Gut microbiota composition correlates with diet and health in the elderly

Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.     

Movement, distribution, and predation: Lepidomeda vittata and nonnative salmonids in eastern Arizona

Nonnative rainbow trout ( Oncorhynchus mykiss ) are stocked into several reservoirs in the range of federally threatened Little Colorado spinedace ( Lepidomeda vittata ), and so have the opportunity to negatively impact Little Colorado spinedace populations. We examined rainbow trout escapement from Nelson Reservior into Nutrioso Creek, critical habitat for L. vittata . We also examined movements of L. vittata and incidence of predation by rainbow trout on L. vittata . We detected no movement of rainbow trout out of Nelson Reservoir over 4 years of study. Lepidomeda vittata marked in 3 streams did not move much; but sample sizes were too small to make any meaningful conclusions regarding movement. Most L. vittata we captured during surveys subsequent to marking were unmarked, suggesting movement out of the study area, low tag retention, mortality, or failure to capture marked fish. Lepidomeda vittata co-occurred with O. mykiss , Salmo trutta , and Salvelinus fontinalis and were typically less than half the size of the sympatric nonnative salmonids. Consequently, they are potential prey fish for these species. We found fish remains in stomachs of 33% of S. trutta , 6% of O. mykiss and 25% of S. fontinalis examined, but remains of L. vittata were found only in a single S. trutta . Because S. fontinalis are rare in the streams examined, they probably do not pose a great threat to L. vittata . Salmo trutta , which are no longer stocked, had the highest piscivory level and may thus pose more of a threat to L. vittata than O. mykiss .     

Spermine synthase

Spermine is present in many organisms including animals, plants, some fungi, some archaea, and some bacteria. It is synthesized by spermine synthase, a highly specific aminopropyltransferase. This review describes spermine synthase structure, genetics, and function. Structural and biochemical studies reveal that human spermine synthase is an obligate dimer. Each monomer contains a C-terminal domain where the active site is located, a central linking domain that also forms the lid of the catalytic domain, and an N-terminal domain that is structurally very similar to S-adenosylmethionine decarboxylase. Gyro mice, which have an X-chromosomal deletion including the spermine synthase (SMS) gene, lack all spermine and have a greatly reduced size, sterility, deafness, neurological abnormalities, and a tendency to sudden death. Mutations in the human SMS lead to a rise in spermidine and reduction of spermine causing Snyder-Robinson syndrome, an X-linked recessive condition characterized by mental retardation, skeletal defects, hypotonia, and movement disorders.     

Asian tapeworm ( Bothriocephalus acheilognathi ) in native fishes from the Little Colorado River, Grand Canyon, Arizona

Examination of gastrointestinal tracts of native cyprinids from the Little Colorado River (LCR) in Grand Canyon, Arizona, 1990-1994, revealed varying rates of prevalence and infrapopulation levels of Asian tapeworm ( Bothriocephalus acheilognathi ). Mean prevalence was 28% (range 0-78%) in humpback chub ( Gila cypha ) and 8% (range 0-46%) in speckled dace ( Rhinichthys osculus ), with infrapopulations as high as 46 and 28, respectively. We also note Asian tapeworm infection of nonnatives common carp ( Cyprinus carpio ), fathead minnow ( Pimephales promelas ), and plains killifish ( Fundulus zebrinus ) from the LCR. Reported pathogenic and chronic effects of this cestode to its definitive hosts add concern for the status of the Grand Canyon population of the federally endangered humpback chub. The rapidity which Asian tapeworm has spread to different drainages of the Colorado River Basin likely portends an eventual cosmopolitan basin distribution in lower elevations suitable to the parasite's thermophilic life history. Such biotic changes must be considered among the most serious threats to conservation and recovery of native fish populations.     

Interferon-like sequence of ovine trophoblast protein secreted by embryonic trophectoderm

In most species the length of a pregnancy exceeds that of the luteal phase of the ovarian cycle. The conceptus within the uterus, therefore, is believed to produce a substance or substances which directly or indirectly prolong the lifespan of the corpus luteum and prevent a return to ovarian cyclicity. This phenomenon is known as maternal recognition of pregnancy. The active substance implicated in signalling maternal recognition of pregnancy in the sheep is an embryonic secretory protein, known as ovine trophoblast protein-1 (oTP-1) (refs 2-4), which is targeted in a paracrine manner to the uterine epithelium of the mother. We report here the primary amino-acid sequence of oTP-1 as inferred from a cloned complementary DNA and demonstrate that the protein is most probably an interferon-alpha.     

Asymptotic properties of univariate sample k-means clusters

A random sample of sizeN is divided intok clusters that minimize the within clusters sum of squares locally. Some large sample properties of this k-means clustering method (ask approaches withN) are obtained. In one dimension, it is established that the sample k-means clusters are such that the within-cluster sums of squares are asymptotically equal, and that the sizes of the cluster intervals are inversely proportional to the one-third power of the underlying density at the midpoints of the intervals. The difficulty involved in generalizing the results to the multivariate case is mentioned.This research was supported in part by the National Science Foundation under Grant MCS75-08374. The author would like to thank John Hartigan and David Pollard for helpful discussions and comments.     

The earliest record of human activity in northern Europe

The colonization of Eurasia by early humans is a key event after their spread out of Africa, but the nature, timing and ecological context of the earliest human occupation of northwest Europe is uncertain and has been the subject of intense debate. The southern Caucasus was occupied about 1.8 million years (Myr) ago, whereas human remains from Atapuerca-TD6, Spain (more than 780 kyr ago) and Ceprano, Italy (about 800 kyr ago) show that early Homo had dispersed to the Mediterranean hinterland before the Brunhes-Matuyama magnetic polarity reversal (780 kyr ago). Until now, the earliest uncontested artefacts from northern Europe were much younger, suggesting that humans were unable to colonize northern latitudes until about 500 kyr ago. Here we report flint artefacts from the Cromer Forest-bed Formation at Pakefield (52 degrees N), Suffolk, UK, from an interglacial sequence yielding a diverse range of plant and animal fossils. Event and lithostratigraphy, palaeomagnetism, amino acid geochronology and biostratigraphy indicate that the artefacts date to the early part of the Brunhes Chron (about 700 kyr ago) and thus represent the earliest unequivocal evidence for human presence north of the Alps.     

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.