Dihydrobenzothiadiazine dioxides with potent diuretic effect

Zusammenfassung Die Gewinnung eines neuen, tierexperimentell und klinisch hochwirksamen Diureticums der Formel III (6-Chlor-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazin-1,1-dioxyd) wird beschrieben.      

Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice

Williams syndrome is a neurodevelopmental disorder caused by the hemizygous deletion of 1.6 Mb on human chromosome 7q11.23. This region comprises the gene CYLN2, encoding CLIP-115, a microtubule-binding protein of 115 kD. Using a gene-targeting approach, we provide evidence that mice with haploinsufficiency for Cyln2 have features reminiscent of Williams syndrome, including mild growth deficiency, brain abnormalities, hippocampal dysfunction and particular deficits in motor coordination. Absence of CLIP-115 also leads to increased levels of CLIP-170 (a closely related cytoplasmic linker protein) and dynactin at the tips of growing microtubules. This protein redistribution may affect dynein motor regulation and, together with the loss of CLIP-115-specific functions, underlie neurological alterations in Williams syndrome.     

Nonlinear dynamics of ice-wedge networks and resulting sensitivity to severe cooling events

Patterns of subsurface wedges of ice that form along cooling-induced tension fractures, expressed at the ground surface by ridges or troughs spaced 10 30 m apart, are ubiquitous in polar lowlands. Fossilized ice wedges, which are widespread at lower latitudes, have been used to infer the duration and mean temperature of cold periods within Proterozoic and Quaternary climates, and recent climate trends have been inferred from fracture frequency in active ice wedges. Here we present simulations from a numerical model for the evolution of ice-wedge networks over a range of climate scenarios, based on the interactions between thermal tensile stress, fracture and ice wedges. We find that short-lived periods of severe cooling permanently alter the spacing between ice wedges as well as their fracture frequency. This affects the rate at which the widths of ice wedges increase as well as the network's response to subsequent climate change. We conclude that wedge spacing and width in ice-wedge networks mainly reflect infrequent episodes of rapidly falling ground temperatures rather than mean conditions.     

Recent decline in the global land evapotranspiration trend due to limited moisture supply

More than half of the solar energy absorbed by land surfaces is currently used to evaporate water. Climate change is expected to intensify the hydrological cycle and to alter evapotranspiration, with implications for ecosystem services and feedback to regional and global climate. Evapotranspiration changes may already be under way, but direct observational constraints are lacking at the global scale. Until such evidence is available, changes in the water cycle on land?a key diagnostic criterion of the effects of climate change and variability?remain uncertain. Here we provide a data-driven estimate of global land evapotranspiration from 1982 to 2008, compiled using a global monitoring network, meteorological and remote-sensing observations, and a machine-learning algorithm. In addition, we have assessed evapotranspiration variations over the same time period using an ensemble of process-based land-surface models. Our results suggest that global annual evapotranspiration increased on average by 7.1?±?1.0?millimetres per year per decade from 1982 to 1997. After that, coincident with the last major El Ni?o event in 1998, the global evapotranspiration increase seems to have ceased until 2008. This change was driven primarily by moisture limitation in the Southern Hemisphere, particularly Africa and Australia. In these regions, microwave satellite observations indicate that soil moisture decreased from 1998 to 2008. Hence, increasing soil-moisture limitations on evapotranspiration largely explain the recent decline of the global land-evapotranspiration trend. Whether the changing behaviour of evapotranspiration is representative of natural climate variability or reflects a more permanent reorganization of the land water cycle is a key question for earth system science.     

Systems thinking,systems practice,and practical philosophy: A program of research

IfSystems Practice is to serve the cause of socially rational decision making, its understanding of systems approach must open itself up to the communicative dimension of rational practice uncovered by contemporary practical philosophy. This programmatic paper argues that building the bridge between the two traditions of systems thinking and practical philosophy is a key challenge to be faced by the systems community. A three-level framework of rational systems practice is suggested as a point of departure for a program of research.     

Retrovirus genomes methylated by mammalian but not bacterial methylase are non-infectious

The biological importance of DNA methylation for gene expression in eukaryotes is becoming increasingly evident, and a direct role of methylation in gene expression has been suggested by an analysis of the infectivity of integrated retroviral genomes in a transfection assay. These studies, however, did not address whether specific methylatable residues are involved in gene regulation. Methylation by sequence-specific bacterial DNA methylases has been shown to suppress the expression of some genes, but not others. To investigate the effect of methylation on gene expression without having to rely on sequence-specific methylases, a rat liver enzyme was used to methylate in vitro all C-G dinucleotides of a proviral genomic clone. This treatment reduced the biological activity of Moloney murine leukaemia virus (M-MuLV) proviral DNA by more than three orders of magnitude, whereas complete methylation of 35 HpaII sites in the same DNA had only a marginal effect. The rat methylase-induced inactivation was reversible, as treatment of recipient cells with 5-azacytidine rendered the non-infectious viral genomes biologically active. This suggests that methylation in other C-G dinucleotides than those detectable with restriction enzymes can be crucial for gene expression.     

The effect of clomiphene and cyclofenil upon pituitary LH and hypothalamic LH-Releasing-Factor content in the female rat

Zusammenfassung Der Effekt von Clomifenhydrogencitrat und von Cyclofenil auf den LH-Gehalt der Hypophyse und den LH-RF-Gehalt des Hypothalamus wurde an kastrierten, weiblichen Ratten untersucht, die mit Östradiol und Progesteron blockiert worden waren. Während die Injektion von Cyclofenil im Dosisbereich von 100 bis 600 g/Tier zu einem Abfall von sowohl LH als auch LH-RF führte, konnte bei Verabreichung von Clomifen nur bei der Gabe von 25 g/Tier eine signifikante Herabsetzung von LH und LH-RF beobachtet werden.