Antimicrobial activities of chemokines: not just a side-effect?

The large family of chemoattractant cytokines (chemokines) embraces multiple, in part unrelated functions that go well beyond chemotaxis. Undoubtedly, the control of immune cell migration (chemotaxis) is the single, unifying response mediated by all chemokines, which involves the sequential engagement of chemokine receptors on migrating target cells. However, numerous additional cellular responses are mediated by some (but not all) chemokines, including angiogenesis, tumor cell growth, T-cell co-stimulation, and control of HIV-1 infection. The recently described antimicrobial activity of several chemokines is of particular interest because antimicrobial peptides are thought to provide an essential first-line defense against invading microbes at the extremely large body surfaces of the skin, lungs, and gastrointestinal-urinary tract. Here we summarize the current knowledge about chemokines with antimicrobial activity and discuss their potential contribution to the control of bacterial infections that may take place at the earliest stage of antimicrobial immunity. In the case of homeostatic chemokines with antimicrobial function, such as CXCL14, we propose an immune surveillance function in healthy epithelial tissues characterized by low-level exposure to environmental microbes. Inflammatory chemokines, i.e., chemokines that are produced in tissue cells in response to microbial antigens (such as pathogen-associated molecular patterns) may be more important in orchestrating the cellular arm in antimicrobial immunity.

Early loss of arteriolar smooth muscle cells: more than just a pericyte loss in diabetic retinopathy

Incipient diabetic retinopathy is characterized by increased capillary permeability and progressive capillary occlusion. The earliest structural change is the loss of pericytes (PC) from the retinal capillaries. With the availability of the XLacZ mouse, which expresses the LacZ reporter in a PC/vascular smooth muscle cell (vSMC) specific fashion, we quantitatively assessed the temporal dynamics of smooth muscle cells in arterioles under hyperglycemic conditions. We induced stable hyperglycemia in XLacZ mice. After 4, 8, and 12 weeks of diabetes retinae were isolated and beta-galactosidase/lectin stained. The numbers of smooth muscle cells were counted in retinal whole mounts, and diameters of retinal radial and branching arterioles and venules were analyzed at different distances apart from the center of the retina. After eight weeks of diabetes, the numbers of vSMCs were significantly reduced in radial arterioles 1000 microm distant from the optic disc. At proximal sites of branching arterioles (400 microm distant from the center), and at distal sites (1000 microm), vSMC were significantly reduced already after 4 weeks (to a maximum of 31 %). These changes were not associated with any measurable variation in vessel diameters. These data indicate quantitatively that hyperglycemia not only causes pericyte loss, but also loss of vSMCs in the retinal vasculature. Our data suggest that arteriolar vSMC in the eye underlie similar regulations which induce early pericyte loss in the diabetic retina.

Pachydermodactyly--just a sign of emotional distress

Pachydermodactyly (PDD) is a benign, asymptomatic soft tissue swelling affecting the skin of the lateral aspects of the proximal interphalangeal joints of the fingers II-IV, mostly in young adolescent males, and could be interpreted as a consequence of tic-like behaviour as an obsessive-compulsive disorder in male adolescents. The differential diagnosis includes numerous diseases; a rapid clinical recognition of PDD would avoid many useless and expensive diagnostic tests. There is no effective medical treatment for PDD, but discontinuation of the tic-like mechanical traumatisation generally leads to a marked amelioration of the finger swelling. In this article we review the world literature, which contains 87 additional cases on this topic.

Early Iron Age Kinneret – Early Aramaean or Just Late Canaanite? Remarks on the Material Culture of a Border Site in Northern Palestine at the Turn of an Era

In recent years, scholars have identified Early Iron Age Kinneret as belonging either to the kingdom of Geshur1 or at least as being part of an early Aramaean polity.2 It is the purpose of this paper to reexamine the archaeological evidence for such an assumption and to critically test the currently available data against this hypothesis.

Good just isn't Good enough. Best System Probabilities and the Foundations of Statistical Mechanics

Statistical physicists assume a probability distribution over micro-states to explain thermodynamic behavior. The question of this paper is whether these probabilities are part of a best system and can thus be interpreted as Humean chances. I consider two strategies, viz. a globalist as suggested by Loewer, and a localist as advocated by Frigg and Hoefer. Both strategies fail because the system they are part of have rivals that are roughly equally good, while ontic probabilities should be part of a clearly winning system. I conclude with the diagnosis that well-defined micro-probabilities under-estimate the robust character of explanations in statistical physics.

More than just Good Luck. How to Explain the Success of Monte Carlo Simulations

Monte Carlo simulation is a powerful method in many natural and social sciences. But what sort of method is it? And where does its power come from? Are Monte Carlo simulations experiments, theories or something else? The aim of this talk is to answer these questions and to explain the power of Monte Carlo simulations. I provide a classification of Monte Carlo techniques and defend the claim that Monte Carlo simulation is a sort of inference.

Good just isn't Good Enough: Humean Chances and Boltzmannian Statistical Physics

Statistical physicists assume a probability distribution over micro-states to explain thermodynamic behavior. The question of this paper is whether these probabilities are part of a best system and can thus be interpreted as Humean chances. I consider two Boltzmannian accounts of the Second Law, viz.\ a globalist and a localist one. In both cases, the probabilities fail to be chances because they have rivals that are roughly equally good. I conclude with the diagnosis that well-defined micro-probabilities under-estimate the robust character of explanations in statistical physics.

Experimenting and modeling: sharp distinctions, integration or just a mess?

At first sight, experimenting and modeling form two distinct modes of scientific inquiry. This spurs philosophical debates about how the distinction should be drawn (e.g. Morgan 2005, Winsberg 2009, Parker 2009). But much scientific practice casts serious doubts on the idea that the distinction makes much sense. There are two worries. First, the practices of modeling and experimenting are often intertwined in intricate ways because much modeling involves experimenting, and the interpretation of many experiments relies upon models. Second, there are borderline cases that seem to blur the distinction between experiment and model (if there is any). My talk tries to defend the philosophical project of distinguishing models from experiment and to advance the related philosophical debate. I begin with providing a minimalist framework of conceptualizing experimenting and modeling and their mutual relationships. The methods are conceptualized as different types of activities that are characterized by a primary goal, respectively. The minimalist framwork, which should be uncontroversial, suffices to accommodate the first worry. I address the second worry by suggesting several ways how to conceptualize the distinction in a more flexible way. I make a concrete suggestion of how the distinction may be drawn. I use examples from the history of science to argue my case. The talk concentrates and models and experiments, but I will comment on simulations too.

Exceptional or just well connected? Political entrepreneurs and brokers in policy making

Policy brokers and policy entrepreneurs are assumed to have a decisive impact on policy outcomes. Their access to social and political resources is contingent on their influence on other agents. In social network analysis (SNA), entrepreneurs are often closely associated with brokers, because both are agents presumed to benefit from bridging structural holes; for example, gaining advantage through occupying a strategic position in relational space. Our aim here is twofold. First, to conceptually and operationally differentiate policy brokers from policy entrepreneurs premised on assumptions in the policy-process literature; and second, via SNA, to use the output of core algorithms in a cross-sectional analysis of political brokerage and political entrepreneurship. We attempt to simplify the use of graph algebra in answering questions relevant to policy analysis by placing each algorithm within its theoretical context. In the methodology employed, we first identify actors and graph their relations of influence within a specific policy event; then we select the most central actors; and compare their rank in a series of statistics that capture different aspects of their network advantage. We examine betweenness centrality, positive and negative Bonacich power, Burt’s effective size and constraint and honest brokerage as paradigmatic. We employ two case studies to demonstrate the advantages and limitations of each algorithm for differentiating between brokers and entrepreneurs: one on Swiss climate policy and one on EU competition and transport policy.

Just Reading? How Gender-Fair Language Triggers Readers' Use of Gender-Fair Forms

Gender-fair language, that is, referring to men and women with symmetrical linguistic forms, has been found to promote gender equality, but it is largely unknown which factors help make gender-fair forms more common in everyday life. Two studies examined whether speakers of German used more gender-fair forms after reading a text with gender-fair wording (vs. masculine generics vs. no personal nouns vs. another topic). Both studies showed consistently that women used more gender-fair forms after reading the gender-fair text than the other texts, whereas men did not. Men employed more gender-fair forms only after being made aware of these forms (Study 2). To conclude, merely reading gender-fair texts enhances women’s inclination to use gender-fair language, whereas men need to be made aware of this type of language use. Both studies highlight the importance of using gender-fair language frequently and consistently in everyday life.