ΔNp63 silencing, DNA methylation shifts, and epithelial-mesenchymal transition resulted from TAp63 genome editing in squamous cell carcinoma.

TP63 (p63) is strongly expressed in lower-grade carcinomas of the head and neck, skin, breast, and urothelium to maintain a well-differentiated phenotype. TP63 has two transcription start sites at exons 1 and 3' that produce TAp63 and ΔNp63 isoforms, respectively. The major protein, ΔNp63α, epigenetically activates genes essential for epidermal/craniofacial differentiation, including ΔNp63 itself.

Novel Bioprinting Application for the Production of Reference Material Containing a Defined Copy Number of Target DNA.

Nucleic acid amplification methods, such as polymerase chain reaction (PCR), are extensively used in many applications to detect target DNA because of their high sensitivity, good reproducibility, and wide dynamic range of quantification. However, analytical quality control when detecting low copy number target DNA is often missing because of a lack of appropriate reference materials. Recent advances in analytical sciences require a method to accurately quantify DNA at the single molecule level.

Potential Risk of Virus Carryover by Fabrics of Personal Protective Gowns.

Personal protective gowns and coveralls are classified based on barrier efficiency that validates protection from fluid penetration under certain pressures. Materials standardized in this system have been found suitable for emergency medical practices confronting highly contagious diseases. Nevertheless, adhesion of blood, and body fluids from virus-infected patients to the surface of protective clothing still imposes a risk of pathogen transmission in the process of doffing, or undressing.

C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression.

Cancer is a leading cause of death and disease worldwide, with a tremendous financial impact. Thus, the development of cost-effective novel approaches for suppressing tumor growth and progression is essential. In an attempt to identify the mechanisms responsible for tumor suppression, we screened for molecules downregulated in a cancer progression model and found that the chemokine CXCL14, also called BRAK, was the most significantly downregulated.

C-terminal α Domain of p63 Binds to p300 to Coactivate β-Catenin.

TP63 (p63), a member of the tumor suppressor TP53 (p53) gene family, is essential for ectodermal tissue development and suppresses malignant progression of carcinomas. The most abundant isoform, ΔNp63α (referred to as p63), lacks the N-terminal transactivation (TA) domain, and was originally characterized as a dominant-negative type suppressor against p53 family proteins. It also binds to TCF/LEF to inhibit β-catenin.

Repression of Wnt/β-catenin response elements by p63 (TP63).

Submitted: TP63 (p63), a member of the tumor suppressor TP53 (p53) gene family, is expressed in keratinocyte stem cells and well-differentiated squamous cell carcinomas to maintain cellular potential for growth and differentiation. Controversially, activation of the Wnt/β-catenin signaling by p63 (Patturajan M. et al.

Association of endogenous retroviruses and long terminal repeats with human disorders.

Since the human genome sequences became available in 2001, our knowledge about the human transposable elements which comprise ∼40% of the total nucleotides has been expanding. Non-long terminal repeat (non-LTR) retrotransposons are actively transposing in the present-day human genome, and have been found to cause ∼100 identified clinical cases of varied disorders. In contrast, almost all of the human endogenous retroviruses (HERVs) originating from ancient infectious retroviruses lost their infectivity and transposing activity at various times before the human-chimpanzee speciation (∼6 million years ago), and no known HERV is presently infectious.

Activation of the long terminal repeat of human endogenous retrovirus K by melanoma-specific transcription factor MITF-M.

The human and Old World primate genomes possess conserved endogenous retrovirus sequences that have been implicated in evolution, reproduction, and carcinogenesis. Human endogenous retrovirus (HERV)-K with 5'LTR-gag-pro-pol-env-rec/np9-3'LTR sequences represents the newest retrovirus family that integrated into the human genome 1 to 5 million years ago. Although a high-level expression of HERV-K in melanomas, breast cancers, and teratocarcinomas has been demonstrated, the mechanism of the lineage-specific activation of the long terminal repeat (LTR) remains obscure.

Induction of ΔNp63 by the newly identified keratinocyte-specific transforming growth factor β Signaling Pathway with Smad2 and IκB Kinase α in squamous cell carcinoma.

The expression of p63 (TP63/p51) occurs in the basal cells of stratified epithelia and is strongly enhanced at the early stages of squamous cell carcinomas (SCCs) of the head and neck, skin, cervix, and others. We analyzed a promoter/enhancer region (2kΔN) that drives the predominant expression of ΔNp63 for sensitivity to Smad signaling pathways. Reporter assays in HepG2 cells showed a moderate activation of 2kΔN by Smad2 and IκB kinase α (IKKα), partners of the newly identified keratinocyte-specific transforming growth factor β (TGF-β) signaling, but not by other Smad molecules.

[Treatment of childhood epilepsies: Japanese Expert Consensus study and a comparison of the results with those of the USA and EU].

We conducted a Japanese Expert Consensus (EC) study for the treatment of childhood epilepsies following the method reported from the USA and EU (Wheless JW, et al., 2005, 2007), and compared the results to reveal differences in the choice of antiepileptic drugs (AEDs). The subjects were 41 pediatric board-certified epileptologists who responded to the 23 questionnaires.

Lung-lung interaction in isolated perfused unilateral hyperventilated rat lungs.

The technique of conducting high tidal volume (TV) ventilation-induced lung inflammation including remote organs is still open to discussion, and our aim is to investigate this issue in isolated ventilated rat lungs perfused with salt solution. Selective right lung (RL) hyperventilation (TV of 15 mL/kg with air containing 5% CO(2) on zero or 2.5 cm H(2)0 end expiratory pressure [ZEEP or PEEP] in addition to left lung (LL) on 2.

Apaf-1-deficient fog mouse cell apoptosis involves hypo-polarization of the mitochondrial inner membrane, ATP depletion and citrate accumulation.

To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog (forebrain overgrowth) mutant mice with an Apaf1 splicing deficiency, we examined spleen and bone marrow cells from Apaf1(+/+) (+/+) and Apaf1(fog/fog) (fog/fog) mice for initiator caspase-9 activation by cellular stresses. When the mitochondrial inner membrane potential (Deltapsim) was disrupted by staurosporine, +/+ cells but not fog/fog cells activated caspase-9 to cause apoptosis, indicating the lack of apoptosome (apoptosis protease activating factor 1 (Apaf-1)/cytochrome c/(d)ATP/procaspase-9) function in fog/fog cells. However, when a marginal ( approximately 20%) decrease in Deltapsim was caused by hydrogen peroxide (0.

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms.

We report here that human MFGE8 encoding milk fat globule-EGF factor 8 protein (MFG-E8), also termed 46 kDa breast epithelial antigen and lactadherin, is transcriptionally activated by p63, or TP63, a p53 (TP53) family protein frequently overexpressed in head-and-neck squamous cell carcinomas, mammary carcinomas and so on. Despite that human MFG-E8 was originally identified as a breast cancer marker, and has recently been reported to provide peptides for cancer immunotherapy, its transcriptional control remains an open question. Observations in immunohistochemical analyses, a tetracycline-induced p63 expression system and keratinocyte cultures suggested a physiological link between p63 and MFGE8.

Chronic contained rupture of an abdominal aortic aneurysm with vertebral erosion: report of a case.

A 73-year-old man had lumbago of unknown cause for several months prior to presentation. At examination prior to surgery for gastric cancer, an abdominal aortic aneurysm (AAA) of 6 cm in maximum diameter, retroperitoneal hematoma and vertebral erosion were found on abdominal computed tomography (CT). Hematological examination revealed mild anemia and stable hemodynamics.

Production of the long and short forms of MFG-E8 by epidermal keratinocytes.

Mouse milk fat globule-EGF factor 8, MFG-E8, is the ortholog to the human mammary tumor marker, lactadherin, and comprises two spliced variants, the L and S forms. Recent studies have suggested that MFG-E8-L produced by macrophages and Langerhans cells in the skin serves as a linker between phagocytic cells and apoptotic cells, and that MFG-E8-S, also termed SED1, facilitates sperm-egg interaction for fertilization. However, Mfge8 gene expression occurs in various tissues apparently unrelated to these critical events.

p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche.

p51/p63, a member of the tumor suppressor p53 gene family, is crucial for skin development. We describe here identification of ITGA3 encoding integrin alpha(3) as a target of its trans-activating function, proposing that p51/p63 allows epidermal stem cells to express laminin receptor alpha(3)beta(1) for anchorage to the basement membrane. When activated by genotoxic stress or overexpressed ectopically in non-adherent cells, p51/p63 transduced a phenotype to attach to extracellular matrices, which was accompanied by expression of ITGA3.

Dimerization and processing of procaspase-9 by redox stress in mitochondria.

We studied the mechanism of intra-mitochondrial death initiator caspase-9 activation by a redox response, in which hydrogen peroxide (H(2)O(2)) caused a subtle decrease in the inner membrane potential (Deltapsim) with little evidence of cytochrome c release. Initiation of the intra-mitochondrial autocleavage of procaspase-9 preceded the onset of caspase cascade induction in the cytosol. Purified mitochondria demonstrated procaspase-9 processing and releasing abilities when exposed to H(2)O(2).

Expression of a novel secretory form (Crb1s) of mouse Crumbs homologue Crb1 in skin development.

Drosophila Crumbs and the mammalian homologues encoded by the Crb genes are transmembrane proteins required for determination of retinal cell polarity. We cloned a novel variant of mouse Crb1 and termed it Crb1s. Since the 3'-end of exon 6 remained unspliced, Crb1s coded for a short secretory protein lacking the transmembrane and cytoplasmic domains required for the function of Crb1.

Evolutionarily conserved expression pattern and trans-regulating activity of Xenopus p51/p63.

p51/p63, a member of the p53 gene family, is structurally conserved among a wide range of organisms, although the transactivator (TA) and N-terminally truncated (deltaN) isotype producing property seems to vary. Since p51/p63 is thought to play important roles in skin, limb, and craniofacial development in mammals, we examined Xenopus laevis larval and adult tissues for expression of p51/p63. Temporal analyses indicated enhanced transcription of the deltaN form of p51/p63 in premetamorphosis phase (at stage 44-48).

Azidothymidine causes functional and structural destruction of mitochondria, glutathione deficiency and HIV-1 promoter sensitization.

Mitochondrial functional and structural impairment and generation of oxidative stress have been implicated in aging, various diseases and chemotherapies. This study analyzed azidothymidine (AZT)-caused failures in mitochondrial functions, in redox regulation and activation of the HIV-1 gene expression. We monitored intracellular concentrations of ATP and glutathione (GSH) as the indicators of energy production and redox conditions, respectively, during the time-course experiments with U937 and MOLT4 human lymphoid cells in the presence of AZT (0.

p53 gene family p51(p63)-encoded, secondary transactivator p51B(TAp63alpha) occurs without forming an immunoprecipitable complex with MDM2, but responds to genotoxic stress by accumulation.

p51(p63), a member of the p53 tumor suppressor gene family, generates multiple isoforms, including the potent and less potent transactivators p51A(TAp63gamma) and p51B(TAp63alpha), respectively, the latter poorly characterized for its protein features and functions. When constitutively expressed in 1-2-3 mouse erythroleukemic cells, p51B(TAp63alpha) appeared as a broad band with an approximate molecular mass of 85 kDa in Western blot. When cells were exposed to genotoxic stress by UV-C irradiation or by DNA-damaging drugs, including actinomycin D, bleomycin, and eptoposide, the protein accumulated intracellularly without an increase in its mRNA.

Analysis of molecular interactions of the p53-family p51(p63) gene products in a yeast two-hybrid system: homotypic and heterotypic interactions and association with p53-regulatory factors.

p51 in the p53 tumor suppressor family, also referred to as p63, encodes multiple isoforms including p51A (TAp63gamma) and p51B (TAp63alpha). The p53 protein forms a tetramer, and its stability and activity are regulated by molecular association with viral and cellular proteins and by biochemical modifications. Using a yeast two-hybrid system, the p51A and p51B isoforms were examined for homotypic and heterotypic interactions in the p53 family proteins and for their affinity to the p53-regulatory factors.