Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.

A major pharmacological assumption is that lowering disease-promoting protein levels is generally beneficial. For example, inhibiting metastasis activator BACH1 is proposed to decrease cancer metastases. Testing such assumptions requires approaches to measure disease phenotypes while precisely adjusting disease-promoting protein levels. Here we developed a two-step strategy to integrate protein-level tuning, noise-aware synthetic gene circuits into a well-defined human genomic safe harbor locus. Unexpectedly, engineered MDA-MB-231 metastatic human breast cancer cells become more, then less and then more invasive as we tune BACH1 levels up, irrespective of the native BACH1. BACH1 expression shifts in invading cells, and expression of BACH1's transcriptional targets confirm BACH1's nonmonotone phenotypic and regulatory effects. Thus, chemical inhibition of BACH1 could have unwanted effects on invasion. Additionally, BACH1's expression variability aids invasion at high BACH1 expression. Overall, precisely engineered, noise-aware protein-level control is necessary and important to unravel disease effects of genes to improve clinical drug efficacy.

Effects of liming on soil respiration and its sensitivity to temperature in Cunninghamia lanceolata plantations.

The primary distribution area of acid deposition coincides with areas of Chinese fir (Cunninghamia lanceolata) plantations. Liming is an effective method of restoring acidified soil. To understand the effects of liming on soil respiration and temperature sensitivity within the context of acid deposition, we measured soil respiration and its components in Chinese fir plantations for one year beginning in June 2020, with 0, 1 and 5 t·hm-2 calcium oxide being added in 2018. The results showed that liming considerably increased soil pH and exchangeable Ca2+ concentration, and that there was no significant difference among different levels of lime application. Soil respiration rate and components in the Chinese fir plantations exhibited seasonal variations, with the highest values during the summer and the lowest values during the winter. Although liming did not alter seasonal dynamics, it strongly inhibited heterotrophic respiration rate and increased autotrophic respiration rate of soil, with minor effect on total soil respiration. The monthly dynamics of soil respiration and temperature were largely consistent. There was a clear exponential relationship between soil respiration and soil temperature. Liming increased temperature sensitivity Q10 of soil respiration and autotrophic respiration but reduced that of soil heterotrophic respiration. In conclusion, liming promoted soil autotrophic respiration and strongly inhibited soil heterotrophic respiration in Chinese fir plantations, which would facilitate soil carbon sequestration.

Effects of Chinese fir planting and phosphorus addition on soil microbial biomass and extracellular enzyme activities.

Plants can alter soil microbial biomass and extracellular enzyme activities related with carbon (C), nitrogen (N), and phosphorus (P), through litter and root exudates, with consequences on soil carbon, nitrogen and phosphorus (P) cycling. However, it is not well known how the changes in soil phosphorus availability affect the relationships between plants and soil microorganisms. In this study, a factorial experiment was conducted to investigate the effects of Chinese fir (Cunninghamia lanceolata) planting and different levels of P addition (0, 1.95, 3.9, 7.8 and 15.6 g P·m-2·a-1) on soil microbial biomass and extracellular enzyme activities. The results showed that planting Chinese fir planting significantly altered soil microbial biomass and C- and N- and P-related extracellular enzyme activities, but the effects were dependent on P addition levels. Without P addition, Chinese fir planting significantly reduced soil nutrient availability and pH, which led to the aggravation of P limitation and lower soil microbial biomass. P addition relieved P limitation, and reduced soil acid phosphatase (ACP) activities by 30.0%, 30.5%, 35.3% and 47.1% with the increasing P addition level (1.95, 3.9, 7.8 and 15.6 g P·m-2·a-1). Under three P addition levels (1.95, 3.9 and 7.8 g P·m-2·a-1), the negative effects of Chinese fir planting on soil microbial growth were alleviated. Under the high P addition level (15.6 g P·m-2·a-1), the negative effects of Chinese fir planting on soil microbial growth occurred again due to soil N limitation. Taken together, Chinese fir planting and soil P availability generally affected soil microbial biomass and extracellular enzyme activities, and changed P limitation.

Effect of leaves damaged by Dendrolimus punctatus and insect frass on soil priming effect.

Insect herbivory in the forest canopy leads to a large amount of damaged leaves and frass input to soil, with consequence on soil carbon cycle. However, the influence of damaged leaves and frass from insect canopy herbivory on the soil priming effect is unclear. We examined the effects of leaf litter, leaf damage caused by Dendrolimus punctatus, and insect frass on soil priming effect by using the 13C natural abundance technique. The results showed that the addition of leaf litter, damaged leaves, and frass significantly increased native soil organic carbon mineralization, producing a positive priming effect. Moreover, significant differences were observed among treatments. The accumulative priming effect induced by frass was the largest, followed by damaged leaves, and that of leaf litter was the smallest. The priming effect was positively correlated with total P, condensed tannin, total phenolic content, and the ratio of condensed tannin to P (condensed tannin/P), and negatively correlated with C/N, lignin/N, C/P, and lignin/P in the early stage of incubation. There was a significant negative correlation between the priming effect and lignin content in the later stage of incubation. Our results indicated that damaged leaves and frass increased the magnitude of positive priming effect, which was influenced by different factors at different incubation stages. Our results would strengthen the understanding in the effects of insect herbivory on soil carbon cycling in forests, and improve the accuracy of the assessment of its effects on forest carbon sink.

Cannabinoids as Immune System Modulators: Cannabidiol Potential Therapeutic Approaches and Limitations.

Introduction: Cannabidiol (CBD) is the second most abundant Phytocannabinoid in Cannabis extracts. CBD has a binding affinity for several cannabinoid and cannabinoid-associated receptors. Epidiolex (oral CBD solution) has been lately licensed by the Food and Drug Administration (FDA) for the treatment of pediatric epileptic seizures. Methods: In this review, we discussed the most promising applications of CBD for chronic inflammatory conditions, namely CBD's anti-inflammatory effects during inflammatory bowel disease, coronavirus disease (antiviral effect), brain pathologies (neuroprotective and anti-inflammatory properties), as well as CBD immunomodulatory and antitumoral activities in the tumor microenvironment. Special focus was shed on the main therapeutic mechanisms of action of CBD, particularly in the control of the immune system and the endocannabinoid system. Results: Findings suggest that CBD is a potent immunomodulatory drug as it has manifested immunosuppressive properties in the context of sterile inflammation (e.g., inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases), and immunoprotective effects during viral infections (e.g. COVID-19) Similarly, CBD has exhibited a selective response toward cancer types by engaging different targets and signaling pathways. These results are in favor of the primary function of the endocannabinoid system which is homeostatic maintenance. Conclusion: The presented evidence suggests that the endocannabinoid system is a prominent target for the treatment of inflammatory and autoimmune diseases, rheumatoid diseases, viral infections, neurological and psychological pathologies, and cancer. Moreover, the antitumoral activities of CBD have been suggested to be potentially used in combination with chemo- or immunotherapy during cancer. However, clinical results are still lacking, which raises a challenge to apply translational cannabis research to the human immune system.

BACH1 Expression Is Promoted by Tank Binding Kinase 1 (TBK1) in Pancreatic Cancer Cells to Increase Iron and Reduce the Expression of E-Cadherin.

BTB and CNC homology 1 (BACH1) represses the expression of genes involved in the metabolism of iron, heme and reactive oxygen species and promotes metastasis of various cancers including pancreatic ductal adenocarcinoma (PDAC). However, it is not clear how BACH1 is regulated in PDAC cells. Knockdown of Tank binding kinase 1 (TBK1) led to reductions of BACH1 mRNA and protein amounts in AsPC-1 human PDAC cells. Gene expression analysis of PDAC cells with knockdown of TBK1 or BACH1 suggested the involvement of TBK1 and BACH1 in the regulation of iron homeostasis. Ferritin mRNA and proteins were both increased upon BACH1 knockdown in AsPC-1 cells. Flow cytometry analysis showed that AsPC-1 cells with BACH1 knockout or knockdown contained lower labile iron than control cells, suggesting that BACH1 increased labile iron by repressing the expression of ferritin genes. We further found that the expression of E-cadherin was upregulated upon the chelation of intracellular iron content. These results suggest that the TBK1-BACH1 pathway promotes cancer cell metastasis by increasing labile iron within cells.

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses.

The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.

Limited inhibition of multiple nodes in a driver network blocks metastasis.

Metastasis suppression by high-dose, multi-drug targeting is unsuccessful due to network heterogeneity and compensatory network activation. Here, we show that targeting driver network signaling capacity by limited inhibition of core pathways is a more effective anti-metastatic strategy. This principle underlies the action of a physiological metastasis suppressor, Raf Kinase Inhibitory Protein (RKIP), that moderately decreases stress-regulated MAP kinase network activity, reducing output to transcription factors such as pro-metastastic BACH1 and motility-related target genes. We developed a low-dose four-drug mimic that blocks metastatic colonization in mouse breast cancer models and increases survival. Experiments and network flow modeling show limited inhibition of multiple pathways is required to overcome variation in MAPK network topology and suppress signaling output across heterogeneous tumor cells. Restricting inhibition of individual kinases dissipates surplus signal, preventing threshold activation of compensatory kinase networks. This low-dose multi-drug approach to decrease signaling capacity of driver networks represents a transformative, clinically relevant strategy for anti-metastatic treatment.

Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response.

The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

Arabidopsis JMJ17 promotes cotyledon greening during de-etiolation by repressing genes involved in tetrapyrrole biosynthesis in etiolated seedlings.

Arabidopsis histone H3 lysine 4 (H3K4) demethylases play crucial roles in several developmental processes, but their involvement in seedling establishment remain unexplored. Here, we show that Arabidopsis JUMONJI DOMAIN-CONTAINING PROTEIN17 (JMJ17), an H3K4me3 demethylase, is involved in cotyledon greening during seedling establishment. Dark-grown seedlings of jmj17 accumulated a high concentration of protochlorophyllide, an intermediate metabolite in the tetrapyrrole biosynthesis (TPB) pathway that generates chlorophyll (Chl) during photomorphogenesis. Upon light irradiation, jmj17 mutants displayed decreased cotyledon greening and reduced Chl level compared with the wild-type; overexpression of JMJ17 completely rescued the jmj17-5 phenotype. Transcriptomics analysis uncovered that several genes encoding key enzymes involved in TPB were upregulated in etiolated jmj17 seedlings. Consistently, chromatin immunoprecipitation-quantitative PCR revealed elevated H3K4me3 level at the promoters of target genes. Chromatin association of JMJ17 was diminished upon light exposure. Furthermore, JMJ17 interacted with PHYTOCHROME INTERACTING FACTOR1 in the yeast two-hybrid assay. JMJ17 binds directly to gene promoters to demethylate H3K4me3 to suppress PROTOCHLOROPHYLLIDE OXIDOREDUCTASE C expression and TPB in the dark. Light results in de-repression of gene expression to modulate seedling greening during de-etiolation. Our study reveals a new role for histone demethylase JMJ17 in controlling cotyledon greening in etiolated seedlings during the dark-to-light transition.

Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response

The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

Dimerization of the ETO1 family proteins plays a crucial role in regulating ethylene biosynthesis in Arabidopsis thaliana.

ETHYLENE OVERPRODUCER1 (ETO1), ETO1-LIKE1 (EOL1), and EOL2 are members of the Broad complex, Tramtrack, Bric-a-brac (BTB) protein family that collectively regulate type-2 1-aminocyclopropane-1-carboxylic acid synthase (ACS) activity in Arabidopsis thaliana. Although ETO1 and EOL1/EOL2 encode structurally related proteins, genetic studies suggest that they do not play an equivalent role in regulating ethylene biosynthesis. The mechanistic details underlying the genetic analysis remain elusive. In this study, we reveal that ETO1 collaborates with EOL1/2 to play a key role in the regulation of type-2 ACS activity via protein-protein interactions. ETO1, EOL1, and EOL2 exhibit overlapping but distinct tissue-specific expression patterns. Nevertheless, neither EOL1 nor EOL2 can fully complement the eto1 phenotype under control of the ETO1 promoter, which suggests differential functions of ETO1 and EOL1/EOL2. ETO1 forms homodimers with itself and heterodimers with EOLs. Furthermore, CULLIN3 (CUL3) interacts preferentially with ETO1. The BTB domain of ETO1 is sufficient for interaction with CUL3 and is required for homodimerization. However, domain-swapping analysis in transgenic Arabidopsis suggests that the BTB domain of ETO1 is essential but not sufficient for a full spectrum of ETO1 function. The missense mutation in eto1-5 generates a substitution of phenylalanine with an isoleucine in ETO1F466I that impairs its dimerization and interaction with EOLs but does not affect binding to CUL3 or ACS5. Overexpression of ETO1F466I in Arabidopsis results in a constitutive triple response phenotype in dark-grown seedlings. Our findings reveal the mechanistic role of protein-protein interactions of ETO1 and EOL1/EOL2 that is crucial for their biological function in ethylene biosynthesis.

CHITINASE LIKE1 Regulates Root Development of Dark-Grown Seedlings by Modulating Ethylene Biosynthesis in Arabidopsis thaliana.

The plant hormone ethylene plays a regulatory role in development in light- and dark-grown seedlings. We previously isolated a group of small-molecule compounds with a quinazolinone backbone, which were named acsinones (for ACC synthase inhibitor quinazolinones), that act as uncompetitive inhibitors of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS). Thus, the triple response phenotype, which consists of shortened hypocotyls and roots, radial swelling of hypocotyls and exaggerated curvature of apical hooks, was suppressed by acsinones in dark-grown (etiolated) ethylene overproducer (eto) seedlings. Here, we describe our isolation and characterization of an Arabidopsis revert to eto1 9 (ret9) mutant, which showed reduced sensitivity to acsinones in etiolated eto1 seedlings. Map-based cloning of RET9 revealed an amino acid substitution in CHITINASE LIKE1 (CTL1), which is required for cell wall biogenesis and stress resistance in Arabidopsis. Etiolated seedlings of ctl1ret9 showed short hypocotyls and roots, which were augmented in combination with eto1-4. Consistently, ctl1ret9 seedlings showed enhanced sensitivity to exogenous ACC to suppress primary root elongation as compared with the wild type. After introducing ctl1ret9 to mutants completely insensitive to ethylene, genetic analysis indicated that an intact ethylene response pathway is essential for the alterations in root and apical hook but not hypocotyl in etiolated ctl1ret9 seedlings. Furthermore, a mild yet significantly increased ethylene level in ctl1 mutants was related to elevated mRNA level and activity of ACC oxidase (ACO). Moreover, genes associated with ethylene biosynthesis (ACO1 and ACO2) and response (ERF1 and EDF1) were upregulated in etiolated ctl1ret9 seedlings. By characterizing a new recessive allele of CTL1, we reveal that CTL1 negatively regulates ACO activity and the ethylene response, which thus contributes to understanding a role for ethylene in root elongation in response to perturbed cell wall integrity.

Recovery time of soil carbon pools of conversional Chinese fir plantations from broadleaved forests in subtropical regions, China.

The conversion from natural forest to plantation has been widely applied, with consequences on ecosystem carbon pool. The experimental results of changes of soil carbon stocks after forest conversion are often contradictory. Moreover, the recovery time of soil carbon stocks after forest conversion varies among different sites. To examine the changes of soil carbon stocks following the forest conversions in the long-term and to estimate the recovery time, we selected 116 subtropical forests, including 29 pair-wise replicates for evergreen broadleaved forests (EBF, 40-100-year-old), young Chinese fir plantations (Cunninghamia lanceolata) (YCP, 4-8-year-old), middle-aged Chinese fir plantations (MACP, 13-20-year-old), and mature Chinese fir plantations (MCP, 23-32-year-old), and estimated soil carbon stocks. Soil carbon stocks of YCP and MACP decreased in average 12.5 and 28.7Mgha-1 compared with EBF, and showed no variation between MCP and EBF. Soil carbon stocks were positively correlated to soil total nitrogen stocks and C:N ratio. Our results showed that the forest conversions didn't cause a variation of soil carbon stocks in the long-term, although there was a short-term decline after conversion. The recovery time of soil carbon stock is 27years. These results indicate that the conversion from evergreen broadleaved forests to Chinese fir plantations in subtropical region of China causes soil carbon release in early stage, but has no effect on soil carbon stocks in the long-term. Prolonging the rotation period (>27years) would offset the adverse effects of the forest conversion on soil carbon stocks, and be critical in alleviating global climate change.

Clinical research of Xingnaojing injection combined with naloxone in the treatment of hypoxic ischemic encephalopathy / 中国基层医药

Objective To observe the clinical effect of Xingnaojing injection combined with naloxone in the treatment of hypoxic ischemic encephalopathy.Methods 62 patients with hypoxia ischemia encephalopathy were randomly assigned into the control group(31 cases)and the treatment group(31 cases).The control group used naloxone treatment on the basis of the conventional treatment.The treatment group received Xingnaojing injection combined with naloxone treatment on the basis of routine treatment.The changes in different time of Glasgow Coma Scale(GCS) scores of the two groups after treatment were compared.Results After treatment for 1 ,5,1 0,1 5d,the GCS scores in the control group were (5.27 ±0.87)points,(9.03 ±0.72)points,(1 0.03 ±0.72)points,(1 3.03 ±0.72)points respectively,which in the treatment group were (5.1 4 ±1 .03)points,(9.24 ±1 .06)points,(1 3.31 ±2.83)points, (15.31 ±0.93)points.The differences of GCS scores after treatment for 15,10d between the two groups were statistically significant(t =1 5.1 1 3,1 0.501 ,P =0.00,0.00).In the control group,the total effective rate was 50.0%,which of the treatment group was 82.7%,the total effective rate between the two groups had statistically significant difference (χ2 =6.437,P <0.05).Conclusion On the basis of routine treatment,Xingnaojing injection combined with naloxone in the treatment of hypoxic ischemic encephalopathy has better effect than the single use of naloxone treatment.

A broadleaf species enhances an autotoxic conifers growth through belowground chemical interactions.

Plants may affect the performance of neighboring plants either positively or negatively through interspecific and intraspecific interactions. Productivity of mixed-species systems is ultimately the net result of positive and negative interactions among the component species. Despite increasing knowledge of positive interactions occurring in mixed-species tree systems, relatively little is known about the mechanisms underlying such interactions. Based on data from 25-year-old experimental stands in situ and a series of controlled experiments, we test the hypothesis that a broadleaf, non-N fixing species, Michelia macclurei, facilitates the performance of an autotoxic conifer Chinese fir (Cunninghamia lanceolata) through belowground chemical interactions. Chinese fir roots released the allelochemical cyclic dipeptide (6-hydroxy-1,3-dimethyl-8-nonadecyl-[1,4]-diazocane- 2,5-diketone) into the soil environment, resulting in self-growth inhibition, and deterioration of soil microorganisms that improve P availability. However, when grown with M. macclurei the growth of Chinese fir was consistently enhanced. In particular, Chinese fir enhanced root growth and distribution in deep soil layers. When compared with monocultures of Chinese fir, the presence of M. macclurei reduced release and increased degradation of cyclic dipeptide in the soil, resulting in a shift from self-inhibition to chemical facilitation. This association also improved the soil microbial community by increasing arbuscular mycorrhizal fungi, and induced the production of Chinese fir roots. We conclude that interspecific interactions are less negative than intraspecific ones between non-N fixing broadleaf and autotoxic conifer species. The impacts are generated by reducing allelochemical levels, enhancing belowground mutualisms, improving soil properties, and changing root distributions as well as the net effects of all the processes within the soil. In particular, allelochemical context alters the consequences of the belowground ecological interactions with a novel mechanism: reduction of self-inhibition through reduced release and increased degradation of an autotoxic compound in the mixed-species plantations. Such a mechanism would be useful in reforestation programs undertaken to rehabilitate forest plantations that suffer from problems associated with autotoxicity.

ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes.

The ERF (ethylene responsive factor) family is composed of transcription factors (TFs) that are critical for appropriate Arabidopsis thaliana responses to biotic and abiotic stresses. Here we identified and characterized a member of the ERF TF group IX, namely ERF96, that when overexpressed enhances Arabidopsis resistance to necrotrophic pathogens such as the fungus Botrytis cinerea and the bacterium Pectobacterium carotovorum. ERF96 is jasmonate (JA) and ethylene (ET) responsive and ERF96 transcripts accumulation was abolished in JA-insensitive coi1-16 and in ET-insensitive ein2-1 mutants. Protoplast transactivation and electrophoresis mobility shift analyses revealed that ERF96 is an activator of transcription that binds to GCC elements. In addition, ERF96 mainly localized to the nucleus. Microarray analysis coupled to chromatin immunoprecipitation-PCR of Arabidopsis overexpressing ERF96 revealed that ERF96 enhances the expression of the JA/ET defence genes PDF1.2a, PR-3 and PR-4 as well as the TF ORA59 by direct binding to GCC elements present in their promoters. While ERF96-RNAi plants demonstrated wild-type resistance to necrotrophic pathogens, basal PDF1.2 expression levels were reduced in ERF96-silenced plants. This work revealed ERF96 as a key player of the ERF network that positively regulates the Arabidopsis resistance response to necrotrophic pathogens.

The Histone Acetyltransferase Gcn5 Regulates ncRNA-ICR1 and FLO11 Expression during Pseudohyphal Development in Saccharomyces cerevisiae.

Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5) in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT). In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development.

Treatment of low lumbar degenerative disease with unilateral pedicle screw combined with contralateral percutaneous transfacet screws fixation / 中国骨伤

<p><b>OBJECTIVE</b>To explore the operative skills and effect of unilateral pedicle screw combined with contralateral percutaneous transfacet screws fixation in treating degenerative low lumbar disease.</p><p><b>METHODS</b>From January 2009 to December 2011,22 patients with degenerative low lumbar disease were treated with transforaminal lumbar interbody fusion, during the operations, unilateral pedicle screw and contralateral percutaneous transfacet screw fixation were performed. There were 16 males and 6 females, aged from 32 to 71 years old with an average of (51.1 ± 10.6) years, including single segment in 20 cases and two segments in 2 cases. Clinical effects were evaluated according to visual analogue score (VAS) and Oswestry Disability Index (ODI).</p><p><b>RESULTS</b>All patients were followed up from 1 to 2.5 years with an average of 18 months. One case complicated with leakage of cerebrospinal fluid after operation and 1 case with lower limb pain of decompression-side on the 3rd day after operation. Twenty-two patients got bony fusion. There were no instability and evidence of instrument failure during follow-up. The VAS and ODI score decreased from preoperative 8.24 ± 0.72, 36.72 ± 6.84 respectively to 3.18 ± 0.66, 4.36 ± 1.12 at the final follow-up (P < 0.05).</p><p><b>CONCLUSION</b>Unilateral pedicle screw combined with contralateral percutaneous transfacet screw fixation is safe and feasible surgical technique in treating low lumbar degenerative disease. It has advantages of little trauma, rigid fixation, high fusion rate, and less complication. etc.</p>

The Surgical Management of Traumatic Lower Cervical Spondylolisthesis with Posterior Percutaneous Pedicle Screw Fixation

We reported a technical report of traumatic lower cervical spondylolisthesisca used by bilateral pedicle fracture, without neurological compression. The patient was treated with the minimally invasive technique of percutaneous pedicle screw fixation. Fracture healing and normal cervical motion were confirmed by plain films and physical examinations on the 18-monthpostoperatively. The technique of percutaneous pedicle screw fixation might be an alternative strategy for the treatment of traumatic lower cervical spondylolisthesis with pedicle fracture.