The complement system in age-related macular degeneration

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

     

A new combination in Penstemon (Scrophulariaceae)

Field and herbarium studies of Penstemon cyananthus Hook. ssp. longiflorus Pennell suggest that this taxon be elevated to species rank.       

Sex ratios of the white-tailed antelope ground squirrel (Ammospermophilus leucurus), Indian Wells Valley, San Bernardino County, California

We studied the white-tailed antelope ground squirrel during spring and summer 2006 to determine young-of-the-year and adult sex ratios in the Indian Wells Valley, San Bernardino County, California. We calculated a young-of-the-year sex ratio of 1.45:1 (female to male), whereas the adult sex ratio was approximately 1:1. Our young-ofthe-year sex ratio was greater than the 1.1:1 (female to male) natal sex ratio previously reported. Differences between young-of-the-year and adult sex ratios may represent low female young-of-the-year survivorship in the Indian Wells Valley.     

A small carnivore survey technique

Thirty-nine previously unpublished reports of the endangered black-footed ferret from Wyoming are listed with dates, locations, number of animals, sources, and comments.     

Popper and Dingle on special relativity and the issue of symmetry

Karl Popper and Herbert Dingle engaged in a fascinating debate concerning the kind of theory the special theory of relativity is. One of the issues was whether applications of the theory could be made consistent with the principle of relativity, a cornerstone of the theory itself. The principle of relativity seems to imply some sort of symmetry in results obtained for similar experiments as observed in two different inertial reference frames. Peter Hayes has recently dealt with the Dingle–Popper debate on this matter, as well as other issues. The present paper seeks to clarify what kind of symmetry is appropriate in a situation discussed by Popper, Dingle, and Hayes.     

Construction of heteroduplex DNA and in vitro model for functional analysis of mismatch repair

Functional deficiency of mismatch repair (MMR) system is one of the mechanisms of tumorigenesis. With the development of the investigation and the requirement from the clinical diagnosis and treatment it is necessary to build up a method to evaluate the functional status of the whole MMR system in the concerned tumors. The original ssDNA and dsDNA from wild type (wt) bacteriophage M13mp2 and its three derivates with mutation points in the     

Specific inhibition of herpesvirus ribonucleotide reductase by synthetic peptides

Ribonucleotide reductase is an essential enzyme for DNA synthesis in all prokaryotic and eukaryotic cells; it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. Several herpesviruses including herpes simplex virus type 1 (HSV-1), HSV-2, pseudorabies virus (PRV), equine herpesvirus type 1 (EHV-1) and Epstein-Barr virus (EBV) have been found to induce novel ribonucleotide reductase activities. There is evidence that the HSV-1 ribonucleotide reductase activity is virus-encoded and essential for virus replication. This makes herpesvirus ribonucleotide reductases potential targets for antiviral chemotherapy. The HSV-1-encoded enzyme consists of two subunits: V136, the large subunit of relative molecular mass (Mr) 136,000 (136K) (RR1), which has been shown to be essential for enzyme activity, and V38, the small subunit (RR2) which forms a complex with the large subunit and is also likely to be essential for enzyme activity. Two particular features of the enzyme make it an attractive antiviral target. First, there is evidence for a common, highly conserved herpesvirus ribonucleotide reductase and second, the interaction between the large and small subunits may itself be exploitable. Here we identify a synthetic peptide which specifically inhibits the activity of virus-induced enzyme. We deduce that the mechanism of inhibition involves interference with the normal interaction between the two types of subunit.