Review: Helicobacter: Inflammation,immunology, and vaccines

Chronic inflammation induced by Helicobacter pylori infection is a critical factor in the development of peptic ulcer disease and gastric cancer. Central to this inflammation is the initiation of pro‐inflammatory signaling cascades within epithelial cells, in particular those mediated by two sensors of bacterial cell wall components, nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) and alpha‐protein kinase 1 (ALPK1). H pylori is, however, also highly adept at mitigating inflammation in the host, thereby restricting tissue damage and favoring bacterial persistence. H pylori modulates host immune responses by altering cytokine signaling in epithelial and myeloid cells, which results in increased proliferation of regulatory T cells and downregulation of effector T‐cell responses. H pylori vacuolating cytotoxin A (VacA) has been shown to play an important role in the dampening of immune responses and induction of immune tolerance capable of protecting against asthma. It is also possible to generate protective immune responses by immunization with various H pylori antigens or their epitopes, in combination with an adjuvant, though this for now has only been shown in mouse models. Novel non‐toxic adjuvants, consisting of modified bacterial enterotoxins or nanoparticles, have recently been developed that may not only enhance vaccine efficacy, but also help translate candidate vaccines to the clinic. This review will summarize the main discoveries in the past year regarding host immune responses to H pylori infection, as well as the design of new vaccine approaches against this infection.     

Indians, Markets, and Rainforests: Theory, Methods, and Analysis

Indians, Markets, and Rainforests: Theory, Methods, and Analysis. Ricardo A. Godoy. New York: Columbia University Press, 2001. 274 pp.     

Phylogeny,classification, and biogeography of Afrotrichloris,Apochiton, Coelachyrum,Dinebra, Eleusine,Leptochloa, Schoenefeldia,and a new genus,Schoenefeldiella (Poaceae: Chloridoideae: Cynodonteae: Eleusininae)

To investigate the evolutionary relationships among species of Afrotrichloris, Apochiton, Coelachyrum, Dinebra, Eleusine, Leptochloa, and Schoenefeldia of subtribe Eleusininae, a phylogeny based on DNA sequences from nine gene regions (ITS, rps16-trnK, rps3, rps16, rpoC2, rpl32-trnL, ndhF, ndhA, ccsA) is presented. Previous molecular phylogenies indicated that Coelachyrum was polyphyletic and Schoenefeldia was paraphyletic, with Afrotrichloris embedded within it. Apochiton burttii was embedded in the Coelachyrum clade paired with C. longiglume, Coelachyrumpoiflorum was placed outside of Coelachyrum and sister to Eleusine, and Schoenefeldia is paraphyletic, with its two species forming a grade sister to Afrotrichoris. Our molecular phylogeny supports recognition of a new genus, Schoenefeldiella, and a new combination, Schoenfeldiella transiens. In addition, we provide generic emendations for Coelachyrum, which now includes five species including a new combination proposed here, Coelachyrum burttii, and Eleusine, which now includes 11 species.     

Allophycocyanin: trimers,monomers, subunits,and homodimers

Allophycocyanin is a photosynthetic light-harvesting pigment-protein complex located in the phycobilisomes of cyanobacteria and red algae. Using dynamic light scattering and circular dichroism, solutions of purified allophycocyanin were shown to consist of homogeneous trimers (alpha3beta3) with a nonspherical shape over a very wide range of protein concentrations at pH 6.0 and 20 degrees C. Deconvolutions of the visible circular dichroism spectrum of the trimer were carried out for the first determination of the individual spectra of all six-component chromophores. The chromophores were shown to be in different microenvironments that helped determine the spectrum of the trimer. Monomers (alpha beta) that were formed in either the presence of 0.50M NaSCN or at 45 degrees C were shown to be completely reversible to trimers. However, subunits (alpha and beta) that were formed in either the presence of 8M urea or at 60 degrees C, using spectroscopy and gel-filtration column chromatography, were observed to only partially reconstitute trimers. Homodimers (alpha2 and/or beta2) formed during the regeneration of trimers. The homodimer, which was detected for the first time when both subunits were present, was shown to be in equilibrium with its subunits. Unlike the trimer situation, subunits were found to fully reconstitute monomers in the presence of 0.50M NaSCN. These results suggest a route to trimer assembly from subunits with monomers serving as intermediaries and the homodimers forming in a nonproductive step that did not interfere with the overall assembly scheme.     

Subjects and Objects: Metaphysics, Biology, Consciousness, and Cognition

Over the past half-century, the Freeman laboratory has accumulated a large volume of data and a correspondingly extensive interpretive framework centered around an alternative perspective on brain function, that of dynamical systems. The purpose of this paper is first briefly to summarise this work, and bring it into dialogue with other perspectives. The contents of consciousness are seen as an inevitably sparse sample of events in the perception–action cycle. The paper proceeds to an attempt to elucidate the contents of this sparse sample. A critical concept is that of selfhood, and how it presents itself phenomenologically. It is argued that our experience of selfhood is an artifact of the necessity of preservation of subject/object relations. As this part of metaphysics has been badly misunderstood, we scrutinise it at some length in quantum mechanics, biology, and cognition. It is argued that Pattee's approach, while valuable, tends to premature closure on these issues. The paper then proceeds to outline a view on how selfhood is best considered wrt the immune response. This is interrelated with phenomenology, and some data are adduced to support this central hypothesis. Finally, consequences for the social sciences in general are hinted at.     

Masking: History, Definitions, and Measurement

Masking and entrainment are two different processes that result in rhythms in physiology and behavior. Considering its functional importance, lamentably little study has been devoted to masking compared to that lavished on entrainment. This paper discusses the origin and definition of terminology (positive and negative masking, paradoxical masking) and methods of quantifying masking. How masking is scored can greatly influence the interpretation of results.     

ChIP-chip: data, model, and analysis

ChIP-chip (or ChIP-on-chip) is a technology for isolation and identification of genomic sites occupied by specific DNA-binding proteins in living cells. The ChIP-chip signals can be obtained over the whole genome by tiling arrays, where a peak shape is generally observed around a protein-binding site. In this article, we describe the ChIP-chip process and present a probability model for ChIP-chip data. We then propose a model-based method for recognizing the peak shapes for the purpose of detecting protein-binding sites. We also investigate the issue of bandwidth in nonparametric kernel smoothing method.     

Lectins: Sources,Activities, and Applications

ABSTRACT:?

Lectins are glycoproteins or oligomeric proteins with one or more sugar-binding site(s) per subunit. These molecules are of nonimmune origin and bind reversibly with specific sugars and precipitate polysaccharides, glycoproteins, and glycolipids bearing specific sugars, thus acting as cell recognizers. They play a key role during the initiation of infections in the altered behavior of cells during metastasis and in protection of neonates against environmental antigens. The specificity of lectins for certain sugars has been used as probes to detect cell surface sugars, enzymes, immunoglo-bulins, and to identify tumorogenic cells. Lectin-liposome conjugates have also found applications for targeted drug delivery. In addition, they have been used for flocculation of bacterial suspensions in the industry. This review discusses various sources of lectins and the mechanism behind their potential role in diverse fields of biological interest.     

Cutinase: Characteristics,preparation, and application

Cutinases (E.C. 3.1.1.74) belong to the α/β-hydrolase superfamily. They were initially discovered because they are secreted by fungi to hydrolyze the ester bonds of the plant polymer cutin. Since then, they have been shown to catalyze the hydrolysis of a variety of polymers, insoluble triacylglycerols, and low-molecular-weight soluble esters. Cutinases are also capable of catalyzing esterification and transesterification reactions. These relatively small, versatile, secreted catalysts have shown promise in a number of industrial applications. This review begins by describing the characteristics of cutinases, pointing out key differences among cutinases, esterases and lipases, and reviewing recent progress in engineering improved cutinases. It continues with a review of the methods used to produce cutinases, with the goal of obtaining sufficient quantities of material for use in industrial processes. Finally, the uses of cutinases in the textile industry are described. The studies presented here demonstrate that the cutinases are poised to become important industrial catalysts, replacing older technologies with more environmentally friendly processes.     

CFTR: Domains, Structure, and Function

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) (Collins, 1992). Over 500 naturally occurring mutations have been identified in CF gene which are located in all of the domains of the protein (Kerem et al., 1990; Mercier et al., 1993; Ghanem et al., 1994; Fanen et al., 1992; Ferec et al., 1992; Cutting et al., 1990). Early studies by several investigators characterized CFTR as a chloride channel (Anderson et al.; 1991b,c; Bear et al., 1991). The complex secondary structure of the protein suggested that CFTR might possess other functions in addition to being a chloride channel. Studies have established that the CFTR functions not only as a chloride channel but is indeed a regulator of sodium channels (Stutts et al., 1995), outwardly rectifying chloride channels (ORCC) (Gray et al., 1989; Garber et al., 1992; Egan et al., 1992; Hwang et al., 1989; Schwiebert et al., 1995) and also the transport of ATP (Schwiebert et al., 1995; Reisin et al., 1994). This mini-review deals with the studies which elucidate the functions of the various domains of CFTR, namely the transmembrane domains, TMD1 and TMD2, the two cytoplasmic nucleotide binding domains, NBD1 and NBD2, and the regulatory, R, domain.     

ADP-Ribosylation: Activation,Recognition, and Removal

ADP-ribosylation is a type of posttranslational modification catalyzed by members of the poly(ADP-ribose) (PAR) polymerase superfamily. ADP-ribosylation is initiated by PARPs, recognized by PAR binding proteins, and removed by PARG and other ADP-ribose hydrolases. These three groups of proteins work together to regulate the cellular and molecular response of PAR signaling, which is critical for a wide range of cellular and physiological functions.     

Matrilysin: Expression, purification, and characterization

The expression vector pGEX-2T under the control of the IPTG-inducibletac promotor is effective for the production of a fusion protein of glutathione transferase (GST, 26 kDa) and promatrilysin (28 kDa) separated from the C-terminus of GST by a thrombin cleavage site. Zwittergen (palmityl sulfobetaine), 2%, solubilizes the fusion protein that is found associated with inclusion bodies. The solubilized fusion protein is purified by affinity chromatography on GSH agarose. Promatrilysin is obtained by thrombin cleavage either on the column or after GSH elution of the fusion protein. Mono S chromatography of the recovered protein yields homogeneous promatrilysin. The zinc content of promatrilysin and its activated enzyme product is slightly greater than 2 mol of zinc per mole of protein. The results indicate that the matrix metalloproteinases (MMPs) contain two metal-binding sites at which zinc is firmly bound and possibly a third site at which it is weakly bound. Primary sequence alignments for all the MMPs have a sequence homologous to the zinc-binding site of astacin,HExxHxxGxxH, suggesting one of the zinc sites is a catalytic one, in agreement with the known inhibition of these enzymes by chelators. However, the other zinc-binding site(s) likely reflect the different ways that astacin and the MMP subfamilies are stabilized, i.e., disulfides in astacin and metal ions in the MMPs.     

Aflatoxins: Detection,toxicity, and biosynthesis

Aflatoxins are toxic and carcinogenic secondary metabolites produced mainly byAspergillus flavus andAspergillus parasiticus. The aflatoxins present in food and feed are hazardous to both human and animal health. A number of studies have been conducted on the detection, toxicity, biosynthesis, and regulation of aflatoxins due to the discovery of serious aflatoxicosis in farm animals, and the presence of aflatoxins in many food products. There are many reviews that focus on the biosynthesis of aflatoxin, yet there are few examinations of the overall aspects of aflatoxins, including detection, toxicity, and the regulation on biosynthesis. Thus, the goal of this article is to give an overview of the overall aspects of aflatoxins. This review consists of four parts; i) detection methods for aflatoxins, ii) the toxicity mechanism of aflatoxin B1, iii) gene cluster for aflatoxin biosynthesis, and iv) the regulation of aflatoxin biosynthesis.     

Lipid,lipoprotein, and apolipoprotein models: past,present, and future

Mones Berman's untimely death on 12 August 1982 put an end to his work in the development of theoretical biology. Arguments are examined, and it is concluded that a formal theory of lipoprotein metabolism flourished and expanded under the guidance of Dr. Berman. Not many scientists in the field of biology spend a major portion of their energies on theoretical work xxx was outstanding because of his early decision to follow the theoretical path.     

Pericytes: developmental, physiological, and pathological perspectives, problems, and promises

Pericytes, the mural cells of blood microvessels, have recently come into focus as regulators of vascular morphogenesis and function during development, cardiovascular homeostasis, and disease. Pericytes are implicated in the development of diabetic retinopathy and tissue fibrosis, and they are potential stromal targets for cancer therapy. Some pericytes are probably mesenchymal stem or progenitor cells, which give rise to adipocytes, cartilage, bone, and muscle. However, there is still confusion about the identity, ontogeny, and progeny of pericytes. Here, we review the history of these investigations, indicate emerging concepts, and point out problems and promise in the field of pericyte biology.