Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa

Both Alzheimer's disease and senile dementia of the Alzheimer type (AD/SDAT) are progressive dementias characterized neuropathologically by the presence in the cerebral cortex of numerous neurofibrillary tangles and neuritic plaques. We use the abbreviation AD/SDAT to denote all such cases, irrespective of age of onset. Studies of neurotransmitter-related parameters in autopsied brain tissues from patients with AD/SDAT have, to date, been confined to five putative transmitter systems. Acetycholine-releasing neurones seem to be most markedly and consistently affected, as judged by the extensive reductions in choline acetyltransferase (ChAT) and acetylcholinesterase activities that have been reported. Despite numerous studies, there is no consistent evidence for the involvement of neurones releasing dopamine, noradrenaline, serotonin, or gamma-aminobutyric acid in AD/SDAT, nor for loss of muscarinic cholinergic receptors. Thus, the involvement of cholinergic neurones in AD/SDAT seems to be specific. However, the possible involvement of neurones using other chemicals as transmitters has yet to be explored. The recent recognition of the existence of so-called 'peptidergic neurones' in the mammalian brain (for review see ref. 8) and the availability of radioimmunoassay (RIA) techniques for studying these peptides, have led us to begin a systematic investigation of neuropeptides in autopsied brain tissue from cases of AD/SDAT, and from neurologically normal individuals. We report here results obtained with a RIA for somatostatin, showing that somatostatin-like immunoreactivity in the cerebral cortex is reduced in tissue from AD/SDAT patients.     

Amplitude spectroscopy of a solid-state artificial atom

The energy-level structure of a quantum system, which has a fundamental role in its behaviour, can be observed as discrete lines and features in absorption and emission spectra. Conventionally, spectra are measured using frequency spectroscopy, whereby the frequency of a harmonic electromagnetic driving field is tuned into resonance with a particular separation between energy levels. Although this technique has been successfully employed in a variety of physical systems, including natural and artificial atoms and molecules, its application is not universally straightforward and becomes extremely challenging for frequencies in the range of tens to hundreds of gigahertz. Here we introduce a complementary approach, amplitude spectroscopy, whereby a harmonic driving field sweeps an artificial atom through the avoided crossings between energy levels at a fixed frequency. Spectroscopic information is obtained from the amplitude dependence of the system's response, thereby overcoming many of the limitations of a broadband-frequency-based approach. The resulting 'spectroscopy diamonds', the regions in parameter space where transitions between specific pairs of levels can occur, exhibit interference patterns and population inversion that serve to distinguish the atom's spectrum. Amplitude spectroscopy provides a means of manipulating and characterizing systems over an extremely broad bandwidth, using only a single driving frequency that may be orders of magnitude smaller than the energy scales being probed.     

Helicobacter exploits integrin for type IV secretion and kinase activation

Integrins are important mammalian receptors involved in normal cellular functions as well as pathogenesis of chronic inflammation and cancer. We propose that integrins are exploited by the gastric pathogen and type-1 carcinogen Helicobacter pylori for injection of the bacterial oncoprotein cytotoxin-associated gene A (CagA) into gastric epithelial cells. Virulent H. pylori express a type-IV secretion pilus that injects CagA into the host cell; CagA then becomes tyrosine-phosphorylated by Src family kinases. However, the identity of the host cell receptor involved in this process has remained unknown. Here we show that the H. pylori CagL protein is a specialized adhesin that is targeted to the pilus surface, where it binds to and activates integrin alpha5beta1 receptor on gastric epithelial cells through an arginine-glycine-aspartate motif. This interaction triggers CagA delivery into target cells as well as activation of focal adhesion kinase and Src. Our findings provide insights into the role of integrins in H.-pylori-induced pathogenesis. CagL may be exploited as a new molecular tool for our further understanding of integrin signalling.     

High-energy colliders and the rise of the standard model

Over the past quarter of a century, experiments at high-energy particle colliders have established the standard model as the precise theory of particle interactions up to the 100 GeV scale. A series of important experimental discoveries and measurements have filled in most of the missing pieces and tested the predictions of the standard model with great precision.     

From artefacts to atoms - A new SI for 2018 to be based on fundamental constants

At the 26th General Conference on Weights and Measures (CGPM) in November 2018, it is planned to adopt a new definition of the International System of Units, SI, based on the fixed numerical values of seven defining constants, broadly the fundamental constants of physics. This will be the culmination of more than two hundred years of metrology, instantiating for the first time the original ideas of the creators of the metric system. The key is the replacement of the present definition of the unit of mass, the kilogram artefact of platinum-iridium, by one based on a fixed numerical value of the Planck constant. This article outlines how this has come about, how it will work, why we need a system of measurement that is uniform, accessible world-wide and stable in the long term, and the international structures that now exist to achieve it.     

Reproductive biology, hybridization and flower visitors of rare Sclerocactus taxa in Utah's Uintah Basin

We studied the mating system and flower visitors of 2 threatened species of Sclerocactus (Cactaceae) in the Uintah Basin of eastern Utah—an area undergoing rapid energy development. We found that both S. wetlandicus and S. brevispinus are predominantly outcrossed and are essentially self-incompatible. A third presumptive taxon (undescribed; here called S. wetlandicus -var1) is fully self-compatible but cannot produce seeds unless the flowers are visited by pollinators. We found tentative evidence for pollinator limitation of fruit set in S. brevispinus but not in the other taxa. Pollinators are largely species of native ground-nesting bees in the subfamily Halictinae. These bees are indiscriminate collectors of pollen and nectar from Sclerocactus flowers and other plant species. The well-being of Sclerocactus populations requires that land managers ensure the preservation of halictid bee habitat, which includes both nesting sites and a diversity of floral resources. These bees are also undoubtedly the pollen vectors responsible for the production of hybrids in areas where S. wetlandicus and S. brevispinus meet. We experimentally confirmed that reciprocal crosses between S. wetlandicus and S. brevispinus are indistinguishable from each other or from pure crosses in fruits/flower, seeds/fruit and seed weights. We suggest that hybridization preceded energy development, that it attests to the ongoing process of evolution in the Sclerocactus group, and that it should not be suppressed by anthropogenic activity.     

Typification and nomenclature of Hedysarum boreale Nutt. (Leguminosae)

The holotype of Hedysarum boreale Nutt. is convarietal with natural populations now known as Hedysarum boreale Nutt. var. cinerascens (Rydb.) Rollins instead of var. boreale. The new combination Hedysarum boreale Nutt. var. rivulare (Williams) Northstrom is proposed for populations formerly known as var. boreale.     

Discretionary databases in forecasting

Information for forecasting databases is often initially under the control of individuals who have no compelling reason to contribute, and who face various significant costs if they do. Such discretionary databases are subject to public goods problems, and are likely to be undersupplied, even when all participants agree that the overall benefits outweigh the overall costs. This paper explores the implications of this incentive structure for the existence, completeness and accuracy of forecasting databases. It also offers some hypotheses as to when the difficulties will be more and less severe, and outlines some directions for possible remedial strategies.