Genetic dissection of haploid male fertility in maize (Zea mays L.)

Haploid genome doubling is a key limiting step of haploid breeding in maize. Spontaneous restoration of haploid male fertility (HMF) provides a more promising method than the artificial doubling process. To reveal the genetic basis of HMF, haploids were obtained from the offspring of 285 F2:3 families, derived from the cross Zheng58 × K22. The F2:3 families were used as the female donor and Yu high inducer No. 1 (YHI‐1) as the male inducer line. The rates of HMF from each family line were evaluated at two field sites over two planting seasons. HMF displayed incomplete dominance. Transgressive segregation of haploids from F2:3 families was observed relative to haploids derived from the two parents of the mapping population. A total of nine quantitative trait loci (QTL) were detected, which were distributed on chromosomes 1, 3, 4, 7 and 8. Three major QTL, qHMF3b, qHMF7a and qHMF7b were detected in both locations, respectively. These QTL could be useful to predict the ability of spontaneous haploid genome doubling, and to accelerate the haploid breeding process by introgression or aggregation of those QTL

DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex

Background: Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer's disease (AD).However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise.Here, we report the first EWAS based on sorted neuronal and non-neuronal (mostly glia) nuclei from postmortem human brain tissues. Results: We show that cell sorting strongly enhances the robust detection of disease-related DNA methylation changes even in a relatively small cohort.We identify numerous genes with eell-type-specific methylation signatures and document differential methylation dynamics associated with aging specifically in neurons such as CLU, SYNJ2 and NCOR2 or in glia RAI1,CXXC5 and INPP5A.Further, we found neuron or glia-specific associations with AD Braak stage progression at genes such as MCF2L,ANK1, MAP2, LRRC8B, STK32C and S100B.A comparison of our study with previous tissue-based EWAS validates multiple AD-associated DNA methylation signals and additionally specifies their origin to neuron, e.g., HOXA3 or glia (ANK1). In a meta-analysis, we reveal two novel previously unrecognized methylation changes at the key AD risk genes APP and ADAM17. Conclusions: Our data highlight the complex interplay between disease, age and cell-type-specific methylation changes in AD risk genes thus offering new perspectives for the validation and interpretation of large EWAS results

Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Despite our substantial understanding of molecular mechanisms and gene mutations involved in cancer, the technical approaches for diagnosis and prognosis of cancer are limited. In routine clinical diagnosis of cancer, the procedure is very basic: nuclear morphology is used as a common assessment of the degree of malignancy, and hence acts as a prognostic and predictive indicator of the disease. Furthermore, though the atypical nuclear morphology of cancer cells is believed to be a consequence of oncogenic signaling, the molecular basis remains unclear. Another common characteristic of human cancer is aneuploidy, but the causes and its role in carcinogenesis are not well established.</p> <p>Methods</p> <p>We investigated the expression of the nuclear envelope proteins lamin A/C in ovarian cancer by immunohistochemistry and studied the consequence of lamin A/C suppression using siRNA in primary human ovarian surface epithelial cells in culture. We used immunofluorescence microscopy to analyze nuclear morphology, flow cytometry to analyze cellular DNA content, and fluorescence <it>in situ </it>hybridization to examine cell ploidy of the lamin A/C-suppressed cells.</p> <p>Results</p> <p>We found that nuclear lamina proteins lamin A/C are often absent (47%) in ovarian cancer cells and tissues. Even in lamin A/C-positive ovarian cancer, the expression is heterogeneous within the population of tumor cells. In most cancer cell lines, a significant fraction of the lamin A/C-negative population was observed to intermix with the lamin A/C-positive cells. Down regulation of lamin A/C in non-cancerous primary ovarian surface epithelial cells led to morphological deformation and development of aneuploidy. The aneuploid cells became growth retarded due to a p53-dependent induction of the cell cycle inhibitor p21.</p> <p>Conclusions</p> <p>We conclude that the loss of nuclear envelope structural proteins, such as lamin A/C, may underlie two of the hallmarks of cancer - aberrations in nuclear morphology and aneuploidy.</p

The climate of a retrograde rotating Earth

To enhance understanding of Earth's climate, numerical experiments are performed contrasting a retrograde and prograde rotating Earth using the Max Planck Institute Earth system model. The experiments show that the sense of rotation has relatively little impact on the globally and zonally averaged energy budgets but leads to large shifts in continental climates, patterns of precipitation, and regions of deep water formation.Changes in the zonal asymmetries of the continental climates are expected given ideas developed more than a hundred years ago. Unexpected was, however, the switch in the character of the European–African climate with that of the Americas, with a drying of the former and a greening of the latter. Also unexpected was a shift in the storm track activity from the oceans to the land in the Northern Hemisphere. The different patterns of storms and changes in the direction of the trades influence fresh water transport, which may underpin the change of the role of the North Atlantic and the Pacific in terms of deep water formation, overturning and northward oceanic heat transport. These changes greatly influence northern hemispheric climate and atmospheric heat transport by eddies in ways that appear energetically consistent with a southward shift of the zonally and annually averaged tropical rain bands. Differences between the zonally averaged energy budget and the rain band shifts leave the door open, however, for an important role for stationary eddies in determining the position of tropical rains. Changes in ocean biogeochemistry largely follow shifts in ocean circulation, but the emergence of a super oxygen minimum zone in the Indian Ocean is not expected. The upwelling of phosphate-enriched and nitrate-depleted water provokes a dominance of cyanobacteria over bulk phytoplankton over vast areas – a phenomenon not observed in the prograde model.What would the climate of Earth look like if it would rotate in the reversed (retrograde) direction? Which of the characteristic climate patterns in the ocean, atmosphere, or land that are observed in a present-day climate are the result of the direction of Earth's rotation? Is, for example, the structure of the oceanic meridional overturning circulation (MOC) a consequence of the interplay of basin location and rotation direction? In experiments with the Max Planck Institute Earth system model (MPI-ESM), we investigate the effects of a retrograde rotation in all aspects of the climate system.The expected consequences of a retrograde rotation are reversals of the zonal wind and ocean circulation patterns. These changes are associated with major shifts in the temperature and precipitation patterns. For example, the temperature gradient between Europe and eastern Siberia is reversed, and the Sahara greens, while large parts of the Americas become deserts. Interestingly, the Intertropical Convergence Zone (ITCZ) shifts southward and the modeled double ITCZ in the Pacific changes to a single ITCZ, a result of zonal asymmetries in the structure of the tropical circulation.One of the most prominent non-trivial effects of a retrograde rotation is a collapse of the Atlantic MOC, while a strong overturning cell emerges in the Pacific. This clearly shows that the position of the MOC is not controlled by the sizes of the basins or by mountain chains splitting the continents in unequal runoff basins but by the location of the basins relative to the dominant wind directions. As a consequence of the changes in the ocean circulation, a super oxygen minimum zone develops in the Indian Ocean leading to upwelling of phosphate-enriched and nitrate-depleted water. These conditions provoke a dominance of cyanobacteria over bulk phytoplankton over vast areas, a phenomenon not observed in the prograde model.</p