Regulatory interrelations between GABA and polyamines. I. Brain GABA levels and polyamine metabolism

Elevation of brain GABA levels by GABA-T inhibition is accompanied by a decrease ofS-adenosylmethionine decarboxylase activity. This is followed by an increase of ornithine decarboxylase activity and a severalfold increase of brain putrescine levels. Spermidine and spermine levels are not significantly affected under these conditions. These unexpected findings support a regulatory interaction between GABA and polyamine metabolism.     

cell clones and pattern formation: Studies onsevenless,a mutant ofDrosophila melanogaster

Summary sev ^LY3,the only existing allele at thesev locus (1–33,2±0,2), behaves as strongly hypomorph or even as amorph. Ommatidia in asev compound eye have only seven receptor cells, the position of the R7 pattern element being vacant. Various criteria showing that the missing cell is R7 have been verified. These include (i) anatomical characteristics ofsev ommatidia; (ii) behaviour of central R cells insev rdgB double mutants; (iii) medullary projection of central R cell axons; and (iv) mitotic pattern ofsev imaginal discs. The analysis of morphogeneticsev-sev ⁺ mosaics has shown thatsev is expressed autonomously by R7 cells, indicating that thesev phenotype is not due to asev genotype of ommatidial pattern elements other than R7. The study of third instarsev imaginal discs has not brought any direct evidence for death of clustered presumptive R7 cells; however, clonal analysis of the developingsev compound eye has given evidence of developmental parameters comparable to those ofsev ⁺, therefore favouring the hypothesis that R7 cells die insev mutants. On the other hand,sev ⁺ seems to be required for the determination of the R7 cells, since thesev phenotype cannot be uncovered during the last mitoses of heterozygous mutant cells.     

The biological role of octopine in the squid,Loligo vulgaris (Lamarck)

Summary The enzymatic activities of glyceraldehyde-3-phosphate dehydrogenase, octopine dehydrogenase and lactate dehydrogenase were determined fromLoligo vulgaris. Octopine dehydrogenase displays the highest activity yet recorded for this enzyme, exceeding glyceraldehyde-3-phosphate dehydrogenase sixfold and lactate dehydrogenase 365-fold (Table 1).During jet propulsion swimming octopine accumulates instead of lactate (Table 2), while phosphoarginine, the phosphagen of the squid, is depleted (Table 3).The formation of octopine is discussed in relation to anaerobic metabolism which might occur during burst activity in cephalopods.The following abbreviations are used AK arginine kinase (2.7.3.3) - GAPDH glyceraldehyde-3-phosphate dehydrogenase (1.2.1.12) - LDH L-lactate - NAD oxidoreductase (1.1.1.27) - ODH octopine - NAD oxidoreductase (1.5.1.11) - DTT dithiothreitol - dw dry weight (about 20% of the fresh weight) This investigation was generously supported by The Deutsche Forschungsgemeinschaft grant No.: (Ze 40/13)     

Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction

Pre-clinical studies have indicated that mitoprotective drugs may add cardioprotection beyond rapid revascularization, antiplatelet therapy and risk modification. We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI-9803, MTP131 and TRO 40303. Whereas cyclosporine may reduce infarct size in patients undergoing primary angioplasty as evaluated by release of myocardial ischaemic biomarkers and infarct size imaging, the other drugs were not capable of demonstrating this effect in the clinical setting. The absent effect leaves the role of the mitochondrial permeability transition pore for reperfusion injury in humans unanswered and indicates that targeting one single mechanism to provide mitoprotection may not be efficient. Moreover, the lack of effect may relate to favourable outcome with current optimal therapy, but conditions such as age, sex, diabetes, dyslipidaemia and concurrent medications may also alter mitochondrial function. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co-medication into account may be of paramount importance during the design of pre-clinical and clinical studies testing mitoprotective drugs.     

Eukaryote specific RNA and protein features facilitate assembly and catalysis of H/ACA snoRNPs

H/ACA Box ribonucleoprotein complexes (RNPs) play a major role in modification of rRNA and snRNA, catalyzing the sequence specific pseudouridylation in eukaryotes and archaea. This enzymatic reaction takes place on a substrate RNA recruited via base pairing to an internal loop of the snoRNA. Eukaryotic snoRNPs contain the four proteins Nop10, Cbf5, Gar1 and Nhp2, with Cbf5 as the catalytic subunit. In contrast to archaeal H/ACA RNPs, eukaryotic snoRNPs contain several conserved features in both the snoRNA as well as the protein components. Here, we reconstituted the eukaryotic H/ACA RNP containing snR81 as a guide RNA in vitro and report on the effects of these eukaryote specific features on complex assembly and enzymatic activity. We compare their contribution to pseudouridylation activity for stand-alone hairpins versus the bipartite RNP. Using single molecule FRET spectroscopy, we investigated the role of the different eukaryote-specific proteins and domains on RNA folding and complex assembly, and assessed binding of substrate RNA to the RNP. Interestingly, we found diverging effects for the two hairpins of snR81, suggesting hairpin-specific requirements for folding and RNP formation. Our results for the first time allow assessing interactions between the individual hairpin RNPs in the context of the full, bipartite snoRNP.     

Adaptor Protein Complex 2–Mediated Endocytosis Is Crucial for Male Reproductive Organ Development in Arabidopsis

Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2–dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.     

Probability packaging of T4 coliphage DNA driven by oscillatory ATP consumption

Abstract

The strategies for packaging the T4 coliphage chromosome are presented. Our probability model based on fractality of DNA “globules” (fasces-like DNA globules) is consistent with transient condensation modelling to the final maximally condensed state.     

Agricultural intensification in Brazil and its effects on land‐use patterns: an analysis of the 1975–2006 period

Does agricultural intensification reduce the area used for agricultural production in Brazil? Census and other data for time periods 1975–1996 and 1996–2006 were processed and analyzed using Geographic Information System and statistical tools to investigate whether and if so, how, changes in yield and stocking rate coincide with changes in cropland and pasture area. Complementary medium‐resolution data on total farmland area changes were used in a spatially explicit assessment of the land‐use transitions that occurred in Brazil during 1960–2006. The analyses show that in agriculturally consolidated areas (mainly southern and southeastern Brazil), land‐use intensification (both on cropland and pastures) coincided with either contraction of both cropland and pasture areas, or cropland expansion at the expense of pastures, both cases resulting in farmland stability or contraction. In contrast, in agricultural frontier areas (i.e., the deforestation zones in central and northern Brazil), land‐use intensification coincided with expansion of agricultural lands. These observations provide support for the thesis that (i) technological improvements create incentives for expansion in agricultural frontier areas; and (ii) farmers are likely to reduce their managed acreage only if land becomes a scarce resource. The spatially explicit examination of land‐use transitions since 1960 reveals an expansion and gradual movement of the agricultural frontier toward the interior (center‐western Cerrado) of Brazil. It also indicates a possible initiation of a reversed trend in line with the forest transition theory, i.e., agricultural contraction and recurring forests in marginally suitable areas in southeastern Brazil, mainly within the Atlantic Forest biome. The significant reduction in deforestation that has taken place in recent years, despite rising food commodity prices, indicates that policies put in place to curb conversion of native vegetation to agriculture land might be effective. This can improve the prospects for protecting native vegetation by investing in agricultural intensification.