Synthesis of tertiary alkylphosphonate oligonucleotides through light-driven radical-polar crossover reactions.

Chemical modification of nucleotides can improve the metabolic stability and target specificity of oligonucleotide therapeutics, and alkylphosphonates have been employed as charge-neutral replacements for naturally-occurring phosphodiester backbones in these compounds. However, at present, the alkyl moieties that can be attached to phosphorus atoms in these compounds are limited to methyl groups or primary/secondary alkyls, and such alkylphosphonate moieties can degrade during oligonucleotide synthesis. The present work demonstrates the tertiary alkylation of the phosphorus atoms of phosphites bearing two 2'-deoxynuclosides.

Photoinduced Generation of the π-Conjugated Zwitterionic State in the ESIPT Fluorophore of 2,4-Bisimidazolylphenol.

We demonstrate that 2,4-bis(4,5-diphenyl-1-imidazol-2-yl)phenol (2,4-bImP) undergoes photoinduced conversion into the so-called "π-conjugated zwitterion" after causing an excited-state intramolecular proton transfer (ESIPT) reaction. The powder sample of 2,4-bImP exhibits largely Stokes-shifted fluorescence characteristics to ESIPT fluorophores. On the other hand, its originally colorless solutions become colored when exposed to UV light for several minutes, whose color depends on the type of solvent.

An Obtuse-angled Corner Unit for Fluctuating Carbon Nanohoops.

The invention of corner units was the key factor that allowed the synthesis of cyclo-para-phenylenes with strained curved π-systems. Despite only a few scarce instances of the development of corner units to date, a variety of structural congeners have been synthesized. These preceding corner units commonly possessed directing angles of ≤90°, which enabled the macrocyclization of multiple units, up to six.

Low-Cost Soil Moisture Profile Probe Using Thin-Film Capacitors and a Capacitive Touch Sensor.

Soil moisture is an important property for agriculture, but currently commercialized soil moisture sensors are too expensive for many farmers. The objective of this study is to develop a low-cost soil moisture sensor using capacitors on a film substrate and a capacitive touch integrated circuit. The performance of the sensor was evaluated in two field experiments: a grape field and a mizuna greenhouse field.

The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media.

Objective: Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM.

Reconstruction of a nonfunctional trabeculectomy bleb using an amniotic membrane-wrapped silicone sponge to treat refractory glaucoma.

Background: This study was conducted to verify the usefulness of nonfunctional trabeculectomy bleb reconstruction using a silicone sponge wrapped with amniotic membrane. Its purpose was to allow aqueous humor to flow from the flap to the posterior orbital space.

Methods: Seven consecutive patients who had undergone two or more surgeries in one eye for refractory glaucoma followed by our operation were included in this study.

[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture and the northern district of Aichi prefecture--2009].

High pathogenicity and drug resistance of Streptococcus pneumoniae are serious problem in clinical practice. Since 1999, we have conducted epidemiologic analyses of S. pneumoniae in Chubu district.

Transcriptional regulation of activating transcription factor 4 under oxidative stress in retinal pigment epithelial ARPE-19/HPV-16 cells.

Purpose: Oxidative stress plays an important role in the pathogenesis of various ocular diseases such as retinopathy, glaucoma, and age-related macular degeneration. Activating transcription factor 4 (ATF4) is induced by various stressors, including endoplasmic reticulum (ER) and oxidative stress, and ATF4 expression is regulated translationally through the PERK pathway of eIF2α phosphorylation. Transcriptional regulation of the ATF4 gene under oxidative stress was investigated in human papillomavirus 16 (HPV-16)-transformed retinal pigment epithelial ARPE-19/HPV-16 cells.

Quercetin induces the expression of peroxiredoxins 3 and 5 via the Nrf2/NRF1 transcription pathway.

Purpose: The flavonoids have potent antioxidant and free-radical scavenging properties and are beneficial in the prevention and treatment of ocular diseases including glaucoma. The authors have previously reported that antiglaucoma agents could transcriptionally activate the antioxidant protein peroxiredoxin (PRDX)2. The purpose of this study was to investigate whether quercetin can activate transcription factors and induce the expression of the PRDX family.

Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth.

Programmed cell death protein 4 (PDCD4) has recently been shown to be involved in both transcription and translation, and to regulate cell growth. However, the mechanisms underlying PDCD4 function are not well understood. In this study, we show that PDCD4 interacts directly with the transcription factor Twist1 and leads to reduced cell growth through the down-regulation of the Twist1 target gene Y-box binding protein-1 (YB-1).

Nipradilol and timolol induce Foxo3a and peroxiredoxin 2 expression and protect trabecular meshwork cells from oxidative stress.

Purpose: Oxidative stress plays an important role in pathogenesis of glaucoma. The purpose of this study is to investigate the novel effect of antiglaucoma drugs on the expression of antioxidant peroxiredoxins of trabecular meshwork (TM) cells.

Methods: The expression of the peroxiredoxin family was investigated using immortalized TM cell lines.

Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high-mobility group protein B1.

Peroxiredoxins (Prdxs) are thiol-specific antioxidant proteins that are highly expressed in human cancer cells. Prdxs have been shown to be involved in tumor cell proliferation under conditions of microenvironmental stress such as hypoxia. We hypothesized that Prdxs could be categorized into two groups, stress-inducible and non-inducible ones.

Tip60 is regulated by circadian transcription factor clock and is involved in cisplatin resistance.

Histone modification is important for maintaining chromatin structure and function. Recently, histone acetylation has been shown to have a critical regulatory role in both transcription and DNA repair. We report here that expression of histone acetyltransferase (HAT) genes is associated with cisplatin resistance.

Twist promotes tumor cell growth through YB-1 expression.

YB-1 controls gene expression through both transcriptional and translational mechanisms and is involved in various biological activities such as brain development, chemoresistance, and tumor progression. We have previously shown that YB-1 is overexpressed in cisplatin-resistant cells and is involved in resistance against DNA-damaging agents. Structural analysis of the YB-1 promoter reveals that several E-boxes may participate in the regulation of YB-1 expression.

p73gamma transactivates the p21 promoter through preferential interaction with the p300/CBP-associated factor in human prostate cancer cells.

Several p73 variants have been reported with different carboxy-terminal structures and transcriptional activities. We showed that p73gamma had stronger transactivation activity than the other splicing variants such as alpha, beta and delta by analysing p21 promoter activity in human prostate cancer PC3 cells. The transactivation activity of p73gamma was similar to that of p53 and was enhanced by co-transfection with p300/CBP-associated factor (PCAF).

DNA topoisomerase inhibitor, etoposide, enhances GC-box-dependent promoter activity via Sp1 phosphorylation.

Modification of transcription factors by anticancer agents plays an important role in both apoptotic and survival signaling. Here we report that both DNA topoisomerase I and II inhibitors such as SN-38 and etoposide, but not cisplatin, 5-fluorouracil or actinomycin D, can induce phosphorylation of the transcription factor Sp1. Furthermore, DNA topoisomerase inhibitors were shown to transactivate GC-box-dependent promoters such as the SV40 and vascular endothelial growth factor promoters.

Transcription factors and drug resistance.

Intrinsic or acquired resistance to anticancer agents is a major obstacle to the success of chemotherapy. Anticancer agents are known to modulate signal transduction pathways and alter expression of genes that play an important role in drug resistance. Emerging evidence suggests that the complexity of genomic response against anticancer agents arise from elaborate gene expression by multiple transcription factors.