פרסומים

The use of gem-diborylalkenes as radical-reactive groups is explored for the first time. These reactions provide an efficient and general method for the photochemical conversion of gem-diborylalkenes to rapidly access 1,1-bisborylalkanes. This method exploits a novel photoredox decarboxylative radical addition to gem-diborylalkenes to afford α-gem-diboryl carbon-centered radicals, which benefit from additional stability by virtue of an interaction with the empty p-orbitals on borons. The reaction offers a highly modular and regioselective approach to γ-amino gem-diborylalkanes. Furthermore, EPR spectroscopy and DFT calculations have provided insight into the radical mechanism underlying the photochemistry reaction and the stability of the bis-metalated radicals, respectively. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

The use of gem-diborylalkenes as light-reactive groups is explored for the first time. These reactions provide an efficient and general method for the photochemical conversion of gem-diborylalkenes to rapidly access 1,1-bisborylalkanes. This method exploits a novel photoredox decarboxylative radical addition to gem-diborylalkenes to afford α-gemdiboryl carbon-centered radicals, which benefit from additional stability by virtue of an interaction with the empty p-orbitals on borons. The reaction offers a highly modular and regioselective approach to γ-amino gem-diborylalkanes. Furthermore, EPR spectroscopy and DFT calculations have provided insight into the radical mechanism underlying the photochemistry reaction.

Cyanobacteria living in the harsh environment of the desert have to protect themselves against high light intensity and prevent photodamage. These cyanobacteria are in a desiccated state during the largest part of the day when both temperature and light intensity are high. In the desiccated state, their photosynthetic activity is stopped, whereas upon rehydration the ability to perform photosynthesis is regained. Earlier reports indicate that light-induced excitations in Leptolyngbya ohadii are heavily quenched in the desiccated state, because of a loss of structural order of the light-harvesting phycobilisome structures (Bar Eyal et al. in Proc Natl Acad Sci 114:9481, 2017) and via the stably oxidized primary electron donor in photosystem I, namely P700⁺ (Bar Eyal et al. in Biochim Biophys Acta Bioenergy 1847:1267–1273, 2015). In this study, we use picosecond fluorescence experiments to demonstrate that a third protection mechanism exists, in which the core of photosystem II is quenched independently.

We assessed the potential of phenolic compounds from Pistacia lentiscus (lentisk) to enhance production of milk constituents in bovine mammary epithelial cells (MEC). MEC were exposed to 0 (control), 1 or 10 ppm of polyphenols from lentisk ethanolic extract (PLEE) for 24 h. PLEE were absorbed by the MEC plasma membrane, but also penetrated the cell to accumulate in and around the nucleus. PLEE increased triglyceride content in the cell and its secretion to the medium, and significantly increased intracellular lipid droplet diameter. Compared to control, PLEE increased dose-dependently the lactose synthesis, secretion of whey proteins, and contents of casein. To evaluate mitochondrial activity under pro-oxidant load, MEC were preincubated with PLEE and exposed for 2 h to H2O2. Exposure to H2O2 increased the proportion of cells with impaired mitochondrial membrane potential twofold in controls, but not in PLEE-pre-treated cells. Accordingly, proton leakage was markedly decreased by PLEE, and coupling efficiency between the respiratory chain and ATP production was significantly enhanced. Thus, lentisk polyphenols divert energy to production of milk fat, protein and lactose, with less energy directed to cellular damage control; alternatively, PLEE enables MEC to maintain energy and oxidative status under extreme metabolic rate required for milk production and secretion, and reduces the limitation on energy required to support production.

Plant domestication is often discussed as a form of mutualism between humans and crop plants. Ethnographies provide records of a multitude of adaptive strategies employed by human societies with varying degrees of reliance on manipulation of wild plant resources. These manipulations have included vegetation clearance, controlled burning, pruning, coppicing, tilling, sowing and more. Such activities can be viewed as cultivation of wild plants (known as “pre-domestication cultivation” in the Near Eastern research milieu, or in a somewhat different framework as “low level food production”), often considered a necessary step leading to domestication. Since cultivated fields are constructed niches, Niche Construction Theory (NCT) has recently been recruited to provide a theoretical evolutionary framework for explaining plant domestication. This review on plant domestication in the Near East discusses elements that we consider intimately related to the abovementioned trajectories of thought: the concept of “pre-domestication cultivation”; the view that domesticated plants arose via evolutionary mutualism; and the conceptualization of plant domestication in terms of NCT. We review and discuss the logic of these approaches, their biological, cultural and archaeological foundations; and highlight their association with the old “dump heap” scenario. We argue that based on the biology of the Near Eastern crop plants and the available archaeological evidence, these approached and respective arguments are inadequate. Rather, we contend that the biological idiosyncrasies of the Near Eastern founder crops depict a picture of a knowledge-based and conscious domestication that emanated from the newly emerging Neolithic world view and Humans-World relationships.

The central dogma in biology defines the flow of genetic information from DNA to RNA to protein. Accordingly, RNA molecules generally accurately follow the sequences of the genes from which they are transcribed. This rule is transgressed by RNA editing, which creates RNA products that differ from their DNA templates. Analyses of the RNA landscapes of terrestrial plants have indicated that RNA editing (in the form of C-U base transitions) is highly prevalent within organelles (that is, mitochondria and chloroplasts). Numerous C→U conversions (and in some plants also U→C) alter the coding sequences of many of the organellar transcripts and can also produce translatable mRNAs by creating AUG start sites or eliminating premature stop codons, or affect the RNA structure, influence splicing and alter the stability of RNAs. RNA-binding proteins are at the heart of post-transcriptional RNA expression. The C-to-U RNA editing process in plant mitochondria involves numerous nuclear-encoded factors, many of which have been identified as pentatricopeptide repeat (PPR) proteins that target editing sites in a sequence-specific manner. In this review we report on major discoveries on RNA editing in plant organelles, since it was first documented 30 years ago. © 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd

Herein, we describe the synthesis, characterization, and biological properties of Pt(IV) derivatives of cisplatin with estramustine at the first axial position, which is known to disrupt the microtubule assembly and act as an androgen antagonist, and varying the second axial position using an innocent ligand (acetate or hydroxyl) to prepare dual-action and triple-action prodrugs with known inhibitors of histone deacetylase, cyclooxygenase, and pyruvate dehydrogenase kinase. We demonstrate superior antiproliferative activity at submicromolar concentrations of the prodrugs against a panel of cancer cell lines, particularly against prostate cancer cell lines. The results obtained in this study exemplify the complex mode of action of "multiaction"Pt(IV) prodrugs. Interestingly, changing the second axial ligand in the Pt-estramustine complex has a significant effect on the mode of action, suggesting that all three components of the Pt(IV) prodrugs (platinum moiety and axial ligands) contribute to the killing of cells and not just one dominant component.

The Last Glacial Maximum (LGM,  21,000 years ago) has been a major focus for evaluating how well state-of-the-art climate models simulate climate changes as large as those expected in the future using paleoclimate reconstructions. A new generation of climate models have been used to generate LGM simulations as part of the Palaeoclimate Modelling Intercomparison Project (PMIP) contributionto CMIP6. Here we provide a preliminary analysis and evaluation of the results of these LGM experiments and compare them with the previous generation of simulations (PMIP3-CMIP5). We show that the PMIP4-CMIP6 are globally less cold and less dry than the PMIP3-CMIP5 simulations, most probably because of the use of a more realistic specification of the northern hemisphere ice sheets in the latest simulations although changes in model configuration may also contribute to this. There are important differences in both atmospheric and ocean circulation between the two sets of experiments, with the northern and southern jet streams being more poleward and the changes in the Atlantic Meridional Overturning Circulation being less pronounced in the PMIP4-CMIP6 simulations than in the PMIP3-CMIP5 simulations. Changes in simulated precipitation patterns are influenced by both temperature and circulation changes. Differences in simulated climate between individual models remain large so, although there are differences in the average behaviour across the two ensembles, the new simulation results are not fundamentally different from the PMIP3-CMIP5 results. Evaluation of large-scale climate features, such as land-sea contrast and polar amplification, confirms that the models capture these well and within the uncertainty of the palaeoclimate reconstructions. Nevertheless, regional climate changes are less well simulated: the models underestimate extratropical cooling, particularly in winter, and precipitation changes. The spatial patterns of increased precipitation associated with changes in the jet streams are also poorly captured. However, changes in the tropics are more realistic, particularly the changes in tropical temperatures over the oceans. Although these results are preliminary in nature, because of the limited number of LGM simulations currently available, they nevertheless point to the utility of using paleoclimate simulations to understand the mechanisms of climate change and evaluate model performance.

Several genes implicated in autism spectrum disorder (ASD) are chromatin regulators, including POGZ. The cellular and molecular mechanisms leading to ASD impaired social and cognitive behavior are unclear. Animal models are crucial for studying the effects of mutations on brain function and behavior as well as unveiling the underlying mechanisms. Here, we generate a brain specific conditional knockout mouse model deficient for Pogz, an ASD risk gene. We demonstrate that Pogz deficient mice show microcephaly, growth impairment, increased sociability, learning and motor deficits, mimicking several of the human symptoms. At the molecular level, luciferase reporter assay indicates that POGZ is a negative regulator of transcription. In accordance, in Pogz deficient mice we find a significant upregulation of gene expression, most notably in the cerebellum. Gene set enrichment analysis revealed that the transcriptional changes encompass genes and pathways disrupted in ASD, including neurogenesis and synaptic processes, underlying the observed behavioral phenotype in mice. Physiologically, Pogz deficiency is associated with a reduction in the firing frequency of simple and complex spikes and an increase in amplitude of the inhibitory synaptic input in cerebellar Purkinje cells. Our findings support a mechanism linking heterochromatin dysregulation to cerebellar circuit dysfunction and behavioral abnormalities in ASD.

This article seeks to improve our understanding of what policy over- and under-design mean; what are the consequences of these suboptimal designs; and how politics matters to these designs. Based on the review of the literature and a variety of examples that focus on the role of information quality in policy design, and drawing on two phenomena from the field of epidemiology (namely, over-adjustment and unnecessary adjustment), the article enhances the definitional clarity of the terms under investigation and allows us to address the difficulty in reconciling technical problem solving with politics. The article proposes new definitional statements of proportionate and disproportionate policy designs that vary according to the extent to which the main design properties are adjusted to low-quality information. It also explores distinct variations in a few policy characteristics resulting from over- and under-design. The policy characteristics examined here include economic efficiency, p