Phosphorylation of p50 NF-kappaB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment

The DNA binding activity of NF-κB is critical for VCAM-1 expression during inflammation. DNA-dependent protein kinase (DNA-PK) is thought to be involved in NF-κB activation. Here we show that DNA-PK is required for VCAM-1 expression in response to TNF. The phosphorylation and subsequent degradation of I-κBα as well as the serine 536 phosphorylation and nuclear translocation of p65 NF-κB were insufficient for VCAM-1 expression in response to TNF. The requirement for p50 NF-κB in TNF-induced VCAM-1 expression may be associated with its interaction with and phosphorylation by DNA-PK, which appears to be dominant over the requirement for p65 NF-κB activation. p50 NF-κB binding to its consensus sequence increased its susceptibility to phosphorylation by DNA-PK. Additionally, DNA-PK activity appeared to increase the association between p50/p50 and p50/p65 NF-κB dimers upon binding to DNA and after binding of p50 NF-κB to the VCAM-1 promoter. Analyses of the p50 NF-κB protein sequence revealed that both serine 20 and serine 227 at the amino terminus of the protein are putative sites for phosphorylation by DNA-PK. Mutation of serine 20 completely eliminated phosphorylation of p50 NF-κB by DNA-PK, suggesting that serine 20 is the only site in p50 NF-κB for phosphorylation by DNA-PK. Re-establishing wild-type p50 NF-κB, but not its serine 20/alanine mutant, in p50 NF-κB(-/-) fibroblasts reversed VCAM-1 expression after TNF treatment, demonstrating the importance of the serine 20 phosphorylation site in the induction of VCAM-1 expression. Together, these results elucidate a novel mechanism for the involvement of DNA-PK in the positive regulation of p50 NF-κB to drive VCAM-1 expression.     

Graphene nanosheet reinforcement of polyurethane nanocomposite for green and sustainable photoluminescence,superhydrophobic, and anticorrosive paint

A simple and environmentally friendly method was developed for smart and efficient waterborne polyurethane (PUR) paint. Sugarcane bagasse was recycled into reduced graphene oxide nanosheets (rGONSs). Both lanthanide-doped aluminate nanoparticles (LAN; photoluminescent agent, 7–9 nm) and rGONSs (reinforcement agent) were integrated into a waterborne polyurethane to produce a novel photoluminescent, hydrophobic, and anticorrosive nanocomposite coating. Using ferrocene-based oxidation under masked circumstances, graphene oxide nanosheets were produced from sugarcane bagasse. The oxidized semicarbazide (SCB) nanostructures were integrated into polyurethane coatings as a drying, anticorrosion, and crosslinking agent. Polyurethane coatings with varying amounts of phosphor pigment were prepared and subsequently applied to mild steel. The produced paints (LAN/rGONSs@PUR) were tested for their hydrophobicity, hardness, and scratch resistance. Commission Internationale de l'éclairage (CIE) Laboratory parameters and photoluminescence analysis established the opacity and colourimetric properties of the nanocomposite coatings. When excited at 365 nm, the luminescent transparent paints emitted a strong greenish light at 517 nm. The anticorrosion characteristics of the coated steel were investigated. The phosphor-containing (11% w/w) polyurethane coatings displayed the most pronounced anticorrosion capability and long-persistent luminosity. The prepared waterborne polyurethane paints were very photostable and durable.     

PDZK1 Is a Novel Factor in Breast Cancer That Is Indirectly Regulated by Estrogen through IGF-1R and Promotes Estrogen-Mediated Growth

Although a relationship between PDZK1 expression and estrogen receptor (ER)-α stimulation has been suggested, the nature of such a connection and the function of PDZK1 in breast cancer remain unknown. Human tissue microarrays (cancer tissue: 262 cores; normal tissue: 87 cores) and breast cancer cell lines were used to conduct the study. We show that PDZK1 protein expression is tightly correlated with human breast malignancy, is negatively correlated with age and had no significant correlation with ER-α expression levels. PDZK1 exhibited an exclusive epithelial expression with mostly cytosolic subcellular localization. Additionally, 17β-estradiol induced PDZK1 expression above its basal level more than 24 h after treatment in MCF-7 cells. PDZK1 expression was indirectly regulated by ER-α stimulation, requiring insulinlike growth factor 1 receptor (IGF-1R) expression and function. The molecular link between PDZK1 and IGF-1R was supported by a significant correlation between protein and mRNA levels (r = 0.591, p < 0.001, and r = 0.537, p < 0.001, respectively) of the two factors in two different cohorts of human breast cancer tissues. Interestingly, PDZK1 knockdown in MCF-7 cells blocked ER-dependent growth and reduced c-Myc expression, whereas ectopic expression of PDZK1 enhanced cell proliferation in the presence or absence of 17β-estradiol potentially through an increase in c-Myc expression, suggesting that PDZK1 has oncogenic activity. PDKZ1 also appeared to interact with the Src/ER-α/epidermal growth factor receptor (EGFR) complex, but not with IGF-1R and enhanced EGFR-stimulated MEK/ERK1/2 signaling. Collectively, our results clarify the relationship between ER-α and PDZK1, propose a direct relationship between PDZK1 and IGF-1R, and identify a novel oncogenic activity for PDZK1 in breast cancer.     

Network Models of Frequency Modulated Sweep Detection

Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The ‘facilitation’ model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The ‘duration tuned’ model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The ‘inhibitory sideband’ model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.     

Tissue allograft coding and traceability in USM Tissue Bank,Malaysia

In Malaysia, tissue banking activities began in Universiti Sains Malaysia (USM) Tissue Bank in early 1990s. Since then a few other bone banks have been set up in other government hospitals and institutions. However, these banks are not governed by the national authority. In addition there is no requirement set by the national regulatory authority on coding and traceability for donated human tissues for transplantation. Hence, USM Tissue Bank has taken the initiatives to adopt a system that enables the traceability of tissues between the donor, the processed tissue and the recipient based on other international standards for tissue banks. The traceability trail has been effective and the bank is certified compliance to the international standard ISO 9001:2008.     

Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease)

Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress‐induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy‐modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin‐1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone‐induced behavioral impairment, augmented autophagy, ameliorated ER stress‐ induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death.     

Importance of plant extract formulations in managing different pests attacking beans in new reclaimed area and under storage conditions

Field evaluation of some botanical formulations like Neem Azal T/S, Neem Azal T/S + TS/fort and petroleum ether extract of Curcuma longa for the management of different pests attacking broad bean crop in a new reclaimed area at El- Noubaria and under storage conditions has been carried out. All tested formulations could be considered efficient in controlling Aphis craccivora infesting broad bean under field conditions. As to the leafminer, the number of living Liriomyza trifolii larvae decreased significantly compared to non-treated control. The number of living larvae continued to decrease until seven days post-treatment after which an increase in their number was noticed after 14 days post-treatment. Neem Azal T/S + additive (TS/fort) ranked first in comparison to other treatments for the control of aphids and leafminers attacking broad bean in the field either by killing, deterrent or antifeedant effect. The yield of treated crop increased significantly in comparison to the control. Another spray was used before harvesting the crop with the same formulations for protection of the stored crop. Neem Azal T/S with adjuvant (TS/fort) protected broad bean seeds from weevil attack for one year. Petroleum ether extract of C. longa could protect the stored crops for two months only. The percentage weight loss in one kg stored seeds treated in the field with Neem formulation + adjuvant was very small compared with those seeds treated with petroleum ether extract of C. longa and control.     

Biocontrol agents against the leafminer,Liriomyza trifolii in faba bean fields

Effect of entomopathogenic fungi formulations, Beauveria bassiana, Verticillium lecanii, Metarhizium anisopliae and Paecilomyces fumosoroseus, in controlling Liriomyza trifolii (Burg.) (Diptera: Agromyzidae), compared with botanical insecticide, Nimbecidine against L. trifolii was studied. Investigated compounds were applied twice at 15?days interval between sprays. The percentage reduction in larvae population and crop yield was estimated. Results showed that M. anisopliae was the most efficient compound among the other entomopathogenic fungi. Also, there were no significant differences between Nimbecidine and Bio-Magic (M. anisopliae). However, Nimbecidine and Bio-Magic caused 69.9 and 68.9% reduction in live larvae population after two applications. Also, Nimbecidine and Bio-Magic plots achieved 14.7 and 10.0?kg dry weight seeds/100 plants, respectively, compared to 5.7?kg dry weight seeds/100 plants in control plots. Nimbecidine and Bio-Magic were considered promising compounds in controlling L. trifolii and it could be exploitation in the integrated pest management programme of faba bean crop.     

Crocin Abrogates Carbon Tetrachloride‐Induced Renal Toxicity in Rats via Modulation of Metabolizing Enzymes and Diminution of Oxidative Stress,Apoptosis, and Inflammatory Cytokines

This work aimed at investigating the potential modulatory effects and mechanisms of crocin against CCl₄‐induced nephrotoxicity. Forty male rats were allocated for three weeks treatment with corn oil, CCl₄, crocin, or crocin plus CCl₄. Crocin effectively mitigated CCl₄‐induced kidney injury as evidenced by amelioration of alterations in kidney histopathology, renal weight/100 g body weight ratio and kidney functions. Crocin modulated CCl₄‐induced disturbance of kidney cytochrom‐P450 subfamily 2E1 and glutathione‐S‐transferase. The attenuation of crocin to kidney injury was also associated with suppression of oxidative stress via reduction of lipid peroxides along with induction of renal glutathione content and enhancement of superoxide dismutase, glutathione peroxidase, and catalase activities. Crocin mitigated CCl₄‐induced elevation of the renal levels of tumor necrosis factor‐alpha, interleukin‐6, prostaglandin E2, and active caspases‐3. Collectively, crocin alleviated CCl₄‐induced renal damage via modulation of kidney metabolizing enzymes, suppression of oxidative stress, inhibition of inflammatory cytokines, PGE2, and active caspase3 in kidney.