Histone deacetylase Hos2 regulates protein expression noise by potentially modulating the protein translation machinery.

Non-genetic variations derived from expression noise at transcript or protein levels can result in cell-to-cell heterogeneity within an isogenic population. Although cells have developed strategies to reduce noise in some cellular functions, this heterogeneity can also facilitate varying levels of regulation and provide evolutionary benefits in specific environments. Despite several general characteristics of cellular noise having been revealed, the detailed molecular pathways underlying noise regulation remain elusive. Here, we established a dual-fluorescent reporter system in Saccharomyces cerevisiae and performed experimental evolution to search for mutations that increase expression noise. By analyzing evolved cells using bulk segregant analysis coupled with whole-genome sequencing, we identified the histone deacetylase Hos2 as a negative noise regulator. A hos2 mutant down-regulated multiple ribosomal protein genes and exhibited partially compromised protein translation, indicating that Hos2 may regulate protein expression noise by modulating the translation machinery. Treating cells with translation inhibitors or introducing mutations into several Hos2-regulated ribosomal protein genes-RPS9A, RPS28B and RPL42A-enhanced protein expression noise. Our study provides an effective strategy for identifying noise regulators and also sheds light on how cells regulate non-genetic variation through protein translation.

Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains.

Enhanced phenotypic diversity increases a population's likelihood of surviving catastrophic conditions. Hsp90, an essential molecular chaperone and a central network hub in eukaryotes, has been observed to suppress or enhance the effects of genetic variation on phenotypic diversity in response to environmental cues. Because many Hsp90-interacting genes are involved in signaling transduction pathways and transcriptional regulation, we tested how common Hsp90-dependent differential gene expression is in natural populations. Many genes exhibited Hsp90-dependent strain-specific differential expression in five diverse yeast strains. We further identified transcription factors (TFs) potentially contributing to variable expression. We found that on Hsp90 inhibition or environmental stress, activities or abundances of Hsp90-dependent TFs varied among strains, resulting in differential strain-specific expression of their target genes, which consequently led to phenotypic diversity. We provide evidence that individual strains can readily display specific Hsp90-dependent gene expression, suggesting that the evolutionary impacts of Hsp90 are widespread in nature.

Rapid evolutionary repair by secondary perturbation of a primary disrupted transcriptional network.

The discrete steps of transcriptional rewiring have been proposed to occur neutrally to ensure steady gene expression under stabilizing selection. A conflict-free switch of a regulon between regulators may require an immediate compensatory evolution to minimize deleterious effects. Here, we perform an evolutionary repair experiment on the Lachancea kluyveri yeast sef1Δ mutant using a suppressor development strategy. Complete loss of SEF1 forces cells to initiate a compensatory process for the pleiotropic defects arising from misexpression of TCA cycle genes. Using different selective conditions, we identify two adaptive loss-of-function mutations of IRA1 and AZF1. Subsequent analyses show that Azf1 is a weak transcriptional activator regulated by the Ras1-PKA pathway. Azf1 loss-of-function triggers extensive gene expression changes responsible for compensatory, beneficial, and trade-off phenotypes. The trade-offs can be alleviated by higher cell density. Our results not only indicate that secondary transcriptional perturbation provides rapid and adaptive mechanisms potentially stabilizing the initial stage of transcriptional rewiring but also suggest how genetic polymorphisms of pleiotropic mutations could be maintained in the population.

Multiple intermolecular interactions facilitate rapid evolution of essential genes.

Essential genes are commonly assumed to function in basic cellular processes and to change slowly. However, it remains unclear whether all essential genes are similarly conserved or if their evolutionary rates can be accelerated by specific factors. To address these questions, we replaced 86 essential genes of Saccharomyces cerevisiae with orthologues from four other species that diverged from S. cerevisiae about 50, 100, 270 and 420 Myr ago. We identify a group of fast-evolving genes that often encode subunits of large protein complexes, including anaphase-promoting complex/cyclosome (APC/C). Incompatibility of fast-evolving genes is rescued by simultaneously replacing interacting components, suggesting it is caused by protein co-evolution. Detailed investigation of APC/C further revealed that co-evolution involves not only primary interacting proteins but also secondary ones, suggesting the evolutionary impact of epistasis. Multiple intermolecular interactions in protein complexes may provide a microenvironment facilitating rapid evolution of their subunits.

Immunomodulatory protein from ganoderma microsporum protects against oxidative damages and cognitive impairments after traumatic brain injury.

A traumatic brain injury (TBI) causes abnormal proliferation of neuroglial cells, and over-release of glutamate induces oxidative stress and inflammation and leads to neuronal death, memory deficits, and even death if the condition is severe. There is currently no effective treatment for TBI. Recent interests have focused on the benefits of supplements or natural products like Ganoderma. Studies have indicated that immunomodulatory protein from Ganoderma microsporum (GMI) inhibits oxidative stress in lung cancer cells A549 and induces cancer cell death by causing intracellular autophagy. However, no evidence has shown the application of GMI on TBI. Thus, this study addressed whether GMI could be used to prevent or treat TBI through its anti-inflammation and antioxidative effects. We used glutamate-induced excitotoxicity as in vitro model and penetrating brain injury as in vivo model of TBI. We found that GMI inhibits the generation of intracellular reactive oxygen species and reduces neuronal death in cortical neurons against glutamate excitotoxicity. In neurite injury assay, GMI promotes neurite regeneration, the length of the regenerated neurite was even longer than that of the control group. The animal data show that GMI alleviates TBI-induced spatial memory deficits, expedites the restoration of the injured areas, induces the secretion of brain-derived neurotrophic factors, increases the superoxide dismutase 1 (SOD-1) and lowers the astroglial proliferation. It is the first paper to apply GMI to brain-injured diseases and confirms that GMI reduces oxidative stress caused by TBI and improves neurocognitive function. Moreover, the effects show that prevention is better than treatment. Thus, this study provides a potential treatment in naturopathy against TBI.

Plastic Rewiring of Sef1 Transcriptional Networks and the Potential of Nonfunctional Transcription Factor Binding in Facilitating Adaptive Evolution.

Prior and extensive plastic rewiring of a transcriptional network, followed by a functional switch of the conserved transcriptional regulator, can shape the evolution of a new network with diverged functions. The presence of three distinct iron regulatory systems in fungi that use orthologous transcriptional regulators suggests that these systems evolved in that manner. Orthologs of the transcriptional activator Sef1 are believed to be central to how iron regulatory systems developed in fungi, involving gene gain, plastic network rewiring, and switches in regulatory function. We show that, in the protoploid yeast Lachancea kluyveri, plastic rewiring of the L. kluyveri Sef1 (Lk-Sef1) network, together with a functional switch, enabled Lk-Sef1 to regulate TCA cycle genes, unlike Candida albicans Sef1 that mainly regulates iron-uptake genes. Moreover, we observed pervasive nonfunctional binding of Sef1 to its target genes. Enhancing Lk-Sef1 activity resuscitated the corresponding transcriptional network, providing immediate adaptive benefits in changing environments. Our study not only sheds light on the evolution of Sef1-centered transcriptional networks but also shows the adaptive potential of nonfunctional transcription factor binding for evolving phenotypic novelty and diversity.

Experimental evolution improves mitochondrial genome quality control in Saccharomyces cerevisiae and extends its replicative lifespan.

The mitochondrion is an ancient endosymbiotic organelle that performs many essential functions in eukaryotic cells.1-3 Mitochondrial impairment often results in physiological defects or diseases.2-8 Since most mitochondrial genes have been copied into the nuclear genome during evolution,9 the regulatory and interaction mechanisms between the mitochondrial and nuclear genomes are very complex. Multiple mechanisms, including antioxidant, DNA repair, mitophagy, and mitochondrial biogenesis pathways, have been shown to monitor the quality and quantity of mitochondria.10-12 Nonetheless, it remains unclear if these pathways can be further modified to enhance mitochondrial stability. Previously, experimental evolution has been used to adapt cells to novel growth conditions. By analyzing the resulting evolved populations, insights have been gained into the underlying molecular mechanisms.13 Here, we experimentally evolved yeast cells under conditions that selected for efficient respiration while continuously assaulting the mitochondrial genome (mtDNA) with ethidium bromide (EtBr). We found that the ability to maintain functional mtDNA was enhanced in most of the evolved lines when challenged with mtDNA-damaging reagents. We identified mutations of the mitochondrial NADH dehydrogenase NDE1 in most of the evolved lines, but other pathways are also involved. Finally, we show that cells displaying enhanced mtDNA retention also exhibit a prolonged replicative lifespan. Our work reveals potential evolutionary trajectories by which cells can maintain functional mitochondria in response to mtDNA stress, as well as the physiological implications of such adaptations.

Green synthesis, characterization and evaluation of catalytic and antibacterial activities of chitosan, glycol chitosan and poly(γ-glutamic acid) capped gold nanoparticles.

Gold nanoparticles capped with chitosan (CH-NGs), glycol chitosan (GC-NGs) and poly(γ-glutamic acid) (PA-NGs) were synthesized separately, characterized and evaluated for catalytic and antibacterial activities. Surface Plasmon resonance peak at 520-530 nm confirmed the formation of NGs, while FTIR spectra revealed the involvement of hydroxyl, amine and amide groups in biopolymers on NGs formation and coating. Particle size, zeta potential and surface coating were respectively 21.7 nm, +50.2 mV and 20% for CH-NGs, 5.6 nm, +46.5 mV and 43.5% for GC-NGs and 7.4 nm, -37.3 mV and 34.5% for PA-NGs. Compared to citrate-capped NGs (CT-NGs), biopolymer-capped NGs exhibited high catalytic activity in a 4-nitrophenol reduction model with the pseudo first-order catalytic rate for PA-NGs being 4-6 fold higher than CH-NGs and GC-NGs. No significant antibacterial effect was shown for CT-NGs. However, PA-NGs was superior to gentamycin in inhibiting Salmonella enterica and Escherichia coli-O157:H7, while CH-NGs and GC-NGs showed the highest antibacterial effect against Listeria monocytogenes, followed by Salmonella enterica, Escherichia coli-O157:H7, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus. TEM images showed that GC-NGs were attached on MRSA surface to alter cell permeability, block nutrient flow and disrupt cell membrane, whereas PA-NGs penetrated into Salmonella enterica to generate cavities, plasmolysis and disintegration.

Facile Generation of Thermally Activated Delayed Fluorescence and Fabrication of Highly Efficient Non-Doped OLEDs Based on Triazine Derivatives.

A series of donor-acceptor-donor triazine-based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain highly efficient blue-emitting OLEDs with non-doped emitting layers (EMLs). The targeted molecules use a triazine core as the electron acceptor, and a benzene ring as the conjugated linker with different electron donors to alternate the energy level of the HOMO to further tune the emission color. The introduction of long alkyl chains on the triazine core inhibits the unwanted intermolecular D-D/A-A-type π-π interactions, resulting in the intermolecular D-A charge transfer. The weak aggregation-caused quenching (ACQ) effect caused by the suppressed intermolecular D-D/A-A-type π-π interaction further enhances the emission. The crowded molecular structure allows the electron donor and acceptor to be nearly orthogonal, thereby reducing the energy gap between triplet and singlet excited states (ΔEST ). As a result, blue-emitting devices with TH-2DMAC and TH-2DPAC non-doped EMLs showed satisfactory efficiencies of 12.8 % and 15.8 %, respectively, which is one of the highest external quantum efficiency (EQEs) reported for blue TADF emitters (λpeak <475 nm), demonstrating that our tailored molecular designs are promising strategies to endow OLEDs with excellent electroluminescent performances.

The Effect of Ganoderma Microsporum immunomodulatory proteins on alleviating PM2.5-induced inflammatory responses in pregnant rats and fine particulate matter-induced neurological damage in the offsprings.

Fine particulate matter 2.5 (PM2.5) induces free radicals and oxidative stress in animals, leading to a range of illnesses. In this study, Ganoderma Microsporum immunomodulatory (GMI) proteins were administered to alleviate PM2.5-induced inflammatory responses in mother rats, and PM2.5-induced inflammatory responses and neurological damage in their offspring. The results suggested that GMI administration decreased the risk of neurological disorders in mother rats and their offspring by reducing the white blood cell count, lessening inflammatory responses and PM2.5-induced memory impairment, and preventing dendritic branches in the hippocampi from declining and microRNAs from PM2.5-induced modulation.

Optically Triggered Planarization of Boryl-Substituted Phenoxazine: Another Horizon of TADF Molecules and High-Performance OLEDs.

We report the unprecedented dual properties of excited-state structural planarization and thermally activated delayed fluorescence (TADF) of 10-dimesitylboryl phenoxazine, i.e., PXZBM. Bearing a nonplanar phenoxazine moiety, PXZBM shows the lowest lying absorption onset at ∼390 nm in nonpolar solvents such as cyclohexane but reveals an anomalously large Stokes-shifted (∼14 500 cm-1) emission maximized at 595 nm. In sharp contrast, when a phenylene spacer is added between phenoxazine and dimesitylboryl moieties of PXZBM, the 10-(4-dimesitylborylphenyl)phenoxazine PXZPBM in cyclohexane reveals a much blue-shifted emission at 470 nm despite its red-shifted absorption maximized at 420 nm (cf. PXZBM). The emission of PXZBM further reveals solvent polarity dependence, being red-shifted from 595 nm in cyclohexane to 645 nm in CH2Cl2. For rationalization, the steric hindrance between phenoxazine and the dimesitylboryl unit in PXZBM caused a puckered arrangement of phenoxazine at the ground state. Upon electronic excitation, as supported by the femtosecond early relaxation dynamics, spectral-temporal evolution and energetics calculated along the reaction potential energy surfaces, the diminution of N → B electron transfer reduces π-conjugation and elongates the N-B bond length, inducing the fast phenoxazine planarization with a time constant of 890 ± 100 fs. The associated charge-transfer reaction from phenoxazine (donor) to dimesitylboryl unit (acceptor) results in a further red-shifted emission in polar solvents. In stark contrast, PXZPBM shows a planar phenoxazine and undergoes excited-state charge transfer only. Despite the distinct difference in excited-state relaxation dynamics, both PXZBM and PXZPBM exhibit efficient TADF capable of producing highly efficient orange and green organic light emitting diodes with peak efficiencies of 10.9% (30.3 cd A-1 and 18.7 lm W-1) and 22.6% (67.7 cd A-1 and 50.0 lm W-1).

[A Systematic Review and Meta-Analysis of the Pros and Cons of Consuming Liquids Preoperatively].

BACKGROUND: Preoperative anesthesia long time fasting, may increase patient hemodynamic instability during surgery and may affect the patient's post-surgery electrolyte balance. No meta-analysis has been conducted to explore the effects of preoperative liquid intake amount on gastric fluid PH, gastric fluid volume, surgery inhalation of pulmonary complications, and patient self-perceptions quality of care systematic review and meta-analysis of the literature. PURPOSE: To assess the pros and cons of preoperative liquid intake using a systematic review of the literature. METHODS: The authors searched ten databases including NRC (Nursing Reference Center), CINAHL (Cumulative Index to Nursing and Allied Health Literature), WOS (Web of Science), PubMed, The Cochrane Library, UpToDate, DynaMed, NGC (National Guideline Clearinghouse), Airiti Library, and National Digital Library of Theses and Dissertations in Taiwan, to identify relevant articles that were published from 2003 to January 2017. Nine qualified articles were included in the analysis from the 30 articles that were selected using an initial keyword search. The Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence was used as the evidence grade and the CASP (Critical Appraisal Skills Program) was used to evaluate the quality of the selected articles. The quantitative results were analyzed using Review Manager, Version 5.1. RESULTS: The quality of the literature was medium to high. A small to moderate dose of fluid consumed at 2 hours prior to surgery did not significantly increase gastric fluid volume during anesthesia, with a combined effect of 2.37 (95% CI [-5.12, 9.85], p = .54), and had no effect on gastric fluid PH, with a combined effect of 0.10 (95% CI [0.00, 0.20], p = .05). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results indicate that consuming a small to moderate dose of liquid at 2 hours prior to the provision of anesthesia does not significantly increase the gastric fluid volume or gastric fluid PH of patients during anesthesia. Moreover, the positive benefits of consuming this dose of liquid include reduced risks of aspiration pneumonia, gastroesophageal reflux disease, and postoperative complications as well as reduced perceptions of thirst and hunger during the immediate preoperative period. Thus, this analysis supports that the advantages of allowing patients to consume a moderate or smaller dose of liquid prior to surgery outweigh the disadvantages.

A General Strategy to Enhance the Performance of Dye-Sensitized Solar Cells by Incorporating a Light-Harvesting Dye with a Hydrophobic Polydiacetylene Electrolyte-Blocking Layer.

A unique strategy to suppress charge recombination effectively and enhance light harvesting in dye-sensitized solar cells (DSSCs) is demonstrated by the design of a new dipolar organic dye functionalized with a diacetylene unit, which is capable of undergoing a photoinduced crosslinking reaction to generate a hydrophobic polydiacetylene layer. The polydiacetylene layer serves as an electrolyte-blocking layer that effectively blocks the approach of the oxidized redox mediator and suppresses the dark current, and also plays a role in light harvesting owing to efficient energy transfer to the dipolar dyes. A 15 % efficiency improvement was achieved on going from the monomer dye (JSC =13.5 mA cm-2 , Voc =0.728 V, fill factor=0.73, η=7.17 %) to the crosslinked dye (JSC =14.9 mA cm-2 , Voc =0.750 V, fill factor=0.74, η=8.27 %) under AM 1.5 conditions.

Structural diversity of new solid-state luminophores based on quinoxaline-ß-ketoiminate boron difluoride complexes with remarkable fluorescence switching properties.

A series of structurally simple yet highly tunable organoboron luminophores was designed and synthesized. The solid-state fluorescence quantum yields exhibit nearly exponential growth by decorating the luminophore with additional sterically demanding substituents. Uniquely, the luminescence of these organoboron dyes can be easily switched on/off by acidic/basic vapors, yielding a solid-state fluorescence switching function.

Structure-performance correlations of organic dyes with an electron-deficient diphenylquinoxaline moiety for dye-sensitized solar cells.

The high performances of dye-sensitized solar cells (DSSCs) based on seven new dyes are disclosed. Herein, the synthesis and electrochemical and photophysical properties of a series of intentionally designed dipolar organic dyes and their application in DSSCs are reported. The molecular structures of the seven organic dyes are composed of a triphenylamine group as an electron donor, a cyanoacrylic acid as an electron acceptor, and an electron-deficient diphenylquinoxaline moiety integrated in the π-conjugated spacer between the electron donor and acceptor moieties. The DSSCs based on the dye DJ104 gave the best overall cell performance of 8.06 %; the efficiency of the DSSC based on the standard N719 dye under the same experimental conditions was 8.82 %. The spectral coverage of incident photon-to-electron conversion efficiencies extends to the onset at the near-infrared region due to strong internal charge-transfer transition as well as the effect of electron-deficient diphenylquinoxaline to lower the energy gap in these organic dyes. A combined tetraphenyl segment as a hydrophobic barrier in these organic dyes effectively slows down the charge recombination from TiO2 to the electrolyte and boosts the photovoltage, comparable to their Ru(II) counterparts. Detailed spectroscopic studies have revealed the dye structure-cell performance correlations, to allow future design of efficient light-harvesting organic dyes.

Control of Kaposi's sarcoma-associated herpesvirus reactivation induced by multiple signals.

The ability to control cellular functions can bring about many developments in basic biological research and its applications. The presence of multiple signals, internal as well as externally imposed, introduces several challenges for controlling cellular functions. Additionally the lack of clear understanding of the cellular signaling network limits our ability to infer the responses to a number of signals. This work investigates the control of Kaposi's sarcoma-associated herpesvirus reactivation upon treatment with a combination of multiple signals. We utilize mathematical model-based as well as experiment-based approaches to achieve the desired goals of maximizing virus reactivation. The results show that appropriately selected control signals can induce virus lytic gene expression about ten folds higher than a single drug; these results were validated by comparing the results of the two approaches, and experimentally using multiple assays. Additionally, we have quantitatively analyzed potential interactions between the used combinations of drugs. Some of these interactions were consistent with existing literature, and new interactions emerged and warrant further studies. The work presents a general method that can be used to quantitatively and systematically study multi-signal induced responses. It enables optimization of combinations to achieve desired responses. It also allows identifying critical nodes mediating the multi-signal induced responses. The concept and the approach used in this work will be directly applicable to other diseases such as AIDS and cancer.

Microbiological quality of 18 degrees C ready-to-eat food products sold in Taiwan.

A total of 164 samples of 18 degrees C ready-to-eat (RTE) food products, purchased in 1999-2000 from convenience stores and supermarkets in central Taiwan, were examined to determine the microbiological quality of these products. The 18 degrees C RTE food products, manufactured by 16 factories, were divided into groups based on the type of food and their major ingredients. Aerobic plate count, coliforms, Escherichia coli, Bacillus cereus, Staphylococcus aureus and psychrotrophic Pseudomonas spp. were evaluated. The incidence of E. coli and coliforms in these 18 degrees C RTE food products was 7.9% and 75.0%, respectively, while 49.8% and 17.9% of the samples were found to contain B. cereus and S. aureus, respectively. Among the samples tested, 1.3% of the food products contained more than 10(5) CFU g(-1) of B. cereus and 0.7% contained more than 10(5) CFU g(-1) of S. aureus. The pH values of the samples were all below 7.0, except for cold noodles, which had pH values ranging from 5.18 to 8.20. Among the five types of 18 degrees C food products tested, the highest incidence of E. coli (16%) and Pseudomonas spp. (64.0%) were detected in hand-rolled sushi in a cone shape. On the other hand, the highest incidence rate of coliforms, B. cereus, and S. aureus were found in sandwiches (88%), cold noodles (66.7%) and rice balls rolled in seaweed (25.0%), respectively. Food products made of ham contained the highest incidence of coliforms (88.0%) and E. coli (16.0%), while food products containing meat and ham as the major ingredients had the highest incidence rates of B. cereus (62.5%) and S. aureus (26.1%), respectively. For coliforms, E. coli, B. cereus and S. aureus, the percentage of 18 degrees C RTE food products exceeding the microbiological standards for RTE food accepted by Republic of China was 75.0%, 7.9%, 49.8% and 17.9%, respectively.