Azurocidin, a Natural Antibiotic from Human Neutrophils: Expression, Antimicrobial Activity, and Secretion

The azurophil granules of human PMN contain four antibiotic proteins, the serprocidins, which have extensive homology to one another and to serine proteases. Azurocidin, a member of this family, is a 29-kDa glycoprotein with broad spectrum antimicrobial activity and chemotactic activity toward monocytes. Insect cells transfected with a baculovirus vector carrying azurocidin cDNA produced a recombinant azurocidin protein. We purified the recombinant azurocidin protein from the culture medium of the infected cells and showed that it retained the antimicrobial activity of the native neutrophil-derived molecule. In addition, we present evidence that a 49-amino-acid region of the recombinant azurocidin protein is required for its secretion from insect cells.     

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14

Background

Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease.

Methodology/Principal Findings

Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals.

Conclusions/Principal Findings

Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.     

Apparent Reversion to Trophism of a Free Omental Graft: A Preliminary Report

In a previous paper we reported evidence which suggested that a free omental graft has trophic characteristics similar to those of the chorionic epithelium of the early embryo, through which it establishes arteriolar or larger connections with aorta, heart and pericardium within 10 days after it has been placed in contact with the denuded surfaces of each structure. The theory of omental trophism was tested by dropping pieces of omentum completely detached into the pleural and peritoneal cavities of white rats. When examined 25 or more days later a percentage of omental grafts appeared healthy and were attached to pleura, lung, heart and to various structures in the peritoneal cavity. In the pleural grafts, histological sections revealed a continuity between the omental grafts and the sub-pleural tissues. A blood-hungry free omental graft appears to seek out its own blood supply. Neither pleura nor serosa was able to repel its primitive probing for a new blood supply.     

The thymus as a target for mycobacterial infections

Mycobacterial infections are among the major health threats worldwide. Ability to fight these infections depends on the host's immune response, particularly on macrophages and T lymphocytes produced by the thymus. Using the mouse as a model, and two different routes of infection (aerogenic or intravenous), we show that the thymus is consistently colonized by Mycobacterium tuberculosis, Mycobacterium avium or Mycobacterium bovis BCG. When compared to organs such as the liver and spleen, the bacterial load reaches a plateau at later time-points after infection. Moreover, in contrast with organs such as the spleen and the lung no granuloma were found in the thymus of mice infected with M. tuberculosis or M. avium. Since T cell differentiation depends, to a large extent, on the antigens encountered within the thymus, infection of this organ might alter the host's immune response to infection. Therefore, from now on, the thymus should be considered in studies addressing the immune response to mycobacterial infection.     

Comparative genetic structure and demographic history in endemic galapagos weevils

The challenge of maintaining genetic diversity within populations can be exacerbated for island endemics if they display population dynamics and behavioral attributes that expose them to genetic drift without the benefits of gene flow. We assess patterns of the genetic structure and demographic history in 27 populations of 9 species of flightless endemic Galápagos weevils from 9 of the islands and 1 winged introduced close relative. Analysis of mitochondrial DNA reveals a significant population structure and moderately variable, though demographically stable, populations for lowland endemics (F(ST) = 0.094-0.541; π: 0.014-0.042; Mismatch P = 0.003-0.026; and D((Tajima)) = -0.601 to 1.203), in contrast to signals of past contractions and expansions in highland specialists on 2 islands (Mismatch P = 0.003-0.026 and D((Tajima)) = -0.601 to 1.203). We interpret this series of variable and highly structured population groups as a system of long-established, independently founded island units, where structuring could be a signal of microallopatric differentiation due to patchy host plant distribution and poor dispersal abilities. We suggest that the severe reduction and subsequent increase of a suitably moist habitat that accompanied past climatic variation could have contributed to the observed population fluctuations in highland specialists. We propose the future exploration of hybridization between the introduced and highland endemic species on Santa Cruz, especially given the expansion of the introduced species into the highlands, the sensitivity to past climatic variation detected in highland populations, and the potentially threatened state of single-island endemics.     

Influence of tree species on carbon sequestration in afforested pastures in a humid temperate region

Plant and Soil - This study examines the influence of tree species in relation to biomass and soil C dynamics in plantations established on former pasture land. Data on the C sink capacity of such...     

Platforms for enrichment of phosphorylated proteins and peptides in proteomics

Protein phosphorylation is a complex and highly dynamic process involved in numerous biological events. Abnormal phosphorylation is one of the underlying mechanisms for the development of cancer and metabolic disorders. The identification and absolute quantification of specific phospho-signatures can help elucidate protein functions in signaling pathways and facilitate the development of new and personalized diagnostic and therapeutic tools. This review presents a variety of strategies currently utilized for the enrichment of phosphorylated proteins and peptides before mass spectrometry analysis during proteomic studies. The investigation of specific affinity reagents, allied to the integration of different enrichment processes, is triggering the development of more selective, rapid and cost-effective high-throughput automated platforms.     

Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development

Little is known about the mechanism by which embryonic liver, lung, and pancreas progenitor cells emerge from the endodermal epithelium to initiate organogenesis. Understanding this process and its genetic control provides insight into ontogeny, developmental abnormalities, and tissue regeneration. We find that shortly after hepatic endoderm cells are specified, they undergo a transition from a columnar, gut morphology to a pseudostratified morphology, with concomitant "interkinetic nuclear migration" (INM) during cell division. INM is a hallmark of pseudostratified epithelia and the process used by neural progenitors to emerge from the neural epithelium. We find that the transition of the hepatic endoderm, but not the neural epithelium, to a pseudostratified epithelium is dependent upon the cell-autonomous activity of the homeobox gene Hex. In the absence of Hex, hepatic endoderm cells survive but maintain a columnar, simple epithelial phenotype and ectopically express Shh and other genes characteristic of the midgut epithelium. Thus, Hex promotes endoderm organogenesis by promoting the transition to a pseudostratified epithelium, which in turn allows hepatoblasts to emerge into the stromal environment and continue differentiating.     

On the occurrence of Cebus flavius (Schreber 1774) in the Caatinga, and the use of semi-arid environments by Cebus species in the Brazilian state of Rio Grande do Norte

Cebus flavius is a recently rediscovered species and a candidate for the 25 most endangered primate species list. It was hypothesized that the distribution of C. flavius was limited to the Atlantic Forest, while the occurrence of C. libidinosus in the Rio Grande do Norte (RN) Caatinga was inferred, given its occurrence in neighboring states. As a result of a survey in ten areas of the RN Caatinga, this paper reports on four Cebus populations, including the first occurrence of C. flavius in the Caatinga, and an expansion of the northwestern limits of distribution for the species. This C. flavius population may be a rare example of a process of geographic distribution retraction, and is probably the most endangered population of this species. New areas of occurrence of C. libidinosus are also described. Tool use sites were observed in association with reports of the presence of both capuchin species.