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Introduction: A recent meta-analysis shows that women have an increased risk of stroke, but no review has been performed to evaluate differences in drug usage after stroke. The aim of this study was to describe the differences in drug usage after a stroke between men and women, through a systematic review. Material and methods: All observational studies on sex difference in poststroke drug usage published until 20 April 2021 were selected from PubMed and Scopus. Articles were selected and assessed by two independent readers; a third reader resolved disagreements. Data extraction was performed using a standardised reading form; articles quality was assessed using the STROBE guidelines. The study is registered on PROSPERO: CRD42021250256. Results: Of the 604 identified articles, 33 were included. Most of them were published before 2015, and presented methodological limitations. These differentially affected studies with significant and non-significant results, questioning the reliability of inconsistencies. The exploration of sex differences in drug use varied between therapeutic classes (25 articles focussed on thrombolytics, 23 on antithrombotics, 13 on antihypertensive drugs, 9 on lipid-lowering drugs). After stroke women were found less likely to be prescribed antithrombotics in 48% of the corresponding articles concerning this class, and lipid-lowering drugs in 56% of the related ones. The opposite appeared for antihypertensive drugs in 31% of the concerned studies. Discussion/Conclusion: Results inconsistency regarding sex-differences in post-stroke treatment might relate to methodological limitations in non-conclusive studies. Their heterogeneity, and the lack of recent data advocates for the conduct of newer and more comprehensive research in the field as few studies simultaneously considered all involved drug classes.

The development of tree inventories and open data bases provides green space managers a better understanding of tree morphological diversity in urban areas. However, studies on tree genetic diversity in cities remain rare. The aim of our study is to provide better knowledge on tree intra- and interspecific diversity to improve tree management in urban areas. We characterized 83 individuals of Tilia species and clones in streets and parks in Paris (France) based on both morphological characters (leaves, fruits and twigs) and genetic profiling by using nuclear microsatellite markers. We found five species through morphological identification: Tilia cordata, Tilia dasystyla, Tilia ×euchlora, Tilia ×europaea and Tilia platyphyllos. Analysis of genetic profiles allowed to distinguish three genetic groups correlated to T. cordata, T. ×euchlora and T. platyphyllos. Tilia ×euchlora had the largest number of the same clonal profile (20 individuals out of 36) in Paris while no clone was found in T. platyphyllos group. In some cases, clones were planted in the same street for aesthetic purposes. This can increase disease risk and diminish resilience to climate change. Knowledge on genetic variability between and within species is essential to hedge those risks and for evaluating individual responses to environmental conditions. Our study shows that production and purchasing practices by green space managers need new insights and that tree nurseries can play a crucial role in supplying trees with diverse genetics. Green space managers can reinforce diversity where possible in some areas (development of urban forests, greening of secondary streets or sidewalks, etc.) to improve ecosystem services in urban areas.

We study whether butterfly diet predicts butterfly distribution along an urban gradient. Data come from a large scale participatory scheme involving the general public reporting butterfly abundance in their gardens (more than 6000 gardens), completed by a special survey on the relationship between butterfly species and flower species based on amateur pictures (more than 3500 pictures). Many studies show that urbanization promotes the loss of native plant species and their replacement by non-native species, so in this context we addressed the question of butterfly diet impacts provided by exotic and native plants in urban landscapes and we quantified diet diversity to identify specialist and generalist butterflies. Diet specialists had a longer proboscis and both specialization and proboscis length were positively correlated to preferences for exotic flowers. Nevertheless, diet specialist butterflies tended to avoid urban areas more strongly than diet generalists, while preference for exotic flowers was surprisingly not correlated to preferences for urban life in butterflies. All together this suggests that diet preferences do not play a strong part in determining butterfly distribution along urban gradients but also that diet specialization must be correlated to other life history traits such as dispersal ability or flexibility in habitat selection. © 2010 Elsevier B.V. All rights reserved.

Large-scale studies investigating impacts of agricultural practices on biodiversity showed that farmland bird population sizes are negatively related to national agricultural intensification indices in Europe. Here, it was tested whether the nesting strategy of farmland species predicted their abundance variations along a gradient of agricultural production intensity. Ground-nesters, which are strongly declining all over Europe, were expected to be impacted more directly by production intensity than hedge-nesters which would be instead impacted by hedge loss. To test this prediction, previously unavailable fine-scale agricultural data were used over an entire country representing highly diverse farmlands. We modelled the local abundance of 43 farmland bird species, using data from the French breeding bird survey, along an index of agricultural production intensity based on standardized crop yields and herbivore stocking rates, controlling the analysis for local climate and farmed habitat type. 68% of ground-nesters had lower relative abundance in more productive farmlands, whereas only 17% of hedge-nesters did. Nesting strategy explained an important part of bird species responses to spatial variation in agricultural production intensity. Our results suggest that although hedge loss and production intensification were parts of the strong agricultural intensification in Europe, these two phenomena are impacting different bird species.

The mdx mouse serves as animal model for Duchenne muscular dystrophy. Energy status in muscles of mdx mice is impaired and we have demonstrated recently that the energy precursor creatine exerts beneficial effects on mdx skeletal muscle cells in culture. Here we show that feeding a creatine-enriched diet to new-born mdx mice strongly reduced the first wave of muscle necrosis four weeks after birth. Necrosis of the fast-twitch muscle extensor digitorum longus was inhibited by 63+/-14% (P

Despite altered regulation of insulin signaling, Pten(+/-) heterodeficient standard diet-fed mice, approximately 4 months old, exhibit normal fasting glucose and insulin levels. We report here a stable isotope flux phenotyping study of this "silent" phenotype, in which tissue-specific insulin effects in whole-body Pten(+/-)-deficient mice were dissected in vivo. Flux phenotyping showed gain of function in Pten(+/-) mice, seen as increased peripheral glucose disposal, and compensation by a metabolic feedback mechanism that 1) decreases hepatic glucose recycling via suppression of glucokinase expression in the basal state to preserve hepatic glucose production and 2) increases hepatic responsiveness in the fasted-to-fed transition. In Pten(+/-) mice, hepatic gene expression of glucokinase was 10-fold less than wild-type (Pten(+/+)) mice in the fasted state and reached Pten(+/+) values in the fed state. Glucose-6-phosphatase expression was the same for Pten(+/-) and Pten(+/+) mice in the fasted state, and its expression for Pten(+/-) was 25% of Pten(+/+) in the fed state. This study demonstrates how intra- and interorgan flux compensations can preserve glucose homeostasis (despite a specific gene defect that accelerates glucose disposal) and how flux phenotyping can dissect these tissue-specific flux compensations in mice presenting with a "silent" phenotype.

Most lymphomas arise by transformation of germinal center (GC) B cells. TCL1, a proto-oncogene first recognized for its role in T-cell transformation, also induces GC B-cell malignancies when dysregulated in pEmu-B29-TCL1 transgenic (TCL1-tg) mice. Clonal B-cell lymphomas develop from polyclonal populations with latencies of 4 months or more, suggesting that secondary genetic events are required for full transformation. The goals of this study were to determine the GC-related effects of TCL1 dysregulation that contribute to tumor initiation and to identify companion genetic alterations in tumors that function in disease progression. We report that compared with wild-type (WT) cells, B cells from TCL1-tg mice activated in a manner resembling a T-dependent GC reaction show enhanced resistance to FAS-mediated apoptosis with CD40 stimulation, independent of a B-cell antigen receptor (BCR) rescue signal. Mitogenic stimulation of TCL1-tg B cells also resulted in increased expression of Aicda. These GC-related enhancements in survival and Aicda expression could underlie B-cell transformation. Supporting this notion, no B-cell lymphomas developed for 20 months when TCL1-tg mice were crossed onto an Oct coactivator from B cell (OCA-B)-deficient background to yield mice incapable of forming GCs. Spectral karyotype analyses showed that GC lymphomas from TCL1-tg mice exhibit recurrent chromosome translocations and trisomy 15, with corresponding MYC overexpression. We conclude that pEmu-B29-TCL1 transgenic B cells primed for transformation must experience the GC environment and, for at least some, develop genome instability to become fully malignant.

A signaling role for T cell leukemia-1 (TCL1) during T cell development or in premalignant T cell expansions and mature T cell tumors is unknown. In this study, TCL1 is shown to regulate the growth and survival of peripheral T cells but not precursor thymocytes. Proliferation is increased by TCL1-induced lowering of the TCR threshold for CD4+ and CD8+ T cell activation through both PI3K-Akt and protein kinase C-MAPK-ERK signaling pathways. This effect is submaximal as CD28 costimulation coupled to TCL1 expression additively accelerates dose-dependent T cell growth. In addition to its role in T cell proliferation, TCL1 also increases IFN-γ levels from Th1-differentiated T cells, an effect that may provide a survival advantage during premalignant T cell expansions and in clonal T cell tumors. Combined, these data indicate a role for TCL1 control of growth and effector T cell functions, paralleling features provided by TCR-CD28 costimulation. These results also provide a more detailed mechanism for TCL1-augmented signaling and help explain the delayed occurrence of mature T cell expansions and leukemias despite tumorigenic TCL1 dysregulation that begins in early thymocytes.

Cis-regions and trans-factors controlling TCL1 oncogene expression are not known. We identified the functional TCL1 promoter by mapping four transcriptional start sites 24-30 bp downstream of a TATA box. A 424-bp fragment upstream of the major start site showed robust promoter activity comparable with SV40 in both TCL1 expressing and non-expressing cell lines. Additional constructs spanning 10 kb upstream and 20 kb downstream of the start site showed only modest increases in reporter activity indicating that TCL1 expression is primarily controlled by the promoter. Ten putative Sp1-binding sites were identified within 300 bp of the start site, and three of these specifically bound Sp1. A dose-dependent transactivation of the TCL1 promoter with Sp1 addition in Sp1-negative Drosophila SL2 cells was observed, and mutation of the three identified Sp1-binding sites significantly repressed reporter gene expression in 293T cells, confirming a key role for Sp1 in activating the TCL1 promoter in vivo. In TCL1 silent cell lines, CpG DNA methylation was rarely observed at functional Sp1 sites, and methylation of a previously reported NotI restriction site was associated with dense CpG methylation rather than endogenous TCL1 gene silencing. Together, these results indicate that Sp1 mediates transactivation of the TCL1 core promoter and that TCL1 gene silencing is not dependent on mechanisms involving Sp1 and NotI site methylation.

TheTCL1protooncogene is overexpressed in many mature B cell lymphomas, especially from AIDS patients. To determine whether aberrant expression promotes B cell transformation, we generated a murine model in which aTCL1transgene was overexpressed at similar levels in both B and T cells. Strikingly, transgenic mice developed Burkitt-like lymphoma (BLL) and diffuse large B cell lymphoma (DLBCL) with attendant Bcl-6 expression and mutated JHgene segments at a very high penetrance beginning at 4 months of age. In contrast, only one mouse developed a T cell malignancy at 15 months, consistent with a longer latency for transformation of T cells byTCL1. Activation of premalignant splenic B cells by means of B cell antigen receptor (BCR) engagement resulted in significantly increased proliferation and augmented AKT-dependent signaling, including increased S6 ribosomal protein phosphorylation. Transgenic spleen cells also survived longer than wild-type spleen cells in long-term culture. Together these data demonstrate thatTCL1is a powerful oncogene that, when overexpressed in both B and T cells, predominantly yields mature B cell lymphomas.