The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Cardiovascular health and particulate vehicular emissions: a critical evaluation of the evidence

A major public health goal is to determine linkages between specific pollution sources and adverse health outcomes. This paper provides an integrative evaluation of the database examining effects of vehicular emissions, such as black carbon (BC), carbonaceous gasses, and ultrafine PM, on cardiovascular (CV) morbidity and mortality. Less than a decade ago, few epidemiological studies had examined effects of traffic emissions specifically on these health endpoints. In 2002, the first of many studies emerged finding significantly higher risks of CV morbidity and mortality for people living in close proximity to major roadways, vs. those living further away. Abundant epidemiological studies now link exposure to vehicular emissions, characterized in many different ways, with CV health endpoints such as cardiopulmonary and ischemic heart disease and circulatory-disease-associated mortality; incidence of coronary artery disease; acute myocardial infarction; survival after heart failure; emergency CV hospital admissions; and markers of atherosclerosis. We identify numerous in vitro, in vivo, and human panel studies elucidating mechanisms which could explain many of these cardiovascular morbidity and mortality associations. These include: oxidative stress, inflammation, lipoperoxidation and atherosclerosis, change in heart rate variability (HRV), arrhythmias, ST-segment depression, and changes in vascular function (such as brachial arterial caliber and blood pressure). Panel studies with accurate exposure information, examining effects of ambient components of vehicular emissions on susceptible human subjects, appear to confirm these mechanisms. Together, this body of evidence supports biological mechanisms which can explain the various CV epidemiological findings. Based upon these studies, the research base suggests that vehicular emissions are a major environmental cause of cardiovascular mortality and morbidity in the United States. As a means to reduce the public health consequences of such emissions, it may be desirable to promulgate a black carbon (BC) PM2.5 standard under the National Ambient Air Quality Standards, which would apply to both on and off-road diesels. Two specific critical research needs are identified. One is to continue research on health effects of vehicular emissions, gaseous as well as particulate. The second is to utilize identical or nearly identical research designs in studies using accurate exposure metrics to determine whether other major PM pollutant sources and types may also underlie the specific health effects found in this evaluation for vehicular emissions

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500 years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview

CCR2 and CD44 Promote Inflammatory Cell Recruitment during Fatty Liver Formation in a Lithogenic Diet Fed Mouse Model

<div><p>Non-alcoholic fatty liver disease (NAFLD) is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR) or susceptible (BALB/c and C57BL/6) to hepatitis followed by molecular and flow cytometric analysis. Following this, a similar approach was taken in congenic mice with specific mutations in immunological genes. The initial study identified a significant and profound increase in multiple ligands for the chemokine receptor CCR2 and an increase in CD44 expression in susceptible C57BL/6 (B6) but not resistant AKR mice. <i>Ccr2^−/−</i> mice were completely protected from hepatitis and <i>Cd44^−/−</i> mice were partially protected. Despite protection from inflammation, both strains displayed similar histological steatosis scores and significant increases in serum liver enzymes. CD45⁺CD44⁺ cells bound to hyaluronic acid (HA) in diet fed B6 mice but not <i>Cd44^−/−</i> or <i>Ccr2^−/−</i> mice. <i>Ccr2^−/−</i> mice displayed a diminished HA binding phenotype most notably in monocytes, and CD8⁺ T-cells. In conclusion, this study demonstrates that absence of CCR2 completely and CD44 partially reduces hepatic leukocyte recruitment. These data also provide evidence that there are multiple redundant CCR2 ligands produced during hepatic lipid accumulation and describes the induction of a strong HA binding phenotype in response to LD feeding in some subsets of leukocytes from susceptible strains.</p></div

Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions

Air pollution, especially emissions derived from traffic sources, is associated with adverse cardiovascular outcomes. However, it remains unclear how inhaled factors drive extrapulmonary pathology

Peroxiredoxin 6 interferes with TRAIL-induced death-inducing signaling complex formation by binding to death effector domain caspase

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent with cancer-selective apoptogenic activity. It evokes the canonical caspase-mediated cell death pathway through death-inducing signaling complex (DISC) formation. We identified that Peroxiredoxin 6 (Prx6) interacts with caspase-10 and caspase-8 via the death effector domain (DED). Prx6 suppresses TRAIL-mediated cell death in human cancer cells, but not that induced by intrinsic apoptosis inducers such as etoposide, staurosporine, or A23187. Among Prx1–6 members, only Prx6 binds to DED caspases and is most effective in suppressing TRAIL or DED caspase-induced cell death. The antiapoptotic activity of Prx6 against TRAIL is not likely associated with its peroxidase activity but is associated with its ability to bind to DED caspases. Increased expression of Prx6 enhances the binding of Prx6 to caspase-10 but reduces TRAIL-induced DISC formation and subsequently caspase activation. Interestingly, Prx6 is highly upregulated in metastatic gastric cancer cells, which are relatively resistant to TRAIL as compared with primary cancer cells. Downregulation of Prx6 sensitizes the metastatic cancer cells to TRAIL-induced cell death. Taken together, these results suggest that Prx6 modulates TRAIL signaling as a negative regulator of caspase-8 and caspase-10 in DISC formation of TRAIL-resistant metastatic cancer cells