Polyamines (PAs) but not small peptides with closely spaced positively charged groups interact with DNA and RNA, but they do not represent a relevant buffer system at physiological pH values

Polyamines (PAs) including putrescine (PUT), spermidine (SPD) and spermine (SPM) are small, versatile molecules with two or more positively charged amino groups. Despite their importance for almost all forms of life, their specific roles in molecular and cellular biology remain partly unknown. The molecular structures of PAs suggest two presumable biological functions: (i) as potential buffer systems and (ii) as interactants with poly-negatively charged molecules like nucleic acids. The present report focuses on the question, whether the molecular structures of PAs are essential for such functions, or whether other simple molecules like small peptides with closely spaced positively charged side chains might be suitable as well. Consequently, we created titration curves for PUT, SPD, and SPM, as well as for oligolysines like tri-, tetra-, and penta-lysine. None of the molecules provided substantial buffering capacity at physiological intracellular pH values. Apparently, the most important mechanism for intracellular pH homeostasis in neurons is not a buffer system but is provided by the actions of the sodium-hydrogen and the bicarbonate-chloride antiporters. In a similar approach we investigated the interaction with DNA by following the extinction at 260 nm when titrating DNA with the above molecules. Again, PUT and tri-lysine were not able to interact with herring sperm DNA, while SPD and SPM were. Obviously, the presence of several positively charged groups on its own is not sufficient for the interaction with nucleic acids. Instead, the precise spacing of these groups is necessary for biological activity

Labour Market Participation of Non-Germans in the Health Sector in Germany: Study within the European Migration Network "Managed Migration and the Labour Market - The Health Sector"

Das Working Paper 6 stellt neben der wirtschaftlichen Bedeutung des Gesundheitssektors die rechtlichen Grundlagen für die Zuwanderung von Arbeitskräften im Gesundheitssektor dar und präsentiert für die einzelnen Berufsgruppen und Herkunftsländer detaillierte Daten zur Beschäftigung. Das Working Paper gibt zunächst einen Überblick über den Gesundheitssektor, um ihn in seiner wirtschaftlichen Bedeutung einordnen zu können. Anschließend wird erläutert, welche rechtlichen Grundlagen für die Erwerbstätigkeit von Ausländern gelten und welche speziellen berufsrechtlichen Voraussetzungen bei Gesundheitsdienstberufen erfüllt werden müssen. Es folgt eine Darstellung der Beschäftigungssituation auf der Basis der Statistiken der Bundesagentur für Arbeit (sozialversicherungspflichtig Beschäftigte) und der Bundesärztekammer, der Bundeszahnärztekammer sowie der Bundesvereinigung deutscher Apothekerverbände. Die Datenanalyse umfasst den Zeitraum von 1999 bis 2005 und ermöglicht es somit, die Entwicklung der Zahl der beschäftigten Ausländer in einzelnen Berufsgruppen und aus einzelnen Herkunftsländern herauszustellen.In addition to the economic significance of the healthcare sector, the Small-scale Study II presents the legal basis for the immigration of workers in the healthcare sector and offers detailed data on employment for the individual professional groups and countries of origin. The study starts by providing an overview of the healthcare sector in order to be able to categorise its economic significance. The legal foundations which apply to gainful employment of foreigners are then explained, together with the specific vocational preconditions which must be met in the healthcare professions. This is followed by a portrayal of the employment situation on the basis of the statistics of the Federal Employment Agency (employment subject to obligatory social insurance) and of the German Medical Association, of the German Dental Association, as well as of the National Union of German Pharmacists’ Associations. The data analysis encompasses the period from 1999 to 2005, and hence makes it possible to emphasise the development of the number of employed foreigners in individual vocational groups and from individual countries of origin

The Satiety Signaling Neuropeptide Perisulfakinin Inhibits the Activity of Central Neurons Promoting General Activity

The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM) due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite

Arbeitsmarktbeteiligung von Ausländern im Gesundheitssektor in Deutschland: Studie im rahmen des europäischen Migrationsnetzwerkes "Managed Migration and the Labour Market - The Health Sector"

Das Working Paper 6 stellt neben der wirtschaftlichen Bedeutung des Gesundheitssektors die rechtlichen Grundlagen für die Zuwanderung von Arbeitskräften im Gesundheitssektor dar und präsentiert für die einzelnen Berufsgruppen und Herkunftsländer detaillierte Daten zur Beschäftigung. Das Working Paper gibt zunächst einen Überblick über den Gesundheitssektor, um ihn in seiner wirtschaftlichen Bedeutung einordnen zu können. Anschließend wird erläutert, welche rechtlichen Grundlagen für die Erwerbstätigkeit von Ausländern gelten und welche speziellen berufsrechtlichen Voraussetzungen bei Gesundheitsdienstberufen erfüllt werden müssen. Es folgt eine Darstellung der Beschäftigungssituation auf der Basis der Statistiken der Bundesagentur für Arbeit (sozialversicherungspflichtig Beschäftigte) und der Bundesärztekammer, der Bundeszahnärztekammer sowie der Bundesvereinigung deutscher Apothekerverbände. Die Datenanalyse umfasst den Zeitraum von 1999 bis 2005 und ermöglicht es somit, die Entwicklung der Zahl der beschäftigten Ausländer in einzelnen Berufsgruppen und aus einzelnen Herkunftsländern herauszustellen.In addition to the economic significance of the healthcare sector, the Small-scale Study II presents the legal basis for the immigration of workers in the healthcare sector and offers detailed data on employment for the individual professional groups and countries of origin. The study starts by providing an overview of the healthcare sector in order to be able to categorise its economic significance. The legal foundations which apply to gainful employment of foreigners are then explained, together with the specific vocational preconditions which must be met in the healthcare professions. This is followed by a portrayal of the employment situation on the basis of the statistics of the Federal Employment Agency (employment subject to obligatory social insurance) and of the German Medical Association, of the German Dental Association, as well as of the National Union of German Pharmacists’ Associations. The data analysis encompasses the period from 1999 to 2005, and hence makes it possible to emphasise the development of the number of employed foreigners in individual vocational groups and from individual countries of origin

Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels

Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K(+) channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the "helix-bundle crossing". However, in the inwardly rectifying (Kir) potassium channel family, the role of this "hinge" residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper "hinge" residues are in close contact with the base of the pore alpha-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the "lower" gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue

Unique Features of a Global Human Ectoparasite Identified Through Sequencing of the Bed Bug Genome

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite