The C2H2 transcription factor ZAT5 negatively regulates pectin demethylesterification by targeting PMEs in Arabidopsis seed mucilage

In recent years, Arabidopsis seed coat mucilage has been proved to be an outstanding model system to study the biosynthesis, modification and interaction of polys accharides, particularly pectin. Pectin is produced in the Golgi apparatus and transferred with a high methyl-esterifiable status to the primary cell wall, where it may be demethylesterified by pectin methylesterases (PMEs). The functional properties of pectin are largely determined by the level and structure of methylesterification, which then influence plant growth and development, stress responses and so on. However, the regulatory mechanisms of pectin demethylesterification remain mostly unexplored. Here, we show that a zinc-finger transcription factor of Arabidopsis thaliana 5 (ZAT5) negatively regulates the pectin demethylesterification in seed mucilage. A mutation of this ZAT5 transcription factor led to a thinner seed coat mucilage layer and a decreased level of pectin methylesterification caused by enhanced PME activity compared with the wild type. Further study indicates that ZAT5 negatively regulates the expression of 4 pectin methylesterase (PME) genes, including PME5, HIGHLY METHYL ESTERIFIED SEEDS (HMS)/PME6, PME12, and PME16, via binding their TGATCA-motif that was identified in this study. Our results proved that ZAT5 negatively regulates pectin demethylesterification. BEL1-Like Homeodomain (BLH) Transcription Factor 2 and BLH4 are transcription factors that were previously identified to positively modulate pectin demethylesterification by directly regulating PME58 expression. We demonstrated that ZAT5 and BLH2/4 physically interact and antagonize each other’s ability in transcriptional regulation of target genes. It was also proved that the mucilage phenotype of zat5-1 blh2 blh4 triple mutant seeds was similar to that of the wild type. In conclusion, our work reveals that ZAT5 and BLH2/4 antagonistically modulate downstream genes encoding PMEs to control pectin demethylesterification in seed coat mucilage

Research advances on tobacco florigen gene FT and its regulatory mechanisms

peer reviewedTobacco (Nicotiana tabacum L.) is an economic crop in which mature leaves are harvested. Early flowering has serious influence on quality and yield of tobacco. Moreover, long growth cycle is also a major factor limiting the progress of tobacco breeding. Initiation of floral development is regulated through the integration of photoperiod, vernalization, gibberellin and/or autonomous signaling pathways. FT is a key regulatory protein at the intersection of these pathways. Four FT-like genes were isolated from tobacco. Only NtFT4 is a floral inducer and others are floral inhibitors. Tobacco CET, CO, FPF1, LFY, NFL, MADS box and other genes also play very important roles in tobacco flowering. In this article, we summarize the research progress on characteristics, function and regulatory mechanisms of tobacco FT gene. It provided useful information for preventing early flowering and accelerating breeding progress in tobacco

Photochemical characteristics of diclofenac and its photodegradation of inclusion complexes with β-cyclodextrins

Diclofenac is one of most frequently detected compounds in the water cycle. In this work, the effect of initial concentration, liquid inclusion complexes with β-Cyclodextrins (β-CDs) on the photodegradation of diclofenac were studied. Six phototransformation products were detected by HPLC chromatograms. UV-absorption spectra of diclofenac and phototransformation products were determined. One of the phototransformation products was identified. The degradation followed pseudo-first-order kinetics. The experiment showed that irradiation of diclofenac in the presence of β-CDs increase photodegradation rate and determined the optimal molar ratio of diclofenac to β-CDs as 1:2. The reduced photohaemolytic activity of diclofenac in the presence of β-CDs may be attributed to the sequestering and stabilizing of the radical intermediates and /or photoproducts by complexation

Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y

Haloperidol is a commonly used antipsychotic drug for treating schizophrenia. Clinical imaging studies have found that haloperidol can cause volume loss of human brain tissue, which is supported by animal studies showing that haloperidol reduces the number of synaptic spines. The mechanism remains unknown. Gut microbiota metabolites, short chain fatty acids including propionate, are reported to have neuroprotective effect and influence gene expression. This study aims to investigate the effect and mechanism of propionate in the protection of neurite lesion induced by haloperidol. This study showed that 10 μM haloperidol (clinical relevant dose) impaired neurite length in human blastoma SH-SY5Y cells, which were confirmed by using primary mouse striatal spiny neurons. We found that haloperidol impaired neurite length were accompanied by a decreased neuropeptide Y (NPY) expression, but no effect on GSK3β signaling. Importantly, this project research found that propionate was capable of protecting against haloperidol-induced neurite lesions and preventing NPY reduction. To confirm this finding, we used specific siRNAs targeting NPY which blocked the protective effect of propionate on haloperidol-induced neurite lesions. Furthermore, since NPY is regulated by the nuclear transcription factor CREB, we measured pCREB that was decreased by haloperidol and was normalized by propionate. Therefore, propionate has a protective effect against pCREB-NPY mediated haloperidol-induced neurite lesions

Controllable ingestion and release of guest components driven by interfacial molecular orientation of host liquid crystal droplets

Controllable construction and manipulation of artificial multi-compartmental structures are crucial in understanding and imitating smart molecular elements such as biological cells and on-demand delivery systems. Here, we report a liquid crystal droplet (LCD) based three-dimensional system for controllable and reversible ingestion and release of guest aqueous droplets (GADs). Induced by interfacial thermodynamic fluctuation and internal topological defect, microscale LCDs with perpendicular anchoring condition at the interface would spontaneously ingest external components from the surroundings and transform them as radially assembled tiny GADs inside LCDs. Landau–de Gennes free-energy model is applied to describe and explain the assembly dynamics and morphologies of these tiny GADs, which presents a good agreement with experimental observations. Furthermore, the release of these ingested GADs can be actively triggered by changing the anchoring conditions at the interface of LCDs. Since those ingestion and release processes are controllable and happen very gently at room temperature and neutral pH environment without extra energy input, these microscale LCDs are very prospective to provide a unique and viable route for constructing hierarchical 3D structures with tunable components and compartments

The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLR) are key innate immunity receptors participating in an immune response. Growing evidence suggests that mutations of TLR2/TLR9 gene are associated with the progress of cancers. The present study aimed to investigate the temporal relationship of single nucleotide polymorphisms (SNP) of TLR2/TLR9 and the risk of hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>In this single center-based case-control study, SNaPshot method was used to genotype sequence variants of TLR2 and TLR9 in 211 patients with HCC and 232 subjects as controls.</p> <p>Results</p> <p>Two synonymous SNPs in the exon of TLR2 were closely associated with risk of HCC. Compared with those carrying wild-type homozygous genotypes (T/T), risk of HCC decreased significantly in individuals carrying the heterozygous genotypes (C/T) of the rs3804099 (adjusted odds ratio (OR), 0.493, 95% CI 0.331 - 0.736, <it>P </it>< 0.01) and rs3804100 (adjusted OR, 0.509, 95% CI 0.342 - 0.759, <it>P </it>< 0.01). There was no significant association found in two TLR9 SNPs concerning the risk of HCC. The haplotype TT for TLR2 was associated significantly with the decreased risk of HCC (OR 0.524, 95% CI 0.394 - 0.697, <it>P </it>= 0.000). Inversely, the risk of HCC increased significantly in patients with the haplotype CC (OR 2.743, 95% CI 1.915 - 3.930, <it>P </it>= 0.000).</p> <p>Conclusions</p> <p>These results suggested that TLR2 rs3804099 C/T and rs3804100 C/T polymorphisms were closely associated with HCC. In addition, the haplotypes composed of these two TLR2 synonymous SNPs have stronger effects on the susceptibility of HCC.</p

Effect of Double-Ovsynch and Presynch-Ovsynch on postpartum ovarian cysts and inactive ovary in high-yielding dairy cows

IntroductionOptimizing the management of dairy cattle reproduction can reduce postpartum ovarian disease in high-yielding dairy cows and thus enhance ranch economic benefit. The hypothesis of this study was that the Double-Ovsynch (DO) protocol in high-producing dairy cows would result in a lower incidence of follicular cysts but a higher incidence of luteal cysts compared to those undergoing the Presynch-Ovsynch (PS) protocol.MethodsIn this experiment, 384 cows (204 primiparous and 180 multiparous) were allocated to the DO group, which followed the protocol: GnRH-7d-PGF2α-3d-GnRH-7d-Ovsynch-56 h (GnRH-7d-PGF2α-56 h-GnRH-16hTAI), starting on 39 ± 3 days in milk (DIM). Additionally, 359 cows (176 primiparous and 183 multiparous) were assigned to the PS group, which followed the protocol: PGF2α-14d-PGF2α-12d-Ovsynch-56 h, starting on 31 ± 3 DIM. In DO, B-mode ultrasound examinations were conducted 1 day after the GnRH-7d-PGF2α-3d-GnRH protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days of suspected cases. In PS, B-mode ultrasound examinations were conducted 1 day after the PGF2α-14d-PGF2α protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days. For all cows confirmed to having ovarian diseases, a second B-mode ultrasound examination was conducted at the time of the second GnRH and timed artificial insemination (TAI). If the ovary showed a normal developing follicle in combination with normal ovulation, the ovarian disease was considered to be cured.ResultsThe current study revealed no significant difference in the overall incidence and cure rate of postpartum ovarian diseases between DO and PS (incidence rate: 3.9% vs. 6.7%, cure rate: 50% vs. 41.7%, DO vs. PS). Also, there was no significant difference in the incidence and cure rate of luteal cysts between DO and PS (incidence rate: 2.9% vs. 2.2%, cure rate: 50.0% vs. 50.0%). The incidence of follicular cysts was significantly lower in the DO group than in the PS group (0.8% vs. 2.8%, DO vs. PS, p = 0.037), but there was no significant difference in the cure rates (66.7% vs. 50%). The occurrence of inactive ovary was lower in DO compared to PS (0.2% vs. 1.7%, p = 0.047). There was no significant difference in the pregnancy rate between the DO and PS groups (48.2% vs. 41.8%), although the DO group had a higher rate. What is different from our assumption is that PS did not effectively reduce the incidence of postpartum luteal cysts

Single Nucleotide Polymorphisms of Toll-Like Receptor 4 Decrease the Risk of Development of Hepatocellular Carcinoma

BACKGROUND: Toll-like receptor 4 (TLR4) is a key innate immunity receptor that initiates an inflammatory response. Growing evidence suggests that mutation of TLR4 gene may play a role in the development of cancers. This study aimed to investigate the temporal relationship of single nucleotide polymorphisms of TLR4 and the risk of hepatocellular carcinoma, a single center-based case-control study was conducted. METHODS: A systematic genetic analysis of sequence variants of TLR4 by evaluating ten single-nucleotide polymorphisms was performed from 216 hepatocellular carcinoma cases and 228 controls. RESULTS: Six single nucleotide polymorphisms of the TLR4 in the 5'-untranslated region and intron were associated with risk of hepatocellular carcinoma. Individuals carrying the heterozygous genotypes for the rs10759930, rs2737190, rs10116253, rs1927914, rs12377632 and rs1927911 had significantly decreased risk of hepatocellular carcinoma (adjusted odds ratio [OR], from 0.527 to 0.578, P<0.01) comparing with those carrying wild-type homozygous genotypes. In haplotype analysis, one haplotype (GCCCTTAG) of TLR4 was associated significantly with decrease of the occurrence of hepatocellular carcinoma (OR, 0.556, 95% confidence interval [CI], 0.407-0.758, P = 0.000). CONCLUSIONS: Collectively, these results suggested that the risk of hepatocellular carcinoma was associated with TLR4 sequence variation. TLR4 single nucleotide polymorphisms may play an important protective role in the development of hepatocellular carcinoma

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

The Roles of Arabidopsis C1-2i Subclass of C2H2-type Zinc-Finger Transcription Factors

The Cys2His2 (C2H2)-type zinc-finger protein (ZFP) family, which includes 176 members in Arabidopsis thaliana, is one of the largest families of putative transcription factors in plants. Of the Arabidopsis ZFP members, only 33 members are conserved in other eukaryotes, with 143 considered to be plant specific. C2H2-type ZFPs have been extensively studied and have been shown to play important roles in plant development and environmental stress responses by transcriptional regulation. The ethylene-responsive element binding-factor-associated amphiphilic repression (EAR) domain (GCC box) has been found to have a critical role in the tolerance response to abiotic stress. Many of the plant ZFPs containing the EAR domain, such as AZF1/2/3, ZAT7, ZAT10, and ZAT12, have been shown to function as transcriptional repressors. In this review, we mainly focus on the C1-2i subclass of C2H2 ZFPs and summarize the latest research into their roles in various stress responses. The role of C2H2-type ZFPs in response to the abiotic and biotic stress signaling network is not well explained, and amongst them, C1-2i is one of the better-characterized classifications in response to environmental stresses. These studies of the C1-2i subclass ought to furnish the basis for future studies to discover the pathways and receptors concerned in stress defense. Research has implied possible protein-protein interactions between members of C1-2i under various stresses, for which we have proposed a hypothetical model