Мои воспоминания об Иване Георгиевиче Спасском

Стислі спогади автора про відомого вченого-нумізмата й музейника І.Г. Спаського та його сім’ю.Краткие воспоминания автора об известном ученом-нумизмате и музейщике И.Г. Спасском и его семье.Short author’s memories about known scientist-numismatist and museum-worker I.G. Spassky and his family

Reduced TCR-dependent activation through citrullination of a T-cell epitope enhances Th17 development by disruption of the STAT3/5 balance

Citrullination is a post-translational modification of arginine that commonly occurs in inflammatory tissues. Because T-cell receptor (TCR) signal quantity and quality can regulate T-cell differentiation, citrullination within a T-cell epitope has potential implications for T-cell effector function. Here, we investigated how citrullination of an immunedominant T-cell epitope affected Th17 development. Murine na¨ıve CD4+ T cells with a transgenic TCR recognising p89-103 of the G1 domain of aggrecan (agg) were co-cultured with syngeneic bone marrow-derived dendritic cells (BMDC) presenting the native or citrullinated peptides. In the presence of pro-Th17 cytokines, the peptide citrullinated on residue 93 (R93Cit) significantly enhanced Th17 development whilst impairing the Th2 response, compared to the native peptide. T cells responding to R93Cit produced less IL-2, expressed lower levels of the IL-2 receptor subunit CD25, and showed reduced STAT5 phosphorylation, whilst STAT3 activation was unaltered. IL-2 blockade in native p89-103-primed T cells enhanced the phosphorylated STAT3/STAT5 ratio, and concomitantly enhanced Th17 development. Our data illustrate how a post-translational modification of a TCR contact point may promote Th17 development by altering the balance between STAT5 and STAT3 activation in responding T cells, and provide new insight into how protein citrullination may influence effector Th-cell development in inflammatory disorders

Mannitol transport and mannitol dehydrogenase activities are coordinated in olea europaea under salt and osmotic stresses

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Plant and Cell Physiology following peer review. The definitive publisher-authenticated version is available online at http://pcp.oxfordjournals.org/cgi/content/abstract/pcr121? ijkey=6orgUM5fkIjedYn&keytype=refThe intracellular accumulation of organic compatible solutes functioning as osmoprotectants, such as polyols, is an important response mechanism of several plants to drought and salinity. In Olea europaea a mannitol transport system (OeMaT1) was previously characterised as a key player in plant response to salinity. In the present study, heterotrophic sink models, such as olive cell suspensions and fruit tissues, and source leaves were used for analytical, biochemical and molecular studies. The kinetic parameters of mannitol dehydrogenase (MTD) determined in mannitol-growing cells, at 25 °C and pH 9.0, were as follows: Km, 54.5 mM mannitol and Vmax, 0.47 μmol h-1 mg-1 protein. The corresponding cDNA was cloned and named OeMTD1. OeMTD1 expression was correlated with MTD activity, OeMaT1 expression and carrier-mediated mannitol transport, in mannitol- and sucrose-growing cells. Furthermore, sucrosegrowing cells displayed only residual OeMTD activity, even though high levels of OeMTD1 transcription were observed. There is evidence OeMTD is regulated at both transcriptional and post-transcriptional levels. MTD activity and OeMTD1 expression were repressed after Na+, K+ and PEG treatments, both in mannitol- and sucrose-growing cells. In contrast, salt and drought significantly increased mannitol transport activity and OeMaT1 expression. Altogether, these studies support that olive tree copes with salinity and drought by coordinating mannitol transport with intracellular metabolism.This work was supported by the Portuguese Foundation for Science and Technology (FCT) (research project ref. PTDC/AGR-ALI/100636/2008; to A. Conde, grant ref. SFRH/BD/47699/2008; to C. Conde, grant ref. SFRH/BPD/34998/2007; to P. Silvagrant ref. SFRH/BD/13460/2003)

'20 days protected learning' - students' experiences of an Overseas Nurses Programme - 4 years on: A retrospective survey

Background From September 2005 the Nursing and Midwifery Council (NMC) introduced new arrangements for the registration of non-EU overseas nurses which requires all applicants to undertake '20 days of protected learning' time in the UK and for some, a period of supervised practice. A survey was undertaken at Bournemouth University, which offers a '20 days protected learning only' programme, to elicit overseas nurses' demographic details, experiences in completing the programme and their 'final destinations' once registered. Methods An online survey was devised which contained a mixture of tick box and open ended questions which covered demographic details, views on the programme and final destinations This was uploaded to www.SurveyMonkey.com and sent out to nurses who had completed the Overseas Nurses Programme (ONP) with Bournemouth University (n=1050). Quantiative data were analysed using descriptive statistics and the qualitative data were coded and analysed using content analysis . Results There were 251 respondents (27.7% response rate). The typical 'profile' of a nurse who responded to the survey was female, aged 25-40 years and had been qualified for more than 5 years with a bachelors degree. The majority came from Australia on a 2 year working holiday visa and the key final destination in the UK, on registration with the NMC, was working for an agency. There were five key findings regarding experience of the programe. Of those surveyed 61.2% did not feel it necessary to undergo an ONP; 71.6% felt that they should be able to complete the programme on-line in their own country; 64.2% that the ONP should only contain information about delivery of healthcare in UK and Legal and professional (NMC) issues; 57% that European nurses should also undergo the same programme and sit an IELTS test; and 68.2% that the programme was too theory orientated; and should have links to practice (21%). Conclusions The NMC set the admissions criteria for entry to the register and Standards for an ONP. The findings of this survey raise issues regarding the percieved value and use of this approach for overseas nurses, and it may be helpful to take this into account when considering future policy

Traditional and Health-Related Philanthropy: The Role of Resources and Personality

I study the relationships of resources and personality characteristics to charitable giving, postmortem organ donation, and blood donation in a nationwide sample of persons in households in the Netherlands. I find that specific personality characteristics are related to specific types of giving: agreeableness to blood donation, empathic concern to charitable giving, and prosocial value orientation to postmortem organ donation. I find that giving has a consistently stronger relation to human and social capital than to personality. Human capital increases giving; social capital increases giving only when it is approved by others. Effects of prosocial personality characteristics decline at higher levels of these characteristics. Effects of empathic concern, helpfulness, and social value orientations on generosity are mediated by verbal proficiency and church attendance.

Implementing Silicon Nanoribbon Field-Effect Transistors as Arrays for Multiple Ion Detection

Ionic gradients play a crucial role in the physiology of the human body, ranging from metabolism in cells to muscle contractions or brain activities. To monitor these ions, inexpensive, label-free chemical sensing devices are needed. Field-effect transistors (FETs) based on silicon (Si) nanowires or nanoribbons (NRs) have a great potential as future biochemical sensors as they allow for the integration in microscopic devices at low production costs. Integrating NRs in dense arrays on a single chip expands the field of applications to implantable electrodes or multifunctional chemical sensing platforms. Ideally, such a platform is capable of detecting numerous species in a complex analyte. Here, we demonstrate the basis for simultaneous sodium and fluoride ion detection with a single sensor chip consisting of arrays of gold-coated SiNR FETs. A microfluidic system with individual channels allows modifying the NR surfaces with self-assembled monolayers of two types of ion receptors sensitive to sodium and fluoride ions. The functionalization procedure results in a differential setup having active fluoride-and sodium-sensitive NRs together with bare gold control NRs on the same chip. Comparing functionalized NRs with control NRs allows the compensation of non-specific contributions from changes in the background electrolyte concentration and reveals the response to the targeted species

Molecular determinants of treatment response in human germ cell tumors

PURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways may influence the efficacy of chemotherapy. Their impact has not been investigated in a comprehensive study of tumor samples from clinically defined subgroups of GCT patients. EXPERIMENTAL DESIGN: We investigated proteins involved in regulation of apoptosis (p53, BAX, BCL-2, and BCL-X(L)), cell cycle control [p21 and retinoblastoma protein (RB)], and drug export and inactivation [P-glycoprotein, multidrug resistance-associated protein (MRP) 1, MRP2, breast cancer resistance protein, lung resistance protein, metallothionein, and glutathione S-transferase pi] immunohistochemically in samples of unselected GCT patients (n = 20), patients with advanced metastatic disease in continuous remission after first-line chemotherapy (n = 12), and chemotherapy-refractory patients (n = 24). Mature teratoma components (n = 10) within tumor samples from all groups were analyzed separately. The apoptotic index was studied by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: Invasive GCTs of all groups showed a correlation between wild-type p53 and apoptotic index (r(s) = 0.66; P < 0.001). The levels of the antiapoptotic proteins BCL-2 and BCL-X(L) were generally low. p21 was hardly detectable and did not correlate with p53 (r(s) = 0.29; P = 0.07). No significant differences among the three patient groups were identified regarding any of the investigated parameters (all Ps were >0.08), even though only individual samples from chemotherapy-resistant cases showed a strong staining for MRP2 and GSTpi. In contrast to other components, mature teratomas showed an intense p21 and RB staining and were mostly positive for MRP2, lung resistance protein, and GSTpi. CONCLUSIONS: Our results indicate a multifactorial basis for the chemosensitivity of GCTs with lack of transporters for cisplatin, of antiapoptotic BCL-2 family members, of p21 induction by p53, and of RB and an intact apoptotic cascade downstream of p53. These findings suggest a preference for apoptosis over cell cycle arrest after up-regulation of p53. None of the examined parameters offers a general explanation for the chemotherapy-resistant phenotype of refractory tumors. The up-regulation of various factors interfering with chemotherapy efficacy and ability for a p21-induced cell cycle arrest may explain the intrinsic chemotherapy resistance of mature teratomas

"Active surfaces" as Possible Functional Systems in Detection and Chemical (Bio) Reactivity

This article presents design strategies to demonstrate approaches to generate functionalized surfaces which have the potential for application in molecular systems; sensing and chemical reactivity applications are exemplified. Some applications are proven, while others are still under active investigation. Adaptation and extension of our strategies will lead to interfacing of different type of surfaces, specific interactions at a molecular level, and possible exchange of signals/cargoes between them. Optimization of the present approaches from each of five research groups within the NCCR will be directed towards expanding the types of functional surfaces and the properties that they exhibit