Genomic divergence in swedish warmblood horses selected for equestrian disciplines

The equestrian sport horse Swedish Warmblood (SWB) originates from versatile cavalry horses. Most modern SWB breeders have specialized their breeding either towards show jumping or dressage disciplines. The aim of this study was to explore the genomic structure of SWB horses to evaluate the presence of genomic subpopulations, and to search for signatures of selection in subgroups of SWB with high or low breeding values (EBVs) for show jumping. We analyzed high density genotype information from 380 SWB horses born in the period 2010–2011, and used Principal Coordinates Analysis and Discriminant Analysis of Principal Components to detect population stratification. Fixation index and Cross Population Extended Haplotype Homozygosity scores were used to scan the genome for potential signatures of selection. In accordance with current breeding practice, this study highlights the development of two separate breed subpopulations with putative signatures of selection in eleven chromosomes. These regions involve genes with known function in, e.g., mentality, endogenous reward system, development of connective tissues and muscles, motor control, body growth and development. This study shows genetic divergence, due to specialization towards different disciplines in SWB horses. This latter evidence can be of interest for SWB and other horse studbooks encountering specialized breeding

Defining biodiverse reforestation: Why it matters for climate change mitigation and biodiversity

Mixed species plantings present an attractive alternative to monoculture reforestation through their added benefits to biodiversity. Yet there is ambiguity in the use of the term ‘biodiversity’ in carbon and biodiversity markets, which may create perverse outcomes when designing schemes and projects. Here, we review how the concept of biodiversity is defined and applied in reforestation projects, and restoration more broadly. Improved transparency around the use of the term biodiversity is urgently needed to provide rigour in emerging market mechanisms, which seek to benefit the environment and people. Summary: Reforestation to capture and store atmospheric carbon is increasingly championed as a climate change mitigation policy response. Reforestation plantings have the potential to provide conservation co-benefits when diverse mixtures of native species are planted, and there are growing attempts to monetise biodiversity benefits from carbon reforestation projects, particularly within emerging carbon markets. But what is meant by ‘biodiverse’ across different stakeholders and groups implementing and overseeing these projects and how do these perceptions compare with long-standing scientific definitions? Here, we discuss approaches to, and definitions of, biodiversity in the context of reforestation for carbon sequestration. Our aim is to review how the concept of biodiversity is defined and applied among stakeholders (e.g., governments, carbon certifiers and farmers) and rights holders (i.e., First Nations people) engaging in reforestation, and to identify best-practice methods for restoring biodiversity in these projects. We find that some stakeholders have a vague understanding of diversity across varying levels of biological organisation (genes to ecosystems). While most understand that biodiversity underpins ecosystem functions and services, many stakeholders may not appreciate the difficulties of restoring biodiversity akin to reference ecosystems. Consequently, biodiversity goals are rarely explicit, and project goals may never be achieved because the levels of restored biodiversity are inadequate to support functional ecosystems and desired ecosystem services. We suggest there is significant value in integrating biodiversity objectives into reforestation projects and setting specific restoration goals with transparent reporting outcomes will pave the way for ensuring reforestation projects have meaningful outcomes for biodiversity, and legitimate incentive payments for biodiversity and natural capital accounting

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5

One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels

HER-2/neu amplification testing in breast cancer by Multiplex Ligation-dependent Probe Amplification: influence of manual- and laser microdissection

<p>Abstract</p> <p>Background</p> <p>Accurate assessment of HER-2/<it>neu </it>status is crucial for proper prognostic information and to offer direct appropriate treatment for breast cancer patients. Next to immunohistochemistry (IHC) to evaluate HER2 protein overexpression, a second line gene amplification test is generally deemed necessary for cases with equivocal protein expression. Recently, a new PCR based test, called Multiplex Ligation-dependent Probe Amplification (MLPA), was introduced as a simple and quick method to assess HER-2/<it>neu </it>gene amplification status in invasive breast cancer. MLPA was previously shown to correlate well with IHC and <it>in situ </it>hybridization (ISH), but a low tumor percentage in the tissue tested could negatively affect the accuracy of MLPA results.</p> <p>Methods</p> <p>To examine this, MLPA was repeated in 42 patients after serial H&E section guided manual dissection with a scalpel and after laser microdissection of the tumor.</p> <p>Results</p> <p>Both dissection techniques led to higher HER2 gene copy number ratios and thereby made MLPA more quantitative. Concordance between MLPA and ISH improved from 61% to 84% after manual microdissection and to 90% after laser microdissection.</p> <p>Conclusion</p> <p>Manual and laser microdissection similarly increase the dynamic range of MLPA copy number ratios which is a technical advantage. As clinically a dichotomization between normal and amplified suffices and MLPA is relatively unsensitive to tumor content, microdissection before MLPA may not be routinely necessary but may be advisable in case of very low tumor content (≤30%), when MLPA results are equivocal, or when extensive ductal carcinoma <it>in situ </it>is present. Since differences between manual and laser microdissection were small, less time consuming manual microdissection appears to be sufficient.</p

Optically written waveguide in an atomic vapor

We present the first demonstration of an optically written waveguide in an atomic vapor. By strongly pumping one rubidium transition, we are able to waveguide a weak probe beam at a different rubidium transition. These effects can be understood with reference to a model of the refractive index for a V system. [S0031-9007(99)08495-1]

Chromogenic in situ hybridization (CISH): a novel alternative in screening archival breast cancer tissue samples for HER-2/neu status

BACKGROUND: Chromogenic in situ hybridization (CISH) is emerging as a practical, cost-effective, and valid alternative to fluorescent in situ hybridization in testing for gene alteration, especially in centers primarily working with immunohistochemistry (IHC). METHODS: We assessed Her-2/neu alteration using CISH on formalin-fixed paraffin-embedded primary invasive ductal carcinoma tumors in which IHC (CB11 antibody) had previously been performed, and we compared the results with IHC. The 160 selected cases were equally stratified randomly into the four IHC categories (scores of 0, 1+, 2+, and 3+). We also compared age at diagnosis and tumor histologic grade with IHC and CISH Her-2/neu. RESULTS: We were able to perform and evaluate CISH successfully on all cases. The agreement between 3+ IHC and CISH-amplified cases as well as between all IHC and CISH Her-2/neu negative cases was 100%, and the concordance on all positive cases was 72.50%, with an overall agreement of 86.25%. All the discordant cases had 2+ IHC scores. Although we noted Her-2/neu positivity more in premenopausal women, the age at diagnosis was not significantly associated with IHC or CISH results. Similarly, although the small group of well-differentiated tumors was apparently Her-2/neu negative in both tests, no significant association was noted between any tumor histologic grade and either IHC or CISH results. CONCLUSIONS: CISH is easily integrated into routine testing in our laboratory. It is a necessary adjunct in determining the subset of non-amplified IHC-positive invasive tumors that will not benefit from trastuzumab therapy. Those cases with 2+ IHC results will be triaged and subjected to CISH. Her-2/neu testing should be done on all breast cancer cases regardless of age at presentation and tumor histologic grade

DR6 as a Diagnostic and Predictive Biomarker in Adult Sarcoma

The Death Receptor 6 (DR6) protein is elevated in the serum of ovarian cancer patients. We tested DR6 serum protein levels as a diagnostic/predictive biomarker in several epithelial tumors and sarcomas.DR6 gene expression profiles were screened in publically available arrays of solid tumors. A quantitative immunofluorescent western blot analysis was developed to test the serum of healthy controls and patients with sarcoma, uterine carcinosarcoma, bladder, liver, and pancreatic carcinomas. Change in DR6 serum levels was used to assay the ability of DR6 to predict the response to therapy of sarcoma patients.DR6 mRNA is highly expressed in all tumor types assayed. Western blot analysis of serum DR6 protein demonstrated high reproducibility (r = 0.97). Compared to healthy donor controls, DR6 serum levels were not elevated in patients with uterine carcinosarcoma, bladder, liver, or pancreatic cancers. Serum DR6 protein levels from adult sarcoma patients were significantly elevated (p<0.001). This was most evident for patients with synovial sarcoma. Change in serum DR6 levels during therapy correlated with clinical benefit from therapy (sensitivity 75%, and positive predictive value 87%).DR6 may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.Diagnosis of sarcoma can be difficult and can lead to improper management of these cancers. DR6 serum protein may be a tool to aid in the diagnosis of some sarcomatous tumors to improve treatment planning. For patients with advanced disease, rising DR6 levels predict non-response to therapy and may expedite therapeutic decision making and reduce reliance on radiologic imaging

Search for residual prostate cancer on pT0 radical prostatectomy after positive biopsy

Reported incidence of no residual prostate cancer (i.e. pathological stage pT0) on radical prostatectomy ranges from 0.07 to 4.2%. The incidence is higher after neoadjuvant endocrine treatment. The aim of this study was to search for residual cancer on radical prostatectomy (RP) specimens when an initial sampling failed to find the cancer in patients with positive biopsy. Our database of 1,328 consecutive patients whose biopsies and RP specimen were both examined at the Polytechnic University-United Hospitals of the Marche Region between March 1995 and June 2006 was reviewed. The radical prostatectomies were grossly completely sampled and examined with the whole mount technique. We identified eight patients (i.e. 0.6%; three untreated and five hormonally treated preoperatively, i.e. 0.3 and 0.8%, respectively, of the total number of RPs included in the study) with positive biopsy and with no residual cancer in the initial routine histological examination of the RP. The RP of this group of eight was subjected to additional sectioning and evaluation of the paraffin blocks of the prostatectomy, also after block-flipping, immunostaining with an antibody against CAM 5.2, p63, PSA, and alpha-methylacyl-CoA racemase, and DNA specimen identity analysis. There were no cases with a false positive biopsy diagnosis, and cancer was not overlooked or missed in the initial routine histological examination of any of the 8 pT0 RPs. A minute focus of cancer (the diameter was always below 2.0 mm) was found on the additional sections in five. In particular, cancer was found after block-flipping in one of them. In an additional case, cancer was eventually discovered after immunostaining tissue sections for cytokeratin CAM 5.2, for p63 and PSA. In the remaining two cases (one untreated and the other hormonally treated), cancer was not found (0.15% of the 1,328 RPs included in the study); the review of the description of the macroscopic appearance of the RP and of its slides revealed that part of the peripheral zone corresponding to the site of the positive biopsy was missing, i.e. not removed from the patient at the time of the operation at least in one of the two. DNA specimen analysis confirmed the identity of the biopsy and prostatectomy in both. An extensive search for residual cancer reduces the number of pT0 RPs after a positive biopsy from 0.6 to 0.15%. It is recommended to have the needle biopsy reviewed, carefully look again at the radical prostatectomy, do deeper sections and then flip certain paraffin blocks. In addition, atypical foci should be stained for basal cell markers and often AMACR, especially in hormone-treated cases. If a block is missing part of the peripheral zone (capsular incision), this should be commented on. DNA analysis for tissue identity should be performed when the other steps have been taken without finding cancer