bluuebunny/crossref_metadata_2025 huggingface dataset:
VARIATION IN ARBOVIRUS INFECTION RATES IN SPECIES OF BIRDS SAMPLED IN A SEROLOGICAL SURVEY DURING AN ENCEPHALITIS EPIDEMIC IN THE MURRAY VALLEY OF SOUTH‐EASTERN AUSTRALIA, FEBRUARY 1974
Authors: Marshall Ian D , Brown Bevan K , Keith Kent , Gard Geoffrey P , Thibos Elspeth
Published: August 2007

There was extensive and exuberant breeding of waterbirds before and during an epidemic of arboviral encephalitis in the Murray Valley of south eastern Australia in 1974. As estimated by haemagglutination inhibition tests on 432 bird sera collected between 4th and 13th February, 1974, infection with Murray Valley encephalitis virus, Kunjin virus and possibly other flaviviruses was concentrated in species of the Order Ciconiiformes (55% positive) and Pelecaniformes (41%), compared with only 5% in Anseriformes. Although Sindbis virus infections were also highest in these 2 Orders (56% and 46%, respectively), the incidence of antibodies was spread more uniformly through other Orders than with the flaviviruses: e.g. Anseriformes, 33%, Podicipitiformes, 27%. As viruses were recovered virtually only from Culex annulirostris mosquitoes, the different patterns of infection seem unrelated to host preference by mosquito species or behavioural response to mosquito attack, and suggest a specific relationship between MVE/KUN and Ciconiiformes and Pelecaniformes. The highest infection rate was 22/25 in mature rufous night herons (formerly nankeen night herons) Nyclicorax calendonicus, and here tolerance to mosquito attack was probably a contributing factor. Assays of sera from 13 horses indicated high infection rates both alphaviruses and flaviviruses.
AN NK‐LIKE CELL LIMITS THE ADOPTIVE RESPONSE FROM “PRE‐PROGENITOR” B CELLS
Authors: Shortman Ken , Wilson Anne , Baker Julie , Burton Robert C
Published: August 2007

Evidence is presented that a dividing, Thy 1·2 positive and NK 1·2 positive cell with a suppressive effect on adoptive responses is present in the spleens of normal and athymic mice, and that its function may be enhanced by non‐specific antigenic stimulation. NK cells may thus exert a controlling function on the proliferation and differentiation of B cells.

The main experimental observation is that under certain assay conditions incubation of spleen cells with 3H‐TdR in order to kill dividing, non‐specifically activated ‘pre‐progenitor’ B cells may actually give a marked increase rather than a decrease in a subsequent hapten‐specific primary adoptive response. An activated ‘suppressor’ population was proposed as the reason for this effect. This anomalous effect may be avoided and the cycle state of the B cells assessed by prior elimination of cells bearing Thy 1 antigen, together with the use of a more reliable hydroxyurea incubation to kill dividing B cells.
ISLET ALLOGRAFTING WITHOUT IMMUNOSUPPRESSION: REVERSAL OF INSULITIS‐ASSOCIATED DIABETES AND A CASE OF SPONTANEOUS JUVENILE ONSET DIABETES IN MICE
Authors: Prowse Stephen J , Steele Edward J , Lafferty Kevin J
Published: August 2007

The development of juvenile onset diabetes may involve an auto immune response causing an insulitis and beta cell destruction. It has been suggested that replacement of the host's beta cells by transplantation may lead to the destruction of the new tissue by the same processes which caused the destruction of the original beta cells. This study does not support this proposal It was possible to reverse insulitis‐induced diabetes and spontaneous murine ‘Juvenile onset’ diabetes by transplantation of cultured islet allografts. The grafts survived and maintained normoglycaemia for periods in excess of 100 days.
RESISTANCE TO KLEBSIELLA PNEVMONIAE AND THE IMPORTANCE OF TWO BACTERIAL ANTIGENS
Authors: Cooper J McA , Rowley D
Published: August 2007

The resistance of mice to a lethal infection with Klebsiella pneumoniae, type I, was investigated. Antibody of both IgG and IgM class produced good protection when given with an intra‐nasal inoculum of the organism. While antibody directed against capsular antigens was highly protective, so too was antibody directed against a second, non‐capsular and heat‐labile antigen. This antigen does not appear to be related to either the K or O antigens of Klebsiella and is present in several strains of Klebsiella. It is suggested that this antigen may play a role in determining resistance to this organism by humans.
IMMUNOPRECIPITATION OF BIOSYNTHETICALLY LABELLED, STAGE‐SPECIFIC PROTEINS FROM CULTURED PLASMODIUM FALCIPARUM USING INHIBITORY HUMAN SERA
Authors: Myler Peter , Chiu Suying , Upcroft Jacqueline , Castelino Daniel , Kidson Chev
Published: August 2007

Proteins from synchronized continuous cultures of Plasmodium falciparum were biosynthetically labelled with [35S]methionine at ring, trophozoite, and schizont stages. Several proteins appeared to be synthesized predominantly at one stage only, especially the schizont stage. Immunoprecipitation using inhibitory human sera revealed that a variety of proteins, from all stages of parasite growth, were recognized. More proteins, especially those with high molecular weight, were precipitated from the schizont stage than from ring and trophozoite stages, but two major proteins (MW ∼ 70,000 daltons and ∼ 45,000 daltons) were recognized in all three stages.
HUMORAL AND CELL‐MEDIATED IMMUNE RESPONSES IN MURINE STRONGYLOIDIASIS
Authors: Dawkins HJS , Carroll SM , Grove DI
Published: August 2007

The immunological changes occurring after primary and challenge infections with Strongyloides ratti in C57B1/6 mice are described. Serum IgM and IgG antibodies against Strongyloides antigen appeared one week after primary infection. The levels of antibody in both immunoglobulin classes increased markedly after secondary infection and persisted for at least 6 weeks. Immediate hypersensitivity (15 min footpad) reactions were transient after a primary infection, but were marked and persistent after a secondary infection. Arthus (5 h footpad) reactions were mild and very transient after a primary infection, but a persistent anamnestic response was seen after challenge infection. Cell‐mediated immune (24 h footpad) reactions were marked 1 week after both primary and secondary infections but were not sustained in either case. Antigen‐reactive cells were present in the mesenteric lymph nodes 1 week after primary infection and 1–4 weeks after challenge infection. No antigen‐reactive cells were noted in the spleen. Mesenteric lymph node (MLN) cells and spleen cells from infected or uninfected animals were stimulated with phytohaemagglutinin (PHA) or lipopolysaccharide (LPS) but did not differ significantly in their 3H thymidine incorporation. A transient eosinophilia was observed after primary infection and an anamnestic response was noted after challenge infection. The possible roles of these immunological responses to worm rejection and immunopathology are considered.
A MECHANISM FOR THE THIAMIN‐SPARING ACTION OF DIETARY XYLITOL IN THE RAT
Authors: Rofe Allan M , Krishnan Ravi , Bais Renze , Edwards John B , Conyers Robert AJ
Published: August 2007

The changes induced by dietary xylitol in the gastrointestinal tract of the rat were investigated in relation to the phenomenon of vitamin‐sparing. Within 18 days of consuming a synthetic diet, deficient in thiamin, riboflavin and pyridoxine, rats ceased to grow and began to lose weight rapidly. If xylitol was then included in the diet (10% w/w), the effect of the vitamin‐deficient diet on growth was reversed. Moreover, within 3 days of the rats ingesting xylitol, the metabolism of this sugar polyol by the caecal microflora was increased 17‐fold and the caecal concentrations of thiamin and thiamin pyrophosphate were increased 5‐fold. Increases were also observed in the caecal size, the weight of the caecal contents, and the weight of the caecal wall. In contrast to the rapid changes observed within the caecum, liver thiamin pyrophosphate levels did not rise until 6–12 days after the feeding of xylitol, at which time the rats had begun to gain weight.

The caecal contents were shown to contain facultative bacteria which have the ability to metabolise and grow on xylitol and which can, at the same time, synthesise thiamin. Species of the genera Klebsiella, Serratia and Micrococcus which have this ability were isolated from the caecal contents of rats. It is assumed that coprophagy is the means by which the thiamin and other vitamins synthesised by enteral bacteria become available to the host, although some absorption from the caecum cannot be excluded.
Pharmacological Onomastics: What's in a name?
Authors: Kenakin T P
Published: August 2007

Drugs are named for their primary receptor target and overt action (agonism, antagonism) but the observation of multiple or collateral efficacies emanating from drugs activating a single receptor target is posing a challenge for drug classification and nomenclature. With increasing abilities to detect alteration in cellular function has come the identification of efficacies that are not necessarily manifest in obvious changes in cell response. Specifically, some agonists selectively activate cellular pathways, demonstrate phenotypic behaviour associated with cell type and some antagonists actively induce receptor internalization without activation. In addition, the effects of allosteric modulators can be linked to the nature of the co‐binding ligand posing a similar complication in classification and naming. Thus, accurate labels for this new generation of selective drugs may require identification of receptor partners (G‐protein type, β‐arrestin) or pathway or, in the case of allosteric modulators, identification of co‐binding ligands. The association of distinct phenotypic behaviours with molecules opens the opportunity to better associate clinical effects with distinct pharmacological properties.

British Journal of Pharmacology(2008)153, 432–438; doi:10.1038/sj.bjp.0707407; published online 13 August 2007
Cyclic GMP and protein kinase‐G in myocardial ischaemia‐reperfusion: opportunities and obstacles for survival signaling
Authors: Burley D S , Ferdinandy P , Baxter G F
Published: August 2007

It is clear that multiple signalling pathways regulate the critical balance between cell death and survival in myocardial ischaemia–reperfusion. Recent attention has focused on the activation of survival or salvage kinases, particularly during reperfusion, as a common mechanism of many cardioprotective interventions. The phosphatidyl inositol 3′‐hydroxy kinase/Akt complex (PI3K/Akt) and p42/p44 mitogen‐activated protein kinase cascades have been widely promoted in this respect but the cyclic guanosine 3′,5′‐monophosphate/cGMP‐dependent protein kinase (cGMP/PKG) signal transduction cassette has been less systematically investigated as a survival cascade. We propose that activation of the cGMP/PKG signalling pathway, following activation of soluble or particulate guanylate cyclases, may play a pivotal role in survival signalling in ischaemia–reperfusion, especially in the classical preconditioning, delayed preconditioning and postconditioning paradigms. The resurgence of interest in reperfusion injury, largely as a result of postconditioning‐related research, has confirmed that the cGMP/PKG pathway is a pivotal salvage mechanism in reperfusion. Numerous studies suggest that the infarct‐limiting effects of preconditioning and postconditioning, exogenously donated nitric oxide (NO), natriuretic peptides, phosphodiesterase inhibitors, and other diverse drugs and mediators such as HMG co‐A reductase inhibitors (statins), Rho‐kinase inhibitors and adrenomedullin, whether given before and during ischaemia, or specifically at the onset of reperfusion, may be mediated by activation or enhancement of the cGMP pathway, either directly or indirectly via endogenous NO generation downstream of PI3K/Akt. Putative mechanisms of protection include PKG regulation of Ca2+homeostasis through the modification of sarcoplasmic reticulum Ca2+uptake mechanisms, and PKG‐induced opening of ATP‐sensitive K+channels during ischaemia and/or reperfusion. At present, significant technical obstacles in defining the precise roles played by cGMP/PKG signalling include the heavy reliance on pharmacological PKG inhibitors of uncertain selectivity, difficulties in determining PKG activity in intact tissue, and the growing recognition that intracellular compartmentalisation of the cGMP pool may contribute markedly to the nucleotide's biological actions and biochemical determination. Overall, the body of experimental evidence suggests that cGMP/PKG survival signalling ameliorates irreversible injury associated with ischaemia–reperfusion and may be a tractable therapeutic target.

British Journal of Pharmacology(2007)152, 855–869; doi:10.1038/sj.bjp.0707409; published online 13 August 2007
Purinergic P2X receptor activation induces emetic responses in ferrets and Suncus murinus (house musk shrews)
Authors: Nagakura Y , Kakimoto S , Matsuoka N
Published: August 2007

Background and purpose:

Despite the rapid progress made in understanding the significant role played by signalling via extracellular ATP in physiology and pathology, there has been no clear information generated on its involvement in the emetic response.

Experimental approach:

In the present study, the emetogenic potential of extracellular ATP signalling in mammalian species was examined using ferrets and Suncus murinus (house musk shrews). A slowly degradable ATP analogue, α,β‐methyleneATP (α,β‐meATP), was used to activate the P2X receptors, and either the non‐selective P2 receptor antagonist, pyridoxal phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), or the specific P2X3 homomer and P2X2/3 heteromer antagonist, A‐317491, were tested against the agonist‐induced response.

Key results:

Intraperitoneal injection of α,β‐meATP produced significant emetic responses in ferrets (1 ‐ 30 mg kg−1) and in Suncus murinus (5 ‐ 50 mg kg−1). The responses occurred frequently within the first 10 min after administration, much less frequently from 11 to 60 min and no responses occurred later than 60 min. The emetic responses were completely inhibited by intraperitoneal pre‐treatment with PPADS (100 mg kg−1) or A‐317491 (100 mg kg−1). Abdominal surgical vagotomy did not reduce the emetic response in Suncus murinus significantly.

Conclusions and implications:

These results for the first time indicate that the activation of P2X receptors evokes emetic responses in mammalian species. The P2X3 homomer and·or P2X2/3 heteromer in the area postrema could be responsible for the emetic response. This finding contributes to the elucidation of the roles played by extracellular ATP signalling in various emetic symptoms.

British Journal of Pharmacology (2007) 152, 464–470; doi:10.1038/sj.bjp.0707418; published online 13 August 2007
Sex ratios, fruit set and size-class structure in the threatened, gynodioecious, sand-dune species Pimelea arenaria (Thymelaeaceae) from New Zealand
Authors: Merrett Merilyn F.
Published: August 2007

Pimelea arenaria sens. str. Cunn. is one of a small suite of native species that occur exclusively on unconsolidated sand dunes and in dune hollows of the North Island and Chatham Islands of New Zealand. It has become extinct at several beaches, and is currently listed in the Gradual Decline category of threatened plants. Eighteen populations of P. arenaria from throughout the North Island of New Zealand were investigated to determine sex ratios, fruit set and population size-class structures. Sex ratios were variable among the 18 study populations; the proportion of females was higher in populations in the northern half of the North Island (15.9–45.5%) than in populations from Kawhia southwards (0–12.7%). Females were absent from three south-western coastal populations. Although fruit set was relatively high, averaging 47% for female and 68% for hermaphroditic plants, recruitment failure was evident at most of the 18 sites surveyed. There was no evidence that sex ratios or fruit set were factors contributing to recruitment failure. Although most of the populations surveyed are not under immediate threat, lack of recruitment could affect population persistence in the long term.
The extent of dryland salinity in remnant woodland and forest within an agricultural landscape
Authors: Seddon Julian A. , Zerger Andre , Doyle Stuart J. , Briggs Sue V.
Published: August 2007

Dryland salinity is considered a significant and increasing threat to sustainable land management and biodiversity across large parts of temperate Australia. However, there is little information on the extent of this threat to terrestrial ecosystems in south-eastern Australia. This paper provides a quantitative assessment of the extent of dryland salinity in remnant native woody vegetation in the agriculture-dominated landscape of the Boorowa Shire located in the South West Slopes bioregion of south-eastern Australia. The amount and type of native woody vegetation in the Boorowa Shire affected by dryland salinity was assessed by analysing the extent of overlap between the following three spatial data layers: (1) woody vegetation mapping derived from high-resolution satellite imagery, (2) existing vegetation community mapping predicted from field data and expert opinion and (3) existing dryland salinity outbreak mapping derived from air photo interpretation and filed verification. There were more than 6000 patches of salt outbreak in woody vegetation in the Boorowa Shire, 383 (6%) of which were 1 ha or larger in area. Almost 2000 ha of woody vegetation were affected by dryland salinity, representing ~3% of the extant native woody vegetation in the Boorowa Shire. The vegetation type with the largest total area affected by dryland salinity was yellow box (Eucalyptus melliodora Cunn. Ex Schauer)–Blakely’s red gum (E. Blakelyi Maiden) woodland. As a proportion of their current extent, vegetation communities lower in the landscape were significantly more affected than those higher up the topographic sequence, with 14% of riparian communities and nearly 6% of yellow box–Blakely’s red gum woodland exhibiting symptoms of dryland salinity. About 1% of white box (E. albens Benth) woodland, and of hill communities which are on mid- and upper slopes, were affected. The pattern of salinity outbreaks in relation to landscape position and vegetation type is significant for biodiversity conservation because the vegetation communities most affected by salinisation are those most heavily cleared and modified post-European settlement. Throughout the South West Slopes of New South Wales, remnants of riparian communities and yellow box–Blakely’s red gum woodland are highly cleared, fragmented and degraded. Dryland salinity represents an additional threat to these vegetation communities and their component species. Salinisation of woodland ecosystems poses significant problems for land managers. The long-term viability of these woodland remnants needs to be considered when allocating limited public funds for woodland conservation, whether on private land or in formal reserves.
Geographic variation in extrafloral nectaries in the ant-associated plant genus Adriana (Euphorbiaceae) and its relationship to water availability
Authors: Whalen M. A. , Mackay D. A.
Published: August 2007

The relationship between geographic variation in extrafloral nectary size and climatic variation was assessed in three taxa within Adriana (Euphorbiaceae). In each taxon, there was a significant association between gland size and moisture-related climatic variables. A glasshouse experiment was conducted to examine the effect of water stress on nectary longevity, and it was found that the secretory activity of nectaries declined more rapidly on drought-stressed plants than on watered plants.
Relating pine-litter intrusion to plant-community structure in native eucalypt woodland adjacent to Pinus radiata (Pinaceae) plantations
Authors: Baker Andrew C. , Murray Brad R. , Hose Grant C.
Published: August 2007

Radiata pine (Pinus radiata D.Don) plantations are often found in close proximity to vegetation set aside for biodiversity conservation. We examined the intrusive effects of radiata pine beyond the confines of plantations by quantifying the penetration of pine litter (needles, cones, twigs and seeds) and wildings from plantations into adjacent eucalypt woodland in the Jenolan Caves Karst Conservation Reserve (south-eastern Australia). We then investigated the relationship between pine-litter intrusion and plant-community structure in adjacent woodland vegetation. We found significantly higher quantities of pine litter and wildings at all sites adjacent to plantations than at reference woodland sites that were not adjacent to plantations. At adjacent sites, pine litter decreased significantly with increasing distance from plantations. Alarmingly, native plant species richness declined and exotic plant species richness increased with increasing quantities of pine litter. Thus, there were fewer native plant species and more exotics in areas bordering pine plantations. Our findings suggest a potentially important link between the intrusion of pine litter and a loss of native biodiversity and facilitation of exotic-species invasion. We suggest the provision of a buffer zone around plantations in order to minimise intrusive impacts of plantations on native biodiversity.
An actual scenario that demonstrates sulcotrione photodegradation on maize leaves after spraying
Authors: ter Halle Alexandra , Piquet Agnès , Richard Claire
Published: August 2007

Environmental context. Recent developments in environmental monitoring have revealed that pesticides are dispersed through all parts of the environment. Air, water and soil are all contaminated. In this context there are tightening regulations on pesticide use with the goal of limiting their environmental impact. We look here at how pesticides can actually break down very quickly after their application on leaves, due to the effect of sunlight, i.e. ‘photodegradation’. Understanding this phenomenon could help to reduce application rates.
Abstract. The fate of sulcotrione (a pesticide and herbicide) has been monitored on maize leaves after spraying. One hour after spraying, 10% of the active ingredient is already transformed by the action of solar light. Sulcotrione mainly undergoes photocyclisation. The photoproduct, which has been fully characterised, is easily detected on the leaf surface. The day after spraying, 90% of the sulcotrione initially detected has disappeared. Twenty three percent is detected as the cyclisation product. Two days after spraying sulcotrione is no longer detected but the photoproduct still represents 7% of the initial amount detected. This study brings out the importance of the photodegradation pathway after crop spraying.
Effects of zeolite application on nitrate and ammonium retention of a loamy soil under saturated conditions
Authors: Sepaskhah A. R. , Yousefi F.
Published: August 2007

Nitrogen (N) loss from irrigated cropland, especially in rice paddies, results in low N-use efficiency and groundwater contamination. Soil conditions that increase ammonium and nitrate ion retention alleviate these problems. Clinoptilolite, a naturally occurring zeolite with high-exchange capacity, may be used to absorb ammonium and retard excess leaching of nitrate. The objectives of this research were to determine the effects of different rates of Ca–K-zeolite application (0, 2, 4, and 8 g/kg soil) on pore water velocity and leaching of ammonium and nitrate applied as ammonium nitrate fertiliser to a loam soil at a rate of 350 kg N/ha under saturated conditions similar to that of a rice paddy. The results indicate that Ca–K-zeolite applications of 4 and 8 g/kg soil increase the pore water velocity by 35% and 74%, respectively. The maximum relative concentration (c/co) for the nitrate breakthrough curve occurring at pore volume of about 0.5 was reduced by 15% with a zeolite application rate of 8 g/kg soil. When applying 40 cm of leaching water, leached nitrate was 75% and 63% of total applied nitrate at the soil surface with zeolite applications of 4 and 8 g/kg soil, respectively. Due to the high ion exchange capacity of zeolite, the application of zeolite at 2 g/kg soil is enough to increase the exchange sites in the soil in order to absorb the applied ammonium and prevent its leaching by the inflow water. The maximum ammonium concentration in the breakthrough curve for the zeolite application rate of 2 g/kg soil was reduced by 43% compared with the control treatment. The relationship between the hydrodynamic dispersion coefficient (D) for nitrate and pore water velocity (v) was not linear and it was correlated with squared pore water velocity. The coefficient of the relationship between D and v2 was dependent on the zeolite application rate and linearly increased with this rate.
Excess vacuolar SNAREs drive lysis and Rab bypass fusion
Authors: Starai Vincent J. , Jun Youngsoo , Wickner William
Published: August 2007

Although concentrated soluble
N
-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) drive liposome fusion and lysis, the fusion of intracellular membranes also requires Rab GTPases, Rab effectors, SM proteins, and specific regulatory lipids and is accompanied by little or no lysis. To rationalize these findings, we generated yeast strains that overexpress all four vacuolar SNAREs (
4SNARE
++
). Although vacuoles with physiological levels of Rab, Rab effector/SM complex, and SNAREs support rapid fusion without Rab- and SNARE-dependent lysis, vacuoles from
4SNARE
++
strains show extensive lysis and a reduced need for the Rab Ypt7p or regulatory lipids for fusion. SNARE overexpression and the addition of pure homotypic fusion and vacuole protein sorting complex (HOPS), which bears the vacuolar SM protein, enables
ypt7
Δ vacuoles to fuse, allowing direct comparison of Rab-dependent and Rab-independent fusion. Because 3- to 40-fold more of each of the five components that form the SNARE/HOPS fusion complex are required for vacuoles from
ypt7
Δ strains to fuse at the same rate as vacuoles from wild-type strains, the apparent forward rate constant of 4SNARE/HOPS complex assembly is enhanced many thousand-fold by Ypt7p. Rabs function in normal membrane fusion by concentrating SNAREs, other proteins (e.g., SM), and key lipids at a fusion site and activating them for fusion without lysis.
Encroaching forests decouple alpine butterfly population dynamics
Authors: Roland Jens , Matter Stephen F.
Published: August 2007

Over the past 50 years, the rising tree line along Jumpingpound Ridge in the Rocky Mountains of Alberta, Canada, has reduced the area of alpine meadows and isolated populations that reside within them. By analyzing an 11-year data set of butterfly population sizes for 17 subpopulations along the ridge, we show that forest habitat separating alpine meadows decouples the dynamics of populations of the alpine butterfly
Parnassius smintheus
. Although the distance between populations is often negatively correlated with synchrony of dynamics, here we show that distance through forest, not Euclidean distance, determines the degree of synchrony. This effect is consistent with previous results demonstrating that encroaching forest reduces dispersal among populations and reduces gene flow. Decoupling dynamics produces more smaller independent populations, each with greater risk of local extinction, but decoupling may produce a lower risk of regional extinction in this capricious environment.
Functions of OsBZR1 and 14-3-3 proteins in brassinosteroid signaling in rice
Authors: Bai Ming-Yi , Zhang Li-Ying , Gampala Srinivas S. , Zhu Sheng-Wei , Song Wen-Yuan , Chong Kang , Wang Zhi-Yong
Published: August 2007

Brassinosteroids (BR) are essential growth hormones found throughout the plant kingdom. BR bind to the receptor kinase BRI1 on the cell surface to activate a signal transduction pathway that regulates nuclear gene expression and plant growth. To understand the downstream BR signaling mechanism in rice, we studied the function of
OsBZR1
using reverse genetic approaches and identified OsBZR1-interacting proteins. Suppressing
OsBZR1
expression by RNAi resulted in dwarfism, erect leaves, reduced BR sensitivity, and altered BR-responsive gene expression in transgenic rice plants, demonstrating an essential role of OsBZR1 in BR responses in rice. Moreover, a yeast two-hybrid screen identified 14-3-3 proteins as OsBZR1-interacting proteins. Mutation of a putative 14-3-3-binding site of OsBZR1 abolished its interaction with the 14-3-3 proteins in yeast and
in vivo
. Such mutant OsBZR1 proteins suppressed the phenotypes of the
Arabidopsis bri1–5
mutant and showed an increased nuclear distribution compared with the wild-type protein, suggesting that 14-3-3 proteins directly inhibit OsBZR1 function at least in part by reducing its nuclear localization. These results demonstrate a conserved function of OsBZR1 and an important role of 14-3-3 proteins in brassinosteroid signal transduction in rice.
Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases
Authors: Frank Daniel N. , St. Amand Allison L. , Feldman Robert A. , Boedeker Edgar C. , Harpaz Noam , Pace Norman R.
Published: August 2007

The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla
Firmicutes
and
Bacteroidetes
. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.
Dual Role of α6β4 Integrin in Epidermal Tumor Growth: Tumor-suppressive Versus Tumor-promoting Function
Authors: Raymond Karine , Kreft Maaike , Song Ji-Ying , Janssen Hans , Sonnenberg Arnoud
Published: August 2007

An increased expression of the integrin α6β4 is correlated with a poor prognosis in patients with squamous cell carcinomas. However, little is known about the role of α6β4 in the early stages of tumor development. We have isolated cells from mouse skin (mouse tumor-initiating cells [mTICs]) that are deficient in both p53 and Smad4 and carry conditional alleles of the β4 gene (Itgb4). The mTICs display many features of multipotent epidermal stem cells and produce well-differentiated tumors after subcutaneous injection into nude mice. Deletion of Itgb4 led to enhanced tumor growth, indicating that α6β4 mediates a tumor-suppressive effect. Reconstitution experiments with β4-chimeras showed that this effect is not dependent on ligation of α6β4 to laminin-5, but on the recruitment by this integrin of the cytoskeletal linker protein plectin to the plasma membrane. Depletion of plectin, like that of β4, led to increased tumor growth. In contrast, when mTICs had been further transformed with oncogenic Ras, α6β4 stimulated tumor growth, as previously observed in human squamous neoplasms. Expression of different effector-loop mutants of RasV12suggests that this effect depends on a strong activation of the Erk pathway. Together, these data show that depending on the mutations involved, α6β4 can either mediate an adhesion-independent tumor-suppressive effect or act as a tumor promotor.
Human Mcm10 Regulates the Catalytic Subunit of DNA Polymerase-α and Prevents DNA Damage during Replication
Authors: Chattopadhyay Sharbani , Bielinsky Anja-Katrin
Published: August 2007

In Saccharomyces cerevisiae, minichromosome maintenance protein (Mcm) 10 interacts with DNA polymerase (pol)-α and functions as a nuclear chaperone for the catalytic subunit, which is rapidly degraded in the absence of Mcm10. We report here that the interaction between Mcm10 and pol-α is conserved in human cells. We used a small interfering RNA-based approach to deplete Mcm10 in HeLa cells, and we observed that the catalytic subunit of pol-α, p180, was degraded with similar kinetics as Mcm10, whereas the regulatory pol-α subunit, p68, remained unaffected. Simultaneous loss of Mcm10 and p180 inhibited S phase entry and led to an accumulation of already replicating cells in late S/G2 as a result of DNA damage, which triggered apoptosis in a subpopulation of cells. These phenotypes differed considerably from analogous studies in Drosophila embryo cells that did not exhibit a similar arrest. To further dissect the roles of Mcm10 and p180 in human cells, we depleted p180 alone and observed a significant delay in S phase entry and fork progression but little effect on cell viability. These results argue that cells can tolerate low levels of p180 as long as Mcm10 is present to “recycle” it. Thus, human Mcm10 regulates both replication initiation and elongation and maintains genome integrity.
Regulation of the Formin for3p by cdc42p and bud6p
Authors: Martin Sophie G. , Rincón Sergio A. , Basu Roshni , Pérez Pilar , Chang Fred
Published: August 2007

Formins are conserved actin nucleators responsible for the assembly of diverse actin structures. Many formins are controlled through an autoinhibitory mechanism involving the interaction of a C-terminal DAD sequence with an N-terminal DID sequence. Here, we show that the fission yeast formin for3p, which mediates actin cable assembly and polarized cell growth, is regulated by a similar autoinhibitory mechanism in vivo. Multiple sites govern for3p localization to cell tips. The localization and activity of for3p are inhibited by an intramolecular interaction of divergent DAD and DID-like sequences. A for3p DAD mutant expressed at endogenous levels produces more robust actin cables, which appear to have normal organization and dynamics. We identify cdc42p as the primary Rho GTPase involved in actin cable assembly and for3p regulation. Both cdc42p, which binds at the N terminus of for3p, and bud6p, which binds near the C-terminal DAD-like sequence, are needed for for3p localization and full activity, but a mutation in the for3p DAD restores for3p localization and other phenotypes of cdc42 and bud6 mutants. In particular, the for3p DAD mutation suppresses the bipolar growth (NETO) defect of bud6Δ cells. These findings suggest that cdc42p and bud6p activate for3p by relieving autoinhibition.
The Chromosomal Passenger Complex Controls Spindle Checkpoint Function Independent from Its Role in Correcting Microtubule–Kinetochore Interactions
Authors: Vader Gerben , Cruijsen Carin W.A. , van Harn Tanja , Vromans Martijn J.M. , Medema René H. , Lens Susanne M.A.
Published: August 2007

The chromosomal passenger complex (CPC) is a critical regulator of chromosome segregation during mitosis by correcting nonbipolar microtubule-kinetochore interactions. By severing these interactions, the CPC is thought to create unattached kinetochores that are subsequently sensed by the spindle assembly checkpoint (SAC) to prevent premature mitotic exit. We now show that spindle checkpoint function of the CPC and its role in eliminating nonbipolar attachments can be uncoupled. Replacing the chromosomal passenger protein INCENP with a mutant allele that lacks its coiled-coil domain results in an overt defect in a SAC-mediated mitotic arrest in response to taxol treatment, indicating that this domain is critical for CPC function in spindle checkpoint control. Surprisingly, this mutant could restore alignment and cytokinesis during unperturbed cell divisions and was capable of resolving syntelic attachments. Also, Aurora-B kinase was localized and activated normally on centromeres in these cells, ruling out a role for the coiled-coil domain in general Aurora-B activation. Thus, mere microtubule destabilization of nonbipolar attachments by the CPC is insufficient to install a checkpoint-dependent mitotic arrest, and additional, microtubule destabilization–independent CPC signaling toward the spindle assembly checkpoint is required for this arrest, potentially through amplification of the unattached kinetochore-derived checkpoint signal.
The use of optical tweezers to study sperm competition and motility in primates
Authors: Nascimento Jaclyn M , Shi Linda Z , Meyers Stuart , Gagneux Pascal , Loskutoff Naida M , Botvinick Elliot L , Berns Michael W
Published: August 2007

Optical trapping is a non-invasive biophysical tool which has been widely applied to study physiological and biomechanical properties of cells. Using laser ‘tweezers’ in combination with custom-designed computer tracking algorithms, the swimming speeds and the relative swimming forces of individual sperm can be measured in real time. This combination of physical and engineering tools has been used to examine the evolutionary effect of sperm competition in primates. The results demonstrate a correlation between mating type and sperm motility: sperm from polygamous (multi-partner) primate species swim faster and with greater force than sperm from polygynous (single partner) primate species. In addition, sperm swimming force linearly increases with swimming speed for each species, yet the regression relating the two parameters is species specific. These results demonstrate the feasibility of using these tools to study rapidly moving (μm s−1) biological cells.
Eliminating human tuberculosis in the twenty-first century
Authors: Dye Christopher , Williams Brian G
Published: August 2007

Recognizing that tuberculosis (TB) is still the leading cause of human death from a curable infection, the international health community has set ambitious targets for disease control. One target is to eliminate TB by 2050; that is, to cut the annual incidence of new cases to less than 1 per million population. National TB control programmes are working to eliminate TB mainly by intensifying efforts to find and cure patients with active disease. Here, we use mathematical modelling to show that, while most TB patients can be cured with present drug regimens, the 2050 target is far more likely to be achieved with a combination of diagnostics, drugs and vaccines that can detect and treat both latent infection and active disease. We find that the coupling of control methods is particularly effective because treatments for latent infection and active disease act in synergy. This synergistic effect offers new perspectives on the cost-effectiveness of treating latent TB infection and the impact of possible new TB vaccines. Our results should be a stimulus to those who develop, manufacture and implement new technology for TB control, and to their financial donors.
Fossil ghost ranges are most common in some of the oldest and some of the youngest strata
Authors: Wills M.A
Published: August 2007

Biologists routinely compare inferences about the order of evolutionary branching (phylogeny) with the order in which groups appear in the fossil record (stratigraphy). Where they conflict, ghost ranges are inferred: intervals of geological time where a fossil lineage
should
exist, but for which there is no direct evidence. The presence of very numerous and/or extensive ghost ranges is often believed to imply spurious phylogenies or a misleadingly patchy fossil record, or both. It has usually been assumed that the frequency of ghost ranges should increase with the age of rocks. Previous studies measuring ghost ranges for whole trees in just a small number of temporal bins have found no significant increase with antiquity. This study uses a much higher resolution approach to investigate the gappiness implied by 1000 animal and plant cladograms over 77 series and stages of the Phanerozoic. It demonstrates that ghost ranges are indeed relatively common in some of the oldest strata. Surprisingly, however, ghost ranges are also relatively common in some of the youngest, fossil-rich rocks. This pattern results from the interplay between several complex factors and is not a simple function of the completeness of the fossil record. The Early Palaeozoic record is likely to be less organismically and stratigraphically complete, and its fossils—many of which are invertebrates—may be more difficult to analyse cladistically. The Late Cenozoic is subject to the pull of the Recent, but this accounts only partially for the increased gappiness in the younger strata.
Human immunodeficiency virus evolution towards reduced replicative fitnessin vivoand the development of AIDS
Authors: Wodarz Dominik , Levy David N
Published: August 2007

Human immunodeficiency virus (HIV) infection progresses to AIDS following an asymptomatic period during which the virus is thought to evolve towards increased fitness and pathogenicity. We show mathematically that progression to the strongest HIV-induced pathology requires evolution of the virus towards reduced replicative fitnessin vivo. This counter-intuitive outcome can happen if multiple viruses co-infect the same cell frequently, which has been shown to occur in recent experiments. According to our model, in the absence of frequent co-infection, the less fit AIDS-inducing strains might never emerge. The frequency of co-infection can correlate with virus load, which in turn is determined by immune responses. Thus, at the beginning of infection when immunity is strong and virus load is low, co-infection is rare and pathogenic virus variants with reduced replicative fitness go extinct. At later stages of infection when immunity is less efficient and virus load is higher, co-infection occurs more frequently and pathogenic virus variants with reduced replicative fitness can emerge, resulting in T-cell depletion. In support of these notions, recent data indicate that pathogenic simian immunodeficiency virus (SIV) strains occurring late in the infection are less fit in specificin vitroexperiments than those isolated at earlier stages. If co-infection is blocked, the model predicts the absence of any disease even if virus loads are high. We hypothesize that non-pathogenic SIV infection within its natural hosts, which is characterized by the absence of disease even in the presence of high virus loads, could be explained by a reduced occurrence of co-infection in this system.
Fractal bird nest distribution produces scale-free colony sizes
Authors: Jovani Roger , Tella José L
Published: August 2007

The spatial distribution of organisms often differs across scales. For instance, colonial bird populations could be described, from large to small scale, as scattered clumps of otherwise regularly distributed breeding pairs. We analysed the distribution of nests of a large colonial population of white storks (Ciconia ciconia) and found a fractal pattern in each of the 4 study years. Moreover, we found that the often-observed, long-tailed frequency distribution of colony sizes was well described by a power law, regardless of the cut-off used to define colonies (from 16 to 1024 m). Thus, although storks were locally highly clumped even with tens of nests in a single tree, the population was not structured in colonies (a simple clustered distribution) as previously thought. Rather, they were distributed in a continuous hierarchical set of clusters within clusters across scales, clusters lacking the commonly assumed characteristic mean size. These quantitative solutions to previously perceived scaling problems will potentially improve our understanding of the ecology and evolution of bird coloniality and animal spacing patterns and group living in general.
The assembly of montane biotas: linking Andean tectonics and climatic oscillations to independent regimes of diversification inPionusparrots
Authors: Ribas Camila C , Moyle Robert G , Miyaki Cristina Y , Cracraft Joel
Published: August 2007

The mechanisms underlying the taxonomic assembly of montane biotas are still poorly understood. Most hypotheses have assumed that the diversification of montane biotas is loosely coupled to Earth history and have emphasized instead the importance of multiple long-distance dispersal events and biotic interactions, particularly competition, for structuring the taxonomic composition and distribution of montane biotic elements. Here we use phylogenetic and biogeographic analyses of species in the parrot genusPionusto demonstrate that standing diversity within montane lineages is directly attributable to events of Earth history. Phylogenetic relationships confirm three independent biogeographic disjunctions between montane lineages, on one hand, and lowland dry-forest/wet-forest lineages on the other. Temporal estimates of lineage diversification are consistent with the interpretation that the three lineages were transported passively to high elevations by mountain building, and that subsequent diversification within the Andes was driven primarily by Pleistocene climatic oscillations and their large-scale effects on habitat change. These results support a mechanistic link between diversification and Earth history and have general implications for explaining high altitudinal disjuncts and the origin of montane biotas.
Habitat fragmentation may not matter to species diversity
Authors: Yaacobi Gal , Ziv Yaron , Rosenzweig Michael L
Published: August 2007

Conservation biologists worry that fragmenting a bloc of natural habitat might reduce its species diversity. However, they also recognize the difficulty and importance of isolating the effect of fragmentation from that of simple loss of area. Using two different methods (species–area curve and Fisher's
α
index of diversity) to analyse the species diversities of plants, tenebrionid beetles and carabid beetles in a highly fragmented Mediterranean scrub landscape, we decoupled the effect of degree of fragmentation from that of area loss. In this system, fragmentation by itself seems not to have influenced the number of species. Our results, obtained at the scale of hectares, agree with similar results at island and continent scales.
Selection for long lifespan in men: benefits of grandfathering?
Authors: Lahdenperä M , Russell A.F , Lummaa V
Published: August 2007

Life-history theory suggests that individuals should live until their reproductive potential declines, and the lifespan of human men is consistent with this idea. However, because women can live long after menopause and this prolonged post-reproductive life can be explained, in part, by the fitness enhancing effects of grandmothering, an alternative hypothesis is that male lifespan is influenced by the potential to gain fitness through grandfathering. Here we investigate whether men, who could not gain fitness through reproduction after their wife's menopause (i.e. married only once), enhanced their fitness through grandfathering in historical Finns. Father presence was associated with reductions in offspring age at first reproduction and birth intervals, but generally not increases in reproductive tenure lengths. Father presence had little influence on offspring lifetime fecundity and no influence on offspring lifetime reproductive success. Overall, in contrast to our results for women in the same population, men do not gain extra fitness (i.e. more grandchildren) through grandfathering. Our results suggest that if evidence for a ‘grandfather’ hypothesis is lacking in a monogamous society, then its general importance in shaping male lifespan during our more promiscuous evolutionary past is likely to be negligible.