Structure-activity study of a laminin α1 chain active peptide segment Ile-Lys-Val-Ala-Val (IKVAV)

AbstractThe IKVAV sequence, one of the most potent active sites of laminin-1, has been shown to promote cell adhesion, neurite outgrowth, and tumor growth. Here we have determined the structural requirements of the IKVAV sequence for cell attachment and neurite outgrowth using various 12-mer synthetic peptide analogs. All-l- and all-d-IKVAV peptides showed cell attachment and neurite outgrowth activities. In contrast, all-l- and all-d-reverse-sequence peptides were not active. Some of the analogs, in which the lysine and isoleucine residues of the IKVAV peptide were substituted with different amino acids, promoted cell attachment, but none of the analog peptides showed neurite outgrowth activity comparable to that of the IKVAV peptide. These results suggest that the lysine and isoleucine residues are critical for the biological functions of the IKVAV peptide

Schizophrenia (maintenance treatment)

One in 100 people will develop schizophrenia; about 75% of people have relapses and continued disability, and a third fail to respond to standard treatment. Positive symptoms include auditory hallucinations, delusions, and thought disorder. Negative symptoms (anhedonia, asociality, flattening of affect, and demotivation) and cognitive dysfunction have not been consistently improved by any treatment

Schizophrenia (maintenance treatment).

INTRODUCTION: One in a hundred people will develop schizophrenia; about 75% of people have relapses and continued disability, and a third fail to respond to standard treatment. Positive symptoms include auditory hallucinations, delusions, and thought disorder. Negative symptoms (demotivation, self-neglect, and reduced emotion) have not been consistently improved by any treatment. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: Which interventions reduce relapse; and improve adherence rates? Which interventions are effective in people resistant to standard antipsychotic drugs? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: behavioural therapy, clozapine, cognitive behavioural therapy (CBT), compliance therapy, continuation of antipsychotic drugs (reduce relapse rates), first-generation antipsychotic drugs in treatment-resistant people, multiple-session family interventions, psychoeducational interventions, second-generation antipsychotic drugs in treatment-resistant people, and social-skills training

Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways.

During neuromuscular junction formation, extracellular matrix-mediated signals cause muscle surface acetylcholine receptors (AChRs) to aggregate at synaptic sites. Two extracellular matrix proteins, agrin and laminin, have each been shown to initiate signaling pathways that culminate in AChR clustering in cultured muscle cells. Here we present evidence that laminin-induced AChR clustering is mediated by the activation of the Rho GTPases Cdc42, Rac and Rho. Clustering in response to laminin is blocked by the dominant negative mutants Cdc42N17, RacN17 and RhoN19, as well as by the Rho inhibitor C3 transferase. Moreover, laminin-induced AChR clustering is impaired by the Rho kinase inhibitor Y-27632. Agrin-induced AChR clustering has previously been shown to require activation of Cdc42, Rac and Rho. Therefore, although agrin and laminin use distinct transmembrane receptors to initiate AChR clustering, their signaling pathways converge at the level of Rho GTPase activation

Cooperative regulation by Rac and Rho of agrin-induced acetylcholine receptor clustering in muscle cells.

A key aspect of neuromuscular synapse formation is the clustering of muscle acetylcholine receptors (AChR) at synaptic sites in response to neurally secreted agrin. Agrin-induced AChR clustering in cultured myotubes proceeds via the initial formation of small microclusters, which then aggregate to form AChR clusters. Here we show that the coupling of agrin signaling to AChR clustering is dependent on the coordinated activities of Rac and Rho GTPases. The addition of agrin induces the sequential activation of Rac and Rho in C2 muscle cells. The activation of Rac is rapid and transient and constitutes a prerequisite for the subsequent activation of Rho. This temporal pattern of agrin-induced Rac and Rho activation reflects their respective roles in AChR cluster formation. Whereas agrin-induced activation of Rac is necessary for the initial phase of AChR cluster formation, which involves the aggregation of diffuse AChR into microclusters, Rho activation is crucial for the subsequent condensation of these microclusters into full-size AChR clusters. Co-expression of constitutively active forms of Rac and Rho is sufficient to induce the formation of mature AChR clusters in the absence of agrin. These results establish that Rac and Rho play distinct but complementary roles in the mechanism of agrin-induced AChR clustering

Henkilöstön vaihtuvuus ja siihen liittyvät tekijät telemarkkinointialalla : case: Gainer Oy

Tämä opinnäytetyö toteutettiin toimeksiantosopimuksena Gainer Oy:lle, joka on toiminut telemarkkinoinnin alalla jo vuodesta 1984. Opinnäytetyön tutkimusstrategiaksi valittiin case study eli tapaustutkimus. Käytimme tutkimusmenetelmänä kvalitatiivista eli laadullista tutkimusta. Tavoitteenamme oli tutkia ja selvittää henkilöstön vaihtuvuutta ja siihen liittyviä tekijöitä alalla, jossa henkilöstön vaihtuvuus koetaan ongelmaksi. Teoriaosuudessa käsittelemme teoreettisen viitekehyksen liittyen työnantajan keinoihin vaikuttaa työntekijän sitouttamiseen. Tämä on jaettu kahteen osa-alueeseen, jotka ovat rekrytointi sekä työhyvinvointi ja osaamisen kehittäminen. Empiirisessä osiossa päädyimme käyttämään puolistrukturoitua teemahaastattelua, joka toteutettiin suurimmaksi osaksi puhelimitse sekä muutama haastattelu tehtiin kasvotusten. Teemahaastattelu valikoitui parhaimmaksi menetelmäksi johtuen aiheen moniulotteisuudesta. Avoimella haastattelulla emme olisi välttämättä saaneet merkittävää tietoa samassa mittakaavassa kuin puolistrukturoidulla mallilla. Opinnäytetyön tuloksena päädyimme esittämään toimeksiantajalle muutamia kehitysehdotuksia. Haastatteluista johdetuilla päätelmillä saatettaisiin parantaa rekrytoinnin onnistumista, joka osaltaan parantaa kannattavuutta niin tuloksellisesti, kuin henkilöstön resurssejakin säästäen. Kehitysehdotuksia muodostui myös muihin osa-alueisiin liittyen. Näillä on myös vaikutusta henkilöstön yleiseen työhyvinvointiin ja työssä jaksamiseen.This thesis was carried out as a commission agreement for Gainer Oy, which has operated in the field of telemarketing since 1984. Our study was carried out as a case study using qualitative approach as our research method. Our objective was to study personnel turnover and matters relating to it in a field where personnel turnover is seen as a problem. In the theoretical section of the study we deal with the theoretical frame of reference related to the employer's means to influence employee engagement. This is divided into two sections that are recruiting, and occupational health and development of skills. In the empirical part of our study, we ended up using half-structured theme interviews, which were mainly carried out by telephone. A few interviews were carried out face-to-face. Theme interview was selected to be the best method because of the multidimensionality of the subject. By using open interviews, we would not necessarily have received as much significant information as by using the half-structured model. As a result of our study, we presented a few development proposals for our client/commissioner. The conclusions drawn from the interviews may lead to more successful recruiting, which in turn improves viability both in terms of productivity and by saving the resources of the personnel. There were also other development proposals concerning other areas. The results of the study may also help to improve the general well-being at work and coping with one’s workload