Imprecatory Speech-Acts in the Book of Acts

Theologies of prayer in Acts have long neglected imprecatory prayers or curses as integral to the theological agenda of Luke. This article seeks to survey the instances of imprecations in Acts to determine how they function as speech-acts. The article makes two conclusions about imprecations in Acts based on the survey. First, imprecations identify the true People of God in the midst of competing claims. Second, imprecations reveal how one can participate in the salvific work of God

Early subretinal allograft rejection is characterized by innate immune activity

Successful subretinal transplantation is limited by considerable early graft loss, despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a non-immunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation and the neutrophil chemoattractant, KC/GRO/CINC, was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, non-immunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7 and 28 days post-operatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b & F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ε) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p<0.001) reduced between post-operative day (POD) 3 (90% ± 4%) and POD 7 (20% ± 7%). CD11b+, F4/80+ and Gr1 Ly-6G+ cells increased significantly (p<0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Co-labeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7 and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ε was low and did not differ significantly between time-points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal for the first time a critical role for innate immune mechanisms early in subretinal graft rejection. The future success of subretinal transplantation will require more emphasis on techniques to limit innate immune-mediated graft loss, rather than focusing exclusively on suppression of the adaptive immune response

Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration

International audiencePhysiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1 À/À mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1 À/À mice prevents patho-genic age-and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1 À/À mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD

Putative cis-regulatory elements in genes highly expressed in rice sperm cells

<p>Abstract</p> <p>Background</p> <p>The male germ line in flowering plants is initiated within developing pollen grains via asymmetric division. The smaller cell then becomes totally encased within a much larger vegetative cell, forming a unique "cell within a cell structure". The generative cell subsequently divides to give rise to two non-motile diminutive sperm cells, which take part in double fertilization and lead to the seed set. Sperm cells are difficult to investigate because of their presence within the confines of the larger vegetative cell. However, recently developed techniques for the isolation of rice sperm cells and the fully annotated rice genome sequence have allowed for the characterization of the transcriptional repertoire of sperm cells. Microarray gene expression data has identified a subset of rice genes that show unique or highly preferential expression in sperm cells. This information has led to the identification of <it>cis</it>-regulatory elements (CREs), which are conserved in sperm-expressed genes and are putatively associated with the control of cell-specific expression.</p> <p>Findings</p> <p>We aimed to identify the CREs associated with rice sperm cell-specific gene expression data using <it>in silico </it>prediction tools. We analyzed 1-kb upstream regions of the top 40 sperm cell co-expressed genes for over-represented conserved and novel motifs. Analysis of upstream regions with the SIGNALSCAN program with the PLACE database, MEME and the Mclip tool helped to find combinatorial sets of known transcriptional factor-binding sites along with two novel motifs putatively associated with the co-expression of sperm cell-specific genes.</p> <p>Conclusions</p> <p>Our data shows the occurrence of novel motifs, which are putative CREs and are likely targets of transcriptional factors regulating sperm cell gene expression. These motifs can be used to design the experimental verification of regulatory elements and the identification of transcriptional factors that regulate sperm cell-specific gene expression.</p

Proton beam therapy

Conventional radiation therapy directs photons (X-rays) and electrons at tumours with the intent of eradicating the neoplastic tissue while preserving adjacent normal tissue. Radiation-induced damage to healthy tissue and second malignancies are always a concern, however, when administering radiation. Proton beam radiotherapy, one form of charged particle therapy, allows for excellent dose distributions, with the added benefit of no exit dose. These characteristics make this form of radiotherapy an excellent choice for the treatment of tumours located next to critical structures such as the spinal cord, eyes, and brain, as well as for paediatric malignancies

Arabidopsis COP1 shapes the temporal pattern of CO accumulation conferring a photoperiodic flowering response

The transcriptional regulator CONSTANS (CO) promotes flowering of Arabidopsis under long summer days (LDs) but not under short winter days (SDs). Post-translational regulation of CO is crucial for this response by stabilizing the protein at the end of a LD, whereas promoting its degradation throughout the night under LD and SD. We show that mutations in CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a component of a ubiquitin ligase, cause extreme early flowering under SDs, and that this is largely dependent on CO activity. Furthermore, transcription of the CO target gene FT is increased in cop1 mutants and decreased in plants overexpressing COP1 in phloem companion cells. COP1 and CO interact in vivo and in vitro through the C-terminal region of CO. COP1 promotes CO degradation mainly in the dark, so that in cop1 mutants CO protein but not CO mRNA abundance is dramatically increased during the night. However, in the morning CO degradation occurs independently of COP1 by a phytochrome B-dependent mechanism. Thus, COP1 contributes to day length perception by reducing the abundance of CO during the night and thereby delaying flowering under SDs

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study

Objectives: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. Methods: The MIPA observational study enrolled women aged 18–80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. Results: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. Conclusions: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. Key Points: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups

The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

Screening and diagnostic breast MRI:how do they impact surgical treatment? Insights from the MIPA study

Objectives: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. Methods: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. Results: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p&nbsp;≤&nbsp;0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p&nbsp;&lt;&nbsp;0.001) for S-MRI, 1.0 (p&nbsp;=&nbsp;0.957) for D-MRI, and 1.9 (p&nbsp;&lt;&nbsp;0.001) for P-MRI. Conclusions: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. Key points: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups