Final Thoughts

I’ve always loved trains; the sound of a locomotive’s air horn piercing the night is as calming to me as a glass of wine. Rail, in my opinion, is the only civilized way to travel, with none of the stress and acrimony that comes from driving or flying. The United States pioneered the art of train travel well over a century ago, and by the 1930s possessed the finest rail infrastructure on Earth—including a vast matrix of streetcars and “inter-urbans” that delivered you practically at your doorstep. Of course, the civility of rail travel was sacrificed after World War II for the holy motor car, which flattered our American individualist ego and— let’s face it—proved awfully convenient for getting around

Emergence of the American elm as a cultural and urban design element in nineteenth-century New England

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 1999.Includes bibliographical references (leaves 214-228).This dissertation is a cultural history of the American elm. It explores the transformation of a native tree into a major icon of New England culture in the nineteenth century-both as a multi valanced symbol of New England life, and a defining element in the spatial design of its villages, towns and cities. Drawing from a wide range of source material-traveler's records, local histories, town and municipal records and contemporary newspaper accounts-the study traces the forces and events which made the elm a ubiquitous feature of the Yankee scene, and a core element in the identity and image of the region. The historical narrative begins with a description of the tree in the pre-European era, and explains how cultural disturbance by both native Americans and colonists amplified the elm's presence in the landscape. Subsequent chapters examine the tree first as a solitary or totemic artifact in the landscape, and then as a element which, following a region-wide "village improvement movement" in the 1840s, was planted in vast numbers in villages, towns and cities. The totemic elm endowed Yankee space with meaning, as a civic centerpiece, a relic of antiquity, or a monument to specific historical events or persons. Planted en masse as a street tree, elms changed the quality of that space itself, transforming the appearance of the common landscape, and forging one of the most powerful images of place in American history-the elm-tossed New England town. The study culminates by examining the symbolic and spatial significance of the tree in the urban context, and argues that city elms were perceived by nineteenth-century observers as a mechanism of synthesis between rus and urbe. Long before the Olmsted park, planting elms on city streets placed the elusive ideal of a "pastoral city" within reach. As Charles Dickens observed of New Haven in his American Notes (1842), city elms brought about "a kind of compromise between town and country; as if each had met the other half-way, and shaken hands upon it." In conclusion, the seminal influence of New England on American culture at large is considered, a factor which eventually made the elm a national icon, and "Elm Street" an American institution.by Thomas J. Campanella.Ph.D

CXCL10 Can Inhibit Endothelial Cell Proliferation Independently of CXCR3

CXCL10 (or Interferon-inducible protein of 10 kDa, IP-10) is an interferon-inducible chemokine with potent chemotactic activity on activated effector T cells and other leukocytes expressing its high affinity G protein-coupled receptor CXCR3. CXCL10 is also active on other cell types, including endothelial cells and fibroblasts. The mechanisms through which CXCL10 mediates its effects on non-leukocytes is not fully understood. In this study, we focus on the anti-proliferative effect of CXCL10 on endothelial cells, and demonstrate that CXCL10 can inhibit endothelial cell proliferation in vitro independently of CXCR3. Four main findings support this conclusion. First, primary mouse endothelial cells isolated from CXCR3-deficient mice were inhibited by CXCL10 as efficiently as wildtype endothelial cells. We also note that the proposed alternative splice form CXCR3-B, which is thought to mediate CXCL10's angiostatic activity, does not exist in mice based on published mouse CXCR3 genomic sequences as an in-frame stop codon would terminate the proposed CXCR3-B splice variant in mice. Second, we demonstrate that human umbilical vein endothelial cells and human lung microvascular endothelial cells that were inhibited by CXL10 did not express CXCR3 by FACS analysis. Third, two different neutralizing CXCR3 antibodies did not inhibit the anti-proliferative effect of CXCL10. Finally, fourth, utilizing a panel of CXCL10 mutants, we show that the ability to inhibit endothelial cell proliferation correlates with CXCL10's glycosaminoglycan binding affinity and not with its CXCR3 binding and signaling. Thus, using a very defined system, we show that CXCL10 can inhibit endothelial cell proliferation through a CXCR3-independent mechanism

Expression and Localization of Mitochondrial Ferritin mRNA in Alzheimer's Disease Cerebral Cortex

Mitochondrial ferritin (MtF) has been identified as a novel ferritin encoded by an intron-lacking gene with specific mitochondrial localization located on chromosome 5q23.1. MtF has been associated with neurodegenerative disorders such as Friedreich ataxia and restless leg syndrome. However, little information is available about MtF in Alzheimer's disease (AD). In this study, therefore, we investigated the expression and localization of MtF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) as well as in situ hybridization histochemistry. We also examined protein expression using western-blot assay. In addition, we used in vitro methods to further explore the effect of oxidative stress and β-amyloid peptide (Aβ) on MtF expression. To do this we examined MtF mRNA and protein expression changes in the human neuroblastoma cell line, IMR-32, after treatment with Aβ, H2O2, or both. The neuroprotective effect of MtF on oxidative stress induced by H2O2 was measured by MTT assay. The in situ hybridization studies revealed that MtF mRNA was detected mainly in neurons to a lesser degree in glial cells in the cerebral cortex. The staining intensity and the number of positive cells were increased in the cerebral cortex of AD patients. Real-time PCR and western-blot confirmed that MtF expression levels in the cerebral cortex were significantly higher in AD cases than that in control cases at both the mRNA and the protein level. Cell culture experiments demonstrated that the expression of both MtF mRNA and protein were increased by treatment with H2O2 or a combination of Aβ and H2O2, but not with Aβ alone. Finally, MtF expression showed a significant neuroprotective effect against H2O2-induced oxidative stress (p<0.05). The present study suggests that MtF is involved in the pathology of AD and may play a neuroprotective role against oxidative stress

Post-Translational Inhibition of IP-10 Secretion in IEC by Probiotic Bacteria: Impact on Chronic Inflammation

Peer reviewedPublisher PD

Structure of the ATP synthase catalytic complex (F(1)) from Escherichia coli in an autoinhibited conformation.

ATP synthase is a membrane-bound rotary motor enzyme that is critical for cellular energy metabolism in all kingdoms of life. Despite conservation of its basic structure and function, autoinhibition by one of its rotary stalk subunits occurs in bacteria and chloroplasts but not in mitochondria. The crystal structure of the ATP synthase catalytic complex (F(1)) from Escherichia coli described here reveals the structural basis for this inhibition. The C-terminal domain of subunit ɛ adopts a heretofore unknown, highly extended conformation that inserts deeply into the central cavity of the enzyme and engages both rotor and stator subunits in extensive contacts that are incompatible with functional rotation. As a result, the three catalytic subunits are stabilized in a set of conformations and rotational positions distinct from previous F(1) structures

How Bodies and Voices Interact in Early Emotion Perception

Successful social communication draws strongly on the correct interpretation of others' body and vocal expressions. Both can provide emotional information and often occur simultaneously. Yet their interplay has hardly been studied. Using electroencephalography, we investigated the temporal development underlying their neural interaction in auditory and visual perception. In particular, we tested whether this interaction qualifies as true integration following multisensory integration principles such as inverse effectiveness. Emotional vocalizations were embedded in either low or high levels of noise and presented with or without video clips of matching emotional body expressions. In both, high and low noise conditions, a reduction in auditory N100 amplitude was observed for audiovisual stimuli. However, only under high noise, the N100 peaked earlier in the audiovisual than the auditory condition, suggesting facilitatory effects as predicted by the inverse effectiveness principle. Similarly, we observed earlier N100 peaks in response to emotional compared to neutral audiovisual stimuli. This was not the case in the unimodal auditory condition. Furthermore, suppression of beta–band oscillations (15–25 Hz) primarily reflecting biological motion perception was modulated 200–400 ms after the vocalization. While larger differences in suppression between audiovisual and audio stimuli in high compared to low noise levels were found for emotional stimuli, no such difference was observed for neutral stimuli. This observation is in accordance with the inverse effectiveness principle and suggests a modulation of integration by emotional content. Overall, results show that ecologically valid, complex stimuli such as joined body and vocal expressions are effectively integrated very early in processing