Search

Nanoparticles exhibit diverse effects when added as additives to oily medium, enhancing tribological properties and surface characteristics. Studies have shown that many oxide ceramic nanoparticles improve friction and wear, while mixtures also demonstrate favorable tribological properties. This study explores the tribological effect of an yttria–silica (Y2O3, SiO2) nanoparticle mixture in a Group III base oil medium. The results reveal that the yttria–silica mixture significantly reduces friction (−8–17%), mean wear scar diameter (−32%), and wear volume (−94%), while increasing load-bearing capacity (+114%) by creating a durable boundary layer. Observations from scanning electron microscopy revealed the original surface is protected. EDX analyses highlight the boundary layer’s elemental composition, which is high in yttrium, silicon, and oxygen and found in higher areas. XRD analysis could not detect the yttria nanoparticle additive within the boundary layer, suggesting that it fragmented due to sliding stress, resulting in an amorphous structure for the new boundary layer. TEM imaging confirmed that the boundary layer thickness is 40–45 nm. These findings demonstrate significant potential for industrial applications in developing advanced, high-performance lubricants for demanding mechanical systems.

Purpose: To present and compare models created by two different rapid prototyping (RP) methods. Materials and methods: Using a three-dimensional graphic program (Blender, Blender Foundation) a 10 × 10 × 2 mm test specimen was created and printed with a Formlabs Form 2 (Formlabs Inc.) SLA printer of photopolymerization resin and with a Stratasys Objet 30 Orthodesk (Stratasys GmbH) Polyjet printer of acrylate. After printing, the post-processing was performed according to the manufacturer’s instructions, and then the specimens were examined by various physical, optical and imaging diagnostic methods. Results: Our results showed that the two different technologies result in different morphological images and parameters. Between the digital reference specimen and the x and y value of the VeroGlaze MED 620 and Dental SG materials, there was a significant difference (P < 0,001). Conclusions: The currently available rapid prototyping methods with limitations are suitable for dental use with the measured parameters.

Auger-emitting radionuclides, exemplified by Pd-103, exhibit considerable therapeutic potential in cancer treatment due to their high cytotoxicity and localized biological impact. Despite these advantages, the separation of such radionuclides presents a complicated challenge, requiring intricate and time-intensive “wet chemistry” methods attributed to the exceptional chemical inertness of the associated metals. This study proposes an innovative solution to this separation challenge through the design and implementation of a piece of radionuclide separation equipment (RSE). The equipment employs a dry distillation approach, capitalizing on differences in partial vapor pressures between irradiated and resulting radioactive metals, with a diffusion-driven extraction method applied to separate Pd-103 radionuclides generated via the proton irradiation of Rh-103 at cyclotron. Our optimization endeavors focused on determining the optimal temperature for effective metal separation and adjusting the diffusion, evaporation, and deposition rates, as well as addressing chemical impurities. The calculations indicate 17% ± 2% separation efficiency with our RSE. Approximately 77 ± 2% and 49 ± 2% of the deposited Pd-103 were isolated on substrates of Nb foil and ZnO-covered W disc, respectively. The proposed innovative dry distillation method that has been experimentally tested offers a promising alternative to conventional separation techniques, enabling enhanced purity and cost-efficient cancer treatment strategies.

Materials developed for wound healing have to meet several criteria, such as being non-cytotoxic, biocompatible, biodegradable, having good mechanical properties, and acting selectively with osteoblasts. The aim of this study was, using an electrospinning method, to prepare a polymer scaffold to get a stable, adequate, hydrophilic structure, which will enhance wound healing during bone regeneration. To achieve that, a cross-linked polyvinyl alcohol fibre net was prepared by heat treatment and applied to the water-based polymer in presence of a citric acid solution. The viscosity of the initial polymer was determined from the flow curve measurements. The surface properties of the fibre nets were monitored by the low-vacuum scanning electron microscopy and the contact angle measurements. It was found that the addition of a citric acid as a cross-linker in a concentration exceeding 2m/m% increased the diameter of the polyvinyl alcohol fibres. When adding 8m/m% citric acid, an initial diameter of 224 ± 52 nm has increased to 269 ± 109 nm. Furthermore, the distribution also became wider due to the development of bonding points for ester bonds. This process was enhanced by a two-hour heating at 120 °C; thus, resulting in modification of the OH groups on the surface. The decrease of hydrophilicity was proved by the increase in contact angles. In addition, it was demonstrated that the scaffold structure prepared with this method does not degrade during the 24–120 h long water treatment.

The surface roughness, surface free energy (SFE) of composites, and composite wettability by dental adhesives are determining factors in achieving a strong and durable adhesion (e.g., composite repair, luting adhesively bonded indirect restorations). In this study, the SFE of one nanohydrid and two bulk-fill composites was investigated in relation to the wetting ability of five different dental adhesives. The profilometry and scanning electron microscopy (SEM) measurement justified that the sandblasting produced a significantly rough surface in which the different filler amounts, filler distribution, and resin-filler ratio participated. The SFE of the tested composite was between 45.65 and 49.07 mJ/m2 regardless of surface treatment. Despite the similarity in SFE, the adhesives wet the surface of the composites in different ways that were between 16.01° and 35.10°. The contact angle of solvent-free dental adhesive was lower due to sandblasting supporting the micromechanical retention. Based on our results, it was found that sandblasting, the most frequently recommended surface treatment, does not change the surface energy but causes a change in the contact angle, which can be explained by the different surface tension of the dental adhesives. It was concluded that the dental adhesive parameters have a more important role in wettability.

Examination of the zeolite and magnesium-exchanged zeolite system on human stem cells culture, different viability and ALP activity values at different concentrations provide information on the factors influencing ossification and bone “turnover”. The aim of our present work was to investigate the effect of zeolite and magnesium ion-exchanged zeolite concentrations (0.605 mM, 0.325 mM, 0.15 mM Mg-zeolite and zeolite) in an in vitro experimental system on culture medium from wisdom tooth cells (DPSC – dental pulp stem cells) at different sampling times (1, 4, 7 and 14 days). Based on our measurements of viability and alkaline phosphatase activity, both components studied, zeolite and magnesium- ion-exchanged zeolite could be promising components of future medical interventions using artificial tissue culture in several areas. Our experiments showed that Mg-zeolite was more effective.

Zirconia-based ceramics have been widely applied in the field of prosthodontics. Yttria stabilized tetragonal zirconia polycristal (Y-TZP) can further enhance the bending strength and fracture toughness of prosthesis remarkably by neutralizing the external strain through phase transformation. In this study seven frequently used Y-TZM ceramics were evaluated. Significant differences were found both in the three point bending test and in the fracture toughness results. Also, coherence was found between the monocline-tetracline phase transformation and fracture toughness results of the different ceramics. These parameters are important factors in the final quality of the Y-TZP prosthesis.

Decreasing the energy loss both by buildings and by vehicles perhaps one of the most important efforts to protect our environment and energy resources. An option to achieve this is to apply thermal insulations moreover, of super insulation materials (such as aerogel) are becoming increasingly justified. However, these are relatively new materials. The main aim of this paper is to present research results based on case studies of a spaceloft type aerogel once to see the temperature, load and thickness effects in the thermal conductivity, secondly to present results of the measurements regarding the two most important calorific parameters as the specific heat and the combustion heat. These results should be very useful for both designers and researchers. Measurements were executed by Netzschh 446 heat flow meter and Cal2 Eco bomb calorimeter. Moreover, calculation results executed on the thermal properties reached from the measured values will be reported. From the measurements, we showed that temperature and external load should affect a significant change in the thermal conductivity of materials, while the thickness should cause only a slight change. Moreover, the gross combustion heat of the aerogel was measured. Changes in the aerogel before and after combustion was investigated by Scanning Electron Microscopy, as well as with Raman microscopy.

Lead oxide (PbO) photoconductors are proposed as X-ray-to-charge transducers for the next generation of direct conversion digital X-ray detectors. Optimized PbO-based detectors have potential for utilization in high-energy and dynamic applications of medical X-ray imaging. Two polymorphs of PbO have been considered so far for imaging applications: polycrystalline lead oxide (poly-PbO) and amorphous lead oxide (a-PbO). Here, we provide the comparative analysis of two PbO-based single-pixel X-ray detector prototypes: one prototype employs only a layer of a-PbO as the photoconductor while the other has a combination of a-PbO and poly-PbO, forming a photoconductive bilayer structure of the same overall thickness as in the first prototype. We characterize the performance of these prototypes in terms of electron–hole creation energy (W±) and signal lag—major properties that define a material’s suitability for low-dose real-time imaging. The results demonstrate that both X-ray photoconductive structures have an adequate temporal response suitable for real-time X-ray imaging, combined with high intrinsic sensitivity. These results are discussed in the context of structural and morphological properties of PbO to better understand the preparation–fabrication–property relationships of this material.

The in situ application of the combination of different types of drugs revolutionized the area of periodontal therapy. The purpose of this study was to develop nanocomposite hydrogel (NCHG) as a pH-sensitive drug delivery system. To achieve local applicability of the NCHG in dental practice, routinely used blue-light photopolymerization was chosen for preparation. The setting time was 60 s, which resulted in stable hydrogel structures. Universal Britton–Robinson buffer solutions were used to investigate the effect of pH in the range 4–12 on the release of drugs that can be used in the periodontal pocket. Metronidazole was released from the NCHGs within 12 h, but chlorhexidine showed a much longer elution time with strong pH dependence, which lasted more than 7 days as it was corroborated by the bactericidal effect. The biocompatibility of the NCHGs was proven by Alamar-blue test and the effectiveness of drug release in the acidic medium was also demonstrated. This fast photo-polymerizable NCHG can help to establish a locally applicable combined drug delivery system which can be loaded with the required amount of medicines and can reduce the side effects of the systemic use of drugs that have to be used in high doses to reach an ideal concentration locally.

β-Tricalcium phosphate was combined with silica aerogel in composites prepared using the sol–gel technique and supercritical drying. The materials were used in this study to check their biological activity and bone regeneration potential with MG63 cell experiments. The composites were sintered in 100 °C steps in the range of 500–1000 °C. Their mechanical properties, porosities, and solubility were determined as a function of sintering temperature. Dissolution studies revealed that the released Ca-/P molar ratios appeared to be in the optimal range to support bone tissue induction. Cell viability, ALP activity, and type I collagen gene expression results all suggested that the sintering of the compound at approximately 700–800 °C as a scaffold could be more powerful in vivo to facilitate bone formation within a bone defect, compared to that documented previously by our research team. We did not observe any detrimental effect on cell viability. Both the alkaline phosphatase enzyme activity and the type I collagen gene expression were significantly higher compared with the control and the other aerogels heat-treated at different temperatures. The mesoporous silica-based aerogel composites containing β-tricalcium phosphate particles treated at temperatures lower than 1000 °C produced a positive effect on the osteoblastic activity of MG63 cells. An in vivo 6 month-long follow-up study of the mechanically strongest 1000 °C sample in rat calvaria experiments provided proof of a complete remodeling of the bone.

In the European Union, almost 40% of all energy consumption comes from buildings, while another 20–25% comes from transport. In the European Union, including Hungary, only buildings with almost-zero energy demand could be built after 2020, and the use of renewable energies must be strengthened. The Renewable Directive stipulated that by 2020, the share of renewable energy in buildings must be 25%, and in transport it must be 10%; the use of electric vehicles is vital. There are about four million dwellings in Hungary, of which approximately three million need to be renovated, and only some of these (a few hundred) meet the cost-optimized level of the 2020 directive. The use of insulation materials is very important in the transport sector, too. Insulation materials are also used by aircraft and electric vehicles. To reduce the energy loss from buildings, different insulation materials can be used; investigations of insulation materials are very important. This paper presents a comprehensive research report on insulation materials which could be used for building elements, HVAC (heating, ventilation, and air conditioning appliances) equipment, and vehicles. In this paper, laboratory investigations will be presented along with calculations to better understand the properties and behavior of these materials. For this, firstly structural analysis with scanning electron microscope will be presented. Moreover, the paper will present thermal conductivity and combustion heat measurement results. The sorption and hydrophobic behavior of the materials will be also revealed. Finally, the article will also display differential scanning calorimetry measurements and Raman spectroscopy results of the samples. The research was conducted on four different types of colorized microfiber lightweight wool insulation.

Though the antibacterial effect is advantageous, silver and silver nanoparticles can negatively affect the viability of human tissues. This study aims to check the viability of cells on surfaces with different particle size and to find the biologically optimal configuration. We investigated the effect of modified thickness of vaporized silver and applied heat and time on the physical characteristics of silver nanoparticle covered titanium surfaces. Samples were examined by scanning electron microscopy, mass spectrometry, and drop shape analyzer. To investigate how different physical surface characteristics influence cell viability, Alamar Blue assay for dental pulp stem cells was carried out. We found that different surface characteristics can be achieved by modifying procedures when creating silver nanoparticle covered titanium. The size of the nanoparticles varied between 60 to 368 nm, and hydrophilicity varied between 63 and 105 degrees of contact angle. Investigations also demonstrated that different physical characteristics are related to a different level of viability. Surfaces covered with 60 nm particle sizes proved to be the most hydrophilic, and the viability of the cells was comparable to the viability measured on the untreated control surface. Physical and biological characteristics of silver nanoparticle covered titanium, including cell viability, have an acceptable level to be used for antibacterial effects to prevent periimplantitis around implants.

Nowadays, besides the use of conventional insulations (plastic foams and wool materials), aerogels are one of the most promising thermal insulation materials. As one of the lightest solid materials available today, aerogels are manufactured through the combination of a polymer with a solvent, forming a gel. For buildings, the fiber-reinforced types are mainly used. In this paper, the changes both in the thermal performance and the material structure of the aerogel blanket are followed after thermal annealing. The samples are put under isothermal heat treatments at 70 °C for weeks, as well as at higher temperatures (up to 210 °C) for one day. The changes in the sorption properties that result from the annealing are presented. Furthermore, the changes in the thermal conductivity are followed by a Holometrix Lambda heat flow meter. The changes in the structure and surface of the material due to the heat treatment are investigated by X-ray diffraction and with scanning electron microscopy. Besides, the above-mentioned measurement results of differential scanning calorimetry experiments are also presented. As a result of using equipment from different laboratories that support each other, we found that the samples go through structural changes after undergoing thermal annealing. We manifested that the aerogel granules separate down from the glass fibers and grow up. This phenomenon might be responsible for the change in the thermal conductivity of the samples.

Abstract Background The postsynaptic density is an elaborate protein network beneath the postsynaptic membrane involved in the molecular processes underlying learning and memory. The postsynaptic density is built up from the same major proteins but its exact composition and organization differs between synapses. Mutations perturbing protein: protein interactions generally occurring in this network might lead to effects specific for cell types or processes, the understanding of which can be especially challenging. Results In this work we use systems biology-based modeling of protein complex distributions in a simplified set of major postsynaptic proteins to investigate the effect of a hypomorphic Shank mutation perturbing a single well-defined interaction. We use data sets with widely variable abundances of the constituent proteins. Our results suggest that the effect of the mutation is heavily dependent on the overall availability of all the protein components of the whole network and no trivial correspondence between the expression level of the directly affected proteins and overall complex distribution can be observed. Conclusions Our results stress the importance of context-dependent interpretation of mutations. Even the weakening of a generally occurring protein: protein interaction might have well-defined effects, and these can not easily be predicted based only on the abundance of the proteins directly affected. Our results provide insight on how cell-specific effects can be exerted by a mutation perturbing a generally occurring interaction even when the wider interaction network is largely similar.

Abstract Yeast colonies are routinely grown on agar plates in everyday experimental settings to understand basic molecular processes, produce novel drugs, improve health, and so on. Standardized conditions ensure these colonies grow in a reproducible fashion, while in nature microbes are under a constantly changing environment. Here we combine the power of computational simulations and laboratory experiments to investigate the impact of non-standard environmental factors on colony growth. We present the developement and parameterization of a quantitative agent-based model for yeast colony growth to reproduce measurements on colony size and cell number in a colony at non-standard environmental conditions. Specifically, we establish experimental conditions that mimic the effects of humidity changes and nutrient gradients. Our results show how colony growth is affected by moisture changes, nutrient availability, and initial colony inoculation conditions. We show that initial colony spread, not initial cell number have higher impact on the final size and cell number of colonies. Parameters of the model were identified by fitting these experiments and the fitted model gives guidance to establish conditions which enable unlimited growth of yeast colonies.

Copyright of Fogorvosi Szemle is the property of Hungarian Dental Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Fogorvosi Szemle is the property of Hungarian Dental Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Temperature compensation and robustness to biological noise are two key characteristics of the circadian clock. These features allow the circadian pacemaker to maintain a steady oscillation in a wide range of environmental conditions. The presence of a time-delayed negative feedback loop in the regulatory network generates autonomous circadian oscillations in eukaryotic systems. In comparison, the circadian clock of cyanobacteria is controlled by a strong positive feedback loop. Positive feedback loops with substrate depletion can also generate oscillations, inspiring other circadian clock models. What makes a circadian oscillatory network robust to extrinsic noise is unclear. We investigated four basic circadian oscillators with negative, positive, and combinations of positive and negative feedback loops to explore network features necessary for circadian clock resilience. We discovered that the negative feedback loop system performs the best in compensating temperature changes. We also show that a positive feedback loop can reduce extrinsic noise in periods of circadian oscillators, while intrinsic noise is reduced by negative feedback loops.

Copyright of Fogorvosi Szemle is the property of Hungarian Dental Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract In eukaryotes the entry into mitosis is initiated by activation of cyclin-dependent kinases (CDKs), which in turn activate a large number of protein kinases to induce all mitotic processes. The general view is that kinases are active in mitosis and phosphatases turn them off in interphase. Kinases activate each other by cross- and self-phosphorylation, while phosphatases remove these phosphate groups to inactivate kinases. Crucial exceptions to this general rule are the interphase kinase Wee1 and the mitotic phosphatase Cdc25. Together they directly control CDK in an opposite way of the general rule of mitotic phosphorylation and interphase dephosphorylation. Here we investigate why this opposite system emerged and got fixed in almost all eukaryotes. Our results show that this reversed action of a kinase-phosphatase pair, Wee1 and Cdc25, on CDK is particularly suited to establish a stable G2 phase and to add checkpoints to the cell cycle. We show that all these regulators appeared together in LECA (Last Eukaryote Common Ancestor) and co-evolved in eukaryotes, suggesting that this twist in kinase-phosphatase regulation was a crucial step happening at the emergence of eukaryotes.

Morphogen gradients can be dynamic and transient yet give rise to stable cellular patterns. Here the authors show that a synthetic morphogen-induced mutual inhibition circuit produces stable boundaries when the spatial average of morphogens falls within the region of bistability.

Pandemic management requires reliable and efficient dynamical simulation to predict and control disease spreading. The COVID-19 (SARS-CoV-2) pandemic is mitigated by several non-pharmaceutical interventions, but it is hard to predict which of these are the most effective for a given population. We developed the computationally effective and scalable, agent-based microsimulation framework PanSim, allowing us to test control measures in multiple infection waves caused by the spread of a new virus variant in a city-sized societal environment using a unified framework fitted to realistic data. We show that vaccination strategies prioritising occupational risk groups minimise the number of infections but allow higher mortality while prioritising vulnerable groups minimises mortality but implies an increased infection rate. We also found that intensive vaccination along with non-pharmaceutical interventions can substantially suppress the spread of the virus, while low levels of vaccination, premature reopening may easily revert the epidemic to an uncontrolled state. Our analysis highlights that while vaccination protects the elderly from COVID-19, a large percentage of children will contract the virus, and we also show the benefits and limitations of various quarantine and testing scenarios. The uniquely detailed spatio-temporal resolution of PanSim allows the design and testing of complex, specifically targeted interventions with a large number of agents under dynamically changing conditions.

The postsynaptic density (PSD) is a dense protein network playing a key role in information processing during learning and memory, and is also indicated in a number of neurological disorders. Efforts to characterize its detailed molecular organization are encumbered by the large variability of the abundance of its constituent proteins both spatially, in different brain areas, and temporally, during development, circadian rhythm, and also in response to various stimuli. In this study we ran large-scale stochastic simulations of protein binding events to predict the presence and distribution of PSD complexes. We simulated the interactions of seven major PSD proteins (NMDAR, AMPAR, PSD-95, SynGAP, GKAP, Shank3, Homer1) based on previously published, experimentally determined protein abundance data from 22 different brain areas and 42 patients (altogether 524 different simulations). Our results demonstrate that the relative ratio of the emerging protein complexes can be sensitive to even subtle changes in protein abundances and thus explicit simulations are invaluable to understand the relationships between protein availability and complex formation. Our observations are compatible with a scenario where larger supercomplexes are formed from available smaller binary and ternary associations of PSD proteins. Specifically, Homer1 and Shank3 self-association reactions substantially promote the emergence of very large protein complexes. The described simulations represent a first approximation to assess PSD complex abundance, and as such, use significant simplifications. Therefore, their direct biological relevance might be limited but we believe that the major qualitative findings can contribute to the understanding of the molecular features of the postsynapse.

Cells can maintain their homeostasis in a noisy environment since their signaling pathways can filter out noise somehow. Several network motifs have been proposed for biological noise filtering and, among these, feed-forward loops have received special attention. Specific feed-forward loops show noise reducing capabilities, but we notice that this feature comes together with a reduced signal transducing performance. In posttranslational signaling pathways feed-forward loops do not function in isolation, rather they are coupled with other motifs to serve a more complex function. Feed-forward loops are often coupled to other feed-forward loops, which could affect their noise-reducing capabilities. Here we systematically study all feed-forward loop motifs and all their pairwise coupled systems with activation-inactivation kinetics to identify which networks are capable of good noise reduction, while keeping their signal transducing performance. Our analysis shows that coupled feed-forward loops can provide better noise reduction and, at the same time, can increase the signal transduction of the system. The coupling of two coherent 1 or one coherent 1 and one incoherent 4 feed-forward loops can give the best performance in both of these measures.

Parkinson’s disease (PD), Alzheimer’s disease (AD) and Amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases hallmarked by the formation of toxic protein aggregates. However, targeting these aggregates therapeutically have thus far shown no success. The treatment of AD has remained particularly problematic since no new drugs have been approved in the last 15 years. Therefore, novel therapeutic targets need to be identified and explored. Here, through the integration of genomic and proteomic data, a set of proteins with strong links to α-synuclein-aggregating neurodegenerative diseases was identified. We propose 17 protein targets that are likely implicated in neurodegeneration and could serve as potential targets. The human phosphatidylinositol 5-phosphatase synaptojanin-1, which has already been independently confirmed to be implicated in Parkinson’s and Alzheimer’s disease, was among those identified. Despite its involvement in PD and AD, structural aspects are currently missing at the molecular level. We present the first atomistic model of the 5-phosphatase domain of synaptojanin-1 and its binding to its substrate phosphatidylinositol 4,5-bisphosphate (PIP2). We determine structural information on the active site including membrane-embedded molecular dynamics simulations. Deficiency of charge within the active site of the protein is observed, which suggests that a second divalent cation is required to complete dephosphorylation of the substrate. The findings in this work shed light on the protein’s binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and give additional insight for future targeting of the protein active site, which might be of interest in neurodegenerative diseases where synaptojanin-1 is overexpressed.

The yeast centrosome or Spindle Pole Body (SPB) is an organelle situated in the nuclear membrane, where it nucleates spindle microtubules and acts as a signaling hub. Various studies have explored the effects of forcing individual proteins to interact with the yeast SPB, however no systematic study has been performed. We used synthetic physical interactions to detect proteins that inhibit growth when forced to associate with the SPB. We found the SPB to be especially sensitive to relocalization, necessitating a novel data analysis approach. This novel analysis of SPI screening data shows that regions of the cell are locally more sensitive to forced relocalization than previously thought. Furthermore, we found a set of associations that result in elevated SPB number and, in some cases, multi-polar spindles. Since hyper-proliferation of centrosomes is a hallmark of cancer cells, these associations point the way for the use of yeast models in the study of spindle formation and chromosome segregation in cancer.

The transition from mitosis into the first gap phase of the cell cycle in budding yeast is controlled by the Mitotic Exit Network (MEN). The network interprets spatiotemporal cues about the progression of mitosis and ensures that release of Cdc14 phosphatase occurs only after completion of key mitotic events. The MEN has been studied intensively; however, a unified understanding of how localisation and protein activity function together as a system is lacking. In this paper, we present a compartmental, logical model of the MEN that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity. We show that our model is capable of correctly predicting the phenotype of the majority of mutants we tested, including mutants that cause proteins to mislocalise. We use a continuous time implementation of the model to demonstrate that Cdc14 Early Anaphase Release (FEAR) ensures robust timing of anaphase, and we verify our findings in living cells. Furthermore, we show that our model can represent measured cell-cell variation in Spindle Position Checkpoint (SPoC) mutants. This work suggests a general approach to incorporate spatial effects into logical models. We anticipate that the model itself will be an important resource to experimental researchers, providing a rigorous platform to test hypotheses about regulation of mitotic exit.

Loss of proteostasis and cellular senescence are key hallmarks of aging, but direct cause-effect relationships are not well understood. We show that most yeast cells arrest in G1 before death with low nuclear levels of Cln3, a key G1 cyclin extremely sensitive to chaperone status. Chaperone availability is seriously compromised in aged cells, and the G1 arrest coincides with massive aggregation of a metastable chaperone-activity reporter. Moreover, G1-cyclin overexpression increases lifespan in a chaperone-dependent manner. As a key prediction of a model integrating autocatalytic protein aggregation and a minimal Start network, enforced protein aggregation causes a severe reduction in lifespan, an effect that is greatly alleviated by increased expression of specific chaperones or cyclin Cln3. Overall, our data show that proteostasis breakdown, by compromising chaperone activity and G1-cyclin function, causes an irreversible arrest in G1, configuring a molecular pathway postulating proteostasis decay as a key contributing effector of cell senescence.

Rare-earth-doped optical materials are important for light sources in optoelectronics, as well as for efficient optical amplification elements and other elements of photonics. On the basis of the previously developed method of anhydrous, low-temperature synthesis of Er/Yb oxides from their chlorides we fabricated proper nanoparticles with defined parameters and used them for the development of optically transparent, luminescent polymer nanocomposite with low optical scattering, suitable for direct, light-induced formation of photonic elements. Introduction of preformed gold nanoparticles in such a nanocomposite was also performed and an enhancement of luminescence due to the influence of plasmon effects was detected.

It is shown in this overview that modern composition depth profiling methods like secondary neutral mass spectroscopy (SNMS) and glow-discharge – time-of-flight mass spectrometry (GD-ToFMS) can be used to gain highly specific composition depth profile information on electrodeposited alloys. In some cases, cross-sectional transmission electron microscopy was also used for gaining complementary information; nevertheless, the basic component distribution derived with each method exhibited the same basic features. When applying the reverse sputtering direction to SNMS analysis, the near-substrate composition evolution can be revealed with unprecedented precision. Results are presented for several specific cases of electrodeposited alloys and mulitlayers. It is shown that upon d.c. plating from an unstirred solution, the preferentially deposited metal accumulates in the near-substrate zone, and the steady-state alloy composition sets in at about 150-200 nm deposit thickness only. If there is more than one preferentially deposited metal in the alloy, the accumulation zones of these metals occur in the order of the deposition preference. This accumulation zone can be eliminated by well-controlled hydrodynamic conditions (like the application of rotating disc electrodes) or by pulse plating where the systematic decrease in the duty cycle provides a gradual transition from a graded to a uniform composition depth profile. The application of composition depth profile measurements enabled detecting the coincidence in the occurrence of some components in the deposits down to the impurity level. This was exemplified by the GD-ToFMS measurements of Ni-Cu/Cu multilayers where all detected impurities accumulated in the Cu layer. The wealth of information obtained by these methods provides a much more detailed picture than the results normally obtained with bulk analysis through conventional integral depth profiling and help in the elucidation of the side reactions taking place during the plating processes.

Characterization of normal breast stem cells is important for understanding their role in breast development and in breast cancer. However, the identity of these cells is a subject of controversy and their localization in the breast epithelium is not known. In this study, we utilized a novel approach to analyze the morphogenesis of mammary lobules, by combining one-dimensional theoretical models and computer-generated 3D fractals. Comparing predictions of these models with immunohistochemical analysis of tissue sections for candidate stem cell markers, we defined distinct areas where stem cells reside in the mammary lobule. An increased representation of stem cells was found in smaller, less developed lobules compared to larger, more mature lobules, with marked differences in the gland of nulliparous versus parous women and that of BRCA1/2 mutation carriers versus non-carriers.

ABSTRACT Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole. Genome sequencing, array-based comparative genome analysis, and gene expression profiling revealed that during the course of evolution in fluconazole, the range of mutational and gene deregulation differences was distinctively different and broader in the hypermistranslating strain, including multiple chromosome duplications, partial chromosome deletions, and polyploidy. Especially, the increased accumulation of loss-of-heterozygosity events, aneuploidy, translational and cell surface modifications, and differences in drug efflux seem to mediate more rapid drug resistance acquisition under mistranslation. Our observations support a pivotal role for adaptive mistranslation in the evolution of drug resistance in C. albicans. IMPORTANCE Infectious diseases caused by drug-resistant fungi are an increasing threat to public health because of the high mortality rates and high costs associated with treatment. Thus, understanding of the molecular mechanisms of drug resistance is of crucial interest for the medical community. Here we investigated the role of regulated protein mistranslation, a characteristic mechanism used by C. albicans to diversify its proteome, in the evolution of fluconazole resistance. Such codon ambiguity is usually considered highly deleterious, yet recent studies found that mistranslation can boost adaptation in stressful environments. Our data reveal that CUG ambiguity diversifies the genome in multiple ways and that the full spectrum of drug resistance mechanisms in C. albicans goes beyond the traditional pathways that either regulate drug efflux or alter the interactions of drugs with their targets. The present work opens new avenues to understand the molecular and genetic basis of microbial drug resistance.

Cells are able to adjust their growth and size to external inputs to comply with specific fates and developmental programs. Molecular pathways controlling growth also have an enormous impact in cell size, and bacteria, yeast, or epithelial cells modify their size as a function of growth rate. This universal feature suggests that growth (mass) and proliferation (cell number) rates are subject to general coordinating mechanisms. However, the underlying molecular connections are still a matter of debate. Here we review the current ideas on growth and cell size control, and focus on the possible mechanisms that could link the biosynthetic machinery to the Start network in budding yeast. In particular, we discuss the role of molecular chaperones in a competition framework to explain cell size control by growth at the individual cell level.

Background Publishing in scientific journals is one of the most important ways in which scientists disseminate research to their peers and to the wider public. Pre-publication peer review underpins this process, but peer review is subject to various criticisms and is under pressure from growth in the number of scientific publications. Methods Here we examine an element of the editorial process at eLife, in which the Reviewing Editor usually serves as one of the referees, to see what effect this has on decision times, decision type, and the number of citations. We analysed a dataset of 8,905 research submissions to eLife since June 2012, of which 2,747 were sent for peer review. This subset of 2747 papers was then analysed in detail. Results The Reviewing Editor serving as one of the peer reviewers results in faster decision times on average, with the time to final decision ten days faster for accepted submissions (n=1,405) and five days faster for papers that were rejected after peer review (n=1,099). Moreover, editors acting as reviewers had no effect on whether submissions were accepted or rejected, and a very small (but significant) effect on citation rates. Conclusions An important aspect of eLife’s peer-review process is shown to be effective, given that decision times are faster when the Reviewing Editor serves as a reviewer. Other journals hoping to improve decision times could consider adopting a similar approach.

Background Publishing in scientific journals is one of the most important ways in which scientists disseminate research to their peers and to the wider public. Pre-publication peer review underpins this process, but peer review is subject to various criticisms and is under pressure from growth in the number of scientific publications. Methods Here we examine an element of the editorial process at eLife, in which the Reviewing Editor usually serves as one of the referees, to see what effect this has on decision times, decision type, and the number of citations. We analysed a dataset of 8,905 research submissions to eLife since June 2012, of which 2,750 were sent for peer review, using R and Python to perform the statistical analysis. Results The Reviewing Editor serving as one of the peer reviewers results in faster decision times on average, with the time to final decision ten days faster for accepted submissions (n=1,405) and 5 days faster for papers that were rejected after peer review (n=1,099). There was no effect on whether submissions were accepted or rejected, and a very small (but significant) effect on citation rates for published articles where the Reviewing Editor served as one of the peer reviewers. Conclusions An important aspect of eLife’s peer-review process is shown to be effective, given that decision times are faster when the Reviewing Editor serves as a reviewer. Other journals hoping to improve decision times could consider adopting a similar approach.