Maternal hypertension induces tissue-specific modulations of the apelinergic system in the fetoplacental unit in rat

Apelin and its receptor APJ are expressed in fetal tissues but their function and regulation remain largely unknown. In rat, maternal treatment with a nitric oxide synthase inhibitor inducing hypertension was used to investigate apelin plasma levels in mother/fetus pairs and on the gene expression level of the apelin/APJ system in fetal tissues and placenta. At term, plasma levels of apelin were not modulated but APJ expression was increased in placenta and lung but reduced in heart. Apelin expression was increased only in the heart. We postulate that the apelinergic system may control fetal growth and cardiovascular functions in utero.     

Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK

The two-pore (2P) domain K(+) channels TREK-1 and TRAAK are opened by membrane stretch as well as arachidonic acid (AA) (Patel, A. J., Honoré, E., Maingret, F., Lesage, F., Fink, M., Duprat, F., and Lazdunski, M. (1998) EMBO J. 17, 4283-4290; Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M., and Honoré, E. (1999) J. Biol. Chem. 274, 26691-26696; Maingret, F., Fosset, M., Lesage, F., Lazdunski, M. , and Honoré, E. (1999) J. Biol. Chem. 274, 1381-1387. We demonstrate that lysophospholipids (LPs) and platelet-activating factor also produce large specific and reversible activations of TREK-1 and TRAAK. LPs activation is a function of the size of the polar head and length of the acyl chain but is independent of the charge of the molecule. Bath application of lysophosphatidylcholine (LPC) immediately opens TREK-1 and TRAAK in the cell-attached patch configuration. In excised patches, LPC activation is lost, whereas AA still produces maximal opening. The carboxyl-terminal region of TREK-1, but not the amino terminus and the extracellular loop M1P1, is critically required for LPC activation. LPC activation is indirect and may possibly involve a cytosolic factor, whereas AA directly interacts with either the channel proteins or the bilayer and mimics stretch. Opening of TREK-1 and TRAAK by fatty acids and LPs may be an important switch in the regulation of synaptic function and may also play a protective role during ischemia and inflammation.     

Mechanism of Kex2p inhibition by its proregion.

Many proteases are produced as zymogens bearing an N-terminal proregion acting both as intramolecular chaperone and as enzyme inhibitor. We studied here the inhibition mechanism of the yeast proprotein convertase Kex2p by its proregion. A recombinant secreted and soluble form of Kex2p was produced in Pichia pastoris and its enzymatic properties toward a fluorogenic synthetic peptide were characterized. Recombinant Escherichia coli-produced Kex2p proregion specifically and potently inhibited the enzyme, with an IC(50) of 160 nM. Exploration of the inhibition mechanism revealed that the proregion behaved as a mixed inhibitor.     

Bestandsentwicklung, Durchzug und Herkunft des KormoransPhalacrocorax carbo an einem Winterrastplatz auf Helgoland

Zusammenfassung Die Rastbestände des Kormorans auf Helgoland sind seit den 1970er Jahren stark angestiegen. Die Summe der Pentadenmaxima nahm von 1984 bis 1989 um jährlich 47 % zu. Obwohl sich die Beobachtungsintensität für Rastbestände seit 1991 stark verringerte, stieg die Maximalzahl bis 1996 auf 661 Kormorane. Bis Ende der siebziger Jahre wurden die Maxima in den Zugzeiten erreicht, seit etwa 1980 wird Helgoland dagegen zunehmend als Winterrastplatz genutzt. Die Rastbestände stiegen vor allem im September/Oktober an, erreichten Maxima von Dezember bis März und sanken von Ende März bis Mai. Der Winterbestand baute sich von 1979 bis 1996 im Herbst zunehmend schneller auf (um mehr als 100 Tage) und nahm im Frühjahr zeitiger ab (um 43 Tage). Ziehende Kormorane wurden hingegen vor allem im März/April (Median: 12. April) und von Ende Juli bis Oktober (Median: 16. September) beobachtet. Im Frühjahr ziehen Kormorane überwiegend in ost-/nordöstliche, im Herbst in west/südwestliche Richtung. 67 % flogen in Trupps mit 11–40 Individuen (Median: 27). Zugbeobachtungen fielen mit 69 % der Individuen in die Zeit bis 12 Uhr (Median: 10:05 Uhr). Von 6 Ringfunden stammen je 1 aus den Niederlanden und Norwegen sowie 4 aus Dänemark. Von 36 Totfunden auf Helgoland seit 1984 gehörten 19 nach Maßen sicher zur UnterartPhalacrocorax c. carbo, nur 9 zuP. c. sinensis. Das Gros der auf Helgoland überwinternden Kormorane stellt demnach vermutlichP. c. carbo. Vögel dieser Subspezies überwintern zudem weniger weit im Süden alssinensis und bevorzugen marine Habitate und felsige Küsten. Ein Wintermaximum vonP. c. sinensis ist daher zwar für Überwinterungsgebiete in Mittel- und Südeuropa bekannt, nicht aber aus dem Bereich der übrigen Nordsee und dem Wattenmeer. Die Brutbestände vonsinensis haben in Dänemark und Südschweden seit 1980/81 stark zugenommen, weniger diejenigen voncarbo in Norwegen. Parallel zur Zunahme der Winterbestände vonsinensis im Skagerrak und Kattegat, einem bisher typischen Überwinterungsraum voncarbo, kam es 1983–1985 zu mindestens 9 Ringfunden norwegischer Vögel in Mittel- und Südeuropa sowie 1976–1989 zu 6 Ringfunden in Nordost-Deutschland. Möglicherweise trug eine zunehmende Konkurrenz im Skagerrak und Kattegat zu dem Aufbau und der starken Zunahme der Winterbestände auf Helgoland bei. Parallelen einer Konkurrenz zwischencarbo undsinensis sind in Westfrankreich zu finden.

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Numbers, migration and origin of CormorantsPhalacrocorax carbo at a wintering site on the island of Helgoland (German Bight, North Sea)

The numbers of Cormorants resting on the island of Helgoland (54° 11 N, 7° 53 E) have increased considerably since the 1970s. Annual totals of the maxima per five-day period rose by 47 % per year from 1984 to 1989. Although the observation effort decreased, annual maxima further increased to 661 birds in 1996 (Fig. 1). Up to the late seventies, annual maxima of resting birds were occurred during the migration periods, whereas since about 1980 Helgoland is increasingly used as a wintering site. Resting numbers grew mainly in September/October, reached their maxima from December to March and fell again from the end of March to May (Fig. 2). Today arrival takes place more than 100 days earlier and departure 43 days earlier than in 1979 (Fig. 3). Migrating Cormorants were mainly observed in March and April (median: 12. April) and from the end of July to October (median: 16. September, Fig. 4). They prefer eastern and north-eastern directions in spring, and western and southwestern directions in autumn (Fig. 5). 67 % of the individuals were observed to migrate in flocks of 11 to 40 individuals (median 27, Fig. 6), and 69 % of migrating individuals were counted before midday (median: 10:05 hours, Fig. 7). Six ringed birds were found or observed at Helgoland. They were ringed in The Netherlands (1), Denmark (4) and Norway (1). According to their body measurements, 19 out of a total of 36 Cormorants found dead at Helgoland are assumed to belong to the subspeciescarbo, whereas only 9 are presumablyP. c. sinensis. Hence, we believe that most birds wintering at Helgoland belong toP. c. carbo. This subspecies winters less far south thansinensis and prefers marine habitats and rocky shores. Winter maxima ofsinensis are only known from wintering sites further south but not from the North Sea and the Wadden Sea, where maxima occur during spring and autumn migration. Breeding numbers ofP. c. sinensis have increased considerably in Denmark and south Sweden since 1980/81, whereas thoseP. c. carbo numbers have increased at a lesser rate. Coinciding with the increase of winteringsinensis in the Skagerrak and Kattegat area (a formerly typical wintering site ofcarbo), there were at least 9 recoveries of birds ringed in Norway in central and south Europe from 1983–85 and 6 in northeastern Germany from 1976–89. Probably, the establishment and growth of the winter population at Helgoland is a result of increasing competition in the Skagerrak and Kattegat. Similar developments betweencarbo andsinensis have been observed in northwest France.

     

Net photosynthetic rate of sour cherry (Prunus cerasus L. ‘Montmorency’) during the growing season with particular reference to fruiting

Diurnal and seasonal net photosynthetic rates (Pn) of sour cherry were determined. Leaf Pn was not significantly affected by shoot excision. Under constant environmental conditions (PFD, 1200 mol m^-2 s^-1; temp. 25; relative humidity, 80–90%) there was no significant diurnal fluctuation in Pn for individual leaves. However, there was a pronounced fluctuation in Pn for whole trees measured under constant temperature but natural variation in sunlight from sunrise to sunset. Maximum Pn occurred before solar noon, remained constant for 1–2 hr, then declined. Photosynthetic rate of recently expanded leaves fluctuated through out the season but, in general, was greatest in the spring as leaves expanded, reached a peak, remained stable for several weeks, then gradually declined. The Pn of leaves on terminal shoots was not significantly different from the Pn of leaves on spurs of the same physiological age. The presence of fruit did not have a consistent effect on the Pn of sour cherry leaves.Michigan Agricultural Experiment Station Journal Article No. 10739.     

Trajectories of Self-Rated Health in People with Diabetes: Associations with Functioning in a Prospective Community Sample

Background

Self-rated health (SRH) is a single-item measure that is one of the most widely used measures of general health in population health research. Relatively little is known about changes and the trajectories of SRH in people with chronic medical conditions. The aims of the present study were to identify and describe longitudinal trajectories of self-rated health (SRH) status in people with diabetes.

Methods

A prospective community study was carried out between 2008 and 2011. SRH was assessed at baseline and yearly at follow-ups (n=1288). Analysis was carried out through trajectory modeling. The trajectory groups were subsequently compared at 4 years follow-up with respect to functioning.

Results

Four distinct trajectories of SRH were identified: 1) 72.2% of the participants were assigned to a persistently good SRH trajectory; 2) 10.1% were assigned to a persistently poor SRH trajectory; 3) mean SRH scores changed from good to poor for one group (7.3%); while 4) mean SRH scores changed from poor to medium/good for another group (10.4%). Those with a persistently poor perception of health status were at higher risk for poor functioning at 4 years follow-up than those whose SRH scores decreased from good to poor.

Conclusions

SRH is an important predictor for poor functioning in diabetes, but the trajectory of SRH seems to be even more important. Health professionals should pay attention to not only SRH per se, but also changes in SRH over time.     

Type 2 diabetes disrupts circadian orchestration of lipid metabolism and membrane fluidity in human pancreatic islets

Recent evidence suggests that circadian clocks ensure temporal orchestration of lipid homeostasis and play a role in pathophysiology of metabolic diseases in humans, including type 2 diabetes (T2D). Nevertheless, circadian regulation of lipid metabolism in human pancreatic islets has not been explored. Employing lipidomic analyses, we conducted temporal profiling in human pancreatic islets derived from 10 nondiabetic (ND) and 6 T2D donors. Among 329 detected lipid species across 8 major lipid classes, 5% exhibited circadian rhythmicity in ND human islets synchronized in vitro. Two-time point-based lipidomic analyses in T2D human islets revealed global and temporal alterations in phospho- and sphingolipids. Key enzymes regulating turnover of sphingolipids were rhythmically expressed in ND islets and exhibited altered levels in ND islets bearing disrupted clocks and in T2D islets. Strikingly, cellular membrane fluidity, measured by a Nile Red derivative NR12S, was reduced in plasma membrane of T2D diabetic human islets, in ND donors’ islets with disrupted circadian clockwork, or treated with sphingolipid pathway modulators. Moreover, inhibiting the glycosphingolipid biosynthesis led to strong reduction of insulin secretion triggered by glucose or KCl, whereas inhibiting earlier steps of de novo ceramide synthesis resulted in milder inhibitory effect on insulin secretion by ND islets. Our data suggest that circadian clocks operative in human pancreatic islets are required for temporal orchestration of lipid homeostasis, and that perturbation of temporal regulation of the islet lipid metabolism upon T2D leads to altered insulin secretion and membrane fluidity. These phenotypes were recapitulated in ND islets bearing disrupted clocks.

A study of circadian regulation of lipid metabolism in human pancreatic islets reveals that Type 2 Diabetes leads to global and temporal alterations of phospholipid and sphingolipid metabolism in islets, resulting in decreased membrane fluidity and insulin secretion defects.     

TREK-1 is a heat-activated background K(+) channel

Peripheral and central thermoreceptors are involved in sensing ambient and body temperature, respectively. Specialized cold and warm receptors are present in dorsal root ganglion sensory fibres as well as in the anterior/preoptic hypothalamus. The two-pore domain mechano-gated K(+) channel TREK-1 is highly expressed within these areas. Moreover, TREK-1 is opened gradually and reversibly by heat. A 10 degrees C rise enhances TREK-1 current amplitude by approximately 7-fold. Prostaglandin E2 and cAMP, which are strong sensitizers of peripheral and central thermoreceptors, reverse the thermal opening of TREK-1 via protein kinase A-mediated phosphorylation of Ser333. Expression of TREK-1 in peripheral sensory neurons as well as in central hypothalamic neurons makes this K(+) channel an ideal candidate as a physiological thermoreceptor.