N-Terminal Domain of Nuclear IL-1α Shows Structural Similarity to the C-Terminal Domain of Snf1 and Binds to the HAT/Core Module of the SAGA Complex

Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly.     

Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

The voltage-gated Na (+) channels (VGSC) are complex membrane proteins responsible for generation and propagation of the electrical signals through the brain, the skeletal muscle and the heart. The levels of sodium channels affect behavior and physical activity. This is illustrated by the maleless mutant allele (mle (napts)) in Drosophila, where the decreased levels of voltage-gated Na(+) channels cause temperature-sensitive paralysis. Here, we report that mle (napts) mutant flies exhibit developmental lethality, decreased fecundity and increased neurodegeneration. The negative effect of decreased levels of Na(+) channels on development and ts-paralysis was more pronounced at 18 and 29°C than at 25°C, suggesting particular sensitivity of the mle (napts) flies to temperatures above and below normal environmental conditions. Similarly, longevity of mle (napts) flies was unexpectedly short at 18 and 29°C compared with flies heterozygous for the mle (napts) mutation. Developmental lethality and neurodegeneration of mle (napts) flies was partially rescued by increasing the dosage of para, confirming a vital role of Na(+) channels in development, longevity and neurodegeneration of flies and their adaptation to temperatures.     

Senescence-induced ectopic expression of the A. tumefaciens ipt gene in wheat delays leaf senescence, increases cytokinin content, nitrate influx, and nitrate reductase activity, but does not affect grain yield

The manipulation of cytokinin levels by senescence-regulated expression of the Agrobacterium tumefaciens ipt gene through its control by the Arabidopsis SAG12 (senescence-associated gene 12) promoter is an efficient tool for the prolongation of leaf photosynthetic activity which potentially can affect plant productivity. In the present study, the efficiency of this approach was tested on wheat (Triticum aestivum L.)-a monocarpic plant characterized by a fast switch from vegetative to reproductive growth, and rapid translocation of metabolites from leaves to developing grains after anthesis. When compared with the wild-type (WT) control plants, the SAG12::ipt wheat plants exhibited delayed chlorophyll degradation only when grown under limited nitrogen (N) supply. Ten days after anthesis the content of chlorophyll and bioactive cytokinins of the first (flag) leaf of the transgenic plants was 32% and 65% higher, respectively, than that of the control. There was a progressive increase in nitrate influx and nitrate reductase activity. However, the SAG12::ipt and the WT plants did not show differences in yield-related parameters including number of grains and grain weight. These results suggest that the delay of leaf senescence in wheat also delays the translocation of metabolites from leaves to developing grains, as indicated by higher accumulation of ((15)N-labelled) N in spikes of control compared with transgenic plants prior to anthesis. This delay interferes with the wheat reproductive strategy that is based on a fast programmed translocation of metabolites from the senescing leaves to the reproductive sinks shortly after anthesis.     

Pleiotropic effects of the yeast Sal1 and Aac2 carriers on mitochondrial function via an activity distinct from adenine nucleotide transport

In Saccharomyces cerevisiae, SAL1 encodes a Ca2+ -binding mitochondrial carrier. Disruption of SAL1 is synthetically lethal with the loss of a specific function associated with the Aac2 isoform of the ATP/ADP translocase. This novel activity of Aac2 is defined as the V function (for Viability of aac2 sal1 double mutant), which is independent of the ATP/ADP exchange activity required for respiratory growth (the R function). We found that co-inactivation of SAL1 and AAC2 leads to defects in mitochondrial translation and mitochondrial DNA (mtDNA) maintenance. Additionally, sal1Delta exacerbates the respiratory deficiency and mtDNA instability of ggc1Delta, shy1Delta and mtg1Delta mutants, which are known to reduce mitochondrial protein synthesis or protein complex assembly. The V function is complemented by the human Short Ca2+ -binding Mitochondrial Carrier (SCaMC) protein, SCaMC-2, a putative ATP-Mg/Pi exchangers on the inner membrane. However, mitochondria lacking both Sal1p and Aac2p are not depleted of adenine nucleotides. The Aac2R252I and Aac2R253I variants mutated at the R252-254 triplet critical for nucleotide transport retain the V function. Likewise, Sal1p remains functionally active when the R479I and R481I mutations were introduced into the structurally equivalent R479-T480-R481 motif. Finally, we found that the naturally occurring V-R+ Aac1 isoform of adenine nucleotide translocase partially gains the V function at the expense of the R function by introducing the mutations P89L and A96 V. Thus, our data support the view that the V function is independent of adenine nucleotide transport associated with Sal1p and Aac2p and this evolutionarily conserved activity affects multiple processes in mitochondria.     

Facies variability in Lower Liassic carbonate successions of the Western Dinarides (Croatia)

Summary In the Western Dinarides the Lower Liassic carbonates are underlain by Upper Triassic “Hauptdolomit”, whereas the first appearance of the foraminiferOrbitopsella praecursor (Gümbel) marks the beginning of the Middle Liassic. Their composition, observed at several localities in Western Croatia, shows a correlation of sedimentation events, which took place during Early Liassic on the Adriatic-Dinaridic carbonate platform. Facies variability is interpreted as result of autocyclic sedimentary processes on which the carbonate platform reacted by periodical oscillations of sea-bottom near the fair-weather wavebase. As a consequence, the Lower Liassic carbonate successions in the Dinarides is characterized by stacking of two main types of coarsening-upward parasequences: (1) the basal part of the Lower Liassic succession is represented by parasequences composed of mudstones or pelletal-bioclastic wackestones as their lower members, and peloidal-bioclastic wackestone/packstones to grain-stones as their upper members; and (2) the upper part of the Lower Liassic succession with parasequences consisting of mudstones or pelletal-bioclastic wackestones overlain by ooid grainstones. Judging from the composition of parasequences and thickness relations of their members, the first type is interpreted to comprise late transgressive system tract (ITST) and/or early highstand system tract (eHST), while the second type corresponds to a late highstand system tract (1HST) and/or early lowstand system tract (eLST) of a third-order sequence.