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IntroductionThis study examined the impact of biochar application on agricultural productivity and greenhouse gas emissions in irrigated regions of northern Xinjiang. The objective of this study was to assess the impact of nitrogen fertilizer and biochar levels on soil respiration rate, enzyme activity, and spring wheat yield.Materials and methodsThe experiment employed a randomized block design comprising two nitrogen fertilizer levels (N1: 300 kg·hm-2 and N2: 255 kg·hm-2) and four biochar levels (B0: 0 kg·hm-2, B1: 10×103 kg·hm-2, B2: 20×103 kg·hm-2, and B3: 30×103 kg·hm-2). This resulted in eight groups (N1B0, N1B1, N1B2, N1B3, N2B0, N2B1, N2B2, and N2B3), each replicated three times.Results and discussionThe findings indicated that the N2B2 group exhibited a reduction in soil CO2 emissions, with a cumulative decrease of 4.42% in CO2 emissions compared to the N2B0 control. The application of biochar and/or nitrogen fertilizer, particularly in combination, was observed to increase soil urease, sucrase, and catalase activities. The N2B2 group exhibited a spring wheat yield of 8301.35 kg·hm-2, representing a 22.1% increase over the N1B0 group. This improvement was attributed to the capacity of biochar to regulate soil water content variability, stabilize soil aggregate composition, mitigate organic carbon mineralization, and reduce farmland carbon emissions. Furthermore, biochar’s nitrogen fixation provided essential nutrients for soil microorganisms, thereby enhancing enzymatic reactions and promoting crop growth.ConclusionIn conclusion, the N2B2 regime was determined to be the optimal approach for spring wheat cultivation in irrigated regions of northern Xinjiang, resulting in enhanced crop productivity and the mitigation of carbon emissions. Nevertheless, further investigation of its long-term impact on farmland is recommended.

Abstract Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.

Abstract In the early stages of diabetic retinopathy (DR), diabetes-related hyperglycemia directly inhibits the AKT signaling pathway by increasing oxidative stress or inhibiting growth factor expression, which leads to retinal cell apoptosis, nerve proliferation and fundus microvascular disease. However, due to compensatory vascular hyperplasia in the late stage of DR, the vascular endothelial growth factor (VEGF)/phosphatidylinositol 3 kinase (PI3K)/AKT cascade is activated, resulting in opposite levels of AKT regulation compared with the early stage. Studies have shown that many factors, including insulin, insulin-like growth factor-1 (IGF-1), VEGF and others, can regulate the AKT pathway. Disruption of the insulin pathway decreases AKT activation. IGF-1 downregulation decreases the activation of AKT in DR, which abrogates the neuroprotective effect, upregulates VEGF expression and thus induces neovascularization. Although inhibiting VEGF is the main treatment for neovascularization in DR, excessive inhibition may lead to apoptosis in inner retinal neurons. AKT pathway substrates, including mammalian target of rapamycin (mTOR), forkhead box O (FOXO), glycogen synthase kinase-3 (GSK-3)/nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-B (NF-κB), are a research focus. mTOR inhibitors can delay or prevent retinal microangiopathy, whereas low mTOR activity can decrease retinal protein synthesis. Inactivated AKT fails to inhibit FOXO and thus causes apoptosis. The GSK-3/Nrf2 cascade regulates oxidation and inflammation in DR. NF-κB is activated in diabetic retinas and is involved in inflammation and apoptosis. Many pathways or vital activities, such as the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathways, interact with the AKT pathway to influence DR development. Numerous regulatory methods can simultaneously impact the AKT pathway and other pathways, and it is essential to consider both the connections and interactions between these pathways. In this review, we summarize changes in the AKT signaling pathway in DR and targeted drugs based on these potential sites.

Dendrobium officinale Kimura & Migo in the genus Dendrobium of Orchidaceae is an important medicinal plant that produces various bibenzyl and phenanthrene derivatives. In some orchids, these derivatives have been reported to increase with fungal infection. Bibenzyl biosynthesis is regulated by bibenzyl synthase (BBS). Although six genes of the BBS family have been registered from D. officinale, their gene regulation mechanisms are unclear. The infection of Dendrobium with mycorrhizal fungi also reportedly increases the expression of genes involved in biosynthesis; however, the effect of mycorrhizal fungi on bibenzyl production is unknown. The present study examined the effects of three mycorrhizal fungi isolated from D. officinale on BBS gene expression and bibenzyl production over time. One of the Tulasnellaceae operational taxonomic units induced BBS gene expression and increased two representative bibenzyls, gigantol and dendrophenol, at specific time points. Furthermore, 19 BBS sequences were cloned from 12 Dendrobium species, and a phylogenetic analysis was performed. The results indicated that repeated BBS gene duplication occurred during the evolution of the genus, and further duplication occurred after speciation. These results suggest that it is possible to optimize metabolite production by selecting suitable symbiotic fungi.

Watermelon is a well-liked fruit containing bioactive compounds and nutrients. Watermelon research on metabolic diseases often involves flesh, yet rind is less explored. This study examined effects of watermelon with rind on satiety, postprandial glucose, and bowel movement with a sensory evaluation in healthy adults. The study included 21 participants (age 23.6 ± 5.7y, BMI 22.6 ± 2.8 kg/m2) in a randomized double-blind crossover design. Participants consumed one cup of blenderized watermelon with and without rind separated by a one-week washout period. Sensory analysis included 23 semi-trained panelists to complete a triangle and a 7-point hedonic scale test. Results revealed significant increase in satiety for both trials over time, with more fullness for watermelon with rind (P

Summary: This study aimed to investigate the effects of long-term pollution from different wavelengths of light on the corneal epithelium (CE) and identify potential biomarkers. Rabbits were exposed to red, green, blue, white, and environmental light for 6 weeks. The CE was assessed using various techniques such as fluorescein sodium staining, transcriptome sequencing, electron microscopy, and molecular assays. In human corneal epithelial cells (hCECs), the downregulation of vascular cell adhesion molecule 1 (VCAM1) in response to blue light (BL) pollution was observed. This downregulation of VCAM1 inhibited migration, increased reactive oxygen species (ROS) levels, and apoptosis, and inhibited the AKT/p70 S6 kinase cascade in hCECs. Animal experiments confirmed that BL pollution caused similar effects on the rabbit cornea, including increased ROS production, apoptosis, delayed wound healing, and decreased VCAM1 expression. Overall, BL-induced VCAM1 downregulation may impair CE and wound healing and promote ROS and apoptosis in vitro and in vivo.

Exploring cost-effective and highly-active oxygen evolution reaction (OER) electrocatalysts is a pressing task to propel water electrolysis for green hydrogen production. Herein, we constructed a class of Fe-doped and S-enriched Ni3S2 nanowires electrocatalysts for optimizing the target intermediates adsorption to decrease the OER overpotentials at various current densities. The optimal Ni3S2-1.4%Fe electrocatalyst possesses the most active sites and exhibits an ultralow overpotential of 190 mV at 10 mA cm−2 with an excellent stability of > 60 h, exceeding the majority of recently-reported Ni3S2-based electrocatalysts. The trivalence Fe-doping not only reduces the electron density of the Ni center, but also enables the sulfur enrichment on the Ni3S2 surface, which greatly improves the intrinsic activity and the number of target intermediates (∗OOH). A novel methanol-assisted electrochemical evaluation further reveals that the Ni3S2-1.4%Fe electrocatalyst demonstrates a weaker binding ability to ∗OH with the rapid generation of ∗OOH species, and thus gives a lower apparent activation energy compared with the surface sulfur reduced ones. This work provides a new perspective for regulating the adsorption of intermediates through doping strategy.

Abstract Background Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs. Methods HLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition. Results TGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells. Conclusion Blue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO.

Abstract Background Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia is unknown. We aimed to explore the potential role and mechanism of retinal glial cells in form deprived myopia. Methods We adapted the mice form-deprivation myopia model by covering the right eye and left the left eye open for control, measured the ocular structure with anterior segment optical coherence tomography, evaluated changes in the morphology and distribution of retinal glial cells by fluorescence staining and western blotting; we also searched the online GEO databases to obtain relative gene lists and confirmed them in the form-deprivation myopia mouse retina at mRNA and protein level. Results Compared with the open eye, the ocular axial length (3.54 ± 0.006 mm v.s. 3.48 ± 0.004 mm, p = 0.027) and vitreous chamber depth (3.07 ± 0.005 mm v.s. 2.98 ± 0.006 mm, p = 0.007) in the covered eye became longer. Both glial fibrillary acidic protein and excitatory amino acid transporters 4 elevated. There were 12 common pathways in human myopia and anoxic astrocytes. The key proteins were also highly relevant to atropine target proteins. In mice, two common pathways were found in myopia and anoxic Müller cells. Seven main genes and four key proteins were significantly changed in the mice form-deprivation myopia retinas. Conclusion Retinal astrocytes and Müller cells were activated in myopia. They may response to stimuli and secretory acting factors, and might be a valid target for atropine.

Chaos generation from a semiconductor laser under band-rejection optical feedback is proposed and investigated numerically and experimentally. The band-rejection feedback performs better than the conventional broadband mirror feedback in concealing the feedback delay time information measured by the time-delay signature (TDS) of optical field and intensity. In this work, the optical band-rejection filter (BRF) is built up based on the transmission of a Bragg grating. The best concealment of delay time information is achieved in the form of simultaneous TDS suppression in optical field and intensity when the BRF is negatively detuned from the free-running laser frequency. Such concealment is due to the suppression of feedback cavity modes by the band-rejection effect. The concealment prefers negative detuning frequency because the laser cavity resonance is red-shifted by optical feedback due to the antiguidance effect. The negatively detuned BRF suppresses the TDS of optical field and intensity by more than an order of magnitude than mirror feedback. The simulation results are qualitatively confirmed by the experimental measurements.

To address the problem of low efficiency of the existing hill-climbing algorithm in Bayesian network structure learning, this paper proposes a Bayesian network structure learning algorithm based on probabilistic incremental analysis and constraints. The algorithm constructs a suitable measure for representing the degree of node association in Bayesian networks based on the principle of random forest feature extraction; then uses the method to construct the initial Bayesian network structure and constrains the search space by setting a corresponding threshold for the probability increment centered on each node; finally takes the initial Bayesian network as the starting point and learns it by the forbidden hill-climbing search and BIC scoring method to obtain the optimal Bayesian network structure. Experimental results show that the correlation degree measure and mutual information proposed in this paper have an approximate correlation expression effect; compared with other Bayesian network structure learning algorithms of the same type, the method in this paper has a faster operation speed while ensuring the quality of the learned network. The experimental results show that the Bayesian network structure learning algorithm based on probabilistic incremental analysis and constraints is an effective and efficient Bayesian network structure learning algorithm.

Dendrobium officinale (Orchidaceae) is an endangered epiphytic orchid that has been well studied as a medicinal plant. Although previous studies have shown that various fungal isolates promote D. officinale seed germination and seedling development in vitro, mycorrhizal associations among its wild populations remain poorly understood. In this study, we identified mycorrhizal fungi associated with D. officinale (36 individuals from six sites) using Sanger sequencing and compared fungal communities among sites and habitats (lithophytic vs. epiphytic individuals). Among the obtained sequences, 76 belonged to orchid mycorrhizal fungi (OMF), among which Tulasnellaceae accounted for 45.8% and Serendipitaceae for 28.1%. The Serendipitaceae operational taxonomic unit (OTU) SE1 was the most dominant partner, accounting for 27.1% of all detected fungal sequences, followed by a Tulasnellaceae OTU, TU27, which accounted for 15.6%. The relative frequencies of Serendipitaceae and Tulasnellaceae differed greatly between lithophytic and epiphytic individuals. Serendipitaceae accounted for 47.3% of the OMF sequences among lithophytes, and Tulasnellaceae for 95.2% among epiphytes. Mycorrhizal community composition also varied among sites. We further conducted in vitro symbiotic culture from seeds with six fungal isolates. Two Serendipitaceae and two Tulasnellaceae isolates, including SE1 and TU27, significantly promoted seed germination and seedling development. These results indicate that D. officinale is mainly associated with Tulasnellaceae and Serendipitaceae as its main fungal partners, which strongly induced seed germination and seedling development in vitro, suggesting their association with D. officinale through its life cycle.

Abstract Background Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes. Methods We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz). Results Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes. Conclusions These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.

The pathogenesis of myopia is driven by genetic and environmental risk factors. Accommodation not only alters the curvature and shape of the lens but also involves contraction of the ciliary and extraocular muscles, which influences intraocular pressure (IOP). Scleral matrix remodeling has been shown to contribute to the biomechanical susceptibility of the sclera to accommodation-induced IOP fluctuations, resulting in reduced scleral thickness, axial length (AL) elongation, and axial myopia. The rise in IOP can increase the burden of scleral stretching and cause axial lengthening. Although the accommodation and IOP hypotheses were proposed long ago, they have not been validated. This review provides a brief and updated overview on studies investigating the potential role of accommodation and IOP in myopia progression.

Mycorrhizal specificity, i.e., the range of fungi allowing mycorrhizal partnerships, differs among orchid species, but that at early developmental stages is unclear. We investigated whether mycorrhizal specificity during seed germination and seedling development differs among three Dendrobium species, D. officinale, D. okinawense and D. moniliforme, in vitro. Nine mycorrhizal fungal strains were obtained from the roots of these species and cultured with a seed of each Dendrobium species. Five to eight fungal strains stimulated seed germination, whereas one to four fungal isolates significantly promoted protocorm development in the three species. To evaluate effects on leafy seedling growth, seedlings obtained from asymbiotic culture were cultured with nine fungal isolates. D. officinale and D. okinawense showed specificity for a single Serendipitaceae or Tulasnellaceae isolate, whereas D. moniliforme exhibited specificity for three isolates of Serendipitaceae and Tulasnellaceae. Therefore, the three Dendrobium species had a growth bottleneck from seed germination to the protocorm stage, and mycorrhizal specificity of protocorm growth and seedling development in vitro varied among the species. Our findings imply divergent mycorrhizal specificity in Dendrobium species at early developmental stages. This study provides insights into the diversity of orchid mycorrhizal specificity, as well as valuable information for conservation of endangered orchids.

Genomic imprinting restricts transcription to predominantly one parental allele. Here the authors perform a screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells and characterize a role for specific nucleoporins in mediating Kcnq1ot1 imprinted regulation.

The mitochondrial genome sequence of Pseudoxenodon stejnegeri (Squamata: Colubridae: Pseudoxenodontinae) from Taishun County, Zhejiang Province, China, which is 18,475 bp in length and contains 25 tRNAs (including extra two tRNA-Tyr genes and extra one tRNA-Met gene), two rRNAs, 13 protein-coding genes and two identical control regions. The overall AT content of the mitogenome is 59.6% (A = 32.6%, T = 27%, C = 27%, G = 13.4%). In BI and ML phylogenetic analyses, the monophyly of the family Colubridae was well supported and P. stejnegeri was a basal clade of Colubridae.

Genomic imprinting is a phenomenon that restricts transcription to predominantly one parental allele. How this transcriptional duality is regulated is poorly understood. Here we perform an RNA interference screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells. Multiple factors are identified, including nucleoporin 107 (NUP107). To determine NUP107’s role and specificity in Kcnq1ot1 imprinted domain regulation, we deplete Nup107, as well as Nup62, Nup98/96 and Nup153. Nup107, Nup62 and Nup153, but not Nup98/96 depletion, reduce Kcnq1ot1 noncoding RNA volume, displace the Kcnq1ot1 domain from the nuclear periphery, reactivate a subset of normally silent paternal alleles in the domain, alter histone modifications with concomitant changes in KMT2A, EZH2 and EHMT2 occupancy, as well as reduce cohesin interactions at the Kcnq1ot1 imprinting control region. Our results establish an important role for specific nucleoporins in mediating Kcnq1ot1 imprinted domain regulation. [ABSTRACT FROM AUTHOR]

Two patterns of synchronization in networks of semiconductor lasers (SLs) induced by symmetries of inherent network topology are presented. One type is termed isolated desynchronization, in which one or more clusters lose stability while all others remain synchronized. Another type is intertwined synchronization, in which some clusters always achieve and lose their synchrony at the same time. The existence of these special synchronization patterns and their relationship with the topology of network is discussed systemically. The results show that such behaviors exist in different topologies of SL networks. We also discussed the influence of significant parameters of SL networks on the stability of cluster synchronization. It is shown that the network dynamics is sensitive to the two key internal parameters of SLs, the linewidth-enhancement factor, and gain saturation coefficient. Our work is very beneficial to the implementation of secure communication and synchronization networks based on SLs. [ABSTRACT FROM AUTHOR]

Multi-bit extraction schemes for fast random bit generation using a semiconductor laser subject to delayed optical feedback are numerically investigated. The simulation shows that the statistical properties of the chaotic signal significantly influence the generation of random bit sequences. More importantly, bit sequences with verified randomness at hundreds of gigabit per second, even up to the order of terabit per second could be numerically generated utilizing some effective postprocessing techniques even though the original statistical distribution substantially differs from a symmetric distribution. Such numerical results frequently required for developing ultrafast random bit generators as the first stage help to evaluate the experimental implementations of the corresponding schemes. [ABSTRACT FROM PUBLISHER]

This paper presents detailed numerical investigations of quantifying the complexity of the chaotic intensity obtained from the well-known Lang-Kobayashi model for an external-cavity semiconductor laser (ECSL) using sample entropy (SampEn). We demonstrate that the modified SampEn could be an alternative to quantify the underlying dynamics of an ECSL under the condition that the dimension, radius, and time delay of the delayed vectors are properly selected. The numerical results are supported by the earlier numerical studies using the permutation entropy and Kolmogorov-Sinai entropy. Furthermore, we also confirm that the SampEn shows certain robustness to the additive observational noise. [ABSTRACT FROM AUTHOR]

To prevent insertional mutagenesis arising from retroviral reactivation, cells of embryonic origin possess a unique capacity to silence retroviruses. Given the distinct modes of X chromosome inactivation between embryonic and extraembryonic lineages, we investigated paradigms of viral extinction. We show that trophectoderm stem cells do not silence retroviral transcription, whereas extraembryonic endoderm stem cells aggressively extinguish proviral transcription, even more rapidly than do embryonic stem cells. By using a short hairpin RNA library, we identified epigenetic modifiers of retroviral extinction in extraembryonic endoderm stem cells. Multiple chromatin remodeling and polycomb repressor complex proteins act to modulate integrated, as well as endogenous, retroviral element silencing, with a subset of factors displaying differential effects between stem cell types. Furthermore, our data suggest that small RNAs play a role in this process through interactions with the Argonaute family. Our results further the understanding of mechanisms regulating retroviral transcription in different stem cell lineages. [ABSTRACT FROM AUTHOR]

Background: A variety of pathways target CDKI p21WAF1/CIP1 expression at transcriptional, post-transcriptional as well as translational levels. We previously found that cell growth suppressing retinoid CD437 enhanced expression of p21WAF1/CIP1 and DNA damage inducible GADD45 proteins in part by elevating their mRNA stability. Results: Here, we investigated molecular mechanisms of CD437-dependent post-transcriptional regulation of p21WAF1/CIP1 expression. By utilizing MDA-MB-468 HBC cells expressing chimeric rabbit β-globin-p21WAF1/CIP1 transcripts we mapped multiple CD437-responsive sequences located within positions 1195 to 1795 of the 3'-untranslated region of p21WAF1/CIP1 mRNA. Several cytoplasmic proteins present in MDA-MB-468, MCF-7 HBC as well as HL-60R leukemia cells bound specifically, in vitro, with these CD437-responsive sequences. CD437 treatment of cells resulted in elevated binding of ~85 kD and ~55 kD cytoplasmic proteins with putative CD437-responsive sequences. A 12 nt RNA sequence (5'-UGUGGUGGCACA-3') present within CD437-responsive region of p21WAF1/CIP1 mRNA displayed specific and elevated binding with the above noted proteins. Treatment of cells with ActD or CHX prior to CD437 exposure did not abrogate RNA-protein interactions. However, treatment of cytoplasmic protein extracts with proteinase K or alkaline phosphatase resulted in loss of RNA-protein interactions. Conclusions: CD437 regulates cell growth in part by regulating stability of p21WAF1/CIP1 mRNA that involves specific RNA-protein interactions that are phosphorylation-dependent, while not requiring nascent transcription or protein synthesis. [ABSTRACT FROM AUTHOR]

Background: CARP-1/CCAR1, a perinuclear phospho-protein, regulates signaling by adriamycin, steroids, or growth factors. However, intracellular events that regulate CARP-1-dependent cell growth are not fully understood. Results: Here we investigated whether CARP-1 is involved in signaling induced by the protein kinase A inhibitor H89. Treatments of human breast cancer cells with H89 resulted in apoptosis that involved enhanced CARP-1 threonine phosphorylation and expression. Depletion of CARP-1, on the other hand, abrogates apoptosis induced by H89. CARP- 1 binds with signal transducer TAZ and over-expression of TAZ inhibits apoptosis by CARP-1. CARP-1 (651-759) interacts with a novel, N-terminal epitope of TAZ. H89 treatment stimulates threonine phosphorylation of CARP-1 (651-759), while substitution of threonine667 to alanine interferes with its binding with TAZ and apoptosis by H89. In addition, expression of wild type or CARP-1 (651-759) causes loss of c-myc expression due, in part, to suppression of c-myc transcription. Conclusions: CARP-1 threonine667 regulates H89-dependent signaling by a novel pathway that involves modulation of CARP-1 interaction with TAZ and transcriptional down-regulation of c-myc. [ABSTRACT FROM AUTHOR]

CARP-1, a novel apoptosis inducer, regulates apoptosis signaling by diverse agents, including adriamycin and growth factors. Epidermal growth factor receptor (EGFR)-related protein (ERRP), a pan-ErbB inhibitor, inhibits EGFR and stimulates apoptosis. Treatments of cells with ERRP or Iressa (an EGFR tyrosine kinase inhibitor) results in elevated CARP-1 levels, whereas antisense-dependent depletion of CARP-1 causes inhibition of apoptosis by ERRP. CARP-1 is a tyrosine- phosphorylated protein, and ERRP treatments cause elevated tyrosine phosphorylation of CARP-1. CARP-1 contains multiple, nonoverlapping apoptosis-inducing subdomains; one such subdomain is present within amino acids 1-198. Wild-type or CARP-1-(1-198) proteins that have substitution of tyrosine 192 to phenylalanine abrogate apoptosis by ERRP. In addition, apoptosis mediated by wild type or CARP-1-(1-198), and not CARP-1-(1-198Y192F), results in activation of caspase-9 and increased phosphorylation of p38 MAPK. However, the expression of dominant-negative forms of p38 MAPK activators MKK3 or MKK6 proteins inhibits apoptosis induced by both the full-length and truncated (amino acids 1-198) proteins. Together, data demonstrate that tyrosine 192 of CARP-1 is a target of apoptosis signaling, and CARP-1, in turn, promotes apoptosis by activating p38 MAPK and caspase-9. [ABSTRACT FROM AUTHOR]

CD437, a novel retinoid, causes cell cycle arrest and apoptosis in a number of cancer cells including human breast carcinoma (HBC) by utilizing an undefined retinoic acid receptor/retinoid X receptor-independent mechanism. To delineate mediators of CD437 signaling, we utilized a random antisense-dependent functional knockout genetic approach. We identified a cDNA that encodes ∼130-kDa HBC cell perinuclear protein (termed CARP-1). Treatments with CD437 or chemotherapeutic agent adriamycin, as well as serum deprivation of HBC cells, stimulate CARP-1 expression. Reduced levels of CARP-1 result in inhibition of apoptosis by CD437 or adriamycin, whereas increased expression of CARP-1 causes elevated levels of cyclin-dependent kinase inhibitor p21[sup WAF1/CIP1] and apoptosis. CARP-1 interacts with 14-3-3 protein as well as causes reduced expression of cell cycle regulatory genes including c-Myc and cyclin BI. Loss of c-Myc sensitizes cells to apoptosis by CARP-1, whereas expression of c-Myc or 14-3-3 inhibits CARP-1-dependent apoptosis. Thus, apoptosis induction by CARP-1 involves sequestration of 14-3-3 and CARP-1-mediated altered expression of multiple cell cycle regulatory genes. Identification of CARP-1 as a key mediator of signaling by CD437 or adriamycin allows for delineation of pathways that, in turn, may prove beneficial for design and targeting of novel antitumor agents. [ABSTRACT FROM AUTHOR]

In previously identified forms of remote synchronization between two nodes, the intermediate portion of the network connecting the two nodes is not synchronized with them but generally exhibits some coherent dynamics. Here we report on a network phenomenon we call incoherence-mediated remote synchronization (IMRS), in which two noncontiguous parts of the network are identically synchronized while the dynamics of the intermediate part is statistically and information-theoretically incoherent. We identify mirror symmetry in the network structure as a mechanism allowing for such behavior, and show that IMRS is robust against dynamical noise as well as against parameter changes. IMRS may underlie neuronal information processing and potentially lead to network solutions for encryption key distribution and secure communication. [ABSTRACT FROM AUTHOR]

CARP-1/CCAR1, a perinuclear phosphoprotein, is a regulator of cell growth and apoptosis signaling. Although CARP-1 is a regulator of chemotherapy-dependent apoptosis, it is also a part of the NF-κB proteome and a co-activator of steroid/thyroid nuclear receptors as well as β-catenin signaling. Our yeast two-hybrid screen revealed CARP-1 binding with the anaphase-promoting complex/cyclosome E3 ubiquitin ligase component APC-2 protein. CARP-1 also binds with anaphase-promoting complex/cyclosome co-activators Cdc20 and Cdh1. Following mapping of the minimal epitopes involved in CARP-1 binding with APC-2, a fluorescence polarization assay was established that indicated a dissociation constant (Kd) of 480 nm for CARP-1/APC-2 binding. Fluorescence polarization assay-based high throughput screening of a chemical library yielded several small molecule antagonists of CARP-1/APC-2 binding, termed CARP-1 functional mimetics. CFM-4 (1(2-chlorobenzyl)-5′-phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one), a lead compound, binds with and stimulates CARP-1 expression. CFM-4 prevents CARP-1 binding with APC-2, causes G2M cell cycle arrest, and induces apoptosis with an IC50 range of 10-15 μm. Apoptosis signaling by CFM-4 involves activation of caspase-8 and -9 and caspase-mediated ubiquitin-proteasome pathway-independent loss of cyclin B1 and Cdc20 proteins. Depletion of CARP-1, however, interferes with CFM-4-dependent cell growth inhibition, activation of caspases, and apoptosis. Because CFM-4 also suppresses growth of drug-resistant human breast cancer cells without affecting the growth of human breast epithelial MCF-10A cells, elevating CARP-1 by CFM-4 and consequent apoptosis could in principle be exploited to further elucidate, and perhaps effectively target, often deregulated cell cycle pathways in pathological conditions, including cancer. [ABSTRACT FROM AUTHOR]