However, origin ssDNA selleck substantially disrupts the interaction between Sld3 and Mcm2-7. GINS and Sld3 compete with one another for binding to Mcm2-7. However, in a mixture of Sld3, GINS, and Mcm2-7, origin ssDNA inhibits the interaction between Sld3 and Mcm2-7, whereas
origin ssDNA promotes the association between GINS and Mcm2-7. We also show that origin single-stranded DNA promotes the formation of the CMG complex. We conclude that origin single-stranded DNA releases Sld3 from Mcm2-7, allowing GINS to bind Mcm2-7.”
“‘Brain and cognitive reserve’ (BCR) refers here to the accumulated neuroprotective reserve and capacity for functional compensation induced by the chronic enhancement of mental and physical activity. BCR is thought to protect against, and compensate for, a range of different neurodegenerative diseases, as well as other neurological and psychiatric disorders. In this review we will discuss BCR, and its potential
check details mechanisms, in neurodegenerative disorders, with a focus on Huntington’s disease (HD) and Alzheimer’s disease (AD). Epidemiological studies of AD, and other forms of dementia, provided early evidence for BCR. The first evidence for the beneficial effects of enhanced mental and physical activity, and associated mechanistic insights, in an animal model of neurodegenerative disease was provided by experiments using HD transgenic mice. More recently, experiments on animal models of HD, AD and various other brain disorders have suggested potential molecular and cellular mechanisms underpinning BCR. We propose that sophisticated insight into the processes underlying BCR, and identification of key molecules mediating these beneficial effects, will pave the way for therapeutic advances targeting these currently incurable neurodegenerative diseases. (C) 2010 Elsevier Inc. All rights reserved.”
“The triphenyl amide/ester 12 was originally reported to be a potent mimic of the natural 3-oxo-dodecanoyl homoserine lactone quorum sensing molecule in Pseudomonas aeruginosa. However, explicit synthesis/chemical characterization was lacking, and a later
report providing protein crystallographic this website data inferred 12 to be incorrect, with 9 now being the surmised structure. Because of these inconsistencies and our interest in quorum sensing molecules utilized by Gram-negative bacteria, we found it necessary to synthesize 9 and 12 to test for agonistic activity in a P. aeruginosa reporter assay. Despite distinct regiochemical differences, both 9 and 12 were found to have comparable EC(50) values. To reconcile these unanticipated findings, modeling studies were conducted, and both compounds were revealed to have comparable properties for binding to the LasR receptor.”
“A series of mini-antibodies (monovalent and bivalent Fabs) targeting the conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR) of HIV-1 gp41 has been previously constructed and reported.
“Purpose of review\n\nImage-guided surgery (IGS) is a new type of surgery in which indirect visualization of the surgical anatomy helps the surgeon to enable minimally invasive percutaneous, laparoscopic, or robotic-aided treatment more precisely and safely, to
achieve complete tumor removal and sparing of the function of critical organs.\n\nRecent findings\n\nAlthough 2D ultrasonography has played a main role as conventional intraoperative image guidance, image-fusion system of ultrasonography with computed tomography (CT) or MRI, 3D ultrasonography imaging, MRI-compatible navigation system, and image-overlay technology of augmented reality navigation system have emerged with computer aid. Development of augmented reality in soft tissue navigation is challenging, especially in tracking of organ motion and deformation. In IGS, the surgeon may see any angled tomogram of the patient’s selleck chemicals selleck kinase inhibitor body, or 3D anatomies beyond the direct vision. IGS would not only provide the delivery of energy or medicines to the therapeutic target, but also monitor the precision and effectiveness of the treatment.\n\nSummary\n\nEmerging imaging technology gives surgeons a new powerful opportunity to realize where surgical pathological targets and vital healthy anatomies
are located beyond the surgeon’s direct vision.”
“OBJECTIVES: Since last decade, Saudi Arabia has been swiftly moving ahead to promote an education and research in the country. This study
aimed to investigate the research outcome of Saudi Arabia in medical sciences Pevonedistat mouse during the period 1996-2012. MATERIAL AND METHODS: In this study, the research papers published in various global science journals during the period 1996-2012 were accessed. We recorded the total number of research documents having an affiliation with Saudi Arabia. The main source for information was Institute of Scientific Information (ISI) Web of Science, Thomson Reuters and SCI-mago/Scopus. RESULTS: In global science data base, Saudi Arabia contributed 103804 documents in all science and social sciences. In medicine the total number of research papers from Saudi Arabia are 16196, citable documents 14732, total citations 102827, citations per documents 6.36 and Hirsch index (h-index) is 92. However, in combined medical and allied health sciences the total number of research papers are 27246, citable documents 25416, total citations 181999, mean citations per documents 7.07 and mean h-index is 41.44. Furthermore, Saudi Arabia contributed 40797 research documents in ISI indexed journals only and also 151 research documents in highly reputable and towering science journals. CONCLUSIONS: Saudi Arabia’s research performance in global medical sciences has markedly increased during the period 2006-2012.
Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity. Results: Forty two published studies were included in the current meta-analysis: BDNF-rs6265
(nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MA0A-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity. Conclusions: In terms of the number of candidate genes included, this is SN-38 one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.”
“Tight control of transposon activity is essential for the integrity of the germline. Recently, a germ-cell-specific organelle, nuage, was proposed KOS 1022 to play a
role in transposon repression. To test this hypothesis, we disrupted a murine homolog of a Drosophila nuage protein Maelstrom. Effects on male meiotic chromosome synapsis and derepression of transposable elements (TEs) were observed. In the adult Mael(-/-) testes, LINE-1 (L1) derepression occurred at the onset STI571 manufacturer of meiosis. As a result, Mael(-/-) spermatocytes were flooded with L1 ribonucleoproteins (RNPs) that accumulated in large cytoplasmic enclaves and nuclei. Mael(-/-) spermatocytes with nuclear L1 RNPs exhibited massive DNA damage and severe chromosome asynapsis even in the absence of SP011-generated meiotic double-strand breaks. This study demonstrates that MAEL, a nuage component, is indispensable for the silencing of TEs and identifies
the initiation of meiosis as an important step in TE control in the male germline.”
“MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) is commonly associated with the A3243G mitochondrial DNA (mtDNA) mutation encoding the transfer RNA of leucine (UUR) (tRNA (Le(UUR))). The pathogenetic mechanisms of this mutation are not completely understood. Neuronal functions are particularly vulnerable to alterations in oxidative phosphorylation, which may affect the function of the neurotransmitter glutamate, leading to excitotoxicity. In order to investigate the possible effects of A3243G upon glutamate homeostasis, we assessed glutamate uptake in osteosarcoma-derived cytoplasmic hybrids (cybrids) expressing high levels of this mutation. High-affinity Na+-dependent glutamate uptake was assessed as radioactive [H-3]-glutamate influx mediated by specific excitatory amino acid transporters (EAATs). The maximal rate (V-max) of Na+-dependent glutamate uptake was significantly reduced in all the mutant clones.
Our data suggest that IKVAV-PA may serve
as a potential therapeutic intervention LDN-193189 purchase for the learning and memory losses in AD. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Myeloid Translocation Gene, Related-1 (MTGR1) CBFA2T2 is a member of the Myeloid Translocation Gene (MTG) family of transcriptional corepressors. The remaining two family members, MTG8 (RUNX1T1) and MTG16 (CBFA2T3) are identified as targets of chromosomal translocations in acute myeloid leukemia (AML). Mtgr1(-/-) mice have defects in intestinal lineage allocation and wound healing. Moreover, these mice show signs of impaired intestinal stem cell function. Based on these phenotypes, we hypothesized that MTGR1 may influence tumorigenesis arising in an inflammatory background. We report that Mtgr1(-/-) mice were protected from tumorigenesis when injected with azoxymethane (AOM) and then subjected to repeated cycles of dextran sodium sulfate (DSS). Tumor cell proliferation was comparable, but Mtgr1(-/-) SB203580 tumors had significantly higher apoptosis rates. These phenotypes were dependent on epithelial injury, the resultant
inflammation, or a combination of both as there was no difference in aberrant crypt foci (ACF) or tumor burden when animals were treated with AOM as the sole agent. Gene expression analysis indicated that Mtgr1(-/-) tumors had significant upregulation of inflammatory networks, and immunohistochemistry (IHC) for immune cell subsets revealed a marked multilineage increase in infiltrates, consisting predominately of CD3(+) and natural killer T (NKT) cells as well as macrophages. selleck products Transplantation of wild type (WT) bone marrow into Mtgr1(-/-) mice, and the reciprocal transplant, did not alter the phenotype, ruling out an
MTGR1 hematopoietic cell-autonomous mechanism. Our findings indicate that MTGR1 is required for efficient inflammatory carcinogenesis in this model, and implicate its dysfunction in colitis-associated carcinoma. This represents the first report functionally linking MTGR1 to intestinal tumorigenesis. Cancer Res; 71(4); 1302-12. (C) 2011 AACR.”
“The CAP(2b) neuropeptide family plays an important role in the regulation of the processes of diuresis and/or antidiuresis in a variety of insects. While Manse-CAP(2b) (pELYAFPRV-NH2) and native CAP(2b)s elicit diuretic activity in a number of species of flies, native CAP(2b) sequences have been shown to elicit antidiuretic activity in the kissing bug Rhodnius prolixus and the green stink bug Acrosternum hilare, the latter being an important pest of cotton and soybean in the southern United States.
Step to step logistic regression to determine the effect of the quantitative data on the assignment to each subgroup.\n\nResults\n\nTwenty-four subjects were classified with MSOA. Among the 32 OHAO patients,
15 had bilateral hip OA and 17 had unilateral hip OA. The latter were classified with “Isolated hip OA” (IHOA). CPII levels were significantly lower in patients with MSOA than in those with OHOA EPZ5676 (99.9 +/- 50.3 ng/mL versus 141.9 +/- 81.2 ng/mL, p=0.04. OR=0.18 for CPII >120 ng/mL, p<0.005). C2C levels were also lower in MSOA (9.7 +/- 2.3 ng/mL) versus OHOA (11.4 +/- 3.2ng/mL, p=0.03. OR=0.26 for C2C >10 ng/mL, p=0.02). There was an inverse correlation between min JSW and C2C only in patients with IHOA (r=0.50, p=0.02).\n\nConclusion\n\nHip OA, in patients with MSOA, might be related to alteration in CII metabolism which may result in a deficient type II collagen repair process. The significant relationship between C2C and JSW in IHOA suggests that this marker is of value in assessing cartilage degradation patients with involvement of a single joint.”
and respiratory syndrome NCT-501 virus (PRRSV) genetic determinants affecting the response of the host primary target cell, the macrophage, to infection are yet to be defined. Here we have used recombinant viruses encompassing ORF 1A to identify PRRSV determinants associated with growth and modulation of pro- and anti-inflammatory cytokine expression in primary pulmonary alveolar macrophages (PAMs) cultures. Three genomic chimeras encompassing ORF 1A of PRRSV live attenuated vaccine Prime Pac (LAV SP) in the genetic background of pathogenic strain NVSL 97-7895 (FL12v) were characterized in vitro. Unlike parental viruses, two of the recombinant viruses encompassing the area of the genome encoding for NSP2 to NSP8 showed reduced growth in PAM cultures. The effect of virus infections on gene activation was studied for 25 immunomodulatory cellular genes in PAMs at 24 and 48 h post-infection (hpi). Steady state mRNA levels in PAMs infected with recombinant and LAV SP viruses
were compared to levels observed in cells infected with parental virus FL12v. Recombinant viruses induced patterns of transcriptional activation differing from patterns induced by Semaxanib parental FL12v, suggesting a regulatory role of PRRSV ORF1A on PAM gene expression. (C) 2009 Elsevier B.V. All rights reserved.”
“Background. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was originally identified as the third member of the TNF superfamily to induce apoptosis. TRAIL is normally expressed in many human tissues including kidney. Circulating soluble TRAIL is a negative marker for inflammation and is inversely associated with the mortality risk in chronic kidney disease patients. One increasingly prevalent complication in heart transplant recipients appears to be chronic kidney disease.\n\nMaterials and Methods.
Deregulated expression of the proto-oncogene MYC has been observed in melanoma, however whether MYC is involved in tumorigenesis in pigment cells has yet to be directly investigated in vivo. We have used our system to over-express MYC in the melanocytic compartment and show for the
first time that increased MYC expression can indeed promote melanocytic tumor formation.”
“Strains of Lactobacillus curvatus, Leuconostoc mesenteroides, Lactobacillus plantarum and Weissella confusa were identified from raw red and yellow peppers (RYPs) by partial 16S rRNA gene sequence and subjected to typing by selleck Random Amplified Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR) analysis. L plantarum PE21, L curvatus PE4 and W confusa PE36 were selected based on the kinetics of growth and acidification, and used as the autochthonous mixed starter for the fermentation of RYPs. A protocol
which included blanching at 85 degrees C for 2 min. fermentation at 35 degrees C for 15 h in brine (1%, w/v), and heat treatment at 85 degrees C for 15 min, followed by storage at room temperature for 30 days with and without sunflower seeds oil was set up. Unstarted RYPs subjected to the same treatments URMC-099 were used as the control. Cell numbers of autochthonous starter in the RYPs were ca. 1000 times higher than presumptive lactic acid bacteria in unstarted RYPs, As shown by RAPD-PCR analysis, all three autochthonous strains persisted during processing and storage. Presumptive lactic acid bacteria found in started RYPs progressively decreased during storage. leading to a microbiota mainly consisting of autochthonous starters. Started RYPs showed rapid decrease of pH (<33), marked consumption of fermentable carbohydrates, and inhibition of total enterobacteria and yeasts.
Unstarted RYPs were subjected to slight acidification (pH ca. 4.87) and considerable contamination by total enterobacteria and yeasts throughout storage. After 30 days of storage, started RYPs had significantly Metabolism inhibitor (P<0.05) higher firmness and colour indexes with respect to unstarted RYPs. The microbial and sensory features of started RYPs stored with sunflower seeds oil were almost similar to those of RYPs stored without suspending liquid. (C) 2009 Elsevier B.V. All rights reserved.”
“The genetic diversity and relationship amongst the bacterial populations were determined in fresh salad samples (Tabbouleh, Fattoush, Hummus, Mutabbel and Caesar) collected from various restaurants located in five different areas (west, north, south, east and center) in Riyadh (the capital city of Saudi Arabia). Isolated colonies found were identified via molecular methods. Total number of identified isolates in the vegetable salads Tabbouleh, Fattoush, Mutabbel, Hummus and Caesar were 24, 20, 18, 16 and 12, respectively. Pseudomonas sp.
5 degrees C during hot matches but reduced the volume of running undertaken, thus preserving the ability to undertake high intensity activities. (C) 2013 Published by Elsevier Ltd on behalf of Sports Medicine
“Laser therapy and fluorescence-guided surgery are highly reliable and predictable methods, but their combination has not been found to yield useful outcomes. We present a new therapeutic approach combining fluorescence-guided Er:YAG laser ablation with Nd:YAG/ diode laser biostimulation for bisphosphonate-related AZD0530 cell line osteonecrosis of the jaw (BRONJ). A woman was treated with zoledronic acid for bone metastasis from clear cell renal cell carcinoma and subsequently developed BRONJ in the left jaw. The management protocol included perioperative medical therapy (1% chlorhexidine gel, rifamycin, and doxycycline for 10 preoperative and 7 postoperative days), Er:YAG laser ablation guided by doxycycline fluorescence in vital bone under UV light, and Nd:YAG/diode laser biostimulation. The lesion regressed from stage 3 to stage 1 and showed nearly complete healing after laser therapy (3 and 23 cycles of ablation C59 Wnt order and biostimulation, respectively). These preliminary findings suggest the feasibility of the new approach, which is minimally invasive and biostimulative
and causes very low morbidity.”
“Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell
differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their learn more equilibrium positions, under the apparent constraint of a radial restoring force of similar to 0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles’ confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them.”
“Objective: Only little is known about the mechanisms of action of corticosteroids in the treatment of inflammatory liver diseases.
Six hours after injury, the animals check details were euthanatized and perfusion fixed, and the brain and eyes were harvested for gross and histopathologic examination by masked neuro-and ocular pathologists.\n\nRESULTS. Ocular hemorrhage was found in 73% of animals (51% bilateral). Intraocular hemorrhage was primarily located near the vitreous base (70% of injured animals had ciliary body hemorrhage, and 11% had peripheral retinal hemorrhage). Hemorrhages were also found in the anterior chamber (11%),
vitreous (5%), and optic nerve (disc, 8%; nerve sheath, 57%). Rapid axial head rotations resulted in a higher incidence of intraocular hemorrhage than coronal or sagittal head rotations, but the difference did not reach statistical significance (P = 0.06). Control eyes had no injuries.\n\nCONCLUSIONS. Optic nerve sheath and ciliary body hemorrhages were common in piglets that experienced a single, rapid head rotation. Retinal hemorrhage was present in a smaller number of animals. Most intraocular hemorrhages were located in regions of strong vitreous attachment, suggesting that this animal model
will be useful in investigating the effect of vitreoretinal adhesion on ocular hemorrhage caused by inertial head rotations. Extrapolation of this model to the human infant should not be made until the effect of anatomic differences between the human and pig on the occurrence and patterns of ocular injuries is further investigated. (Invest Ophthalmol Vis Sci. 2010;51:4792 -4797) DOI:10.1167/iovs.10-5211″
“Background. Few studies have examined spontaneous remission from major depression. CT99021 solubility dmso This study investigated the proportion of prevalent cases of untreated major depression that will remit without treatment in a year, and whether remission rates vary by disorder severity.\n\nMethod. Wait-list controlled trials and observational
cohort Bindarit clinical trial studies published up to 2010 with data describing remission from untreated depression at <= 2-year follow-up were identified. Remission was defined as rescinded diagnoses or below threshold scores on standardized symptom measures. Nineteen studies were included in a regression model predicting the probability of 12-month remission from untreated depression, using logit transformed remission proportion as the dependent variable. Covariates included age, gender, study type and diagnostic measure.\n\nResults. Wait-listed compared to primary-care samples, studies with longer follow-up duration and older adult compared to adult samples were associated with lower probability of remission. Child and adolescent samples were associated with higher probability of remission. Based on adult samples recruited from primary-care settings, the model estimated that 23% of prevalent cases of untreated depression will remit within 3 months, 32% within 6 months and 53% within 12 months.\n\nConclusions.
The Se concentration correlated with the Hg concentration in the livers and kidneys, and with the Cd concentration in the kidneys. The Hg and Cd levels correlated in the three tissue groups. The Cu and Zn levels also correlated in the livers and kidneys. In general, the element concentrations were within the ranges reported by previous studies
of this species from European countries, except for Cd and Hg, the levels of which were mostly lower than those reported previously. These findings may provide selleck kinase inhibitor baseline information to facilitate the conservation of the Eurasian otter. To the best of our knowledge, this is the first available study of trace element concentrations in the tissues of Eurasian otters from South Korea or Asian countries.”
“Strontium stimulates cartilage matrix formation in vitro. Prexasertib However, the mechanisms governing these effects have not yet been extensively
reported. In this study, chondrocytes were isolated from rat articular cartilage by enzymatic digestion and cultured for 24-72 h with 1-5 mM strontium. We investigated the effects of different concentrations of strontium on collagen content, type II collagen, insulin-like growth factor (IGF-1) and matrix metalloproteinase (MMP)-13 expression in rat cultured articular chondrocytes in vitro. The collagen content of the chondrocytes, determined as hydroxyproline, was measured by a colorimetry method. Type II collagen, IGF-1, and MMP-13 mRNA abundance and protein expression levels were determined by real-time polymerase chain reaction (real-time PCR) and western Selleck Lonafarnib blot, respectively. The results showed that collagen content from the chondrocytes extracellular matrix
increased with increasing strontium concentration. Moreover, 3 and 5 mM strontium strongly stimulated protein expression and mRNA levels of type II collagen and IGF-1. Conversely, MMP-13 expression in chondrocytes decreased dose-dependently with increasing strontium concentration. These results should provide insight into the ability of strontium to promote chondrocyte extracellular matrix synthesis. Strontium could promote collagen synthesis and suppress collagen degradation via the repression of MMP-13 expression.”
“Here we describe the purification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from normal leukocytes of healthy subjects and leukocytes of chronic myeloid leukemia (CML) patients and from normal mouse muscle and sarcoma tissue. The data indicate that some properties of GAPDH of leukocytes of CML patients and sarcoma tissues are similar and also similar to those of EAC (Ehrlich ascites carcinoma) cellular GAPDH but distinctly different from those of the normal cellular GAPDH.
Subcapsular FFCHs immunoreactive at the capsular front for 3-deazaneplanocin A tenascin-C, a tumor invasion marker of extracellular matrix protein, showed
high proliferation activity.\n\nSubcapsular FFCH-forming cells can potentially spread directly into the fibrously thickened capsule to form CICs by accelerating cell-cycle activity.”
“We established a novel screening method to survey endocrine-disrupting chemicals by means of in silica, docking calculations. Endocrine disruptors target the human nuclear receptor, which bind a chemical in a pocket presenting in the ligand-binding domain (LBD). The LBD alters its conformation, depending upon the binding of either agonist or antagonist. We discovered that the chemicals Vorinostat order can be differentiated into either agonist or antagonist by the docking calculations of the chemical for the LBD. We used the crystal structures of both agonist-bound LBDs and antagonist-bond LBDs as templates in the docking calculations, and estimated binding energies to discriminate between agonist and antagonist bindings. This agonist/antagonist differential-docking screening (AADS)
method predicted, for example, 4-(1-adamantyl)phenol as an agonist of the human estrogen receptor alpha (hER alpha). Indeed, this compound, one of the essential raw materials for nanoporous organosilicate thin films, was confirmed to exhibit strong agonist activity in the reporter-gene assay for hER alpha with a high binding affinity. The AADS method is an approach that appears to foresee both the binding ability and the agonist/antagonist function of chemicals for Bcl-2 apoptosis the target nuclear receptors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Background: Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1). Little is known about the function of human RAI1.\n\nResults:
We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity.