The role of acyl carrier protein in strawberry fruit ripening

Strawberry (Fragaria ananassa) is an economically important soft fruit that is highly valued as a fresh product and flavouring. During ripening, strawberry fruits undergo a number of physiological changes affecting colour, texture and flavour. An understanding of these changes at the biochemical and molecular level will be important in developing strategies for enhancing the quality attributes of this fruit. A cDNA encoding a ripening- enhanced acyl carrier protein (RE-ACP) was previously isolated from strawberry fruit. AC? is an essential component of fatty acid synthesis in both plants and animals. The aims of this thesis were to isolate and characterise this and other members of the ACP multigene family expressed in strawberry fruit. Six closely related putative AC? cDNA isoforms were identified from strawberry. Two of these were obtained by screening a cDNA library from ripe fruit and three were obtained by a technique known as candidate fragment length polymorphism (CFLP) that utilised ACP gene-specific primers for AFLP-cDNA display. Northern analysis was not able to differentiate their expression but ACP was highly up-regulated in ripening fruit whereas low levels of expression were detected in other strawberry tissues, including achenes (seeds), expanding leaves and flowers. The RE-ACP was over-expressed in E. coli and the recombinant protein partially purified. The over-expressed protein had a M(_r) of 20kDa on SDS-PAGE and appeared to form a dimer. A genomic library was constructed from F. ananassa from which two different genomic clones closely related to RE-ACP were obtained. Promoter analysis indicated the presence of regulatory elements. The characterization of putative ACP cDNA and genomic clones, including the 5' upstream regions, is described and their possible role in strawberry fruit is discussed. Key words: Strawberry, fruit, ripening, gene expression, genomic, cDNA, fatty acid, acyl carrier protein, aroma, promoter

Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature

This article is available open access through the publisher’s website at the link below. Copyright @ 2014 The American Society of Gene & Cell Therapy.Lentiviral vectors are widely used in basic research and clinical applications for gene transfer and long-term expression; however, safety issues have not yet been completely resolved. In this study, we characterized hepatocarcinomas that developed in mice 1 year after in utero administration of a feline-derived lentiviral vector. Mapped viral integration sites differed among tumors and did not coincide with the regions of chromosomal aberrations. Furthermore, gene expression profiling revealed that no known cancer-associated genes were deregulated in the vicinity of viral integrations. Nevertheless, five of the six tumors exhibited highly significant upregulation of E2F target genes, of which a majority are associated with oncogenesis, DNA damage response, and chromosomal instability. We further show in vivo and in vitro that E2F activation occurs early on following transduction of both fetal mice and cultured human hepatocytes. On the basis of the similarities in E2F target gene expression patterns among tumors and the lack of evidence implicating insertional mutagenesis, we propose that transduction of fetal mice with a feline lentiviral vector induces E2F-mediated major cellular processes that drive hepatocytes toward uncontrolled proliferation culminating in tumorigenesis.ISF, DFG, the Kamea Scientific Foundation, the European Research Council, the Lillyan & Alfy Nathan, Barbara Fox Miller, and Wolfson Foundations

Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life

ImportanceThe utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested.ObjectivesTo assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group.Data Source and Study SelectionLongitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece).Data Extraction and SynthesisParticipants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines.Main Outcomes and MeasuresThe key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group.ResultsThe analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses.Conclusions and RelevanceThis individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls

Electric dipole moments and the search for new physics

Static electric dipole moments of nondegenerate systems probe mass scales for physics beyond the Standard Model well beyond those reached directly at high energy colliders. Discrimination between different physics models, however, requires complementary searches in atomic-molecular-and-optical, nuclear and particle physics. In this report, we discuss the current status and prospects in the near future for a compelling suite of such experiments, along with developments needed in the encompassing theoretical framework.Comment: Contribution to Snowmass 2021; updated with community edits and endorsement

Passivation and Stabilization of Aluminum Nanoparticles for Energetic Materials

In aircraft applications, fuel is used not only as a propellant but also as a coolant and improving both the thermal conductivity and combustion enthalpy of the fuel is beneficial in these applications. These properties can be enhanced by dispersing aluminum nanoparticles into the fuel; however, the nanoparticles require stabilization from agglomeration and passivation from oxidation in order for these benefits to be realized in aircraft applications. To provide this passivation and stabilization, aluminum nanoparticles were encapsulated with a coating by the plasma enhanced chemical vapor deposition (PE-CVD) method from toluene precursors. The thermal conductivity, combustion and ignition properties, and stability of the nanoparticles dispersed in RP-2 fuel were subsequently evaluated. In addition, the effect of dispersing aluminum nanoparticles in RP-2 fuel on the erosion rate of fuel nozzles was evaluated. The dispersion of PE-CVD coated aluminum nanoparticles at a concentration of 3.0% by volume exhibited a 17.7% and 0.9% increase in thermal conductivity and volumetric enthalpy of combustion, respectively, compared to the baseline RP-2 fuel. Additionally, particle size analysis (PSA) of the PE-CVD coated aluminum nanofuel exhibited retention of particle size over a five-month storage period and erosion testing of a 1 mm stainless steel nozzle exhibited a negligible 1% change in discharge coefficient after 100 hours of testing

Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1

Familial hypercholesterolemia is an autosomal dominant disorder with a gene-dosage effect that is usually caused by mutations in the LDL receptor gene that disrupt normal clearance of LDL. In the homozygous form, it results in a distinctive clinical phenotype, characterized by inherited hypercholesterolemia, cholesterol deposition in tendons, and severe premature coronary disease. We described previously two families with autosomal recessive hypercholesterolemia that is not due to mutations in the LDL receptor gene but is characterized by defective LDL receptor–dependent internalization and degradation of LDL by transformed lymphocytes from the patients. We mapped the defective gene to chromosome 1p36 and now show that the disorder in these and a third English family is due to novel mutations in ARH1, a newly identified gene encoding an adaptor-like protein. Cultured skin fibroblasts from affected individuals exhibit normal LDL receptor activity, but their monocyte-derived macrophages are similar to transformed lymphocytes, being unable to internalize and degrade LDL. Retroviral expression of normal human ARH1 restores LDL receptor internalization in transformed lymphocytes from an affected individual, as demonstrated by uptake and degradation of (125)I-labeled LDL and confocal microscopy of cells labeled with anti–LDL-receptor Ab

Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice

Gene therapy by use of integrating vectors carrying therapeutic transgene sequences offers the potential for a permanent cure of genetic diseases by stable vector insertion into the patients' chromosomes. However, three cases of T cell lymphoproliferative disease have been identified almost 3 years after retrovirus gene therapy for X-linked severe combined immune deficiency. In two of these cases vector insertion into the LMO2 locus was implicated in leukemogenesis, demonstrating that a more profound understanding is required of the genetic and molecular effects imposed on the host by vector integration or transgene expression. In vivo models to test for retro- and lentiviral vector safety prior to clinical application are therefore needed. Here we present a high incidence of lentiviral vector-associated tumorigenesis following in utero and neonatal gene transfer in mice. This system may provide a highly sensitive model to investigate integrating vector safety prior to clinical application