Early development and tuning of a global coupled cloud resolving model, and its fast response to increasing CO2

Since the dawn of functioning numerical dynamical atmosphere- and ocean models, their resolution has steadily increased, fed by an exponential growth in computational capabilities. However, because resolution of models is at all times limited by computational power a number of mostly small-scale or micro-scale processes have to be parameterised. Particularly those of atmospheric moist convection and ocean eddies are problematic when scientists seek to interpret output from model experiments. Here we present the first coupled ocean-atmosphere model experiments with sufficient resolution to dispose of moist convection and ocean eddy parameterisations. We describe the early development and discuss the challenges associated with conducting the simulations with a focus on tuning the global mean radiation balance in order to limit drifts. A four-month experiment with quadrupled CO2 is then compared with a ten-member ensemble of low-resolution simulations using MPI-ESM1.2-LR. We find broad similarities of the response, albeit with a more diversified spatial pattern with both stronger and weaker regional warming, as well as a sharpening of precipitation in the inter tropical convergence zone. These early results demonstrate that it is already now possible to learn from such coupled model experiments, even if short by nature

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

One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency.

BACKGROUND: Inborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans. OBJECTIVE: We sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency. METHODS: We assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells. RESULTS: SOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients. CONCLUSIONS: SOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients

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