Consequences of a short pulse of pesticide exposure for survival and reproduction of \u3ci\u3eGammarus pulex\u3c/i\u3e

The aim of the present study was to examine the effects of a short and environmentally realistic pulse exposure of different life stages of the freshwater amphipod, Gammarus pulex, to the pyrethroid insecticide, esfenvalerate. We were particularly interested in determining the extent to which detectable effects on key life-history traits persisted following cessation of a brief exposure to this pesticide. Our results indicate that environmentally realistic exposure concentrations of this widely used insecticide can have a significant effect on the survival and reproduction of Gammarus pulex. Comparison of LC50 values indicates that G. pulex has a similar sensitivity to esfenvalerate as the standard test invertebrate, Daphnia magna and is more sensitive than other common stream invertebrates. Despite 100% survival during pulses of up to 2 μg l−1, mortality increased, in some cases markedly, following transfer to clean conditions. Pulse exposure to esfenvalerate at concentrations in the range 0.1–0.6 μg l−1 for as little as 1 h can have effects on G. pulex survival, pairing behavior, and reproductive output that can still be detected at least 2 weeks following the pulse. Reproductive traits were very sensitive to esfenvalerate, and exposure to 0.05 μg l−1 for 1 h led to immediate disruption of reproducing pairs, release of eggs or offspring from the brood pouch, and substantial delays in pair formation and subsequent reproduction following transfer to clean water. The kinds of effects on reproductive behavior observed in this study could potentially impact the population dynamics of G. pulex in the field. Whether such effects occur will depend on the frequency, duration, timing, and spatial extent of pesticide exposure in freshwater stream ecosystems, about which relatively little is known. Such information is essential if effects on non-target aquatic species are to be more accurately assessed

Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPPIRI3L/iASPP

Background: Previous results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls. Methods and Results: Studying one marker at a time, we found a region spanning the gene RAI ( alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age. In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3' d1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41 - 4.23, p = 0.0008, all cases; RR = 6.29 (1.49 - 26.6), p = 0.01, cases up to 55 years of age). Conclusion: We expect the marker RAI-3' d1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer

Breast cancer in young women

Although uncommon, breast cancer in young women is worthy of special attention due to the unique and complex issues that are raised. This article reviews specific challenges associated with the care of younger breast cancer patients, which include fertility preservation, management of inherited breast cancer syndromes, maintenance of bone health, secondary prevention, and attention to psychosocial issues

Development of a ⁶⁴Cu-labeled CD4⁺ T cell targeting PET tracer:evaluation of CD4 specificity and its potential use in collagen-induced arthritis

BACKGROUND: CD4(+) T cells are central inflammatory mediators in the pathogenesis of autoimmune rheumatoid arthritis (RA), as they are one of the dominating cell types in synovial inflammation. Molecular imaging of CD4(+) T cells has potential role for early detection and monitoring of RA. Here, we developed a new radiotracer for in vivo immunoPET imaging of murine CD4(+) T cells and tested it in the collagen-induced arthritis (CIA) mouse model of human RA. RESULTS: The tracer, [(64)Cu]Cu-NOTA-CD4-F(ab)’2 ([(64)Cu]Cu-NOTA-CD4), was generated from F(ab)’2 fragments of R-anti-mouse CD4 antibodies conjugated to the 2-S-(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) chelator and radiolabeled with copper-64. Accumulation of the tracer and isotype control was evaluated in the CIA model and mice receiving whole-body irradiation (WBI) (5 Gy). The potential of [(64)Cu]Cu-NOTA-CD4 for response assessment was evaluated in CIA induced mice treated with dexamethasone (DXM). Imaging data were compared with flow cytometry and immunohistochemistry (IHC) of inflammatory cells including CD4(+) T cells. [(64)Cu]Cu-NOTA-CD4 showed increased accumulation in T cell-rich tissues compared with isotype control (p < 0.0001). In addition, reduced accumulation of [(64)Cu]Cu-NOTA-CD4 was observed in T cell-depleted tissue (p < 0.0001). Flow cytometry and IHC confirmed the increased infiltration of CD4(+) T cells in CIA mice. CONCLUSIONS: We developed and evaluated a new radiotracer, [(64)Cu]Cu-NOTA-CD4, for immunoPET imaging of murine CD4(+) T cells. [(64)Cu]Cu-NOTA-CD4 was successfully synthesized by F(ab)’2 fragments of R-anti-mouse CD4 antibodies conjugated to a chelator and radiolabeled with copper-64. We found that our novel CD4 PET tracer can be used for noninvasive visualization of murine CD4(+) T cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-022-00934-7