A case of breast milk-acquired cytomegalovirus infection in an extremely low birth weight infant.

INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection. Preterm infants with postnatal CMV infections are susceptible to a variety of life-threatening conditions. CASE SUMMARY: Twin male infants were delivered via emergency caesarian section at 27 weeks' gestation secondary to maternal complete uterine rupture. The Apgar scores at 1 and 5 min were 1 and 1 for the older twin (Twin A) and 0 and 3 for the younger twin (Twin B). Their birth weights were 1203 g (+ 0.65SD) and 495 g (- 3.79SD) respectively. On day 41, laboratory blood test results for Twin B showed a moderate elevation in C-reactive protein (CRP), thrombocytopenia. CMV quantitative polymerase chain reaction (qPCR) tests in Twin B's urine and blood as well as in the mother's breast milk were positive, but stored, dried umbilical cord CMV qPCR tests were negative. Twin B was diagnosed with a postnatal CMV infection secondary to infected breast milk and ganciclovir was commenced on day 52. Treatment was switched to valganciclovir at 74 days of age, but a negative CMV-DNA level in the blood was not achieved. Postnatal CMV infection in this infant led to an exacerbation of pre-existing bronchopulmonary dysplasia (BPD) and he demised at 182 days of age. CONCLUSION: Postnatal cytomegalovirus infections may lead to exacerbations of BPD. Early use of raw breast milk in preterm infants should be done with careful consideration of this potential complication.

Transient Hyperintensity of the Infant Thyroid Gland on T1-Weighted MR Imaging: Correlation with Postnatal Age, Gestational Age, and Signal Intensity of the Pituitary Gland.

BACKGROUND AND PURPOSE: The signal intensity of the thyroid in neonates is high on T1WI. It is affected by gestational and postnatal ages. However, the extent of the influence of these ages is unknown. This study investigated the relationship of signal intensities of the infant thyroid with postnatal and gestational ages and anterior pituitary using 3D gradient-echo T1WI. MATERIALS AND METHODS: This retrospective study included 183 T1-weighted images from 181 infants. Using a multiple linear regression analysis, we evaluated the effects of postnatal and gestational ages on the thyroid-muscle signal intensity ratio. The relationship between the thyroid and anterior pituitary signal intensities on T1WI and the age of the infants was evaluated. RESULTS: Multiple linear regression analysis showed that the thyroid signal intensity was affected negatively by postnatal age at examination and positively by gestational age at birth (P < .01 and P = .04, respectively). According to the standardized partial regression coefficients, the influence of postnatal age at examination was stronger than that of gestational age at birth (-0.72 and 0.13, respectively). The thyroid and anterior pituitary signal intensities reached constant values at 12 weeks' postnatal age, and the mean thyroid-anterior pituitary signal intensity ratios were almost 1 throughout the entire period. CONCLUSIONS: The signal intensity of the infant thyroid on T1WI was more strongly influenced by the postnatal age at examination than the gestational age at birth, and it was almost equal to that of the anterior pituitary.

Improving the electron spin properties of nitrogen-vacancy centres in nanodiamonds by near-field etching.

The nitrogen-vacancy (NV) centre in diamond is a promising candidate for quantum computing applications and magnetic sensing applications, because it is an atomic-scale defect with stable coherence time (T2) and reliable accessibility at room temperature. We demonstrated a method for improving the NV spin properties (the full width half maximum (FWHM) value of the magnetic resonance spectrum and T2) through a near-field (NF) etching method under ambient conditions. The NF etching method, based on a He-Cd ultraviolet laser (325 nm), which is longer than the absorption edge of the oxygen molecule, enabled selective removal of defects on the nanodiamond surface. We observed a decrease in the FWHM value close to 15% and an increase in T2 close to 25%. Since our technique can be easily reproduced, a wide range of NV centre applications could be improved, especially magnetic sensing applications. Our results are especially attractive, because they have been obtained under ambient conditions and only require a light source with wavelength slightly above the O2 absorption edge.

Extending coherence time of macro-scale diamond magnetometer by dynamical decoupling with coplanar waveguide resonator.

Ultimate sensitivity for quantum magnetometry using nitrogen-vacancy (NV) centers in a diamond is limited by a number of NV centers and coherence time. Microwave irradiation with a high and homogeneous power density for a large detection volume is necessary to achieve a highly sensitive magnetometer. Here, we demonstrate a microwave resonator to enhance the power density of the microwave field and an optical system with a detection volume of 1.4 × 10-3 mm3. The strong microwave field enables us to achieve 48 ns Rabi oscillation which is sufficiently faster than the phase relaxation time of NV centers. This system combined with a decoupling pulse sequence, XY16, extends the spin coherence time (T 2) up to 27 times longer than that with a spin echo method. Consequently, we obtained an AC magnetic field sensitivity of 10.8 pt/ Hz using the dynamical decoupling pulse sequence.

Cerebrovascular Accident Rate Is Different Between Centrifugal and Axial-Flow Pumps, but Survival and Driveline Infection Rates Are Similar.

OBJECTIVES: We analyzed the outcome of patients with implantable left ventricular assist devices (LVADs) at the University of Tokyo Hospital to compare those with centrifugal pumps (CE group: Duraheart and Evaheart) and those with axial-flow pumps (AX group: Heartmate II and Jarvik 2000). METHODS: A total of 68 patients who underwent implantation of LVADs (Duraheart: n = 15; Evaheart: n = 23; Heartmate II: n = 22; Jarvik 2000: n = 8) as a bridge to transplantation at our institution from May 2011 to April 2015 were retrospectively reviewed. All patients were followed through December 2015. RESULTS: The mean follow-up time of the CE group was 1.95 ± 0.92 year (total 74.1 patient-years) and that of the AX group was 1.56 ± 0.56 year (total 46.8 patient-years). Whether the patients underwent centrifugal or axial-flow pump implantations was not associated with survival or driveline infection according to log-rank test (1-year survival rate: 89% vs 100% [P = .221]; 1-year freedom rate: 40% vs 43% [P = .952]). The rates of freedom from cerebrovascular accident (CVA) at 1 year after LVAD implantation in the CE and AX groups were 70% and 96%, respectively (P < .001). The CE group showed a higher frequency of CVA (0.472 vs 0.021 event per patient-year). CONCLUSIONS: Our findings indicate that overall survival and driveline infection rates are similar between centrifugal and axial-flow pumps, but they suggest that patients with centrifugal pumps are more likely to develop CVAs than those with axial-flow pumps.

Association of the Number of HLA-DR Mismatches With Early Post-transplant Acute Cellular Rejection Among Heart Transplantation Recipients: A Cohort Study in Japanese Population.

BACKGROUND: Although many risk factors are reported about graft rejection after heart transplantation (HTx), the effect of HLA mismatch (MM) still remains unknown, especially in the Japanese population. The aim of the present study was to investigate the influence of HLA MM on graft rejection among HTx recipients in Japan. METHODS: We retrospectively investigated the association of the number of HLA MM including class I (A, B) and class II (DR) (for each locus MM: 0 to 2, total MM: 0 to 6) and the incidence of moderate to severe acute cellular rejection (ACR) confirmed by endomyocardial biopsy (International Society for Heart and Lung Transplantation grade ≥ 3A/2R) within 1 year after HTx. RESULTS: Between 2007 and 2014, we had 49 HTx cases in our institute. After excluding those with insufficient data and positive donor-specific antigen, finally 35 patients were enrolled. Moderate to severe ACR was observed in 16 (45.7%) patients. The number of HLA-DR MM was significantly associated with the development of ACR (ACR+: 1.50 ± 0.63, ACR-: 1.11 ± 0.46, P = .029). From univariate analysis, DR MM = 2 was the only independent risk factor for ACR episodes (P = .017). The frequency of ACR within 1 year was significantly higher in those with DR MM = 2 (DR MM = 0 to 1: 0.3 ± 0.47, DR MM = 2: 1.17 ± 1.34 times, P = .007). CONCLUSIONS: The number of HLA-DR MMs was associated with the development and recurrence of ACR episodes among HTx recipients within 1 year after transplantation in Japanese population.

Recovery After Critical Illness Polyneuropathy in a Patient With Orthotopic Liver Transplantation: A Case Report.

After liver transplantation, some patients show neuromuscular abnormalities. A 43-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation. He developed severe neuromuscular dysfunction after sepsis, and acute respiratory distress syndrome. After the inflammatory reaction gradually improved, we observed bilateral weakness of the extremities and foot drop. Electrophysiological studies indicated primary axonal degeneration of peripheral motor and sensory fibers without inflammation. Critical illness polyneuropathy was diagnosed. During follow-up, complaints gradually recovered with rehabilitation by approximately 1 year later. Based on this case, we suggest that paralysis should be evaluated for critical illness polyneuropathy in patients with unexplained muscle weakness.

Ontogenetic metamorphosis and extreme sexual dimorphism in lumpsuckers: Eumicrotremus asperrimus, Cyclopteropsis bergi and Cyclopteropsis lindbergi, may be synonymous.

Cyclopterids were hatched from egg batches that were laid in two empty buccinid snail shells collected from a depth of 340 m in the Sea of Japan. Larvae were reared to identify species and to describe the morphological changes associated with metamorphosis. The fin rays of all fins were mostly complete and the pelvic fins were modified to form suckers, or adhesive discs, at the time of hatching. Juveniles immediately attached themselves to the bottom and there was no planktonic stage. The body surface was smooth with no spines or bony tubercles. At 4 months after hatching, the fine spines present on the head and trunk of juveniles transformed into bony tubercles. At 7 months after hatching, fishes became sexually dimorphic including the position and development patterns of bony tubercles. Importantly, these sexually dimorphic changes in morphology corresponded closely with descriptions of different species. Specifically, females could be classified as Eumicrotremus asperrimus, and young and fully developed males as Cyclopteropsis bergi and Cyclopteropsis lindbergi, respectively. These observations resolved a previously ambiguous hypothesis regarding the taxonomy of these cyclopterid taxa. Cyclopteropsis bergi and C. lindbergi may be synonyms of E. asperrimus.

Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways.

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells.

BACKGROUND: Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels and clinical severity of atopic patients. However, the precise mechanism has not been fully elucidated. We investigated the role of Phf11 in class switch recombination (CSR) to IgE by activated B cells. METHODS: We generated Phf11 transgenic (Lckd-Phf11-Tg) mice that express the exogenous murine Phf11 in lymphocytes under the control of distal Lck promoter. We examined IL-4-induced CSR to IgE in activated Lckd-Phf11-Tg B cells in vitro. We analyzed production of ovalbumin (OVA)-specific IgE and nose-scratching symptoms in Lckd-Phf11-Tg mice using an OVA-induced allergic rhinitis model. RESULTS: The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (GLT) γ1 and GLT ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT γ1 and GLT ε promoters through permissive histone modifications and binding of NF-κB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT ε promoter with increased binding of NF-κB. Silencing of the endogenous Phf11 reduced the frequency of CSR to IgE and GLT ε expression, but not to IgG1 or GLT γ1 expression, in activated B cells. In an allergic rhinitis model, Lckd-Phf11-Tg mice showed a significant increase in the production of OVA-specific IgE and the frequency of nose scratching. CONCLUSION: Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of GLT ε promoter and contributes to the exacerbation of allergic responses. These findings provide a novel therapeutic target for allergic diseases.

Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.

Effects of optimized mixtures containing phenolic compounds on the oxidative stability of sausages.

Phenolic compounds were applied in a sausage formulation as a substitute for artificial sodium erythorbate used as antioxidant. Five assays were prepared in which sodium erythorbate control at 0.05 g/100 g was replaced with a hydrosoluble mixture containing caffeic acid + carnosic acid (47% + 53%) and a liposoluble mixture containing quercetin + rutin (67% + 33%) in two final concentrations (0.05 g/100 g and 0.08 g/100 g). Physico-chemical, color, texture, and sensory parameters were measured on the first day and after 45 days of storage at 4 °C. All phenolic compound mixtures were able to maintain oxidative stability in the sausages when measured by the malondialdehyde concentration, which was expressed as TBARS. The mixture containing quercetin + rutin at 0.05 g/100 g showed lower malondialdehyde formation after 45 days of storage, and no sensory differences from the sausage adopted as control.

Effects of bosentan on nondigital ulcers in patients with systemic sclerosis.

BACKGROUND: Bosentan is an oral dual endothelin receptor antagonist, which has been shown to be efficacious for preventing new digital ulcers in patients with systemic sclerosis (SSc) in two high-quality randomized controlled trials. However, its efficacy for nondigital ulcers in SSc remains unknown. OBJECTIVES: To evaluate the efficacy of bosentan on nondigital ulcers in patients with SSc. METHODS: Bosentan was administered to five patients with SSc with pulmonary arterial hypertension, who also had nondigital ulcers refractory to conventional treatments. The efficacy of bosentan on nondigital ulcers and its association with clinical features of ulcers were analysed. RESULTS: The nondigital ulcers refractory to conventional treatments were significantly improved by the administration of bosentan in cases surrounded with severe cyanosis. In contrast, nondigital ulcers without cyanosis were still refractory to bosentan therapy. CONCLUSIONS: Bosentan may be efficacious for accelerating the healing of nondigital ulcers with severe cyanosis, suggesting that nondigital ulcers caused by severely impaired peripheral circulation are highly responsive to this treatment.

Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation.

BACKGROUND: There is synteny in the CC-type chemokine gene clusters between humans (CCL2/MCP-1, CCL7MCP-3, CCL11/eotaxin, CCL8/MCP-2, CCL13/MCP-4, and CCL1/I-309) and mice (CCL2, CCL7, CCL11, CCL12/MCP-5, CCL8, and CCL1). OBJECTIVE: As many putative Bcl6/STAT-binding sequences are observed in the clusters, we examined the roles of a transcriptional repressor Bcl6 and the regional histone modification in the expression of these chemokine genes in pulmonary epithelium. METHODS: We generated transgenic (Tg) mice carrying the Bcl6 or the dominant-negative (DN)-Bcl6 gene under the control of the surfactant protein C (SPC) promoter that induces the exogenous gene expression in the distal lung epithelium. For in vitro studies, A549, alveolar type II-like epithelial cell line transfected with the SPC-DN-Bcl6 gene were stimulated with IL-4+TNF-α, and Bcl6 or STAT6 binding to and histone modification of the cluster in the transfectants were analysed by chromatin immunoprecipitation assays. Tg mice sensitized with ovalbumin (OVA) were challenged with OVA inhalation. The amounts of mRNAs in each sample were analysed by quantitative RT-PCR. RESULTS: The amount of Bcl6 bound to the cluster decreased in A549 cells stimulated with IL-4 and TNF-α, whereas STAT6 binding increased in association with regional histone H3-K9/14 acetylation and H3-K4 methylation. The expression of all chemokine genes in the gene cluster was augmented in activated A549 cells transfected with the DN-Bcl6 gene. We also induced allergic airway inflammation in Tg mice. Expression of the chemokine genes and infiltrated cell numbers in the lungs of these Tg mice with allergic airway inflammation were inversely correlated with the amount of Bcl6 in the lungs. CONCLUSION AND CLINICAL RELEVANCE: Expression of the pulmonary epithelium-derived CC-type chemokine genes in the cluster is orchestrated by the conserved machinery related to Bcl6. Thus, Bcl6 in pulmonary epithelium may be a critical regulator for pathogenesis of various pulmonary inflammatory diseases.

Effect of the partial substitution of soy proteins by highly methyl-esterified pectin on chemical and sensory characteristics of sausages.

Pectin can be used as a natural emulsifier in food formulations. In this study, textured soybean protein (TSP), used as an emulsifier in commercial sausages, was partially replaced by a mixture containing pectin and isolated soybean proteins, which were either extruded (EXT) or not extruded (MIX), and the chemical and sensory characteristics of samples were evaluated after 60 days of storage at 4 °C. Responses such as oxidation measured by PV and TBARS, hardness, color, pH and sensory characteristics were compared with those of a commercial sausage (CON). The mixture containing highly methyl-esterified pectin, textured soybean proteins and isolated soybean proteins, as emulsifier agent, reduced the hardness (EXT: 21.69±0.98 and MIX: 20.17 ±2.76 N) and the pH (EXT: 5.46±0.03 and MIX: 5.29±0.01) of the samples and increased the concentration of peroxides (EXT: 0.10±0.01 and MIX: 0.15 ±0.01 meq/kg) when compared with samples formulated only with TSP (28.57 ± 2.54 N, pH of 6.92±0.04 and PV = 0.07 ± 0.01 meq/ kg). These effects were likely caused by the anionic character of the emulsifier. However, no sensory difference was observed between the sausages containing highly methyl-esterified pectin, textured soybean proteins and isolated soybean proteins submitted to the extrusion process (EXT) and the control sausages, suggesting that the formulation proposed in this study can be a potential alternative for the further development of sausages that have functional properties or are free of artificial additives.

Low-dose MTX for the treatment of acute and chronic graft-versus-host disease in children.

We report the results of a retrospective analysis in 27 pediatric patients who received low-dose MTX as the second-line treatment for steroid-refractory or -dependent acute and chronic GVHD. Between July 2000 and May 2006, 10 patients with aGVHD and 17 with cGVHD were treated with MTX at a dose of 3-10 mg/m(2) weekly. Seven of ten patients (70%) with aGVHD responded well to MTX, thus resulting in the achievement of either a complete response (CR) or a partial response (PR). The dose of prednisone could be reduced to equal to or lower than 1 mg/kg in the responding patients at the end of MTX therapy. The median number of MTX administrations was five (range, 1-7). Ten (58.8%) of seventeen patients with cGVHD achieved CR or PR. The dose of prednisone could be reduced to lower than 0.4 mg/kg in 16 of 17 patients and seven patients could discontinue prednisone. The median duration of MTX administration was 18 months (range, 1-68). The toxicities of grade III to IV occurred in only six patients presenting cytopenias or elevated levels of serum transaminases. Low-dose MTX was tolerable and effective for the steroid-refractory or -dependent GVHD in reducing the dose of steroid without increasing the risk of opportunistic infection.

Resolving the discrepancy of 135 MeV pd elastic scattering cross sections and relativistic effects.

Three precise measurements for elastic pd scattering at 135 MeV/A have been performed with the three different experimental setups. The cross sections are described well by the theoretical predictions based on modern nucleon-nucleon forces combined with three-nucleon forces. Relativistic Faddeev calculations show that relativistic effects are restricted to backward angles. This result supports the two measurements recently reported by RIKEN and contradicts the KVI data.

Syenergistic effect of 15-deoxyspergualin with costimulation blockade on alloimmune response.

INTRODUCTION: A virally induced alloreactive memory seems to represent a potent barrier to tolerance induction but the combination of 15-deoxyspergualin (DSG), an inhibitor of NFkB translocation, with costimulation blockade (CB)-based chimerism as an induction regimen can overcome a preformed anti-donor memory response. In this study, we investigate the ability of DSG with CB to inhibit a naive alloimmune responses. METHODS: A BALB/c (H-2d) skin or heart was transplanted into a C57BL/6 (H-2b) recipient treated with anti-CD154 mAb (MR1; 500 mcg/d on days 0, 2, 4, 6) alone, DSG (5 mg/kg/d, days 0 to 7) alone, or both agents. Proliferation of alloreactive T cells after each treatment was also examined using a graft-versus-host disease (GvHD) model using the fluorescent dye CFSE. RESULTS: Treatment with DSG alone induced prolonged survival of the cardiac allografts (median survival time [MST]: 97.5 days). MR1 alone induced indefinite survival of cardiac allografts, although at 150 days after transplantation, the histology showed changes characteristic of chronic rejection, including interstitial fibrosis, infiltration of mononuclear cells, and intimal hyperplasia in coronary vessels. Combined treatment with DSG and MR1 induced donor-specific unresponsiveness in all recipients, graft histology showed only minimal infiltration. Treatment with DSG and MR1 also significantly prolonged the survival of skin allografts (MST: 31 days) compared with that of DSG or MR1 alone (MST: 17 and 14 days, respectively). In the GvHD model assessed with CFSE, the combined treatment was the more effective to suppress proliferation of alloreactive T cells while DSG alone inhibited proliferation more than MR1 alone. CONCLUSION: DSG potentiates anti-CD154 therapy to suppress the alloimmune response.

Isoform-dependent interaction of BRDG1 with Tec kinase.

Tec is the prototype of an emerging family of protein-tyrosine kinases. Tec and Btk, another member of this family, together participate in the development of B-cell immune system. We previously identified one of the downstream messengers for human Tec kinase, BRDG1. BRDG1 is associated with Tec and becomes tyrosine-phosphorylated in B-cells by the engagement of B-cell antigen receptor (BCR). Here we show that overexpression of BRDG1 strongly augments BCR-mediated activation of cAMP-response element binding protein (CREB) but not that of c-Jun and the promoters of c-MYC and BCL-xL genes. Furthermore, we isolated the murine orthologue of BRDG1. Three isoforms of BRDG1 are generated by alternative splicing of the message. Two of them have a deletion of 33 amino acids in a Pleckstrin homology (PH) domain of BRDG1. Both the tyrosine-phosphorylation and CREB-activating ability of BRDG1 were isoform-dependent, suggesting a role of the PH domain of BRDG1. These data have identified a novel regulatory mechanism of CREB family of transcriptional factors.