Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells

INTRODUCTION: Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin. METHODS: Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75. RESULTS: We found the cell adhesion protein desmoplakin to be upregulated by progesterone – a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines. CONCLUSION: Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action

Temporal change in groundwater level following the 1999 (Mw = 7.5) Chi-Chi earthquake, Taiwan

We examine the post-seismic change in the groundwater level following the 1999 (Mw = 7.5) Chi-Chi earthquake in central Taiwan, as recorded by a network of 70 evenly distributed hydrological stations over a large alluvial fan near the epicenter. Four types of post-seismic responses may be distinguished: In type 1, the groundwater level declined exponentially with time following a coseismic rise. This was the most common response in the study area and occurred in unconsolidated sediments on the Choshui River fan. In type 2, the groundwater level rose exponentially with time following a coseismic fall. This occurred in the deformed and fractured sedimentary rocks in the foothills near the Chelungpu fault that ruptured in the Chi-Chi earthquake. In type 3, the groundwater level continued to decline with time following a coseismic fall. This also occurred in the deformed and fractured sedimentary rocks near the ruptured fault. Finally, in type 4, the groundwater level, following a coseismic rise, stayed at the same level or even rose with time before it eventually declined. This occurred mostly in unconsolidated sediments along the coast of central Taiwan and along the Peikang Stream. We analyze these post-seismic responses by using a one-dimensional model. Together with the results from well test, the analysis show that the type 1 response may be explained by an aquifer model with coseismic recharge and post-seismic subhorizontal discharge across a length of 500-5,000 m; the type 2 response may be explained by a model of coseismic discharge and post-seismic recharge from surface water; the type 3 response may be explained by a model of coseismic discharge and post-seismic subhorizontal discharge across a length of 500-5,000 m; and the type 4 response may be explained by a model of coseismic recharge and sustained post-seismic recharge from surface water. The characteristic time for the post-seismic changes is similar to that for the groundwater-level decline during dry seasons before the earthquake, suggesting that there was no earthquake-induced changes in the aquifer properties (i.e., hydraulic conductivity), confirming the earlier results from recession analyses of the post-seismic streamflow elsewhere after several earthquakes

HSPVdb—the Human Short Peptide Variation Database for improved mass spectrometry-based detection of polymorphic HLA-ligands

T cell epitopes derived from polymorphic proteins or from proteins encoded by alternative reading frames (ARFs) play an important role in (tumor) immunology. Identification of these peptides is successfully performed with mass spectrometry. In a mass spectrometry-based approach, the recorded tandem mass spectra are matched against hypothetical spectra generated from known protein sequence databases. Commonly used protein databases contain a minimal level of redundancy, and thus, are not suitable data sources for searching polymorphic T cell epitopes, either in normal or ARFs. At the same time, however, these databases contain much non-polymorphic sequence information, thereby complicating the matching of recorded and theoretical spectra, and increasing the potential for finding false positives. Therefore, we created a database with peptides from ARFs and peptide variation arising from single nucleotide polymorphisms (SNPs). It is based on the human mRNA sequences from the well-annotated reference sequence (RefSeq) database and associated variation information derived from the Single Nucleotide Polymorphism Database (dbSNP). In this process, we removed all non-polymorphic information. Investigation of the frequency of SNPs in the dbSNP revealed that many SNPs are non-polymorphic “SNPs”. Therefore, we removed those from our dedicated database, and this resulted in a comprehensive high quality database, which we coined the Human Short Peptide Variation Database (HSPVdb). The value of our HSPVdb is shown by identification of the majority of published polymorphic SNP- and/or ARF-derived epitopes from a mass spectrometry-based proteomics workflow, and by a large variety of polymorphic peptides identified as potential T cell epitopes in the HLA-ligandome presented by the Epstein–Barr virus cells

Immune mechanisms in malaria: new insights in vaccine development.

Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination

Structure of a Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase at 2.5 Å resolution

peer reviewedBacteria possess proteases that are specific for the peptide bonds between D-alanine residues, one of which has a free alpha-carboxyl group. These D-alanyl-D-alanine peptidases catalyse carboxypeptidation and transpeptidation reactions involved in bacterial cell wall metabolism1,2, and are inactivated by beta-lactam antibiotics. We have now elucidated the structure, at 2.5 Å resolution, of the penicillin-resistant Zn2+-containing D-alanyl-D-alanine peptidase of Streptomyces albus (Zn2+ G peptidase)3,4. The enzyme is shown to consist of two globular domains, connected by a single link. The N-terminal domain has three alpha-helices, and the C-terminal domain has three alpha-helices and five beta-strands. The Zn2+ ion is ligated by three histidine residues, and located in a cleft in the C-terminal domain. The mechanism of action of the enzyme may be related to that of other carboxypeptidases, which also contain functional Zn2+ ions

Nut crop yield records show that budbreak-based chilling requirements may not reflect yield decline chill thresholds.

Warming winters due to climate change may critically affect temperate tree species. Insufficiently cold winters are thought to result in fewer viable flower buds and the subsequent development of fewer fruits or nuts, decreasing the yield of an orchard or fecundity of a species. The best existing approximation for a threshold of sufficient cold accumulation, the "chilling requirement" of a species or variety, has been quantified by manipulating or modeling the conditions that result in dormant bud breaking. However, the physiological processes that affect budbreak are not the same as those that determine yield. This study sought to test whether budbreak-based chilling thresholds can reasonably approximate the thresholds that affect yield, particularly regarding the potential impacts of climate change on temperate tree crop yields. County-wide yield records for almond (Prunus dulcis), pistachio (Pistacia vera), and walnut (Juglans regia) in the Central Valley of California were compared with 50 years of weather records. Bayesian nonparametric function estimation was used to model yield potentials at varying amounts of chill accumulation. In almonds, average yields occurred when chill accumulation was close to the budbreak-based chilling requirement. However, in the other two crops, pistachios and walnuts, the best previous estimate of the budbreak-based chilling requirements was 19-32 % higher than the chilling accumulations associated with average or above average yields. This research indicates that physiological processes beyond requirements for budbreak should be considered when estimating chill accumulation thresholds of yield decline and potential impacts of climate change

Mini tunelizador moldável: um avanço técnico no acesso vascular para hemodiálise Mini moldable tunneler: a technical improvement for hemodialysis access

CONTEXTO: A confecção de fístula para hemodiálise pode envolver a criação de túnel para a acomodação do enxerto - veia autóloga ou prótese sintética. O trajeto e a extensão dependem do local escolhido para a realização das anastomoses e posicionamento do trajeto do enxerto. Na atualidade, os tunelizadores utilizados são constituídos de estruturas cilíndricas metálicas rígidas, que tornam necessário o uso de múltiplos tamanhos e conformações. OBJETIVO: Testar a utilização de um único mini tunelizador universal metálico e moldável na cirurgia de confecção de fístula para hemodiálise. MÉTODOS: Trata-se de um estudo piloto. O tunelizador desenvolvido consiste de uma estrutura cilíndrica e modular composta de fio de aço inoxidável moldável interno, com manopla em extremidade proximal e dupla ponta cônica intercambiável em extremidade distal e bainha cilíndrica externa de polietileno. O tunelizador foi utilizado em dez cirurgias de confecção de fístulas para hemodiálise em membros superiores e inferiores, e o sucesso de sua aplicabilidade e a frequência de complicações precoces foram observados. RESULTADOS: Suas características de maleabilidade e conformibilidade permitiram a utilização do mesmo tunelizador nos diversos tipos de fístulas realizadas. A ponta cônica distal com duplo diâmetro, intercambiável, permitiu que o mesmo aparato fosse aplicado na utilização de veia autógena ou prótese sintética. Todas as cirurgias foram seguidas de sucesso e com baixos índices de complicações precoces. CONCLUSÃO: A versatilidade do mini tunelizador metálico maleável e moldável permitiu sua utilização em todas as fístulas realizadas, independentemente do sítio das anastomoses e o trajeto de acomodação escolhido, sem complicações e com excelente índice de perviedade. Os dados sugerem que o mini tunelizador metálico maleável moldável pode ser utilizado com segurança e vantagens nas cirurgias de confecção de fístula para hemodiálise. Sua versatilidade e baixo custo de produção podem levá-lo a substituir os tunelizadores rígidos utilizados na atualidade e apontam para estudos mais elaborados e com casuística adequada para avaliação do real valor do novo instrumento.<br>BACKGROUND: Hemodialysis access fistula may involve creation of a tunnel for the accommodation of autologous vein or synthetic graft. The route and extent depend on the location of the anastomosis and fistula body.Currently, the tunnelers used are rigid metallic cylindrical structures. Various sizes and conformations may be necessary. OBJECTIVE: Testing the use of a mini universal moldable tunnel maker in hemodialysis access fistula surgical creation. METHODS: This is a pilot study. The tunneler developed consists of a cylindrical structure composed of stainless steel wire with a handle at the proximal end and dual interchangeable conical tip at the distal end. It is covered with a cylindrical sheath of polyethylene. Its technical surgical application and complications were studied during ten hemodialysis fistula creation. RESULTS: Characteristics of flexibility and conformability made possible the same mini tunnel maker to be used in various types of fistulas performed. The tapered distal tip with double diameter, interchangeable head, allowed the same apparatus to be used in autogenos and graft fistulas surgical creation. CONCLUSION: The same mini malleable tunneler was used in all fistulas, regardless of the site of anastomosis and type of fistula performed without complications and with excellent patency rate

Utilization of Papanicolaou Smears by South Asian Women Living in the United States

OBJECTIVES: Papanicolaou (Pap) smears are an underutilized screening modality among racial and ethnic minorities. However, no data exist on Pap smear utilization among South Asians, a rapidly growing population in the United States, whose country of origin includes India, Pakistan, Bangladesh, and Sri Lanka. We determined rates and identified variables associated with Pap smear receipt by South Asians. DESIGN: A self-administered survey instrument was mailed to a random sample of South Asians nationwide over a 3-month time period. South Asian households were identified by surnames that were used to search white pages in telephone directories, Department of Motor Vehicle records, and voter registries. Questions regarding Pap smear receipt were taken from the 1999 National Health Interview Survey. Sociodemographic information and measures of acculturation were obtained. PARTICIPANTS: A nationwide nonprobability sample of South Asian women. INTERVENTION: Cross-sectional observational study. MEASUREMENTS AND MAIN RESULTS: The overall response rate was 42%. In this sample, South Asians belonged to a high socioeconomic strata (SES), with 45% having a household income of >$80,000 and 42% having a master's degree. Three quarters of the respondents (73%) reported having a Pap smear in the last 3 years. In multivariate logistic regression analysis, South Asian women had greater odds of having had a Pap smear if they were married (P < .001), more educated (P = .004), had a usual source of care (P = .002), and were more acculturated (P = .004). CONCLUSIONS: Despite the high SES of South Asian women, their rates of Pap smear receipt were lower than national recommendations. Marital status, socioeconomic status, and acculturation are all associated with Pap smear receipt. South Asian communities should be targeted for outreach to promote Pap smear utilization