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Public parental leave schemes aim to facilitate women's reconciliation of family and employment after their transition into motherhood. While parental leave policies underwent several reforms over the past decades, adapting to changing female labour market participation and family cultures, the available entitlements are not tailored to women's individual circumstances and needs. It remains unclear how these affect the women's parental leave uptake, particularly the leave length. In this paper, we followed an exploratory and descriptive approach to study the selection of women into different parental leave lengths with changing public parental leave entitlements in Germany and according to their individual characteristics. We use data from the German Statutory Pension Fund on 29,001 women born between 1955 and 1984 who had their first child between 1991 and 2016 at the ages 20–39. We estimate linear regression and discrete-time proportional hazard models to examine associations between women's characteristics and their length of leave. We identify the effects of two major parental leave reforms in Germany in 1992 and 2007 in a Regression Discontinuity Design. Our results show that the general extension of available parental leave entitlements in 1992 increased the likelihood of women's parental leave uptake between 25 and 36 months. For women who became mothers at an older age, had a high income before transitioning into motherhood, or with higher education; however, the likelihood of parental leave uptake of 2 months increased. The reform of 2007 led to an increased likelihood of leave uptake longer than 2 months for these women. These findings suggest that women with a higher labour market attachment have responded more strongly to the changes in parental leave benefits in Germany. [ABSTRACT FROM AUTHOR]

Retinoblastoma are childhood eye tumors arising from retinal precursor cells. Two distinct retinoblastoma subtypes with different clinical behavior have been described based on gene expression and methylation profiling. Using consensus clustering of DNA methylation analysis from 61 retinoblastomas, we identify a MYCN-driven cluster of subtype 2 retinoblastomas characterized by DNA hypomethylation and high expression of genes involved in protein synthesis. Subtype 2 retinoblastomas outside the MYCN-driven cluster are characterized by high expression of genes from mesodermal development, including NKX2-5. Knockdown of MYCN expression in retinoblastoma cell models causes growth arrest and reactivates a subtype 1-specific photoreceptor signature. These molecular changes suggest that removing the driving force of MYCN oncogenic activity rescues molecular circuitry driving subtype 1 biology. The MYCN-RB gene signature generated from the cell models better identifies MYCN-driven retinoblastoma than MYCN amplification and can identify cases that may benefit from MYCN-targeted therapy. MYCN drives tumor progression in a molecularly defined retinoblastoma subgroup, and inhibiting MYCN activity could restore a more differentiated and less aggressive tumor biology. DNA methylation analysis identifies a MYCN-driven subgroup of aggressive retinoblastoma that may benefit from MYCN-targeted therapy. [ABSTRACT FROM AUTHOR]

Purpose: In recent decades, Europe has seen a steady increase in psychiatric diagnoses, which, besides affecting the population in many ways, also challenges the organization of welfare. This paper explores how welfare classification processes impact the contemporary production of mental (ill) health and social inequality in the German welfare state. Methods: Based on comprehensive ethnographic research in the public mental healthcare landscape in Berlin between 2011 and 2017, this paper discusses in detail the case of a mandatory prescription of a psychosocial rehabilitation measure for Ms Reisch, a psychiatric service user and ethnographic research partner. The analysis draws on the methodological approach of praxeography to examine how this case challenges the social determinants of mental health framework and the conceptual work of the sociology of inequality on which the categories of welfare are largely built. Results: The paper highlights the essentializing properties of social categories, whether in the sociology of inequality or in social and mental health policy. It also demonstrates the strength of praxeography to expose how multiple welfare categorization processes shape experiences and events of dis/ability in practice, potentially contradicting the stated intentions of social policy. Conclusion: The results suggest that the attachment of categories to people in public welfare needs to be changed to make public administration more flexible to responding to the situated processes that bring about differentiations of equal and unequal in practice. The paper, therefore, encourages social inquiry into the potentialities of a post-categorical social policy framework. [ABSTRACT FROM AUTHOR]

Purpose: Severe cartilage damage and advanced knee osteoarthritis (OA) might be associated with poor outcomes of meniscal allograft transplantation (MAT). The purpose of this prospective follow-up study was to explore MAT survivorship and patient satisfaction among young patients with symptomatic meniscal deficiency and radiological OA of different Kellgren–Lawrence (K–L) grades. Methods: Thirty-five consecutive MAT patients were prospectively followed up for 2 years. The lateral meniscus was replaced in 29 patients and the medial meniscus in 6 patients. Outcomes were assessed using the KOOS4 composite score, KOOS subscales, Lysholm knee score, and OA K–L grade progression from weight-bearing knee radiographs. For the outcome analysis, patients were categorized into two groups: 19 in Group A (K–L classification 0–1) and 16 in Group B (K–L classification 2). Results: In terms of KOOS4 and Lysholm scores, the patients showed a clinically significant improvement from baseline to the 1-year follow-up (22.2 points, 95% CI 16.6–27.8 for KOOS4 and 16.8 points, 95% CI 8.9–24.6 for Lysholm), and the improvement remained at 2 years (20.6 points, 95% CI 13.2–28.1 for KOOS4 and 21.5, 95% CI 12.5–30.7 for Lysholm). At the 6-month follow-up, this improvement was not yet observed. Minor between-group differences were observed in the KOOS4 and Lysholm scores for the K–L 0–1 and K–L 2 OA groups, but the estimates were imprecise with wide confidence intervals. A clinically relevant difference between these two study groups could not be found at any timepoint. The reoperation rate was higher in the K–L 2 group than in the K–L 0–1 group (31% vs. 11%). Conclusions: MAT yielded improved patient-reported outcomes and subjective satisfaction at 1 and 2 years postoperatively. The differences from baseline exceeded the minimal clinically important difference (MCID) at all timepoints. The severity of cartilage damage and knee OA in terms of the K–L grade at the time of surgery did not affect the KOOS and Lysholm scores after the MAT procedure. Knee OA progression in terms of K–L grade worsening was not observed in any patients. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Purpose of the Study: Femoral neck fracture osteosynthesis is usually performed by using dynamic hip screw (DHS) or multiple parallel cannulated screws (MCS). In orthopedic surgery training, certain hip fractures are one of the most common operations performed by residents. It has been questioned, whether residents can provide as safe treatment and patient outcomes as those of more experienced surgeons. The aim of this study was to evaluate the effect of surgical experience on risk of complications by comparing the surgical performance and clinical outcomes in femoral neck osteosyntheses between surgical residents and orthopaedic surgeons. Methods: All patients with femoral neck fracture admitted to Helsinki and Uusimaa Hospital District (HUS) Hyvinkää Hospital from 2011 to 2016 were collected as research material. 88 hip fractures (87 patients) treated with DHS or MCS osteosyntheses were included in this study. The patients were divided into 2 groups, based on the surgeon's experience: an orthopedic surgeon group (n = 68) and a surgical resident group (n = 20). All data from complications, reoperations, and the duration of operations were collected. Results: There was no significant difference in characteristics of operated patients between orthopaedics and residents group. There was no significant difference in complications or re-operations between groups (p = 0.4, p = 0.2). Surgical residents had statistically longer surgical time (mean 76 min, 95% CI 62.92 min, mean 46 min, 95% Cl 42.51 min; p-value < 0.001). Still surgical time was not a risk factor for complication (p-value 0.5). Conclusion: Our results show that surgical residents´ outcomes in femoral neck fracture osteosynthesis seem to be as favorable as those of orthopedic surgeons; the operations just last slightly longer. [ABSTRACT FROM AUTHOR]

In this work, uranium-and plutonium-baring particles were produced by fast iron co-precipitation for the purpose of creating homogeneous multi-element standards. A set of single isolated particles showing no inhomogeneities in the element distribution were selected. These particles were used to determine the maximal achievable suppression ratios for uranium in Resonant Laser Secondary Neutral Mass Spectrometry (rL-SNMS) measurements of plutonium. It was shown for the first time directly that suppression-ratios in the order of three magnitudes are achievable with a resonant two-step excitation scheme for non-destructive measurements. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma" published in Communications Biology. The correction addresses an error in the spelling of the author's name, Hanenberg, which was incorrectly written as Hannenberg. The original article has been corrected. The authors of the article are Tatsiana Ryl, Elena Afanasyeva, Till Hartmann, Melanie Schwermer, Markus Schneider, Christopher Schröder, Maren Wagemanns, Arthur Bister, Deniz Kanber, Laura Steenpass, Kathrin Schramm, Barbara Jones, David T. W. Jones, Eva Biewald, Kathy Astrahantseff, Helmut Hanenberg, Sven Rahmann, Dietmar R. Lohmann, Alexander Schramm, and Petra Ketteler. [Extracted from the article]

The inference of physical parameters from measured distributions constitutes a core task in physics data analyses. Among recent deep learning methods, so-called conditional invertible neural networks provide an elegant approach owing to their probability-preserving bijective mapping properties. They enable training the parameter-observation correspondence in one mapping direction and evaluating the parameter posterior distributions in the reverse direction. Here, we study the inference of cosmic-ray source properties from cosmic-ray observations on Earth using extensive astrophysical simulations. We compare the performance of conditional invertible neural networks (cINNs) with the frequently used Markov Chain Monte Carlo (MCMC) method. While cINNs are trained to directly predict the parameters' posterior distributions, the MCMC method extracts the posterior distributions through a likelihood function that matches simulations with observations. Overall, we find good agreement between the physics parameters derived by the two different methods. As a result of its computational efficiency, the cINN method allows for a swift assessment of inference quality. [ABSTRACT FROM AUTHOR]

The c-myc protooncogene encodes the Myc transcription factor, a global regulator of fundamental cellular processes. Deregulation of c-myc leads to tumorigenesis, and c-myc is an important driver in human cancer. Myc and its dimerization partner Max are bHLH-Zip DNA binding proteins involved in transcriptional regulation of target genes. Non-transcriptional functions have also been attributed to the Myc protein, notably direct interaction with the pre-replicative complex (pre-RC) controlling the initiation of DNA replication. A key component of the pre-RC is the CdT1 protein, an essential factor in origin licensing. Here we present data suggesting that the CDT1 gene is a transcriptional target of the Myc-Max complex. Expression of the CDT1 gene in v-myc-transformed cells directly correlates with myc expression. Also, human tumor cells with elevated c-myc expression display increased CDT1 expression. Occupation of the CDT1 promoter by Myc-Max is demonstrated by chromatin immunoprecipitation, and transactivation by Myc-Max is shown in reporter assays. Ectopic expression of CDT1 leads to cell transformation. Our results provide a possible direct mechanistic link of Myc's canonical function as a transcription factor to DNA replication. Furthermore, we suggest that aberrant transcriptional activation of CDT1 by deregulated myc alleles contributes to the genomic instabilities observed in tumor cells. [ABSTRACT FROM AUTHOR]

The contamination of Japan after the Fukushima accident has been investigated mainly for volatile fission products, but only sparsely for actinides such as plutonium. Only small releases of actinides were estimated in Fukushima. Plutonium is still omnipresent in the environment from previous atmospheric nuclear weapons tests. We investigated soil and plants sampled at different hot spots in Japan, searching for reactor-borne plutonium using its isotopic ratio 240Pu/239Pu. By using accelerator mass spectrometry, we clearly demonstrated the release of Pu from the Fukushima Daiichi power plant: While most samples contained only the radionuclide signature of fallout plutonium, there is at least one vegetation sample whose isotope ratio (0.381 ± 0.046) evidences that the Pu originates from a nuclear reactor (239+240Pu activity concentration 0.49 Bq/kg). Plutonium content and isotope ratios differ considerably even for very close sampling locations, e.g. the soil and the plants growing on it. This strong localization indicates a particulate Pu release, which is of high radiological risk if incorporated. [ABSTRACT FROM AUTHOR]

The oncogenic transcription factor Myc is one of the most interesting members of the basic-helix-loop-helix-zipper (bHLHZip) protein family. Deregulation of Myc via gene amplification, chromosomal translocation or other mechanisms lead to tumorigenesis including Burkitt lymphoma, multiple myeloma, and many other malignancies. The oncogene myc is a highly potent transforming gene and capable to transform various cell types in vivo and in vitro. Its oncogenic activity initialized by deregulated expression leads to a shift of the equilibrium in the Myc/Max/Mad network towards Myc/Max complexes. The Myc/Max heterodimerization is a prerequisite for transcriptional functionality of Myc. Primarily, we are focusing on the apo-state of the C-terminal domain of v-Myc, the retroviral homolog of human c-Myc. Based on multi-dimensional NMR measurements v-Myc appears to be neither a fully structured nor a completely unstructured protein. The bHLHZip domain of v-Myc does not exist as a random coil but exhibits partially pre-formed α-helical regions in its apo-state. In order to elucidate the structural propensities of Myc in more detail, the backbone and side-chain assignments obtained here for apo-Myc are a crucial prerequisite for further NMR measurements. [ABSTRACT FROM AUTHOR]

The Mulde River is a left side tributary of the Elbe River and mainly situated in Saxony. The river system consists of the Freiberger Mulde River and the Zwickauer Mulde River, which merge to form the Vereinigte Mulde River. The Zwickauer Mulde River drains the former uranium mining and milling areas in Saxony. This research project was established to quantify the long-term effect of the former uranium mining and milling activities by investigating the content of uranium of the water of the Mulde River. The activity concentration of uranium in samples from the Zwickauer Mulde River is still high compared with the natural background. The values measured in the water of the Vereinigte Mulde River are also elevated, but to a lesser extent due to the dilution effect caused by the merging with the uncontaminated Freiberger Mulde River. Furthermore, the level of contamination of the river water decreased by at least a factor of three as compared to the early 1990s. [ABSTRACT FROM AUTHOR]

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Feature selection is a task of great importance. Many feature selection methods have been proposed, and can be divided generally into two groups based on their dependence on the learning algorithm/classifier. Recently, a feature selection method that selects features at the same time as it evolves neural networks that use those features as inputs called Feature Selective NeuroEvolution of Augmenting Topologies (FS-NEAT) was proposed by Whiteson et al. In this paper, a novel feature selection method called Feature Deselective NeuroEvolution of Augmenting Topologies (FD-NEAT) is presented. FD-NEAT begins with fully connected inputs in its networks, and drops irrelevant or redundant inputs as evolution progresses. Herein, the performances of FD-NEAT, FS-NEAT and traditional NEAT are compared in some mathematical problems, and in a challenging race car simulator domain (RARS). On the whole, the results show that FD-NEAT significantly outperforms FS-NEAT in terms of network performance and feature selection, and evolves networks that offer the best compromise between network size and performance. [ABSTRACT FROM AUTHOR]

We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc–Max complex and a binding site for transcription factor C/EBPα. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPα bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPα-binding site are essential for strong transcriptional activation, and that Myc and C/EBPα synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.Oncogene (2007) 26, 1769–1779. doi:10.1038/sj.onc.1209975; published online 11 September 2006 [ABSTRACT FROM AUTHOR]

Avian fibroblasts transformed simultaneously by the v-myc and v-mil(raf) oncogenes of acute leukemia and carcinoma virus MH2 contain elevated levels of c-Fos and c-Jun, major components of the transcription factor complex AP-1. To define specific transcriptional targets in these cells, subtractive hybridization techniques were employed leading to the identification of strongly upregulated genes including OPN (osteopontin), 126MRP, and rac2. OPN is a cytokine and cell attachment protein which has been implicated in human tumor progression and metastasis, the calcium binding 126MRP protein is related to the human S100 protein family involved in invasive cell growth, and the Rac2 protein belongs to the Rho family of small GTPases regulating actin reorganization and cell migration. Promoter analysis indicated that OPN activation is mediated by a non-consensus AP-1 binding site located close to the transcription start site. Electrophoretic mobility shift assays, chromatin immunoprecipitation and transcriptional reporter gene analyses showed that c-Fos and c-Jun bind specifically to this site and that c-Fos efficiently transactivates the OPN promoter. High-level expression of OPN, 126MRP, or Rac2 proteins from a retroviral vector led to partial cell transformation, documented by morphological changes and anchorage-independent growth. The specific activation in v-myc/v-mil(raf)-transformed cells of target genes with intrinsic oncogenic potential may provide an explanation for the longstanding observation that concomitant expression of these oncogenes leads to strongly enhanced oncogenicity in vivo and in vitro compared to cell transformation by v-myc or v-mil(raf) alone.Oncogene (2006) 25, 4043–4055. doi:10.1038/sj.onc.1209441; published online 20 February 2006 [ABSTRACT FROM AUTHOR]

Increased inter-equipment connectivity coupled with advances in Web technology allows ever escalating amounts of physiological data to be produced, far too much to be displayed adequately on a single computer screen. The consequence is that large quantities of insignificant data will be transmitted and reviewed. This carries an increased risk of overlooking vitally important transients. This paper describes a technique to provide an integrated solution based on a single algorithm for the efficient analysis, compression and remote display of long-term physiological signals with infrequent short duration, yet vital events, to effect a reduction in data transmission and display cluttering and to facilitate reliable data interpretation. The algorithm analyses data at the server end and flags significant events. It produces a compressed version of the signal at a lower resolution that can be satisfactorily viewed in a single screen width. This reduced set of data is initially transmitted together with a set of ‘flags’ indicating where significant events occur. Subsequent transmissions need only involve transmission of flagged data segments of interest at the required resolution. Efficient processing and code protection with decomposition alone is novel. The fixed transmission length method ensures clutter-less display, irrespective of the data length. The flagging of annotated events in arterial oxygen saturation, electroencephalogram and electrocardiogram illustrates the generic property of the algorithm. Data reduction of 87% to 99% and improved displays are demonstrated. [ABSTRACT FROM AUTHOR]

This paper attempts to improve the diagnostic quality of magnetic resonance (MR) images through application of lossy compression as a noise-reducing filter. The amount of imaging noise present in MR images is compared with the amount of noise introduced by the compression, with particular attention given to the situation where the compression noise is a fraction of the imaging noise. A popular wavelet-based algorithm with good performance, Set Partitioning in Hierarchical Trees (SPIHT), was employed for the lossy compression. Tests were conducted with a number of MR patient images and corresponding phantom images. Different plausible ratios between imaging noise and compression noise (ICR) were considered, and the achievable compression gain through the controlled lossy compression was evaluated. Preliminary results show that at certain ICR’s, it becomes virtually impossible to distinguish between the original and compressed–decompressed image. Radiologists presented with a blind test, in certain cases, showed preference to the compressed image rather than the original uncompressed ones, indicating that under controlled circumstances, lossy image compression can be used to improve the diagnostic quality of the MR images. [ABSTRACT FROM AUTHOR]

Salmochelins represent novel carbohydrate containing catecholate siderophores, which are excreted by Salmonella enterica and uropathogenic Escherichia coli strains under low-iron stress. While previous analytical data showed salmochelins to contain 2,3-dihydroxybenzoyl-L-serine and glucose, the molecular structure remained elusive. Structure elucidation with electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), GC-MS and 2D-NMR now revealed that salmochelins are enterobactin-related compounds, which are ß-C-glucosylated at the 5-position of a 2,3-dihydroxybenzoyl residue. The key compound salmochelin S4 is a twofold ß-C-glucosylated enterobactin analogue. Comparison of partial structures of salmochelin with a C-glycosylated compound previously characterized by another group strongly suggest that salmochelins represent the long sought compounds termed Salmonella resistance factors (SRF) or pacifarins. Transformation of iro-genes into enterobactin-producing E. coli K12 confers the ability to produce salmochelins. A detailed analysis proved iroB to be the sole gene with glycosyltransferase activity necessary for salmochelin production. Salmochelins compared to enterobactin are the better siderophores in the presence of serum albumin. This may indicate for salmochelins a considerably more important role for pathogenic processes in certain Escherichia coli and Salmonella infections than formerly assigned to enterobactin. This conclusion is supported by the location of the iro genes on pathogenicity islands of uropathogenic E. coli strains. [ABSTRACT FROM AUTHOR]

Salmochelins represent novel carbohydrate containing catecholate siderophores, which are excreted by Salmonella enterica and uropathogenic Escherichia coli strains under low-iron stress. While previous analytical data showed salmochelins to contain 2,3-dihydroxybenzoyl-L-serine and glucose, the molecular structure remained elusive. Structure elucidation with electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), GC-MS and 2D-NMR now revealed that salmochelins are enterobactin-related compounds, which are β-C-glucosylated at the 5-position of a 2,3-dihydroxybenzoyl residue. The key compound salmochelin S4 is a twofold β-C-glucosylated enterobactin analogue. Comparison of partial structures of salmochelin with a C-glycosylated compound previously characterized by another group strongly suggest that salmochelins represent the long sought compounds termed Salmonella resistance factors (SRF) or pacifarins. Transformation of iro-genes into enterobactin-producing E. coli K12 confers the ability to produce salmochelins. A detailed analysis proved iroB to be the sole gene with glycosyltransferase activity necessary for salmochelin production. Salmochelins compared to enterobactin are the better siderophores in the presence of serum albumin. This may indicate for salmochelins a considerably more important role for pathogenic processes in certain Escherichia coli and Salmonella infections than formerly assigned to enterobactin. This conclusion is supported by the location of the iro genes on pathogenicity islands of uropathogenic E. coli strains. [ABSTRACT FROM AUTHOR]

Several matrix metalloproteinases (MMPs) have been implicated in intestinal inflammation, mucosal wound healing, and cancer progression. The purpose of this study was to examine the cellular location and putative function of MMP-19, MMP-26 (matrilysin-2), and MMP-28 (epilysin), in normal, inflammatory, and malignant conditions of the intestine. Peroperative tissue specimens from patients with ulcerative colitis (UC) (n = 16) and archival tissue samples of ischemic colitis (n = 9), Crohn's disease (n = 7), UC (n = 8), colon cancer (n = 20), and healthy intestine (n = 5) were examined using immunohistochemical analyses with polyclonal antibodies. Unlike many classical MMPs, MMP-19, MMP-26, and MMP-28 were all expressed in normal intestine. In inflammatory bowel disease (IBD), MMP- 19 was expressed in nonmigrating enterocytes and shedding epithelium. MMP-26 was detected in migrating enterocytes, unlike MMP-28. In colon carcinomas, MMP-19 and MMP-28 expression was downregulated in tumor epithelium. Staining for MMP-26 revealed a meshwork-like pattern between cancer islets, which was absent from most dedifferentiated areas. Our results suggest that MMP-19 is involved in epithelial proliferation and MMP-26 in enterocyte migration, while MMP-28 expression is not associated with inflammatory and destructive changes seen in IBD. In contrast to many previously characterized MMPs, MMP-19 and MMP-28 are downregulated during malignant transformation of the colon and may play a prominent role in tissue homeostasis. [ABSTRACT FROM AUTHOR]

Several matrix metalloproteinases (MMPs) have been implicated in intestinal inflammation, mucosal wound healing, and cancer progression. The purpose of this study was to examine the cellular location and putative function of MMP-19, MMP-26 (matrilysin-2), and MMP-28 (epilysin), in normal, inflammatory, and malignant conditions of the intestine. Peroperative tissue specimens from patients with ulcerative colitis (UC) (n = 16) and archival tissue samples of ischemic colitis (n = 9), Crohn's disease (n = 7), UC (n = 8), colon cancer (n = 20), and healthy intestine (n = 5) were examined using immunohistochemical analyses with polyclonal antibodies. Unlike many classical MMPs, MMP-19, MMP-26, and MMP-28 were all expressed in normal intestine. In inflammatory bowel disease (IBD), MMP-19 was expressed in nonmigrating enterocytes and shedding epithelium. MMP-26 was detected in migrating enterocytes, unlike MMP–28. In colon carcinomas, MMP-19 and MMP-28 expression was downregulated in tumor epithelium. Staining for MMP-26 revealed a meshwork-like pattern between cancer islets, which was absent from most dedifferentiated areas. Our results suggest that MMP-19 is involved in epithelial proliferation and MMP-26 in enterocyte migration, while MMP-28 expression is not associated with inflammatory and destructive changes seen in IBD. In contrast to many previously characterized MMPs, MMP-19 and MMP-28 are downregulated during malignant transformation of the colon and may play a prominent role in tissue homeostasis. [ABSTRACT FROM AUTHOR]

Using the established quail cell line Q/d3 conditionally transformed by the v-jun oncogene, cDNA clones (TOJ2, TOJ3, TOJ5, TOJ6) were isolated by representational difference analysis (RDA) that correspond to genes which were induced immediately upon conditional activation of v-jun. One of these genes, TOJ3, is immediately and specifically activated after doxycycline-mediated v-jun induction, with kinetics similar to the induction of well characterized direct AP-1 target genes. TOJ3 is neither activated upon conditional activation of v-myc, nor in cells or cell lines non-conditionally transformed by oncogenes other than v-jun. Sequence analysis revealed that the TOJ3-specific cDNA encodes a 530-amino acid protein with significant sequence similarities to the murine or human microspherule protein 1 (MCRS1, MSP58), a nucleolar protein that directly interacts with the ICP22 regulatory protein from herpes simplex virus 1 or with p120, a proliferation-related protein expressed at high levels in most human malignant tumor cells. Similar to its mammalian counterparts, the TOJ3 protein contains a bipartite nuclear localization motif and a forkhead associated domain (FHA). Using polyclonal antibodies directed against a recombinant amino-terminal TOJ3 protein segment, the activation of TOJ3 in jun-transformed fibroblasts was also demonstrated at the protein level by specific detection of a polypeptide with an apparent Mr of 65 000. Retroviral expression of the TOJ3 gene in quail or chicken embryo fibroblasts induces anchorage-independent growth, indicating that the immediate activation of TOJ3 in fibroblasts transformed by the v-jun oncogene contributes to cell transformation. Oncogene (2001) 20, 7524–7535. [ABSTRACT FROM AUTHOR]

The BKJ gene was originally identified based on its specific transcriptional activation in jun-transformed avian fibroblasts. We now show that BKJ is a direct transcriptional target of the AP-1 transcription factor components Jun and Fos. The complete structural organization of the quail BKJ gene was determined by nucleotide sequence analysis and transcriptional mapping. The gene contains three exons with the coding region confined to the third exon. A major mRNA species of 0.8 kb and a minor one of 1.3 kb are produced by variable usage of two transcriptional initiation sites. The BKJ promoter region contains two authentic AP-1 binding sites. By transactivation of reporter gene constructs and direct binding of Jun recombinant protein, the proximal AP-1 element was shown to be essential for BKJ promoter activation. Using polyclonal antiserum directed against recombinant BKJ protein, the activation of BKJ in jun-transformed avian fibroblasts was also demonstrated at the protein level. BKJ is a novel gene related to the avian β-keratin gene family whose members display highly specific expression patterns during embryogenesis and epidermal development. Activation of BKJ in fibroblasts by retroviral or deregulated cellular jun or fos alleles may contribute to cell transformation. [ABSTRACT FROM AUTHOR]

Gene expression patterns in normal and v-myc-transformed quail embryo fibroblasts were compared by mRNA differential display. Displaying approximately 2500 mRNA species by reverse transcription/PCR, reamplification of 73 differential cDNA fragments and rescreening by Northern analysis led to the isolation of a clone, termed CO6, that hybridized to an mRNA species present only in the normal but not in the transformed fibroblasts. Further analyses revealed that the 0.95-kb CO6 mRNA was present in all normal quail and chicken embryo fibroblasts tested, but that it was undetectable in a variety of established quail cell lines transformed by the v-myc, v-myc/v-mil, v-jun/junD or v-src oncogenes or by a chemical carcinogen. Furthermore, CO6 mRNA was not detectable in fibroblasts newly transformed by retroviral constructs carrying v-myc or v-jun alleles or by the avian sarcoma virus ASV17. In fibroblasts transformed by a temperature-sensitive v-src mutant, expression of CO6 was strongly induced at the non-permissive temperature and reduced at the permissive temperature. Nucleotide sequence analysis of quail CO6 cDNA indicated that the corresponding gene encodes a 200-amino acid protein with 46 to 48% amino acid sequence identity to the regulatory β subunits (KVCaβ) of the bovine, human and canine high conductance Ca2+-activated K+ channels. No sequence homology to other ion channel subunits or to any other proteins in the databases was found. Like the KVCaβ subunits, the CO6 protein contains two putative transmembrane segments. Based on the relationship to mammalian KVCaβ both in primary structure and domain topology, the CO6 protein may represent the regulatory subunit of a yet unidentified avian Ca2+-activated potassium channel or a related membrane protein possibly involved in the regulation of cell proliferation. [ABSTRACT FROM AUTHOR]

Dissipative heating has not been accounted for in either numerical simulations of hurricanes or in theories for the maximum intensity of hurricanes. We argue that the bulk of dissipative heating occurs in the atmospheric boundary layer near the radius of maximum winds and, using both theory and numerical simulation, show that dissipative heating increases maximum wind speeds in tropical cyclones by about 20%. [ABSTRACT FROM AUTHOR]

The lifetimes for the second excited state inNa and for the second to ninth excited states inNa have been determined with the DSA method using TaO and Ta as stopping materials. In the DSA analysis the experimental stopping parameters determined in the present and earlier works were utilized. The reanalysis of some earlier studies has brought very good consistency to the scattered results. Comparison of the observed transition strengths with theory has also been made. [ABSTRACT FROM AUTHOR]

Resonances in the reactionFe( p, γ)Co have been studied in the analogue region E=2.20-2.25 MeV. The γ-ray decays of fourteen resonances and the energies of nine bound states have been obtained using a 80 cm Ge(Li)-detector. The Q-value was found to be 7359.7±3.0 keV. One lifetime and six lifetime limits were determined from the Doppler-shift attenuation method for bound states. [ABSTRACT FROM AUTHOR]

Fortyeight resonances of theS( p, γ)Cl reaction in the proton range E=1-2 MeV have been observed. Gamma decay of twentyeight of these was investigated by means of a 55 cm Ge(Li) detector, and the energies and branching ratios of several bound states have been determined. The Q-value was found to be 6367.0 ± 1.5 keV. The lifetimes 150±20, 400±140, 19±4, 14±2, 145±50, 20±5, 20±4, 42±4 and 7±3 fs were determined with the DSA method for the states at 1219, 1763, 2694, 3003, 3944, 3967, 4059, 4178 and 4882 keV, respectively. The experimental transition strengths were found to be in agreement with those given by manyparticle shell-modell calculations. [ABSTRACT FROM AUTHOR]

From the yield curve of theAl( p, γ)Si reaction obtained with implanted targets, the range distributions and mean ranges of 50 keV Al-ions have been determined in C, Cu, Mo and Ta. The energy straggling of protons has been taken into account in the analysis. The DSA lifetime values in different backing materials are in good agreement when measured ranges are used for the determination of the stopping parameters. [ABSTRACT FROM AUTHOR]

FourteenNe( p, γ)Na resonances have been observed in the range E=300-1,300 keV. The γ-decay of all these resonances has been investigated by means of a 38 cm Ge(Li) detector. Energies and branching ratios of several bound states have been determined. The Q-value was determined as 6,738.5±1.7 keV. Lifetimes of seven states were determined with the Doppler-shift attenuation method. The observed upper limit ( τ≦4 fs) of the lifetime for the 4,071 keV state, regarded as the analogue of the third excited state inNe, and the transition observed from this state to the 1,528 keV state do not support the proposed rotational band structure of theNa low-lying states. [ABSTRACT FROM AUTHOR]

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OPN is an RGD-containing protein overexpressed in cells transformed by v-myc and v-mil( raf) oncogenes. Here we report the resonance assignment of recombinant quail OPN and provide NMR evidence that quail OPN is an intrinsically unstructured protein in solution. [ABSTRACT FROM AUTHOR]

The growth improvement of a Cardamine pratensis cell suspension can be obtained by the addition of casein hydrolysate to the medium. This component can be replaced by the same concentration of glutamine. Moreover on two cell suspensions, C. pratensis and Silene alba, this glutamine effect appears only when the medium has a phosphorus deficiency. Consequently, casein hydrolysate effectiveness would be due to its high concentration of glutamine and its contribution would balance the shortage of this amino acid synthesis when the medium has a phosphorus deficiency. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor commenting on sequence-specific resonance assignments of Q83, a lipocalin highly expressed in v-myc-transformed avian fibroblasts.

Membrane receptor-sensed input signals affect and modulate intracellular protein-protein interactions (PPIs). Consequent changes occur to the compositions of protein complexes, protein localization and intermolecular binding affinities. Alterations of compartmentalized PPIs emanating from certain deregulated kinases are implicated in the manifestation of diseases such as cancer. Here we describe the application of a genetically encoded Protein-fragment Complementation Assay (PCA) based on the Renilla Luciferase (Rluc) enzyme to compare binary PPIs of the spatially and temporally controlled protein kinase A (PKA) network in diverse eukaryotic model systems. The simplicity and sensitivity of this cell-based reporter allows for real-time recordings of mutually exclusive PPIs of PKA upon activation of selected endogenous G protein-coupled receptors (GPCRs) in cancer cells, xenografts of mice, budding yeast, and zebrafish embryos. This extends the application spectrum of Rluc PCA for the quantification of PPI-based receptor-effector relationships in physiological and pathological model systems. [ABSTRACT FROM AUTHOR]