Genetic research in a public-private research consortium: prospects for indirect use of Elige breeding germplasm in academic research

The creation of a public¿private research partnership between plant breeding industry and academia can be beneficial for all parties involved. Academic partners benefit from the material contributions by industry and a practically relevant research focus, while industry benefits from increased insights and methodology tailored to a relevant set of data. However, plant breeding industry is highly competitive and there are obvious limits to the data and material partners are willing and able to share. This will usually include current and historic released cultivated materials, but will very often not include the elite germplasm used in-house to create new cultivars. Especially for crops where hybrid cultivars dominate the market, parental lines of hybrid cultivars are considered core assets that are never provided to outside parties. However, this limitation often does not apply to DNA or genetic fingerprints of these parental lines. We developed a procedure to take advantage of elite breeding materials for the creation of new promising research populations, through indirect selection of parents. The procedure starts with the identification of a number of traits for further study based on the presence of marker-trait associations and a priori knowledge within the participating companies about promising traits for quality improvement. Next, regression-based multi-QTL models are fitted to hybrid cultivar data to identify QTLs. Fingerprint data of parental lines of a limited number of specific hybrids are then used to predict parental phenotypes using the multi-QTL model fitted on hybrid data. The specific hybrids spanned the whole of the sensory space adequately. Finally, a choice of parental lines is made based on the QTL model predictions and new promising line combinations are identified. Breeding industry is then asked to create and provide progeny of these line combinations for further research. This approach will be illustrated with a case study in tomato

Iron chelators inhibit amyloid-beta-induced production of lipocalin 2 in cultured astrocytes

Lipocalin 2 (Lcn2) has been implicated to play a role in various neurodegenerative diseases, and normalizing its overexpression may be of therapeutic potential. Iron chelators were found to reduce Lcn2 levels in certain animal models of CNS injury. Focusing on Alzheimer's disease (AD), we found that the iron chelators deferoxamine and deferiprone inhibited amyloid-β (Aβ)-induced Lcn2 production in cultured primary astrocytes. Accordingly, Aβ-exposure increased astrocytic ferritin production, indicating the possibility that Aβ induces iron accumulation in astrocytes. This effect was not significantly modulated by Lcn2. Known neuroprotective effects of iron chelators may rely in part on normalization of Lcn2 levels

Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases

Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes many conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity and cardiovascular disease. Lipocalin 2 (Lcn2) is an inflammatory protein shown to be involved in different age-related CNS diseases, as well as risk factor conditions thereof. Lcn2 expression is increased in the periphery and the brain in different age-related CNS diseases and also their risk factor conditions. Experimental studies indicate that Lcn2 contributes to various neuropathophysiological processes of age-related CNS diseases, including exacerbated neuroinflammation, cell death and iron dysregulation, which may negatively impact cognitive function. We hypothesize that increased Lcn2 levels as a result of age-related risk factor conditions may sensitize the brain and increase the risk to develop age-related CNS diseases. In this review we first provide a comprehensive overview of the known functions of Lcn2, and its effects in the CNS. Subsequently, this review explores Lcn2 as a potential (neuro)inflammatory link between different risk factor conditions and the development of age-related CNS disorders. Altogether, evidence convincingly indicates Lcn2 as a key constituent in ageing and age-related brain diseases

Thyrotroph Embryonic Factor Regulates Light-Induced Transcription of Repair Genes in Zebrafish Embryonic Cells

Numerous responses are triggered by light in the cell. How the light signal is detected and transduced into a cellular response is still an enigma. Each zebrafish cell has the capacity to directly detect light, making this organism particularly suitable for the study of light dependent transcription. To gain insight into the light signalling mechanism we identified genes that are activated by light exposure at an early embryonic stage, when specialised light sensing organs have not yet formed. We screened over 14,900 genes using micro-array GeneChips, and identified 19 light-induced genes that function primarily in light signalling, stress response, and DNA repair. Here we reveal that PAR Response Elements are present in all promoters of the light-induced genes, and demonstrate a pivotal role for the PAR bZip transcription factor Thyrotroph embryonic factor (Tef) in regulating the majority of light-induced genes. We show that tefβ transcription is directly regulated by light while transcription of tefα is under circadian clock control at later stages of development. These data leads us to propose their involvement in light-induced UV tolerance in the zebrafish embryo

Patterns and mechanisms of early Pliocene warmth

About five to four million years ago, in the early Pliocene epoch, Earth had a warm, temperate climate. The gradual cooling that followed led to the establishment of modern temperature patterns, possibly in response to a decrease in atmospheric CO2 concentration, of the order of 100 parts per million, towards preindustrial values. Here we synthesize the available geochemical proxy records of sea surface temperature and show that, compared with that of today, the early Pliocene climate had substantially lower meridional and zonal temperature gradients but similar maximum ocean temperatures. Using an Earth system model, we show that none of the mechanisms currently proposed to explain Pliocene warmth can simultaneously reproduce all three crucial features. We suggest that a combination of several dynamical feedbacks underestimated in the models at present, such as those related to ocean mixing and cloud albedo, may have been responsible for these climate conditions

Lipocalin 2 contributes to brain iron dysregulation but does not affect cognition, plaque load, and glial activation in the J20 Alzheimer mouse model

BackgroundLipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Interestingly, both neuroprotective and neurodegenerative effects have been described for Lcn2. Increased Lcn2 levels were found in human post-mortem Alzheimer (AD) brain tissue, and in vitro studies indicated that Lcn2 aggravates amyloid--induced toxicity. However, the role of Lcn2 has not been studied in an in vivo AD model. Therefore, in the current study, the effects of Lcn2 were studied in the J20 mouse model of AD.MethodsJ20 mice and Lcn2-deficient J20 (J20xLcn2 KO) mice were compared at the behavioral and neuropathological level.ResultsJ20xLcn2 KO and J20 mice presented equally strong AD-like behavioral changes, cognitive impairment, plaque load, and glial activation. Interestingly, hippocampal iron accumulation was significantly decreased in J20xLcn2 KO mice as compared to J20 mice.ConclusionsLcn2 contributes to AD-like brain iron dysregulation, and future research should further explore the importance of Lcn2 in AD

Cohort profile: LifeLines DEEP, a prospective, general population cohort study in the northern Netherlands:Study design and baseline characteristics

Purpose There is a critical need for population-based prospective cohort studies because they follow individuals before the onset of disease, allowing for studies that can identify biomarkers and disease-modifying effects, and thereby contributing to systems epidemiology. Participants This paper describes the design and baseline characteristics of an intensively examined subpopulation of the LifeLines cohort in the Netherlands. In this unique subcohort, LifeLines DEEP, we included 1539 participants aged 18 years and older. Findings to date We collected additional blood (n=1387), exhaled air (n=1425) and faecal samples (n=1248), and elicited responses to gastrointestinal health questionnaires (n=1176) for analysis of the genome, epigenome, transcriptome, microbiome, metabolome and other biological levels. Here, we provide an overview of the different data layers in LifeLines DEEP and present baseline characteristics of the study population including food intake and quality of life. We also describe how the LifeLines DEEP cohort allows for the detailed investigation of genetic, genomic and metabolic variation for a wide range of phenotypic outcomes. Finally, we examine the determinants of gastrointestinal health, an area of particular interest to us that can be addressed by LifeLines DEEP. Future plans We have established a cohort of which multiple data levels allow for the integrative analysis of populations for translation of this information into biomarkers for disease, and which will offer new insights into disease mechanisms and prevention

Meridional shifts of the Atlantic intertropical convergence zone since the Last Glacial Maximum

The intertropical convergence zone is a near-equatorial band of intense rainfall and convection. Over the modern Atlantic Ocean, its annual average position is approximately 5° N, and it is associated with low sea surface salinity and high surface temperatures. This average position has varied since the Last Glacial Maximum, in response to changing climate boundary conditions. The nature of this variation is less clear, with suggestions that the intertropical convergence zone migrated north–south away from the colder hemisphere or that it contracted and expanded symmetrically around its present position2. Here we use paired Mg/Ca and δ18O measurements of planktonic foraminifera for a transect of ocean sediment cores to reconstruct past changes in tropical surface ocean temperature and salinity in the Atlantic Ocean over the past 25,000 years. We show that the low-salinity, high-temperature surface waters associated with the intertropical convergence zone migrated southward of their present position during the Last Glacial Maximum, when the Northern Hemisphere cooled, and northward during the warmer early Holocene, by about ±7° of latitude. Our evidence suggests that the intertropical convergence zone moved latitudinally over the ocean, rather than expanding or contracting. We conclude that the marine intertropical convergence zone has migrated significantly away from its present position owing to external climate forcing during the past 25,000 years

Neutrophil Gelatinase-Associated Lipocalin and its Receptors in Alzheimer's Disease (AD) Brain Regions:Differential Findings in AD with and without Depression

Co-existing depression worsens Alzheimer’s disease (AD) pathology. Neutrophil gelatinase-associated lipocalin (NGAL) is a newly identified (neuro)inflammatory mediator in the pathophysiologies of both AD and depression. This study aimed to compare NGAL levels in healthy controls, AD without depression (AD–D), and AD with co-existing depression (AD+D) patients. Protein levels of NGAL and its receptors, 24p3R and megalin, were assessed in nine brain regions from healthy controls (n = 19), AD–D (n = 19), and AD+D (n = 21) patients. NGAL levels in AD–D patients were significantly increased in brain regions commonly associated with AD. In the hippocampus, NGAL levels were even further increased in AD+D subjects. Unexpectedly, NGAL levels in the prefrontal cortex of AD+D patients were comparable to those in controls. Megalin levels were increased in BA11 and amygdala of AD+D patients, while no changes in 24p3R were detected. These findings indicate significant differences in neuroimmunological regulation between AD patients with and without co-existing depression. Considering its known effects, elevated NGAL levels might actively promote neuropathological processes in AD with and without depression

Workplace impact on employees:A Lifelines Corona Research Initiative on the return to work

A large proportion of the global workforce migrated home during the COVID-19 pandemic and subsequent lockdowns. It remains unclear what the exact differences between home workers and non-home workers were, especially during the pandemic when a return to work was imminent. How were building, workplace, and related facilities associated with workers’ perceptions and health? What are the lessons to be learned? Lifelines Corona Research Initiative was used to compare employees’ workplaces and related concerns, facilities, work quality, and health in a complete case analysis (N = 12,776) when return to work was imminent. Mann-Whitney U, logistic regression, and Wilcoxon matched-pairs were used for analyses. Notwithstanding small differences, the results show that home workers had less favourable scores for concerns about and facilities of on-site buildings and workplaces upon return to work, but better scores for work quality and health than non-home workers. However, additional analyses also suggest that building, workplace, and related facilities may have had the capacity to positively influence employees’ affective responses and work quality, but not always their health.</p