Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2-6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.     

Error‐free and mutagenic processing of topoisomerase 1‐provoked damage at genomic ribonucleotides

Genomic ribonucleotides incorporated during DNA replication are commonly repaired by RNase H2‐dependent ribonucleotide excision repair (RER). When RNase H2 is compromised, such as in Aicardi‐Goutières patients, genomic ribonucleotides either persist or are processed by DNA topoisomerase 1 (Top1) by either error‐free or mutagenic repair. Here, we present a biochemical analysis of these pathways. Top1 cleavage at genomic ribonucleotides can produce ribonucleoside‐2′,3′‐cyclic phosphate‐terminated nicks. Remarkably, this nick is rapidly reverted by Top1, thereby providing another opportunity for repair by RER. However, the 2′,3′‐cyclic phosphate‐terminated nick is also processed by Top1 incision, generally 2 nucleotides upstream of the nick, which produces a covalent Top1–DNA complex with a 2‐nucleotide gap. We show that these covalent complexes can be processed by proteolysis, followed by removal of the phospho‐peptide by Tdp1 and the 3′‐phosphate by Tpp1 to mediate error‐free repair. However, when the 2‐nucleotide gap is associated with a dinucleotide repeat sequence, sequence slippage re‐alignment followed by Top1‐mediated religation can occur which results in 2‐nucleotide deletion. The efficiency of deletion formation shows strong sequence‐context dependence.     

Changing Times, Changing Faces: Franz Boas's Immigrant Study in Modern Perspective

Franz Boas's study of the changes in bodily form of descendants of immigrants has stood for over ninety years as proof of environmental influences on cranial form. Recent reanalysis of his data have shown differing interpretations of the importance of his findings. Here, we explore the historical, political, and social setting of the study that could have led Boas to overstate the importance of his findings. We also include a discussion of the issue at large with respect to the study of modern and prehistoric human variation. Given the current state of population research using craniometric data we conclude, as many of Boas's early criticism have, that while some of the changes observed by Boas have statistical credibility, they generally lack biological meaning when considered in the scope of the degree of modern human variation. [Keywords: plasticity, immigration, craniometries, cranial index, human variation]     

Field performance of maize grown from <Emphasis Type="Italic">Fusarium verticillioides</Emphasis>-inoculated seed

Fusarium verticillioides is an important fungus occupying dual roles in the maize plant. The fungus functions as an endophyte, a fungal/host interaction beneficial to the growth of some plants. At other times, the fungus may function as a mycotoxin producing pathogen. The advantages and/or disadvantages of the endophytic relationship must be established in order to target appropriate sites for controlling diseases and mycotoxins in maize. One possibility could be to ensure seed maize is fungal free prior to planting. Reciprocal inoculations were made with two fungal isolates on seed of two maize genotypes. Yield was measured at harvest by ear and seed characters and vegetative growth at one-month intervals for plant survival, height, weight and stem diameter. Yield and vegetative growth differed among mature plants only once based on seed inoculation status. In 1998, plant weight was reduced and seed weight per ear was increased for the dent maize, GT-MAS: gk, grown from F. verticillioides RRC 374- inoculated seed compared to other seed treatments. Most vegetative characters were reduced at the first collection for Silver Queen plants grown from F. verticillioides-inoculated seed in 1997 and 1999, but not in 1998. However, no significant differences occurred among mature Silver Queen plants during any of the three growing seasons. In conclusion, yield and vegetative growth of mature maize plants grown from F. verticillioides-inoculated seed were equal to or greater than plants grown from non-inoculated seed under south Georgia field conditions during 1997, 1998, and 1999.     

A Michaelis-Menten-style model for the autocatalytic enzyme prostaglandin H synthase

Prostaglandin H synthase (PGHS) is an autocatalytic enzyme which plays a key role in the arachidonic acid metabolic pathway. PGHS mediates the formation of prostaglandin H₂, the precursor for a number of prostaglandins which are important in a wide variety of biological processes, including inflammation, blood clotting, renal function, and tumorigenesis. Here we present a Michaelis-Menten-style model for PGHS. A stability analysis determines when the reaction becomes self-sustaining, and can help explain the regulation of PGHS activity in vivo. We also consider a quasi-steady-state approximation (QSSA) for the model, and present conditions under which the QSSA is expected to be a good approximation. Applying the QSSA for this model can be useful in computationally intensive modeling endeavors involving PGHS.     

The Modification of Ancient Woodland Ground Flora at Arable Edges

The last five decades have witnessed an intensification of agriculture with a marked increase in the use of agrochemicals. This study investigated whether arable edges affect ancient woods and the extent of any modifications to the ground flora. Plant species were recorded from a total of 84 transects into the centre of the woods, of which 59 were taken from the arable–woodland interface and 25 were taken from non-arable land or woodland rides. Ellenberg indicator and CSR values were used to infer fertility and features of the environment. Results suggested that, after adjusting for light and moisture conditions, elevated nitrogen levels might occur in ancient woodlands to a distance of at least 100 m from arable farmland. Furthermore, the transects from the arable fields had a substantially altered herb-layer with respect to species composition, notably a greater percentage cover of ruderal and nitrophilous species, and a lower cover of stress tolerator species. Smaller woods contained a greater cover of competitor and nitrophilous species and a lower cover of stress tolerators and ancient woodland indicator species. We conclude that farming may be unwittingly modifying the ground flora of ancient woodlands adjacent to arable land and that small and irregularly shaped woods are most at risk. It is recommended that farmers apply agrochemicals in such a way that drift is minimised, and that large, valuable ancient woods be protected by a substantial buffer zone.     

Observations on the history of non-insect invertebrate pathology from the perspective of a participant

This paper discusses diseases of commercially important non-insect invertebrates from both a historical and a personal perspective. Early studies of curious scientists such as Metchnikoff using invertebrate systems led to important discoveries with much wider impact. As commercial culture of oysters, shrimp, and other invertebrates grew, so did studies of their diseases. Here, the impact of pioneering scientists and important new techniques on our understanding of these diseases is described.