directly on FA, without any requirement of additional landfill soil amendment. Finally, we believe that fly ash revegetation with MxG could be an effective strategy for cost effective and long term FA disposal site rehabilitation.

Incidence and persistence of 8-oxo-7,8-dihydroguanine within a hairpin intermediate exacerbates a toxic oxidation cycle associated with trinucleotide repeat expansion

The repair protein 8-oxo-7,8-dihydroguanine glycosylase (OGG1) initiates base excision repair (BER) in mammalian cells by removing the oxidized base 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Interestingly, OGG1 has been implicated in somatic expansion of the trinucleotide repeat (TNR) sequence CAG/CTG. Furthermore, a ‘toxic oxidation cycle’ has been proposed for age-dependent expansion in somatic cells. In this cycle, duplex TNR DNA is (1) oxidized by endogenous species; (2) BER is initiated by OGG1 and the DNA is further processed by AP endonuclease 1 (APE1); (3) a stem-loop hairpin forms during strand-displacement synthesis by polymerase β (pol β); (4) the hairpin is ligated and (5) incorporated into duplex DNA to generate an expanded CAG/CTG region. This expanded region is again subject to oxidation and the cycle continues. We reported previously that the hairpin adopted by TNR repeats contains a hot spot for oxidation. This finding prompted us to examine the possibility that the generation of a hairpin during a BER event exacerbates the toxic oxidation cycle due to accumulation of damage. Therefore, in this work we used mixed-sequence and TNR substrates containing a site-specific 8-oxoG lesion to define the kinetic parameters of human OGG1 (hOGG1) activity on duplex and hairpin substrates. We report that hOGG1 activity on TNR duplexes is indistinguishable from a mixed-sequence control. Thus, BER is initiated on TNR sequences as readily as non-repetitive DNA in order to start the toxic oxidation cycle. However, we find that for hairpin substrates hOGG1 has reduced affinity and excises 8-oxoG at a significantly slower rate as compared to duplexes. Therefore, 8-oxoG is expected to accumulate in the hairpin intermediate. This damage-containing hairpin can then be incorporated into duplex, resulting in an expanded TNR tract that now contains an oxidative lesion. Thus, the cycle restarts and the DNA can incrementally expand.

Loss of H3 K79 Trimethylation Leads to Suppression of Rtt107-dependent DNA Damage Sensitivity through the Translesion Synthesis Pathway

Genomic integrity is maintained by the coordinated interaction of many DNA damage response pathways, including checkpoints, DNA repair processes, and cell cycle restart. In Saccharomyces cerevisiae, the BRCA1 C-terminal domain-containing protein Rtt107/Esc4 is required for restart of DNA replication after successful repair of DNA damage and for cellular resistance to DNA-damaging agents. Rtt107 and its interaction partner Slx4 are phosphorylated during the initial phase of DNA damage response by the checkpoint kinases Mec1 and Tel1. Because the natural chromatin template plays an important role during the DNA damage response, we tested whether chromatin modifications affected the requirement for Rtt107 and Slx4 during DNA damage repair. Here, we report that the sensitivity to DNA-damaging agents of rtt107Δ and slx4Δ mutants was rescued by inactivation of the chromatin regulatory pathway leading to H3 K79 trimethylation. Further analysis revealed that lack of Dot1, the H3 K79 methyltransferase, led to activation of the translesion synthesis pathway, thereby allowing the survival in the presence of DNA damage. The DNA damage-induced phosphorylation of Rtt107 and Slx4, which was mutually dependent, was not restored in the absence of Dot1. The antagonistic relationship between Rtt107 and Dot1 was specific for DNA damage-induced phenotypes, whereas the genomic instability caused by loss of Rtt107 was not rescued. These data revealed a multifaceted functional relationship between Rtt107 and Dot1 in the DNA damage response and maintenance of genome integrity.

Essential Role of Nuclear Localization for Yeast Ulp2 SUMO Protease Function

The SUMO protein is covalently attached to many different substrates throughout the cell. This modification is rapidly reversed by SUMO proteases. The Saccharomyces cerevisiae SUMO protease Ulp2 is a nuclear protein required for chromosome stability and cell cycle restart after checkpoint arrest. Ulp2 is related to the human SENP6 protease, also a nuclear protein. All members of the Ulp2/SENP6 family of SUMO proteases have large but poorly conserved N-terminal domains (NTDs) adjacent to the catalytic domain. Ulp2 also has a long C-terminal domain (CTD). We show that CTD deletion has modest effects on yeast growth, but poly-SUMO conjugates accumulate. In contrast, the NTD is essential for Ulp2 function and is required for nuclear targeting. Two short, widely separated sequences within the NTD confer nuclear localization. Efficient Ulp2 import into the nucleus requires the beta-importin Kap95, which functions on classical nuclear-localization signal (NLS)-bearing substrates. Remarkably, replacement of the entire >400-residue NTD by a heterologous NLS results in near-normal Ulp2 function. These data demonstrate that nuclear localization of Ulp2 is crucial in vivo, yet only small segments of the NTD provide the key functional elements, explaining the minimal sequence conservation of the NTDs in the Ulp2/SENP6 family of enzymes.

HOW TO SIMULATE THERMAL AND FLUID DYNAMICAL PROCESSES IN CLOSED GREENHOUSES INCLUDING WATER INTERACTIONS BETWEEN PLANTS AND AIR

A new type of greenhouse is presented. It is a closed system using buoyancy as driving force for ventilation. The greenhouse is equipped with a tower in which the air is cooled or heated to maintain the inner temperatures in the required band and then conducted back to the plants. During the cooling process the water in the humid air condenses and can be reused. The subject of this article is the way of prediction of the thermal behaviour of closed greenhouses by means of dynamic simulations. Several model approaches are discussed. The simulation environment Smile is presented as a flexible program for this purpose. INTRODUCTION Closed greenhouses were designed hoping for various advantages. First the possi- bility of injecting CO2 without important losses for increased fruit production, second the reduction of water losses by the absence of wind and the potential of reusing water from condensation processes, and third the use of the greenhouse as a solar collector extracting excess energy during hot days for heating purposes in cold periods thus stretching its operation time without external energy supply. The main disadvantage of closed greenhouses in contrast is the non trivial thermal and humidity behaviour of the combined system consisting of greenhouse cover, air, plants, soil, and heating/cooling facilities. Therefore an EU funded research project, named Watergy, has been created (Buchholz et al., 2005). In this paper the chosen approach to the simulation of the investigated systems will be shown. WATERGY The objective of Watergy is the development of a closed humid air solar collector (Fig. 1) driven by natural convection forces due to buoyancy. The solar collector could be either a solitary greenhouse or an attached greenhouse in front of a building. The buoyancy resulting from the warmed up plant region causes an air flow to the top of the collector. From there the air will be conducted back to the plants through a colder heat exchanger which is installed in a return duct. The cooled air flows back to the plant region where the cycle restarts. During the circulation of the air the moisture content varies in a wide range. The air will be humidified by the transpiration of the plants and the evaporation from the soil. Furthermore the air is additionally humidified with grey or salty water. To prevent contact of this water with the plants, an extra so called inner roof has been installed collecting the remaining drain water that is not evaporated. In the cold heat exchanger the water vapour will condense and can be collected for irrigation or other purposes (Fig. 2). Through the humidification of the air by evapo-transpiration and the additional sprinkler system the air temperature can be kept relatively cold. This results in smaller heat losses to the environment. A heat storage is needed to extract the heat from the collector and supply the heat exchanger with cold water. Cold water can be obtained by heating the greenhouse with the same heat exchanger during colder periods, in the case of diurnal storage during the night or in the case of a seasonal storage during the colder season.

Menstrual cycle length during methadone maintenance

While the menstrual disruption of heroin has been demonstrated, there are few published data concerning methadone maintenance and menstrual function. This study was conducted to evaluate whether cycle length was more regular during methadone maintenance. An out-patient research treatment program in Baltimore, Maryland, USA. A total of 191 heroin and cocaine-using women from two clinical trials, lasting 25-29 weeks; each woman was maintained on 70-100 mg of methadone. Start/end dates of each menses were collected. Menstrual patterns were classified as regular, irregular, transient amenorrhea, persistent amenorrhea or cycle restart. Repeated-measures regression modeling determined correlates of cycle length and predictors of long cycles (> 40 days) and short cycles (< 20 days). Bleeding episodes were defined as 1 or more bleeding days, bound by at least 2 non-bleeding days. Correlates/predictors examined were body mass index, drug use, methadone dose and race. In the 133 women for whom menstrual patterns could be determined, cycle-length irregularity was common: irregular, 62 (46.7%); regular, 37 (27.8%); cycle restart, 16 (12%); persistent amenorrhea, 11 (8.3%); transient amenorrhea, seven (5.3%). Each additional week on methadone maintenance was associated with decreased risk of long (OR = 0.96, P < 0.01 and short (OR = 0.92, P < 0.01) cycles. Of 27 women with secondary amenorrhea pre-study, 16 (59%) restarted menses. Positivity for opioids or cocaine was not significantly associated with short or long cycles. Cycle length begins to normalize during methadone maintenance. Menses resumption may occur. Methadone maintenance, despite interfering with menstrual function in an absolute sense, may interfere less than illicit heroin abuse.