Single cell analysis reveals similar functional competence of dominant and non-dominant CD8 T-cell clonotypes

The properties of CD8 T-cells requiredfor protection from infectiousdisease and cancer are only partiallycharacterized, and only limited data isavailable regarding T-cell clonotypes.It has been proposed that dominantT-cell clonotypes may have higherprotective potential than their nondominantcounterparts. Our objectiveswere to assess memory andeffector functions, stage of differentiationand clonotype selection of tumor-reactive T lymphocytes followingpeptide vaccination in melanomapatients.We also characterized dominantversus non-dominant clonotypesto further understand the in vivo functionof these T-cells based on theirprevalence. Using a novel single-cellapproach for simultaneous ex vivomolecular and functional analysis, wereport the preferential selection andexpansion of several tumor-specificco-dominant clonotypes of intermediateto high frequencies, irrespectiveof whether native or analog peptidewas used for vaccination. Theseclonotypes made up 40 - 95% of thedifferentiated "effector-like" T-cells,but only 25% of the less-differentiated"effector-memory" cells. Bothsubsets also contained non-dominantT-cell clonotypes, but these were significantlymore frequent in the lessdifferentiatedcells. Thus, cell differentiationwas clonotype-dependent.Surprisingly however, the acquisitionof memory and effector T-cell propertieswas clonotype independent, as wefound similar functional profiles indominant and low/ non-dominantT-cell clonotypes. In contrast to analogpeptide vaccination, native peptidevaccination induced T-cell functionsthat were more comprehensive,with more pronounced effector functionscombined with memory cellproperties. In summary, this study revealsthat T-cell functions are determinedprimarily by the antigen andthe stage of T-cell differentiation, butare similar in dominant and non-dominantclonotypes participating in aCD8 T-cell response. The identifiedclonotypic basis of T-cell responsescontributes to the rational developmentof vaccines.

The future of leadership

The good news with regard to this (or any) chapter on the future of leadership is that there is one. There was a time when researchers called for a moratorium on new leadership theory and research (e.g., Miner, 1975) citing the uncertain future of the field. Then for a time there was a popular academic perspective that leadership did not really matter when it came to shaping organizational outcomes (Meindl & Ehrlich, 1987; Meindl, Ehrlich, & Dukerich, 1985; Pfeffer, 1977). That perspective was laid to rest by "realists" in the field (Day & Antonakis, 2012a) by means of empirical re-interpretation of the results used to support the position that leadership does not matter (Lieberson & O'Connor, 1972; Salancik & Pfeffer, 1977). Specifically, Day and Lord (1988) showed that when proper methodological concerns were addressed (e.g., controlling for industry and company size effects; incorporating appropriate time lags) that the impact of top-level leadership was considerable - explaining as much as 45% of the variance in measures of organizational performance. Despite some recent pessimistic sentiments about the "curiously unformed" state of leadership research and theory (Hackman & Wageman, 2007), others have argued that the field has continued to evolve and is potentially on the threshold of some significant breakthroughs (Day & Antonakis, 2012a). Leadership scholars have been re-energized by new directions in the field and research efforts have revitalized areas previously abandoned for apparent lack of consistency in findings (e.g., leadership trait theory). Our accumulated knowledge now allows us to explain the nature of leadership including its biological bases and other antecedents, and consequences with some degree of confidence. There are other comprehensive sources that review the extensive theoretical and empirical foundation of leadership (Bass, 2008; Day & Antonakis, 2012b) so that will not be the focus of the present chapter. Instead, we will take a future-oriented perspective in identifying particular areas within the leadership field that we believe offer promising perspectives on the future of leadership. Nonetheless, it is worthwhile as background to first provide an overview of how we see the leadership field changing over the past decade or so. This short chronicle will set the stage for a keener understanding of where the future contributions are likely to emerge. Overall, across nine major schools of leadership - trait, behavioural, contingency, contextual, relational, sceptics, information processing, New Leadership, biological and evolutionary - researchers have seen a resurgence in interest in one area, a high level of activity in at least four other areas, inactivity in three areas, and one that was modestly active in the previous decade but we think holds strong promise for the future (Gardner, Lowe, Moss, Mahoney, & Cogliser, 2010). We will next provide brief overviews of these nine schools and their respective levels of research activity (see Figure 1).

3

De manière générale, l'autonomie des établissements de formation influence positivement la performance scolaire. Une enquête réalisée en Suisse romande auprès de 219 cadres scolaires permet, dans la présente contribution, de mesurer l'écart existant entre le degré d'autonomie souhaitée par les cadres scolaires d'une part et le degré d'autonomie dont ils disent disposer d'autre part. Le traitement descriptif des données de l'enquête démontre que, dans tous les domaines de gestion, les cadres scolaires souhaitent disposer de plus d'autonomie qu'ils n'en perçoivent. Ce constat est valable dans tous les cantons, tous les degrés du système éducatif et toutes les fonctions. Le degré d'autonomie souhaitée ne varie que peu selon les cantons, les degrés ou les fonctions. Sur cette base, il n'est pas possible de conclure à la nécessité ou à la pertinence d'un degré d'autonomie différenciée selon les cantons, les degrés ou les fonctions. Le traitement analytique des données de l'enquête identifie les facteurs expliquant l'écart entre les degrés d'autonomie souhaitée et perçue. Cet écart est plus élevé que la moyenne dans les cantons de Fribourg et de Genève, dans le degré primaire et dans la fonction de directeur. En d'autres termes, l'adéquation entre les degrés d'autonomie souhaitée et perçue est moins bonne dans ces cantons, ce degré et cette fonction. Un rattrapage en matière de délégation d'autonomie est dès lors possible. La reconnaissance, à l'intérieur de l'établissement, d'une faculté de conduite et de pilotage à la direction exerce un effet positif sur le degré d'autonomie souhaitée et un effet positif plus important encore sur le degré perçu. Par conséquent, il apparaît qu'une direction dont la faculté de conduite est avérée souhaite non seulement disposer de plus d'autonomie mais parvienne à obtenir (ou à « gagner ») plus d'autonomie. School autonomy has a positive influence on pupils' performance. This article presents the results of a survey conducted in the French-speaking part of Switzerland on 219 school leaders. The objective of the survey is to measure and to explain the gap between the level of autonomy desired by school leaders, and the level of autonomy that they perceive. Descriptive statistics show that, in every single management area, school leaders wish to have more autonomy than they actually have. This result is valid in all cantons, all levels of the education system and all types of job. The desired level of autonomy varies only slightly depending on the cantons, the levels of the education system and the types of job. On this basis, it is not possible to conclude that it is necessary and relevant to differentiate the level of autonomy depending on the cantons, the levels of the education system and the types of job. Analytical statistics identify the explanatory variables of the gap between the desired level of autonomy and the perceived level of autonomy. This gap is higher than average in the cantons of Fribourg and Geneva, in the primary level of education and in the position of head-teacher. In other words, the adequacy between the desired and the perceived levels of autonomy is worse in these cantons, this level and this position. As a result, a catch-up on the delegation of school autonomy is possible. Results also show that school leaders, whose management competence is recognized by its staff, not only want more autonomy but succeed in securing (or "gaining") more autonomy.

Iowa Cultural Leadership Partners 2013 Interview Highlights, September 2013

The Cultural Leadership Partners Program of the Iowa Arts Council and Iowa Department of Cultural Affairs (IAC/DCA) engages leaders in Iowa’s arts and cultural community that have demonstrated an exemplary record of programming and managerial excellence, as well as exceptional community service to the citizens of Iowa on a year-round basis. After a rigorous application process, organizations selected to become Cultural Leadership Partners (CLPs) receive annual operating support from IAC/DCA. This document will not only serve to communicate to CLPs what the IAC/DCA has learned from these conversations, but that it will act as a catalyst for further development of the program and inform how IAC/DCA can support, challenge, connect, and partner with Iowa’s leading arts and cultural institutions.

Women in leadership: Three essays

GENDER EMPOWERMENT: EFFECTS OF GODS, GEOGRAPHY, AND GDP¦Fenley, M., & Antonakis, J.¦ABSTRACT¦We examined the determinants of women's empowerment in the economy and political leadership in 178 countries. Given the androcentric nature of most religions, we hypothesized that high degrees of country-level theistic belief create social conditions that impede the progression of women to power. The dependent variable was the Gender Empowerment index of the United Nations Development Program, which captures the participation of women in political leadership, management, and their share of national income. Controlling for GDP per capita as well as the fixed-effects of the dominant type of religion and legal origin and instrumenting all endogenous variables with geographic or historical variables, our results show that atheism has a significant positive effect on gender empowerment. These results are driven by the rule of law, which in addition to being a catalyst for economic development, appears to crowd-out the informal regulation of behavior due to religious norms.¦DEVELOPING WOMEN LEADERS: COMPARING A TRANSFORMATIONAL AND A CHARISMATIC LEADERSHIP INTERVENTION¦Fenley, M., Jacquart, P., & Antonakis, J.¦ABSTRACT¦Along with a gender imbalance in leadership role occupancy, most leadership interventions have been conducted with samples of men. We conducted an experiment wherein we assigned female participants (n = 38, mean age = 35 years) to one of two conditions: Transformational (i.e., "standard") leadership training or charismatic leadership training. The two interventions were essentially equivalent, except that we also focused on developing the "charismatic leadership tactics" (e.g., rhetorical skills) of participants in the charismatic condition. After the interventions, we randomly assigned participants into problem-solving teams that required extensive interaction. Each team had an equal number of participants having received transformational training or charismatic training. At the end of the team exercises, participants rated each of their team members on a leadership prototypicality measure. Results indicated that those who received charismatic training scored higher (a) on prototypicality (standardized  = .42) and (b) on a test of declarative knowledge of charismatic rhetorical strategies (i.e., a manipulation check, standardized  = .76). Furthermore, the score on the test fully mediated the effect of the treatment on prototypicality (standardized indirect  = .32). We discuss the importance and practical implications of these results.¦CHANGING ATTITUDES TOWARDS WOMEN IN A MALE SEX-TYPE WORK ENVIRONMENT: EVIDENCE FROM A FIELD EXPERIMENT IN EUROPEAN ATHLETICS¦Fenley, M.¦ABSTRACT¦Most sports organizations have a similar gender gap in leadership as do the majority of non-sport organizations. Women's careers sputter somewhere at coaching level positions and few women obtain top leadership positions. Greater awareness of gender inequalities in general, and in leadership in particular, could decrease gender discrimination and increase women's presence at upper levels. The goal of this study was to evaluate the impact of an intervention using an online gender awareness exercise. Participants (n = 1,001 participants, n = 32 countries) were randomly assigned to one of eight conditions in a 2 (a discriminating perspective-taking story or a non-discriminating perspective-taking story) by 2 (gender quiz or no gender quiz) by 2 (diversity quiz or no diversity quiz) factorial design. The results show that the online perspective taking exercise changed initial sexist attitudes. Participants having taken a diversity quiz had less sexist attitudes (as measured by the Modern- and Old-fashioned sexism scale) than did participants who did not take the diversity quiz (irrespective of perspective-taking story). The combination of having taken a diversity quiz with a gender quiz had the biggest impact on attitudes for the non-discriminating story.

Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression.

Glucagon-like peptide-1 (GLP-1) protects beta-cells against apoptosis, increases their glucose competence, and induces their proliferation. We previously demonstrated that the anti-apoptotic effect was mediated by an increase in insulin-like growth factor-1 receptor (IGF-1R) expression and signaling, which was dependent on autocrine secretion of insulin-like growth factor 2 (IGF-2). Here, we further investigated how GLP-1 induces IGF-1R expression and whether the IGF-2/IGF-1R autocrine loop is also involved in mediating GLP-1-increase in glucose competence and proliferation. We show that GLP-1 up-regulated IGF-1R expression by a protein kinase A-dependent translational control mechanism, whereas isobutylmethylxanthine, which led to higher intracellular accumulation of cAMP than GLP-1, increased both IGF-1R transcription and translation. We then demonstrated, using MIN6 cells and primary islets, that the glucose competence of these cells was dependent on the level of IGF-1R expression and on IGF-2 secretion. We showed that GLP-1-induced primary beta-cell proliferation was suppressed by Igf-1r gene inactivation and by IGF-2 immunoneutralization or knockdown. Together our data show that regulation of beta-cell number and function by GLP-1 depends on the cAMP/protein kinase A mediated-induction of IGF-1R expression and the increased activity of an IGF-2/IGF-1R autocrine loop.

Osaamisen johtamisen mahdollisuudet tietohallinnon palvelutuotannossa

Tässä diplomityössä tutkitaan osaamisen johtamisen mahdollisuuksia tietopalveluja tuottavan organisaation toiminnassa. Tarkoituksena on selvittää vaatimukset osaamisen johtamiselle kohdeorganisaation toiminnassa. Tutkimuksen lähtökohtana oli tietohallinnon palveluympäristön ja toimintatavan muutoksessa. Tarkastelunkohteina olivat osaamisen kehittäminen kohdeorganisaatiossa ja teoreettiset perusteet oppivasta organisaatiosta ja osaamisen johtamisesta. Empiirisen aineistonkerääminen toteutettiin kvalitatiivisilla haastatteluilla. Empiirisen aineistonosia liitettiin tutkimusraporttiin. Tutkimuksen perusteella saatiin selkeä kuva osaamisen johtamisesta kohdeorganisaatiossa ja vaatimukset osaamisen johtamisen toteuttamiselle. Osaamisen johtaminen oli kohdeorganisaatiossa kohtuullisen uusi asia, jonka vuoksi se ei ollut vakiintunutta käytäntöään. Teoreettisesta näkökulmasta kohde organisaation osaamisen johtaminen painottui yksilöosaamisen johtamiseen. Tutkimuksessa löydettiin myös käytännöllisiä kehittämisen kohteita, joiden perusteella osaamisen johtamisen kehittämiseksi esimiesten tulisi lisätä vuorovaikutusta organisaatiossaan, parantaa alaistensa tietämystä ydinosaamisista ja rakentaa oppimista tukevaa ilmapiiriä.

Tavaratalojohtajien osaamisesta kohti koko organisaation kehittämistä - Case K-citymarket Oy

Tämän tutkimuksen tavoitteena oli tarkastella tietojohtamista organisaation inhimillisen pääoman (human capital) näkökulmasta. Erityisesti tässä työssä tarkasteltiin johtajien osaamista, motivaatiota ja motivointia, sitoutumista ja sitouttamista sekä johtajien vuorovaikutustaitoja ja edellä mainittujen aiheiden merkitystä organisaatiolle pääomien kasvattamisen näkökulmasta. Tutkimuksen empiirisessä osassa käytettiin kvantitatiivista ja kvalitatiivista tutkimusotetta. Tutkimusmenetelmänä käytettiin SPSS for Windows (12.0.1.) -tilasto-ohjelmaa sekä puolistrukturoituja teemahaastatteluja. Tutkimus osoitti selkeästi inhimillisen pääoman (osaamisen, motivaation ja sitoutumisen) tärkeyden ja merkityksen organisaatiolle. Tulevaisuuden kilpailukyky rakentuu paljolti juuri inhimillisen pääoman varaan. Kilpailukyvyn kannalta juuri inhimillisen pääoman merkityksen tunnistaminen ja hyödyntäminen on tärkeää. Johtajilla on oma merkityksensä organisaation kehitykselle, kuitenkin organisaation koostuu kaikista siinä vaikuttavista ihmisistä.

Hepatic glucose sensing is required to preserve β cell glucose competence.

Liver glucose metabolism plays a central role in glucose homeostasis and may also regulate feeding and energy expenditure. Here we assessed the impact of glucose transporter 2 (Glut2) gene inactivation in adult mouse liver (LG2KO mice). Loss of Glut2 suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate-responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was initially normal after Glut2 inactivation, but LG2KO mice exhibited progressive impairment of glucose-stimulated insulin secretion even though β cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinated downregulation of cholesterol biosynthesis genes in LG2KO mice that was associated with reduced hepatic cholesterol in fasted mice and reduced bile acids (BAs) in feces, with a similar trend in plasma. We showed that chronic BAs or farnesoid X receptor (FXR) agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from Fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls β cell glucose competence and suggest BAs as a potential mechanistic link.