Mini Review: Specificity in cytokine signal transduction: lessons learned from the IL-3:IL-5:GM-CSF receptor family

Cytokines mediate the transduction of proliferative, differentiation and survival signals in the hematopoietic system. Although the cytokine family is large and diverse, many different cytokines display broadly overlapping functions. This can be explained by the fact that cytokine receptors often share multiple subunits. Specificity in signal transduction can however be achieved through several mechanisms. This review focuses on how signal specificity can be achieved within the IL-3, IL-5 and GM-CSF receptor family. This is discussed in terms of receptor expression, recent advances in our understanding of intracellular signalling components, and analysis of null mutant knock-out mice

Persons at risk during interrogations in police custody:Different perspectives on vulnerable suspects

A false confession given by a suspect has major implications for the suspect himself or herself, the criminal investigation and ultimately the credibility of police and justice. Mentally vulnerable suspects in particular may give false confessions. This study shows that police officers frequently deal with vulnerable suspects – much more frequently than they are aware of. Therefore, Geijsen argues in favour of every suspect being treated as a vulnerable suspect and recording interrogations. He also argues in favour of the introduction of investigative interviewing in the Netherlands. Finally, he concludes that police cell complexes equipped according to the basic principles of environmental psychology may contribute to the mental wellbeing of suspects

Cytokine-mediated cPLA2 phosphorylation is regulated by multiple MAPK family members

Cytosolic phospholipase A2 (cPLA2) plays a critical role in various neutrophil functions including the generation of leukotrienes and platelet-activating factor release. Enzyme activity is regulated both by translocation to the membrane in a Ca^(2+) -dependent manner and serine phosphorylation by members of the mitogen-activated protein kinase (MAPK) family. In this report, we have investigated the role of granulocyte/macrophage colony-stimulating factor (GM-CSF)- mediated signalling pathways in the regulation of cPLA2. GM- CSF-induced cPLA2 phosphorylation was not affected by pharmacological inhibition of p38 MAPK, phosphatidylinositol 3-kinase or Src. However, inhibition of extracellular signal- regulated kinase (ERK) MAPK activation resulted in a partial inhibition of cPLA2 phosphorylation, revealed in a slower onset of phosphorylation. A cell line stably transfected with the GM- CSF receptor was used to further analyze GM-CSF-mediated cPLA2 phosphorylation. Mutation of tyrosine residues 577 and 612 resulted in a delayed cPLA2 phosphorylation similar to the pharmacological ERK inhibition. Furthermore, inhibition of p38 MAPK in cells bearing the double mutant ßc577/612 completely abrogated GM-CSF-induced cPLA2 phosphorylation. We con- clude that GM-CSF can mediate cPLA2 phosphorylation through the redundant activation of both p38 and ERK MAP kinases

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Comparison of the roles of mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase signal transduction in neutrophil effector function

Although it is known that many stimuli can activate mitogen- activated protein kinases (MAPKs) and phosphatidylinositol 3- kinases (PI3K) in human neutrophils, little is known concerning either the mechanisms or function of this activation. We have utilized a selective inhibitor of MAPKkinase (MEK), PD098059, and two inhibitors of PI3K, wortmannin and LY294002, to investigate the roles of these kinases in the regulation of neutrophil effector functions. Granulocyte/macrophage colony- stimulating factor, platelet-activating factor (PAF) and N-for- mylmethionyl-leucyl-phenylalanine are capable of activating both p44^(ERK1) and p42^(ERK2) MAPKs and phosphotyrosine-asso- ciated PI3K in human neutrophils. The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21^(ras) by both tyrosine kinase and G-protein- coupled receptors as measured by a novel assay for GTP loading. Wortmannin and LY294002 inhibit, to various degrees, super- oxide generation, neutrophil migration and PAF release. In- cubation with PD098059, however, inhibits only the PAF release stimulated by serum-treated zymosan. This demonstrates that, while neither MEK nor ERK kinases are involved in the acti- vation of respiratory burst or neutrophil migration, inhibition of PAF release suggests a potential role in the activation of cytosolic phospholipase A2 . PI3K isoforms, however, seem to have a much wider role in regulating neutrophil functioning

Staying overnight in police custody:A study into psychological wellbeing and sleep problems in suspects

In dit onderzoek werd de invloed van de omgeving van een politiecellencomplex op het psychologisch welzijn en slaapproblemen van verdachten onderzocht. Resultaten tonen aan dat verdachten in een politiecel een verminderd psychologisch welzijn ervaren, dat zij slechter slapen, en dat een verminderd psychisch welzijn is gerelateerd aan slaapproblemen. Consequenties van het verblijf in politiecellencomplexen voor het psychisch welzijn en de slaapproblemen van verdachten, alsmede richtingen voor verder onderzoek naar omstandigheden in politiecellencomplexen, worden besproken

Optimizing eHealth tools for older patients: Collaborative redesign of a hospital website

Most hospital websites have not been developed in collaboration with patients and, therefore, rarely take into account the preferences and abilities of older patients. This study describes the systematic redesign of an existing hospital website in a co‐design process with patients and professional stakeholders (e.g. researchers, physicians, nurses, department heads, policymakers, website designers), with the aim to make it more user‐friendly for older patients with colorectal cancer (CRC). The redesign process consisted of three phases, where (I) both existing content and design were evaluated among CRC patients; (II) a prototype website was developed based on these insights; which (III) was evaluated again before making final adjustments. Mixed research methods were used for the redesign process. Specifically, insights from existing literature, outcomes from qualitative and quantitative empirical studies conducted by our team, and expert knowledge from relevant stakeholders, were collected and discussed in multidisciplinary consensus meetings, and served as input for the redesigned website. While the existing website was evaluated poorly, the qualitative evaluation of the prototype website in phase 3 showed that the newly redesigned website was usable for older CRC patients. A practical roadmap on how to collaboratively redesign and optimise existing eHealth tools to make them suitable for and operational in clinical settings is provided

Повернення в Ніжин (корпус документів з епістолярію І.Г. Спаського)

Підготовка до друку та переднє слово Наталії ДМИТРЕНКО (Ніжин), коментарі Сергія ЗОЗУЛІ (Київ–Ніжин): Уперше вводиться до наукового обігу корпус джерел з епістолярію українського та російського радянського історика-нумізмата, музейника І.Г. Спаського. Корпус джерел який містить кореспонденцію, отриману відомим науковцем від кореспондентів-ніжинців, і де, здебільшого, відображена “ніжинська тематика” – проблеми збереження культурної спадщини Ніжина, післявоєнного розвитку міста тощо.Подготовка к печати и предисловие Наталии ДМИТРЕНКО (Нежин), комментарии Сергея ЗОЗУЛИ (Киев–Нежин): Впервые вводится в научный оборот корпус источников из эпистолярия украинского и российского советского историка-нумизмата, музейщика И.Г. Спасского. Корпус источников содержит корреспонденцию, полученную известным ученым от корреспондентов-нежинцев, и в котором преимущественно отображена “нежинская тематика” – проблемы сохранения культурного наследия Нежина, послевоенного развития города и т.п.Preparation to the print and preface of Nataliya DMYTRENKO (Nizhyn), comments of Serhiy ZOZULYA (Kyiv–Nizhyn): The corps of sources from the epistolary legacy of the Ukrainian and Russian soviet historiannumismatist and museum worker I.G. Spas’kiy is entered to the scientific appeal in the first time. This corps of sources contains correspondence got the known scientist from Nizhynians and contains mostly “Nizhyn themes” – problems of protect of Nizhyn’s cultural legacy, post-war development of this town etc