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Generalized immune activation as a direct result of activated CD4+ T cell
killing
Rute Marques1, Adam Williams2,5, Urszula Eksmond1, Andy Wullaert3, Nigel Killeen4, Manolis
Pasparakis3, Dimitris Kioussis2 and George Kassiotis1
Journal of Biology 2009, 8:9
T lymphocyte numbers in the human body are kept constant by homeostatic mechanisms
balancing cell gain and loss. These mechanisms eventually fail in HIV infection, which is
characterized by progressive immune deficiency, because of loss of CD4+ T cell function [1].
HIV infection is also associated with increased T cell turnover and activation, which extends to
uninfected cells, resulting in a state of chronic generalized immune activation [2-5]. Indeed, the
level of activation and turnover in CD8+ T cells, which are not infected by HIV, can be higher
than in CD4+ T cells, and this is a powerful predictor of disease progression [2,4,5]. Early views
of generalized immune activation as a compensatory mechanism to achieve T cell homeostasis
after virus-mediated CD4+ T cell destruction [6-8] have been replaced by alternative models in
which immune activation is the cause, rather than the consequence, of CD4+ T cell loss. In the
latter models, immune activation is considered to be directly responsible for increased
proliferation and death of both CD4+ and CD8+ T cells [9-11]. There is a strong positive
correlation between T cell immune activation and CD4+ T cell loss in HIV infection [12].
However, as the precise origin of generalized immune activation is still not fully understood, the
direction of causality between CD4+ T cell loss and immune activation remains unclear.
Time Is on My Side: Time, General Mental Ability, Human Capital, and
Extrinsic Career Success
Timothy A. Judge, Ryan L. Klinger, and Lauren S. Simon
Journal of Applied Psychology 2010, Vol. 95, No. 1, 92–107
General mental ability (GMA) can be considered one of the more useful constructs in
psychological science (Gottfredson, 2002; Schmidt & Hunter, 2004). One durable finding is the
substantial relationship between GMA and job performance (Schmidt & Hunter, 1998), which
generalizes across both jobs (Schmidt, 2002) and cultures (Salgado & Anderson, 2002). GMA
has also been shown to predict many other work-related criteria, including job satisfaction
(Ganzach, 1998), leadership (Judge, Colbert, & Ilies, 2004), creativity (Kuncel, Hezlett, & Ones,
2004), and counterproductive behavior (Dilchert, Ones, Davis, & Rostow, 2007), as well as nonwork-related criteria, including marital and familial stability, health, and longevity (Gottfredson,
1997; Gottfredson & Deary, 2004). In reviewing the vast array of criteria that GMA predicts,
Gottfredson (1997) unequivocally concluded, “Intelligence is important in social life” (p. 79).
Given these findings, it is somewhat surprising that relatively few studies have linked GMA to
career success. Although there are some such studies—according to a recent meta-analysis by
Ng, Eby, Sorensen, and Feldman (2005), eight studies have linked GMA to salary—the literature
could not be described as voluminous. Moreover, although some studies suggest that the GMA–
career success link is due to education (Deary et al., 2005), other possible explanations remain to
be discovered.
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How to Write a Research Introduction
Sources of Corruption in Authoritarian Regimes
Eric Chang and Miriam A. Golden
Social Science Quarterly, Volume 91, Number 1, March 2010
The last decade has witnessed an explosion in studies of comparative corruption, thanks in part
to the availability of new sources of cross-national data on perceptions of corruption.1 Although
nondemocratic regimes exhibit considerable variation in the extent of corruption and are on
average more corrupt than regimes where political leaders are freely elected, the focus of the
current literature has been heavily weighted toward democratic and not authoritarian countries.
However, the patterns of corruption observed in democratic settings are not likely to obtain
under authoritarianism. Even when authoritarian regimes establish legislatures, political parties,
and regular elections, political accountability is considerably more compromised than in
competitive electoral democracies. For instance, if electoral authoritarianism exists in part to coopt potential political opponents, corruption may well be used by rulers as part of a larger
strategy of political patronage. As a result, elections may have the perverse effect of encouraging
corruption rather than reducing it.2 However, this is purely speculative. We know very little
about corruption in nondemocratic polities, where political accountability is not regulated by the
competitive struggle for political office and the routinized circulation of elites.
These considerations suggest that a useful analytic strategy for investigating the determinants of
corruption should be tailored to the specific characteristics of nondemocratic regimes, at least at
this still provisional state of knowledge. The chief goal of this article is to provide a preliminary
empirical mapping of some correlates of corruption in the nondemocratic world. Drawing on
existing theories of rent seeking in settings that lack genuine electoral competition and political
accountability, we estimate empirical sources of variation in perceptions of corruption. The
contributing factors that we investigate are especially pertinent to authoritarian regimes.
Specifically, we examine whether the time horizons of the autocrat—the ruler’s expectation of
remaining in power for a shorter or longer duration—and the nature of the ruling coalition affect
the level of corruption. We thereby contribute to the growing literature that studies the effects of
institutional variations among nondemocratic polities on a wide range of consequential
outcomes, including economic growth, popular protest and rebellion, regime stability and
duration, and the economic activities of government.
Our article proceeds in four parts. In the first, we provide additional information about our main
concepts, theories, and hypotheses. A second section describes the measures and data we use. A
third reports the results of our statistical analysis and robustness tests. A final section concludes
with a discussion of theoretical implications and some considerations for further research.
Fractalkine/CX3CL1 Enhances GABA Synaptic Activity at Serotonin
Neurons in the Rat Dorsal Raphe Nucleus
S. Heinisch and L. G Kirbys
Neuroscience 164 (2009) 1210–1223
[Establishes the broad value context] Psychological stress alters immune responses and confers
vulnerability to a wide spectrum of autoimmune, cardiovascular, and neurological diseases
(Glaser and Kiecolt-Glaser, 2005 review). [Narrows to serotonin (5_HT)] The neurotransmitter
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serotonin (5-hydroxytryptamine; 5-HT) has an important role in the neuronal response to stress
(Chaouloff, 2000), and dysfunction of 5-HT is characteristically associated with stress-related
psychiatric disorders including depression and anxiety (Charney et al., 1990; Meltzer, 1990).
Recent reports also describe widespread serotonin interactions with the immune system,
including regulation of T cells, delayed-type hypersensitivity responses, and natural immunity, as
well as activation of natural killer cells (Mössner and Lesch, 1998 review). Functional studies
indicate that 5-HT may modulate cytokine release, including interleukin (IL)-1_, IL-6, IL-8, IL12, and tumor necrosis factor (TNF)-_ (Du rk et al., 2005; Idzko et al., 2004). [Narrows to
chemokines] Chemokines may likewise modulate 5-HT activity, as already reported for the
chemokine monocyte chemotactic protein 1, which was shown to enhance the mitogenic effect of
5-HT on vascular smooth muscle (Watanabe et al., 2001). Furthermore, the injection of
cytokines elicits a behavioral response referred to as “sickness behavior,” resembling the central
symptoms of depression including loss of appetite, social withdrawal, and fatigue (Dantzer and
Kelley, 2007). Thus, it appears that chemokine-5-HT interactions may occur in a bi-directional
manner.
[Continues focus on chemokines] Chemokines (chemoattractant cytokines) are small (7–11
kDa) heparin-binding chemoattractant proteins that mediate cell-to-cell communication to
promote chemotaxis and cellular adhesion. They form a specialized subclass of cytokines and
appear to be over-expressed in diseases such as meningitis, rheumatoid arthritis, multiple
sclerosis, cancer, and HIV encephalopathy (Bajetto et al., 2001 review). [Sets up division of
chemokines in order to narrow to research focus] The chemokine superfamily is divided into
four subclasses, C, CC, CXC, and CX3C, based on the location of the first two cysteine residues
in the N-terminus. [Establishes focus on CX3CL1 and begins lit review for specific research]As
the only member of the CX3C family, CX3CL1 is a unique chemokine since it has cysteines
separated by three amino acids and can exist as either a membrane-anchored protein or a soluble
glycoprotein. The cell surface-bound CX3CL1 promotes robust cellular adhesion, whereas the
soluble glycoprotein form of the protein serves as a potent chemoattractant for T cells, natural
killer cells, and monocytes (Bazan et al., 1997). [Narrows to CX3CL1 interactions with
CX3CR1] CX3CL1 mediates leukocyte chemotaxis to inflammatory regions by binding to its
Gprotein coupled receptor (GPCR), CX3CR1. CX3CR1 specifically interacts with CX3CL1,
unlike other chemokine GPCRs which are less specific and interact with multiple chemokines
(Imai et al., 1997; Combadiere et al., 1998; Allen et al., 2007 review).
[Narrows to interactions in the brain] CX3CL1 and CX3CR1 are constitutively expressed in
various non-hematopoietic tissues, including the brain. Recent reports describe the localization
of CX3CL1 to neurons and astrocytes and CX3CR1 to neurons and microglia in the
hippocampus, cortex, thalamic nuclei, spinal cord, and dorsal root ganglia (Harrison et al., 1998;
Nishiyori et al., 1998; Meucci et al., 2000; Tong et al., 2000; Hughes et al., 2002; Hatori et al.,
2002; Verge et al., 2004; Zhuang et al., 2007). Furthermore, there is a unique neuronal-glial
interaction between neurons and CX3CR1-expressing microglia under normal and pathological
states in the central nervous system (CNS) (Harrison et al., 1998).
[Narrows to neuroprotective action] Although CX3CL1 may induce monocytic infiltrates during
CNS inflammation (Chapman et al., 2000), it appears to exert an overall neuroprotective action.
Mizuno et al. (2003) reported CX3CL1-mediated inhibition both of neuronal apoptosis and of
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activated microglial nitric oxide, IL-6, and TNF-_ production. Interestingly, CX3CL1 is also upregulated in HIV encephalitis brain tissue, indicating that its induction may be in response to
chronic activation of the neurotoxic glutamate-mediated excitatory neurotransmission by HIV
neurotoxins platelet-activating factor and Tat (Tong et al., 2000). In fact, CX3CL1 is a reported
inhibitor of glutamate synaptic activity in the hippocampus under basal conditions (Bertollini et
al., 2006). The ability of CX3CL1 to modulate glutamate function appears to be the mechanism
involved in its neuroprotective actions, and it provides support for a chemokine-neuromodulatory
role in the CNS (Adler and Rogers, 2005; Adler et al., 2006; Callewaere et al., 2007; Guyon and
Nahon, 2007).
[Narrows to dorsal raphe nucleus] The dorsal raphe nucleus (DRN) contains the largest
population of forebrain-projecting serotonergic neurons (Jacobs and Azmitia, 1992).
[Establishes research problem] Although chemokines are expressed in the brain, little is known
about chemokine regulation of 5-HT neuronal functions. [Connects research problem to value
context] An impact of chemokines, including CX3CL1, on the 5-HT system would have
implications for stress-induced immunological dysfunction as well as our understanding of
anxiety and depressive disorders associated with immune disorders. [Previews study] In the
present study, we examined the neuroanatomical relationship between CX3CL1 and the 5-HT
system as well as the functional impact of CX3CL1 on 5-HT neurons using whole-cell patchclamp recordings in an in vitro rat brain
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