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Sample records for employing msh2 protein

  1. Diagnostic method employing MSH2 protein

    DOEpatents

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    1998-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  2. Diagnostic method employing MSH2 protein

    DOEpatents

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1998-11-17

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  3. Human MSH2 protein

    DOEpatents

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    1997-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  4. Human MSH2 protein

    DOEpatents

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  5. Diagnostic method employing MSH2 nucleic acids

    DOEpatents

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-12-02

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +}(RER{sup +}) tumor cells. 19 figs.

  6. Diagnostic method employing MSH2 nucleic acids

    DOEpatents

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    1997-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  7. Proteasome inhibition rescues clinically significant unstable variants of the mismatch repair protein Msh2

    PubMed Central

    Arlow, Tim; Scott, Kristan; Wagenseller, Aubrey; Gammie, Alison

    2013-01-01

    MSH2 is required for DNA mismatch repair recognition in eukaryotes. Deleterious mutations in human MSH2 account for approximately half of the alleles associated with a common hereditary cancer syndrome. Previously, we characterized clinically identified MSH2 missense mutations, using yeast as a model system, and found that the most common cause of defective DNA mismatch repair was low levels of the variant Msh2 proteins. Here, we show that increased protein turnover is responsible for the reduced cellular levels. Increasing gene dosage of more than half of the missense alleles fully restored function. A titration experiment revealed that raising the expression level of one variant to less than wild-type levels restored mismatch repair, suggesting that overexpression is not always required to regain function. We found that the ubiquitin-mediated proteasome degradation pathway is the major mechanism for increased turnover of the Msh2 variants and identified the primary ubiquitin ligase as San1. Deletion of San1 restored protein levels for all but one variant, but did not elevate wild-type Msh2 levels. The unstable variants interacted with San1, whereas wild-type Msh2 did not. Additionally, san1Δ suppressed the mismatch repair defect of unstable variants. Of medical significance, the clinically approved drug Bortezomib partially restored protein levels and mismatch repair function for low-level variants and reversed the resistance to cisplatin, a common chemotherapeutic. Our results provide the foundation for an innovative therapeutic regime for certain mismatch-repair-defective cancers that are refractory to conventional chemotherapies. PMID:23248292

  8. Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

    PubMed

    Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

    2016-01-01

    The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an

  9. Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene MSH2 in Human Uterine Fibroids.

    PubMed

    Yang, Qiwei; Laknaur, Archana; Elam, Lelyand; Ismail, Nahed; Gavrilova-Jordan, Larisa; Lue, John; Diamond, Michael P; Al-Hendy, Ayman

    2016-10-01

    Uterine fibroids (UFs) are benign smooth muscle neoplasms affecting up to 70% of reproductive age women. Treatment of symptomatic UFs places a significant economic burden on the US health-care system. Several specific genetic abnormalities have been described as etiologic factors of UFs, suggesting that a low DNA damage repair capacity may be involved in the formation of UF. In this study, we used human fibroid and adjacent myometrial tissues, as well as an in vitro cell culture model, to evaluate the expression of MutS homolog 2 (MSH2), which encodes a protein belongs to the mismatch repair system. In addition, we deciphered the mechanism by which polycomb repressive complex 2 protein, EZH2, deregulates MSH2 in UFs. The RNA expression analysis demonstrated the deregulation of MSH2 expression in UF tissues in comparison to its adjacent myometrium. Notably, protein levels of MSH2 were upregulated in 90% of fibroid tissues (9 of 10) as compared to matched adjacent myometrial tissues. Human fibroid primary cells treated with 3-deazaneplanocin A (DZNep), chemical inhibitor of EZH2, exhibited a significant increase in MSH2 expression (P < .05). Overexpression of EZH2 using an adenoviral vector approach significantly downregulated the expression of MSH2 (P < .05). Chromatin immunoprecipitation assay demonstrated that enrichment of H3K27me3 in promoter regions of MSH2 was significantly decreased in DZNep-treated fibroid cells as compared to vehicle control. These data suggest that EZH2-H3K27me3 regulatory mechanism dynamically changes the expression levels of DNA mismatch repair gene MSH2, through epigenetic mark H3K27me3. MSH2 may be considered as a marker for early detection of UFs. © The Author(s) 2016.

  10. Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer.

    PubMed

    Lopes, Maria Luiza Diniz de Sousa; de Oliveira, Denise Hélen Imaculada Pereira; Sarmento, Dmitry José de Santana; Queiroz, Lélia Maria Guedes; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

    2016-04-01

    This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p > 0.05). Immunoexpression of p53 was higher in SCC than in AC (p < 0.001), while p21 expression was more observed in AC when compared to SCC group (p = 0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r = -0.30, p = 0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process.

  11. Exonic deletions of mismatch repair genes MLH1 and MSH2 correlate with prognosis and protein expression levels in malignant melanomas.

    PubMed

    Korabiowska, Monika; Brinck, Ulrich; Stachura, Jerzy; Jawien, Jacek; Hasse, Frank Michael; Cordon-Cardos, Carlos; Fischer, Gösta

    2006-01-01

    The mutations of MLH1 and MSH2 have been reported to be responsible for malignant transformation and tumour progression in several sporadic tumours. Eighty-six primary malignant melanomas with known follow-up were investigated. Point mutations of DNA mismatch repair MLH1 and MSH2 in malignant melanomas were not found. Exon 12 (MSH2) was not present in 26 out of the 86 melanomas and exon 13 (MSH2) was lost in 25 of the tumours. The loss of exon 15 (MLH1) was observed in 22 out of the 86 tumours and the loss of exon 16 (MLH1) in 24 melanomas. The loss of exons correlated strongly with the loss of MLH1 and MSH2 protein expression. In multivariate analysis, including all 4 exons and expressions of MLH1 and MSH2, prognostic significance was found only for loss of exon 12 (MSH2) and loss of exon 15 (MLH1).

  12. Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide.

    PubMed

    McFaline-Figueroa, José L; Braun, Christian J; Stanciu, Monica; Nagel, Zachary D; Mazzucato, Patrizia; Sangaraju, Dewakar; Cerniauskas, Edvinas; Barford, Kelly; Vargas, Amanda; Chen, Yimin; Tretyakova, Natalia; Lees, Jacqueline A; Hemann, Michael T; White, Forest M; Samson, Leona D

    2015-08-01

    Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity. RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases provided an unexpectedly strong mechanism of temozolomide resistance. In a mouse xenograft model of human GBM, small changes in MSH2 were sufficient to suppress temozolomide-induced tumor regression. Using The Cancer Genome Atlas to analyze mRNA expression patterns in tumors from temozolomide-treated GBM patients, we found that MSH2 transcripts in primary GBM could predict patient responses to initial temozolomide therapy. In recurrent disease, the absence of microsatellite instability (the standard marker for MMR deficiency) suggests a lack of involvement of MMR in the resistant phenotype of recurrent disease. However, more recent studies reveal that decreased MMR protein levels occur often in recurrent GBM. In accordance with our findings, these reported decreases may constitute a mechanism by which GBM evades temozolomide sensitivity while maintaining microsatellite stability. Overall, our results highlight the powerful effects of MSH2 attenuation as a potent mediator of temozolomide resistance and argue that MMR activity offers a predictive marker for initial therapeutic response to temozolomide treatment.

  13. Expression of hMSH2 protein of the human DNA mismatch repair system in oral lichen planus

    PubMed Central

    2004-01-01

    Lichen planus is a mucocutaneous disease of inflammatory nature and unknown etiology. It is characterized by a cell-mediated immunological response to induced antigenic change in skin and/or mucosa. The possible malignant transformation of lichen planus remains a subject of controversial discussions in the literature. hMSH2 is one of the human DNA mismatch repair (hMMR) genes and it plays an important role in reducing mutation and maintaining genomic stability. hMSH2 alterations have been reported in oral squamous cell carcinoma and there are evidences suggesting the association between oral lichen planus and squamous cell carcinoma. In this study, we aim to investigate the immunolocalization of hMSH2 protein in oral lichen planus compared to oral normal mucosa epithelium. We examined the expression of hMSH2 protein by immunohistochemistry in twenty-six cases of oral lichen planus. Clinically, 12 of them were categorized into reticular subtype and 14 were atrophic/erosive. Ten cases of normal mucosa were added to the control group. Results showed that the percentage of positive cells to hMSH2 was smaller in reticular (46.54%; p=0,006) and atrophic/erosive (48.79%; p=0,028) subtypes of oral lichen planus compared to normal mucosa (61.29%). The reduced expression of hMSH2 protein in oral lichen planus suggests that this lesion is more susceptible to mutation and therefore facilitate the development of oral squamous cell carcinoma. PMID:15912193

  14. MSH-2 and MLH-1 Protein Expression in Muir Torre Syndrome-Related and Sporadic Sebaceous Neoplasms

    PubMed Central

    Morales-Burgos, Adisbeth; Sánchez, Jorge L.; Figueroa, Luz D.; De Jesús-Monge, Wilfredo E.; Cruz-Correa, Marcia R.; González-Keelan, Carmen; Nazario, Cruz María

    2009-01-01

    Background Muir-Torre Syndrome (MTS) is a rare autosomal-dominant disorder characterized by the predisposition to both sebaceous neoplasm and internal malignancies. MTS-associated sebaceous neoplasms reveal mutations in DNA mismatch repair (MMR) genes and microsatellite instability. A significant part of MTS patients represents a phenotypic variant, the hereditary nonpolyposis colorectal cancer (HNPCC). A strong correlation between microsatellite instability and immunostaining has been demonstrated. The early recognition of sebaceous neoplasm as part of MTS, and their differentiation from sporadic sebaceous neoplasm may have an important application in a clinical setting. The absence of MLH-1 or MSH-2 expression by immunostaining identifies tumors with mismatch repair deficiency. Objectives Our aim is to determine whether an immunohistochemical approach, targeting DNA repair proteins MSH-2 and MLH-1 in MTS-related sebaceous neoplasm and their sporadic counterparts, can be used for their identification. Methods We examined 15 sebaceous neoplasms (including 6 internal malignancy- associated sebaceous neoplasms and 8 sporadic sebaceous neoplasms) from 11 patients for the expression of MSH-2 and MLH-1 by immunohistochemistry. Results Four of 5 internal malignancy-associated sebaceous neoplasms showed loss of expression of MSH-2 or MLH-1. Correlation of the immunostaining pattern of the sebaceous neoplasms and the patients’ positive history of colon carcinoma was 80%. Seven of 8 sporadic sebaceous neoplasms showed a positive expression of MSH-2 and MLH-1. The prevalence for loss of expression of MMR proteins in sebaceous neoplasms was 38.5%. MMR immunostaining had 87.5% specificity and 80% sensitivity. Limitations This study is limited by a small sample size, and by bias selection due to the use of non nationwide data-base as the resource of cases. Conclusions Our findings demonstrate that immunohistochemical testing for internal malignancy-associated sebaceous

  15. Diffusion and Binding of Mismatch Repair Protein, MSH2, in Breast Cancer Cells at Different Stages of Neoplastic Transformation.

    PubMed

    Sigley, Justin; Jarzen, John; Scarpinato, Karin; Guthold, Martin; Pu, Tracey; Nelli, Daniel; Low, Josiah; Bonin, Keith

    2017-01-01

    The interior of cells is a highly complex medium, containing numerous organelles, a matrix of different fibers and a viscous, aqueous fluid of proteins and small molecules. The interior of cells is also a highly dynamic medium, in which many components move, either by active transport or passive diffusion. The mobility and localization of proteins inside cells can provide important insights into protein function and also general cellular properties, such as viscosity. Neoplastic transformation affects numerous cellular properties, and our goal was to investigate the diffusional and binding behavior of the important mismatch repair (MMR) protein MSH2 in live human cells at various stages of neoplastic transformation. Toward this end, noncancerous, immortal, tumorigenic, and metastatic mammary epithelial cells were transfected with EGFP and EGFP-tagged MSH2. MSH2 forms two MMR proteins (MutSα and MutSβ) and we assume MSH2 is in the complex MutSα, though our results are similar in either case. Unlike the MutS complexes that bind to nuclear DNA, EGFP diffuses freely. EGFP and MutSα-EGFP diffusion coefficients were determined in the cytoplasm and nucleus of each cell type using fluorescence recovery after photobleaching. Diffusion coefficients were 14-24 μm2/s for EGFP and 3-7 μm2/s for MutSα-EGFP. EGFP diffusion increased in going from noncancerous to immortal cells, indicating a decrease in viscosity, with smaller changes in subsequent stages. MutSα produces an effective diffusion coefficient that, coupled with the free EGFP diffusion measurements, can be used to extract a pure diffusion coefficient and a pseudo-equilibrium constant K*. The MutSα nuclear K* increased sixfold in the first stage of cancer and then decreased in the more advanced stages. The ratio of nuclear to cytoplasmic K*for MutSα increased almost two orders of magnitude in going from noncancerous to immortal cells, suggesting that this quantity may be a sensitive metric for recognizing the

  16. Diffusion and Binding of Mismatch Repair Protein, MSH2, in Breast Cancer Cells at Different Stages of Neoplastic Transformation

    PubMed Central

    Sigley, Justin; Jarzen, John; Scarpinato, Karin; Guthold, Martin; Pu, Tracey; Nelli, Daniel; Low, Josiah

    2017-01-01

    The interior of cells is a highly complex medium, containing numerous organelles, a matrix of different fibers and a viscous, aqueous fluid of proteins and small molecules. The interior of cells is also a highly dynamic medium, in which many components move, either by active transport or passive diffusion. The mobility and localization of proteins inside cells can provide important insights into protein function and also general cellular properties, such as viscosity. Neoplastic transformation affects numerous cellular properties, and our goal was to investigate the diffusional and binding behavior of the important mismatch repair (MMR) protein MSH2 in live human cells at various stages of neoplastic transformation. Toward this end, noncancerous, immortal, tumorigenic, and metastatic mammary epithelial cells were transfected with EGFP and EGFP-tagged MSH2. MSH2 forms two MMR proteins (MutSα and MutSβ) and we assume MSH2 is in the complex MutSα, though our results are similar in either case. Unlike the MutS complexes that bind to nuclear DNA, EGFP diffuses freely. EGFP and MutSα-EGFP diffusion coefficients were determined in the cytoplasm and nucleus of each cell type using fluorescence recovery after photobleaching. Diffusion coefficients were 14–24 μm2/s for EGFP and 3–7 μm2/s for MutSα-EGFP. EGFP diffusion increased in going from noncancerous to immortal cells, indicating a decrease in viscosity, with smaller changes in subsequent stages. MutSα produces an effective diffusion coefficient that, coupled with the free EGFP diffusion measurements, can be used to extract a pure diffusion coefficient and a pseudo-equilibrium constant K*. The MutSα nuclear K* increased sixfold in the first stage of cancer and then decreased in the more advanced stages. The ratio of nuclear to cytoplasmic K*for MutSα increased almost two orders of magnitude in going from noncancerous to immortal cells, suggesting that this quantity may be a sensitive metric for recognizing

  17. Myc down-regulation sensitizes melanoma cells to radiotherapy by inhibiting MLH1 and MSH2 mismatch repair proteins.

    PubMed

    Bucci, Barbara; D'Agnano, Igea; Amendola, Donatella; Citti, Arianna; Raza, Giorgio H; Miceli, Roberto; De Paula, Ugo; Marchese, Rodolfo; Albini, Sonia; Felsani, Armando; Brunetti, Ercole; Vecchione, Aldo

    2005-04-01

    Melanoma patients have a very poor prognosis with a response rate of <1% due to advanced diagnosis. This type of tumor is particularly resistant to conventional chemotherapy and radiotherapy, and the surgery remains the principal treatment for patients with localized melanoma. For this reason, there is particular interest in the melanoma biological therapy. Using two p53 mutant melanoma models stably expressing an inducible c-myc antisense RNA, we have investigated whether Myc protein down-regulation could render melanoma cells more susceptible to radiotherapy, reestablishing apoptotic p53-independent pathway. In addition to address the role of p53 in the activation of apoptosis, we studied the effect of Myc down-regulation on radiotherapy sensitivity also in a p53 wild-type melanoma cell line. Myc down-regulation is able per se to induce apoptosis in a fraction of the cell population (approximately 40% at 72 hours) and in combination with gamma radiation efficiently enhances the death process. In fact, approximately 80% of apoptotic cells are evident in Myc down-regulated cells exposed to gamma radiation for 72 hours compared with approximately 13% observed after only gamma radiation treatment. Consistent with the enhanced apoptosis is the inhibition of the MLH1 and MSH2 mismatch repair proteins, which, preventing the correction of ionizing radiation mismatches occurring during DNA replication, renders the cells more prone to radiation-induced apoptosis. Data herein reported show that Myc down-regulation lowers the apoptotic threshold in melanoma cells by inhibiting MLH1 and MSH2 proteins, thus increasing cell sensitivity to gamma radiation in a p53-independent fashion. Our results indicate the basis for developing new antitumoral therapeutic strategy, improving the management of melanoma patients.

  18. Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis*

    PubMed Central

    Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

    2016-01-01

    Background The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. Objective To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. Methods We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Results Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. Conclusion This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis. PMID:27579741

  19. Mismatch repair proteins MSH2, MLH1, and EXO1 are important for class-switch recombination events occurring in B cells that lack nonhomologous end joining.

    PubMed

    Eccleston, Jennifer; Yan, Catherine; Yuan, Karen; Alt, Frederick W; Selsing, Erik

    2011-02-15

    In the absence of core nonhomologous end-joining (NHEJ) factors, Ab gene class-switch recombination (CSR) uses an alternative end-joining (A-EJ) pathway to recombine switch (S) region DNA breaks. Previous reports showing decreased S-junction microhomologies in MSH2-deficient mice and an exonuclease 1 (EXO1) role in yeast microhomology-mediated end joining suggest that mismatch repair (MMR) proteins might influence A-EJ-mediated CSR. We have directly investigated whether MMR proteins collectively or differentially influence the A-EJ mechanism of CSR by analyzing CSR in mice deficient in both XRCC4 and individual MMR proteins. We find CSR is reduced and that Igh locus chromosome breaks are reduced in the MMR/XRCC4 double-deficient B cells compared with B cells deficient in XRCC4 alone, suggesting MMR proteins function upstream of double-strand break formation to influence CSR efficiency in these cells. Our results show that MLH1, EXO1, and MSH2 are all important for efficient A-EJ-mediated CSR, and we propose that MMR proteins convert DNA nicks and point mutations into dsDNA breaks for both C-NHEJ and A-EJ pathways of CSR. We also find Mlh1-XRCC4(-) B cells have an increased frequency of direct S junctions, suggesting that MLH1 proteins may have additional functions that influence A-EJ-mediated CSR.

  20. Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study

    PubMed Central

    Ismael, Nour El Hoda S.; El Sheikh, Samar A.; Talaat, Suzan M.; Salem, Eman M.

    2017-01-01

    BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy. AIM: The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). MATERIAL AND METHODS: Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters. RESULTS: There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status. CONCLUSION: Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs. PMID:28293308

  1. Characterization of pathogenic human MSH2 missense mutations using yeast as a model system: a laboratory course in molecular biology.

    PubMed

    Gammie, Alison E; Erdeniz, Naz

    2004-01-01

    This work describes the project for an advanced undergraduate laboratory course in cell and molecular biology. One objective of the course is to teach students a variety of cellular and molecular techniques while conducting original research. A second objective is to provide instruction in science writing and data presentation by requiring comprehensive laboratory reports modeled on the primary literature. The project for the course focuses on a gene, MSH2, implicated in the most common form of inherited colorectal cancer. Msh2 is important for maintaining the fidelity of genetic material where it functions as an important component of the DNA mismatch repair machinery. The goal of the project has two parts. The first part is to create mapped missense mutation listed in the human databases in the cognate yeast MSH2 gene and to assay for defects in DNA mismatch repair. The second part of the course is directed towards understanding in what way are the variant proteins defective for mismatch repair. Protein levels are analyzed to determine if the missense alleles display decreased expression. Furthermore, the students establish whether the Msh2p variants are properly localized to the nucleus using indirect immunofluorescence and whether the altered proteins have lost their ability to interact with other subunits of the MMR complex by creating recombinant DNA molecules and employing the yeast 2-hybrid assay.

  2. Characterization of Pathogenic Human MSH2 Missense Mutations Using Yeast as a Model System: A Laboratory Course in Molecular Biology

    PubMed Central

    Gammie, Alison E.; Erdeniz, Naz

    2004-01-01

    This work describes the project for an advanced undergraduate laboratory course in cell and molecular biology. One objective of the course is to teach students a variety of cellular and molecular techniques while conducting original research. A second objective is to provide instruction in science writing and data presentation by requiring comprehensive laboratory reports modeled on the primary literature. The project for the course focuses on a gene, MSH2, implicated in the most common form of inherited colorectal cancer. Msh2 is important for maintaining the fidelity of genetic material where it functions as an important component of the DNA mismatch repair machinery. The goal of the project has two parts. The first part is to create mapped missense mutation listed in the human databases in the cognate yeast MSH2 gene and to assay for defects in DNA mismatch repair. The second part of the course is directed towards understanding in what way are the variant proteins defective for mismatch repair. Protein levels are analyzed to determine if the missense alleles display decreased expression. Furthermore, the students establish whether the Msh2p variants are properly localized to the nucleus using indirect immunofluorescence and whether the altered proteins have lost their ability to interact with other subunits of the MMR complex by creating recombinant DNA molecules and employing the yeast 2-hybrid assay. PMID:22039344

  3. The effect of Msh2 knockdown on methylating agent induced toxicity in DNA glycosylase deficient cells.

    PubMed

    Cooley, N; Elder, R H; Povey, A C

    2010-01-31

    The DNA structure recognition protein MSH2 is an important protein in DNA mismatch repair due to its role in initiating the repair process. To examine the potential interactions between mismatch repair and base excision repair (BER) we have examined the effect of MSH2 knockdown on 6-thioguanine (6-TG), temozolomide (TMZ) and methylmethane sulphonate (MMS) induced toxicity in BER proficient and deficient cell lines. An shRNA expression vector containing Msh2 target sequences was designed and used to transfect mouse embryonic fibroblasts lacking either alkylpurine DNA N-glycosylase (Mpg) or endonuclease III homologue (Nth1). Significant knockdown of Msh2 gene expression was achieved with three different target sequences, with the highest level being shown by Msh2(283). Clonal selection resulted in differing levels of knockdown in Mpg(-/-) cells: (69.0+/-12.1% from 5 cell clones). Transfection of the Msh2(283) sequence in Mpg+/+, Nth1+/+ and Nth1(-/-) cells resulted in average knockdowns of 45.1+/-40.5% (3 clones), 58.0+/-21.4% (5 clones) and 74.9+/-14.8% (3 clones), respectively. Msh2 knockdown resulted in increased resistance to 6-TG in BER (MPG and NTH1) proficient and deficient cell lines with similar levels of knockdown (84+/-4%) but increased resistance to TMZ only in Mpg+/+ and Nth1(-/-) cell lines and not Mpg(-/-) or Nth1+/+ cells as assessed by an MTT assay. Msh2 knockdown had no effect on sensitivity to MMS induced toxicity. In a clonogenic assay, Msh2 silenced Mpg+/+, Mpg(-/-), Nth1+/+ and Nth1(-/-) cells were more resistant to TMZ. These results confirm previous studies showing that MSH2 is a key protein in influencing 6-TG and O(6)-methylguanine induced toxicity but also suggest that the effect of this protein depends upon the presence of other proteins in different DNA repair pathways. 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts.

    PubMed

    Andrew, S E; Xu, X S; Baross-Francis, A; Narayanan, L; Milhausen, K; Liskay, R M; Jirik, F R; Glazer, P M

    2000-07-01

    DNA mismatch repair (MMR) deficiency leads to an increased mutation frequency and a predisposition to neoplasia. 'Knockout' mice deficient in the MMR proteins Msh2 and Pms2 crossed with mutation detection reporter (supF, lacI and cII) transgenic mice have been used to facilitate a comparison of the changes in mutation frequency and spectra. We find that the mutation frequency was consistently higher in Msh2-deficient mice than Pms2-deficient mice. The lacI target gene, which is highly sensitive to point mutations, demonstrated that both Msh2- and Pms2-deficient mice accumulate transition mutations as the predominant mutation. However, when compared with Msh2(-/-) mice, lacI and cII mutants from Pms2-deficient mice revealed an increased proportion of +/-1 bp frameshift mutations and a corresponding decrease in transversion mutations. The supF target gene, which is sensitive to frameshift mutations, and the cII target gene revealed a strong tendency for -1 bp deletions over +1 bp insertions in Msh2(-/-) compared with Pms2(-/-) mice. These data indicate that Msh2 and Pms2 deficiency have subtle but differing effects on mutation avoidance which may contribute to the differences in tumor spectra observed in the two 'knockout' mouse models. These variances in mutation accumulation may also play a role, in part, in the differences seen in prevalence of MSH2 and PMS2 germline mutations in hereditary non-polyposis colorectal cancer patients.

  5. Cerebral primitive neuroectodermal tumor in an adult with a heterozygous MSH2 mutation.

    PubMed

    Jeans, Alexander F; Frayling, Ian; Jasani, Bharat; Side, Lucy; Blesing, Claire; Ansorge, Olaf

    2009-05-01

    A 37-year-old woman presented with a supratentorial cerebral mass, which was diagnosed histologically as a primitive neuroectodermal tumor. She had been treated for rectal adenocarcinoma 7 years previously. A family history revealed a young-onset colorectal carcinoma in the patient's father. Immunohistochemical analysis for DNA mismatch repair proteins, germline mutation analysis of MSH2. Lynch syndrome with a heterozygous germline mutation in MSH2. Debulking of the cerebral tumor, craniospinal axis radiotherapy, and genetic counseling of family.

  6. Case-case study of factors associated to hMLH1, hMSH2, and hMSH6 protein expression among endometrial cancer patients of the University District Hospital of San Juan, Puerto Rico

    PubMed Central

    González, Lorena; Ortiz, Ana P.; Suárez, Erick; Umpierre, Sharee; Marcos, Maria J.; Billoch, Jorge; Joy, Leilani; Charneco, Eileen; Lacourt, Mercedes Y.; Bernabe-Dones, Raúl D.; Cruz-Correa, Marcia

    2012-01-01

    Lynch syndrome (LS) is an autosomal dominant disorder caused by DNA mismatch repair (MMR) system deficiencies. Women affected by LS present a 40 to 60% lifetime risk of endometrial cancer (EC). Objective This case-case study aims to determine the frequency of the hMLH1, hMSH2, and hMSH6 MMR proteins and the factors (age, family history of cancer [FHC] related to LS, and body mass index [BMI]) associated to their absence in EC patients attending the University District Hospital of San Juan, Puerto Rico. Method/Materials Twenty cases were preliminary evaluated for the MMR protein expression by immunohistochemistry testing and classified as positive-cases (presence of protein) or negative-cases (absence of protein). The statistical analysis was based on the logistic regression model using the Maximum Likelihood estimation (MLE). The Bayesian approach was used to determine the posterior probability {posterior Pr[OR>1]}. Results Results showed absence for at least one MMR protein in 25% of the cases; 15% for hMLH1 and 10% for hMSH2. None of the cases showed an absence for hMSH6. The MLE demonstrated that women diagnosed with EC before the age of 50 (OR: 12.4; 95%CI = 0.5–322.7), having FHC related to LS (OR: 17.7; 95%CI = 0.6–534.6), and having lower BMI (OR: 2.38; 95%CI = 0.39–14.28) present higher odds than their counterparts of lacking an MMR protein, once adjusting for potential predictors (p > .05). The posterior probability that an excess risk of lacking an MMR protein occurs was ≥ 95% for each predictor. Conclusion Our study in this Hispanic population supports previous studies in that younger age, FHC, and lower BMI are associated with increased odds of having an absence of MMR protein expression. Further studies with larger sample sizes should be performed. PMID:22635031

  7. Msh2 deficiency leads to dysmyelination of the corpus callosum, impaired locomotion, and altered sensory function in mice

    PubMed Central

    Diouf, Barthelemy; Devaraju, Prakash; Janke, Laura J.; Fan, Yiping; Frase, Sharon; Eddins, Donnie; Peters, Jennifer L.; Kim, Jieun; Pei, Deqing; Cheng, Cheng; Zakharenko, Stanislav S.; Evans, William E.

    2016-01-01

    A feature in patients with constitutional DNA-mismatch repair deficiency is agenesis of the corpus callosum, the cause of which has not been established. Here we report a previously unrecognized consequence of deficiency in MSH2, a protein known primarily for its function in correcting nucleotide mismatches or insertions and deletions in duplex DNA caused by errors in DNA replication or recombination. We documented that Msh2 deficiency causes dysmyelination of the axonal projections in the corpus callosum. Evoked action potentials in the myelinated corpus callosum projections of Msh2-null mice were smaller than wild-type mice, whereas unmyelinated axons showed no difference. Msh2-null mice were also impaired in locomotive activity and had an abnormal response to heat. These findings reveal a novel pathogenic consequence of MSH2 deficiency, providing a new mechanistic hint to previously recognized neurological disorders in patients with inherited DNA-mismatch repair deficiency. PMID:27476972

  8. Mechanism of cadmium-mediated inhibition of Msh2-Msh6 function in DNA mismatch repair.

    PubMed

    Wieland, Markus; Levin, Mikhail K; Hingorani, Karan S; Biro, F Noah; Hingorani, Manju M

    2009-10-13

    The observation that Cadmium (Cd(2+)) inhibits Msh2-Msh6, which is responsible for identifying base pair mismatches and other discrepancies in DNA, has led to the proposal that selective targeting of this protein and consequent suppression of DNA repair or apoptosis promote the carcinogenic effects of the heavy metal toxin. It has been suggested that Cd(2+) binding to specific sites on Msh2-Msh6 blocks its DNA binding and ATPase activities. To investigate the mechanism of inhibition, we measured Cd(2+) binding to Msh2-Msh6, directly and by monitoring changes in protein structure and enzymatic activity. Global fitting of the data to a multiligand binding model revealed that binding of about 100 Cd(2+) ions per Msh2-Msh6 results in its inactivation. This finding indicates that the inhibitory effect of Cd(2+) occurs via a nonspecific mechanism. Cd(2+) and Msh2-Msh6 interactions involve cysteine sulfhydryl groups, and the high Cd(2+):Msh2-Msh6 ratio implicates other ligands such as histidine, aspartate, glutamate, and the peptide backbone as well. Our study also shows that cadmium inactivates several unrelated enzymes similarly, consistent with a nonspecific mechanism of inhibition. Targeting of a variety of proteins, including Msh2-Msh6, in this generic manner would explain the marked broad-spectrum impact of Cd(2+) on biological processes. We propose that the presence of multiple nonspecific Cd(2+) binding sites on proteins and their propensity to change conformation on interaction with Cd(2+) are critical determinants of the susceptibility of corresponding biological systems to cadmium toxicity.

  9. Correlations of MC4R and MSH2 expression with obesity in colon cancer patients.

    PubMed

    Liu, Y-Z; Wang, K-Q; Ji, D-H; Zhang, L-C; Bi, M; Shi, B-Y

    2017-05-01

    To investigate the correlations of MC4R and MSH2 with adult obesity, a total of 46 patients with early-stage colon cancer were treated in our hospital between February 2008 and February 2009 and were enrolled. Venous blood was regularly drawn from subjects of the observation group and 48 healthy subjects for 6 years. Expression levels of MC4R and MSH2 genes were tested using quantitative polymerase chain reaction analyses, and the ensuing proteins were determined using enzyme-linked immunosorbent assays and Western blotting and immunohistochemical analyses. Finally, correlations with body mass index (BMI) and the presence of colon cancer were identified using multivariate analyses. Compared with the control group, MSH2 mRNA and protein expression increased significantly over time (p < 0.05) in patients with colon cancer. Moreover, MSH2 expression was correlated with colon cancer progression, and MC4R mRNA and protein expression increase concurrently in comparison with the control group (p < 0.05). Also, the mean BMI among patients with colon cancer was 30.8, whereas that among control subjects was only 21.4. These data indicate a relationship between BMI and colon cancer. Expression of MSH2 in patients with colon cancer may promote the expression of the obesity gene MC4R, potentially contributing to body weight gains.

  10. Repair genes expression profile of MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers.

    PubMed

    Alves, Mônica Ghislaine Oliveira; Carta, Celina Faig Lima; de Barros, Patrícia Pimentel; Issa, Jaqueline Scholz; Nunes, Fábio Daumas; Almeida, Janete Dias

    2017-01-01

    The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with p<0.05. MLH1, MSH2 and ATM genes were downregulated in the smoking group compared to the control with significant values for MLH1 (p=0.006), MSH2 (p=0.0001) and ATM (p=0.0001). Immunocytochemical staining for anti-MLH1, anti-MSH2 and anti-ATM was negative in Never Smokers; in Smokers it was rarely positive. No significant correlation was observed among the expression of MLH1, MSH2, ATM and age, number of cigarettes consumed per day, time of smoking during life, smoking history or levels of CO in expired air. The expression of genes and proteins related to DNA repair mechanism MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers was reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. hMSH2 and GTBP expression in advanced stage epithelial ovarian cancer

    PubMed Central

    Ercoli, A; Ferrandina, G; Raspaglio, G; Marone, M; Maggiano, N; Mastro, P Del; Panici, P Benedetti; Mancuso, S; Scambia, G

    1999-01-01

    Defects in DNA mismatch repair have been associated with both hereditary and sporadic forms of human cancer. Most of the attention has been focused on the incidence and genetics of mismatch repair defects, while little is known about the expression levels of the mismatch repair proteins and their significance in cancer cell biology. In this study, both the expression levels of hMSH2 and GTBP proteins were investigated by Western blotting in 20 untreated epithelial ovarian cancers. For these analyses, a commercial anti-hMSH2 monoclonal antibody and a newly generated mouse monoclonal anti-GTBP antibody were used. hMSH2 and GTBP proteins were detected by Western blotting in 19 out of 20 (95%) samples analysed and were found to be directly correlated (r = +0.51, P = 0.025). hMSH2 expression was significantly higher in ovarian cancer cells originating from solid tumours than from ascites (H = 4.5, P = 0.033), whereas GTBP content did not significantly differ according to the origin of cancer cells. No statistically significant differences were found in the distribution of hMSH2 and GTBP levels according to the age of the patients, grade of differentiation, histotype and extent of surgical debulking. The amount of hMSH2 protein was demonstrated to be significantly lower in stage IV than in stage III patients (H = 7.35, P = 0.007). Moreover, significantly lower hMSH2 levels were observed in non-responding patients compared to patients who achieved complete or partial response to cisplatin-based chemotherapy (H = 4.88, P = 0.027). Conversely, GTBP levels were not distributed differently according to stage of disease and chemotherapy response. Our study suggests a possible involvement of hMSH2 in ovarian cancer cell biology and susceptibility to chemotherapy. The possible biological and/or clinical role of GTBP expression in ovarian cancer patients remains to be elucidated. © 1999 Cancer Research Campaign PMID:10408416

  12. Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients.

    PubMed

    Nakai, Katsuya; Mitomi, Hiroyuki; Alkam, Yimit; Arakawa, Atsushi; Yao, Takashi; Tokuda, Emi; Saito, Mitsue; Kasumi, Fujio

    2012-04-01

    To evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in patients with locally advanced basal-like breast cancers (BLBCs). Thirty-two BLBC patients receiving NACT with an anthracycline-based regimen plus taxane were included in this study. The immunoreactivities of MGMT, MLH1, MSH2 and BRCA1 before and after NACT were evaluated. A pCR was obtained in 10 of 32 cases (31%). Cancer-related (P = 0.013) and disease-free (P = 0.023) survival rates were significantly higher in the pCR group than in the non-pCR group. In biopsy samples before NACT, attenuated expression of MGMT, MLH1, MSH2 and BRCA1 was observed in 12/32 (38%), 0/32 (0%), 5/32 (16%) and 28/32 (88%) cases, respectively. On evaluation of pCR, patients' characteristics (patients' age, menopausal status, or clinical and pathological stages) and immunohistochemical patterns, attenuated expression of MGMT was only found to be significantly predictive of a pCR (P = 0.018). Paired biopsy sample before NACT and a surgical tumor material after NACT were available for 19 cases of non-pCR. In these cases, decrease in expression during NACT were more frequently observed for MGMT as compared to MLH1, MSH2 or BRCA1 (P = 0.021). MGMT status is a predictive factor for pCR with neoadjuvant anthracycline-based plus taxane combination chemotherapy, which may be helpful in the selection of appropriate NACT for Japanese patients with BLBC.

  13. Crosstalk between BRCA-Fanconi anemia and mismatch repair pathways prevents MSH2-dependent aberrant DNA damage responses.

    PubMed

    Peng, Min; Xie, Jenny; Ucher, Anna; Stavnezer, Janet; Cantor, Sharon B

    2014-08-01

    Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is suppressed by depletion of the upstream mismatch recognition factor MSH2. MSH2 depletion suppresses an aberrant DNA damage response, restores cell cycle progression, and promotes ICL resistance through a Rad18-dependent mechanism. MSH2 depletion also suppresses ICL sensitivity in cells deficient for BRCA1 or FANCD2, but not FANCA. Rescue by Msh2 loss was confirmed in Fancd2-null primary mouse cells. Thus, we propose that regulation of MSH2-dependent DNA damage response underlies the importance of interactions between BRCA-FA and MMR pathways.

  14. Crosstalk between BRCA-Fanconi anemia and mismatch repair pathways prevents MSH2-dependent aberrant DNA damage responses

    PubMed Central

    Peng, Min; Xie, Jenny; Ucher, Anna; Stavnezer, Janet; Cantor, Sharon B

    2014-01-01

    Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is suppressed by depletion of the upstream mismatch recognition factor MSH2. MSH2 depletion suppresses an aberrant DNA damage response, restores cell cycle progression, and promotes ICL resistance through a Rad18-dependent mechanism. MSH2 depletion also suppresses ICL sensitivity in cells deficient for BRCA1 or FANCD2, but not FANCA. Rescue by Msh2 loss was confirmed in Fancd2-null primary mouse cells. Thus, we propose that regulation of MSH2-dependent DNA damage response underlies the importance of interactions between BRCA-FA and MMR pathways. PMID:24966277

  15. BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations

    PubMed Central

    Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A.; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L.; El-Deiry, Wafik S.

    2017-01-01

    Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P < 0.0001) in BRCA2. Of 1104 profiled CRCs from a second cohort (COSMIC), MSH2/MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P < 0.0000001). BRCA2 mutations in MSH2/MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P < 0.0000001). Approximately 15% of EGFR mutations found may be actionable through TKI therapy, including N700D, G719D, T725M, T790M, and E884K. NTRK gene mutations were identified in MSH2/MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency. PMID:28591715

  16. Cancer risks for MLH1 and MSH2 mutation carriers

    PubMed Central

    Dowty, James G.; Win, Aung K.; Buchanan, Daniel D.; Lindor, Noralane M.; Macrae, Finlay A.; Clendenning, Mark; Antill, Yoland C.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steve; Le Marchand, Loic; Newcomb, Polly A.; Haile, Robert W.; Young, Graeme P.; James, Paul A.; Giles, Graham G.; Gunawardena, Shanaka R.; Leggett, Barbara A.; Gattas, Michael; Boussioutas, Alex; Ahnen, Dennis J.; Baron, John A.; Parry, Susan; Goldblatt, Jack; Young, Joanne P.; Hopper, John L.; Jenkins, Mark A.

    2013-01-01

    We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks to age 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%-50%) and 47% (36%-60%) for male carriers and 36% (25%-51%) and 37% (27%-50%) for female carriers. Corresponding EC risks were 18% (9.1%-34%) and 30% (18%-45%). A high level of CRC risk heterogeneity was observed (p<0.001), with cumulative risks to age 70 years estimated to follow U-shaped distributions. For example 17% of male MSH2 mutation carriers have estimated lifetime risks of 0-10% while 18% have risks of 90-100%. Therefore, average risks are similar for the two genes but there is so much individual variation about the average that large proportions of carriers have either very low or very high lifetime cancer risks. Our estimates of CRC and EC cumulative risks for MLH1 and MSH2 mutation carriers are the most precise currently available. PMID:23255516

  17. Cancer risks for MLH1 and MSH2 mutation carriers.

    PubMed

    Dowty, James G; Win, Aung K; Buchanan, Daniel D; Lindor, Noralane M; Macrae, Finlay A; Clendenning, Mark; Antill, Yoland C; Thibodeau, Stephen N; Casey, Graham; Gallinger, Steve; Marchand, Loic Le; Newcomb, Polly A; Haile, Robert W; Young, Graeme P; James, Paul A; Giles, Graham G; Gunawardena, Shanaka R; Leggett, Barbara A; Gattas, Michael; Boussioutas, Alex; Ahnen, Dennis J; Baron, John A; Parry, Susan; Goldblatt, Jack; Young, Joanne P; Hopper, John L; Jenkins, Mark A

    2013-03-01

    We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks at the age of 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%-50%) and 47% (36%-60%) for male carriers and 36% (25%-51%) and 37% (27%-50%) for female carriers. Corresponding EC risks were 18% (9.1%-34%) and 30% (18%-45%). A high level of CRC risk heterogeneity was observed (P < 0.001), with cumulative risks at the age of 70 years estimated to follow U-shaped distributions. For example, 17% of male MSH2 mutation carriers have estimated lifetime risks of 0%-10% and 18% have risks of 90%-100%. Therefore, average risks are similar for the two genes but there is so much individual variation about the average that large proportions of carriers have either very low or very high lifetime cancer risks. Our estimates of CRC and EC cumulative risks for MLH1 and MSH2 mutation carriers are the most precise currently available.

  18. Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome

    PubMed Central

    Moreno-Ortiz, Jose Miguel; Ayala-Madrigal, María de la Luz; Corona-Rivera, Jorge Román; Maciel-Gutiérrez, Víctor; Franco-Topete, Ramón Antonio; Armendáriz-Borunda, Juan; Pérez-Carbonell, Lucia; Rhees, Jennifer; Gutiérrez-Angulo, Melva

    2016-01-01

    Background. Lynch Syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC) and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC), and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del) and c.1852_1853delinsGC (p.K618A) in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs) in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel. PMID:27247567

  19. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    PubMed

    Kovalenko, Marina; Dragileva, Ella; St Claire, Jason; Gillis, Tammy; Guide, Jolene R; New, Jaclyn; Dong, Hualing; Kucherlapati, Raju; Kucherlapati, Melanie H; Ehrlich, Michelle E; Lee, Jong-Min; Wheeler, Vanessa C

    2012-01-01

    The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT) exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR) pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111) with mice carrying a conditional (floxed) Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  20. Role of Red Meat and Resistant Starch in Promutagenic Adduct Formation, MGMT Repair, Thymic Lymphoma and Intestinal Tumourigenesis in Msh2 -Deficient Mice.

    PubMed

    Winter, Jean M; Hu, Ying; Young, Graeme P; Kohonen-Corish, Maija R J; Le Leu, Richard K

    2014-01-01

    Red meat may increase promutagenic lesions in the colon. Resistant starch (RS) can reduce these lesions and chemically induced colon tumours in rodents. Msh2 is a mismatch repair (MMR) protein, recognising unrepaired promutagenic adducts for removal. We determined if red meat and/or RS modulated DNA adducts or oncogenesis in Msh2-deficient mice. A total of 100 Msh2-/- and 60 wild-type mice consumed 1 of 4 diets for 6 months: control, RS, red meat and red meat+RS. Survival time, aberrant crypt foci (ACF), colon and small intestinal tumours, lymphoma, colonic O6-methyl-2-deoxyguanosine (O6MeG) adducts, methylguanine methyltransferase (MGMT) and cell proliferation were examined. In Msh2-/- mice, red meat enhanced survival compared to control (p<0.01) and lowered total tumour burden compared to RS (p<0.167). Msh2-/- mice had more ACF than wild-type mice (p<0.014), but no colon tumours developed. Msh2-/- increased cell proliferation (p<0.001), lowered DNA O6MeG adducts (p<0.143) and enhanced MGMT protein levels (p<0.001) compared to wild-type mice, with RS supplementation also protecting against DNA adducts (p<0.01). No link between red meat-induced promutagenic adducts and risk for colorectal cancer was observed after 6 months' feeding. Colonic epithelial changes after red meat and RS consumption with MMR deficiency will differ from normal epithelial cells.

  1. Rev1 is essential in generating G to C transversions downstream of the Ung2 pathway but not the Msh2+Ung2 hybrid pathway.

    PubMed

    Krijger, Peter Hugo Lodewijk; Tsaalbi-Shtylik, Anastasia; Wit, Niek; van den Berk, Paul Cornelius Maria; de Wind, Niels; Jacobs, Heinz

    2013-10-01

    Somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes are initiated by the enzymatic deamination of cytosine (C) to uracil (U). Uracil-DNA-glycosylase (Ung2) converts uracils into apyrimidinic (AP) sites, which is essential for the generation of transversions (TVs) at G/C basepairs during SHM and for efficient DNA break formation during CSR. Besides Ung2, the mismatch repair protein Msh2 and the translesion synthesis (TLS) DNA polymerase (Pol) Rev1 are implicated in SHM and CSR. To further unravel the role of Rev1, we studied WT, Rev1-deficient, Msh2-deficient, and Rev1, Msh2 double-deficient B cells. Loss of Rev1 only slightly reduced CSR. During SHM G/C to C/G TVs are generated in both Ung2- and Ung+Msh2-dependent fashions. We found that Rev1 is essential for the Msh2-independent generation of these TVs downstream of Ung2-induced AP sites. In the Ung+Msh2 hybrid pathway, Rev1 is not essential and can be substituted by an alternative TLS Pol, especially when Rev1 is lacking.

  2. Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect

    SciTech Connect

    Wang, Yisong; Liu, Yie

    2006-01-01

    Msh2 is a key mammalian DNA mismatch repair (MMR) gene and mutations or deficiencies in mammalian Msh2 gene result in microsatellite instability (MSI+) and the development of cancer. Here, we report that primary mouse embryonic fibroblasts (MEFs) deficient in the murine MMR gene Msh2 (Msh2-/-) showed a significant increase in chromosome aneuploidy, centrosome amplification, and defective mitotic spindle organization and unequal chromosome segregation. Although Msh2-/- mouse tissues or primary MEFs had no apparent change in telomerase activity, telomere length, or recombination at telomeres, Msh2-/- MEFs showed an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA. These data suggest that MSH2 helps to maintain genomic stability through the regulation of the centrosome and normal telomere capping in vivo and that defects in MMR can contribute to oncogenesis through multiple pathways.

  3. Characterization of Insertion Mutations in the Saccharomyces Cerevisiae Msh1 and Msh2 Genes: Evidence for Separate Mitochondrial and Nuclear Functions

    PubMed Central

    Reenan, RAG.; Kolodner, R. D.

    1992-01-01

    The MSH1 and MSH2 genes of Saccharomyces cerevisiae are predicted to encode proteins that are homologous to the Escherichia coli MutS and Streptococcus pneumoniae HexA proteins and their homologs. Disruption of the MSH1 gene caused a petite phenotype which was established rapidly. A functional MSH1 gene present on a single-copy centromere plasmid was incapable of rescuing the established msh1 petite phenotype. Analysis of msh1 strains demonstrated that mutagenesis and large-scale rearrangement of mitochondrial DNA had occurred. 4',6-Diamidino-2-phenylindole (DAPI) staining of msh1 yeast revealed an aberrant distribution of mtDNA. Haploid msh2 mutants displayed an increase of 85-fold in the rate of spontaneous mutation to canavanine resistance. Sporulation of homozygous msh2/msh2 diploids gave rise to a high level of lethality which was compounded during increased vegetative growth prior to sporulation. msh2 mutations also affected gene conversion of two HIS4 alleles. The his4x mutation, lying near the 5' end of the gene, was converted with equal frequency in both wild-type and msh2 strains. However, many of the events in the msh2 background were post-meiotic segregation (PMS) events (46.4%) while none (<0.25%) of the aberrant segregations in wild type were PMS events. The his4b allele, lying 1.6 kb downstream of his4x, was converted at a 10-fold higher frequency in the msh2 background than in the corresponding wild-type strain. Like the his4x allele, his4b showed a high level of PMS (30%) in the msh2 background compared to the corresponding wild-type strain where no (<0.26%) PMS events were observed. These results indicate that MSH1 plays a role in repair or stability of mtDNA and MSH2 plays a role in repair of 4-bp insertion/deletion mispairs in the nucleus. PMID:1334021

  4. Dynamic basis for one-dimensional DNA scanning by the mismatch repair complex Msh2-Msh6.

    PubMed

    Gorman, Jason; Chowdhury, Arindam; Surtees, Jennifer A; Shimada, Jun; Reichman, David R; Alani, Eric; Greene, Eric C

    2007-11-09

    The ability of proteins to locate specific sites or structures among a vast excess of nonspecific DNA is a fundamental theme in biology. Yet the basic principles that govern these mechanisms remain poorly understood. For example, mismatch repair proteins must scan millions of base pairs to find rare biosynthetic errors, and they then must probe the surrounding region to identify the strand discrimination signals necessary to distinguish the parental and daughter strands. To determine how these proteins might function we used single-molecule optical microscopy to answer the following question: how does the mismatch repair complex Msh2-Msh6 interrogate undamaged DNA? Here we show that Msh2-Msh6 slides along DNA via one-dimensional diffusion. These findings indicate that interactions between Msh2-Msh6 and DNA are dominated by lateral movement of the protein along the helical axis and have implications for how MutS family members travel along DNA at different stages of the repair reaction.

  5. Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions.

    PubMed

    Hatta, Naohito; Takata, Akiko; Ishizawa, Shin; Niida, Yo

    2015-11-01

    Muir-Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non-polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46-year-old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80-year-old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients. © 2015 Japanese Dermatological Association.

  6. Deciphering the mismatch recognition cycle in MutS and MSH2-MSH6 using normal-mode analysis.

    PubMed

    Mukherjee, Shayantani; Law, Sean M; Feig, Michael

    2009-03-04

    Postreplication DNA mismatch repair is essential for maintaining the integrity of genomic information in prokaryotes and eukaryotes. The first step in mismatch repair is the recognition of base-base mismatches and insertions/deletions by bacterial MutS or eukaryotic MSH2-MSH6. Crystal structures of both proteins bound to mismatch DNA reveal a similar molecular architecture but provide limited insight into the detailed molecular mechanism of long-range allostery involved in mismatch recognition and repair initiation. This study describes normal-mode calculations of MutS and MSH2-MSH6 with and without DNA. The results reveal similar protein flexibilities and suggest common dynamic and functional characteristics. A strongly correlated motion is present between the lever domain and ATPase domains, which suggests a pathway for long-range allostery from the N-terminal DNA binding domain to the C-terminal ATPase domains, as indicated by experimental studies. A detailed analysis of individual low-frequency modes of both MutS and MSH2-MSH6 shows changes in the DNA-binding domains coupled to the ATPase sites, which are interpreted in the context of experimental data to arrive at a complete molecular-level mismatch recognition cycle. Distinct conformational states are proposed for DNA scanning, mismatch recognition, repair initiation, and sliding along DNA after mismatch recognition. Hypotheses based on the results presented here form the basis for further experimental and computational studies.

  7. Elucidating the molecular basis of MSH2-deficient tumors by combined germline and somatic analysis.

    PubMed

    Vargas-Parra, Gardenia M; González-Acosta, Maribel; Thompson, Bryony A; Gómez, Carolina; Fernández, Anna; Dámaso, Estela; Pons, Tirso; Morak, Monika; Del Valle, Jesús; Iglesias, Silvia; Velasco, Àngela; Solanes, Ares; Sanjuan, Xavier; Padilla, Natàlia; de la Cruz, Xavier; Valencia, Alfonso; Holinski-Feder, Elke; Brunet, Joan; Feliubadaló, Lídia; Lázaro, Conxi; Navarro, Matilde; Pineda, Marta; Capellá, Gabriel

    2017-10-01

    In a proportion of patients presenting mismatch repair (MMR)-deficient tumors, no germline MMR mutations are identified, the so-called Lynch-like syndrome (LLS). Recently, MMR-deficient tumors have been associated with germline mutations in POLE and MUTYH or double somatic MMR events. Our aim was to elucidate the molecular basis of MSH2-deficient LS-suspected cases using a comprehensive analysis of colorectal cancer (CRC)-associated genes at germline and somatic level. Fifty-eight probands harboring MSH2-deficient tumors were included. Germline mutational analysis of MSH2 (including EPCAM deletions) and MSH6 was performed. Pathogenicity of MSH2 variants was assessed by RNA analysis and multifactorial likelihood calculations. MSH2 cDNA and methylation of MSH2 and MSH6 promoters were studied. Matched blood and tumor DNA were analyzed using a customized next generation sequencing panel. Thirty-five individuals were carriers of pathogenic or probably pathogenic variants in MSH2 and EPCAM. Five patients harbored 4 different MSH2 variants of unknown significance (VUS) and one had 2 novel MSH6 promoter VUS. Pathogenicity assessment allowed the reclassification of the 4 MSH2 VUS and 6 probably pathogenic variants as pathogenic mutations, enabling a total of 40 LS diagnostics. Predicted pathogenic germline variants in BUB1, SETD2, FAN1 and MUTYH were identified in 5 cases. Three patients had double somatic hits in MSH2 or MSH6, and another 2 had somatic alterations in other MMR genes and/or proofreading polymerases. In conclusion, our comprehensive strategy combining germline and somatic mutational status of CRC-associated genes by means of a subexome panel allows the elucidation of up to 86% of MSH2-deficient suspected LS tumors. © 2017 UICC.

  8. MSH2/BRCA1 expression as a DNA-repair signature predicting survival in early–stage lung cancer patients from the IFCT-0002 Phase 3 Trial

    PubMed Central

    Levallet, Guénaëlle; Dubois, Fatéméh; Fouret, Pierre; Antoine, Martine; Brosseau, Solenn; Bergot, Emmanuel; Beau-Faller, Michèle; Gounant, Valérie; Brambilla, Elisabeth; Debieuvre, Didier; Molinier, Olivier; Galateau-Sallé, Françoise; Mazieres, Julien; Quoix, Elisabeth; Pujol, Jean-Louis; Moro-Sibilot, Denis; Langlais, Alexandra; Morin, Franck; Westeel, Virginie; Zalcman, Gérard

    2017-01-01

    Introduction DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. Methods We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002). O6MGMT promoter gene methylation was analyzed in a subset of 208 patients of the same trial with available snap-frozen specimens. Results Median follow-up was from 90 months onwards. Only high BRCA1 (n = 221, hazard ratio [HR] = 1.58, 95% confidence interval [CI] [1.07-2.34], p = 0.02) and low MSH2 expression (n = 356, HR = 1.52, 95% CI [1.11-2.08], p = 0.008) significantly predicted better overall survival (OS) in univariate and multivariate analysis. A bootstrap re-sampling strategy distinguished three patient groups at high (n = 55, low BRCA1 and high MSH2, median OS >96 months, HR = 2.5, 95% CI [1.45-4.33], p = 0.001), intermediate (n = 82, median OS = 73.4 p = 0.0596), and low (high BRCA1 and low MSH2, n = 67, median OS = ND, HR = 0.51, 95% CI [0.31-0.83], p = 0.006) risk of death. Interpretation DNA repair protein expression assessment identified three different groups of risk of death in early-stage lung cancer patients, according to their tumor MSH2 and BRCA1 expression levels. These results deserve prospective evaluation of MSH2/BRCA1 theranostic value in lung cancer patients treated with combinations of DNA-damaging chemotherapy and drugs targeting DNA repair, such as Poly(ADP-ribose) polymerase (PARP) inhibitors. PMID:28008145

  9. MSH2/BRCA1 expression as a DNA-repair signature predicting survival in early-stage lung cancer patients from the IFCT-0002 Phase 3 Trial.

    PubMed

    Levallet, Guénaëlle; Dubois, Fatéméh; Fouret, Pierre; Antoine, Martine; Brosseau, Solenn; Bergot, Emmanuel; Beau-Faller, Michèle; Gounant, Valérie; Brambilla, Elisabeth; Debieuvre, Didier; Molinier, Olivier; Galateau-Sallé, Françoise; Mazieres, Julien; Quoix, Elisabeth; Pujol, Jean-Louis; Moro-Sibilot, Denis; Langlais, Alexandra; Morin, Franck; Westeel, Virginie; Zalcman, Gérard

    2017-01-17

    DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002). O6MGMT promoter gene methylation was analyzed in a subset of 208 patients of the same trial with available snap-frozen specimens. Median follow-up was from 90 months onwards. Only high BRCA1 (n = 221, hazard ratio [HR] = 1.58, 95% confidence interval [CI] [1.07-2.34], p = 0.02) and low MSH2 expression (n = 356, HR = 1.52, 95% CI [1.11-2.08], p = 0.008) significantly predicted better overall survival (OS) in univariate and multivariate analysis. A bootstrap re-sampling strategy distinguished three patient groups at high (n = 55, low BRCA1 and high MSH2, median OS >96 months, HR = 2.5, 95% CI [1.45-4.33], p = 0.001), intermediate (n = 82, median OS = 73.4 p = 0.0596), and low (high BRCA1 and low MSH2, n = 67, median OS = ND, HR = 0.51, 95% CI [0.31-0.83], p = 0.006) risk of death. DNA repair protein expression assessment identified three different groups of risk of death in early-stage lung cancer patients, according to their tumor MSH2 and BRCA1 expression levels. These results deserve prospective evaluation of MSH2/BRCA1 theranostic value in lung cancer patients treated with combinations of DNA-damaging chemotherapy and drugs targeting DNA repair, such as Poly(ADP-ribose) polymerase (PARP) inhibitors.

  10. Evidence for Msh2 haploinsufficiency in mice revealed by MNU-induced sister-chromatid exchange analysis

    PubMed Central

    Bouffler, S D; Hofland, N; Cox, R; Fodde, R

    2000-01-01

    The role of Msh2 in chromosome stability has been investigated in a targeted mouse model for HNPCC Msh2Δ7N. Chromosome aberration frequencies were similar in bone marrow of Msh2+/+Msh2+/–and Msh2–/–mice and no differential effects of in vivo X-irradiation were noted. By contrast, the induction of sister-chromatid exchanges (SCEs) by methyl nitrosourea (MNU) was reduced in Msh2–/–and Msh2+/–cells to ~20% and ~45% wild-type levels respectively indicating a phenotypic effect of haploinsufficiency of the mouse Msh2 gene. © 2000 CancerResearch Campaign PMID:11044352

  11. A germline missense mutation in exon 3 of the MSH2 gene in a Lynch syndrome family: correlation with phenotype and localization assay.

    PubMed

    Bianchi, Francesca; Maccaroni, Elena; Belvederesi, Laura; Brugiati, Cristiana; Giampieri, Riccardo; Bini, Federica; Bracci, Raffaella; Pagliaretta, Silvia; Del Prete, Michela; Piva, Francesco; Mandolesi, Alessandra; Scarpelli, Marina; Berardi, Rossana

    2017-08-07

    Lynch syndrome is caused by germline mutations in any of the MisMatch Repair (MMR) genes. About 37% of MSH2 variants are missense variants causing single amino-acid substitutions. Whether missense variants affect the normal function of MMR proteins is crucial both to provide affected families a more accurate risk assessment and to offer predictive testing to family members. Here we report one family, fulfilling both Amsterdam I and II criteria and Bethesda guidelines, referred to our center for genetic counselling. The proband and some of her relatives have been investigated for microsatellite instability (MSI), immunohistochemical MMR protein staining, direct sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). Also Subcellular Localization Assay and Splice site predictions analyses were used. A germline missense variant of uncertain significance (exon 3, p.Val161Asp) was found in MSH2 gene in proband and in some relatives. The variant was associated with lack of expression of MSH2 protein (DMMR) and MSI-High status in tumour tissues. The localization assay of the MSH2 protein showed an abnormal subcellular localization pattern of the corresponding protein. Finally, splice-site prediction analysis ruled out a potential role of new splice sites as the cause behind the lack of expression of MSH2 protein and we suppose a potential correlation with other forms of post-transcriptional regulation (circular RNAs). The variant here reported shows a high correlation with phenotype and is located in an evolutionary conserved domain. The localization assay also suggest a potential pathogenic role, thus supporting further research on this matter.

  12. The Founder Mutation MSH2*1906G→C Is an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Ashkenazi Jewish Population

    PubMed Central

    Foulkes, W. D.; Thiffault, I.; Gruber, S. B.; Horwitz, M.; Hamel, N.; Lee, C.; Shia, J.; Markowitz, A.; Figer, A.; Friedman, E.; Farber, D.; Greenwood, C. M. T.; Bonner, J. D.; Nafa, K.; Walsh, T.; Marcus, V.; Tomsho, L.; Gebert, J.; Macrae, F. A.; Gaff, C. L.; Paillerets, B. Bressac-de; Gregersen, P. K.; Weitzel, J. N.; Gordon, P. H.; MacNamara, E.; King, M.-C.; Hampel, H.; de la Chapelle, A.; Boyd, J.; Offit, K.; Rennert, G.; Chong, G.; Ellis, N. A.

    2002-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906G→C, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (P=.042), and those with colorectal cancer who carried the mutation were, on average, younger than affected individuals who did not carry it (P=.033). The mutation was not detected in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%–3% of colorectal cancer in those whose age at diagnosis is <60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria. PMID:12454801

  13. Activity (transcription) of the genes for MLH1, MSH2 and p53 in sporadic colorectal tumours with micro-satellite instability.

    PubMed

    Tou, S I H; Drye, E R; Boulos, P B; Hollingsworth, S J

    2004-05-17

    Micro-satellite instability (MSI) is relevant in the management of colorectal cancers (CRC) and relies on analysis of gene mutations, or production of the proteins involved in DNA mismatch repair (e.g. MLH1, MSH2). p53 mutation is also relevant in MSI, but high-level CRC (MSI-H) demonstrate fewer mutations than low-level (MSI-L) or stable (MSS) cancers. Recently, the importance of gene activity (transcription) in MSI has been identified, where rather than being mutated genes have been downregulated. In this study, 67 sporadic CRC and eight samples of normal bowel were analysed for MSI status (by SSCP) and levels of MLH1, MSH2 and p53 gene transcription (by RT-PCR and scanning densitometry). Micro-satellite instability correlated with gender and site, with more MSI-H CRC in females (P<0.02) and in the right colon (P<0.04). In MSI-H, p53 transcription was markedly reduced (P<0.003). Compared to normal bowel, MLH1 transcription was elevated in all cancers (P<0.01), while MSH2 transcription was elevated only in MSI-H (P<0.04). There was a direct correlation between MLH1 and MSH2 transcription (P<0.001). Although fewer mutations are reported in MSI-H than MSI-L/MSS, these results suggest that reduced p53 transcription might account for decreased tumour suppression in MSI-H. The direct correlation between MLH1 and MSH2 transcription suggests that control of these genes might be coordinated.

  14. Parotid Sebaceous Carcinoma in Patient with Muir Torre Syndrome, Caused by MSH2 Mutation.

    PubMed

    Neelakantan, Iyer Vishwas; Di Palma, Silvana; Smith, C E T; McCoombe, A

    2016-09-01

    Sebaceous carcinoma of parotid gland are extremely rare with only 29 cases reported so far. The development of parotid sebaceous carcinoma in association with mutation in the mismatch repair gene that causes Muir Torre Syndrome (MTS), a subset of Lynch Syndrome, is still unclear. This study describes such a case and reviews the literature to see if an association between parotid sebaceous carcinoma and multiple visceral malignancies seen in Lynch Syndrome has ever been described. MTS represents a small subset of the Hereditary Non Polyposis Colorectal Carcinoma family, thought to be a subtype of Lynch Syndrome, where patients are prone to develop multiple visceral cancers involving gastrointestinal and genitourinary tract along with sebaceous and non-sebaceous tumours of the skin. MTS is a rare hereditary, autosomal dominant cancer syndrome caused by Microsatellite Instability and defect in DNA mismatch repair protein. The germline mutation involves mostly hMSH2 and hMLH1 genes. In MTS the skin of the head and neck area with the periocular region in particular, is affected but sebaceous carcinomas of the parotid associated with visceral malignancies has not yet been reported in literature. Here we report an index case of sebaceous carcinoma of parotid gland in a patient with MTS.

  15. Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch repair and is causative for Lynch syndrome.

    PubMed

    Wielders, Eva; Delzenne-Goette, Elly; Dekker, Rob; van der Valk, Martin; Te Riele, Hein

    2017-04-01

    Missense variants of DNA mismatch repair (MMR) genes pose a problem in clinical genetics as long as they cannot unambiguously be assigned as the cause of Lynch syndrome (LS). To study such variants of uncertain clinical significance, we have developed a functional assay based on direct measurement of MMR activity in mouse embryonic stem cells expressing mutant protein from the endogenous alleles. We have applied this protocol to a specific truncation mutant of MSH2 that removes 60 C-terminal amino acids and has been found in suspected LS families. We show that the stability of the MSH2/MSH6 heterodimer is severely perturbed, causing attenuated MMR in in vitro assays and cancer predisposition in mice. This mutation can therefore unambiguously be considered as deleterious and causative for LS.

  16. Altered expression and new mutations in DNA mismatch repair genes MLH1 and MSH2 in melanoma brain metastases.

    PubMed

    Korabiowska, Monika; König, Fatima; Verheggen, Raphaela; Schlott, Thilo; Cordon-Cardo, Carlos; Romeike, Bernd; Brinck, Ulrich

    2004-01-01

    Brain metastases, including those of malignant melanoma (known for its high genomic instability), are the most common intracranial tumors. The main objective of this study was to investigate expression and mutation in the DNA mismatch repair system in melanoma brain metastases. Expression of MLH1, MSH2, PMS1 and PMS2 was investigated immunohistochemically in 31 melanoma metastatic tumors. Mutational analysis of MLH1 and MSH2 was performed in 17 melanoma brain metastases. Loss of MLH1 and MSH2 expression was found in 10/31 and 12/31 tumors. PMS1 (27/31) and PMS2 (28/31) expression was preserved in the majority of lesions. Potential missense mutation was found in MSH2 (exon 13) in 2/17 melanomas. Mutation in the intron sequence between exon 14 and 15 of MLH1 (exon 15) was observed in 4/17 cases. Our results indicate that the two major DNA mismatch repair genes, MLH1 and MSH2, are more frequently affected by alterations in the DNA mismatch repair system than the helper genes PMS1 and PMS2. The presence of mutations of MSH2 and MLH1 in melanoma brain metastases, which has not been found in primary melanomas, indicates the high genomic instability of melanoma brain metastases.

  17. Seven New Mutations in hMSH2, an HNPCC Gene, Identified by Denaturing Gradient-Gel Electrophoresis

    PubMed Central

    Wijnen, Juul; Vasen, Hans; Khan, P. Meera; Menko, Fred H.; van der Klift, Heleen; van Leeuwen, Claus; van den Broek, Marianne; van Leeuwen-Cornelisse, Inge; Nagengast, Fokko; Meijers-Heijboer, Anne; Lindhout, Dick; Griffioen, Gerrit; Cats, Annemieke; Kleibeuker, Jan; Varesco, Liliana; Bertario, Lucio; Bisgaard, Marie Luise; Mohr, Jan; Fodde, Riccardo

    1995-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup. ImagesFigure 1 PMID:7726159

  18. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2).

    PubMed

    Valeri, Nicola; Gasparini, Pierluigi; Braconi, Chiara; Paone, Alessio; Lovat, Francesca; Fabbri, Muller; Sumani, Khlea M; Alder, Hansjuerg; Amadori, Dino; Patel, Tushar; Nuovo, Gerard J; Fishel, Richard; Croce, Carlo M

    2010-12-07

    The overexpression of microRNA-21 (miR-21) is linked to a number of human tumors including colorectal cancer, where it appears to regulate the expression of tumor suppressor genes including p21, phosphatase and tensin homolog, TGFβ receptor II, and B-cell leukemia/lymphoma 2 -associated X protein. Here we demonstrate that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition protein complex, human mutS homolog 2 (hMSH2) and 6 (hMSH6). Colorectal tumors that express a high level of miR-21 display reduced hMSH2 protein expression. Cells that overproduce miR-21 exhibit significantly reduced 5-fluorouracil (5-FU)-induced G2/M damage arrest and apoptosis that is characteristic of defects in the core MMR component. Moreover, xenograft studies demonstrate that miR-21 overexpression dramatically reduces the therapeutic efficacy of 5-FU. These studies suggest that the down-regulation of the MMR mutator gene associated with miR-21 overexpression may be an important clinical indicator of therapeutic efficacy in colorectal cancer.

  19. Stimulation of oligonucleotide-directed gene correction by Redβ expression and MSH2 depletion in human HT1080 cells.

    PubMed

    Xu, Ke; Stewart, A Francis; Porter, Andrew C G

    2015-01-31

    The correction of disease-causing mutations by single-strand oligonucleotide-templated DNA repair (ssOR) is an attractive approach to gene therapy, but major improvements in ssOR efficiency and consistency are needed. The mechanism of ssOR is poorly understood but may involve annealing of oligonucleotides to transiently exposed single-stranded regions in the target duplex. In bacteria and yeast it has been shown that ssOR is promoted by expression of Redβ, a single-strand DNA annealing protein from bacteriophage lambda. Here we show that Redβ expression is well tolerated in a human cell line where it consistently promotes ssOR. By use of short interfering RNA, we also show that ssOR is stimulated by the transient depletion of the endogenous DNA mismatch repair protein MSH2. Furthermore, we find that the effects of Redβ expression and MSH2 depletion on ssOR can be combined with a degree of cooperativity. These results suggest that oligonucleotide annealing and mismatch recognition are distinct but interdependent events in ssOR that can be usefully modulated in gene correction strategies.

  20. Genomic rearrangements in MSH2 and MLH1 are rare mutational events in Spanish patients with hereditary nonpolyposis colorectal cancer.

    PubMed

    Castellví-Bel, Sergi; Castells, Antoni; Strunk, Mark; Ferrández, Angel; Piazuelo, Elena; Milà, Montserrat; Piñol, Virgínia; Rodríguez-Moranta, Francisco; Andreu, Montserrat; Lanas, Angel; Piqué, Josep Maria

    2005-07-08

    Colorectal cancer (CRC) is one of the most common neoplasms and a leading cause of death related to cancer worldwide. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition to the development of CRC, accounting for approximately 2.5% of the total CRC burden in Spain. Genomic rearrangements in the MSH2 and MLH1 genes have been reported to account for an important proportion of the mutation spectrum in HNPCC, and DNA dosage techniques have been developed facilitating molecular screening of such deletions/duplications. We screened for MSH2 and MLH1 genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA) in 142 Spanish patients at risk for HNPCC prior to the exon-by-exon mutation scanning and found a deletion encompassing exons 9-16 of MSH2 and a duplication encompassing exons 11-16 of MSH2, both only in one case. These results showed that MSH2/MLH1 rearrangements in Spanish patients at risk for HNPCC seem to be a less frequent mutational event than in other populations.

  1. Molecular Analysis of Hereditary Nonpolyposis Colorectal Cancer in the United States: High Mutation Detection Rate among Clinically Selected Families and Characterization of an American Founder Genomic Deletion of the MSH2 Gene

    PubMed Central

    Wagner, Anja; Barrows, Alicia; Wijnen, Juul Th.; van der Klift, Heleen; Franken, Patrick F.; Verkuijlen, Paul; Nakagawa, Hidewaki; Geugien, Marjan; Jaghmohan-Changur, Shantie; Breukel, Cor; Meijers-Heijboer, Hanne; Morreau, Hans; van Puijenbroek, Marjo; Burn, John; Coronel, Stephany; Kinarski, Yulia; Okimoto, Ross; Watson, Patrice; Lynch, Jane F.; de la Chapelle, Albert; Lynch, Henry T.; Fodde, Riccardo

    2003-01-01

    The identification of germline mutations in families with HNPCC is hampered by genetic heterogeneity and clinical variability. In previous studies, MSH2 and MLH1 mutations were found in approximately two-thirds of the Amsterdam-criteria–positive families and in much lower percentages of the Amsterdam-criteria–negative families. Therefore, a considerable proportion of HNPCC seems not to be accounted for by the major mismatch repair (MMR) genes. Does the latter result from a lack of sensitivity of mutation detection techniques, or do additional genes underlie the remaining cases? In this study we address these questions by thoroughly investigating a cohort of clinically selected North American families with HNPCC. We analyzed 59 clinically well-defined U.S. families with HNPCC for MSH2, MLH1, and MSH6 mutations. To maximize mutation detection, different techniques were employed, including denaturing gradient gel electrophoresis, Southern analysis, microsatellite instability, immunohistochemistry, and monoallelic expression analysis. In 45 (92%) of the 49 Amsterdam-criteria–positive families and in 7 (70%) of the 10 Amsterdam-criteria–negative families, a mutation was detected in one of the three analyzed MMR genes. Forty-nine mutations were in MSH2 or MLH1, and only three were in MSH6. A considerable proportion (27%) of the mutations were genomic rearrangements (12 in MSH2 and 2 in MLH1). Notably, a deletion encompassing exons 1–6 of MSH2 was detected in seven apparently unrelated families (12% of the total cohort) and was subsequently proven to be a founder. Screening of a second U.S. cohort with HNPCC from Ohio allowed the identification of two additional kindreds with the identical founder deletion. In the present study, we show that optimal mutation detection in HNPCC is achieved by combining accurate and expert clinical selection with an extensive mutation detection strategy. Notably, we identified a common North American deletion in MSH2, accounting

  2. Comparative study of mutations in SNP loci of K-RAS, hMLH1 and hMSH2 genes in neoplastic intestinal polyps and colorectal cancer

    PubMed Central

    Yan, Zhi-Hui; Cui, Li-Hong; Wang, Xiao-Hui; Li, Chao; He, Xing

    2014-01-01

    AIM: To clarify the molecular mechanism involved in pathogenesis of colorectal cancer as well as clinical significance of genetic analysis of histological samples. METHODS: A total of 480 blood and tissue specimens were collected in our hospital from January 2011 to October 2012. In the observation group, there were 120 blood specimens and 120 intestinal tract tissue specimens collected from patients with neoplastic intestinal polyps. In the control group I there were 80 blood specimens and 80 intestinal tract tissue specimens collected from patients with colorectal cancer. In the control group II there were 40 blood specimens and 40 intestinal tract tissue specimens collected from healthy individuals. The gene segments were amplified using PCR and DNA gel electrophoresis along with DNA sequence analysis were employed for the detection of the following single nucleotide polymorphisms (SNPs): K-RAS codons 12 and 13; hMLH1 (human mutS homolog 1) gene missense mutation at Va1384Asp; hMSH2 (human mutS homolog 2) gene missense mutation at 2783C/A. RESULTS: The mutation rate of the SNP at Va1384Asp locus of the hMLH1 gene from blood and tissue specimens in the observation group showed no statistical difference from those in the control group I. The mutation rates of SNPs in codons 12 and 13 of K-RAS and at 2783C/A locus of the hMSH2 gene were significantly lower in the observation group than in the control group I (χ2 = 15.476, 29.670, 10.811, 16.618, 33.538, 7.898, P < 0.05). The mutation rate of SNP at Va1384Asp locus of the hMLH1 gene was significantly higher in the observation group when compared to the control group II (χ2 = 10.486, 4.876, P < 0.05). The mutation rates of SNPs in codons 12 and 13 of K-RAS and at 2783C/A locus of the hMSH2 gene did not show any statistical difference from those in the control group II. CONCLUSION: There may be important clinical significance and relevance between neoplastic intestinal polyps and colorectal cancer in terms

  3. Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Bukovac, Anja; Vladušić, Tomislav; Tomas, Davor; Hrašćan, Reno

    2017-07-01

    Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1 (D16S3399), and CDH1 (D16S752) were also investigated for microsatellite instability. Our study revealed constant presence of microsatellite instability in meningioma patients when compared to their autologous blood DNA. Altogether 38% of meningiomas showed microsatellite instability at one microsatellite locus, 16% on two, and 13.3% on three loci. The percent of detected microsatellite instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (p = 0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were observed when MLH1 or MSH2 was tested against specific histopathological meningioma subtype or World Health Organization grade. However, genetic changes in DVL3 were strongly associated with anaplastic histology of meningioma (χ(2) = 9.14; p = 0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.

  4. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.

    PubMed

    Bonadona, Valérie; Bonaïti, Bernard; Olschwang, Sylviane; Grandjouan, Sophie; Huiart, Laetitia; Longy, Michel; Guimbaud, Rosine; Buecher, Bruno; Bignon, Yves-Jean; Caron, Olivier; Colas, Chrystelle; Noguès, Catherine; Lejeune-Dumoulin, Sophie; Olivier-Faivre, Laurence; Polycarpe-Osaer, Florence; Nguyen, Tan Dat; Desseigne, Françoise; Saurin, Jean-Christophe; Berthet, Pascaline; Leroux, Dominique; Duffour, Jacqueline; Manouvrier, Sylvie; Frébourg, Thierry; Sobol, Hagay; Lasset, Christine; Bonaïti-Pellié, Catherine

    2011-06-08

    Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome. To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes. Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed. Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias. Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations. MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with MLH1 or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.

  5. ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2-Msh3 are differentially modulated by mismatch and double-strand break repair DNA substrates.

    PubMed

    Kumar, Charanya; Eichmiller, Robin; Wang, Bangchen; Williams, Gregory M; Bianco, Piero R; Surtees, Jennifer A

    2014-06-01

    In Saccharomyces cerevisiae, Msh2-Msh3-mediated mismatch repair (MMR) recognizes and targets insertion/deletion loops for repair. Msh2-Msh3 is also required for 3' non-homologous tail removal (3'NHTR) in double-strand break repair. In both pathways, Msh2-Msh3 binds double-strand/single-strand junctions and initiates repair in an ATP-dependent manner. However, we recently demonstrated that the two pathways have distinct requirements with respect to Msh2-Msh3 activities. We identified a set of aromatic residues in the nucleotide binding pocket (FLY motif) of Msh3 that, when mutated, disrupted MMR, but left 3'NHTR largely intact. One of these mutations, msh3Y942A, was predicted to disrupt the nucleotide sandwich and allow altered positioning of ATP within the pocket. To develop a mechanistic understanding of the differential requirements for ATP binding and/or hydrolysis in the two pathways, we characterized Msh2-Msh3 and Msh2-msh3Y942A ATP binding and hydrolysis activities in the presence of MMR and 3'NHTR DNA substrates. We observed distinct, substrate-dependent ATP hydrolysis and nucleotide turnover by Msh2-Msh3, indicating that the MMR and 3'NHTR DNA substrates differentially modify the ATP binding/hydrolysis activities of Msh2-Msh3. Msh2-msh3Y942A retained the ability to bind DNA and ATP but exhibited altered ATP hydrolysis and nucleotide turnover. We propose that both ATP and structure-specific repair substrates cooperate to direct Msh2-Msh3-mediated repair and suggest an explanation for the msh3Y942A separation-of-function phenotype.

  6. Distinct Phenotypes Caused by Mutation of MSH2 in Trypanosome Insect and Mammalian Life Cycle Forms Are Associated with Parasite Adaptation to Oxidative Stress

    PubMed Central

    Bolderson, Jason; Campos, Priscila C.; Miranda, Julia B.; Alves, Ceres L.; Machado, Carlos R.; McCulloch, Richard; Teixeira, Santuza M. R.

    2015-01-01

    Background DNA repair mechanisms are crucial for maintenance of the genome in all organisms, including parasites where successful infection is dependent both on genomic stability and sequence variation. MSH2 is an early acting, central component of the Mismatch Repair (MMR) pathway, which is responsible for the recognition and correction of base mismatches that occur during DNA replication and recombination. In addition, recent evidence suggests that MSH2 might also play an important, but poorly understood, role in responding to oxidative damage in both African and American trypanosomes. Methodology/Principal Findings To investigate the involvement of MMR in the oxidative stress response, null mutants of MSH2 were generated in Trypanosoma brucei procyclic forms and in Trypanosoma cruzi epimastigote forms. Unexpectedly, the MSH2 null mutants showed increased resistance to H2O2 exposure when compared with wild type cells, a phenotype distinct from the previously observed increased sensitivity of T. brucei bloodstream forms MSH2 mutants. Complementation studies indicated that the increased oxidative resistance of procyclic T. brucei was due to adaptation to MSH2 loss. In both parasites, loss of MSH2 was shown to result in increased tolerance to alkylation by MNNG and increased accumulation of 8-oxo-guanine in the nuclear and mitochondrial genomes, indicating impaired MMR. In T. cruzi, loss of MSH2 also increases the parasite capacity to survive within host macrophages. Conclusions/Significance Taken together, these results indicate MSH2 displays conserved, dual roles in MMR and in the response to oxidative stress. Loss of the latter function results in life cycle dependent differences in phenotypic outcomes in T. brucei MSH2 mutants, most likely because of the greater burden of oxidative stress in the insect stage of the parasite. PMID:26083967

  7. ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2-Msh3 are differentially modulated by Mismatch and Double-strand Break Repair DNA substrates

    PubMed Central

    Kumar, Charanya; Eichmiller, Robin; Wang, Bangchen; Williams, Gregory M.; Bianco, Piero R.; Surtees, Jennifer A.

    2014-01-01

    In Saccharomyces cerevisiae, Msh2-Msh3-mediated mismatch repair (MMR) recognizes and targets insertion/deletion loops for repair. Msh2-Msh3 is also required for 3′ non-homologous tail removal (3′NHTR) in double-strand break repair. In both pathways, Msh2-Msh3 binds double-strand/single-strand junctions and initiates repair in an ATP-dependent manner. However, we recently demonstrated that the two pathways have distinct requirements with respect to Msh2-Msh3 activities. We identified a set of aromatic residues in the nucleotide binding pocket (FLY motif) of Msh3 that, when mutated, disrupted MMR, but left 3′ NHTR largely intact. One of these mutations, msh3Y942A, was predicted to disrupt the nucleotide sandwich and allow altered positioning of ATP within the pocket. To develop a mechanistic understanding of the differential requirements for ATP binding and/or hydrolysis in the two pathways, we characterized Msh2-Msh3 and Msh2-msh3Y942A ATP binding and hydrolysis activities in the presence of MMR and 3′ NHTR DNA substrates. We observed distinct, substrate-dependent ATP hydrolysis and nucleotide turnover by Msh2-Msh3, indicating that the MMR and 3′ NHTR DNA substrates differentially modify the ATP binding/hydrolysis activities of Msh2-Msh3. Msh2-msh3Y942A retained the ability to bind DNA and ATP but exhibited altered ATP hydrolysis and nucleotide turnover. We propose that both ATP and structure-specific repair substrates cooperate to direct Msh2-Msh3-mediated repair and suggest an explanation for the msh3Y942A separation-of-function phenotype. PMID:24746922

  8. miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer.

    PubMed

    Zhong, Zhiwei; Dong, Zhuo; Yang, Lihua; Gong, Zhaohui

    2012-10-01

    MicroRNAs regulate critical genes associated with lung cancer. Human mutS homolog 2 (hMSH2), one of the core mismatch repair genes, is affected in lung cancer development. The aim of this study is to investigate the role of miR-21 in hMSH2 gene expression and the effect of miR-21 on cell proliferation and cell cycle in lung cancer. The targets of miR-21 were predicted by a bioinformatics tool, and hMSH2 was validated as a direct target of miR-21 by luciferase activity assay. MiRNA mimics or inhibitors were used to stimulate or attenuate the effect of endogenous miR-21 on hMSH2 expression. MiR-21 and hMSH2 expressions were assessed with real-time RT-PCR and Western blotting. Cell cycle was determined by flow cytometry, and cell growth was analyzed by MTT assay and real-time cell analysis system. MiR-21 expression was inversely correlated with hMSH2 expression in human lung cancer cell lines. Further validation showed hMSH2 was directly regulated by miR-21. The up-regulation of miR-21 significantly promoted cell proliferation and revealed a higher proportion of cells at S phase. However, knockdown of miR-21 expression resulted in cell cycle arrest at G2/M phase and inhibited cell proliferation. These data suggest miR-21 is a key regulator of hMSH2 and modulates cell cycle and proliferation by targeting hMSH2 in human lung cancer.

  9. Penetrance of colorectal cancer among MLH1/MSH2 carriers participating in the colorectal cancer familial registry in Ontario

    PubMed Central

    Choi, Yun-Hee; Cotterchio, Michelle; McKeown-Eyssen, Gail; Neerav, Monga; Bapat, Bharati; Boyd, Kevin; Gallinger, Steven; McLaughlin, John; Aronson, Melyssa; Briollais, Laurent

    2009-01-01

    Background Several DNA mismatch repair (MMR) genes, responsible for the majority of Lynch Syndrome cancers, have been identified, predominantly MLH1 and MSH2, but the risk associated with these mutations is still not well established. The aim of this study is to provide population-based estimates of the risks of colorectal cancer (CRC) by gender and mutation type from the Ontario population. Methods We analyzed 32 families segregating MMR mutations selected from the Ontario Familial Colorectal Cancer Registry and including 199 first-degree and 421 second-degree relatives. The cumulative risks were estimated using a modified segregation-based approach, which allows correction for the ascertainment of the Lynch Syndrome families and permits account to be taken for missing genotype information. Results The risks of developing CRC by age 70 were 60% and 47% among men and women carriers of any MMR mutation, respectively. Among MLH1 mutation carriers, males had significantly higher risks than females at all ages (67% vs. 35% by age 70, p-value = 0.02), while the risks were similar in MSH2 carriers (about 54%). The relative risk associated with MLH1 was almost constant with age (hazard ratio (HR) varied between 5.5-5.1 over age 30–70), while the HR for MSH2 decreased with age (from 13.1 at age 30 to 5.4 at age 70). Conclusion This study provides a unique population-based study of CRC risks among MSH2/MLH1 mutation carriers in a Canadian population and can help to better define and understand the patterns of risks among members of Lynch Syndrome families. PMID:19698169

  10. UMD-MLH1/MSH2/MSH6 databases: description and analysis of genetic variations in French Lynch syndrome families

    PubMed Central

    Grandval, Philippe; Fabre, Aurélie J.; Gaildrat, Pascaline; Baert-Desurmont, Stéphanie; Buisine, Marie-Pierre; Ferrari, Anthony; Wang, Qing; Béroud, Christophe; Olschwang, Sylviane

    2013-01-01

    Lynch syndrome is an autosomal dominant disease caused by germ line heterozygous mutations mainly involving the MSH2, MLH1 and MSH6 genes that belong to the DNA MisMatch Repair (MMR) genes family. The French network counting the 16 licensed laboratories involved in Lynch syndrome genetic testing developed three locus-specific databases with the UMD® software (www.umd.be/MLH1/, www.umd.be/MSH2/ and www.umd.be/MSH6/) that presently contain a total of 7047 sequence variations including 707 distinct variations of a priori unknown functional significance (VUS) that were identified through complete mutation screening or targeted predictive testing. Mutation carriers are at high risk for developing early-onset colorectal and endometrial adenocarcinomas. Consensus clinical guidelines have been proposed, allowing the efficient detection of curable lesions. The major challenge of genetic testing is to reliably classify the genomic variations in those patients who seek genetic counseling. Combining the interactive tools of the software, the relevant published data and mainly original information produced by the French MisMatch Repair network, the UMD-MLH1/MSH2/MSH6 databases provide interpretation data for the 707 VUS that were classified according to the IARC 5-Class system. These public databases are regularly updated to improve the classification of all registered VUS, exploring their role in cancer pre-disposition based on structural and functional approaches. PMID:23729658

  11. Crosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair

    PubMed Central

    Lai, Yanhao; Budworth, Helen; Beaver, Jill M.; Chan, Nelson L. S.; Zhang, Zunzhen; McMurray, Cynthia T.; Liu, Yuan

    2016-01-01

    Studies in knockout mice provide evidence that MSH2–MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2–MSH3 is used as a component of the BER machinery to cause expansion. On its own, pol β fails to copy TNRs during DNA synthesis, and bypasses them on the template strand to cause deletion. Remarkably, MSH2–MSH3 not only stimulates pol β to copy through the repeats but also enhances formation of the flap precursor for expansion. Our results provide direct evidence that MMR and BER, operating together, form a novel hybrid pathway that changes the outcome of TNR instability from deletion to expansion during the removal of oxidized bases. We propose that cells implement crosstalk strategies and share machinery when a canonical pathway is ineffective in removing a difficult lesion. PMID:27546332

  12. Association of a novel point mutation in MSH2 gene with familial multiple primary cancers.

    PubMed

    Hu, Hai; Li, Hong; Jiao, Feng; Han, Ting; Zhuo, Meng; Cui, Jiujie; Li, Yixue; Wang, Liwei

    2017-10-03

    Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues. We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC. We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients. Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.

  13. Identification of a deletion in the mismatch repair gene, MSH2, using mouse-human cell hybrids monosomal for chromosome 2.

    PubMed

    Pyatt, R E; Nakagawa, H; Hampel, H; Sedra, M; Fuchik, M B; Comeras, I; de la Chapelle, A; Prior, T W

    2003-03-01

    Hereditary non-polyposis colorectal cancer is characterized by mutations in one of the DNA mismatch repair genes, primarily MLH1, MSH2, or MSH6. We report here the identification of a genomic deletion of approximately 11.4 kb encompassing the first two exons of the MSH2 gene in two generations of an Ohio family. By Southern blot analysis, using a cDNA probe spanning the first seven exons of MSH2, an alteration in each of three different enzyme digests (including a unique 13-kb band on HindIII digests) was observed, which suggested the presence of a large alteration in the 5' region of this gene. Mouse-human cell hybrids from a mutation carrier were then generated which contained a single copy each of human chromosome 2 on which the MSH2 gene resides. Southern blots on DNA from the cell hybrids demonstrated the same, unique 13-kb band from one MSH2 allele, as seen in the diploid DNA. DNA from this same monosomal cell hybrid failed to amplify in polymerase chain reactions (PCRs) using primers to exons 1 and 2, demonstrating the deletion of these sequences in one MSH2 allele, and the breakpoints involving Alu repeats were identified by PCR amplification and sequence analysis.

  14. High proportion of large genomic rearrangements in hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families of the Basque Country.

    PubMed

    Martínez-Bouzas, Cristina; Ojembarrena, Enrique; Beristain, Elena; Errasti, Javier; Viguera, Noelia; Tejada Minguéz, Maria-Isabel

    2007-10-08

    Hereditary nonpolyposis colorectal cancer (HNPCC), which represents the most common form of inherited colorectal cancer, results from germline alterations of the mismatch repair genes MSH2, MLH1 and MSH6. Rearrangements of MSH2 and MLH1 are involved in at least 10% and 4.3%, respectively, of the HNPCC families fulfilling the Amsterdam (AMS) criteria. We applied a recently developed method, multiplex ligation-dependent probe amplification (MLPA), to study MLH1/MSH2 copy number changes in 29 unrelated Basque Country HNPCC families. We detected six different genomic rearrangements in total (6/29=20.69%), four in MSH2 gene (13.79%), and two in MLH1 gene. All of the MSH2 rearrangements were genomic deletions involving several exons. The MLH1 rearrangements were initially detected as one deletion of exon 18 and one deletion of exon 19, but after sequencing analysis, these deletions were not confirmed and corresponded to base pair mutations. We conclude that MLPA is an excellent tool for detecting exon copy number changes in MLH1 and MSH2 in the DNA from HNPCC patients, although all detected rearrangements should be confirmed by an independent molecular methodology. Furthermore, our results in the Basque Country show higher percentages of rearrangements than previously published by other authors.

  15. Evidence that hMLH3 functions primarily in meiosis and in hMSH2-hMSH3 mismatch repair.

    PubMed

    Charbonneau, Nicole; Amunugama, Ravindra; Schmutte, Christoph; Yoder, Kristine; Fishel, Richard

    2009-07-01

    The MutS (MSH) and MutL (MLH) homologs are conserved proteins that function in mismatch repair (MMR) and meiosis. We examined mRNA and protein expression of hMLH3 compared to other human MSH and MLH in a panel of human tissues and the HeLa cell line. Quantitative PCR suggests that MSH and MLH transcripts are expressed ubiquitously. hMLH3 mRNA is present at low levels in numerous tissues. Protein expression appears to correlate with a threshold of mRNA expression with hMLH3 present at high levels in testis. In addition, we have found and mapped interactions between hMLH1 and hMLH3 with hMSH3. These data are consistent with yeast studies and suggest a role for hMLH3 in meiosis as well as hMSH2-hMSH3 repair processes and little if any role in Hereditary Non-Polyposis Colorectal Cancer (HNPCC).

  16. Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in Malaysia.

    PubMed

    Abdul Murad, Nor Azian; Othman, Zulhabri; Khalid, Melati; Abdul Razak, Zuraini; Hussain, Rosniza; Nadesan, Sukumar; Sagap, Ismail; Mohamed Rose, Isa; Wan Ngah, Wan Zurinah; Jamal, Rahman

    2012-11-01

    Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.

  17. Relationship between MLH-1, MSH-2, PMS-2,MSH-6 expression and clinicopathological features in colorectal cancer.

    PubMed

    Karahan, Birgül; Argon, Asuman; Yıldırım, Mehmet; Vardar, Enver

    2015-01-01

    Colorectal cancers are the third most common in both sexes and they are the second most common cause of cancer-related death. 12-15% of colorectal cancers develop through microsatellite instability (the hereditary mutation in at least one of DNA mismatch repair genes) pathway and they are 2-5% hereditary. In this study, we investigated the correlation between the clinicopathological features themselves and also the correlation between them and the immunohistochemical MLH-1, MSH-2, PMS-2, MSH-6 expressions in a total of 186 resection materials with colorectal adenocarcinoma between 2008 and 2012. All the cases were retrospectively evaluated in terms of age, sex, localization, size, accompanying polyp, multiple tumor, arising from polyp, differentiation, mucinous differentiation, pathological tumor stage, lymphovascular and perineural invasion, lymphocyte amount in the tumor microenvironment, surgical border and lymph node metastasis. We prepared multiple tissue blocks which had 4-millimeter tumor. Immunohistochemically, MLH-1, MSH-2, PMS-2, MSH-6 primary antibodies were studied. Statistically, "Kruskal-Wallis" ve "Pearson's chi-squared" tests were used. We found a positive correlation between loss of MLH-1 and PMS-2 expressions and the right-colon location, poor and mucinous differentiation and dense lymphocytic infiltration. In addition, loss of MSH-2 and MSH-6 expressions was correlated with the right-colon location, poor and mucinous differentiation. We found a meaningful relationship between immunohistochemical markers and clinicopathological features usually observed in tumors with microsatellite instability. This finding may arouse suspicion for MSI. However, the findings in our study must be supported with studies conducted in large series including molecular methods.

  18. The MSH2 c.388_389del mutation shows a founder effect in Portuguese Lynch syndrome families.

    PubMed

    Pinheiro, M; Pinto, C; Peixoto, A; Veiga, I; Mesquita, B; Henrique, R; Lopes, P; Sousa, O; Fragoso, M; Dias, L M; Baptista, M; Marinho, C; Mangold, E; Vaccaro, C; Evans, D G; Farrington, S; Dunlop, M G; Teixeira, M R

    2013-09-01

    The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study.

    PubMed

    Gunes, S; Agarwal, A; Henkel, R; Mahmutoglu, A M; Sharma, R; Esteves, S C; Aljowair, A; Emirzeoglu, D; Alkhani, A; Pelegrini, L; Joumah, A; Sabanegh, E

    2017-10-06

    MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation. © 2017 Blackwell Verlag GmbH.

  20. Assessment of the InSiGHT Interpretation Criteria for the Clinical Classification of 24 MLH1 and MSH2 Gene Variants.

    PubMed

    Tricarico, Rossella; Kasela, Mariann; Mareni, Cristina; Thompson, Bryony A; Drouet, Aurélie; Staderini, Lucia; Gorelli, Greta; Crucianelli, Francesca; Ingrosso, Valentina; Kantelinen, Jukka; Papi, Laura; De Angioletti, Maria; Berardi, Margherita; Gaildrat, Pascaline; Soukarieh, Omar; Turchetti, Daniela; Martins, Alexandra; Spurdle, Amanda B; Nyström, Minna; Genuardi, Maurizio

    2017-01-01

    Pathogenicity assessment of DNA variants in disease genes to explain their clinical consequences is an integral component of diagnostic molecular testing. The International Society for Gastrointestinal Hereditary Tumors (InSiGHT) has developed specific criteria for the interpretation of mismatch repair (MMR) gene variants. Here, we performed a systematic investigation of 24 MLH1 and MSH2 variants. The assessments were done by analyzing population frequency, segregation, tumor molecular characteristics, RNA effects, protein expression levels, and in vitro MMR activity. Classifications were confirmed for 15 variants and changed for three, and for the first time determined for six novel variants. Overall, based on our results, we propose the introduction of some refinements to the InSiGHT classification rules. The proposed changes have the advantage of homogenizing the InSIGHT interpretation criteria with those set out by the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium for the BRCA1/BRCA2 genes. We also observed that the addition of only few clinical data was sufficient to obtain a more stable classification for variants considered as "likely pathogenic" or "likely nonpathogenic." This shows the importance of obtaining as many as possible points of evidence for variant interpretation, especially from the clinical setting.

  1. Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemistry and tumor stage.

    PubMed

    Korabiowska, Monika; Cordon-Cardo, Carlos; Jaenckel, Fredericke; Stachura, Jerzy; Fischer, Gösta; Brinck, Ulrich

    2004-12-01

    Defects in DNA mismatch-repair genes MLH1 and MSH2 reported primarily in hereditary nonpolyposis colorectal carcinoma are present in many sporadic tumors, including malignant melanomas. The main aim of this study was to investigate the expression of these genes in malignant melanomas in relation to tumor stage. An experiment was performed on paraffin-embedded tissue microarrays of malignant melanomas applying in situ hybridization with probes produced by our research group and immunohistochemical techniques. In situ hybridization demonstrated MLH1 expression in 45 of 59 melanomas and MSH2 expression in 51 of 59 melanomas. Immunohistochemistry detected MLH1 expression in 46 of 59 melanomas and MSH2 expression in 50 of 59 melanomas. Down-regulation of expression of both DNA mismatch repair genes in malignant melanomas was observed. The findings obtained by in situ hybridization and immunohistochemistry correlated significantly. Our study demonstrates the suitability of in situ hybridization with MLH1 and MSH2 probes for paraffin-embedded tissue. Tissue microarrays can be used successfully in both in situ hybridization and immunohistochemistry to analyze the expression of DNA mismatch-repair genes.

  2. A study on MSH2 and MLH1 mutations in hereditary nonpolyposis colorectal cancer families from the Basque Country, describing four new germline mutations.

    PubMed

    Martínez-Bouzas, Cristina; Beristain, Elena; Ojembarrena, Enrique; Errasti, Jose; Mujika, Karmele; Viguera, Noelia; Tejada, Maria Isabel

    2009-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome underlies between 2 and 5% of all colorectal cancer. It is inherited as an autosomal dominant condition due to mutations in the mismatch repair genes. Fifty-four non-related index cases, 21 of them fulfilling Amsterdam criteria I or II, were studied. Ten (10/21 = 47.6%) different pathological mutations were found in this group, two of which had not previously been reported--one in MLH1 and the other in MSH2-. In the remaining patients, we also found another family with one of these new mutations, and four additional changes, two of which were also new--a pathological change in MSH2 and a second change of uncertain significance in MLH1-, while the other two changes had already been reported. Of all mutations, eight were found in MSH2 (8/15 = 53.3%) and seven in MLH1 (7/15 = 46.6%), suggesting a slightly greater involvement of MSH2 in HNPCC than MLH1 in our population, in contrast to the results reported by other authors.

  3. The PREMM1,2,6 Model Predicts Risk of MLH1, MSH2, and MSH6 Germline Mutations Based on Cancer History

    PubMed Central

    Kastrinos, Fay; Steyerberg, Ewout W.; Mercado, Rowena; Balmaña, Judith; Holter, Spring; Gallinger, Steven; Siegmund, Kimberly D.; Church, James M.; Jenkins, Mark A.; Lindor, Noralane M.; Thibodeau, Stephen N.; Burbidge, Lynn Anne; Wenstrup, Richard J.; Syngal, Sapna

    2011-01-01

    BACKGROUND & AIMS We developed and validated a model to estimate the risks for mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6 based on personal and family history of cancer. METHODS Data were analyzed from 4539 probands tested for mutations in MLH1, MSH2, and MSH6. A multivariable polytomous logistic regression model (PREMM1,2,6) was developed to predict the overall risk of MMR gene mutations and the risk of mutation in each of the 3 genes. The model’s discriminative ability was validated in 1827 population-based CRC cases. RESULTS Twelve percent of the original cohort carried pathogenic mutations (204 in MLH1, 250 in MSH2, and 71 in MSH6). The PREMM1,2,6 model incorporated the following factors from the probands and first- and second-degree relatives (odds ratio; 95% confidence intervals [CI]): male sex (1.9; 1.5–2.4), a CRC (4.3; 3.3–5.6), multiple CRCs (13.7; 8.5–22), endometrial cancer (6.1; 4.6–8.2), and extracolonic cancers (3.3; 2.4–4.6). The areas under the receiver operating characteristic curves were 0.86 (95% CI: 0.82–0.91) for MLH1 mutation carriers, 0.87 (95% CI: 0.83–0.92) for MSH2, and 0.81 (95% CI: 0.69– 0.93) for MSH6; in validation, they were 0.88 for the overall cohort (95% CI: 0.86–0.90) and the population-based cases (95% CI: 0.83–0.92). CONCLUSIONS We developed the PREMM1,2,6 model that incorporates information on cancer history from probands and their relatives to estimate an individual’s risk for mutations in the MMR genes MLH1, MSH2, and MSH6. This web-based decision making tool can be used to assess risk for hereditary CRC and guide clinical management. PMID:20727894

  4. DNA Methylation Identifies Loci Distinguishing Hereditary Nonpolyposis Colorectal Cancer Without Germ-Line MLH1/MSH2 Mutation from Sporadic Colorectal Cancer

    PubMed Central

    Chen, Chung-Hsing; Sheng Jiang, Shih; Hsieh, Ling-Ling; Tang, Reiping; Hsiung, Chao A; Tsai, Hui-Ju; Chang, I-Shou

    2016-01-01

    Objectives: Roughly half of hereditary nonpolyposis colorectal cancer (HNPCC) cases are Lynch syndrome and exhibit germ-line mutations in DNA mismatch repair (MMR) genes; the other half are familial colorectal cancer (CRC) type X (FCCTX) and are MMR proficient. About 70% of Lynch syndrome tumors have germ-line MLH1 or MSH2 mutations. The clinical presentation, histopathological features, and carcinogenesis of FCCTX resemble those of sporadic MMR-proficient colorectal tumors. It is of interest to obtain biomarkers that distinguish FCCTX from sporadic microsatellite stable (MSS) CRC, to develop preventive strategies. Methods: The tumors and adjacent normal tissues of 40 patients with HNPCC were assayed using the Illumina Infinium HumanMethylation27 (HM27) BeadChip to assess the DNA methylation level at about 27,000 loci. The germ-line mutation status of MLH1 and MSH2 and the microsatellite instability status in these patients were obtained. Genome-wide DNA methylation measurements of three groups of patients with general CRC were downloaded from public domain databases. Probes with DNA methylation levels that differed significantly between patients with sporadic MSS CRC and FCCTX were examined, to explore their potential as biomarkers. Results: We found that MSS HNPCC tumors were overwhelmingly hypomethylated compared with those from patient groups with other types of CRC, including germ-line MLH1/MSH2-mutated HNPCC and sporadic MSS CRC. Five gene-marker panels that exhibited a sensitivity of 100% and a specificity higher than 90% in both discovery and validation cohorts were proposed to distinguish MSS HNPCC tumors from sporadic MSS CRC. Conclusions: Our results warrant further investigation and validation. The loci identified here may become useful biomarkers for distinguishing between FCCTX and sporadic MSS CRC tumors. PMID:27977020

  5. Fluconazole and Echinocandin Resistance of Candida glabrata Correlates Better with Antifungal Drug Exposure Rather than with MSH2 Mutator Genotype in a French Cohort of Patients Harboring Low Rates of Resistance

    PubMed Central

    Dellière, Sarah; Healey, Kelley; Gits-Muselli, Maud; Carrara, Bastien; Barbaro, Alessandro; Guigue, Nicolas; Lecefel, Christophe; Touratier, Sophie; Desnos-Ollivier, Marie; Perlin, David S.; Bretagne, Stéphane; Alanio, Alexandre

    2016-01-01

    Candida glabrata is a major pathogenic yeast in humans that is known to rapidly acquire resistance to triazole and echinocandin antifungal drugs. A mutator genotype (MSH2 polymorphism) inducing a mismatch repair defect has been recently proposed to be responsible for resistance acquisition in C. glabrata clinical isolates. Our objectives were to evaluate the prevalence of antifungal resistance in a large cohort of patients in Saint-Louis hospital, Paris, France, some of whom were pre-exposed to antifungal drugs, as well as to determine whether MSH2 polymorphisms are associated with an increased rate of fluconazole or echinocandin resistance. We collected 268 isolates from 147 patients along with clinical data and previous antifungal exposure. Fluconazole and micafungin minimal inhibition concentrations (MICs) were tested, short tandem repeat genotyping was performed, and the MSH2 gene was sequenced. According to the European Committee on Antimicrobial Susceptibility breakpoints, 15.7% of isolates were resistant to fluconazole (MIC > 32 mg/L) and 0.7% were resistant to micafungin (MIC > 0.03 mg/L). A non-synonymous mutation within MSH2 occurred in 44% of the isolates, and 17% were fluconazole resistant. In comparison, fluconazole resistant isolates with no MSH2 mutation represented 15% (P = 0.65). MSH2 polymorphisms were associated with the short tandem repeat genotype. The rate of echinocandin resistance is low and correlates with prior exposure to echinocandin. The mutator genotype was not associated with enrichment in fluconazole resistance but instead corresponded to rare and specific genotypes. PMID:28066361

  6. Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families

    PubMed Central

    2010-01-01

    Background Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Methods Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Results Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. Conclusion The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect. PMID:20937110

  7. Mechanism of Chromophore Assisted Laser Inactivation Employing Fluorescent Proteins

    PubMed Central

    McLean, Mark A.; Rajfur, Zenon; Chen, Zaozao; Humphrey, David; Yang, Bing; Sligar, Stephen G.; Jacobson, Ken

    2009-01-01

    Chromophore Assisted Laser Inactivation (CALI) is a technique that uses irradiation of chromophores proximate to a target protein to inactivate function. Previously, EGFP mediated CALI has been used to inactivate EGFP-fusion proteins in a spatio-temporally defined manner within cells but the mechanism of inactivation is unknown 1, 2. To help elucidate the mechanism of protein inactivation mediated by fluorescent protein CALI ([FP]-CALI), the activities of purified Glutathione-S-transferase-FP (GST-EXFP) fusions were measured after laser irradiation in vitro. Singlet oxygen and free radical quenchers as well as the removal of oxygen inhibited CALI, indicating the involvement of a reactive oxygen species (ROS). At higher concentrations of protein, turbidity after CALI increased significantly indicating cross-linking of proximate fusion proteins suggesting that damage of residues on the surface the protein, distant from the active site, results in inactivation. Control experiments removed sample heating as a possible cause of these effects. Different FP mutants fused to GST vary in their CALI efficiency in the order EGFP>EYFP>ECFP, while a GST construct that binds FlAsH results in significantly higher CALI efficiency than any of the XFPs tested. It is likely that the hierarchy of XFP effectiveness reflects the balance between ROS that are trapped within the XFP structure and cause fluorophore and chromophore bleaching and those that escape to effect CALI of proximate proteins. PMID:19199572

  8. Impact of 226C>T MSH2 gene mutation on cancer phenotypes in two HNPCC-associated highly-consanguineous families from Kuwait: emphasis on premarital genetic testing.

    PubMed

    Marafie, Makia J; Al-Awadi, Sadiqa; Al-Mosawi, Fatemah; Elshafey, Alaa; Al-Ali, Waleed; Al-Mulla, Fahd

    2009-01-01

    Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is one of the commonest cancer susceptibility syndromes. It is characterized by early onset colon cancer and a variety of extracolonic tumours. Germline mutations in the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS1, and PMS2) are responsible for this disorder. Identifying an affected individual depends on the tumour histopathology, family history that fulfils the Amsterdam and/or Bethesda criteria, tumour immunohistochemistry, microsatellite instability, and finally molecular analysis of an affected member. It is a laborious, time consuming and expensive procedure, which needs the effort of a multi-disciplinary team. However, once the diagnosis is established and germline defect is identified, other high risk pre-symptomatic carriers could be offered intensive surveillance and management as a preventive measure against cancer development. Here, we present two large highly consanguineous HNPCC-families from Kuwait in whom a founder MSH2 mutation was identified. The relationship between this mutation and cancer expressivity in two large consanguineous families harbouring other genetic defects is discussed. Moreover, we shed light on the challenges pertaining to diagnosis, screening, premarital counselling of couples and prenatal diagnosis of offspring with biallelic MSH2 gene mutation.

  9. Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

    SciTech Connect

    Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

    2011-09-01

    Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be

  10. Employing proteomic analysis to compare Paracoccidioides lutzii yeast and mycelium cell wall proteins.

    PubMed

    Araújo, Danielle Silva; de Sousa Lima, Patrícia; Baeza, Lilian Cristiane; Parente, Ana Flávia Alves; Melo Bailão, Alexandre; Borges, Clayton Luiz; de Almeida Soares, Célia Maria

    2017-11-01

    Paracoccidioidomycosis is an important systemic mycosis caused by thermodimorphic fungi of the Paracoccidioides genus. During the infective process, the cell wall acts at the interface between the fungus and the host. In this way, the cell wall has a key role in growth, environment sensing and interaction, as well as morphogenesis of the fungus. Since the cell wall is absent in mammals, it may present molecules that are described as target sites for new antifungal drugs. Despite its importance, up to now few studies have been conducted employing proteomics in for the identification of cell wall proteins in Paracoccidioides spp. Here, a detailed proteomic approach, including cell wall-fractionation coupled to NanoUPLC-MS(E), was used to study and compare the cell wall fractions from Paracoccidioides lutzii mycelia and yeast cells. The analyzed samples consisted of cell wall proteins extracted by hot SDS followed by extraction by mild alkali. In summary, 512 proteins constituting different cell wall fractions were identified, including 7 predicted GPI-dependent cell wall proteins that are potentially involved in cell wall metabolism. Adhesins previously described in Paracoccidioides spp. such as enolase, glyceraldehyde-3-phosphate dehydrogenase were identified. Comparing the proteins in mycelium and yeast cells, we detected some that are common to both fungal phases, such as Ecm33, and some specific proteins, as glucanase Crf1. All of those proteins were described in the metabolism of cell wall. Our study provides an important elucidation of cell wall composition of fractions in Paracoccidioides, opening a way to understand the fungus cell wall architecture. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. DNA mismatch repair proteins are required for efficient herpes simplex virus 1 replication.

    PubMed

    Mohni, Kareem N; Mastrocola, Adam S; Bai, Ping; Weller, Sandra K; Heinen, Christopher D

    2011-12-01

    Herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that replicates in the nucleus of its human host cell and is known to interact with many cellular DNA repair proteins. In this study, we examined the role of cellular mismatch repair (MMR) proteins in the virus life cycle. Both MSH2 and MLH1 are required for efficient replication of HSV-1 in normal human cells and are localized to viral replication compartments. In addition, a previously reported interaction between MSH6 and ICP8 was confirmed by coimmunoprecipitation and extended to show that UL12 is also present in this complex. We also report for the first time that MLH1 associates with ND10 nuclear bodies and that like other ND10 proteins, MLH1 is recruited to the incoming genome. Knockdown of MLH1 inhibits immediate-early viral gene expression. MSH2, on the other hand, which is generally thought to play a role in mismatch repair at a step prior to that of MLH1, is not recruited to incoming genomes and appears to act at a later step in the viral life cycle. Silencing of MSH2 appears to inhibit early gene expression. Thus, both MLH1 and MSH2 are required but appear to participate in distinct events in the virus life cycle. The observation that MLH1 plays an earlier role in HSV-1 infection than does MSH2 is surprising and may indicate a novel function for MLH1 distinct from its known MSH2-dependent role in mismatch repair.

  12. Characterizing Protein Interactions Employing a Genome-Wide siRNA Cellular Phenotyping Screen

    PubMed Central

    Suratanee, Apichat; Schaefer, Martin H.; Betts, Matthew J.; Soons, Zita; Mannsperger, Heiko; Harder, Nathalie; Oswald, Marcus; Gipp, Markus; Ramminger, Ellen; Marcus, Guillermo; Männer, Reinhard; Rohr, Karl; Wanker, Erich; Russell, Robert B.; Andrade-Navarro, Miguel A.; Eils, Roland; König, Rainer

    2014-01-01

    Characterizing the activating and inhibiting effect of protein-protein interactions (PPI) is fundamental to gain insight into the complex signaling system of a human cell. A plethora of methods has been suggested to infer PPI from data on a large scale, but none of them is able to characterize the effect of this interaction. Here, we present a novel computational development that employs mitotic phenotypes of a genome-wide RNAi knockdown screen and enables identifying the activating and inhibiting effects of PPIs. Exemplarily, we applied our technique to a knockdown screen of HeLa cells cultivated at standard conditions. Using a machine learning approach, we obtained high accuracy (82% AUC of the receiver operating characteristics) by cross-validation using 6,870 known activating and inhibiting PPIs as gold standard. We predicted de novo unknown activating and inhibiting effects for 1,954 PPIs in HeLa cells covering the ten major signaling pathways of the Kyoto Encyclopedia of Genes and Genomes, and made these predictions publicly available in a database. We finally demonstrate that the predicted effects can be used to cluster knockdown genes of similar biological processes in coherent subgroups. The characterization of the activating or inhibiting effect of individual PPIs opens up new perspectives for the interpretation of large datasets of PPIs and thus considerably increases the value of PPIs as an integrated resource for studying the detailed function of signaling pathways of the cellular system of interest. PMID:25255318

  13. Immunoglobulin G elution in protein A chromatography employing the method of chromatofocusing for reducing the co-elution of impurities.

    PubMed

    Pinto, Nuno D S; Uplekar, Shaunak D; Moreira, Antonio R; Rao, Govind; Frey, Douglas D

    2017-01-01

    Purification processes for monoclonal Immunoglobulin G (IgG) typically employ protein A chromatography as a capture step to remove most of the impurities. One major concern of the post-protein A chromatography processes is the co-elution of some of the host cell proteins (HCPs) with IgG in the capture step. In this work, a novel method for IgG elution in protein A chromatography that reduces the co-elution of HCPs is presented where a two-step pH gradient is self-formed inside a protein A chromatography column. The complexities involved in using an internally produced pH gradient in a protein A chromatography column employing adsorbed buffering species are discussed though equation-based modeling. Under the conditions employed, ELISA assays show a 60% reduction in the HCPs co-eluting with the IgG fraction when using the method as compared to conventional protein A elution without affecting the IgG yield. Evidence is also obtained which indicates that the amount of leached protein A present in free solution in the purified product is reduced by the new method. Biotechnol. Bioeng. 2017;114: 154-162. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Homologous and homeologous intermolecular gene conversion are not differentially affected by mutations in the DNA damage or the mismatch repair genes RAD1, RAD50, RAD51, RAD52, RAD54, PMS1 and MSH2

    SciTech Connect

    Porter, G.; Westmoreland, J.; Priebe, S.

    1996-06-01

    Mismatch repair (MMR) genes or genes involved in both DNA damage repair and homologous recombination might affect homeologous vs. homologous recombination differentially. Spontaneous mitotic gene conversion between a chromosome and a homologous or homeologous donor sequence (14% diverged) on a single copy plasmid was examined in wild-type Saccharomyces cerevisiae strains and in MMR or DNA damage repair mutants. Homologous recombination in rad51, rad52 and rad54 mutants was considerably reduced, while there was little effect of rad1, rad50, pms1 and msh2 null mutations. DNA divergence resulted in no differential effect on recombination rates in the wild type or the mutants; there was only a five- to 10-fold reduction in homeologous relative to homologous recombination regardless of background. Since DNA divergence is known to affect recombination in some systems, we propose that differences in the role of MMR depends on the mode of recombination and/or the level of divergence. Based on analysis of the recombination breakpoints, there is a minimum of three homologous bases required at a recombination junction. A comparison of Rad{sup +} vs. rad52 strains revealed that while all conversion tracts are continuous, elimination of RAD52 leads to the appearance of a novel class of very short conversion tracts. 67 refs., 5 figs., 4 tabs.

  15. Homologous and Homeologous Intermolecular Gene Conversion Are Not Differentially Affected by Mutations in the DNA Damage or the Mismatch Repair Genes Rad1, Rad50, Rad51, Rad52, Rad54, Pms1 and Msh2

    PubMed Central

    Porter, G.; Westmoreland, J.; Priebe, S.; Resnick, M. A.

    1996-01-01

    Mismatch repair (MMR) genes or genes involved in both DNA damage repair and homologous recombination might affect homeologous vs. homologous recombination differentially. Spontaneous mitotic gene conversion between a chromosome and a homologous or homeologous donor sequence (14% diverged) on a single copy plasmid was examined in wild-type Saccharomyces cerevisiae strains and in MMR or DNA damage repair mutants. Homologous recombination in rad51, rad52 and rad54 mutants was considerably reduced, while there was little effect of rad1, rad50, pms1 and msh2 null mutations. DNA divergence resulted in no differential effect on recombination rates in the wild type or the mutants; there was only a five- to 10-fold reduction in homeologous relative to homologous recombination regardless of background. Since DNA divergence is known to affect recombination in some systems, we propose that differences in the role of MMR depends on the mode of recombination and/or the level of divergence. Based on analysis of the recombination breakpoints, there is a minimum of three homologous bases required at a recombination junction. A comparison of Rad(+) vs. rad52 strains revealed that while all conversion tracts are continuous, elimination of RAD52 leads to the appearance of a novel class of very short conversion tracts. PMID:8725224

  16. Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.

    PubMed

    da Silva Calixto, Poliane; Lopes, Otávio Sérgio; Dos Santos Maia, Mayara; Herrero, Sylvia Satomi Takeno; Longui, Carlos Alberto; Melo, Cynthia Germoglio Farias; de Carvalho Filho, Ivan Rodrigues; Soares, Leonardo Ferreira; de Medeiros, Arnaldo Correia; Delatorre, Plínio; Khayat, André Salim; Burbano, Rommel Rodriguez; Lima, Eleonidas Moura

    2017-06-30

    Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific - PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.

  17. Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma.

    PubMed

    Wagner, Vivian Petersen; Webber, Liana Preto; Salvadori, Gabriela; Meurer, Luise; Fonseca, Felipe Paiva; Castilho, Rogério Moraes; Squarize, Cristiane Helena; Vargas, Pablo Agustin; Martins, Manoela Domingues

    2016-05-01

    The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.

  18. Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma

    PubMed Central

    Wagner, Vivian Petersen; Webber, Liana Preto; Salvadori, Gabriela; Meurer, Luise; Fonseca, Felipe Paiva; Castilho, Rogério Moraes; Squarize, Cristiane Helena; Vargas, Pablo Agustin; Martins, Manoela Domingues

    2016-01-01

    Abstract The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC). The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC. All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02). This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC. PMID:27258499

  19. Quantitative proteomic investigation employing stable isotope labeling by peptide dimethylation on proteins of strawberry fruit at different ripening stages.

    PubMed

    Li, Li; Song, Jun; Kalt, Wilhelmina; Forney, Charles; Tsao, Rong; Pinto, Devanand; Chisholm, Kenneth; Campbell, Leslie; Fillmore, Sherry; Li, Xihong

    2013-12-06

    A quantitative proteomic investigation of strawberry fruit ripening employing stable isotope labeling by peptide dimethylation was conducted on 'Mira' and 'Honeoye' strawberry fruit. Postharvest physiological quality indices, including volatile production, total phenolics, total anthocyanins, antioxidant capacity, soluble solids and titratable acidity, were also characterized in white, pink and red fruit. More than 892 and 848 proteins were identified and quantified in the 'Mira' and 'Honeoye' fruit, respectively, using at least two peptides for each protein identification. Using the normalized ratio of protein abundance changes, proteins that changed two-fold or more were identified as proteins that are up- or down-regulated during fruit ripening. Among the quantified proteins, 111 proteins were common to both cultivars and represented five significant clusters based on quantitative changes. Among the up-regulated proteins were proteins involved in metabolic pathways including flavonoid/anthocyanin biosynthesis, volatile biosynthesis, antioxidant metabolism, stress responses and allergen formation. Proteins that decreased during fruit ripening were found to be responsible for methionine metabolism, antioxidant-redox, energy metabolism and protein synthesis. Our results show that strawberry ripening is a highly complex system involving multi-physiological processes made possible through changes in protein expression. This study provides new insights on the regulation of proteins during strawberry fruit ripening that lay the foundation for further targeted studies. Research on the postharvest physiology and biochemistry of strawberry fruit as a model of non-climacteric fruit ripening has been conducted for many years. However, the mechanism(s) for the initiation and metabolic regulation of non-climacteric fruit ripening remains unknown. Little information on strawberry fruit ripening is available at the proteome level. This paper is the first report of a

  20. MR imaging of protein folding in vitro employing nuclear-Overhauser-mediated saturation transfer.

    PubMed

    Zaiss, Moritz; Kunz, Patrick; Goerke, Steffen; Radbruch, Alexander; Bachert, Peter

    2013-12-01

    MR Z-spectroscopy allows enhanced imaging contrast on the basis of saturation transfer between the proton pools of cellular compounds and water, occurring via chemical exchange (chemical exchange saturation transfer, CEST) or dipole-dipole coupling (nuclear Overhauser effect, NOE). In previous studies, signals observed in the aliphatic proton region of Z-spectra have been assigned to NOEs between protons in water molecules and protons at the surface of proteins. We investigated a possible relationship between the signal strength of NOE peaks in Z-spectra obtained at B0 = 7 T and protein structure. Here, we report a correlation of NOE-mediated saturation transfer with the structural state of bovine serum albumin (BSA), which was monitored by fluorescence spectroscopy. Encouraged by CEST signal changes observed in tumor tissue, our observation also points to a possible contrast mechanism for MRI sensitive to the structural integrity of proteins in cells. Therefore, protein folding should be considered as an additional property affecting saturation transfer between water and proteins, in combination with the microenvironment and physiological quantities, such as metabolite concentration, temperature and pH. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Direct detection of x-rays for protein crystallography employing a thick, large area CCD

    DOEpatents

    Atac, Muzaffer; McKay, Timothy

    1999-01-01

    An apparatus and method for directly determining the crystalline structure of a protein crystal. The crystal is irradiated by a finely collimated x-ray beam. The interaction of the x-ray beam with the crystal produces scattered x-rays. These scattered x-rays are detected by means of a large area, thick CCD which is capable of measuring a significant number of scattered x-rays which impact its surface. The CCD is capable of detecting the position of impact of the scattered x-ray on the surface of the CCD and the quantity of scattered x-rays which impact the same cell or pixel. This data is then processed in real-time and the processed data is outputted to produce a image of the structure of the crystal. If this crystal is a protein the molecular structure of the protein can be determined from the data received.

  2. Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

    DOE PAGES

    Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne; ...

    2014-12-11

    The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

  3. Development of chromatofocusing techniques employing mixed-mode column packings for protein separations.

    PubMed

    Guo, Hui; Li, Xiang; Frey, Douglas D

    2014-01-03

    Recent studies reported in the literature using mixed-mode chromatography (MMC) column packings have shown that multiple modes of interactions between the column packing and proteins can be usefully exploited to yield excellent resolution as well as salt-tolerant adsorption of the target protein. In this study, a mixed-mode separation method using commercially available column packings was explored which combines the techniques of hydrophobic-interaction chromatography and chromatofocusing. Two different column packings, one based on mercapto-ethyl-pyridine (MEP) and the other based on hexylamine (HEA) were investigated with regard to their ability to separate proteins when using internally generated, retained pH gradients. The effects of added salt and urea on the behavior of the retained pH gradient and the protein separation achieved when using MMC column packings for chromatofocusing were also investigated. Numerical simulations using methods developed in previous work were shown to agree with experimental results when using reasonable physical parameters. These numerical simulations were also shown to be a useful qualitative method to select the compositions of the starting and elution buffers in order to achieve desired shapes for the pH and ionic strength gradients. The use of the method to fractionate blood serum was explored as a prototype example application. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Mild and cost-effective green fluorescent protein purification employing small synthetic ligands.

    PubMed

    Pina, Ana Sofia; Dias, Ana Margarida G C; Ustok, Fatma Isik; El Khoury, Graziella; Fernandes, Cláudia S M; Branco, Ricardo J F; Lowe, Christopher R; Roque, A Cecília A

    2015-10-30

    The green fluorescent protein (GFP) is a useful indicator in a broad range of applications including cell biology, gene expression and biosensing. However, its full potential is hampered by the lack of a selective, mild and low-cost purification scheme. In order to address this demand, a novel adsorbent was developed as a generic platform for the purification of GFP or GFP fusion proteins, giving GFP a dual function as reporter and purification tag. After screening a solid-phase combinatorial library of small synthetic ligands based on the Ugi-reaction, the lead ligand (A4C7) selectively recovered GFP with 94% yield and 94% purity under mild conditions and directly from Escherichia coli extracts. Adsorbents containing the ligand A4C7 maintained the selectivity to recover other proteins fused to GFP. The performance of A4C7 adsorbents was compared with two commercially available methods (immunoprecipitation and hydrophobic interaction chromatography), confirming the new adsorbent as a low-cost viable alternative for GFP purification. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Proteinase assay by capillary electrophoresis employing fluorescence-quenched protein-dye conjugates.

    PubMed

    Welder, Frank; McCorquodale, Elizabeth Moody; Colyer, Christa L

    2002-06-01

    Determination of proteinases--enzymes that catalyze the hydrolysis of peptide bonds--is often difficult due to the presence of interferences in complex biological media and limited sample size. Capillary electrophoresis (CE), with laser-induced fluorescence (LIF) can serve as a useful tool for such determinations. LIF detection offers the advantages of increased sensitivity and increased selectivity. However, direct LIF detection requires the proteinase analyte to be fluorescently derivatized prior to analysis. A viable alternative is offered by the present work, in which protein substrates are first labeled with BODIPY dye, a relatively pH-insensitive, high-fluorescence quantum yield dye. Upon binding of some 4-10 molecules of dye to a single protein, the dye is effectively fluorescence-quenched. Digestion of the BODIPY--labeled and quenched protein by an unlabeled enzyme yields smaller peptide fragments in which the fluorescence of associated BODIPY tags is restored. We will present how the fragmentation pattern of BODIPY-labeled casein changes as a function of incubation time with trypsin, as well as the effect of varying concentrations of trypsin on the BODIPY-casein digest.

  6. Immunohistochemical analysis of DNA mismatch repair protein and O6-methylguanine-DNA methyltransferase in melanoma metastases in relation to clinical response to DTIC-based chemotherapy.

    PubMed

    Ma, Shuhua; Egyházi, Suzanne; Ringborg, Ulrik; Hansson, Johan

    2002-01-01

    DNA mismatch repair (MMR) deficiency and increased O6-methylguanine-DNA methyltransferase (MGMT) activity have been related to resistance to O6-guanine methylating agents in tumour cell lines. However, the clinical relevance of MMR and MGMT as drug resistance factors is still unclear. In a retrospective study, the expression levels of the MMR proteins, hMSH2, hMSH6 and hMLH1, were analysed by immunohistochemistry in melanoma metastases from 64 patients, who had received dacarbazine (DTIC) based chemotherapy. More than half of the melanoma patients had tumours with no nuclear staining for either hMSH2 or hMSH6 or both, while all tumours showed positive nuclear staining for hMLH1. The response rates were similar in patients with hMSH2 and/or hMSH6 positive tumours to these in patients with negative tumours. By combination of MMR with previously obtained MGMT data, only 2 of 12 responders had tumours with low MGMT and positive MMR expression. Still all except 3 of the non-responders were identified by having either high MGMT expression or absent staining for hMSH2 or hMSH6 or both in their tumours. However, there was no significant correlation of MMR expression alone or combined with MGMT levels with clinical response to DTIC-based chemotherapy in metastatic melanoma.

  7. Microcapsule production employing chickpea or lentil protein isolates and maltodextrin: physicochemical properties and oxidative protection of encapsulated flaxseed oil.

    PubMed

    Karaca, Asli Can; Nickerson, Michael; Low, Nicholas H

    2013-08-15

    Flaxseed oil was microencapsulated, employing a wall material matrix of either chickpea (CPI) or lentil protein isolate (LPI) and maltodextrin, followed by freeze-drying. Effects of oil concentration (5.3-21.0%), protein source (CPI vs. LPI) and maltodextrin type (DE 9 and 18) and concentration (25.0-40.7%), on both the physicochemical characteristics and microstructure of the microcapsules, were investigated. It was found that an increase in emulsion oil concentration resulted in a concomitant increase in oil droplet diameter and microcapsule surface oil content, and a decrease in oil encapsulation efficiency. Optimum flaxseed oil encapsulation efficiency (∼83.5%), minimum surface oil content (∼2.8%) and acceptable mean droplet diameter (3.0 μm) were afforded with 35.5% maltodextrin-DE 9 and 10.5% oil. Microcapsules, formed by employing these experimental conditions, showed a protective effect against oxidation versus free oil over a storage period of 25 d at room temperature.

  8. Receptor-Drug Interaction: Europium Employment for Studying the Biochemical Pathway of G-Protein-Coupled Receptor Activation

    PubMed Central

    Antonio, Colabufo Nicola; Grazia, Perrone Maria; Marialessandra, Contino; Francesco, Berardi; Roberto, Perrone

    2007-01-01

    In medicinal chemistry field, the biochemical pathways, involved in 7-transmembrane domains G-protein coupled receptors (GPCRs) activation, are commonly studied to establish the activity of ligands towards GPCRs. The most studied steps are the measurement of activated GTP-α subunit and stimulated intracellular cAMP. At the present, many researchers defined agonist or antagonist activity of potential GPCRs drugs employing [35S]GTPγS or [3H]cAMP as probes. Recently, the corresponding lanthanide labels Eu-GTP and Eu-cAMP as alternative to radiochemicals have been developed because they are highly sensitive, easy to automate, easily synthesized, they display a much longer shelf-life and they can be used in multilabel experiments. In the present review, the receptor-drug interaction by europium employment for studying the biochemical pathway of GPCR activation has been focused. Moreover, comparative studies between lanthanide label probes and the corresponding radiolabeled compounds have been carried out. PMID:18350113

  9. Helicobacter pylori infection and expression of DNA mismatch repair proteins

    PubMed Central

    Mirzaee, Vahid; Molaei, Mahsa; Shalmani, Hamid Mohaghegh; Zali, Mohammad Reza

    2008-01-01

    AIM: To determine the expression of DNA (MMR) proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori (H pylori)-infected gastritis. METHODS: Fifty H pylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination (Giemsa stain) and for immunohistochemical staining of hMLH1 and hMSH2. RESULTS: The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 ± 7.32% in H pylori-negative patients, while it was 73.34 ± 10.10% in H pylori-positive patients (P < 0.0001). No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining (81.16 ± 8.32% in H pylori-negative versus 78.24 ± 8.71% in H pylori-positive patients; P = 0.09). CONCLUSION: This study indicates that H pylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system. PMID:19034977

  10. A combinatorial approach to studying protein complex composition by employing size-exclusion chromatography and proteome analysis.

    SciTech Connect

    Li, S.; Giometti, C.; Biosciences Division

    2007-07-01

    The genome sequences of numerous organisms are available now, but gene sequences alone do not provide sufficient information to accurately deduce protein functions. Protein function is largely dependent on the association of multiple polypeptide chains into large structures with interacting subunits that regulate and support each other. Therefore, the mapping of protein interaction networks in a physiological context is conducive to deciphering protein functions, including those of hypothetical proteins. Although several high-throughput methods to globally identify protein interactions have been reported in recent years, these approaches often have a high rate of nonspecific or artificial interactions detected. For instance, the fraction of false positives of the protein interactions identified by yeast two-hybrid assay has been predicted to be of the order of 50%. We have developed a strategy to globally map Bacillus subtilis protein-protein interactions in a physiological context by fractionating the cell lysates using size-exclusion chromatography (SEC), followed by proteome analysis. Components of both known and unknown protein complexes, multisubunits and multiproteins, have been identified using this strategy. In one case, the partners of the B. subtilis protein complex have been coexpressed in Escherichia coli, and the formation of the overexpressed protein complex has been further confirmed by a pull-down assay.

  11. Solid phase extraction of proteins from buffer solutions employing capillary-channeled polymer (C-CP) fibers as the stationary phase.

    PubMed

    Burdette, Carolyn Q; Marcus, R Kenneth

    2013-02-21

    Polypropylene (PP) capillary-channeled polymer (C-CP) fibers are applied for solid phase extraction (SPE) of proteins from aqueous buffer solutions using a micropipette tip-based format. A process was developed in which centrifugation is used as the moving force for solution passage in the loading/washing steps instead of the previously employed manual aspiration. The complete procedure requires ~15 minutes, with the number of samples run in parallel limited only by the capacity of the centrifuge. The method performance was evaluated based on adsorption and elution characteristics of several proteins (cytochrome c, lysozyme, myoglobin, and glucose oxidase) from 150 mM phosphate buffered saline (PBS) solutions. Protein concentration ranges of ~2 to 100 μg mL(-1) were employed and the recovery characteristics determined through UV-Vis absorbance spectrophotometry for protein quantification. The protein loading capacities across the range of proteins was ~1.5 μg for the 5 mg fiber tips. Average recoveries from PBS were determined for each protein sample; cytochrome c ~86%, lysozyme ~80%, myoglobin ~86%, and glucose oxidase ~89%. Recoveries from more complex matrices, synthetic urine and synthetic saliva, were determined to be ~90%. A 10× dilution study for a fixed 1 μg protein application yielded 94 ± 3.2% recoveries. The C-CP tips provided significantly higher recoveries for myoglobin in a 150 mM PBS matrix in comparison to a commercially available protein SPE product, with the added advantages of low cost, rapid processing, and reusability.

  12. Accelerated Identification of Proteins by Mass Spectrometry by Employing Covalent Pre-Gel Staining with Uniblue A

    PubMed Central

    Mata-Gómez, Marco A.; Yasui, Matthew T.; Guerrero-Rangel, Armando; Valdés-Rodríguez, Silvia; Winkler, Robert

    2012-01-01

    Background The identification of proteins by mass spectrometry is a standard method in biopharmaceutical quality control and biochemical research. Prior to identification by mass spectrometry, proteins are usually pre-separated by electrophoresis. However, current protein staining and de-staining protocols are tedious and time consuming, and therefore prolong the sample preparation time for mass spectrometry. Methodology and Principal Findings We developed a 1-minute covalent pre-gel staining protocol for proteins, which does not require de-staining before the mass spectrometry analysis. We investigated the electrophoretic properties of derivatized proteins and peptides and studied their behavior in mass spectrometry. Further, we elucidated the preferred reaction of proteins with Uniblue A and demonstrate the integration of the peptide derivatization into typical informatics tools. Conclusions and Significance The Uniblue A staining method drastically speeds up the sample preparation for the mass spectrometry based identification of proteins. The application of this chemo-proteomic strategy will be advantageous for routine quality control of proteins and for time-critical tasks in protein analysis. PMID:22363648

  13. Strategies and solid-phase formats for the analysis of protein and peptide phosphorylation employing a novel fluorescent phosphorylation sensor dye.

    PubMed

    Martin, Karen; Steinberg, Thomas H; Goodman, Terrie; Schulenberg, Birte; Kilgore, Jason A; Gee, Kyle R; Beechem, Joseph M; Patton, Wayne F

    2003-06-01

    Protein kinases represent one of the largest families of regulatory enzymes, with more than 2,000 of them being encoded for by the human genome. Many cellular processes are regulated by the reversible phosphorylation of proteins and upwards of 30% of the proteins comprising the eukaryotic proteome are likely to be phosphorylated at some point during their existence. In the past, analysis of global protein phosphorylation has been accomplished through radiolabelling of samples with inorganic (32P or [gamma-32)P] ATP. The approach is limited to specimens amenable to radiolabelling and poses certain safety and disposal problems. Alternatively, immunodetection with antibodies to the common phosphoamino acids may be employed, but the antibodies are relatively expensive and exhibit limited specificity and a certain degree of cross-reactivity. Pro-Q Diamond dye is a new fluorescent phosphosensor technology suitable for the detection of phosphoserine-, phosphothreonine- and phosphotyrosine-containing proteins directly in isoelectric focusing gels, SDS-polyacrylamide gels and two-dimensional gels. Additionally, the technology is appropriate for the detection of phosphoproteins or phosphopeptides arrayed on protein chips or affixed to beads. Dye-stained proteins and peptides can be excited with a laser-based light source of 532 or 543 nm or with a xenon-arc lamp-based system equipped with appropriate band pass filters. Alternatively, ultraviolet light of about 302 nm may be employed, providing that sufficiently long exposure times are used to collect the fluorescence signal. Pro-Q Diamond dye emits maximally at approximately 580 nm. The fluorescence-based detection technology is easy to conduct, cost effective and allows rapid large-scale screening of protein and peptide phosphorylation in a variety of solid-phase assay formats.

  14. Identification of early salt stress responsive proteins in seedling roots of upland cotton (Gossypium hirsutum L.) employing iTRAQ-based proteomic technique

    PubMed Central

    Li, Wu; Zhao, Fu'an; Fang, Weiping; Xie, Deyi; Hou, Jianan; Yang, Xiaojie; Zhao, Yuanming; Tang, Zhongjie; Nie, Lihong; Lv, Shuping

    2015-01-01

    Soil salinity is a major abiotic stress that limits plant growth and agricultural productivity. Upland cotton (Gossypium hirsutum L.) is highly tolerant to salinity; however, large-scale proteomic data of cotton in response to salt stress are still scant. Here, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic technique was employed to identify the early differentially expressed proteins (DEPs) from salt-treated cotton roots. One hundred and twenty-eight DEPs were identified, 76 of which displayed increased abundance and 52 decreased under salt stress conditions. The majority of the proteins have functions related to carbohydrate and energy metabolism, transcription, protein metabolism, cell wall and cytoskeleton metabolism, membrane and transport, signal transduction, in addition to stress and defense. It is worth emphasizing that some novel salt-responsive proteins were identified, which are involved in cell cytoskeleton metabolism (actin-related protein2, ARP2, and fasciclin-like arabinogalactan proteins, FLAs), membrane transport (tonoplast intrinsic proteins, TIPs, and plasma membrane intrinsic proteins, PIPs), signal transduction (leucine-rich repeat receptor-like kinase encoding genes, LRR-RLKs) and stress responses (thaumatin-like protein, TLP, universal stress protein, USP, dirigent-like protein, DIR, desiccation-related protein PCC13-62). High positive correlation between the abundance of some altered proteins (superoxide dismutase, SOD, peroxidase, POD, glutathione S-transferase, GST, monodehydroascorbate reductase, MDAR, and malate dehydrogenase, MDH) and their enzyme activity was evaluated. The results demonstrate that the iTRAQ-based proteomic technique is reliable for identifying and quantifying a large number of cotton root proteins. qRT-PCR was used to study the gene expression levels of the five above-mentioned proteins; four patterns are consistent with those of induced protein. These results showed that the proteome

  15. Identification of early salt stress responsive proteins in seedling roots of upland cotton (Gossypium hirsutum L.) employing iTRAQ-based proteomic technique.

    PubMed

    Li, Wu; Zhao, Fu'an; Fang, Weiping; Xie, Deyi; Hou, Jianan; Yang, Xiaojie; Zhao, Yuanming; Tang, Zhongjie; Nie, Lihong; Lv, Shuping

    2015-01-01

    Soil salinity is a major abiotic stress that limits plant growth and agricultural productivity. Upland cotton (Gossypium hirsutum L.) is highly tolerant to salinity; however, large-scale proteomic data of cotton in response to salt stress are still scant. Here, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic technique was employed to identify the early differentially expressed proteins (DEPs) from salt-treated cotton roots. One hundred and twenty-eight DEPs were identified, 76 of which displayed increased abundance and 52 decreased under salt stress conditions. The majority of the proteins have functions related to carbohydrate and energy metabolism, transcription, protein metabolism, cell wall and cytoskeleton metabolism, membrane and transport, signal transduction, in addition to stress and defense. It is worth emphasizing that some novel salt-responsive proteins were identified, which are involved in cell cytoskeleton metabolism (actin-related protein2, ARP2, and fasciclin-like arabinogalactan proteins, FLAs), membrane transport (tonoplast intrinsic proteins, TIPs, and plasma membrane intrinsic proteins, PIPs), signal transduction (leucine-rich repeat receptor-like kinase encoding genes, LRR-RLKs) and stress responses (thaumatin-like protein, TLP, universal stress protein, USP, dirigent-like protein, DIR, desiccation-related protein PCC13-62). High positive correlation between the abundance of some altered proteins (superoxide dismutase, SOD, peroxidase, POD, glutathione S-transferase, GST, monodehydroascorbate reductase, MDAR, and malate dehydrogenase, MDH) and their enzyme activity was evaluated. The results demonstrate that the iTRAQ-based proteomic technique is reliable for identifying and quantifying a large number of cotton root proteins. qRT-PCR was used to study the gene expression levels of the five above-mentioned proteins; four patterns are consistent with those of induced protein. These results showed that the proteome

  16. Employment of colorimetric enzyme assay for monitoring expression and solubility of GST fusion proteins targeted to inclusion bodies.

    PubMed

    Mačinković, Igor S; Abughren, Mohamed; Mrkic, Ivan; Grozdanović, Milica M; Prodanović, Radivoje; Gavrović-Jankulović, Marija

    2013-12-01

    High levels of recombinant protein expression can lead to the formation of insoluble inclusion bodies. These complex aggregates are commonly solubilized in strong denaturants, such as 6-8M urea, although, if possible, solubilization under milder conditions could facilitate subsequent refolding and purification of bioactive proteins. Commercially available GST-tag assays are designed for quantitative measurement of GST activity under native conditions. GST fusion proteins accumulated in inclusion bodies are considered to be undetectable by such assays. In this work, solubilization of recombinantly produced proteins was performed in 4M urea. The activity of rGST was assayed in 2M urea and it was shown that rGST preserves 85% of its activity under such denaturing conditions. A colorimetric GST activity assay with 1-chloro-2, 4-dinitrobenzene (CDNB) was examined for use in rapid detection of expression targeted to inclusion bodies and for the identification of inclusion body proteins which can be solubilized in low concentrations of chaotropic agents. Applicability of the assay was evaluated by tracking protein expression of two GST-fused allergens of biopharmaceutical value in E. coli, GST-Der p 2 and GST-Mus a 5, both targeted to inclusion bodies. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Simultaneous photometric determination of albumin and total protein in animal blood plasma employing a multicommutated flow system to carried out on line dilution and reagents solutions handling

    NASA Astrophysics Data System (ADS)

    Luca, Gilmara C.; Reis, Boaventura F.

    2004-02-01

    An automatic flow procedure for the simultaneous determination of albumin and total protein in blood plasma samples is proposed. The flow network comprised a set of three-way solenoid valves assembled to implement the multicommutation. The flow set up was controlled by means of a computer equipped with an electronic interface card which running a software wrote in QUICKBASIC 4.5 performed on line programmed dilution to allow the determination of both albumin and total protein in blood plasma. The photometric methods based on Bromocresol Green and Biuret reagents were selected for determination of albumin and total protein, respectively. Two LEDs based photometers coupled together the flow cells were employed as detector. After the adjustment of the operational parameters the proposed system presented the following features: an analytical throughput of 45 sample processing per hour for two analytes; relative standard deviations of 1.5 and 0.8% ( n=10) for a typical sample presenting 34 g l -1 albumin and 90 g l -1 total protein, respectively; linear responses ranging from 0 to 15 g l -1 albumin ( r=0.998) and total protein ( r=0.999); sample and reagents consumption, 140 μl serum solution, 0.015 mg VBC and 0.432 mg CuSO 4 per determination, respectively. Applying the paired t-test between results obtained using the proposed system and reference methods no significant difference at 95 and 90% confidence level for albumin and total protein, respectively, were observed.

  18. Top-Down Protein Identification of Proteasome Proteins with nanoLC FT-ICR MS Employing Data-Independent Fragmentation Methods

    PubMed Central

    Lakshmanan, Rajeswari; Wolff, Jeremy J.; Alvarado, Rudy; Loo, Joseph A.

    2014-01-01

    A comparison of different data-independent fragmentation methods combined with liquid chromatography (LC) coupled to high resolution Fourier-transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry (MS) is presented for top-down MS of protein mixtures. Proteins composing the 20S and 19S proteasome complex and their post-translational modifications were identified using a 15-Tesla FT-ICR mass spectrometer. The data-independent fragmentation modes with LC timescales allowed for higher duty cycle measurements that better suit on-line LC-FT-ICR-MS. Protein top-down dissociation was effected by funnel-skimmer collisionally activated dissociation (FS-CAD) and CASI (Continuous Accumulation of Selected Ions)-CAD. The N-terminus for 9 out of the 14 20S proteasome proteins were found to be modified, and the α3 protein was found to be phosphorylated; these results are consistent with previous reports. Mass measurement accuracy with the LC-FT-ICR system for the 20–30 kDa 20S proteasome proteins was 1 ppm. The intact mass of the 100 kDa Rpn1 subunit from the 19S proteasome complex regulatory particle was measured with a deviation of 17 ppm. The CASI-CAD technique is a complementary tool for intact protein fragmentation and is an effective addition to the growing inventory of dissociation methods which are compatible with on-line protein separation coupled to FT-ICR MS. PMID:24478249

  19. A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes

    PubMed Central

    Carmell, Michelle A; Dokshin, Gregoriy A; Skaletsky, Helen; Hu, Yueh-Chiang; van Wolfswinkel, Josien C; Igarashi, Kyomi J; Bellott, Daniel W; Nefedov, Michael; Reddien, Peter W; Enders, George C; Uversky, Vladimir N; Mello, Craig C; Page, David C

    2016-01-01

    The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya – either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome. DOI: http://dx.doi.org/10.7554/eLife.19993.001 PMID:27718356

  20. Support Vector Machines Trained with Evolutionary Algorithms Employing Kernel Adatron for Large Scale Classification of Protein Structures.

    PubMed

    Arana-Daniel, Nancy; Gallegos, Alberto A; López-Franco, Carlos; Alanís, Alma Y; Morales, Jacob; López-Franco, Adriana

    2016-01-01

    With the increasing power of computers, the amount of data that can be processed in small periods of time has grown exponentially, as has the importance of classifying large-scale data efficiently. Support vector machines have shown good results classifying large amounts of high-dimensional data, such as data generated by protein structure prediction, spam recognition, medical diagnosis, optical character recognition and text classification, etc. Most state of the art approaches for large-scale learning use traditional optimization methods, such as quadratic programming or gradient descent, which makes the use of evolutionary algorithms for training support vector machines an area to be explored. The present paper proposes an approach that is simple to implement based on evolutionary algorithms and Kernel-Adatron for solving large-scale classification problems, focusing on protein structure prediction. The functional properties of proteins depend upon their three-dimensional structures. Knowing the structures of proteins is crucial for biology and can lead to improvements in areas such as medicine, agriculture and biofuels.

  1. Heat shock protein 70 kDa chaperone/DnaJ cochaperone complex employs an unusual dynamic interface.

    PubMed

    Ahmad, Atta; Bhattacharya, Akash; McDonald, Ramsay A; Cordes, Melissa; Ellington, Benjamin; Bertelsen, Eric B; Zuiderweg, Erik R P

    2011-11-22

    The heat shock protein 70 kDa (Hsp70)/DnaJ/nucleotide exchange factor system assists in intracellular protein (re)folding. Using solution NMR, we obtained a three-dimensional structure for a 75-kDa Hsp70-DnaJ complex in the ADP state, loaded with substrate peptide. We establish that the J domain (residues 1-70) binds with its positively charged helix II to a negatively charged loop in the Hsp70 nucleotide-binding domain. The complex shows an unusual "tethered" binding mode which is stoichiometric and saturable, but which has a dynamic interface. The complex represents part of a triple complex of Hsp70 and DnaJ both bound to substrate protein. Mutagenesis data indicate that the interface is also of relevance for the interaction of Hsp70 and DnaJ in the ATP state. The solution complex is completely different from a crystal structure of a disulfide-linked complex of homologous proteins [Jiang, et al. (2007) Mol Cell 28:422-433].

  2. Support Vector Machines Trained with Evolutionary Algorithms Employing Kernel Adatron for Large Scale Classification of Protein Structures

    PubMed Central

    Arana-Daniel, Nancy; Gallegos, Alberto A.; López-Franco, Carlos; Alanís, Alma Y.; Morales, Jacob; López-Franco, Adriana

    2016-01-01

    With the increasing power of computers, the amount of data that can be processed in small periods of time has grown exponentially, as has the importance of classifying large-scale data efficiently. Support vector machines have shown good results classifying large amounts of high-dimensional data, such as data generated by protein structure prediction, spam recognition, medical diagnosis, optical character recognition and text classification, etc. Most state of the art approaches for large-scale learning use traditional optimization methods, such as quadratic programming or gradient descent, which makes the use of evolutionary algorithms for training support vector machines an area to be explored. The present paper proposes an approach that is simple to implement based on evolutionary algorithms and Kernel-Adatron for solving large-scale classification problems, focusing on protein structure prediction. The functional properties of proteins depend upon their three-dimensional structures. Knowing the structures of proteins is crucial for biology and can lead to improvements in areas such as medicine, agriculture and biofuels. PMID:27980384

  3. The maize tapetum employs diverse mechanisms to synthesize and store proteins and flavonoids and transfer them to the pollen surface.

    PubMed

    Li, Yubing; Suen, Der Fen; Huang, Chien-Yu; Kung, Shung-Yee; Huang, Anthony H C

    2012-04-01

    In anthers, the tapetum synthesizes and stores proteins and flavonoids, which will be transferred to the surface of adjacent microspores. The mechanism of synthesis, storage, and transfer of these pollen-coat materials in maize (Zea mays) differs completely from that reported in Arabidopsis (Arabidopsis thaliana), which stores major pollen-coat materials in tapetosomes and elaioplasts. On maize pollen, three proteins, glucanase, xylanase, and a novel protease, Zea mays pollen coat protease (ZmPCP), are predominant. During anther development, glucanase and xylanase transcripts appeared at a mid developmental stage, whereas protease transcript emerged at a late developmental stage. Protease and xylanase transcripts were present only in the anther tapetum of the plant, whereas glucanase transcript was distributed ubiquitously. ZmPCP belongs to the cysteine protease family but has no closely related paralogs. Its nascent polypeptide has a putative amino-terminal endoplasmic reticulum (ER)-targeting peptide and a propeptide. All three proteins were synthesized in the tapetum and were present on mature pollen after tapetum death. Electron microscopy of tapetum cells of mid to late developmental stages revealed small vacuoles distributed throughout the cytoplasm and numerous secretory vesicles concentrated near the locular side. Immunofluorescence microscopy and subcellular fractionation localized glucanase in ER-derived vesicles in the cytoplasm and the wall facing the locule, xylanase in the cytosol, protease in vacuoles, and flavonoids in subdomains of ER rather than in vacuoles. The nonoverlapping subcellular locations of the three proteins and flavonoids indicate distinct modes of their storage in tapetum cells and transfer to the pollen surface, which in turn reflect their respective functions in tapetum cells or the pollen surface.

  4. Ligand identification of carbohydrate-binding proteins employing a biotinylated glycan binding assay and tandem mass spectrometry.

    PubMed

    Wuhrer, Manfred; van Remoortere, Alexandra; Balog, Crina I A; Deelder, André M; Hokke, Cornelis H

    2010-11-15

    Characterization of protein-carbohydrate interactions at the molecular level is important for understanding many glycan-mediated processes. Here we present a method for the identification of glycan ligands of carbohydrate-binding proteins. The glycans released from natural sources are labeled with biotinamidocaproyl hydrazide (BACH) and subsequently fractionated by high-performance liquid chromatography. Glycan fractions are screened for binding to carbohydrate-binding proteins (CBPs) using a microtitration plate binding assay; CBPs are immobilized, BACH-glycan fractions are added, and bound BACH-glycans are detected using alkaline phosphatase-conjugated streptavidin. The glycan structures in binding fractions are studied by (tandem) mass spectrometry, exoglycosidase treatment, and rechromatography, thereby revealing the glycan motifs recognized by the CBPs. Subsequent surface plasmon resonance experiments using a reverse setup with immobilization of the BACH-glycan ligands on streptavidin-coated surfaces provide more information on glycan-CBP interactions via association and dissociation curves. The presented method is easy and fast, and the required instrumentation is available in many laboratories. The assay is very sensitive given that both the mass spectrometric analysis and the microtitration plate binding assay can be performed on femtomole amounts of BACH-glycans. This approach should be generally applicable to study and structurally identify carbohydrate ligands of anti-glycan antibodies and lectins.

  5. Salts employed in hydrophobic interaction chromatography can change protein structure - insights from protein-ligand interaction thermodynamics, circular dichroism spectroscopy and small angle X-ray scattering.

    PubMed

    Komaromy, Andras Z; Kulsing, Chadin; Boysen, Reinhard I; Hearn, Milton T W

    2015-03-01

    Key requirements of protein purification by hydrophobic interaction chromatography (HIC) are preservation of the tertiary/quaternary structure, maintenance of biological function, and separation of the correctly folded protein from its unfolded forms or aggregates. This study examines the relationship between the HIC retention behavior of hen egg white lysozyme (HEWL) in high concentrations of several kosmotropic salts and its conformation, assessed by circular dichroism (CD) spectroscopy. Further, the physicochemical properties of HEWL in the presence of high concentrations of ammonium sulfate, sodium chloride and magnesium chloride were investigated by small angle X-ray scattering (SAXS) at different temperatures. Radii of gyration were extrapolated from Guinier approximations and the indirect transform program GNOM with protein-protein interaction and contrast variation taken into account. A bead model simulation provided information on protein structural changes using ab initio reconstruction with GASBOR. These results correlated to the secondary structure content obtained from CD spectroscopy of HEWL. These changes in SAXS and CD data were consistent with heat capacity ΔCp -values obtained from van't Hoff plot analyses of the retention data. Collectively, these insights enable informed decisions to be made on the choice of chromatographic conditions, leading to improved separation selectivity and opportunities for innovative column-assisted protein refolding methods.

  6. Employment equality.

    PubMed

    2004-03-01

    Two new sets of employment regulations that came into force at the end of last year are now available on the internet, writes Steven Black. The Employment Equality (Religion or Belief) Regulations 2003 are available at www.legislation.hmso.gov.uk/si/si2003/20031660.htm and The Employment Equality (Sexual Orientation) Regulations 2003 are at www.legislation.hmso.gov.uk/si/si2003/20031661.htm.

  7. Industry Employment

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2012

    2012-01-01

    This article illustrates projected employment change by industry and industry sector over 2010-20 decade. Workers are grouped into an industry according to the type of good produced or service provided by the establishment for which they work. Industry employment projections are shown in terms of numeric change (growth or decline in the total…

  8. Industry Employment

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2010

    2010-01-01

    This article illustrates projected employment change from an industry perspective over the 2008-2018 decade. Workers are grouped into an industry according to the type of good produced or service provided by the establishment in which they work. Industry employment projections are shown in terms of numeric change (growth or decline in the total…

  9. Quantitative changes in proteins responsible for flavonoid and anthocyanin biosynthesis in strawberry fruit at different ripening stages: A targeted quantitative proteomic investigation employing multiple reaction monitoring.

    PubMed

    Song, Jun; Du, Lina; Li, Li; Kalt, Wilhelmina; Palmer, Leslie Campbell; Fillmore, Sherry; Zhang, Ying; Zhang, ZhaoQi; Li, XiHong

    2015-06-03

    To better understand the regulation of flavonoid and anthocyanin biosynthesis, a targeted quantitative proteomic investigation employing LC-MS with multiple reaction monitoring was conducted on two strawberry cultivars at three ripening stages. This quantitative proteomic workflow was improved through an OFFGEL electrophoresis to fractionate peptides from total protein digests. A total of 154 peptide transitions from 47 peptides covering 21 proteins and isoforms related to anthocyanin biosynthesis were investigated. The normalized protein abundance, which was measured using isotopically-labeled standards, was significantly changed concurrently with increased anthocyanin content and advanced fruit maturity. The protein abundance of phenylalanine ammonia-lyase; anthocyanidin synthase, chalcone isomerase; flavanone 3-hydroxylase; dihydroflavonol 4-reductase, UDP-glucose:flavonoid-3-O-glucosyltransferase, cytochrome c and cytochrome C oxidase subunit 2, was all significantly increased in fruit of more advanced ripeness. An interaction between cultivar and maturity was also shown with respect to chalcone isomerase. The good correlation between protein abundance and anthocyanin content suggested that a metabolic control point may exist for anthocyanin biosynthesis. This research provides insights into the process of anthocyanin formation in strawberry fruit at the level of protein concentration and reveals possible candidates in the regulation of anthocyanin formation during fruit ripening. To gain insight into the molecular mechanisms contributing to flavonoids and anthocyanin biosynthesis and regulation of strawberry fruit during ripening is challenging due to limited molecular biology tools and established hypothesis. Our targeted proteomic approach employing LC-MS/MS analysis and MRM technique to quantify proteins in relation to flavonoids and anthocyanin biosynthesis and regulation in strawberry fruit during fruit ripening is novel. The identification of peptides

  10. Human Immunodeficiency Virus Type 1 Employs the Cellular Dynein Light Chain 1 Protein for Reverse Transcription through Interaction with Its Integrase Protein

    PubMed Central

    Jayappa, Kallesh Danappa; Ao, Zhujun; Wang, Xiaoxia; Mouland, Andrew J.; Shekhar, Sudhanshu; Yang, Xi

    2015-01-01

    ABSTRACT In this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Glued in early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150Glued, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction motifs in IN, we identified the motifs 52GQVD and 250VIQD in IN as essential for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1INQ53A/Q252A) exhibited impaired reverse transcription. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1INQ53A/Q252A mutant virus. Overall, our study demonstrates the novel interaction between HIV-1 IN and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1. IMPORTANCE Host cellular DYNLL1, DYNLT1, and p150Glued proteins have been implicated in the replication of several viruses. However, their roles in HIV-1 replication have not been investigated. For the first time, we demonstrated that during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was found to have a role in proper uncoating and efficient reverse transcription of HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN in HIV-1 uncoating and reverse transcription, it also predicts a possible mechanism by which IN contributes to these early viral

  11. Mismatch repair proteins recruit DNA methyltransferase 1 to sites of oxidative DNA damage.

    PubMed

    Ding, Ning; Bonham, Emily M; Hannon, Brooke E; Amick, Thomas R; Baylin, Stephen B; O'Hagan, Heather M

    2016-06-01

    At sites of chronic inflammation, epithelial cells are exposed to high levels of reactive oxygen species and undergo cancer-associated DNA methylation changes, suggesting that inflammation may initiate epigenetic alterations. Previously, we demonstrated that oxidative damage causes epigenetic silencing proteins to become part of a large complex that is localized to GC-rich regions of the genome, including promoter CpG islands that are epigenetically silenced in cancer. However, whether these proteins were recruited directly to damaged DNA or during the DNA repair process was unknown. Here we demonstrate that the mismatch repair protein heterodimer MSH2-MSH6 participates in the oxidative damage-induced recruitment of DNA methyltransferase 1 (DNMT1) to chromatin. Hydrogen peroxide treatment induces the interaction of MSH2-MSH6 with DNMT1, suggesting that the recruitment is through a protein-protein interaction. Importantly, the reduction in transcription for genes with CpG island-containing promoters caused by oxidative damage is abrogated by knockdown of MSH6 and/or DNMT1. Our findings provide evidence that the role of DNMT1 at sites of oxidative damage is to reduce transcription, potentially preventing transcription from interfering with the repair process. This study uniquely brings together several factors that are known to contribute to colon cancer, namely inflammation, mismatch repair proteins, and epigenetic changes. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  12. Supported Employment.

    ERIC Educational Resources Information Center

    Erickson, Ron, Ed.; And Others

    1989-01-01

    This "feature issue" reports on major shifts in attitudes, practices, and policies that have led to the growth of supported employment programs for people with disabilities, with special focus on the situation in Minnesota. It contains the following articles: "To the Year 2000 and Beyond: Jobs Won't Be the Problem" (David R.…

  13. Occupational Employment

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2012

    2012-01-01

    When choosing a career, jobseekers often want to know which occupations offer the best prospects. Generally, occupations that have rapid job growth, many new jobs, or many job openings--and good wages--promise better opportunities. This paper shows how employment in particular occupations is projected to change from 2010 to 2020. It presents…

  14. Frequent Mismatch Repair Protein Deficiency in Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium.

    PubMed

    Köbel, Martin; Tessier-Cloutier, Basile; Leo, Joyce; Hoang, Lien N; Gilks, C Blake; Soslow, Robert A; Delair, Deborah; Stewart, Colin J R; Lee, Cheng-Han

    2017-01-20

    Mixed endometrioid and clear cell carcinoma of the endometrium refers to a scenario in which the tumor exhibits histologic features of both endometrioid and clear cell carcinoma. We observed a tendency for these tumors to occur in a mismatch repair (MMR) protein-deficient molecular background in a prior study that examined a small cohort of mixed-type endometrial carcinomas. The aim of this study was to determine the rate of MMR protein deficiency in a larger series of endometrial mixed endometrioid and clear cell carcinomas, through a retrospective survey of MLH1, PMS2, MSH2, and MSH6 expression in such tumors at 5 tertiary centers. A total of 41 cases were identified and 27 (66%) tumors demonstrated MMR protein deficiency with a comparable frequency across the contributing centers (ranging from 56% to 83%). Among the MMR protein-deficient cases, 59% showed concurrent MLH1 and PMS2 loss, 33% showed concurrent MSH2 and MSH6 loss, and 4% showed isolated PMS2 or MSH6 loss. Compared with a previously published series of 15 pure endometrial clear cell carcinomas, mixed endometrioid and clear cell carcinomas are associated with significantly better disease-specific survival (P=0.02). In summary, endometrial carcinomas with mixed endometrioid and clear cell histology are frequently MMR protein deficient. This finding has implications both for our understanding of its tumor biology and for the identification of patients with potential Lynch syndrome.

  15. How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?

    PubMed

    Vilkin, Alex; Halpern, Marisa; Morgenstern, Sara; Brazovski, Eli; Gingold-Belfer, Rachel; Boltin, Doron; Purim, Ofer; Kundel, Yulia; Welinsky, Sara; Brenner, Baruch; Niv, Yaron; Levi, Zohar

    2014-10-01

    Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control (P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group (P = .009). In the neoadjuvant group, a disagreement pattern of "endoscopic strong operative focal" was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.

  16. A cascade targeting strategy for brain neuroglial cells employing nanoparticles modified with angiopep-2 peptide and EGFP-EGF1 protein.

    PubMed

    Huile, Gao; Shuaiqi, Pan; Zhi, Yang; Shijie, Cao; Chen, Chen; Xinguo, Jiang; Shun, Shen; Zhiqing, Pang; Yu, Hu

    2011-11-01

    Targeted drug delivery to selected brain cell types is a crucial step in enhancing therapeutic effects while limiting side effects in non-target cells. Here we report on the development and evaluation of a new cascade targeting delivery system that employs PEG-PCL nanoparticles modified with both an angiopep-2 peptide and a EGFP-EGF1 protein for precise targeting of brain neuroglial cells. Angiopep-2 penetrates the blood-brain barrier and EGFP-EGF1 binds neuroglial cells, providing the system with two stages of targeting. In vitro studies demonstrated that both bEnd.3 cells and neuroglial cells had a higher uptake of angiopep-2 and EGFP-EGF1 conjugated nanoparticles (AENP) as compared to unmodified nanoparticles. Ex vivo imaging showed that AENP had higher accumulation in the brain over unmodified nanoparticles and EGFP-EGF1 modified nanoparticles. Fluorescent in situ hybridization of brain slides demonstrated that AENP co-localized with neuroglial cells. Transmission electron microscopy further showed that AENP could target and enter neuroglial cells. This newly developed cascade targeting delivery system that precisely targets neuroglial cells has great potential in the diagnosis and treatment of neuroglial related diseases. Replacing EGFP-EGF1 and angiopep-2 with other ligands may extend the utility of the system to diagnose and treat organ diseases beyond brain.

  17. Measurement of fexofenadine concentration in micro-sample human plasma by a rapid and sensitive LC-MS/MS employing protein precipitation: application to a clinical pharmacokinetic study.

    PubMed

    Guo, Daqing; Zou, Jianjun; Zhu, Yubing; Lou, Sheng; Fan, Hongwei; Qin, Qun

    2010-03-01

    A simple, rapid and sensitive liquid chromatography/positive ion electro-spray tandem mass spectrometry method (LC-MS/MS) was developed and validated for the quantification of fexofenadine with 100 microL human plasma employing glipizide as internal standard (IS). Protein precipitation was used in the sample preparation procedure. Chromatographic separation was achieved on a reversed-phase C(18 )column (5 microm, 100 x 2.1 mm) with methanol : buffer (containing 10 mmol/L ammonium acetate and 0.1% formic acid; 70 : 30, v/v) as mobile phase. The total chromatographic runtime was approximately 3.0 min with retention time for fexofenadine and IS at approximately 1.9 and 2.1 min, respectively. Detection of fexofenadine and IS was achieved by LC-MS/MS in positive ion mode using 502.1 --> 466.2 and 446.0 --> 321.1 transitions, respectively. The method was proved to be accurate and precise at linearity range of 1-600 ng/mL with a correlation coefficient (r) of > or =0.9976. The validated method was applied to a pharmacokinetic study in human volunteers following oral administration of 60 or 120 mg fexofenadine formulations, successfully.

  18. Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens.

    PubMed

    Asbach, Benedikt; Kliche, Alexander; Köstler, Josef; Perdiguero, Beatriz; Esteban, Mariano; Jacobs, Bertram L; Montefiori, David C; LaBranche, Celia C; Yates, Nicole L; Tomaras, Georgia D; Ferrari, Guido; Foulds, Kathryn E; Roederer, Mario; Landucci, Gary; Forthal, Donald N; Seaman, Michael S; Hawkins, Natalie; Self, Steven G; Sato, Alicia; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan W; Burke, Brian; Cristillo, Anthony D; Weiss, Deborah E; Francis, Jesse; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L; Pantaleo, Giuseppe; Wagner, Ralf

    2016-04-01

    In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8(+)and CD4(+)T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens

  19. Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

    PubMed Central

    Asbach, Benedikt; Kliche, Alexander; Köstler, Josef; Perdiguero, Beatriz; Esteban, Mariano; Jacobs, Bertram L.; Montefiori, David C.; LaBranche, Celia C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Landucci, Gary; Forthal, Donald N.; Seaman, Michael S.; Hawkins, Natalie; Self, Steven G.; Sato, Alicia; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Francis, Jesse; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Pantaleo, Giuseppe

    2016-01-01

    ABSTRACT In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8+ and CD4+ T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE Within the EuroVacc clinical trials, we previously assessed the immunogenicity of

  20. Purification, crystallization and preliminary X-ray diffraction analysis of the human mismatch repair protein MutS[beta

    SciTech Connect

    Tseng, Quincy; Orans, Jillian; Hast, Michael A.; Iyer, Ravi R.; Changela, Anita; Modrich, Paul L.; Beese, Lorena S.

    2012-03-16

    MutS{beta} is a eukaryotic mismatch repair protein that preferentially targets extrahelical unpaired nucleotides and shares partial functional redundancy with MutS{alpha} (MSH2-MSH6). Although mismatch recognition by MutS{alpha} has been shown to involve a conserved Phe-X-Glu motif, little is known about the lesion-binding mechanism of MutS{beta}. Combined MSH3/MSH6 deficiency triggers a strong predisposition to cancer in mice and defects in msh2 and msh6 account for roughly half of hereditary nonpolyposis colorectal cancer mutations. These three MutS homologs are also believed to play a role in trinucleotide repeat instability, which is a hallmark of many neurodegenerative disorders. The baculovirus overexpression and purification of recombinant human MutS{beta} and three truncation mutants are presented here. Binding assays with heteroduplex DNA were carried out for biochemical characterization. Crystallization and preliminary X-ray diffraction analysis of the protein bound to a heteroduplex DNA substrate are also reported.

  1. Mismatch repair protein deficient endometrioid adenocarcinomas, metastasizing to adrenal gland and lymph nodes: Unusual cases with diagnostic implications.

    PubMed

    Rekhi, Bharat

    2015-01-01

    Recently, certain endometrial carcinomas have been found to be associated with mismatch repair (MMR) protein defects/deficiency. A 39-year-old female presented with cough, decreased appetite and significant weight loss since 2 months. Earlier, she had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) for endometrioid adenocarcinoma. Imaging disclosed an 8 cm-sized adrenal mass that was surgically excised. Histopathology of the adrenal tumor, endocervical tumor, and endometrial biopsy revealed Federation of Gynecology and Obstetrics (FIGO) Grade II to III endometrioid adenocarcinoma. By immunohistochemistry, tumor cells were positive for cytokeratin 7, epithelial membrane antigen, PAX8, MLH1 and PMS2 while negative for estrogen receptor (ER), progesterone receptor (PR), MSH2 and MSH6. She underwent adjuvant radiotherapy and chemotherapy. A 34-year-old lady presented with vaginal bleeding since 9 months. She underwent TAH-BSO, reported as FIGO Grade III endometrioid adenocarcinoma. By immunohistochemistry, tumor cells were negative for ER, PR, MLH1, and PMS2 while positive for MSH2 and MSH6. She underwent adjuvant radiotherapy and chemotherapy. However, she developed multiple nodal and pericardial metastases and succumbed to the disease within a year post-diagnosis. Certain high-grade endometrioid adenocarcinomas occurring in younger women are MMR protein deficient and display an aggressive clinical course. Adrenal metastasis in endometrial carcinomas is rare.

  2. Evaluating Employability Skills: Employer and Student Perceptions

    ERIC Educational Resources Information Center

    Saunders, Venetia; Zuzel, Katherine

    2010-01-01

    Graduate employability is a key issue for Higher Education. In this two-part study student employability skills have been evaluated from the perspective of sandwich students and graduates in biomolecular science, and their employers. A strong correlation was found between employer and sandwich student/graduate perceptions of the relative…

  3. Evaluating Employability Skills: Employer and Student Perceptions

    ERIC Educational Resources Information Center

    Saunders, Venetia; Zuzel, Katherine

    2010-01-01

    Graduate employability is a key issue for Higher Education. In this two-part study student employability skills have been evaluated from the perspective of sandwich students and graduates in biomolecular science, and their employers. A strong correlation was found between employer and sandwich student/graduate perceptions of the relative…

  4. Food safety knowledge on the Bt mutant protein Cry8Ka5 employed in the development of coleopteran-resistant transgenic cotton plants.

    PubMed

    Farias, Davi F; Peijnenburg, Ad A C M; Grossi-de-Sá, Maria F; Carvalho, Ana F U

    2015-01-01

    Insecticidal Cry proteins from Bacillus thuringiensis (Bt) have been exploited in the development of genetically modified (GM) crops for pest control. However, several pests are still difficult to control such as the coleopteran boll weevil Anthonomus grandis. By applying in vitro molecular evolution to the cry8Ka1 gene sequence, variants were generated with improved activity against A. grandis. Among them, Cry8Ka5 mutant protein showed coleoptericidal activity 3-fold higher (LC50 2.83 μg/mL) than that of the original protein (Cry8Ka1). Cry8Ka5 has been used in breeding programs in order to obtain coleopteran-resistant cotton plants. Nevertheless, there is some concern in relation to the food safety of transgenic crops, especially to the heterologously expressed proteins. In this context, our research group has performed risk assessment studies on Cry8Ka5, using the tests recommended by Codex as well as tests that we proposed as alternative and/or complementary approaches. Our results on the risk analysis of Cry8Ka5 taken together with those of other Cry proteins, point out that there is a high degree of certainty on their food safety. It is reasonable to emphasize that most safety studies on Cry proteins have essentially used the Codex approach. However, other methodologies would potentially provide additional information such as studies on the effects of Cry proteins and derived peptides on the indigenous gastrointestinal microbiota and on intestinal epithelial cells of humans. Additionally, emerging technologies such as toxicogenomics potentially will offer sensitive alternatives for some current approaches or methods.

  5. Food safety knowledge on the Bt mutant protein Cry8Ka5 employed in the development of coleopteran-resistant transgenic cotton plants

    PubMed Central

    Farias, Davi F; Peijnenburg, Ad A C M; Grossi-de-Sá, Maria F; Carvalho, Ana F U

    2015-01-01

    Insecticidal Cry proteins from Bacillus thuringiensis (Bt) have been exploited in the development of genetically modified (GM) crops for pest control. However, several pests are still difficult to control such as the coleopteran boll weevil Anthonomus grandis. By applying in vitro molecular evolution to the cry8Ka1 gene sequence, variants were generated with improved activity against A. grandis. Among them, Cry8Ka5 mutant protein showed coleoptericidal activity 3-fold higher (LC50 2.83 μg/mL) than that of the original protein (Cry8Ka1). Cry8Ka5 has been used in breeding programs in order to obtain coleopteran-resistant cotton plants. Nevertheless, there is some concern in relation to the food safety of transgenic crops, especially to the heterologously expressed proteins. In this context, our research group has performed risk assessment studies on Cry8Ka5, using the tests recommended by Codex as well as tests that we proposed as alternative and/or complementary approaches. Our results on the risk analysis of Cry8Ka5 taken together with those of other Cry proteins, point out that there is a high degree of certainty on their food safety. It is reasonable to emphasize that most safety studies on Cry proteins have essentially used the Codex approach. However, other methodologies would potentially provide additional information such as studies on the effects of Cry proteins and derived peptides on the indigenous gastrointestinal microbiota and on intestinal epithelial cells of humans. Additionally, emerging technologies such as toxicogenomics potentially will offer sensitive alternatives for some current approaches or methods. PMID:26513483

  6. An ELISA immunoassay employing a conserved Leishmania hypothetical protein for the serodiagnosis of visceral and tegumentary leishmaniasis in dogs and humans.

    PubMed

    Carvalho, Ana Maria R S; Costa, Lourena E; Salles, Beatriz C S; Santos, Thaís T O; Ramos, Fernanda F; Lima, Mariana P; Chávez-Fumagalli, Miguel A; Silvestre, Bruna T; Portela, Áquila S B; Roatt, Bruno M; Silveira, Julia A G; Gonçalves, Denise U; Magalhães-Soares, Danielle F; Duarte, Mariana C; Menezes-Souza, Daniel; Coelho, Eduardo A F

    2017-08-01

    In the present study, a conserved Leishmania hypothetical protein, namely LiHypA, was evaluated for the serodiagnosis of visceral and tegumentary leishmaniasis in dogs and humans. This protein showed a high amino acid sequence homology between viscerotropic and cutaneotropic Leishmania species. An enzyme-linked immunosorbent assay (ELISA) was developed using the recombinant antigen (rLiHypA), in addition to the A2 protein and two parasite antigenic preparations, which were used as controls. Regarding human diagnosis, results showed that rLiHypA was more sensitive and specific than ELISA-L. braziliensis SLA in detecting both cutaneous or mucosal leishmaniasis patients, but not those from Chagas disease patients or healthy subjects. Regarding canine diagnosis, this recombinant antigen showed higher sensitivity and specificity values, as well as a perfect accuracy to identify asymptomatic and symptomatic visceral leishmaniasis (VL) in dogs, but not those from vaccinated animals or those developing babesiosis, ehrlichiosis, or Chagas disease. However, using the rA2 protein or L. braziliensis SLA as controls, significant cross-reactivity was found when these samples were used, hampering their sensitivity and specificity values for the diagnosis. In this context, LiHypA could be considered a candidate to be evaluated for the serodiagnosis of visceral and tegumentary leishmaniasis in dogs and humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Maize Tapetum Employs Diverse Mechanisms to Synthesize and Store Proteins and Flavonoids and Transfer Them to the Pollen Surface1[W][OA

    PubMed Central

    Li, Yubing; Suen, Der Fen; Huang, Chien-Yu; Kung, Shung-Yee; Huang, Anthony H.C.

    2012-01-01

    In anthers, the tapetum synthesizes and stores proteins and flavonoids, which will be transferred to the surface of adjacent microspores. The mechanism of synthesis, storage, and transfer of these pollen-coat materials in maize (Zea mays) differs completely from that reported in Arabidopsis (Arabidopsis thaliana), which stores major pollen-coat materials in tapetosomes and elaioplasts. On maize pollen, three proteins, glucanase, xylanase, and a novel protease, Zea mays pollen coat protease (ZmPCP), are predominant. During anther development, glucanase and xylanase transcripts appeared at a mid developmental stage, whereas protease transcript emerged at a late developmental stage. Protease and xylanase transcripts were present only in the anther tapetum of the plant, whereas glucanase transcript was distributed ubiquitously. ZmPCP belongs to the cysteine protease family but has no closely related paralogs. Its nascent polypeptide has a putative amino-terminal endoplasmic reticulum (ER)-targeting peptide and a propeptide. All three proteins were synthesized in the tapetum and were present on mature pollen after tapetum death. Electron microscopy of tapetum cells of mid to late developmental stages revealed small vacuoles distributed throughout the cytoplasm and numerous secretory vesicles concentrated near the locular side. Immunofluorescence microscopy and subcellular fractionation localized glucanase in ER-derived vesicles in the cytoplasm and the wall facing the locule, xylanase in the cytosol, protease in vacuoles, and flavonoids in subdomains of ER rather than in vacuoles. The nonoverlapping subcellular locations of the three proteins and flavonoids indicate distinct modes of their storage in tapetum cells and transfer to the pollen surface, which in turn reflect their respective functions in tapetum cells or the pollen surface. PMID:22291199

  8. Formation of C-terminally truncated version of the Taz1 protein employs cleavage-box structure in mRNA

    SciTech Connect

    Gunisova, Stanislava; Bartosova, Zdenka; Kramara, Juraj; Nosek, Jozef; Tomaska, Lubomir

    2010-02-12

    When expressed in various hosts the taz1{sup +} gene encoding the fission yeast telomere-binding protein produces two forms of polypeptides: full-length (Taz1p) and truncated (Taz1p{Delta}C) version lacking almost entire Myb-domain. Whereas Taz1p binds telomeric DNA in vitro, Taz1p{Delta}C forms long filaments unable of DNA binding. The formation of Taz1p{Delta}C is a result of neither site-specific proteolysis, nor premature termination of transcription. In silico analysis of the taz1{sup +} RNA transcript revealed a stem-loop structure at the site of cleavage (cleavage box; CB). In order to explore whether it possesses inherent destabilizing effects, we cloned CB sequence into the open reading frame (ORF) of glutathione-S-transferase (GST) and observed that when expressed in Escherichia coli the engineered gene produced two forms of the reporter protein. The formation of the truncated version of GST was abolished, when CB was replaced with recoded sequence containing synonymous codons thus indicating that the truncation is based on structural properties of taz1{sup +} mRNA.

  9. Employing Discourse: Universities and Graduate "Employability"

    ERIC Educational Resources Information Center

    Boden, Rebecca; Nedeva, Maria

    2010-01-01

    What constitutes graduate employability is discursively framed. In this paper we argue that whilst universities in the UK have long had an involvement in producing useful and productive citizens, the ongoing neoliberalisation of higher education has engendered a discursive shift in definitions of employability. Traditionally, universities regarded…

  10. Employers' Views on Youth Literacy and Employability

    ERIC Educational Resources Information Center

    Macey, Emma

    2013-01-01

    This report looks at whether employers think schools are equipping young people with the literacy skills required for the workplace. It is primarily based on secondary literature sources and introductory conversations with a small sample of key employers and agencies. A complementary report presents evidence on young people's views on literacy and…

  11. Employing Discourse: Universities and Graduate "Employability"

    ERIC Educational Resources Information Center

    Boden, Rebecca; Nedeva, Maria

    2010-01-01

    What constitutes graduate employability is discursively framed. In this paper we argue that whilst universities in the UK have long had an involvement in producing useful and productive citizens, the ongoing neoliberalisation of higher education has engendered a discursive shift in definitions of employability. Traditionally, universities regarded…

  12. Learning, Labour and Employability

    ERIC Educational Resources Information Center

    Ball, Malcolm J.

    2009-01-01

    Public policy in the UK has adopted employability to define the relationship of globalisation, work and learning. This article claims that employability serves the interests of capital. It helps capital to exercise its domination/hegemony over labour and employs a redefined vision of learning as its principal vehicle. Employability is a term that…

  13. Becoming Self-Employed.

    ERIC Educational Resources Information Center

    Lee, Grant; Cochran, Larry

    1997-01-01

    Explored how persons become self-employed. In critical incident interviews with five self-employed persons the critical events that assisted or hindered progress toward self-employment were listed in chronological order. In general, becoming self-employed involved establishing conditions of action that enhanced a sense of agency, thus enabling…

  14. Identification of a site in the phosphocarrier protein, HPr, which influences its interactions with sugar permeases of the bacterial phosphotransferase system: kinetic analyses employing site-specific mutants.

    PubMed Central

    Koch, S; Sutrina, S L; Wu, L F; Reizer, J; Schnetz, K; Rak, B; Saier, M H

    1996-01-01

    The permeases of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system (PTS), the sugar-specific enzymes II, are energized by sequential phosphoryl transfer from phosphoenolpyruvate to (i) enzyme I, (ii) the phosphocarrier protein HPr, (iii) the enzyme IIA domains of the permeases, and (iv) the enzyme IIBC domains of the permeases which transport and phosphorylate their sugar substrates. A number of site-specific mutants of HPr were examined by using kinetic approaches. Most of the mutations exerted minimal effects on the kinetic parameters characterizing reactions involving phosphoryl transfer from phospho-HPr to various sugars. However, when the well-conserved aspartyl 69 residue in HPr was changed to a glutamyl residue, the affinities for phospho-HPr of the enzymes II specific for mannitol, N-acetylglucosamine, and beta-glucosides decreased markedly without changing the maximal reaction rates. The same mutation reduced the spontaneous rate of phosphohistidyl HPr hydrolysis but did not appear to alter the rate of phosphoryl transfer from phospho-enzyme I to HPr. When the adjacent glutamyl residue 70 in HPr was changed to a lysyl residue, the Vmax values of the reactions catalyzed by the enzymes II were reduced, but the Km values remained unaltered. Changing this residue to alanine exerted little effect. Site-specific alterations in the C terminus of the beta-glucoside enzyme II which reduced the maximal reaction rate of phosphoryl transfer about 20-fold did not alter the relative kinetic parameters because of the aforementioned mutations in HPr. Published three-dimensional structural analyses of HPr and the complex of HPr with the glucose-specific enzyme IIA (IIAGlc) (homologous to the beta-glucoside and N-acetylglucosamine enzyme IIA domains) have revealed that residues 69 and 70 in HPr are distant from the active phosphorylation site and the IIAGlc binding interface in HPr. The results reported therefore suggest that residues D-69 and E-70 in

  15. Development of a model for functional studies of ABCG2 (breast cancer resistance protein) efflux employing a standard BeWo clone (B24).

    PubMed

    Crowe, Andrew; Keelan, Jeffrey A

    2012-10-01

    Human choriocarcinoma-derived BeWo cells express high levels of breast cancer resistance protein (BCRP/ABCG2) with no functional P-glycoprotein (P-gp) (ABCB1) activity, making them a potential model to study bidirectional ABCG2-mediated drug transport. However, the original BeWo clone (B24) available to researchers does not form confluent monolayers with tight junctions required by the model. Our aim was to adapt culture conditions to attempt to generate confluent BeWo monolayers for drug transport studies using the standard B24 clone. BeWo cells (B24; American Type Culture collection [ATCC]) were cultured in six-well plates or polycarbonate millicell inserts in a number of media formulations, growth supplements, and basement membrane substitutes. Cells were examined for confluence by microscopy, and transepithelial electrical resistance (TEER) was measured daily; monolayer permeability was assessed when TEER had stabilized. Optimal growth rates were achieved in culture conditions consisting of Medium 199 (M199) supplemented with epidermal growth factor (EGF; 20 ng/mL), vitamin supplements, and 10% fetal calf serum (FCS) with collagen coating. A TEER of 170 Ω in 0.6 cm(2) inserts was achieved 2 weeks after seeding under optimal conditions. The cell-impermeable diffusion marker 5(6) carboxy-2,7dichlorodihydrofluorescein (C-DCDHF) had a permeability coefficient of 3.5×10(-6) cm/s, indicative of minimal paracellular permeability. ABCG2 expression, as determined by immunoblotting, remained unaffected by confluency. In conclusion, we describe culture conditions for the B24 BeWo clone that facilitate the formation of monolayers with tighter junctions and reduced paracellular transport compared to previously published models. These growth conditions provide a good model of ABCG2-mediated drug transport in a human placental cell line.

  16. Employment Outlook '73

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1972

    1972-01-01

    Describes career opportunities for chemists considering employment areas of opportunity, salaries, college chemistry enrollments, research and development budgets, long term forecasts of supply and demand for chemists. Includes career planning aids, and an employers directory of chemical professions. (DF)

  17. Employment Testing and Discrimination

    ERIC Educational Resources Information Center

    Robertson, David E.

    1975-01-01

    The article deals with personnel problems associated with the status of employment testing practices as affected by equal employment opportunity legislation. A coordinated effort by business, government, and education is needed to provide clear step-by-step guidelines. (EA)

  18. Youth Employment. Policy Statement.

    ERIC Educational Resources Information Center

    National Collaboration for Youth, Washington, DC.

    This paper presents the policy statement on youth employment from the National Collaboration for Youth (NCY). An introduction briefly explains the role of the NCY with regard to youth employment and describes the types of programs and services supported by NCY. A section on background provides statistics on teenagers and employment from the Bureau…

  19. Graduate Identity and Employability

    ERIC Educational Resources Information Center

    Hinchliffe, Geoffrey William; Jolly, Adrienne

    2011-01-01

    This paper develops the concept of graduate identity as a way of deepening the understanding of graduate employability. It does this through presenting research in which over 100 employers in East Anglia were asked to record their perceptions of graduates in respect of their employability. The findings suggest a composite and complex graduate…

  20. 1982 Employment Outlook.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1981

    1981-01-01

    Presents highlights of Chemical and Engineering News survey of the employment picture for chemical professionals. Focuses on the question of needing a Ph.D.; employment opportunities; salaries; and career planning, including the names and addresses of many employers of chemists and chemical engineers. (SK)

  1. 1987 Employment Outlook.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1986

    1986-01-01

    Traces the decline in employment opportunities for chemists and chemical engineers. Discusses the employment outlook for 1987. Includes information on continuing education opportunities for chemical professionals already employed, the drop in demand for chemistry professionals, the decline in salaries of bachelor's degree chemists, and several…

  2. 1976 Employment Outlook

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1975

    1975-01-01

    Presents an extended annual review of employment for chemists and chemical engineers. Includes 1975 employment statistics, a discussion of what employers are seeking, salaries of professional chemists, the status of U.S. spending in research and development, and a variety of aids available to both new and experienced chemical professionals in…

  3. The New Employment Contract?

    ERIC Educational Resources Information Center

    Levine, David I.

    2002-01-01

    In the classic employment contract, especially at large companies, wages were not strongly responsive to the labor market. Instead, individual companies had distinctive company wage levels and patterns. An exhaustive study of employers and employees in the United States and Japan examined whether the "old employment contract" has been…

  4. Recognition for Employed Inventors.

    ERIC Educational Resources Information Center

    Sanders, Howard J.

    1980-01-01

    Presents arguments for monetary rewards and other forms of recognition by employers for inventions of employed inventors, particularly as the concept applies to stimulating innovativeness in America. Discusses the controversy of federally mandated compensation for employed inventors. The efforts of the American Chemical Society along these lines…

  5. Employment in Agribusiness.

    ERIC Educational Resources Information Center

    Hilgenberg, Gene; Huston, Jane

    This curriculum guide is intended to assist persons teaching a course in employment in agribusiness. Addressed in the individual units of instruction are the following topics: employment information (training plans/agreements and wages, taxes, and fringe benefits); human relations (employer/employee/customer relations and communication skills);…

  6. The New Employment Contract?

    ERIC Educational Resources Information Center

    Levine, David I.

    2002-01-01

    In the classic employment contract, especially at large companies, wages were not strongly responsive to the labor market. Instead, individual companies had distinctive company wage levels and patterns. An exhaustive study of employers and employees in the United States and Japan examined whether the "old employment contract" has been…

  7. Proteins.

    ERIC Educational Resources Information Center

    Doolittle, Russell F.

    1985-01-01

    Examines proteins which give rise to structure and, by virtue of selective binding to other molecules, make genes. Binding sites, amino acids, protein evolution, and molecular paleontology are discussed. Work with encoding segments of deoxyribonucleic acid (exons) and noncoding stretches (introns) provides new information for hypotheses. (DH)

  8. Proteins.

    ERIC Educational Resources Information Center

    Doolittle, Russell F.

    1985-01-01

    Examines proteins which give rise to structure and, by virtue of selective binding to other molecules, make genes. Binding sites, amino acids, protein evolution, and molecular paleontology are discussed. Work with encoding segments of deoxyribonucleic acid (exons) and noncoding stretches (introns) provides new information for hypotheses. (DH)

  9. Protein

    USDA-ARS?s Scientific Manuscript database

    Proteins are the major structural and functional components of all cells in the body. They are macromolecules that comprise 1 or more chains of amino acids that vary in their sequence and length and are folded into specific 3-dimensional structures. The sizes and conformations of proteins, therefor...

  10. Employers Roundtable: Employer Supported Child Care.

    ERIC Educational Resources Information Center

    Delaware Valley Child Care Council, Philadelphia, PA.

    This booklet outlines a number of options available to employers to enable them to better cope with child care issues that they and their employees face. Major options include: (1) flexible work policies, such as flexible scheduling, alternate work places, shorter work weeks, and the consolidating of sick leave, holidays, and vacation time into…

  11. Protein

    MedlinePlus

    ... Search for: Harvard T.H. Chan School of Public Health Email People Departments Calendar Careers Give my.harvard ... Nutrition Source Harvard T.H. Chan School of Public Health > The Nutrition Source > What Should I Eat? > Protein ...

  12. Employment specialist competencies as predictors of employment outcomes.

    PubMed

    Taylor, Amanda C; Bond, Gary R

    2014-01-01

    Employment specialist competencies were examined as predictors of employment outcomes for consumers with serious mental illness participating in supported employment. Self-report and supervisor-rated performance measures from 57 employment specialists were correlated with three consumer employment outcomes (i.e., competitive employment rate, 90-day employment rate, and dropout rate). Employment specialists varied from 0 to 80 % in the competitive employment rates for their caseloads. Supervisor ratings of job performance and employment specialist efficacy, percentage of time in the community, and frequency of contacts with consumers were associated with employment outcomes. Employment specialist self-report measures were unrelated to employment outcomes. Surprisingly, employment specialists with larger caseload sizes had higher employment rates. Employment specialists vary widely in their effectiveness. Behavioral measures and supervisory ratings of employment specialists were most predictive of employment outcomes. Direct observation of employment specialist job performance appears to be the most promising method for identifying competencies predictive of employment outcome.

  13. Maine's Employability Skills Program

    ERIC Educational Resources Information Center

    McMahon, John M.; Wolffe, Karen E.; Wolfe, Judy; Brooker, Carrie

    2013-01-01

    This Practice Report describes the development and implementation of the "Maine Employability Skills Program," a model employment program developed by the Maine Division for the Blind and Visually Impaired (DBVI). The program was designed to support the efforts of the chronically unemployed or underemployed. These consumers were either…

  14. Employment Policy and Territories.

    ERIC Educational Resources Information Center

    Berthet, Thierry; Cuntigh, Philippe; Guitton, Christophe

    2002-01-01

    France's employment policy has historically been governed by a strategy of interventions aimed at specific categories of individuals, including victims of industrial restructuring, entry workers, the long-term unemployed, and the disabled. Since the 1980s, France has had the following main lines of employment policy: (1) assistance to victims of…

  15. Does Supported Employment Work?

    ERIC Educational Resources Information Center

    Morgan McInnes, Melayne; Ozturk, Orgul Demet; McDermott, Suzanne; Mann, Joshua R.

    2010-01-01

    Providing employment-related services, including supported employment through job coaches, has been a priority in federal policy since the enactment of the Developmental Disabilities Assistance and Bill of Rights Act in 1984. We take advantage of a unique panel data set of all clients served by the South Carolina Department of Disabilities and…

  16. Supported Employment in Spain.

    ERIC Educational Resources Information Center

    Verdugo, Miguel Angel; Borja, F.; de Urries, Jordan; Bellver, Fernando; Martinez, Salvador

    1998-01-01

    Supported employment is growing in Spain, assisted by models from other countries and national legislation. The Spanish Association of Supported Employment is providing a framework for program development. The field must deal with the lack of systematic evaluation and with funding problems. (SK)

  17. Employment and Training Programs.

    ERIC Educational Resources Information Center

    Minnesota State Office of the Legislative Auditor, St. Paul. Program Evaluation Div.

    This report examines the effectiveness of employment and training programs in Minnesota and discusses the impact of the 1985 Jobs Bill state legislation. Chapter 1 provides an introduction to Minnesota's programs and to studies of employment and training programs conducted nationwide. Chapter 2 studies the use of Job Training Partnership Act funds…

  18. An Employer Needs Assessment.

    ERIC Educational Resources Information Center

    Becker, Aliza; And Others

    1986-01-01

    A Chicago vocational English language training program (VELT) conducted a needs assessment survey of employers of limited-English-proficient (LEP) workers in assembly, packing, shipping, janitorial and housekeeping, machine operation, and food preparation jobs. The purposes of the survey were to determine: (1) the employers' methods of obtaining…

  19. Addressing Employer Services.

    ERIC Educational Resources Information Center

    Perspective: Essays and Reviews of Issues in Employment Security and Employment and Training Programs, 1986

    1986-01-01

    This volume of an annual journal contains 21 articles focusing on the many services that state Employment Security (ES) agencies are providing to improve outreach to employers who pay for the programs through the dedicated revenues of the Federal Unemployment Tax Act and state benefit taxes and to improve their own staff ability to deliver…

  20. Youth-Education-Employment.

    ERIC Educational Resources Information Center

    Wirtz, Willard; And Others

    The document presents the proceedings of an international symposium analyzing the relationship among youth, education, and employment, with emphasis on youth employment trends and the need to find solutions for unemployment problems. The objectives are to evaluate the existing relationship in the light of changing values and expectations of young…

  1. Listening to Employers

    ERIC Educational Resources Information Center

    Machalski, Jan; Riley, Alison; Aubrey, Karl

    2009-01-01

    Various government initiatives have highlighted the importance of employer engagement in schools, further education and higher education. However, speaking as a team of lecturers in HE the authors have found that there is a tension between the perceptions of government and those of employers. Clearly, it would be a good thing if, particularly in…

  2. Addressing Employer Services.

    ERIC Educational Resources Information Center

    Perspective: Essays and Reviews of Issues in Employment Security and Employment and Training Programs, 1986

    1986-01-01

    This volume of an annual journal contains 21 articles focusing on the many services that state Employment Security (ES) agencies are providing to improve outreach to employers who pay for the programs through the dedicated revenues of the Federal Unemployment Tax Act and state benefit taxes and to improve their own staff ability to deliver…

  3. Maine's Employability Skills Program

    ERIC Educational Resources Information Center

    McMahon, John M.; Wolffe, Karen E.; Wolfe, Judy; Brooker, Carrie

    2013-01-01

    This Practice Report describes the development and implementation of the "Maine Employability Skills Program," a model employment program developed by the Maine Division for the Blind and Visually Impaired (DBVI). The program was designed to support the efforts of the chronically unemployed or underemployed. These consumers were either…

  4. Employment and Unemployment.

    ERIC Educational Resources Information Center

    Simler, N. J.

    Three sections of information are presented in this report on employment and unemployment. Section 1 discusses how the concepts of employment, unemployment, and the labor force are defined and measured. Included in the discussion is an explanation of the current population survey. Section 2 examines the principal trends and cyclical movements of…

  5. Energy and employment

    SciTech Connect

    Nordlund, W.J.; Robson, R.T.

    1980-01-01

    The relationship of energy and employment is an essential ingredient of the current energy-policy debate. Energy, in its various forms, is an almost universal input to the production and consumption of goods and services in modern society, yet little attention is paid to its employment impacts. Far too little attention is being paid to the impact that changes in the sources, uses, and prices of energy will have on the level, location, and structure of employment in the U.S. economy. Unless their consequences are foreseen, energy solutions may have profound and sometimes devastating effects upon regions, industries, and jobs. This study addresses eight areas of this relationship: labor supply and demand in the energy sector; socio-economic impacts of energy development; coal, electricity, and employment; energy as a factor in the production/consumption process; alternative technologies and employment; developing an energy/employment modeling capability; research priorities; and policy recommendations related to energy/employment relationships. 40 references, 7 figures, 22 tables.

  6. Placement: The Employer's View.

    ERIC Educational Resources Information Center

    Teff, Donald R.

    1979-01-01

    A bank vice president reviews three barriers to the employment of handicapped persons: misunderstanding and lack of knowledge concerning the handicapped, the traditional lag between recognition of a problem and its solution, and apathy and disinterest. (CL)

  7. Placement: The Employer's View.

    ERIC Educational Resources Information Center

    Teff, Donald R.

    1979-01-01

    A bank vice president reviews three barriers to the employment of handicapped persons: misunderstanding and lack of knowledge concerning the handicapped, the traditional lag between recognition of a problem and its solution, and apathy and disinterest. (CL)

  8. Farm Employment Trends

    ERIC Educational Resources Information Center

    Rural Manpower Developments, 1973

    1973-01-01

    The heavy spring rains of 1973 led to delays and reduced acreage in planting, resulting in a sharp decline in vegetable and cotton employment. Seasonal farmworker job levels are reported by state and activity. (MS)

  9. Small Bowel Adenocarcinoma Frequently Exhibits Lynch Syndrome-associated Mismatch Repair Protein Deficiency But Does Not Harbor Sporadic MLH1 Deficiency.

    PubMed

    Xia, Michelle; Singhi, Aatur D; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

    2017-07-01

    Universal screening for Lynch syndrome has been advocated for colorectal carcinoma but its utility in small bowel adenocarcinoma has not been reported. We analyzed a consecutive series of 71 small bowel adenocarcinomas identified over an 8-year period for DNA mismatch repair (MMR) protein expression to (1) compare the clinicopathologic features of small bowel adenocarcinoma stratified into MMR-deficient (MMRD) and MMR-proficient (MMRP) groups and (2) examine the patterns of MMR protein expression in small bowel adenocarcinoma compared with colorectal carcinoma. Six of 71 (8.5%) small bowel adenocarcinomas and 149 of 1291 (11.5%) colorectal carcinomas demonstrated MMRD. The 6 MMRD small bowel adenocarcinomas had the following expression pattern: 3 with concurrent loss of MSH2 and MSH6, 1 with isolated loss of MSH6, and 2 with concurrent loss of MLH1 and PMS2 in patients with a family history suggestive of genetic cancer susceptibility. Histopathology suggestive of MMR protein deficiency as proposed by the revised Bethesda guidelines was commonly seen in both MMRP (63%) and MMRD (67%) small bowel adenocarcinomas (P>0.05). MMRD small bowel adenocarcinoma more frequently demonstrated abnormalities of MSH2 and/or MSH6 (4/6, 67%) compared with MMRD colorectal carcinoma (23/149, 15%) (P=0.01). None of the MMRD small bowel adenocarcinomas harbored the BRAF V600E mutation, whereas 60% of MMRD colorectal carcinomas were positive for BRAF V600E with concurrent loss of MLH1 and PMS2 expression. Small bowel adenocarcinoma more frequently harbored Lynch syndrome-associated MMRD compared with colorectal carcinoma, providing support for screening of small bowel adenocarcinoma to identify patients at risk for Lynch syndrome. In contrast to colorectal carcinoma, sporadic MLH1 deficiency is not seen in small bowel adenocarcinoma. Clinicopathologic and histologic features do not distinguish between MMRP and MMRD small bowel adenocarcinoma indicating that universal screening in small

  10. Ergonomics of bridge employment.

    PubMed

    Mohamed, Mokdad

    2012-01-01

    In many countries of the world, retirement is mandatory at the age at which persons who hold certain jobs or offices are required by employment law to leave their employment, or retire (60 to 65 years). Typically, this is justified by the argument that certain occupations are either too dangerous or require high levels of physical skills and mental work. Every worker has to leave the workforce at that age. However, starting from the last two decades of the last century, it is observed that retirees live more years in retirement than ever before. This relatively long retirement as well as retirees' body fitness made many of them engage in new jobs which are either similar to their career jobs, or completely different from them. In this new type of employment which is called "bridge employment', the retired worker may spend more than ten years. But, to what extent these new jobs are fitted to the aged worker? Considering that experiencing any type of event increases the risk of worse health outcomes over time, bridge employment should be ergonomically designed if it is to fit the aged worker characteristics (physical, mental and affective).

  11. Equal Employment Opportunity. 1968 Report.

    ERIC Educational Resources Information Center

    Wisconsin State Dept. of Industry, Labor and Human Relations, Madison.

    The Equal Employment Opportunity survey reported employment levels and information in the state of Wisconsin for 1968. A sample of 2,132 business firms employing 532,231 persons took part in the survey. Information categories were: (1) minority group employment, (2) major industry group firms, (3) women in employment, (4) employment by job…

  12. Mgm101: A double-duty Rad52-like protein

    PubMed Central

    Rendeková, Jana; Šimoničová, Lucia; Thomas, Peter H.; McHugh, Peter J.; Chovanec, Miroslav

    2016-01-01

    ABSTRACT Mgm101 has well-characterized activity for the repair and replication of the mitochondrial genome. Recent work has demonstrated a further role for Mgm101 in nuclear DNA metabolism, contributing to an S-phase specific DNA interstrand cross-link repair pathway that acts redundantly with a pathway controlled by Pso2 exonuclease. Due to involvement of FANCM, FANCJ and FANCP homologues (Mph1, Chl1 and Slx4), this pathway has been described as a Fanconi anemia-like pathway. In this pathway, Mgm101 physically interacts with the DNA helicase Mph1 and the MutSα (Msh2/Msh6) heterodimer, but its precise role is yet to be elucidated. Data presented here suggests that Mgm101 functionally overlaps with Rad52, supporting previous suggestions that, based on protein structure and biochemical properties, Mgm101 and Rad52 belong to a family of proteins with similar function. In addition, our data shows that this overlap extends to the function of both proteins at telomeres, where Mgm101 is required for telomere elongation during chromosome replication in rad52 defective cells. We hypothesize that Mgm101 could, in Rad52-like manner, preferentially bind single-stranded DNAs (such as at stalled replication forks, broken chromosomes and natural chromosome ends), stabilize them and mediate single-strand annealing-like homologous recombination event to prevent them from converting into toxic structures. PMID:27636878

  13. Reduction of DNA mismatch repair protein expression in airway epithelial cells of premenopausal women chronically exposed to biomass smoke.

    PubMed

    Mukherjee, Bidisha; Dutta, Anindita; Chowdhury, Saswati; Roychoudhury, Sanghita; Ray, Manas Ranjan

    2014-02-01

    Biomass burning is a major source of indoor air pollution in rural India. This study examined whether chronic inhalation of biomass smoke causes change in the DNA mismatch repair (MMR) pathway in the airway cells. For this, airway cells exfoliated in sputum were collected from 72 premenopausal nonsmoking rural women (median age 34 years) who cooked with biomass (wood, dung, crop residues) and 68 control women who cooked with cleaner fuel liquefied petroleum gas (LPG) for the past 5 years or more. The levels of particulate matters with diameters less than 10 and 2.5 μm (PM10 and PM2.5) in indoor air were measured by real-time aerosol monitor. Benzene exposure was monitored by measuring trans,trans-muconic acid (t,t-MA) in urine by high-performance liquid chromatography with ultraviolet detector. Generation of reactive oxygen species (ROS) and level of superoxide dismutase (SOD) in airway cells were measured by flow cytometry and spectrophotometry, respectively. Immunocytochemical assay revealed lower percentage of airway epithelial cells expressing MMR proteins mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) in biomass-using women compared to LPG-using controls. Women who cooked with biomass had 6.7 times higher level of urinary t,t-MA, twofold increase in ROS generation, and 31 % depletion of SOD. Indoor air of biomass-using households had three times more particulate matters than that of controls. ROS, urinary t,t-MA, and particulate pollution in biomass-using kitchen had negative correlation, while SOD showed positive correlation with MSH2 and MLH1 expression. It appears that chronic exposure to biomass smoke reduces MMR response in airway epithelial cells, and oxidative stress plays an important role in the process.

  14. Examining the Role of Msh2 and Mre11 in Telomere Rescue

    DTIC Science & Technology

    2006-04-01

    genome stability, and how these dynamics may contribute to cancer and genome evolution . 15. SUBJECT TERMS Genetics,Molecular Biology,DNA Repair...dynamics and genome stability, and how these dynamics may contribute to cancer and genome evolution . Body: Task 1: Creation of the mutant...suggests a 30 generation delay in replicative senescence compared to haploid est2 mutants. This suggests a potential growth advantage in diploids that

  15. Examining the Role of Msh2 and Mre11 in Telomere Rescue

    DTIC Science & Technology

    2007-04-01

    polymerase genes REV1 and REV7. Finally, we have identified a new role for telomerase in facilitating the formation of translocations after double -strand...the formation of translocations after double -strand breaks are made on two different chromosomes. 4 Table of Contents Cover...prone polymerase genes REV1 and REV7. Finally, we have identified a new role for telomerase in facilitating the formation of translocations after double

  16. Disability Employment 101

    ERIC Educational Resources Information Center

    US Department of Education, 2007

    2007-01-01

    Business is about productivity and maintaining a competitive advantage. To do this, business needs qualified workers. Hiring people with disabilities adds value to a business and will attract new customers. Disability is not inability. Employers can make sound business decisions and gain a competitive advantage by using this guide to increase the…

  17. Employability Skills Center.

    ERIC Educational Resources Information Center

    Sweetwater Union High School District, Chula Vista, CA.

    The Employability Skills Center (ESC) of the Division of Adult and Continuing Education (DACE) of the Sweetwater Union High School District (California) was created out of a need to help adult students develop the basic skills that are required for success in their chosen vocational programs but not taught in regular adult basic education classes.…

  18. A Stochastic Employment Problem

    ERIC Educational Resources Information Center

    Wu, Teng

    2013-01-01

    The Stochastic Employment Problem(SEP) is a variation of the Stochastic Assignment Problem which analyzes the scenario that one assigns balls into boxes. Balls arrive sequentially with each one having a binary vector X = (X[subscript 1], X[subscript 2],...,X[subscript n]) attached, with the interpretation being that if X[subscript i] = 1 the ball…

  19. Westchester County Employers Survey.

    ERIC Educational Resources Information Center

    Lee, Marcia M.

    The Westchester County Employers Survey was done in May 2003 in order learn more about employee training needs, how they accomplished these needs, and how it would be possible for the Westchester Community College to fulfill these needs. Out of the 639 surveys sent, 145 were returned in a satisfactory format, which produces a 22.6% return rate.…

  20. Vietnamese Students Employability Skills

    ERIC Educational Resources Information Center

    Tuan, Nguyen Minh

    2011-01-01

    This paper attempts to investigate if the International University (IU) students' core competencies can meet the requirements set by employers, what are the differences in core competencies in final year students (or undergraduates), and how they view themselves compared with ex-students after one or two years in working environment, how…

  1. Industrialisation, Exports and Employment.

    ERIC Educational Resources Information Center

    Sabolo, Yves

    1980-01-01

    After reviewing trends in industrial production, exports, and employment in the Third World since 1960, the author discusses industrialization strategies based on the local processing of raw materials for export. Such processing has proved to be a major factor in job creation. (Author/SK)

  2. The Employability Skills Portfolio.

    ERIC Educational Resources Information Center

    Stemmer, Paul; And Others

    1992-01-01

    During 1990-91, Michigan schools piloted an innovative portfolio approach enabling students to discover, document, and develop employability skills in academics, personal management, and teamwork. Not an improved sorting system, the project encourages students to recognize successes, seek opportunities to improve skills, and gain confidence in…

  3. Employment. Feature Issue.

    ERIC Educational Resources Information Center

    Wallace, Teri, Ed.; And Others

    1993-01-01

    This theme issue addresses current trends and new developments in ensuring that individuals with disabilities have meaningful employment opportunities, especially in the context of recent federal legislation. Stressed throughout is the importance of collaboration among professionals, individuals with disabilities, and family members in achieving…

  4. Summer Employment for Youth.

    ERIC Educational Resources Information Center

    Jeppson, David L.; Hammer, Fran

    1992-01-01

    This article describes the Summer Work Experience Program developed by 3 agencies in Dallas, Texas, for students (ages 14-18) with visual impairments. The article describes student training; expectations for employees; attitudes of students, parents, and employers; and problems encountered. (JDD)

  5. The Employment Mismatch

    ERIC Educational Resources Information Center

    Fischer, Karin

    2013-01-01

    Employers value a four-year college degree, many of them more than ever. Yet half of those surveyed recently by "The Chronicle" and American Public Media's "Marketplace" said they had trouble finding recent graduates qualified to fill positions at their company or organization. Nearly a third gave colleges just fair to poor marks for producing…

  6. Engaging Employers in Assessment

    ERIC Educational Resources Information Center

    Brown, Gary; DesRosier, Theron; Peterson, Nils; Chida, Meriem; Lagier, Randy

    2009-01-01

    In this article, the authors describe a pilot project in which formative feedback from industry professionals creates a genuine learning experience for students. Industry is giving feedback to higher education that many graduates are not employable or that they need substantial postcollegiate on-the-job training. Higher education is struggling to…

  7. 1985 Employment Outlook: Demand.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1984

    1984-01-01

    Findings from an American Chemical Society survey show that the pessimism that characterized the job market in 1983 has given way to a much brighter outlook as employers hire more chemists and chemical engineers. Data from the survey on the supply and demand of chemical professionals are provided and discussed. (JN)

  8. 1983 Employment Outlook.

    ERIC Educational Resources Information Center

    Sanders, Howard J., Ed.

    1982-01-01

    Presents findings on employment situations for chemists and chemical engineers, focusing on: (1) comparison of chemists and chemical engineers; (2) salaries; (3) career planning; and (4) demand, indicated to be decidedly less than in previous years as a result of the deep business recession. (JN)

  9. Engaging Employers in Assessment

    ERIC Educational Resources Information Center

    Brown, Gary; DesRosier, Theron; Peterson, Nils; Chida, Meriem; Lagier, Randy

    2009-01-01

    In this article, the authors describe a pilot project in which formative feedback from industry professionals creates a genuine learning experience for students. Industry is giving feedback to higher education that many graduates are not employable or that they need substantial postcollegiate on-the-job training. Higher education is struggling to…

  10. Employability of Research Specialists.

    ERIC Educational Resources Information Center

    Rainey, Robert G.

    With new developments taking place in planning strategies for change in schools, new schemes and tactics are needed. Minneapolis Public Schools have developed the kind of organizational plan needed to find entry points into schools, systems for data gathering, and employment roles for research specialists. The Model for Local School Evaluation,…

  11. Declining Black Employment.

    ERIC Educational Resources Information Center

    Vedder, Richard; Gallaway, Lowell

    1993-01-01

    Explores income inequality during declining African-American employment, examines current welfare systems, and suggests ways to improve the economic disadvantages of minority groups. Letting markets work can improve the economic status of African Americans. The present dual African-American economy, a market economy and an entitlement economy, is…

  12. Survey of Employers.

    ERIC Educational Resources Information Center

    European Social Fund, Dublin (Ireland).

    A study examined attitudes of Irish employers toward vocational training (VT) activities, state agencies responsible for administering VT, and the skills that employees would need in the future. Of a sample of 500 firms that were selected as being representative from the standpoints of size, sector, location, and form of ownership, 219 were…

  13. Employer Needs Assessment.

    ERIC Educational Resources Information Center

    Shaffer, Richard A.

    In 1990, Cuesta College (CC) conducted a needs assessment of local employers to determine the type of work done by their employees, number of employees, hiring plans, the current level of employee training, and training needs. The mailed survey had 266 usable responses for a 40.9% return rate. Study findings included the following: (1) 31% of the…

  14. Age Discrimination in Employment

    ERIC Educational Resources Information Center

    New York University Law Review, 1975

    1975-01-01

    Economic, psychological, and social effects of age discrimination in employment are examined. This note analyzes constitutional challenges to hiring-age ceiling and mandatory retirement policies, as well as the constitutional criteria against which those ceilings and policies should be measured. Federal statutory prohibitions and their judicial…

  15. Discrimination in Employment

    ERIC Educational Resources Information Center

    Abzug, Bella

    1975-01-01

    This testimony, before a public hearing of the New York City Commission on Human Rights in May 1974, expressly focuses on discrimination in employment, asserting that this has had the most direct effect on minorities and women in the country; while legal protections have grown stronger, they have not been used effectively. (Author/JM)

  16. The Employment Mismatch

    ERIC Educational Resources Information Center

    Fischer, Karin

    2013-01-01

    Employers value a four-year college degree, many of them more than ever. Yet half of those surveyed recently by "The Chronicle" and American Public Media's "Marketplace" said they had trouble finding recent graduates qualified to fill positions at their company or organization. Nearly a third gave colleges just fair to poor marks for producing…

  17. Employment Prospects for Biologists.

    ERIC Educational Resources Information Center

    Korschgen, Ann J.; Davis, Jerry D.

    1983-01-01

    Assesses the results of a survey of organizations which hire individuals with a biological background, focusing on future hiring plans, level of education, employment selection factors, typical positions, and where jobs are listed. Recommends developing communication skills, maintaining high grades, and relevant work experience as keys to…

  18. Technology and employment

    SciTech Connect

    Cooper, M.H.

    1983-07-22

    The influence of technology on today's high unemployment picture is discussed. Employment in the high-technology sector is seen by some to be a panacea for workers who have lost their jobs due to irreversible structural causes. Some federal, regional, state, and local efforts being made to ease structural adjustment are included. 28 references, 2 figures, 3 tables.

  19. Employers, Families and Education.

    ERIC Educational Resources Information Center

    Partnership for Family Involvement in Education (ED), Washington, DC.

    Family involvement in education is good for business, critical to children's school achievement, and important in creating strong and vibrant communities. This report discusses the role of businesses and employers in helping partners and family members be more involved in children's learning. Throughout the report, programs at specific companies…

  20. Should Universities Promote Employability?

    ERIC Educational Resources Information Center

    McCowan, Tristan

    2015-01-01

    Employability is becoming increasingly central to the mission and functioning of universities, spurred on by national and supranational agencies, and the demands of marketisation. This article provides a response to the normative dimensions of the question, progressing through four stages: first, there is a brief consideration of the meaning and…

  1. Employer Satisfaction Survey.

    ERIC Educational Resources Information Center

    Broadbent, William A.

    A three-part, state-wide survey was conducted in Spring 1979, to determine employer satisfaction with the vocational programs offered at Hawaii's high schools and community colleges. Three populations were involved in the survey: (1) the personnel directors of 29 firms representing approximately 25% of the businesses in Hawaii with 250 or more…

  2. A Stochastic Employment Problem

    ERIC Educational Resources Information Center

    Wu, Teng

    2013-01-01

    The Stochastic Employment Problem(SEP) is a variation of the Stochastic Assignment Problem which analyzes the scenario that one assigns balls into boxes. Balls arrive sequentially with each one having a binary vector X = (X[subscript 1], X[subscript 2],...,X[subscript n]) attached, with the interpretation being that if X[subscript i] = 1 the ball…

  3. Toward Equality Through Employment

    ERIC Educational Resources Information Center

    Lekachman, Robert

    1974-01-01

    An indication of the rearrangements of power, privilege, income and wealth distribution that are necessary for the establishment of full employment with price stability; involving policies of guaranteed public service jobs, income maintenance, prices and wages controls, a redistributive taxation system, and the eventual "socialization of…

  4. Employer Engagement in Education

    ERIC Educational Resources Information Center

    Mann, Anthony; Dawkins, James

    2014-01-01

    The subject of this paper is employer engagement in education as it supports the learning and progression of young people through activities including work experience, job shadowing, workplace visits, career talks, mock interviews, CV workshops, business mentoring, enterprise competitions and the provision of learning resources. Interest has grown…

  5. Equal Opportunity in Employment

    ERIC Educational Resources Information Center

    Bullock, Paul

    This book focuses on discrimination in employment, defined as the denial of equal opportunity in the labor market to qualified persons on the basis of race, color, religion, national origin, age, sex, or any other factor not related to their individual qualifications for work. The average nonwhite college graduate can expect to earn less during…

  6. Learning Disabilities and Employment.

    ERIC Educational Resources Information Center

    Gerber, Paul J., Ed.; Brown, Dale S., Ed.

    This book provides information on preparing individuals with learning disabilities for the challenges of employment and outlines the rights of those with learning disabilities in the workplace. Introductory chapters in Part 1 include: "Life after School: Challenges in the Workplace" (Paul J. Gerber); "The New Economy in the 21st…

  7. Employment spectrum of IDDM.

    PubMed

    Songer, T J; LaPorte, R E; Dorman, J S; Orchard, T J; Becker, D J; Drash, A L

    1989-10-01

    Occupational issues in 158 insulin-dependent diabetes mellitus (IDDM) individuals and 158 matched nondiabetic siblings were examined in a case-control design to evaluate the role of diabetes in the employability of people with IDDM. Overall, the IDDM cases were more likely to report refusal for a job at some point in their lives (56 vs. 42%, P = .02) than were the nondiabetic control siblings. Surprisingly, individuals who told job interviewers about their diabetes were more likely to report job refusal than their siblings (64 vs. 42%, P = .005), whereas individuals who did not mention their diabetes reported rates of refusal similar to their siblings (44 vs. 41%). IDDM cases were also less likely to be employed full time compared with siblings (55 vs. 73%, P = .001). Reduced employment in IDDM respondents was related to work disability. Reported work disability was more than seven times greater in the IDDM than the sibling group. The presence of diabetic complications was the primary factor related to work disability. Although 13% of IDDM respondents were unable to work because of disability, absenteeism among IDDM cases currently working did not differ from that of the nondiabetic siblings. Diabetes was not significantly associated with career levels or household income levels reported by the IDDM group. Disability, however, had a strong detrimental influence on these variables. The results suggest that hiring practices by employers may still be discriminatory toward individuals with IDDM. Once hired, the employment experiences of the IDDM population appear to be similar to the experiences of the nondiabetic population, provided the development of disabling diabetic complications has not taken place.

  8. Employment in multiple sclerosis

    PubMed Central

    Vella, Lea; Vollmer, Tim; Hadjimichael, Olympia; Mohr, David C.

    2011-01-01

    Multiple sclerosis (MS) is associated with significant economic burden and high rates of unemployment. This investigation evaluated patient and disease characteristics associated with work loss and work initiation using the NARCOMS patient registry. Patient and disease characteristics associated with transitions to unemployment or employment were evaluated cross-sectionally and prospectively over the course of two assessment periods (mean interval of 1.56 ± 0.93 years). Eligible participants included 8,867 patients for the cross-sectional component, and 8,122 for longitudinal analyses. At Time 1 and Time 2 56–58 % of MS patients were not employed. At Time 1, unemployed participants more likely to have a progressive disease course, had a longer symptom duration, greater levels of disability as measured by the PDDS, and greater functional limitations across all domains of the performance scales (p < 0.0001 for all). At Time 2, increasing MS symptoms in the past 6 months increased the odds of becoming unemployed. In addition, specific problems in mobility, hand function, fatigue, and cognitive performance domains were associated with increased odds of becoming unemployed. Less severe problems in similar areas, including mobility, hand function, and cognitive functioning were also predictive of work initiation among patients not employed. MS is associated with high rates of unemployment. Specific physical and mental health limitations confer risk of employment cessation over time, as well as the likelihood of employment initiation. This study has implications for rehabilitation interventions to target specific MS related limitations that place patients at greatest risk for work status changes. PMID:18677639

  9. Consistency Between Maternal Employment Attitudes and Employment Status

    PubMed Central

    Youngblut, JoAnne M.

    2013-01-01

    The stability of mothers’ attitudes toward employment, employment status, and consistency between employment attitudes and behavior over a 15-month period was examined. Factors such as family finances, availability of child care, and child’s health status that could influence either employment attitudes or employment behavior were explored. Mothers of preterm infants (N = 98) and mothers of full-term, healthy infants (N = 101) completed questionnaires regarding home/employment orientation, choice and satisfaction with the employment decision, and employment behavior as part of a battery of instruments administered when their infants were 3,9, and 18 months old. Analyses indicated considerable stability in attitudes, behaviors, and consistency over a 15-month period for mothers of both full-term and preterm infants. Consistency groups were created based on employment status (employed versus not employed) and consistency status (consistent versus inconsistent) at each time point. Consistency groups differed on ratings of financial need and availability of child care. PMID:7480851

  10. Full Employment in Industrialized Countries.

    ERIC Educational Resources Information Center

    Britton, Andrew

    1997-01-01

    Argues that full employment must be acceptable on both social and economic grounds. Examines profound changes in industrialized economies since the 1970s and the diversity of employment contracts. Suggests that difficult policy decisions surround full employment. (SK)

  11. Employment security and health

    PubMed Central

    Virtanen, P; Vahtera, J; Kivimaki, M; Pentti, J; Ferrie, J

    2002-01-01

    Design: Cross sectional survey. Setting: Municipal sector employees in eight Finnish towns. Participants: 5981 employees with a permanent contract and 2786 employees with a non-permanent contract (2194 fixed term contract, 682 government subsidised contract). Outcome measures: Poor self rated health, chronic disease, and psychological distress. Results: Compared with permanent employees, fixed term men and women had better self rated health (men odds ratio 0.70; 95% confidence intervals 0.50 to 0.98, women 0.70 (0.60 to 0.82) and less chronic disease (men 0.69; 0.52 to 0.91; women 0.89; 0.79 to 1.02), but women had more psychological distress (1.26; 1.09 to 1.45). The only difference between subsidised employees and permanent employees was the high level of psychological distress in women (1.35; 1.09 to 1.68). Low perceived employment security was associated with poor health across all three indicators. The association of low perceived security with psychological distress was significantly stronger in permanent employees than among fixed term and subsidised employees, indicating that perceived security is more important for mental health among employees with a permanent contract. Conclusions: Contractual security and perceived security of employment are differently associated with health. It is therefore important to distinguish between these aspects of employment security in studies of labour market status and health. Such studies will also need to control for health selection, which is unlikely to operate in the same way among permanent and non-permanent employees. PMID:12118045

  12. Termination of employment.

    PubMed

    Quinlan, P J; Birt, K M

    1995-01-01

    The following questions and recommendations, taken from Jeffrey Hirsch & William Farrell's Labor and Employment in Rhode Island, provide a synopsis of the basic issues which employers should consider before making a decision to fire an employee: 1. Review all documentation and other company records considered when making the decision. Make sure all stated policies were followed by management. 2. Interview all managers who provided input on the decisions. 3. Be satisfied that the decision was made for the correct reason. 4. Was the employee aware that termination was likely? Can you document that awareness? 5. Was the individual given an opportunity to improve his or her performance? 6. Has the company discharged others for similar reasons in the past? 7. Has the company acted promptly and avoided relying on "stale" offense? 8. Is the employee protected by anti-discrimination statutes? (i.e. race, age, sex, national origin, handicapped or religion)? 9. Meet with the employee personally; do not discharge by phone or letter unless absolutely necessary. 10. Have a "passive" management witness at the meeting. 11. Conduct the meeting in a private area where other employees will not be able to see or hear the discussion. 12. Both the executive and management witness should prepare file memoranda concerning what is said at the discharge meeting. 13. Always tell the employee the reason for her or his discharge. 14. Discuss health insurance continuation (COBRA). 15. Discuss life and disability insurance, and pension/profit sharing status. 16. Discuss other issues, such as references and out placement policies. By taking the time to follow these suggestions and answer these questions, an employer can feel more secure that the termination has been conducted properly, and minimize the chances of becoming implicated in legal action related to the termination.

  13. Graduate Employability: A Conceptual Framework for Understanding Employers' Perceptions

    ERIC Educational Resources Information Center

    Cai, Yuzhuo

    2013-01-01

    This study provides a conceptual framework for understanding what employers think about the value of graduates with similar educational credentials in the workplace (their employability), using insights from the new institutionalism. In this framework, the development of employers' beliefs about graduates' employability is broken into a number of…

  14. Graduate Employability: A Conceptual Framework for Understanding Employers' Perceptions

    ERIC Educational Resources Information Center

    Cai, Yuzhuo

    2013-01-01

    This study provides a conceptual framework for understanding what employers think about the value of graduates with similar educational credentials in the workplace (their employability), using insights from the new institutionalism. In this framework, the development of employers' beliefs about graduates' employability is broken into a number of…

  15. Employers toe the line.

    PubMed

    2006-10-11

    It is no wonder that staff unions are unhappy about NHS Employers' evidence to the nurses' pay review body this year. There are many reasons why a rise of 2 per cent from next April would be inadequate. For a start, 2 per cent is still only a government inflation target; the latest Consumer Price Index of annual inflation rose to 2.5 per cent in August, up from 2.4 per cent in July, so ministers cannot even claim that prices are moving in the right direction.

  16. Employability. NIACE Briefing Sheet 88

    ERIC Educational Resources Information Center

    National Institute of Adult Continuing Education, 2009

    2009-01-01

    Employability skills are central to gaining and keeping employment (e.g. whether paid or unpaid, as an employee or self employed) as well as career progression. The lack of such skills is regularly referred to as one reason for the United Kingdom's often cited long tail of underachievement. Employability skills are at the forefront of government…

  17. Employability Skills Assessment Tool Development

    ERIC Educational Resources Information Center

    Rasul, Mohamad Sattar; Rauf, Rose Amnah Abd; Mansor, Azlin Norhaini; Puvanasvaran, A. P.

    2012-01-01

    Research nationally and internationally found that technical graduates are lacking in employability skills. As employability skills are crucial in outcome-based education, the main goal of this research is to develop an Employability Skill Assessment Tool to help students and lecturers produce competent graduates in employability skills needed by…

  18. Clerical Employment and Technological Change.

    ERIC Educational Resources Information Center

    Hunt, H. Allan; Hunt, Timothy

    The potential employment impact of office automation is the topic of the study described in this book. The study reviews trends in clerical employment over the last 30 years in a search for evidence of the impact of changes in process technology on clerical employment levels. Specifically, it examines clerical employment trends from 1950 to 1980…

  19. Undergraduates' Perceptions of Employer Expectations

    ERIC Educational Resources Information Center

    DuPre, Carrie; Williams, Kate

    2011-01-01

    Research conducted by the National Association of Colleges and Employers (NACE) indicates that employers across industries seek similar skills in job applicants; yet employers often report finding these desired skills lacking in new hires. This study closes the gap in understanding between employer expectations and student perceptions regarding…

  20. Employability. NIACE Briefing Sheet 88

    ERIC Educational Resources Information Center

    National Institute of Adult Continuing Education, 2009

    2009-01-01

    Employability skills are central to gaining and keeping employment (e.g. whether paid or unpaid, as an employee or self employed) as well as career progression. The lack of such skills is regularly referred to as one reason for the United Kingdom's often cited long tail of underachievement. Employability skills are at the forefront of government…

  1. Employment Trajectories Beyond Retirement.

    PubMed

    Burkert, Carola; Hochfellner, Daniela

    2017-01-01

    Within the political and academic debate on working longer, post-retirement employment is discussed as an alternative to maintain older workers in the labor market. Our article enhances this discussion by studying determinants of transitions into post-retirement jobs within differing work environments of birth cohorts 1940-1942. We estimate proportional subhazard models accounting for competing risks using unique German social security data linked to pension accounts. Our findings suggest that individuals' preferences to take up post-retirement jobs are not mutually exclusive. Our study provides evidence that taking up post-retirement jobs is related to seeking financial security, continuity, and work ability, suggesting that public policy has to develop target-oriented support through a public policy mix of different measures aligned to the different peer groups in the labor market.

  2. HIV and employment.

    PubMed

    McGoldrick, C

    2012-06-01

    According to 2009 statistics, the human immunodeficiency virus (HIV) infected an estimated 86,500 individuals within the UK, although around one-quarter were unaware of their infection. In the majority of cases, it is now considered a long-term controllable but incurable infection. Indeed, most HIV-positive individuals are able to work. Employment is across most, if not all, workforce sectors and protection against workplace discrimination is provided by the Equality Act 2010. Issues including confidentiality, workplace adjustments, vaccinations and travel restrictions may be relevant to the occupational health of HIV-positive workers. There are special considerations concerning HIV-infected health care workers, including avoidance of performing exposure-prone procedures. Prevention of HIV acquisition in the workplace is relevant to a diverse range of occupational environments, and HIV post-exposure prophylaxis should be considered after potential HIV exposure incidents. If a worker contracts HIV by occupational means, financial help may be available.

  3. A Conceptual Understanding of Employability: The Employers' View in Rwanda

    ERIC Educational Resources Information Center

    Bamwesiga, Penelope Mbabazi

    2013-01-01

    Many governments believe that investing in human capital should increase citizens' employability, which is why it is often presented as a solution to the problems of knowledge-based economies and societies, rising unemployment rates and economic competiveness. The aim of this study is to understand employers' views regarding the employability of…

  4. Temporary Employment and Perceived Employability: Mediation by Impression Management

    ERIC Educational Resources Information Center

    De Cuyper, Nele; De Witte, Hans

    2010-01-01

    Perceived employability (PE) has been advanced as the upcoming resource for career development, particularly for temporary workers. The question is how temporary workers become employable. Our hypothesis is that temporary workers more than permanent workers use impression management to become employable, both on the internal and the external labor…

  5. School Transition to Employment Partnership (STEP): Employability Curriculum.

    ERIC Educational Resources Information Center

    Wika, Jim; Rudrud, Eric H.

    The School Transition to Employment Partnership (STEP) Employability Curriculum is a competency-based evaluation and training program for special needs students, designed to ensure successful transition from school to employment. The STEP curriculum was developed through a partnership of state and local education agencies, representatives of state…

  6. Disability and Supported Employment: Impact on Employment, Income, and Allowances

    ERIC Educational Resources Information Center

    Germundsson, Per; Gustafsson, Johanna; Lind, Martin; Danermark, Berth

    2012-01-01

    In this article, we examine supported employment and its impact on the level of employment, disposable income, and sum of allowances, targeting a group of individuals with disabilities. We have particularly focused on individuals with psychiatric disabilities. Supported employment is a vocational rehabilitation service with an empowerment approach…

  7. Disability and Supported Employment: Impact on Employment, Income, and Allowances

    ERIC Educational Resources Information Center

    Germundsson, Per; Gustafsson, Johanna; Lind, Martin; Danermark, Berth

    2012-01-01

    In this article, we examine supported employment and its impact on the level of employment, disposable income, and sum of allowances, targeting a group of individuals with disabilities. We have particularly focused on individuals with psychiatric disabilities. Supported employment is a vocational rehabilitation service with an empowerment approach…

  8. Competitive Employment and Autism Spectrum Disorder: Employer Perspectives

    ERIC Educational Resources Information Center

    Stuckey, Wanietta C.

    2016-01-01

    Competitive employment for individuals with Autism Spectrum Disorder (ASD) is important because this group is described as the most employable, yet least employed. Historically, females have been more likely to hire/work with individuals with disabilities than males but the gap between the sexes has been closing. A survey focusing on work…

  9. Barriers to Employment: Personality and Cognitive Predictors of Employment Status

    ERIC Educational Resources Information Center

    McTurk, Carolyn; Shakespeare-Finch, Jane

    2006-01-01

    Barriers to employment are linked to individual factors such as thinking styles and personality traits. Personality and cognitive differences between employed (n = 55) and unemployed (n = 57) cohorts were analysed to quantify the association between these variables and employment status. Using the Myers-Briggs Type Indicator (MBTI) and the…

  10. Consumer and Employer Strategies for Overcoming Employment Barriers. Technical Report.

    ERIC Educational Resources Information Center

    Crudden, Adele; Williams, Wendy; McBroom, Lynn W.; Moore, J. Elton

    This report on strategies for overcoming employment barriers for persons with visual impairments summarizes comments and suggestions of 7 focus groups comprised of either consumers (n=49) or employers (n=19). The report first reviews the literature concerning employment barriers and how consumers in previous studies suggested these barriers be…

  11. Competitive Employment and Autism Spectrum Disorder: Employer Perspectives

    ERIC Educational Resources Information Center

    Stuckey, Wanietta C.

    2016-01-01

    Competitive employment for individuals with Autism Spectrum Disorder (ASD) is important because this group is described as the most employable, yet least employed. Historically, females have been more likely to hire/work with individuals with disabilities than males but the gap between the sexes has been closing. A survey focusing on work…

  12. Barriers to Employment: Personality and Cognitive Predictors of Employment Status

    ERIC Educational Resources Information Center

    McTurk, Carolyn; Shakespeare-Finch, Jane

    2006-01-01

    Barriers to employment are linked to individual factors such as thinking styles and personality traits. Personality and cognitive differences between employed (n = 55) and unemployed (n = 57) cohorts were analysed to quantify the association between these variables and employment status. Using the Myers-Briggs Type Indicator (MBTI) and the…

  13. A Conceptual Understanding of Employability: The Employers' View in Rwanda

    ERIC Educational Resources Information Center

    Bamwesiga, Penelope Mbabazi

    2013-01-01

    Many governments believe that investing in human capital should increase citizens' employability, which is why it is often presented as a solution to the problems of knowledge-based economies and societies, rising unemployment rates and economic competiveness. The aim of this study is to understand employers' views regarding the employability of…

  14. Office of Disability Employment Policy

    MedlinePlus

    ... OF LABOR Facebook Twitter RSS Email Office of Disability Employment Policy (ODEP) Menu About ODEP About ODEP ... Youth in Transition Publications for Order and Download Disability Statistics September 2017 Disability Employment Statistics Ages 16 ...

  15. The Liberal Arts Employment Dilemma.

    ERIC Educational Resources Information Center

    Hillstrom, J. K.

    1984-01-01

    Discusses five identifiable causes for the employment difficulties of liberal arts graduates. Suggests that evidence of a focused commitment and training in preparation for a professsional career are keys to success in the employment search. (JAC)

  16. Employment Impact of Electronic Business.

    ERIC Educational Resources Information Center

    Hecker, Daniel E.

    2001-01-01

    Electronic business is stimulating employment in some sectors across industries, such as computer-related and customer service occupations, and diminishing employment in others, such as administrative support and marketing/sales. Similarly, employment impacts will vary by industry. (Contains 56 notes and references.) (SK)

  17. Learning from Sweden's Employment Policies.

    ERIC Educational Resources Information Center

    Feldman, Lloyd

    1978-01-01

    Describes the labor market and employment policies in Sweden, which have been studied by the United States Department of Labor's Employment and Training Administration in planning its employment programs to increase the involvment of business and labor, provide countercyclical program capacity, and expand the role of occupational training. (MF)

  18. Third Annual Employer Satisfaction Survey.

    ERIC Educational Resources Information Center

    Broadbent, William A.

    A study was conducted in 1980 to ascertain employer attitudes toward and satisfaction with the performance of graduates of vocational education programs in Hawaii. Interviews with 41 employers, who employed an average of 132 workers, sought general perceptions of the knowledge, quality of work, written and oral skills, dependability, adaptability,…

  19. Youth Employment in American Industry.

    ERIC Educational Resources Information Center

    Hill, Robert B.; Nixon, Regina

    The persistent high level of unemployment among young people has become an issue of national concern. This study examines nationwide attitudes, practices, and policies of private employers toward hiring youth. A survey was conducted in 1981-82 among a random cross-sample of 535 private employers taken from the Equal Employment Opportunity…

  20. Employment status, employment functioning, and barriers to employment among VA primary care patients.

    PubMed

    Zivin, Kara; Yosef, Matheos; Levine, Debra S; Abraham, Kristen M; Miller, Erin M; Henry, Jennifer; Nelson, C Beau; Pfeiffer, Paul N; Sripada, Rebecca K; Harrod, Molly; Valenstein, Marcia

    2016-03-15

    Prior research found lower employment rates among working-aged patients who use the VA than among non-Veterans or Veterans who do not use the VA, with the lowest reported employment rates among VA patients with mental disorders. This study assessed employment status, employment functioning, and barriers to employment among VA patients treated in primary care settings, and examined how depression and anxiety were associated with these outcomes. The sample included 287 VA patients treated in primary care in a large Midwestern VA Medical Center. Bivariate and multivariable analyses were conducted examining associations between socio-demographic and clinical predictors of six employment domains, including: employment status, job search self-efficacy, work performance, concerns about job loss among employed Veterans, and employment barriers and likelihood of job seeking among not employed Veterans. 54% of respondents were employed, 36% were not employed, and 10% were economically inactive. In adjusted analyses, participants with depression or anxiety (43%) were less likely to be employed, had lower job search self-efficacy, had lower levels of work performance, and reported more employment barriers. Depression and anxiety were not associated with perceived likelihood of job loss among employed or likelihood of job seeking among not employed. Single VA primary care clinic; cross-sectional study. Employment rates are low among working-aged VA primary care patients, particularly those with mental health conditions. Offering primary care interventions to patients that address mental health issues, job search self-efficacy, and work performance may be important in improving health, work, and economic outcomes. Published by Elsevier B.V.

  1. Disability and supported employment: impact on employment, income, and allowances.

    PubMed

    Germundsson, Per; Gustafsson, Johanna; Lind, Martin; Danermark, Berth

    2012-09-01

    In this article, we examine supported employment and its impact on the level of employment, disposable income, and sum of allowances, targeting a group of individuals with disabilities. We have particularly focused on individuals with psychiatric disabilities. Supported employment is a vocational rehabilitation service with an empowerment approach that has competitive employment as an expressed goal. Data collected from two Swedish organizations, providing services based on supported employment, have been used. Two groups have been considered: one group focusing on individuals who have received vocational rehabilitation, according to the supported employment approach, and the other group focusing on individuals who declined supported employment (control group). The groups have been examined according to a 'before-and-after the intervention' design. Outcome measures have been retrospectively analyzed. The results indicate that the individuals who received supported employment were hired faster, earned a higher disposable income, and at the same time, had lower individual allowances. The same pattern as that for the overall population emerged for individuals with psychiatric disorders. Vocational rehabilitation based on the principles of supported employment may be very effective for individuals to gain employment, a better disposable income, and a substantial cutback in allowances. The intervention should be tailored according to individual needs rather than organizational rules.

  2. The Employer Perspective on Sustainable Employability in the Construction Industry.

    PubMed

    Tonnon, Susanne C; van der Veen, Rozan; Westerman, Marjan J; Robroek, Suzan J W; van der Ploeg, Hidde P; van der Beek, Allard J; Proper, Karin I

    2017-01-01

    To determine the measures employers in the construction industry take to promote sustainable employability, the barriers and facilitators that influence implementation and employer needs. Questionnaire among 499 employers and interviews with 17 employers. Employers expressed a need for alternative jobs for workers who can no longer perform physically demanding tasks, as well as means to stimulate proactive employee behavior. Measures frequently targeted the work environment (95%) and employee health (79%), less frequently personal development (63%) and organization (65%). Implementation was influenced by economic factors, rules and regulations, client demands, employee demands, company vision, company culture, and time/manpower/expertise. Implementation of measures aimed at reducing physical load and the promotion of personal development are needed.

  3. Conceptualizing Learning and Employability "Learning and Employability Framework"

    ERIC Educational Resources Information Center

    Sumanasiri, Erabaddage Gishan Tharanga; Yajid, Mohd Shukri Ab; Khatibi, Ali

    2015-01-01

    Extensive studies have been done on employability and the factors that lead to employability. Previous studies have focused on career development programs, internships, work experience programs, soft-skill development programs, and even university admission criteria which can be considered external factors to university student learning…

  4. Employer Needs Assessment Results for Pima County Employers, 1992.

    ERIC Educational Resources Information Center

    Pima Community Coll., Tucson, AZ. Office of Research and Planning.

    In an effort to inform the program and services review, develop new instructional programs, and assist marketing efforts at Pima Community College (PCC), in Arizona, a survey was conducted in fall 1992 of Pima County employers' training needs, employment needs, and opinions about PCC. Questionnaires were mailed to a random sample of 759 local…

  5. Young People and Employment (1): Employers' Use of Educational Qualifications.

    ERIC Educational Resources Information Center

    Reed, Eileen

    1980-01-01

    A survey of recruitment officers in England and Wales concerning the entry to employment of young people who leave school with no formal qualifications or with qualifications below the GCE A level is discussed. Findings suggest that employers are not dissatisfied with their recruits. (Author/MLW)

  6. Graduates' Employment and the Discourse of Employability: A Critical Analysis

    ERIC Educational Resources Information Center

    Moreau, Marie-Pierre; Leathwood, Carole

    2006-01-01

    In a context of considerable changes in the labour market and higher education sector in the UK, a discourse of employability has become increasingly dominant. Universities are urged to ensure that they produce "employable" graduates, and graduates themselves are exhorted to continually develop their personal skills, qualities and…

  7. Graduates', University Lecturers' and Employers' Perceptions towards Employability Skills

    ERIC Educational Resources Information Center

    Wickramasinghe, Vathsala; Perera, Lasantha

    2010-01-01

    Purpose: The purpose of this study is to explore employability skills that employers, university lecturers and graduates value to bring to the workplace, when graduates are applying for entry-level graduate jobs in the field of computer science in Sri Lanka. Design/methodology/approach: A total of three samples were selected for this exploratory…

  8. Linking with Employment: Training from the Perspective of Employers.

    ERIC Educational Resources Information Center

    Herschbach, Dennis R.

    Employers need training, want it, and are willing to pay for it providing it is relevant to their requirements, results in improved product quality, and fosters increased productivity. Firm characteristics make a difference not only with regard to the kinds of skills wanted by employers but also with regard to how training can best be delivered.…

  9. Schizophrenia and employment - a review.

    PubMed

    Marwaha, Steven; Johnson, Sonia

    2004-05-01

    Little is known about the extent to which work contributes to the recovery of people with schizophrenia. There is increasing interest in the subject because of new service models and the economic cost of unemployment in people with severe mental illness. A literature search was carried out with the aim of investigating: a). employment rates in schizophrenia and first-episode psychosis and the extent to which they have changed over time; b). the barriers to work; c). the factors associated with being employed among people with schizophrenia; and d). whether employment influences other outcomes in schizophrenia. There are wide variations in reported employment rates in schizophrenia. Most recent European studies report rates between 10 % and 20%, while the rate in the US is less clear. There is a higher level of employment among first-episode patients. The employment rate in schizophrenia appears to have declined over the last 50 years in the UK. Barriers to getting employment include stigma,discrimination, fear of loss of benefits and a lack of appropriate professional help. The most consistent predictor of employment is previous work history. Working is correlated with positive outcomes in social functioning, symptom levels, quality of life and self esteem, but a clear causal relationship has not been established. Very low employment rates are not intrinsic to schizophrenia, but appear to reflect an interplay between the social and economic pressures that patients face, the labour market and psychological and social barriers to working.

  10. Vocational Rehabilitation and Employment program--self-employment. Final rule.

    PubMed

    2010-01-20

    This document amends the vocational rehabilitation and employment regulations of the Department of Veterans Affairs (VA) concerning self-employment for individuals with qualifying disabilities. We are making changes to conform VA's regulations for self-employment programs for veterans, and for servicemembers awaiting discharge, to statutory provisions, including provisions limiting eligibility for certain supplies, equipment, stock, and license fees to individuals with the most severe service-connected disabilities. We are also making related changes in VA's regulations affecting eligibility for such assistance for certain veterans' children with birth defects in self-employment programs. In addition, we are amending our regulations regarding the approval authority for self-employment plans to make certain requirements less restrictive and less burdensome, to remove a vague and overly broad requirement, to make changes to reflect longstanding VA policy, and to make nonsubstantive clarifying changes.

  11. Breastfeeding and employment: an assessment of employer attitudes.

    PubMed

    Libbus, M Kay; Bullock, Linda F C

    2002-08-01

    Both research and anecdotal reports suggest that maternal employment is associated with failure to initiate breastfeeding and early breastfeeding attrition. The objective of this study was to describe the experience with and attitudes toward breastfeeding of a sample of employers in a small Midwestern city in the United States. Based on an analysis of 85 mail-out questionnaires, we found that less than half of the employers had personal experience with breastfeeding. A large percentage of the sample, however, indicated that they would be willing to facilitate women who wished to breastfeed or express milk in the workplace. However, these employers also stated that they saw little value to their business of supporting breastfeeding in the work environment. Thus, enhancement of breastfeeding opportunity in the work environment may come as a result of public and employer education but, more likely, will require some type of directive from official sources.

  12. AID-GFP chimeric protein increases hypermutation of Ig genes with no evidence of nuclear localization

    PubMed Central

    Rada, Cristina; Jarvis, John M.; Milstein, César

    2002-01-01

    Somatic hypermutation generates variants of antibody genes and underpins the affinity maturation of antibodies. It is restricted to the V-gene segments, and although it decays exponentially toward the 3′end, it includes recognizable hot spots. Although the detailed mechanism of hypermutation remains elusive, the process may take place in two separate stages, preferentially targeting G/Cs in the first and A/Ts in the second stage. It seems that MSH2 is involved in the second stage, and that activation induced deaminase (AID) is implicated in the control of hypermutation. The constitutively hypermutating cell line Ramos expresses AID, and we have prepared transfectants that express a chimeric AID-green fluorescent protein. The fluorescence is strongly detected in the cytoplasm but not in the nucleus. Yet, the chimeric protein increases the hypermutation rate either directly or, more likely, indirectly, by favoring the transport of AID into the nucleus. Thus, in Ramos, AID seems to be rate limiting. Unexpectedly, the proportion of deletions also is increased. The increase in mutation rate detected by a fast cytofluorimetric method based on the accumulation of sIgM-loss mutants correlates with the increase measured by mutations defined by sequence analysis. The higher mutation rate is largely explained by the higher proportion of mutated clones, indicating that AID controls the number of cells that undergo hypermutation but not the number of mutations that are incorporated in each mutation round. PMID:12011459

  13. Preferential Remedies for Employment Discrimination

    ERIC Educational Resources Information Center

    Edwards, Harry T.; Zaretsky, Barry L.

    1975-01-01

    An overview of the problem of preferential remedies to achieve equal employment opportunities for women and minority groups. Contends that "color blindness" will not end discrimination but that some form of "color conscious" affirmative action program must be employed. Temporary preferential treatment is justified, according to…

  14. Preselection: How Students Prescreen Employers.

    ERIC Educational Resources Information Center

    Reardon, Thomas

    1979-01-01

    College relations personnel can no longer afford to ignore the factors which attract college grads to employers. Top-notch college students may be less impressed by traditional recruiting incentives as they research and prescreen employers. The article reviews the current incentives for average and above-average students. (Author/CMG)

  15. Employability and Finnish University Graduates

    ERIC Educational Resources Information Center

    Puhakka, Antero; Rautopuro, Juhani; Tuominen, Visa

    2010-01-01

    In this article the authors concentrate on the change in the concept of employability during the Bologna process. They show that employability has gradually moved from a peripheral to a core presence in the most recent Bologna process documents. Using a Finnish university merger (University of Eastern Finland) as an example, the authors…

  16. Employer Demands from Business Graduates

    ERIC Educational Resources Information Center

    McMurray, Stephen; Dutton, Matthew; McQuaid, Ronald; Richard, Alec

    2016-01-01

    Purpose: The purpose of this paper is to report on research carried out with employers to determine demand for business and management skills in the Scottish workforce. Design/methodology/approach: The research used a questionnaire in which employers were interviewed (either telephone or face to face), completed themselves and returned by e-mail,…

  17. Employment Obtaining and Business Starting

    ERIC Educational Resources Information Center

    Lan, Jian

    2009-01-01

    The implementation of business starting education in higher vocational colleges is of important and realistic meanings for cultivating advanced technology application-type talents and for releasing the employment obtaining pressure of higher vocational students. Based on the analysis on the employment situation of higher vocational graduates, this…

  18. Working Classes? Preparing for Employability

    ERIC Educational Resources Information Center

    Harney, John O.

    2017-01-01

    On June 28, the New England Board of Higher Education (NEBHE) convened members of the Commission on Higher Education and Employability (CHEE) in Providence to discuss concrete ways New England employers, education leaders and policymakers can work together to ensure a successful, equitable workforce future. The Commission comprises high-powered…

  19. Preferential Remedies for Employment Discrimination

    ERIC Educational Resources Information Center

    Edwards, Harry T.; Zaretsky, Barry L.

    1975-01-01

    An overview of the problem of preferential remedies to achieve equal employment opportunities for women and minority groups. Contends that "color blindness" will not end discrimination but that some form of "color conscious" affirmative action program must be employed. Temporary preferential treatment is justified, according to…

  20. Employment Equity for Aboriginal Teachers

    ERIC Educational Resources Information Center

    British Columbia Teachers' Federation, 2012

    2012-01-01

    This paper is a letter of understanding between British Columbia Teachers' Federation (BCTF) and British Columbia Public School Employers' Association (BCPSEA) in response to Employment Equity for Aboriginal Teachers. The parties recognize that Aboriginal teachers are under-represented in the public education system. The parties are committed to…

  1. Leading Gainful Employment Metric Reporting

    ERIC Educational Resources Information Center

    Powers, Kristina; MacPherson, Derek

    2016-01-01

    This chapter will address the importance of intercampus involvement in reporting of gainful employment student-level data that will be used in the calculation of gainful employment metrics by the U.S. Department of Education. The authors will discuss why building relationships within the institution is critical for effective gainful employment…

  2. Employability Skills. At a Glance

    ERIC Educational Resources Information Center

    Wibrow, Bridget

    2011-01-01

    In a competitive workforce it is not just having the right qualification or technical skills that will land an individual a job; it could very well be their interpersonal skills. How someone communicates is often the first impression an employer has of a possible worker. Yet, it is precisely communication skills that employers feel applicants are…

  3. Employment Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Hustoles, Thomas P.; Griffin, Oren R.

    2000-01-01

    Reviews court decisions related to employment discrimination in higher education. The most significant development was a series of cases affirming that Eleventh Amendment immunity from private money damage claims brought pursuant to various federal employment discrimination statutes applied to state colleges and universities. (SLD)

  4. Employability: Review and Research Prospects

    ERIC Educational Resources Information Center

    Guilbert, Laure; Bernaud, Jean-Luc; Gouvernet, Brice; Rossier, Jérôme

    2016-01-01

    Professional transition, employment, and reemployment are major concerns for nations facing adverse economic situations. The employability construct represents a scientific challenge in order to better understand the relationship between the job seekers' issues and the expectations of the world of work. This paper presents a review of the concept…

  5. Leading Gainful Employment Metric Reporting

    ERIC Educational Resources Information Center

    Powers, Kristina; MacPherson, Derek

    2016-01-01

    This chapter will address the importance of intercampus involvement in reporting of gainful employment student-level data that will be used in the calculation of gainful employment metrics by the U.S. Department of Education. The authors will discuss why building relationships within the institution is critical for effective gainful employment…

  6. Assessing Employability Skills. ERIC Digest.

    ERIC Educational Resources Information Center

    Saterfiel, Thomas H.; McLarty, Joyce R.

    The term "employability skills" refers to those skills required to acquire and retain a job. In the past, employability skills were considered primarily of a vocational or job-specific nature; they were not thought to include the academic skills most commonly taught in schools. Current thinking, however, has broadened the definition to…

  7. Survey of Auto Mechanic Employers.

    ERIC Educational Resources Information Center

    Page, Charles; Scott, David C.

    In order to build auto mechanics curricula and instructional programs responsive to the needs of employers, Bakersfield College (BC) sent a questionnaire to all employers listed under "Automobile Repairing and Services" in the yellow pages of the local telephone book. Only 43 (20 percent) of the 215 questionnaires sent out were returned;…

  8. Employer Demands from Business Graduates

    ERIC Educational Resources Information Center

    McMurray, Stephen; Dutton, Matthew; McQuaid, Ronald; Richard, Alec

    2016-01-01

    Purpose: The purpose of this paper is to report on research carried out with employers to determine demand for business and management skills in the Scottish workforce. Design/methodology/approach: The research used a questionnaire in which employers were interviewed (either telephone or face to face), completed themselves and returned by e-mail,…

  9. Employer Evaluation of Occupational Programs.

    ERIC Educational Resources Information Center

    Willett, Lynn H.; Piland, William E.

    In an effort to meet the need for a more comprehensive program evaluation, staff at Moraine Valley Community College developed a questionnaire and interview schedule to obtain feedback from employers concerning career programs. Questionnaires were sent to all employers who hired graduates of occupational programs between 1969-71; over 80% returned…

  10. The employment of elderly persons*

    PubMed Central

    Davies, T. A. Lloyd

    1955-01-01

    Not every old person is fit for employment, and consequently employment agencies must reserve the right of selection. Retirement at the customary age with, if desired, re-employment for defined periods seems to offer the best method of employing old people, avoiding damaging loss of dignity and the blocking of promotion of younger people. Under suitable conditions, old persons are capable of a high level of employment. The possibilities of employment, however, vary very much with different types of industries and industrial regions. The elderly usually have a higher sickness absenteeism than young people, but have fewer absences for other reasons than sickness. Elderly workers seem to be able to carry out manual labour with efficiency if they are put into jobs without time-stress. If retraining is necessary, the utmost possible use should be made of already established skills. Heavy work does not seem to be necessarily harmful for old people. Little knowledge is yet available on the health problems of professional workers or executives at increasing age. Lack of decisiveness, failure of critical judgement, and increasing irritability—resulting from difficulty in organizing new information—will call for transfer to less responsible positions. Many more studies of old age are needed before the circumstances under which they may best be employed in present-day industry can be determined. Full employment and the need for production make this problem still more urgent. PMID:13276813

  11. The employment of elderly persons.

    PubMed

    DAVIES, T A L

    1955-01-01

    Not every old person is fit for employment, and consequently employment agencies must reserve the right of selection. Retirement at the customary age with, if desired, re-employment for defined periods seems to offer the best method of employing old people, avoiding damaging loss of dignity and the blocking of promotion of younger people.Under suitable conditions, old persons are capable of a high level of employment. The possibilities of employment, however, vary very much with different types of industries and industrial regions. The elderly usually have a higher sickness absenteeism than young people, but have fewer absences for other reasons than sickness. Elderly workers seem to be able to carry out manual labour with efficiency if they are put into jobs without time-stress. If retraining is necessary, the utmost possible use should be made of already established skills. Heavy work does not seem to be necessarily harmful for old people.Little knowledge is yet available on the health problems of professional workers or executives at increasing age. Lack of decisiveness, failure of critical judgement, and increasing irritability-resulting from difficulty in organizing new information-will call for transfer to less responsible positions.Many more studies of old age are needed before the circumstances under which they may best be employed in present-day industry can be determined. Full employment and the need for production make this problem still more urgent.

  12. Employment and People with Disabilities.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1990-01-01

    This newsletter issue offers six articles on employment of people with disabilities. "Employment and People with Disabilities: Challenges for the Nineties" (Frank Bowe) discusses the Americans with Disabilities Act, issues in unemployment and under-education, earnings, and implications for the Office of Special Education and Rehabilitative…

  13. Employment Survey 1980. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    The employment status of 1980 degree recipients in physics and astronomy was surveyed. For physics degree recipients, the majority of bachelors and masters required two months or less to accept suitable employment, while the majority of doctoral graduates required three months or longer. Information is presented on changes in occupational status…

  14. Employment Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Hustoles, Thomas P.; Griffin, Oren R.

    2000-01-01

    Reviews court decisions related to employment discrimination in higher education. The most significant development was a series of cases affirming that Eleventh Amendment immunity from private money damage claims brought pursuant to various federal employment discrimination statutes applied to state colleges and universities. (SLD)

  15. Employment Survey 1976. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    This document presents the summary results of the 1976 employment survey of physics and astronomy graduates of the class of 1975-76 as conducted by the American Institute of Physics (AIP). Data presented include employment status 6-18 months after graduation; background characteristics of doctoral, master's and bachelor's level physicists; time…

  16. Employability: Review and Research Prospects

    ERIC Educational Resources Information Center

    Guilbert, Laure; Bernaud, Jean-Luc; Gouvernet, Brice; Rossier, Jérôme

    2016-01-01

    Professional transition, employment, and reemployment are major concerns for nations facing adverse economic situations. The employability construct represents a scientific challenge in order to better understand the relationship between the job seekers' issues and the expectations of the world of work. This paper presents a review of the concept…

  17. Primer of Equal Employment Opportunity.

    ERIC Educational Resources Information Center

    Anderson, Howard J.

    This booklet presents laws and court cases concerning discrimination in hiring. It begins with a presentation of the laws and orders regulating equal employment opportunity and the remedies available. It lists those employees and employers to whom the laws apply and exemptions. Sections deal with discrimination on the basis of race, sex, sexual…

  18. Special Issue on Casual Employment.

    ERIC Educational Resources Information Center

    Australian Bulletin of Labour, 2001

    2001-01-01

    Includes "Editor's Introduction" (Cully); "A New Estimate of Casual Employment?" (Campbell, Burgess); "A New Estimate of Casual Employment?: Reply" (Murtough, Waite); "The 'Long-term or Permanent Casual'--An Oxymoron or 'A Well Enough Understood Australianism' in the Law?" (Owens); and "The ACTU's…

  19. Consumer Leadership in Supported Employment.

    ERIC Educational Resources Information Center

    Inge, Katherine J., Ed.

    1992-01-01

    This newsletter issue provides rehabilitation professionals with various information pieces concerning consumer leadership in supported employment of people with disabilities. First, a chart lists five questions concerning self advocacy and supported employment, and provides consumer responses to the questions. A second item describes…

  20. Maternal Employment and Adolescent Development.

    ERIC Educational Resources Information Center

    Montemayor, Raymond; Clayton, Mark D.

    1983-01-01

    The relationship between maternal employment and adolescent development is enormously complex, and no simple generalizations are possible. Many intervening variables alter the impact that maternal employment has on adolescent development. There is an urgent need to discover what impact this arrangement has on adolescent development. (CJ)

  1. Employment Survey 1984. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    The employment status of 1984-1985 degree recipients in physics and astronomy was surveyed. Information is presented on changes in occupational status of physics and astronomy degree recipients between summer of 1984 and the following winter. The characteristics of graduates of both fields who were employed full-time or undertaking postdoctoral…

  2. Employment Survey 1982. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    The employment status of 1981-1982 degree recipients in physics and astronomy was surveyed. Information is presented on changes in occupational status of physics and astronomy degree recipients which occurred between the summer of 1982 and the following winter. The characteristics of graduates of both fields who were employed full-time or…

  3. Employment Survey 1980. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    The employment status of 1980 degree recipients in physics and astronomy was surveyed. For physics degree recipients, the majority of bachelors and masters required two months or less to accept suitable employment, while the majority of doctoral graduates required three months or longer. Information is presented on changes in occupational status…

  4. Employment Survey 1985. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    Results of the American Institute of Physics' 1985 annual employment survey in physics and astronomy are presented in table form accompanied by narrative analysis. Information includes: time spent by 1984-85 physics degree recipients in securing employment, by degree level; changes in occupational status of physics and astronomy degree recipients…

  5. Employment Survey 1986. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    Results of the American Institute of Physics' 1986 annual employment survey in physics and astronomy are presented in table form accompanied by narrative analysis. Information includes: time spent by 1985-86 physics degree recipients in securing employment, by degree level; changes in occupational status of physics and astronomy degree recipients…

  6. Employment Survey 1984. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    The employment status of 1984-1985 degree recipients in physics and astronomy was surveyed. Information is presented on changes in occupational status of physics and astronomy degree recipients between summer of 1984 and the following winter. The characteristics of graduates of both fields who were employed full-time or undertaking postdoctoral…

  7. Employment Survey 1976. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    This document presents the summary results of the 1976 employment survey of physics and astronomy graduates of the class of 1975-76 as conducted by the American Institute of Physics (AIP). Data presented include employment status 6-18 months after graduation; background characteristics of doctoral, master's and bachelor's level physicists; time…

  8. Protein expression of Fragile Histidine Triad and cyclooxgenase-2 in serrated neoplasia of the colorectum

    PubMed Central

    Tamoto, Akihiro; Yashima, Kazuo; Hosoda, Kohei; Yamamoto, Sohei; Kawata, Soichiro; Ikebuchi, Yuichiro; Matsumoto, Kazuya; Kawaguchi, Koichiro; Harada, Kenichi; Murawaki, Yoshikazu; Isomoto, Hajime

    2017-01-01

    The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma (CRC). However, the mechanism triggered by the serrated pathway remains unclear. Therefore, to clarify the molecular and clinicopathological characteristics of the serrated tumorigenic pathway, immunohistochemistry was used to examine the expression of Fragile Histidine Triad (FHIT), cyclooxygenase-2 (COX-2), MutL homolog 1 (MLH1), MutS protein homolog 2 (MSH2) and P53 in endoscopically resected samples of 62 serrated polyps. These samples included 20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs), 26 sessile serrated adenoma/polyps (SSA/Ps), 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure CRCs without any adenoma component (EPCs). FHIT expression was markedly reduced or absent in 50% of TSA samples, 92.3% of SSA/Ps and 44% of EPCs, but only rarely in HPs, non-serrated adenomas and CIAs. COX-2 expression was more common in non-serrated adenomas compared with in serrated polyps, and was present in 25 and 3.2% of the cases respectively (P<0.01). Furthermore, COX-2 expression was more frequent in CIAs (60%) compared with in EPCs (22.2%; P<0.05). The incidence of negative COX-2 expression was higher in FHIT-negative SSA/Ps compared with in FHIT-positive SSA/Ps (P=0.08). A total of 16.7% of EPC samples and 11.5% of SSA/Ps demonstrated a loss of MLH1/MSH2 expression, but none of the other tumor types did. P53 overexpression was significantly increased in EPC (77.8%) and CIA (60%) samples compared with in HP (0%), TSA (6.6%), SSA/P (0%) and non-serrated adenoma (10%) samples (P<0.01). These findings demonstrated that there are different expression patterns between the serrated pathway and ACS, indicating that aberrant FHIT and inhibited COX-2 expression may be associated with serrated tumorigenesis. In addition, this data indicated that EPC may contain tumors derived from the

  9. 29 CFR 1607.10 - Employment agencies and employment services.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... UNIFORM GUIDELINES ON EMPLOYEE SELECTION PROCEDURES (1978) General Principles § 1607.10 Employment... agency or service seeks to comply with these guidelines by reliance upon validity studies or other data...

  10. Equal Employment Law and the Employer--An Overview.

    ERIC Educational Resources Information Center

    Levins, Will

    1979-01-01

    Sets forth in simple terms some of the requirements of the Equal Employment Opportunities Act of 1972. Available from the New York State Bar Association, One Elk Street, Albany, N.Y. 12207; sc $2.00. (Author/IRT)

  11. Equal Employment Law and the Employer--An Overview.

    ERIC Educational Resources Information Center

    Levins, Will

    1979-01-01

    Sets forth in simple terms some of the requirements of the Equal Employment Opportunities Act of 1972. Available from the New York State Bar Association, One Elk Street, Albany, N.Y. 12207; sc $2.00. (Author/IRT)

  12. Employment.

    ERIC Educational Resources Information Center

    Witter, William D.; And Others

    1986-01-01

    Beginning with a conceptual introduction which covers the topics of work in the United States, why people work, the labor force, labor markets, unemployment, and work and the young, this document goes on to offer four instructional units for preschool through sixth grade students. The preschool and kindergarten unit called "Earning More than…

  13. Employment equity and mental disability.

    PubMed

    Stuart, Heather

    2007-09-01

    Recent research on the civil rights issue of employment equity for people with psychiatric disabilities is reviewed. Mental disorders, particularly depression, are the most frequent source of occupational disability worldwide and are expected to grow. Employers are increasingly aware of the productivity costs associated with mental disorders and the importance of fostering a mentally healthy workforce. Few firms, however, have explicit policies to include disabled people in their workforce, and many employers continue to express prejudicial views toward people with mental disabilities which would exclude them from competitive work. At the same time, disability legislation has not offered the hoped-for protection for people with mental disorders. Employers have expressed concerns over the costs of making workplace accommodations and have successfully battled for a legal definition of disability that excludes many individuals with mental disorders. In the absence of antistigma efforts directed toward the business community, one wonders if the growing awareness of the productivity costs associated with mental disability will foster greater employment equity, or fuel more subtle forms of employment discrimination. Low employment levels among people with disabilities remain a major determinant of the social disparities they face.

  14. Toward the Employability-Link Model: Current Employment Transition to Future Employment Perspectives

    ERIC Educational Resources Information Center

    Thijssen, Johannes G. L.; Van der Heijden, Beatrice I. J. M.; Rocco, Tonette S.

    2008-01-01

    This article goes into a critical analysis of the concept of employability, its development across historical periods, its components, and different strategic approaches to enhance workers' employability throughout their career. Given the need for a systematic analysis and more empirical research in the field, the authors come up with the…

  15. Toward the Employability-Link Model: Current Employment Transition to Future Employment Perspectives

    ERIC Educational Resources Information Center

    Thijssen, Johannes G. L.; Van der Heijden, Beatrice I. J. M.; Rocco, Tonette S.

    2008-01-01

    This article goes into a critical analysis of the concept of employability, its development across historical periods, its components, and different strategic approaches to enhance workers' employability throughout their career. Given the need for a systematic analysis and more empirical research in the field, the authors come up with the…

  16. Invisible Disability Disclosure in an Employment Interview: Impact on Employers' Hiring Decisions and Views of Employability

    ERIC Educational Resources Information Center

    Dalgin, Rebecca Spirito; Bellini, James

    2008-01-01

    This study investigated the impact of disclosure of invisible disabilities (physical and psychiatric) within the employment interview process. Both the type of disability and the extent of disclosure were manipulated in an analogue experimental design. Employers (N = 60) were exposed to a short interview vignette of a potential candidate and were…

  17. 20 CFR 404.1003 - Employment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Employment. 404.1003 Section 404.1003 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Employment § 404.1003 Employment. Employment...

  18. 20 CFR 404.1003 - Employment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Employment. 404.1003 Section 404.1003 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Employment § 404.1003 Employment. Employment...

  19. 20 CFR 404.1003 - Employment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Employment. 404.1003 Section 404.1003 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Employment § 404.1003 Employment. Employment...

  20. 20 CFR 404.1003 - Employment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Employment. 404.1003 Section 404.1003 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Employment § 404.1003 Employment. Employment...

  1. 20 CFR 404.1003 - Employment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Employment. 404.1003 Section 404.1003 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Employment § 404.1003 Employment. Employment...

  2. Are Sanctions on Employers Constitutional?

    ERIC Educational Resources Information Center

    Gollobin, Ira

    1988-01-01

    Questions the constitutional validity of employer sanctions used to deter illegal immigration under the Immigration Reform and Control Act. Points out the anomaly of using criminal penalties to deter a civil, administrative violation. (FMW)

  3. Genetic Screening for Employment Purposes.

    ERIC Educational Resources Information Center

    Olian, Judy D.

    1984-01-01

    Discusses genetic screening in the employment context, which involves identification of individuals hypersusceptible to toxins in the work environment. Examines the status of genetic screening devices against standard testing and legal criteria. (LLL)

  4. Pre-Employment Laboratory Training

    ERIC Educational Resources Information Center

    Vela, Rene H.; Correa, Jose

    1976-01-01

    The article describes the development of a pre-employment laboratory training program in meat processing and its successful use in conjunction with a cooperative training program in a high school agriculture curriculum. (MS)

  5. Selling College Graduates to Employers.

    ERIC Educational Resources Information Center

    Nagy, Daniel R.; Biehl, Kimberly A.

    1980-01-01

    Describes a University of Pittsburgh placement office program to increase placement of graduates with local businesses. To challenge the employment agencies' monopoly on this market, an advertising and direct communications program was launched with continuing good results. (JAC)

  6. Are Sanctions on Employers Constitutional?

    ERIC Educational Resources Information Center

    Gollobin, Ira

    1988-01-01

    Questions the constitutional validity of employer sanctions used to deter illegal immigration under the Immigration Reform and Control Act. Points out the anomaly of using criminal penalties to deter a civil, administrative violation. (FMW)

  7. Employers' concerns regarding research participation.

    PubMed

    Johnson, Alicia M; Dale, Ann Marie; Strickland, Jaime R; Venditti, Pat; Evanoff, Bradley A

    2008-01-01

    Occupational health research depends on the cooperation and participation of employers. The authors describe employers' reasons for non-participation in a prospective study examining risk factors for carpal tunnel syndrome (CTS) and the usefulness of preplacement, post-offer nerve conduction screening. Companies were contacted to solicit participation. Non-participation explanations were reviewed. Of 73 eligible employers, 58 declined participation (participation rate: 20.5%). Reasons for non-participation included lack of interest (32.8%), liability concerns (awareness of CTS may increase workers' compensation claims) (22.4%), time constraints (19%), lack of direct benefit to the employer (8.6%), and company policy restraints (6.9%). Data from one employer were reviewed to determine whether workers' compensation claims for upper extremity disorders increased as a result of study participation. Claim rates showed no change in trend pre- and post-study inception. Expanding much-needed research to prevent occupational injuries and illnesses requires addressing employers' concerns and promoting research benefits.

  8. Employee to employer communication skills: balancing cancer treatment and employment.

    PubMed

    Brown, Richard F; Owens, Myra; Bradley, Cathy

    2013-02-01

    Cancer patients face difficulties in accessing legally mandated benefits and accommodations when they return to the workplace. Poor employer-employee communication inflates these difficulties. Although proven methods to facilitate physician-patient communication exist, these have not been applied to the workplace. Thus, we aimed to assess the feasibility and utility of applying these methods to educate patients about their workplace rights and provide them with communication skills training to aid their conversations with their employers. A DVD was produced to educate patients and facilitate workplace communication. Participants consisted of 28 solid tumor cancer patients (14 women and 14 men) who completed primary cancer treatment in the past 12 months and were employed at the time of diagnosis. Participants watched a communication skills training DVD and completed a telephone interview. The interview elicited information about workplace experiences and evaluation of the DVD training program. The physician-patient communication skills training model utilized was successfully translated to the employer-employee setting. All but one participant found the DVD useful and easy to understand and indicated a high degree of confidence in using the communication skills to help them ask for workplace accommodations. All participants agreed that it would help newly diagnosed patients in discussions with their employers. Our data provides promising preliminary evidence that patient communication skills training can be applied to the workplace setting and is a welcomed aid to newly diagnosed cancer patients in their discussions with employers regarding the impact of treatment on their work performance and needs for accommodations. Copyright © 2011 John Wiley & Sons, Ltd.

  9. 29 CFR 1625.3 - Employment agency.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Employment agency. 1625.3 Section 1625.3 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN EMPLOYMENT ACT Interpretations § 1625.3 Employment agency. (a) As long as an employment agency regularly procures employees for at least one covered employer...

  10. Employment, Employability and Higher Education in India: The Missing Links

    ERIC Educational Resources Information Center

    Khare, Mona

    2014-01-01

    The demand for labour in India is likely to remain high and robust in the coming years, both nationally and internationally. But this would demand skilled and qualified labour. The employability of Indian youth has emerged as a major concern in recent years. Ironically, it is not just the uneducated and untrained that lack skills but it is also…

  11. 29 CFR 779.19 - Employer, employee, and employ.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., 331 U.S. 704; Rutherford Food Corp. v. McComb, 331 U.S. 722). An “employer”, as defined in section 3(d... Act's major provisions impose certain requirements and prohibitions on every “employer” subject to... of oppressive child labor. The Act provides its own definitions of “employer,” “employee”,...

  12. Employer's Pocket Guide on Youth Employment. Youth Rules!

    ERIC Educational Resources Information Center

    US Department of Labor, 2004

    2004-01-01

    Through the YouthRules! initiative, the U.S. Department of Labor and its strategic partners seek to promote positive and safe work experiences for young workers. YouthRules! strives to educate teens, parents, educators, employers and the public on Federal and State rules regarding young workers. Components of the initiative include a website…

  13. Age Discrimination in Employment: A Guide for Employers.

    ERIC Educational Resources Information Center

    Linenberger, Patricia; Keaveny, Timothy J.

    1979-01-01

    Explains and illustrates the enforcement of the Age Discrimination in Employment Act of 1967 through the use of definitions in the act, interpretative statements issued by the Department of Labor, current court decisions, and discussion of the 1978 amendments. (Author/IRT)

  14. Graduates' Employability: What Do Graduates and Employers Think?

    ERIC Educational Resources Information Center

    Matsouka, Kyriaki; Mihail, Dimitrios M.

    2016-01-01

    The purpose of this article is to investigate the views of university graduates and human resource managers (HRMs) on graduates' employability in terms of the soft skills required by the labour market. Soft skills (personal attributes that enhance an individual's interactions, job performance and career prospects) are necessary in the labour…

  15. Graduates' Employability: What Do Graduates and Employers Think?

    ERIC Educational Resources Information Center

    Matsouka, Kyriaki; Mihail, Dimitrios M.

    2016-01-01

    The purpose of this article is to investigate the views of university graduates and human resource managers (HRMs) on graduates' employability in terms of the soft skills required by the labour market. Soft skills (personal attributes that enhance an individual's interactions, job performance and career prospects) are necessary in the labour…

  16. Employability and Employment Outcomes of No-Fee Preservice Students

    ERIC Educational Resources Information Center

    Jin, Yule; Li, Ling; Ding, Shujing; Li, Zhichao

    2013-01-01

    This study used interviews and questionnaires to survey 770 no-fee preservice students. Its findings were as follows: (1) Their employability encompasses five dimensions: teaching skills, ability to learn specialized knowledge, ability to grasp elementary and secondary teaching materials and methods, communication skills, and ability to apply for…

  17. Employability and Employment Outcomes of No-Fee Preservice Students

    ERIC Educational Resources Information Center

    Jin, Yule; Li, Ling; Ding, Shujing; Li, Zhichao

    2013-01-01

    This study used interviews and questionnaires to survey 770 no-fee preservice students. Its findings were as follows: (1) Their employability encompasses five dimensions: teaching skills, ability to learn specialized knowledge, ability to grasp elementary and secondary teaching materials and methods, communication skills, and ability to apply for…

  18. Research on population and employment under the world employment program.

    PubMed

    1974-01-01

    In 1972 the ILO launched a comprehensive research project to: 1) for mulate a series of economic-demographic simulation models dealing with the direct and indirect effects of population on employment, output, and income distribution, and vice versa; 2) fund empirical studies dealing with important elements in the relationship between population and employment growth and focusing on policy issues. The project has 2 special features, the feedback between the empirical research and the model activity and the joint participation of the ILO with national research organizations in different regions. A large number of economic-demographic models have been developed in recent years. However, most of them take demographic variables as exogenous and analyze consequences in a neoclassical framework or they seek to analyze demographic responses to economic and social changes which are treated as exogenous variables. Interaction among different sets of variables is closer to reality, not uni-directional causation. Effective demand is as important as the increase in resource inputs. The situation in de veloping economies is further complicated by the coexistence of modern and traditional sectors which show many fundamental differences. Detail ed descriptions of several models under development are given. Studies being conducted include: labor force analysis, with special emphasis on developing countries; the socioeconomic determinants of fertility; studies on population, consumption patterns, and savings; an analysis of the extent to which the labor market signals through wage adjustments the rapid growth of population and labor force and the resulting excess supply of labor in relation to modern sector jobs; capital accumulation and employment in a labor-surplus situation; and the effects of population pressure on land tenure, agricultural productivity, and employment. It is hoped this research will suggest possible optimal mixes of demographic, economic, and social policies

  19. Lynch Syndrome from a surgeon perspective: retrospective study of clinical impact of mismatch repair protein expression analysis in colorectal cancer patients less than 50 years old

    PubMed Central

    2014-01-01

    Background In clinical practice, unexpected diagnosis of colorectal cancer in young patients requires prompt surgery, thus genetic testing for Lynch Syndrome is frequently missed, and clinical management may result incorrect. Methods Patients younger than 50 years old undergoing colorectal resection for cancer in the period 1994-2007 were identified (Group A, 49 cases), and compared to a group of randomly selected patients more than 50 (Group B, 85 cases). In 31 group A patients, immunohistochemical expression analysis of MLH1, MSH2 and MSH6 was performed; personal and familial history of patients with defective MMR proteins expression was further investigated, searching for synchronous and metachronous tumors in probands and their families. Results Fifty-one percent of patients did not express one or more MMR proteins (MMR-) and should be considered Lynch Syndrome carriers (16 patients, group A1); while only 31.2% of them were positive for Amsterdam criteria, 50% had almost another tumor, 37.5% had another colorectal tumor and 68% had relatives with colorectal tumor. This group of patients, compared with A2 group (< 50 years old, MMR+) and B group, showed typical characteristics of HNPCC, such as proximal location, mucinous histotype, poor differentiation, high stage and shorter survival. Conclusions The present study confirms that preoperative knowledge of MMR proteins expression in colorectal cancer patients would allow correct staging, more extended colonic resection, specific follow-up and familial screening. PMID:24533633

  20. Employment Services Needs of Veterans.

    ERIC Educational Resources Information Center

    Perspective: Essays and Reviews of Issues in Employment Security and Employment and Training Programs, 1989

    1989-01-01

    This issue of an annual journal contains 20 papers reflecting on the efforts of U.S. employment security and training programs to meet the needs of veterans. Part I, "National Perspective," contains five essays: "Policy Issues for Veteran Job Training Programs" (Martin F. Smith); "Cognizant Ramblings: Superfluous Lags the Veteran on the Stage…

  1. Army Spouse Employment Literature Review

    DTIC Science & Technology

    1990-09-01

    segregation. He employs a hedonic price model that puts occupational choice into a human capital framework. As discussed earlier, human capital models...Insurance Society, Hewlett-Packard, Honeywell, IBM, 3M, General Electric , Mobil and Citibank (Sekaran, 1986; Collie, 1986; Sekas, 1984; Moore 1987

  2. Working Parents, Employers, and Schools.

    ERIC Educational Resources Information Center

    Espinoza, Renato

    1988-01-01

    Discusses the Working Parents Project, a study of both single-parent families and dual-career families. This study explored working parents' perceptions of how personnel policies and practices affected family life. Topics covered include (1) short-term leave policies, (2) day care, and (3) how schools, community agencies, and employers can help…

  3. Admission Conditions and Graduates' Employability

    ERIC Educational Resources Information Center

    Alexandre, Fernando; Portela, Miguel; Sa, Carla

    2009-01-01

    In a context of increasing competition for students, admission conditions have been used as an instrument in a strategy of differentiation. Such a strategy is guided by short-run concerns, that is, the immediate need to attract more students. This article takes a longer term view, by examining graduates' employability. The authors find that…

  4. Employment Conditions and Induction Opportunities.

    ERIC Educational Resources Information Center

    Wilson, J. A.; D'Arcy, J. M.

    1987-01-01

    Teachers who were newly trained in Northern Ireland in 1985 and who found employment completed a questionnaire regarding their participation in either external or school-based induction programs. Secondary teachers were compared with primary teachers. Results are discussed. (Author/MT)

  5. A Perspective on Student Employment.

    ERIC Educational Resources Information Center

    Barton, Paul E.

    The time has come to start to improve students' job experiences and to improve the relationship between the work and school experiences. In rural and agricultural economies, student work was so important to the family that the school year was fashioned to accommodate it. As the nation became more urban, student employment for pay and student…

  6. Higher Education, Employability and Competitiveness

    ERIC Educational Resources Information Center

    Pavlin, Samo; Svetlicic, Marjan

    2012-01-01

    This paper studies the relationship between competitiveness and higher education systems in Europe. It explores whether more competitive countries have developed more labour-market-oriented systems of higher education (HE) that thereby give their graduates greater short term employability potential. Based on and a large-scale survey among 45.000…

  7. Employer Resource Manual. Project Path.

    ERIC Educational Resources Information Center

    Kane, Karen R.; Del George, Eve

    Project Path at Illinois' College of DuPage was established to provide pre-employment training and career counseling for disabled students. To encourage the integration of qualified individuals with disabilities into the workplace, the project compiled this resource manual for area businesses, providing tips for interacting with disabled people…

  8. Employability. Occupational Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP) is one of a series of competency lists, verified by expert workers, that have evolved from a modified DACUM (Developing a Curriculum) job analysis process involving business, industry, labor, and community agency representatives from throughout Ohio. This OCAP identifies the employability skills…

  9. Employment Trends in Energy Extraction.

    ERIC Educational Resources Information Center

    Greene, Richard

    1981-01-01

    Between 1973 and 1980, employment in the basic energy extraction industries--coal, oil, and natural gas--has risen by more than 91 percent. The Arab oil embargo and subsequent emphasis on development of domestic energy sources are responsible for this trend. (Author/SK)

  10. Youth Employment and Job Creation.

    ERIC Educational Resources Information Center

    Connors, Tad

    A policy that addresses youth unemployment with monetary expansion for similar fiscal policies is criticized as compounding the problem, and alternative solutions are offered. Accordingly, a brief look at youth labor market characteristics, pertinent labor market theory, and the present industrial distribution of employed youth is offered. A…

  11. Teaching Soft Skills Employers Need

    ERIC Educational Resources Information Center

    Ellis, Maureen; Kisling, Eric; Hackworth, Robbie G.

    2014-01-01

    This study identifies the soft skills community colleges teach in an office technology course and determines whether the skills taught are congruent with the soft skills employers require in today's entry-level office work. A qualitative content analysis of a community college office technology soft skills course was performed using 23 soft skills…

  12. Towards a New Employment Policy.

    ERIC Educational Resources Information Center

    Laroque, Pierre

    1989-01-01

    International employment policy must change in order to provide people with work suited to their abilities at every life stage. If technology fails to create sufficient jobs, available work should be redistributed to ensure that large numbers of people do not remain inactive at the community's expense. (Author/CH)

  13. Building the Bridge to Employment.

    ERIC Educational Resources Information Center

    Fox, Janna; Jones, Regina

    1982-01-01

    Describes Manpower ESL courses sponsored by Canada Employment and Immigration Commission and Ministry of Colleges and Universities to provide language instruction for newly arrived immigrants seeking jobs. Concentrates on interview, locating job prospects, application forms, getting ready for interview, cultural expectations on the job and…

  14. Overseas Employment Opportunities for Educators.

    ERIC Educational Resources Information Center

    Dependents Schools (DOD), Washington, DC.

    This brochure contains information regarding recruitment procedures for elementary and secondary teachers seeking employment in schools operating on United States military bases. Sections cover the following areas: (1) eligibility; (2) position categories and special requirements; (3) application procedures; (4) basic program information and…

  15. Employer Attitudes toward Study Abroad

    ERIC Educational Resources Information Center

    Trooboff, Stevan; Vande Berg, Michael; Rayman, Jack

    2008-01-01

    In recent years, as study abroad professionals have come to focus more squarely on the question of what students are in fact learning abroad, there has been increasing speculation about the extent to which study abroad increases prospects for employability following graduation. Common wisdom has it that undergraduates who study abroad have an…

  16. Employment Effects of Trade Expansion

    ERIC Educational Resources Information Center

    Lydall, H. F.

    1975-01-01

    The study to estimate the employment effects of an increase of manufactured and semi-manufactured products exported from developing to developed countries concluded that the lower the degree of development, the greater the number of jobs generated. Available from: ILO Publications, International Labour Office, CH-1211, Geneva 22, Switzerland.…

  17. Supported employment: randomised controlled trial*

    PubMed Central

    Howard, Louise M.; Heslin, Margaret; Leese, Morven; McCrone, Paul; Rice, Christopher; Jarrett, Manuela; Spokes, Terry; Huxley, Peter; Thornicroft, Graham

    2010-01-01

    Background There is evidence from North American trials that supported employment using the individual placement and support (IPS) model is effective in helping individuals with severe mental illness gain competitive employment. There have been few trials in other parts of the world. Aims To investigate the effectiveness and cost-effectiveness of IPS in the UK. Method Individuals with severe mental illness in South London were randomised to IPS or local traditional vocational services (treatment as usual) (ISRCTN96677673). Results Two hundred and nineteen participants were randomised, and 90% assessed 1 year later. There were no significant differences between the treatment as usual and intervention groups in obtaining competitive employment (13% in the intervention group and 7% in controls; risk ratio 1.35, 95% CI 0.95–1.93, P = 0.15), nor in secondary outcomes. Conclusions There was no evidence that IPS was of significant benefit in achieving competitive employment for individuals in South London at 1-year follow-up, which may reflect suboptimal implementation. Implementation of IPS can be challenging in the UK context where IPS is not structurally integrated with mental health services, and economic disincentives may lead to lower levels of motivation in individuals with severe mental illness and psychiatric professionals. PMID:20435968

  18. Employment Trends in Energy Extraction.

    ERIC Educational Resources Information Center

    Greene, Richard

    1981-01-01

    Between 1973 and 1980, employment in the basic energy extraction industries--coal, oil, and natural gas--has risen by more than 91 percent. The Arab oil embargo and subsequent emphasis on development of domestic energy sources are responsible for this trend. (Author/SK)

  19. Employment Support as Knowledge Creation

    ERIC Educational Resources Information Center

    O'Brien, John; Callahan, Michael

    2010-01-01

    Traditional practice in employment of persons with disabilities has been to assess the skills and interests of the job seeker in relation to normative standards or to others. That comparative approach often results in job seekers with significant developmental disabilities being viewed as having few skills and lacking requisite work readiness,…

  20. Youth Employability Training: Two Experiments

    ERIC Educational Resources Information Center

    Brown, Travor; Hillier, Tara-Lynn; Warren, Amy M.

    2010-01-01

    Purpose: This paper aims to assess the effectiveness of verbal self-guidance (VSG) and self-management on youth employability. It seeks to access the joint effectiveness of these interventions, grounded in social cognitive and goal setting theories, for youth job seekers. Design/methodology/approach: The studies used experimental designs involving…

  1. Sex Discrimination in Employment Practices.

    ERIC Educational Resources Information Center

    California Univ., Los Angeles. Univ. Extension.

    The conference on sex discrimination in employment practices was held at the University of California at Los Angeles in cooperation with the Women's Bureau of the Department of Labor. Speeches included: (1) "New Legislation--New Action" by Rosalind K. Loring and William Foster, (2) "Compliance Policies and Procedures for Business and Industry" by…

  2. Supported Employment and Social Validity.

    ERIC Educational Resources Information Center

    Test, David W.

    1994-01-01

    Thirty studies on supported employment for people with disabilities were evaluated using a proposed Social Validity Matrix. Results suggested further research should investigate alternative strategies for assessing social validity, develop systematic procedures for collecting and using social validity data, and establish functional variables…

  3. Employers Often Distrust Online Degrees

    ERIC Educational Resources Information Center

    Carnevale, Dan

    2007-01-01

    This article explains why employers are reluctant to accept potential employees with online degrees. The results of several surveys of those who evaluate potential employees and make hiring decisions indicate a bias against online degrees, even as more and more colleges are offering programs online. To those officials, the words "online…

  4. Age Discrimination in Campus Employment

    ERIC Educational Resources Information Center

    Haslam, C. L.

    1975-01-01

    This analysis of the Age Discrimination in Employment Act of 1967 (ADEA) traces the issues that have emerged in litigation and summarizes the developing law, showing the implications in the university context and suggesting rules of thumb for accommodating the Act with the valid educational demands of the affected institutions. (JT)

  5. Employment Initiatives. Third Year Report.

    ERIC Educational Resources Information Center

    Maryland State Dept. of Human Resources, Baltimore.

    The third operational year of the Employment Initiatives (EI) saw expansion throughout Maryland with the addition of new projects in Anne Arundel, Allegany, Dorchester, Frederick, and Harford counties during October 1984. In July 1985, other projects were funded in Baltimore City, Southern Maryland, and Montgomery County. EI offered a package of…

  6. ESL Instruction for Refugee Employment.

    ERIC Educational Resources Information Center

    Beare, Sophie

    1984-01-01

    Describes a 24-week language training course designed to help refugees and/or immigrants become better able to obtain and do the work of their occupation, in English. The course stresses written and oral communication with employers, job search techniques, as well as those skills and vocabulary/phrases necessary for filling out job application…

  7. Employment Support as Knowledge Creation

    ERIC Educational Resources Information Center

    O'Brien, John; Callahan, Michael

    2010-01-01

    Traditional practice in employment of persons with disabilities has been to assess the skills and interests of the job seeker in relation to normative standards or to others. That comparative approach often results in job seekers with significant developmental disabilities being viewed as having few skills and lacking requisite work readiness,…

  8. High School Preparation for Employment.

    ERIC Educational Resources Information Center

    Hotchkiss, Lawrence; And Others

    This report contains four studies related to preparation of youth for employment after leaving school. The first study, "Learning as a Product of Exposure and Readiness" (Hotchkiss), examined the effects of curriculum on the learning of basic skills using an interaction model. The data collected revealed statistically significant interactions…

  9. Somerset County Employer Needs Assessment.

    ERIC Educational Resources Information Center

    Rephann, Terance J.

    Allegany Community College in Cumberland, Maryland, conducted an employer assessment survey of Somerset County businesses during the winter of 1995 in order to provide evaluation data for planning and curriculum development for the secondary and postsecondary educational institutions. The survey was mailed to 760 establishments, with a 29 percent…

  10. Employment Services Needs of Veterans.

    ERIC Educational Resources Information Center

    Perspective: Essays and Reviews of Issues in Employment Security and Employment and Training Programs, 1989

    1989-01-01

    This issue of an annual journal contains 20 papers reflecting on the efforts of U.S. employment security and training programs to meet the needs of veterans. Part I, "National Perspective," contains five essays: "Policy Issues for Veteran Job Training Programs" (Martin F. Smith); "Cognizant Ramblings: Superfluous Lags the Veteran on the Stage…

  11. Second Annual Employer Satisfaction Survey.

    ERIC Educational Resources Information Center

    Broadbent, William A.

    A state-wide survey of the personnel directors at 31 randomly selected firms with 180 employees or more was conducted to determine employer attitudes toward those employees who had graduated from high school or community college vocational education programs. The survey, administered during personal interviews, asked participants to: (1) indicate…

  12. Transnational Education and Employability Development

    ERIC Educational Resources Information Center

    Mellors-Bourne, Robin; Jones, Elspeth; Woodfield, Steve

    2015-01-01

    Internationalisation and employability development are important themes for UK higher education (HE) and the Higher Education Academy (HEA). One aspect of many UK HE institutions' internationalisation strategies has been to increase the number and range of UK programmes delivered "offshore" as transnational education (TNE)--through…

  13. Teenage Employment and Career Readiness

    ERIC Educational Resources Information Center

    Greene, Kaylin M.; Staff, Jeremy

    2012-01-01

    Most American youth hold a job at some point during adolescence, but should they work? This article presents a broad overview of teenage employment in the United States. It begins by describing which teenagers work and for how long and then focuses attention on the consequences (both good and bad) of paid work in adolescence. It then presents…

  14. Legal Aspects of Employment Testing.

    ERIC Educational Resources Information Center

    Shulman, Bernard H.

    Chapter 10 of a book on school law reviews court rulings on the use of tests and testing procedures for employment purposes. Title VII of the Civil Rights Act of 1964 contains a section authorizing the use of any professionally developed ability test, provided that it is not designed, intended, or used to discriminate. The courts have held…

  15. Employer-Led Quality Assurance

    ERIC Educational Resources Information Center

    Tyszko, Jason A.

    2017-01-01

    Recent criticism of higher education accreditation has prompted calls for reform and sparked interest in piloting alternative quality assurance methods that better address student learning and employment outcomes. Although this debate has brought much needed attention to improving the outcomes of graduates and safeguarding federal investment in…

  16. Higher Education, Employability and Competitiveness

    ERIC Educational Resources Information Center

    Pavlin, Samo; Svetlicic, Marjan

    2012-01-01

    This paper studies the relationship between competitiveness and higher education systems in Europe. It explores whether more competitive countries have developed more labour-market-oriented systems of higher education (HE) that thereby give their graduates greater short term employability potential. Based on and a large-scale survey among 45.000…

  17. Transnational Education and Employability Development

    ERIC Educational Resources Information Center

    Mellors-Bourne, Robin; Jones, Elspeth; Woodfield, Steve

    2015-01-01

    Internationalisation and employability development are important themes for UK higher education (HE) and the Higher Education Academy (HEA). One aspect of many UK HE institutions' internationalisation strategies has been to increase the number and range of UK programmes delivered "offshore" as transnational education (TNE)--through…

  18. Mental illness and employment discrimination.

    PubMed

    Stuart, Heather

    2006-09-01

    Work is a major determinant of mental health and a socially integrating force. To be excluded from the workforce creates material deprivation, erodes self-confidence, creates a sense of isolation and marginalization and is a key risk factor for mental disability. This review summarizes recent evidence pertaining to employment-related stigma and discrimination experienced by people with mental disabilities. A broad understanding of the stigmatization process is adopted, which includes cognitive, attitudinal, behavioural and structural disadvantages. Stigma is both a proximate and a distal cause of employment inequity for people with a mental disability who experience direct discrimination because of prejudicial attitudes from employers and workmates and indirect discrimination owing to historical patterns of disadvantage, structural disincentives against competitive employment and generalized policy neglect. Against this background, modern mental health rehabilitation models and legislative philosophies, which focus on citizenship rights and full social participation, are to be welcomed. Yet, recent findings demonstrate that the legislation remains vulnerable to the very prejudicial attitudes they are intended to abate. Research conducted during the past year continues to highlight multiple attitudinal and structural barriers that prevent people with mental disabilities from becoming active participants in the competitive labour market.

  19. Employers' Perspectives of Online Education

    ERIC Educational Resources Information Center

    Linardopoulos, Nikolaos

    2012-01-01

    Purpose: The purpose of this paper is to describe the strengths and weaknesses of seven representative studies pertaining to the employers' perceptions of online education. Design/methodology/approach: The paper retrieved and analysed representative studies on the subject from two scholarly databases and Google. Findings: The results indicate that…

  20. Teaching Soft Skills Employers Need

    ERIC Educational Resources Information Center

    Ellis, Maureen; Kisling, Eric; Hackworth, Robbie G.

    2014-01-01

    This study identifies the soft skills community colleges teach in an office technology course and determines whether the skills taught are congruent with the soft skills employers require in today's entry-level office work. A qualitative content analysis of a community college office technology soft skills course was performed using 23 soft skills…

  1. Employment Survey 1977. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.

    Employment opportunities for physics and astronomy graduates were surveyed in December 1977. At that time the graduates of 1976-77 had explored the job market for at least six months or had held their positions long enough to evaluate them and offer advice to prospective graduates. The time required for new graduates to obtain the first…

  2. Employment Survey 1987. AIP Report.

    ERIC Educational Resources Information Center

    Ellis, Susanne D.; Mulvey, Patrick J.

    Information from a 1987 survey of employment statistics by the American Institute of Physics is presented. This annual survey reports how new physicists and astronomers accomplish their transitions from student to employee and how they evaluate that transfer in retrospect. The 11 tables look at the following: changes in occupational status of…

  3. Employment, Social Networks and Undocumented Migrants: The Employer Perspective

    PubMed Central

    Bloch, Alice; McKay, Sonia

    2015-01-01

    This article draws on data from qualitative interviews with ethnic enclave and ethnic economy business entrepreneurs from Chinese, Bangladeshi and Turkish-speaking communities in London. Routes into business and worker recruitment practices are explored, demonstrating the centrality of social capital in the form of family and other social networks within these processes. The article investigates what employers consider the desirable characteristics of workers: trust, kinship, gender, social networks, language compatibility and the needs of the business intersect with racialised notions of workers’ strengths and characteristics. Finally, we consider changing practices in relation to the employment of undocumented migrants, in the context of an increasingly punitive legislative regime. The complex and variable impact of policy alongside the ways in which other obligations and positions outweigh the fear and risks of sanctions associated with non-compliance is revealed. PMID:25866421

  4. Employment, Social Networks and Undocumented Migrants: The Employer Perspective.

    PubMed

    Bloch, Alice; McKay, Sonia

    2015-02-01

    This article draws on data from qualitative interviews with ethnic enclave and ethnic economy business entrepreneurs from Chinese, Bangladeshi and Turkish-speaking communities in London. Routes into business and worker recruitment practices are explored, demonstrating the centrality of social capital in the form of family and other social networks within these processes. The article investigates what employers consider the desirable characteristics of workers: trust, kinship, gender, social networks, language compatibility and the needs of the business intersect with racialised notions of workers' strengths and characteristics. Finally, we consider changing practices in relation to the employment of undocumented migrants, in the context of an increasingly punitive legislative regime. The complex and variable impact of policy alongside the ways in which other obligations and positions outweigh the fear and risks of sanctions associated with non-compliance is revealed.

  5. EEOC claims employer refused reasonable accommodation. Equal Employment Opportunity Commission.

    PubMed

    1995-06-30

    The Equal Employment Opportunity Commission (EEOC) has sued Spectacor, one of the largest stadium-management companies, on behalf of employee [name removed]. [Name removed], who claimed his employer refused to grant him flexible work hours to accommodate his AIDS diagnosis. [Name removed] had submitted a note from one of his doctors stating that [name removed] had AIDS and was taking an experimental medicine. The doctors requested some added flexibility in working hours to enable [name removed] to prepare special meals and take showers to reduce the discomfort of the experimental medicines he was taking. Spectacor, instead of granting the request, informed [name removed] that his job was in jeopardy and that he would be discharged because of absenteeism and declining productivity. The suit alleges Spectacor violated the Americans with Disabilities Act (ADA) by refusing to grant [name removed] a reasonable accommodation for his disability and that the employer had breached its obligation to keep confidential his medical information. Spectacor denied that its refusal to accommodate [name removed]'s scheduling requests constituted a violation of the ADA.

  6. Career Education from the Employers' Viewpoint.

    ERIC Educational Resources Information Center

    Burton, Louise F.; And Others

    Sixty-five competitive employers (44 males and 21 females) were interviewed regarding their perceptions of specific career/vocational skills needed by handicapped people for successful employment. All employers had experience with handicapped workers and held supervisory and managerial positions at their employment site. Employers were distributed…

  7. Career Education from the Employers' Viewpoint.

    ERIC Educational Resources Information Center

    Burton, Louise F.; And Others

    Sixty-five competitive employers (44 males and 21 females) were interviewed regarding their perceptions of specific career/vocational skills needed by handicapped people for successful employment. All employers had experience with handicapped workers and held supervisory and managerial positions at their employment site. Employers were distributed…

  8. Florida Employer Opinion Survey. Annual Report.

    ERIC Educational Resources Information Center

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    Two surveys were directed to Florida employers that employed former vocational education students in 1988. The surveys obtained information describing employer opinions regarding general and specific vocational preparation of workers for employment. The 1989-90 employer general opinion survey examined hiring needs, general preparation, and…

  9. 29 CFR 1625.5 - Employment applications.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Employment applications. 1625.5 Section 1625.5 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN EMPLOYMENT ACT Interpretations § 1625.5 Employment applications. A request on the part of an employer for information such as Date of Birth or age on a...

  10. Characterization of Pathogenic Human MSH2 Missense Mutations Using Yeast as a Model System: A Laboratory Course in Molecular Biology

    ERIC Educational Resources Information Center

    Gammie, Alison E.; Erdeniz, Naz

    2004-01-01

    This work describes the project for an advanced undergraduate laboratory course in cell and molecular biology. One objective of the course is to teach students a variety of cellular and molecular techniques while conducting original research. A second objective is to provide instruction in science writing and data presentation by requiring…

  11. Characterization of Pathogenic Human MSH2 Missense Mutations Using Yeast as a Model System: A Laboratory Course in Molecular Biology

    ERIC Educational Resources Information Center

    Gammie, Alison E.; Erdeniz, Naz

    2004-01-01

    This work describes the project for an advanced undergraduate laboratory course in cell and molecular biology. One objective of the course is to teach students a variety of cellular and molecular techniques while conducting original research. A second objective is to provide instruction in science writing and data presentation by requiring…

  12. Maintenance of employment on dialysis.

    PubMed

    Rasgon, S; James-Rogers, A; Chemleski, B; Ledezma, M; Mercado, L; Besario, M; Trivedi, J; Miller, M; Dee, L; Pryor, L; Yeoh, H

    1997-04-01

    This article describes the components of a multidisciplinary effort focused on promoting, among other goals, continued employment during end-stage renal disease (ESRD) treatment. The education and guidance of the patient begin during the pre-ESRD period, intensify through dialysis treatment, and continue even through posttransplantation follow-up. Such focused programs support patients in retaining their usual lifestyle, staying in their current jobs where possible, and maximizing self-esteem and quality of life.

  13. Veterans Benefits: Federal Employment Assistance

    DTIC Science & Technology

    2010-04-09

    Services Employment and Reemployment Rights Act of 1994 (USERRA, P.L. 103-353). All VETS activities are required partners in the One - Stop Career Center...please see CRS Report RL34024, Veterans and Homelessness, by Libby Perl. 8 Local one - stop service centers can be found online at http...through state job services or one stop offices, and may post job openings on the federal online service (America’s Job Bank).15 Veterans Hiring

  14. Veterans Benefits: Federal Employment Assistance

    DTIC Science & Technology

    2008-01-14

    enhance workforce investment activities CRS-4 7 Local one - stop service centers can be found online at [http://www.servicelocator.org/]. 8 For federal...Employment and Reemployment Rights Act of 1994 (USERRA, P.L. 103-353). All VETS activities are required partners in the One - Stop Career Center system...veterans. Contractors and subcontractors are required to post job openings through state job services or one stop offices, and may post job openings

  15. Diamond Synthesis Employing Nanoparticle Seeds

    NASA Technical Reports Server (NTRS)

    Uppireddi, Kishore (Inventor); Morell, Gerardo (Inventor); Weiner, Brad R. (Inventor)

    2014-01-01

    Iron nanoparticles were employed to induce the synthesis of diamond on molybdenum, silicon, and quartz substrates. Diamond films were grown using conventional conditions for diamond synthesis by hot filament chemical vapor deposition, except that dispersed iron oxide nanoparticles replaced the seeding. This approach to diamond induction can be combined with dip pen nanolithography for the selective deposition of diamond and diamond patterning while avoiding surface damage associated to diamond-seeding methods.

  16. Achieving and sustaining full employment.

    PubMed

    Rosen, S M

    1995-01-01

    Human rights and public health considerations provide strong support for policies that maximize employment. Ample historical and conceptual evidence supports the feasibility of full employment policies. New factors affecting the labor force, the rate of technological change, and the globalization of economic activity require appropriate policies--international as well as national--but do not invalidate the ability of modern states to apply the measures needed. Among these the most important include: (I) systematic reduction in working time with no loss of income, (2) active labor market policies, (3) use of fiscal and monetary measures to sustain the needed level of aggregate demand, (4) restoration of equal bargaining power between labor and capital, (5) social investment in neglected and outmoded infrastructure, (6) accountability of corporations for decisions to shift or reduce capital investment, (7) major reductions in military spending, to be replaced by socially needed and economically productive expenditures, (8) direct public sector job creation, (9) reform of monetary policy to restore emphasis on minimizing unemployment and promoting full employment. None are without precedent in modern economies. The obstacles are ideological and political. To overcome them will require intellectual clarity and effective advocacy.

  17. 38 CFR 21.58 - Redetermination of employment handicap and serious employment handicap.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... employment handicap and serious employment handicap. 21.58 Section 21.58 Pensions, Bonuses, and Veterans... of employment handicap and serious employment handicap. (a) Prior to induction into a program. A determination as to employment handicap, serious employment handicap, or eligibility for a program of employment...

  18. 75 FR 55392 - Employment Network Report Card

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION Employment Network Report Card AGENCY: Social Security Administration (SSA). ACTION: Notice of... public comments on Employment Network quality assurance, including a ticket consumer Employment...

  19. 45 CFR 400.154 - Employability services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... training is provided at the employment site and is expected to result in full-time, permanent, unsubsidized employment with the employer who is providing the training. (d) English language instruction, with an...

  20. 45 CFR 400.154 - Employability services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... training is provided at the employment site and is expected to result in full-time, permanent, unsubsidized employment with the employer who is providing the training. (d) English language instruction, with an...

  1. 76 FR 5212 - Employment and Training Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

    ... Employment and Training Administration Comment Request for Information Collection for Internal Fraud and...: Employment and Training Administration (ETA), Department of Labor. ACTION: Notice. SUMMARY: The Department of.... Currently, the Employment and Training Administration is soliciting comments concerning the Office...

  2. 78 FR 32470 - Employment and Training Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... Employment and Training Administration Investigations Regarding Eligibility To Apply for Worker Adjustment..., the Director of the Office of Trade Adjustment Assistance, Employment and Training Administration, has... Trade Adjustment Assistance, Employment and Training Administration, U.S. Department of Labor, Room...

  3. 76 FR 45621 - Employment and Training Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... Employment and Training Administration Comment Request for Extension of Information Collection (Without... Temporary Employment Certification AGENCY: Employment and Training Administration. ACTION: Notice. SUMMARY... Training Administration (ETA) is soliciting comments concerning the extension of the approval for...

  4. Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity.

    PubMed

    Gurzu, Simona; Kadar, Zoltan; Sugimura, Haruhiko; Bara, Tivadar; Bara, Tivadar; Halmaciu, Ioana; Jung, Ioan

    2015-03-01

    Increasing number of early-onset gastric carcinomas (GCs) and controversial results regarding the differences among young and older patients with this type of cancer are the reasons why correlation of clinicopathological factors with molecular markers is necessary. The aim of our study was to compare the demographic, clinical and immunohistochemical (IHC) aspects in Romanian patients with GC diagnosed below and above 45 years old. In 191 samples provided from patients with GC, the clinicopathological parameters were correlated with a panel of 15 antibodies: E-cadherin, HER-2, VEGF, CD31, CD105, COX-2, maspin, bax, bcl-2, p53, Ki67, MLH-1, MSH-2, mena protein and vimentin. Compared to the conventional cases, GCs diagnosed below 45 years old were more frequently located at the gastroesophageal junction and presented a higher percentage of lymph node metastases. The diffuse type E-cadherin/mena/p53/Ki67/bax-negative cases that displayed nuclear maspin positivity were also more frequently in younger patients. The intestinal type early-onset GCs were the most angiogenic ones, the apoptotic rate being lower than in the intestinal type GCs of the aged. Compared to the conventional cases, in the early-onset GCs the nuclear maspin-mediated antiproliferative activity is more intense in diffuse type while the mena-dependent tumor cell proliferation is more characteristic for intestinal type GCs.

  5. Employer`s contributions to the training of professional statisticians

    SciTech Connect

    Rustagi, J.S.; Wright, T. |

    1995-07-01

    Statistical science provides important techniques for decision making in a large variety of fields of human endeavor mainly through statistical practice. According to Deming (1965), ``Statistical practice is mostly a collaborative venture between (professional) statisticians and experts in subject-matter (area).`` The professional statistician must be properly trained in areas of statistical science most suited to the discipline in which the applications are made. Due to a large variety of applications. The education of a professional statistician by universities can only be very general. Higher education provides the theoretical basis of statistical science whereas the specific expertise needed by the professional statistician is given by the application areas. In this paper, the authors review the approach of academic programs which are geared towards applications and discuss some of the innovative strategies for preparing statisticians as consultants in industry and business. A survey (census) of statisticians at the national laboratories of the US Department of Energy was made to assess their training by universities and to get a broad view of additional training which has brought them to their present professional status. A particular interest is the extent to which employers have contributed to the training of statisticians. A few recommendations are made which may serve to improve the future training of statisticians for applied collaborative work by universities and employers.

  6. Purchasing cooperatives for small employers.

    PubMed

    Mallozzi, J

    1997-12-01

    Despite a booming economy, the number of uninsured Americans is rising. It hit nearly 42 million in 1996. Many of the uninsured work at businesses with fewer than 50 employees. Because small firms have traditionally found it difficult to provide health benefits, purchasing cooperatives have grown in scope and size across the country in recent years. By bringing small businesses together to buy insurance as a group, these organizations can help employers provide greater choice to their workers at a lower cost. However, to operate well in the insurance market, purchasing cooperatives must be well-designed and provided with adequate legal protections.

  7. Contrasting views on STEM employment

    NASA Astrophysics Data System (ADS)

    Jones, Matthew; Huber, Michael

    2015-07-01

    In reply to “Unemployed and STEM” (Careers, May pp46-47), in which Penny Jackson described how her efforts to find a job in science, technology, engineering or mathematics (STEM) met with little success at first, even though she has a BSc in physics and a Master's in accelerator science. And in reply to “STEM paradox revisited” (Editorial, June p15), on why employers are expressing concerns about STEM shortages at a time when many recent STEM graduates are struggling to find jobs.

  8. Veterans Benefits: Federal Employment Assistance

    DTIC Science & Technology

    2007-05-25

    and the VWIP program, the VETS office in DOL also: CRS-4 7 Local one - stop service centers can be found online at [http://www.servicelocator.org/]. 8...USERRA, P.L. 103-353). All VETS activities are required partners in the One - Stop Career Center system established by WIA.7 Federal Employment...required to post job openings through state job services or one stop offices, and may post job openings on the federal online service (America’s Job Bank

  9. Employability Skills, Personal Qualities, and Early Employment Problems of Entry-Level Auditors: Perspectives from Employers, Lecturers, Auditors, and Students

    ERIC Educational Resources Information Center

    Lim, Yet-Mee; Lee, Teck Heang; Yap, Ching Seng; Ling, Chui Ching

    2016-01-01

    The authors examine the issue of employability of university accounting students from the perspectives of accounting firm employers, junior auditors, accounting lecturers, and accounting students. Areas of investigation include perceived importance of employability skills and desirable personal qualities; and early employment problems encountered…

  10. Employability Skills, Personal Qualities, and Early Employment Problems of Entry-Level Auditors: Perspectives from Employers, Lecturers, Auditors, and Students

    ERIC Educational Resources Information Center

    Lim, Yet-Mee; Lee, Teck Heang; Yap, Ching Seng; Ling, Chui Ching

    2016-01-01

    The authors examine the issue of employability of university accounting students from the perspectives of accounting firm employers, junior auditors, accounting lecturers, and accounting students. Areas of investigation include perceived importance of employability skills and desirable personal qualities; and early employment problems encountered…

  11. Building Employer Capacity to Support Meaningful Employment for Persons with Developmental Disabilities: A Grounded Theory Study of Employment Support Perspectives.

    PubMed

    Rashid, Marghalara; Hodgetts, Sandra; Nicholas, David

    2017-08-29

    To explore strategies to build employer capacity to support people with DD in meaningful employment from perspective of employment support workers. A grounded theory study was conducted with 34 employment support individuals. A theoretical sampling approach was used to identify and recruit participants from multiple sites in Ontario and Alberta. Three main themes, with seven sub-themes, emerged: (1) experiences of supporting employment finding for people with DD, (2) institutional influences on employee experiences, and (3) attitudes, assumptions and stigma. Several recommendations related to building employer capacity were offered. Our findings provide insight on specific elements and strategies that can support building employer capacity for persons with DD.

  12. 75 FR 36154 - Proposed Information Collection (Request to Employer for Employment Information in Connection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-24

    ... is used to request employment information from an employer in connection with a claim for disability... AFFAIRS Proposed Information Collection (Request to Employer for Employment Information in Connection With Claim for Disability Benefits) Activity: Comment Request AGENCY: Veterans Benefits Administration...

  13. Expression of Mismatch Repair Proteins in Early and Advanced Gastric Cancer in Poland

    PubMed Central

    Karpińska-Kaczmarczyk, Katarzyna; Lewandowska, Magdalena; Ławniczak, Małgorzata; Białek, Andrzej; Urasińska, Elżbieta

    2016-01-01

    Background Mutations in DNA of mismatch repair (MMR) genes result in failure to repair errors that occur during DNA replication in microsatellites, resulting in accumulation of frameshift mutations in these genes and leading to DNA mismatch replication errors and microsatellite instability. Gastric cancers (GCs) with high MSI (MSI-H) are a well-defined subset of carcinomas showing distinctive clinicopathological features. In this study we investigated the rate of MSI and the correlation between MSI status and clinicopathological features of GC. Material/Methods The study included 107 patients with GCs: 61 with advanced gastric cancers (AGC) and 46 with early gastric cancer (EGC). MSI deficiency in GCs was assessed by the immunohistochemical analysis of expression of MMR proteins – MLH1, MSH2, MSH6, and PMS2 – using formalin-fixed and paraffin-embedded tissue. Results A total of 6 (5.6%) MSI-H were observed. The loss of MMR proteins expression was associated with the intestinal type of GC in Lauren classification, and tubular and papillary architecture in WHO classification. There was no statistically significant association between negative MMR expression and other selected clinical parameters: age, sex, tumor location, depth of invasion (EGC and AGC), lymph nodes status, presence of the ulceration, and lymphocytic infiltrate. Conclusions In the present era of personalized medicine, the histological type of GC and MMR proteins status in cancer cells are very important for the proper surveillance of patients with familial GC and sporadic GCs, as well as for selecting the proper follow-up and treatment. Larger collaborative studies are needed to verify the features of MSI-H GCs in Poland. PMID:27527654

  14. Clinical Impact of Mismatch Repair Protein Testing on Outcome of Early Staged Colorectal Carcinomas.

    PubMed

    Gandhi, Jatin Sundersham; Goswami, Malini; Sharma, Anila; Tanwar, Parul; Gupta, Gurudutt; Gupta, Nikhil; Pasricha, Sunil; Mehta, Anurag; Singh, Shivender; Agarwal, Mohit; Gupta, Nitin

    2017-06-05

    Colorectal cancer is the third most common cancer in men and second most common in women globally. In the present study, we aimed to analyse the proportion of patients with loss of immunostaining for mismatch repair (MMR) proteins in all newly diagnosed stage II cases of colorectal cancer for the purpose of prognostication, for determination of further chemotherapeutic strategy and for familial screening. From January 2014 to December 2015, 62 consecutive newly diagnosed cases of stage II colorectal cancer were included in the study. Details of each patient related to their demographic profile and tumour profile were recorded. All the cases were grossed and staged according to College of American Pathologist (CAP) guidelines. The expression of MMR proteins (which was earlier validated on normal as well as tumour tissue) in FFPE tumour tissue using IHC for mut L homologue 1 (MLH1), mut S homologue 2 (MSH2), mut S homologue 6 (MSH6) and post-meiotic segregation increased 2 (PMS2) was studied. Information regarding stage, treatment, clinical outcome and overall survival was retrieved when available. Out of a total of 371 cases, 62 (16.7%) cases were of stage II CRC, out of which 43 (12%) were treatment naive. Among the selected 62 cases, 26 (41.9%) demonstrated loss of MMR proteins and 36 (58.0%) cases had intact nuclear expression. Out of the cases with MMR loss, 38.4% showed loss of MLH1 and PMS2, 30.7% showed loss of MSH2 and MSH6, 26.9% showed isolated loss of PMS2 and 3.8% showed isolated loss of MSH6. Right-sided location (57.6%) was more common than left-sided (19.2%) and transverse colon (23.0%). Majority of the cases were moderately differentiated (65.3%) in morphology. There was no intratumoural infiltrate in most of the cases (53.8%), and only 3.8% cases showed marked intratumoural infiltrate. Also, peritumoural lymphocytic infiltrate was mild to moderate in most of the cases (26.9%) and marked Crohn's-like infiltrate was seen in only 7.6% cases. Our study

  15. 12 CFR 239.41 - Employment contracts.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Employment contracts. 239.41 Section 239.41... (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Indemnification; Employment Contracts § 239.41 Employment contracts. (a) General. A mutual holding company may enter into an employment contract with its...

  16. Legal Consequences of Employer Discharge Procedures

    ERIC Educational Resources Information Center

    Joseph, Stephanie

    2008-01-01

    The employment contract is sometimes misunderstood by both employees and employers. Drafters of employee manuals, policies, and procedures should be aware that the nature of the at-will employment relationship can be transformed into a binding employment contract by the words and phrases chosen. In this article, the author uses the case of Eric,…

  17. Legal Consequences of Employer Discharge Procedures

    ERIC Educational Resources Information Center

    Joseph, Stephanie

    2008-01-01

    The employment contract is sometimes misunderstood by both employees and employers. Drafters of employee manuals, policies, and procedures should be aware that the nature of the at-will employment relationship can be transformed into a binding employment contract by the words and phrases chosen. In this article, the author uses the case of Eric,…

  18. 20 CFR 702.111 - Employer's records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Employer's records. 702.111 Section 702.111 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR... § 702.111 Employer's records. Every employer shall maintain adequate records of injury sustained by...

  19. 14 CFR 1253.500 - Employment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... in Employment in Education Programs or Activities Prohibited § 1253.500 Employment. (a) General. (1... receives Federal financial assistance. (2) A recipient shall make all employment decisions in any education... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Employment. 1253.500 Section...

  20. 28 CFR 54.500 - Employment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... in Employment in Education Programs or Activities Prohibited § 54.500 Employment. (a) General. (1) No... Federal financial assistance. (2) A recipient shall make all employment decisions in any education program... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Employment. 54.500 Section...

  1. Employer Intermediaries: A Briefing Paper [and Profiles].

    ERIC Educational Resources Information Center

    Jobs for the Future, Boston, MA.

    In the late 1990s, many employers were facing short-term and longer-term human resource challenges. Those challenges have prompted many employers to pursue new strategies for finding and retaining qualified employers. Intermediary organizations have emerged as a valuable resource for helping employers find and keep qualified workers. Whatever…

  2. 29 CFR 401.5 - Employer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Employer. 401.5 Section 401.5 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.5 Employer. Employer means any employer or any group or...

  3. 45 CFR 400.81 - Criteria for appropriate employability services and employment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Criteria for appropriate employability services... REFUGEE RESETTLEMENT PROGRAM Requirements for Employability Services and Employment Criteria for Appropriate Employability Services and Employment § 400.81 Criteria for appropriate employability services...

  4. Employability Skills Valued by Employers as Important for Entry-Level Employees with and without Disabilities

    ERIC Educational Resources Information Center

    Ju, Song; Zhang, Dalun; Pacha, Jacqueline

    2012-01-01

    Individuals with disabilities face persistent challenges in gaining meaningful employment. One of the barriers to successful employment is a lack of employability skills. The purpose of this study was to identify employability skills that employers value as being important and to examine whether employers have different expectations for…

  5. Employability Skills Valued by Employers as Important for Entry-Level Employees with and without Disabilities

    ERIC Educational Resources Information Center

    Ju, Song; Zhang, Dalun; Pacha, Jacqueline

    2012-01-01

    Individuals with disabilities face persistent challenges in gaining meaningful employment. One of the barriers to successful employment is a lack of employability skills. The purpose of this study was to identify employability skills that employers value as being important and to examine whether employers have different expectations for…

  6. Sperm cells manipulation employing dielectrophoresis.

    PubMed

    Rosales-Cruzaley, E; Cota-Elizondo, P A; Sánchez, D; Lapizco-Encinas, Blanca H

    2013-10-01

    Infertility studies are an important growing field, where new methods for the manipulation, enrichment and selection of sperm cells are required. Microfluidic techniques offer attractive advantages such as requirement of low sample volume and short processing times in the range of second or minutes. Presented here is the application of insulator-based dielectrophoresis (iDEP) for the enrichment and separation of mature and spermatogenic cells by employing a microchannel with cylindrical insulating structures with DC electric potentials in the range of 200-1500 V. The results demonstrated that iDEP has the potential to concentrate sperm cells and distinguish between mature and spermatogenic cells by exploiting the differences in shape which lead to differences in electric polarization. Viability assessments revealed that a significant percentage of the cells are viable after the dielectrophoretic treatment, opening the possibility for iDEP to be developed as a tool in infertility studies.

  7. Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions

    PubMed Central

    Brown, Maxwell W.; Kim, Yoori; Williams, Gregory M.; Huck, John D.; Surtees, Jennifer A.; Finkelstein, Ilya J.

    2016-01-01

    DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2–Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2–Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2–Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2–Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2–Msh3 and Msh2–Msh6 navigate on a crowded genome and suggest how Msh2–Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin. PMID:26837705

  8. Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting.

    PubMed

    Overbeek, Lucia I H; Ligtenberg, Marjolijn J L; Willems, Riki W; Hermens, Rosella P M G; Blokx, Willeke A M; Dubois, Stefan V; van der Linden, Hans; Meijer, Jos W R; Mlynek-Kersjes, Maria L; Hoogerbrugge, Nicoline; Hebeda, Konnie M; van Krieken, Joannes H J M

    2008-08-01

    We examined the validity of immunohistochemistry for mismatch repair (MMR) proteins in colorectal cancer specimens to identify patients at risk for Lynch syndrome (hereditary nonpolyposis colorectal cancer) and patients with sporadic microsatellite instable colorectal cancer. This was assessed by observer agreement for and accuracy of interpretation of immunohistochemistry. Seven pathologists from 5 different pathology laboratories evaluated 100 molecularly defined colorectal cancers stained for MLH1, PMS2, MSH2, and MSH6. Two of the pathologists were experienced in interpretation of immunohistochemistry for MMR proteins. After evaluation of a subset of 20 cases, a discussion meeting was organized, after which pathologists evaluated all 100 cases. Staining patterns were interpreted as aberrant, normal, or indefinite. In 82% of tumors, 5 or more pathologists reached the same interpretation, which was considered the consensus diagnosis. Consensus was reached slightly less frequently in microsatellite instable than in stable tumors, and interobserver variation was moderate to substantial (kappa: 0.49-0.79). More microsatellite instable tumors showed an indefinite staining pattern compared with microsatellite stable tumors. Three out of 7 pathologists, including the 2 experienced pathologists, did not miss a microsatellite instable tumor. Each pathologist found at least 1 tumor with an aberrant staining pattern, whereas consensus was a normal staining pattern and the tumor was microsatellite stable. We conclude that, if restricted to experienced pathologists, immunohistochemistry is a valid tool to identify patients at risk for Lynch syndrome and patients with sporadic microsatellite instable colorectal cancer. An indefinite or aberrant staining result has to be followed by molecular microsatellite instability analysis to confirm the presence of a defective DNA MMR system.

  9. Mismatch repair mRNA and protein expression in intestinal adenocarcinoma in sika deer (Cervus nippon) resembling heritable non-polyposis colorectal cancer in man.

    PubMed

    Jahns, H; Browne, J A

    2015-01-01

    Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation occurs in the deer tumours, the expression of the four most important MMR genes, MSH2, MLH1, MSH6 and PMS2, was examined at the mRNA level by reverse transcriptase polymerase chain reaction (n = 12) and at the protein level by immunohistochemistry (n = 40) in tumour and control tissues. All four genes were expressed equally in normal and neoplastic tissues, so MMR gene inactivation could not be implicated in the carcinogenesis of this tumour in sika deer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Differences of protein expression profiles, KRAS and BRAF mutation, and prognosis in right-sided colon, left-sided colon and rectal cancer.

    PubMed

    Gao, Xian Hua; Yu, Guan Yu; Gong, Hai Feng; Liu, Lian Jie; Xu, Yi; Hao, Li Qiang; Liu, Peng; Liu, Zhi Hong; Bai, Chen Guang; Zhang, Wei

    2017-08-11

    To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.

  11. Employability and Employers: The Missing Piece of the Jigsaw. IES Report 361.

    ERIC Educational Resources Information Center

    Tamkin, P.; Hillage, J.

    The approaches to employability being taken by United Kingdom employers were examined in a study that included three components: a literature review to develop a definition of employability and isolate its key elements; case studies of six organizations to identify employers' approaches to employability; and examination of related literature on…

  12. 5 CFR 315.704 - Conversion to career employment from indefinite or temporary employment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.704 Conversion to career employment from... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Conversion to career employment from...

  13. 5 CFR 315.704 - Conversion to career employment from indefinite or temporary employment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Conversion to career employment from... MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.704 Conversion to career employment...

  14. 45 CFR 400.82 - Failure or refusal to accept employability services or employment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Failure or refusal to accept employability... SERVICES REFUGEE RESETTLEMENT PROGRAM Requirements for Employability Services and Employment Failure Or Refusal to Accept Employability Services Or Employment § 400.82 Failure or refusal to accept...

  15. 5 CFR 315.704 - Conversion to career employment from indefinite or temporary employment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Conversion to career employment from... MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.704 Conversion to career employment from...

  16. 5 CFR 315.704 - Conversion to career employment from indefinite or temporary employment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Conversion to career employment from... MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.704 Conversion to career employment from...

  17. 5 CFR 315.704 - Conversion to career employment from indefinite or temporary employment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Conversion to career employment from... MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Conversion to Career or Career-Conditional Employment From Other Types of Employment § 315.704 Conversion to career employment from...

  18. Employer's Perceptions of Agribusiness Placement SOE Programs.

    ERIC Educational Resources Information Center

    Fletcher, Gregory W.; And Others

    1985-01-01

    Research was conducted to determine the benefits derived from agribusiness supervised occupational experience programs and to identify factors important in planning and/or conducting students' agribusiness employment experiences as perceived by employers of vocational agriculture students. (CT)

  19. Updating Economic Theory: The Employment Relationship.

    ERIC Educational Resources Information Center

    Winston, Gordon

    1983-01-01

    Faculty jobs have a remarkable degree of freedom compared to other jobs, but they have comparatively low salaries. The income difference between academic employment and employment in corporations, law firms, and medicine causes morale problems in faculties. (MLW)

  20. The Future of Employment and Unemployment.

    ERIC Educational Resources Information Center

    Bradshaw, Patricia; Burke, Ronald J.

    1983-01-01

    Discusses the impact of microprocessor technology on employment. Examines the changing nature of work and questions whether full employment is natural or necessary. Outlines physical, psychological, social, and material aspects of work. Notes implications for teachers, counselors, and students. (RC)

  1. Women's Employment in France: Protection or Equality.

    ERIC Educational Resources Information Center

    Devaud, Marcelle; Levy, Martine

    1980-01-01

    Reviews the origin and evolution of special protection laws in France for employed women, describes those measures that still exist, and explains what employers, unions, and the authorities think of them. Discusses pregnancy, family responsibilities, and technological progress. (CT)

  2. SEEMP: A Networked Marketplace for Employment Services

    NASA Astrophysics Data System (ADS)

    Celino, Irene; Cerizza, Dario; Cesarini, Mirko; Valle, Emanuele Della; de Paoli, Flavio; Estublier, Jacky; Fugini, Mariagrazia; Pérez, Asuncion Gómez; Kerrigan, Mick; Guarrera, Pascal; Mezzanzanica, Mario; Ramìrez, Jaime; Villazon, Boris; Zhao, Gang

    Human capital is more and more the key factor of economic growth and competitiveness in the information age and knowledge economy. But due to a still fragmented employment market compounded by the enlargement of the EU, the human resources are not effectively exchanged and deployed. The business innovation of SEEMP1 develops a vision of an Employment Mediation Marketplace (EMM) for market transparency and effic ient mediation. Its technological innovation provides a federated marketplace of employment agencies through a peer-to-peer network of employment data and mediation services. In other words, the solution under development is a de-fragmentation of the employment market by a web-based collaborative network. The SEEMP-enabled employment marketplace will strengthen the social organization of public employment administration, maximize the business turnover of private employment agencies, improve citizens' productivity and welfare, and increase the competitiveness and performance of business.

  3. 49 CFR 380.509 - Employer responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... REQUIREMENTS Entry-Level Driver Training Requirements § 380.509 Employer responsibilities. (a) Each employer must ensure each entry-level driver who first began operating a CMV requiring a CDL in...

  4. 49 CFR 380.509 - Employer responsibilities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... REQUIREMENTS Entry-Level Driver Training Requirements § 380.509 Employer responsibilities. (a) Each employer must ensure each entry-level driver who first began operating a CMV requiring a CDL in...

  5. 49 CFR 380.509 - Employer responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... REQUIREMENTS Entry-Level Driver Training Requirements § 380.509 Employer responsibilities. (a) Each employer must ensure each entry-level driver who first began operating a CMV requiring a CDL in...

  6. 49 CFR 380.509 - Employer responsibilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... REQUIREMENTS Entry-Level Driver Training Requirements § 380.509 Employer responsibilities. (a) Each employer must ensure each entry-level driver who first began operating a CMV requiring a CDL in...

  7. 49 CFR 380.509 - Employer responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REQUIREMENTS Entry-Level Driver Training Requirements § 380.509 Employer responsibilities. (a) Each employer must ensure each entry-level driver who first began operating a CMV requiring a CDL in...

  8. 29 CFR 1604.6 - Employment agencies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... BECAUSE OF SEX § 1604.6 Employment agencies. (a) Section 703(b) of the Civil Rights Act specifically... of sex. The Commission has determined that private employment agencies which deal exclusively with one sex are engaged in an unlawful employment practice, except to the extent that such agencies...

  9. 29 CFR 1604.6 - Employment agencies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... BECAUSE OF SEX § 1604.6 Employment agencies. (a) Section 703(b) of the Civil Rights Act specifically... of sex. The Commission has determined that private employment agencies which deal exclusively with one sex are engaged in an unlawful employment practice, except to the extent that such agencies...

  10. Employment Policy in the Global Economy.

    ERIC Educational Resources Information Center

    Lee, Eddy; And Others

    1995-01-01

    This special issue on employment policy in the global economy looks at macroeconomic policies and employment, institutional requirements for full employment, the world trade system, foreign investment, the marginalism of Africa, productivity enhancing policies, influence of information and communication technology, industrialized countries, and…

  11. Handbook of Employment Skills for Displaced Homemakers.

    ERIC Educational Resources Information Center

    White, Carol R.; Pollack, Steve

    This guidebook is designed to aid former homemakers to assess their skills and realize the transferability of them to the present day job market. It gives practical tips for all aspects of getting and holding a job, including the following: sources of employment; resumes; employer contact; application forms; employment tests; job interviews;…

  12. 5 CFR 340.402 - Seasonal employment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ....402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Seasonal and intermittent.... Seasonal employment may not be used as a substitute for full-time employment or as a buffer for the...

  13. Employer Preferences for Resumes and Cover Letters

    ERIC Educational Resources Information Center

    Schullery, Nancy M.; Ickes, Linda; Schullery, Stephen E.

    2009-01-01

    This article reports the results of a survey of employers' preferences for resume style, resume delivery method, and cover letters. Employers still widely prefer the standard chronological resume, with only 3% desiring a scannable resume. The vast majority of employers prefer electronic delivery, either by email (46%) or at the company's Web site…

  14. 29 CFR 1604.6 - Employment agencies.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... BECAUSE OF SEX § 1604.6 Employment agencies. (a) Section 703(b) of the Civil Rights Act specifically... of sex. The Commission has determined that private employment agencies which deal exclusively with one sex are engaged in an unlawful employment practice, except to the extent that such agencies...

  15. 29 CFR 825.104 - Covered employer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... employer covered by FMLA is any person engaged in commerce or in any industry or activity affecting... workweeks in the current or preceding calendar year. Employers covered by FMLA also include any person...)), as set forth in the definitions at § 825.800 of this part. For purposes of the FMLA, employers who...

  16. 29 CFR 825.104 - Covered employer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... employer covered by FMLA is any person engaged in commerce or in any industry or activity affecting... workweeks in the current or preceding calendar year. Employers covered by FMLA also include any person... (3)), as set forth in the definitions at § 825.800 of this part. For purposes of the FMLA, employers...

  17. 29 CFR 825.104 - Covered employer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... employer covered by FMLA is any person engaged in commerce or in any industry or activity affecting... workweeks in the current or preceding calendar year. Employers covered by FMLA also include any person... (3)), as set forth in the definitions at § 825.800 of this part. For purposes of the FMLA, employers...

  18. 29 CFR 825.104 - Covered employer.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... employer covered by FMLA is any person engaged in commerce or in any industry or activity affecting... workweeks in the current or preceding calendar year. Employers covered by FMLA also include any person... (3)), as set forth in the definitions at § 825.800 of this part. For purposes of the FMLA, employers...

  19. 29 CFR 825.104 - Covered employer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... employer covered by FMLA is any person engaged in commerce or in any industry or activity affecting... workweeks in the current or preceding calendar year. Employers covered by FMLA also include any person...)), as set forth in the definitions at § 825.800 of this part. For purposes of the FMLA, employers who...

  20. Employment Patterns of Methadone Maintenance Clients

    ERIC Educational Resources Information Center

    Bloch, Harriet I.; And Others

    1977-01-01

    Analysis of employment patterns of methadone maintenance clients had indicated that the majority were not employed at time of program admission. At time of evaluation, 70 percent of the sample were employed; 88 percent of these clients had previous work histories and brought marketable skills with them. (Author)

  1. "At-Will" Employment and Illinois Libraries.

    ERIC Educational Resources Information Center

    Uhler, Scott; Weiss, Philippe

    1995-01-01

    Illinois libraries and library districts should be aware of the employment "at-will" doctrine in their hiring, firing, and employment policy decisions. Because changes in the law require greater scrutiny of employment manuals and policies, recommendations are made for reducing administrative burdens, record keeping, reviewing employment…

  2. Farm Labor Developments. Employment and Wage Supplement.

    ERIC Educational Resources Information Center

    Bureau of Employment Security (DOL), Washington, DC.

    Estimated employment, wage rates, and origin of seasonal hired agricultural workers in selected activities are presented in tabular form. Employment information was obtained by the Bureau of Employment Security from 269 agricultural reporting areas throughout the country. Agricultural workers were defined as those engaged in the production of…

  3. Employability Assessment & Planning in Rehabilitation & Educational Settings.

    ERIC Educational Resources Information Center

    Farley, Roy C.; And Others

    A model for employability development is introduced to improve employability assessment and planning programs in rehabilitation and educational settings. The major components of an employability assessment and planning program are vocational choice, job acquisition, and job retention. The model offers strategies for empowering the consumer and…

  4. 12 CFR 563.39 - Employment contracts.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Employment contracts. 563.39 Section 563.39...-OPERATIONS Operation and Structure § 563.39 Employment contracts. (a) General. A savings association may enter into an employment contract with its officers and other employees only in accordance with the...

  5. Workplace Basics: The Skills Employers Want.

    ERIC Educational Resources Information Center

    Carnevale, Anthony P.; And Others

    A two-year research project was conducted to determine the skills employers consider necessary for the workplace. Recent changes in the economy have made employers begin to realize that they must assist their current and future workers in achieving competency in workplace basics if they are to be competitive. Employers have come to realize the…

  6. Partner Stalking and Implications for Women's Employment

    ERIC Educational Resources Information Center

    Logan, TK; Shannon, Lisa; Cole, Jennifer; Swanberg, Jennifer

    2007-01-01

    In general research suggests partner violence has a negative impact on women's employment. However, there has been limited examination of partner stalking and consequences for employment. The purpose of this study was to examine partner stalking and employment consequences among two samples of women. One sample was women who had obtained a…

  7. Employability and workability among Danish employees.

    PubMed

    Nielsen, J

    1999-01-01

    The study is based on a cross-sectional study of 5575 employees interviewed by telephone in 1995. The response rate was 80%. The purpose of the study was to examine the association between employability, workability, and age. The findings of this study support the hypothesis of a correlation between employability and workability. Furthermore, it shows a strong association between employability, age, and gender.

  8. Employer Preferences for Resumes and Cover Letters

    ERIC Educational Resources Information Center

    Schullery, Nancy M.; Ickes, Linda; Schullery, Stephen E.

    2009-01-01

    This article reports the results of a survey of employers' preferences for resume style, resume delivery method, and cover letters. Employers still widely prefer the standard chronological resume, with only 3% desiring a scannable resume. The vast majority of employers prefer electronic delivery, either by email (46%) or at the company's Web site…

  9. Higher Education and Employment in Spain.

    ERIC Educational Resources Information Center

    Fuente, Gloria de la

    1995-01-01

    An examination of the relationship of higher education and employment in Spain looks at: issues in the internal debate over the relationship; the evolution of the job market within the Spanish economy; existing analyses of employment trends and labor needs; and the response of Spanish universities to graduate employment problems and the…

  10. Discourses on Employability: Constituting the Responsible Citizen

    ERIC Educational Resources Information Center

    Fejes, Andreas

    2010-01-01

    In the last couple of decades, there has been a shift from speaking about employment to speaking about employability. The interest in this article is directed at how discourses on employability are mobilised in the wider discursive terrain of governance. How does governance operate, what subject is produced and, more specifically, who is…

  11. 20 CFR 702.111 - Employer's records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Employer's records. 702.111 Section 702.111 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR... § 702.111 Employer's records. Every employer shall maintain adequate records of injury sustained by...

  12. The Self-Employment Experience of Immigrants.

    ERIC Educational Resources Information Center

    Borjas, George J.

    1986-01-01

    Using the 1970 and 1980 U.S. Censuses, the analysis shows that self-employment rates of immigrants exceed those of native-born men, that there is a strong, positive impact of assimilation on self-employment rates; and that more recent waves of immigrants are opting with increasing frequency for the self-employment option. (Author/CT)

  13. 22 CFR 146.505 - Employment criteria.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employment in Education Programs or Activities Prohibited § 146.505 Employment criteria. A recipient shall... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment criteria. 146.505 Section 146.505 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS NONDISCRIMINATION ON THE BASIS OF SEX IN...

  14. 22 CFR 146.500 - Employment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Education Programs or Activities Prohibited § 146.500 Employment. (a) General. (1) No person shall, on the... assistance. (2) A recipient shall make all employment decisions in any education program or activity operated... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment. 146.500 Section 146.500...

  15. 75 FR 43615 - Program Integrity: Gainful Employment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... Education 34 CFR Part 668 Program Integrity: Gainful Employment; Proposed Rule #0;#0;Federal Register / Vol... RIN 1840-AD04 Program Integrity: Gainful Employment AGENCY: Office of Postsecondary Education... against the education and training (and increased employment income) that higher education can provide....

  16. 7 CFR 15a.51 - Employment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs and...) A recipient shall make all employment decisions in any education program or activity operated by... 7 Agriculture 1 2010-01-01 2010-01-01 false Employment. 15a.51 Section 15a.51 Agriculture...

  17. 22 CFR 229.505 - Employment criteria.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employment in Education Programs or Activities Prohibited § 229.505 Employment criteria. A recipient shall... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment criteria. 229.505 Section 229.505 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NONDISCRIMINATION ON THE BASIS OF SEX IN...

  18. 14 CFR 1253.505 - Employment criteria.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 1253.505 Employment... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Employment criteria. 1253.505 Section...

  19. 28 CFR 54.505 - Employment criteria.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 54.505 Employment criteria. A... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Employment criteria. 54.505 Section...

  20. 29 CFR 788.16 - Employment relationship.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Employment relationship. 788.16 Section 788.16 Labor... MORE THAN EIGHT EMPLOYEES ARE EMPLOYED § 788.16 Employment relationship. (a) The Supreme Court has made..., the permanency of the relationship, the opportunities for profit or loss, the initiative judgment or...

  1. 29 CFR 801.8 - Employment relationship.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Employment relationship. 801.8 Section 801.8 Labor... OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 General § 801.8 Employment relationship. (a) EPPA... employer in relationship to an employee or prospective employee” (EPPA section 2(2)). (b) EPPA restrictions...

  2. 29 CFR 801.8 - Employment relationship.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Employment relationship. 801.8 Section 801.8 Labor... OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 General § 801.8 Employment relationship. (a) EPPA... employer in relationship to an employee or prospective employee” (EPPA section 2(2)). (b) EPPA restrictions...

  3. 29 CFR 788.16 - Employment relationship.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Employment relationship. 788.16 Section 788.16 Labor... MORE THAN EIGHT EMPLOYEES ARE EMPLOYED § 788.16 Employment relationship. (a) The Supreme Court has made..., the permanency of the relationship, the opportunities for profit or loss, the initiative judgment or...

  4. 29 CFR 801.8 - Employment relationship.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Employment relationship. 801.8 Section 801.8 Labor... OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 General § 801.8 Employment relationship. (a) EPPA... employer in relationship to an employee or prospective employee” (EPPA section 2(2)). (b) EPPA restrictions...

  5. 29 CFR 801.8 - Employment relationship.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Employment relationship. 801.8 Section 801.8 Labor... OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 General § 801.8 Employment relationship. (a) EPPA... employer in relationship to an employee or prospective employee” (EPPA section 2(2)). (b) EPPA restrictions...

  6. 29 CFR 788.16 - Employment relationship.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Employment relationship. 788.16 Section 788.16 Labor... MORE THAN EIGHT EMPLOYEES ARE EMPLOYED § 788.16 Employment relationship. (a) The Supreme Court has made..., the permanency of the relationship, the opportunities for profit or loss, the initiative judgment or...

  7. 29 CFR 801.8 - Employment relationship.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Employment relationship. 801.8 Section 801.8 Labor... OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 General § 801.8 Employment relationship. (a) EPPA... employer in relationship to an employee or prospective employee” (EPPA section 2(2)). (b) EPPA restrictions...

  8. 34 CFR 34.22 - Employer responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Employer responsibilities. 34.22 Section 34.22 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.22 Employer responsibilities. (a)(1) Our garnishment order indicates a reasonable period of time within which an employer...

  9. 34 CFR 34.21 - Employer certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Employer certification. 34.21 Section 34.21 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.21 Employer certification. (a) Along with a garnishment order, we send to an employer a certification in a form...

  10. 34 CFR 34.21 - Employer certification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Employer certification. 34.21 Section 34.21 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.21 Employer certification. (a) Along with a garnishment order, we send to an employer a certification in a form...

  11. 34 CFR 34.22 - Employer responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Employer responsibilities. 34.22 Section 34.22 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.22 Employer responsibilities. (a)(1) Our garnishment order indicates a reasonable period of time within which an employer...

  12. 34 CFR 34.22 - Employer responsibilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Employer responsibilities. 34.22 Section 34.22 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.22 Employer responsibilities. (a)(1) Our garnishment order indicates a reasonable period of time within which an employer...

  13. 34 CFR 34.22 - Employer responsibilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Employer responsibilities. 34.22 Section 34.22 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.22 Employer responsibilities. (a)(1) Our garnishment order indicates a reasonable period of time within which an employer...

  14. 34 CFR 34.21 - Employer certification.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Employer certification. 34.21 Section 34.21 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.21 Employer certification. (a) Along with a garnishment order, we send to an employer a certification in a form...

  15. 34 CFR 34.21 - Employer certification.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Employer certification. 34.21 Section 34.21 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.21 Employer certification. (a) Along with a garnishment order, we send to an employer a certification in a form...

  16. 34 CFR 34.22 - Employer responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Employer responsibilities. 34.22 Section 34.22 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.22 Employer responsibilities. (a)(1) Our garnishment order indicates a reasonable period of time within which an employer...

  17. 34 CFR 34.21 - Employer certification.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Employer certification. 34.21 Section 34.21 Education Office of the Secretary, Department of Education ADMINISTRATIVE WAGE GARNISHMENT § 34.21 Employer certification. (a) Along with a garnishment order, we send to an employer a certification in a form...

  18. Employment Equity for Women: A University Handbook.

    ERIC Educational Resources Information Center

    Council of Ontario Universities, Toronto.

    Information, suggestions and guidelines are provided regarding employment equity for women in Ontario universities. Information is provided on the following topics: the office of the Employment Equity Coordinator; data and program development; employment systems (hiring, career development, compensation, and employees with family…

  19. 5 CFR 340.402 - Seasonal employment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Seasonal and intermittent.... Seasonal employment may not be used as a substitute for full-time employment or as a buffer for the full...

  20. 5 CFR 340.402 - Seasonal employment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Seasonal and intermittent.... Seasonal employment may not be used as a substitute for full-time employment or as a buffer for the full...