bluuebunny/crossref_metadata_2025 huggingface dataset:
A system for Cre-regulated RNA interference
in vivo
Authors: Stern Patrick , Astrof Sophie , Erkeland Stefan J. , Schustak Joshua , Sharp Phillip A. , Hynes Richard O.
Published: September 2008

We report a system for Cre-regulated expression of RNA interference
in vivo
. Expression cassettes comprise selectable and FACS-sortable markers in tandem with additional marker genes and shRNAs in the antisense orientation. The cassettes are flanked by tandem LoxP sites arranged so that Cre expression inverts the marker–shRNA construct, allowing its regulated expression (and, at the same time, deletes the original selection/marker genes). The cassettes can be incorporated into retroviral or lentiviral vectors and delivered to cells in culture or used to generate transgenic mice. We describe cassettes incorporating various combinations of reporter genes, miRNA-based RNAi (including two shRNA constructs at once), and oncogenes and demonstrate the delivery of effective RNA interference in cells in culture, efficient transduction into hematopoietic stem cells with cell-type-specific knockdown in their progeny, and rapid generation of regulated shRNA knockdown in transgenic mice. These vector systems allow regulated combinatorial manipulation (both overexpression and loss of function) of gene expression in multiple systems
in vitro
and
in vivo
.
Making insulin-deficient type 1 diabetic rodents thrive without insulin
Authors: Yu Xinxin , Park Byung-Hyun , Wang May-Yun , Wang Zhao V. , Unger Roger H.
Published: September 2008

Terminally ill insulin-deficient rodents with uncontrolled diabetes due to autoimmune or chemical destruction of β-cells were made hyperleptinemic by adenoviral transfer of the leptin gene. Within ≈10 days their severe hyperglycemia and ketosis were corrected. Despite the lack of insulin, moribund animals resumed linear growth and appeared normal. Normoglycemia persisted 10–80 days without other treatment; normal physiological conditions lasted for ≈175 days despite reappearance of moderate hyperglycemia. Inhibition of gluconeogenesis by suppression of hyperglucagonemia and reduction of hepatic cAMP response element-binding protein, phoshoenolpyruvate carboxykinase, and peroxisome proliferator-activated receptor-γ-coactivator-1α may explain the anticatabolic effect. Up-regulation of insulin-like growth factor 1 (IGF-1) expression and plasma levels and increasing IGF-1 receptor phosphorylation in muscle may explain the increased insulin receptor substrate 1, PI3K, and ERK phosphorylation in skeletal muscle. These findings suggest that leptin reverses the catabolic consequences of total lack of insulin, potentially by suppressing glucagon action on liver and enhancing the insulinomimetic actions of IGF-1 on skeletal muscle, and suggest strategies for making type 1 diabetes insulin-independent.
C-terminal peptides coassemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity
Authors: Fradinger Erica A. , Monien Bernhard H. , Urbanc Brigita , Lomakin Aleksey , Tan Miao , Li Huiyuan , Spring Sean M. , Condron Margaret M. , Cruz Luis , Xie Cui-Wei , Benedek George B. , Bitan Gal
Published: September 2008

Alzheimer's disease (AD) is an age-related disorder that threatens to become an epidemic as the world population ages. Neurotoxic oligomers of Aβ42 are believed to be the main cause of AD; therefore, disruption of Aβ oligomerization is a promising approach for developing therapeutics for AD. Formation of Aβ42 oligomers is mediated by intermolecular interactions in which the C terminus plays a central role. We hypothesized that peptides derived from the C terminus of Aβ42 may get incorporated into oligomers of Aβ42, disrupt their structure, and thereby inhibit their toxicity. We tested this hypothesis using Aβ fragments with the general formula Aβ(
x
−42) (
x
= 28–39). A cell viability screen identified Aβ(31–42) as the most potent inhibitor. In addition, the shortest peptide, Aβ(39–42), also had high activity. Both Aβ(31–42) and Aβ(39–42) inhibited Aβ-induced cell death and rescued disruption of synaptic activity by Aβ42 oligomers at micromolar concentrations. Biophysical characterization indicated that the action of these peptides likely involved stabilization of Aβ42 in nontoxic oligomers. Computer simulations suggested a mechanism by which the fragments coassembled with Aβ42 to form heterooligomers. Thus, Aβ(31–42) and Aβ(39–42) are leads for obtaining mechanism-based drugs for treatment of AD using a systematic structure–activity approach.
Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins
Authors: Ruby Maxwell A. , Nomura Daniel K. , Hudak Carolyn S. S. , Mangravite Lara M. , Chiu Sally , Casida John E. , Krauss Ronald M.
Published: September 2008

The endocannabinoid (EC) system regulates food intake and energy metabolism. Cannabinoid receptor type 1 (CB1) antagonists show promise in the treatment of obesity and its metabolic consequences. Although the reduction in adiposity resulting from therapy with CB1 antagonists may not account fully for the concomitant improvements in dyslipidemia, direct effects of overactive EC signaling on plasma lipoprotein metabolism have not been documented. The present study used a chemical approach to evaluate the direct effects of increased EC signaling in mice by inducing acute elevations of endogenously produced cannabinoids through pharmacological inhibition of their enzymatic hydrolysis by isopropyl dodecylfluorophosphonate (IDFP). Acute IDFP treatment increased plasma levels of triglyceride (TG) (2.0- to 3.1-fold) and cholesterol (1.3- to 1.4-fold) in conjunction with an accumulation in plasma of apolipoprotein (apo)E-depleted TG-rich lipoproteins. These changes did not occur in either CB1-null or apoE-null mice, were prevented by pretreatment with CB1 antagonists, and were not associated with reduced hepatic apoE gene expression. Although IDFP treatment increased hepatic mRNA levels of lipogenic genes (
Srebp1
and
Fas
), there was no effect on TG secretion into plasma. Instead, IDFP treatment impaired clearance of an intravenously administered TG emulsion, despite increased postheparin lipoprotein lipase activity. Therefore, overactive EC signaling elicits an increase in plasma triglyceride levels associated with reduced plasma TG clearance and an accumulation in plasma of apoE-depleted TG-rich lipoproteins. These findings suggest a role of CB1 activation in the pathogenesis of obesity-related hypertriglyceridemia and underscore the potential efficacy of CB1 antagonists in treating metabolic disease.
Light verbs as classifiers in Udi
Authors: Harris Alice C.
Published: September 2008

In Udi, most verbal lexemes are composed, in all tense-aspect-mood categories, of a light verb and an ‘initial’. It is argued here that in the first stage of this development, simplex verbs were juxtaposed with focused constituents. In the second stage, initials and verbs formed compounds, and this pattern spread beyond those that had once involved focus. In the third stage, the subject of this paper, light verbs become classifiers, classifying the verb type — inchoatives, other unaccusatives, unergatives, transitive verbs of inherently directed motion, transitive change-of-state verbs, other transitives. I argue also that the classes identified by (some of) the light verbs have not become less semantically motivated; rather the semantics has shifted from a relatively narrow meaning to one of the three major classes.
REducing Deaths due to OXidative Stress (The REDOXS© Study): rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients
Authors: Heyland Daren K. , Dhaliwal Rupinder , Day Andrew G. , Muscedere John , Drover John , Suchner Ulrich , Cook Deborah ,   Canadian Critical Care Trials Group
Published: September 2008

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2×2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.
Nutritional factors and immunological ageing
Authors: Lesourd Bruno
Published: September 2008

Undernutrition profoundly affects immune responses, particularly at the extremities of life: in infants and in the elderly. The present review focuses on this interrelationship in the elderly. It describes three different stages of ageing: stage 1, healthy ageing, which is observed in very healthy elderly individuals who have no nutritional deficit; stage 2, common ageing, which is observed in most elderly individuals in whom various micronutrient deficits are found; stage 3, pathological ageing, which is observed in patients with protein–energy deficiency. Stage 1, primary immune ageing, is essentially characterized by changes in T-cell subsets but no change in T-cell function; T-cell function is reduced only in the very elderly (>90 years old). Stage 2, secondary immune ageing, is influenced by micronutrient deficits that may be corrected by providing nutritional supplements. Furthermore, immune responses may also be enhanced by supplementation of subjects who have no micronutrient deficits, indicating that the immune system of elderly individuals is highly susceptible to the influence of micronutrients. In stage 3, tertiary immune ageing, the immune responses are strongly related to the decreased nutritional status. In these patients decreased immune responses lead to long-lasting acute-phase responses, which induce greater use of nutritional reserves during disease and lead to increased frailty. As nutritional status has a marked effect on immune responses in elderly individuals, nutritional therapy should be given to elderly individuals who have nutrient deficits, and perhaps also to individuals who do not have nutrient deficits in order to promote healthy ageing and extend the lifespan.
Gender ‘matters’ in the primary classroom: Pupils' and teachers' perspectives
Authors: Skelton C. , Carrington B. , Francis B. , Hutchings M. , Read B. , Hall I.
Published: September 2008

A recent project involving Year 3 (seven–eight year‐old) pupils and their teachers revealed that ‘gender matters’ differently to boys and girls, and teachers. The study sought to elicit whether pupils and their teachers felt the gender of a teacher mattered to their experiences of schooling. Pupils were concerned about how effective teachers were in carrying out their professional functions and a teacher's gender was subsumed within this. For these pupils, ‘gender mattered’ in terms of the construction of their own gender identities. In contrast, teachers were aware of and attentive to the gender of pupils in managing and organising classroom interactions. The variety of differing views expressed and positions adopted towards the place of gender in teacher–pupil interactions demonstrates the complexity of developing ‘one size fits all’ approaches to tackling gender equity in the classroom.
Ly6c+ “inflammatory monocytes” are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis
Authors: Getts Daniel R. , Terry Rachael L. , Getts Meghann Teague , Müller Marcus , Rana Sabita , Shrestha Bimmi , Radford Jane , Van Rooijen Nico , Campbell Iain L. , King Nicholas J.C.
Published: September 2008

In a lethal West Nile virus (WNV) model, central nervous system infection triggered a threefold increase in CD45int/CD11b+/CD11c− microglia at days 6–7 postinfection (p.i.). Few microglia were proliferating, suggesting that the increased numbers were derived from a migratory precursor cell. Depletion of “circulating” (Gr1−(Ly6Clo)CX3CR1+) and “inflammatory” (Gr1hi/Ly6Chi/CCR2+) classical monocytes during infection abrogated the increase in microglia. C57BL/6 chimeras reconstituted with cFMS–enhanced green fluorescent protein (EGFP) bone marrow (BM) showed large numbers of peripherally derived (GFP+) microglia expressing GR1+(Ly6C+) at day 7 p.i., suggesting that the inflammatory monocyte is a microglial precursor. This was confirmed by adoptive transfer of labeled BM (Ly6Chi/CD115+) or circulating inflammatory monocytes that trafficked to the WNV-infected brain and expressed a microglial phenotype. CCL2 is a chemokine that is highly expressed during WNV infection and important in inflammatory monocyte trafficking. Neutralization of CCL2 not only reduced the number of GFP+ microglia in the brain during WNV infection but prolonged the life of infected animals. Therefore, CCL2-dependent inflammatory monocyte migration is critical for increases in microglia during WNV infection and may also play a pathogenic role during WNV encephalitis.
ADZE: a rarefaction approach for counting alleles private to combinations of populations
Authors: Szpiech Zachary A. , Jakobsson Mattias , Rosenberg Noah A.
Published: September 2008

Motivation: Analysis of the distribution of alleles across populations is a useful tool for examining population diversity and relationships. However, sample sizes often differ across populations, sometimes making it difficult to assess allelic distributions across groups.

Results: We introduce a generalized rarefaction approach for counting alleles private to combinations of populations. Our method evaluates the number of alleles found in each of a set of populations but absent in all remaining populations, considering equal-sized subsamples from each population. Applying this method to a worldwide human microsatellite dataset, we observe a high number of alleles private to the combination of African and Oceanian populations. This result supports the possibility of a migration out of Africa into Oceania separate from the migrations responsible for the majority of the ancestry of the modern populations of Asia, and it highlights the utility of our approach to sample size correction in evaluating hypotheses about population history.

Availability: We have implemented our method in the computer pro-gram ADZE, which is available for download at http://rosenberglab.bioinformatics.med.umich.edu/adze.html.

Contact:  szpiechz@umich.edu
Growth, reproduction, and feeding of large monkfish, Lophius americanus
Authors: Johnson A. K. , Richards R. Anne , Cullen Daniel W. , Sutherland Sandra J.
Published: September 2008

Johnson, A. K., Richards, R. A., Cullen, D. W., and Sutherland, S. J. 2008. Growth, reproduction, and feeding of large monkfish, Lophius americanus. – ICES Journal of Marine Science, 65: 1306–1315. The American monkfish, Lophius americanus, supports important commercial fisheries in the Northwest Atlantic. Although life history information is available for smaller L. americanus, the biology of large monkfish (>70 cm) is poorly understood because relatively few large fish are caught in standard resource surveys. Between 2006 and 2008, 699 L. americanus of 71–118 cm total length were collected from commercial gillnet fishers operating in the mid-Atlantic Bight (n = 689) and in the Gulf of Maine (n = 10) to investigate growth rates, reproductive biology, and feeding habits of large monkfish. All those collected were mature females ranging in age from 7 to 13 years. Growth was linear at an average annual rate of 7.6 cm. Hepatosomatic indices peaked in February and gonadosomatic indices between February and April. Postovulatory follicles and vitellogenic oocytes were observed in the same ovaries, evidence that monkfish spawn over a protracted period and possibly more than once annually. Food habits were similar to those reported for smaller benthic phase monkfish, but cannibalism was more prevalent in large fish (5.6% frequency of occurrence). Frequencies of feeding and cannibalism were greatest in females in the final stage of oocyte maturation.
Validation of a method of estimating age, modelling growth, and describing the age composition of Coilia mystus from the Yangtze Estuary, China
Authors: He Wenping , Li Zhongjie , Liu Jiashou , Li Yuxuan , Murphy Brian R. , Xie Songguang
Published: September 2008

He, W., Li, Z., Liu, J., Li, Y., Murphy, B. R., and Xie, S. 2008. Validation of a method of estimating age, modelling growth, and describing the age composition of Coilia mystus from the Yangtze Estuary, China. – ICES Journal of Marine Science, 65: 1655–1661. A collection of 577 Coilia mystus was made during April 2006 and 2007 from China’s Yangtze Estuary to estimate the age structure and growth patterns of the population. Examination of sectioned sagittal otoliths revealed a periodic straight/curved growth pattern. The straight zone was from April to November, and the curved zone from October to May, indicating annual periodicity. Annual periodicity was also verified by margin zone analysis. The shift from a curved-zone to the next straight-zone stanza was defined as an annulus. The fish from which the otoliths were taken were 0–5 years old. The von Bertalanffy growth function was fitted to standard length (LS)-at-age data as LS = 215.16 (1 – e−0.53 (t+ 0.30)) (n = 577, r2 = 0.81, p < 0.05). The mature females included five age classes, ages 1 and 2 accounting for 74.3% of the population. The mature males included fish aged 1 and 2, those at age 1 accounting for 86.4% of the population. Mean length was smaller, and annual growth less, for mature males than for females of comparable age. The study demonstrated that the Yangtze population of C. mystus consists of more age classes than previously thought and that the age structure of the population needs to be considered in management decisions.
Fine-scale cospeciation betweenBrachycaudusandBuchnera aphidicola: bacterial genome helps define species and evolutionary relationships in aphids
Authors: Jousselin Emmanuelle , Desdevises Yves , Coeur d'acier Armelle
Published: September 2008

Aphids harbour an obligatory symbiont,Buchnera aphidicola, providing essential amino acids not supplied by their diet. These bacteria are transmitted vertically and phylogenic analyses suggest that they have ‘cospeciated’ with their hosts. We investigated this cospeciation phenomenon at a fine taxonomic level, within the aphid genusBrachycaudus. We used DNA-based methods of species delimitation in both organisms, to avoid biases in the definition of aphid andBuchneraspecies and to infer association patterns without the presumption of a specific interaction. Our results call into question certain ‘taxonomic’ species ofBrachycaudusand suggest thatB. aphidicolahas diversified into independently evolving entities, each specific to a ‘phylogenetic’Brachycaudusspecies. We also found thatBuchneraand their hosts simultaneously diversified, in parallel. These results validate the use ofBuchneraDNA data for inferring the evolutionary history of their host. TheBuchneragenome evolves rapidly, making it the perfect tool for resolving ambiguities in aphid taxonomy. This study also highlights the usefulness of species delimitation methods in cospeciation studies involving species difficult to conceptualize—as is the case for bacteria—and in cases in which the taxonomy of the interacting organisms has not been determined independently and species definition depends on host association.
Different functions for homologous serotonergic interneurons and serotonin in species-specific rhythmic behaviours
Authors: Newcomb James M , Katz Paul S
Published: September 2008

Closely related species can exhibit different behaviours despite homologous neural substrates. The nudibranch molluscsTritonia diomedeaandMelibe leoninaswim differently, yet their nervous systems contain homologous serotonergic neurons. InTritonia, the dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and their neurotransmitter serotonin is both necessary and sufficient to elicit a swim motor pattern. Here it is shown that the DSI homologues inMelibe, the cerebral serotonergic posterior-A neurons (CeSP-As), are extrinsic to the swim CPG, and that neither theCeSP-As nor their neurotransmitter serotonin is necessary for swim motor pattern initiation, which occurred when theCeSP-As were inactive. Furthermore, the serotonin antagonist methysergide blocked the effects of both the serotonin andCeSP-As but did not prevent the production of a swim motor pattern. However, theCeSP-As and serotonin could influence theMelibeswim circuit; depolarization of a cerebral serotonergic posterior-A was sufficient to initiate a swim motor pattern and hyperpolarization of aCeSP-A temporarily halted an ongoing swim motor pattern. Serotonin itself was sufficient to initiate a swim motor pattern or make an ongoing swim motor pattern more regular. Thus, evolution of species-specific behaviour involved alterations in the functions of identified homologous neurons and their neurotransmitter.
Pattern formation on the combs of honeybees: increasing fitness by coupling self-organization with templates
Authors: Johnson Brian R
Published: September 2008

Biological patterns are often constructed via a combination of mechanisms including self-organization, templates and recipes. Our understanding of self-organization is becoming increasingly clear, yet how multiple mechanisms work together and what selective advantage they confer over simpler mechanisms is poorly understood. Honeybee (Apis mellifera) combs exhibit a pattern of brood at the bottom, pollen in a band next to it and honey at the top. This study constructs an agent-based model, derived from experimental studies, to determine both how self-organization interacts with two templates and to elucidate a selective basis for the use of multiple mechanisms. The vertical pattern of honey and brood is shown to be dependent on a gravity-based template, while the pollen band is shown to form via the interaction of a queen-based template and self-organization. The study suggests that the selective basis for this complex mechanism may be that colonies have higher growth rates when multiple mechanisms are used as opposed to self-organization alone. As self-organization is used in many contexts in which the addition of supplemental mechanisms could be advantageous, this result may be of general significance to many biological systems.
Trophic and individual efficiencies of size-structured communities
Authors: Andersen K.H , Beyer J.E , Lundberg P
Published: September 2008

Individual and trophic efficiencies of size-structured communities are derived from mechanistically based principles at the individual level. The derivations are relevant for communities with a size-based trophic structure, i.e. where trophic level is strongly correlated with individual size as in many aquatic systems. The derivations are used to link Lindeman's trophic theory and trophic theory based on average individuals with explicit individual-level size spectrum theory. The trophic efficiency based on the transfer of mass between trophic levels through predator–prey interactions is demonstrated to be valid only when somatic growth can be ignored. Taking somatic growth into account yields an average individual growth efficiency that is smaller than the trophic efficiency.
Diversification of New Zealand weta (Orthoptera: Ensifera: Anostostomatidae) and their relationships in Australasia
Authors: Pratt Renae C , Morgan-Richards Mary , Trewick Steve A
Published: September 2008

New Zealand taxa from the Orthopteran family Anostostomatidae have been shown to consist of three broad groups,
Hemiandrus
(ground weta),
Anisoura/Motuweta
(tusked weta) and
Hemideina
–
Deinacrida
(tree–giant weta). The family is also present in Australia and New Caledonia, the nearest large land masses to New Zealand. All genera are endemic to their respective countries except
Hemiandrus
that occurs in New Zealand and Australia. We used nuclear and mitochondrial DNA sequence data to study within genera and among species-level genetic diversity within New Zealand and to examine phylogenetic relationships of taxa in Australasia. We found the Anostostomatidae to be monophyletic within Ensifera, and justifiably distinguished from the Stenopelmatidae among which they were formerly placed. However, the New Zealand Anostostomatidae are not monophyletic with respect to Australian and New Caledonian species in our analyses. Two of the New Zealand groups have closer allies in Australia and one in New Caledonia. We carried out maximum-likelihood and Bayesian analyses to reveal several well supported subgroupings. Our analysis included the most extensive sampling to date of
Hemiandrus
species and indicate that Australian and New Zealand
Hemiandrus
are not monophyletic. We used molecular dating approaches to test the plausibility of alternative biogeographic hypotheses for the origin of the New Zealand anostostomatid fauna and found support for divergence of the main clades at, or shortly after, Gondwanan break-up, and dispersal across the Tasman much more recently.
Evolution of New Zealand's terrestrial fauna: a review of molecular evidence
Authors: Goldberg Julia , Trewick Steven A , Paterson Adrian M
Published: September 2008

New Zealand biogeography has been dominated by the knowledge that its geophysical history is continental in nature. The continental crust (Zealandia) from which New Zealand is formed broke from Gondwanalandca80 Ma, and there has existed a pervading view that the native biota is primarily a product of this long isolation. However, molecular studies of terrestrial animals and plants in New Zealand indicate that many taxa arrived since isolation of the land, and that diversification in most groups is relatively recent. This is consistent with evidence for species turnover from the fossil record, taxonomic affinity, tectonic evidence and observations of biological composition and interactions. Extinction, colonization and speciation have yielded a biota in New Zealand which is, in most respects, more like that of an oceanic archipelago than a continent.
Colonization and diversification of Galápagos terrestrial fauna: a phylogenetic and biogeographical synthesis
Authors: Parent Christine E , Caccone Adalgisa , Petren Kenneth
Published: September 2008

Remote oceanic islands have long been recognized as natural models for the study of evolutionary processes involved in diversification. Their remoteness provides opportunities for isolation and divergence of populations, which make islands remarkable settings for the study of diversification. Groups of islands may share a relatively similar geological history and comparable climate, but their inhabitants experience subtly different environments and have distinct evolutionary histories, offering the potential for comparative studies. A range of organisms have colonized the Galápagos Islands, and various lineages have radiated throughout the archipelago to form unique assemblages. This review pays particular attention to molecular phylogenetic studies of Galápagos terrestrial fauna. We find that most of the Galápagos terrestrial fauna have diversified in parallel to the geological formation of the islands. Lineages have occasionally diversified within islands, and the clearest cases occur in taxa with very low vagility and on large islands with diverse habitats. Ecology and habitat specialization appear to be critical in speciation both within and between islands. Although the number of phylogenetic studies is continuously increasing, studies of natural history, ecology, evolution and behaviour are essential to completely reveal how diversification proceeded on these islands.
Molecular and morphological analysis of the critically endangered Fijian iguanas reveals cryptic diversity and a complex biogeographic history
Authors: Keogh J. Scott , Edwards Danielle L , Fisher Robert N , Harlow Peter S
Published: September 2008

The Pacific iguanas of the Fijian and Tongan archipelagos are a biogeographic enigma in that their closest relatives are found only in the New World. They currently comprise two genera and four species of extinct and extant taxa. The two extant species,
Brachylophus fasciatus
from Fiji, Tonga, and Vanuatu and
Brachylophus vitiensis
from western Fiji, are of considerable conservation concern with
B. vitiensis
listed as critically endangered. A recent molecular study has shown that
Brachylophus
comprised three evolutionarily significant units. To test these conclusions and to reevaluate the phylogenetic and biogeographic relationships within
Brachylophus
, we generated an mtDNA dataset consisting of 1462 base pairs for 61 individuals from 13 islands, representing both
Brachylophus
species. Unweighted parsimony analyses and Bayesian analyses produced a well-resolved phylogenetic hypothesis supported by high bootstrap values and posterior probabilities within
Brachylophus
. Our data reject the monophyly of specimens previously believed to comprise
B. fasciatus
. Instead, our data demonstrate that living
Brachylophus
comprise three robust and well-supported clades that do not correspond to current taxonomy. One of these clades comprises
B. fasciatus
from the Lau group of Fiji and Tonga (type locality for
B. fasciatus
), while a second comprises putative
B. fasciatus
from the central regions of Fiji, which we refer to here as
B
. n. sp. Animals in this clade form the sister group to
B. vitiensis
rather than other
B. fasciatus
. We herein describe this clade as a new species of
Brachylophus
based on molecular and morphological data. With only one exception, every island is home to one or more unique haplotypes. We discuss alternative biogeographic hypotheses to explain their distribution in the Pacific and the difficulties of distinguishing these. Together, our molecular and taxonomic results have important implications for future conservation initiatives for the Pacific iguanas.
Biogeography of the fauna of French Polynesia: diversification within and between a series of hot spot archipelagos
Authors: Gillespie Rosemary G , Claridge Elin M , Goodacre Sara L
Published: September 2008

The islands of French Polynesia cover an area the size of Europe, though total land area is smaller than Rhode Island. Each hot spot archipelago (Societies, Marquesas, Australs) is chronologically arranged. With the advent of molecular techniques, relatively precise estimations of timing and source of colonization have become feasible. We compile data for the region, first examining colonization (some lineages dispersed from the west, others from the east). Within archipelagos, blackflies (Simulium) provide the best example of adaptive radiation in the Societies, though a similar radiation occurs in weevils (Rhyncogonus). Both lineages indicate that Tahiti hosts the highest diversity. The more remote Marquesas show clear examples of adaptive radiation in birds, arthropods and snails. The Austral Islands, though generally depauperate, host astonishing diversity on the single island of Rapa, while lineages on other islands are generally widespread but with large genetic distances between islands. More recent human colonization has changed the face of Polynesian biogeography. Molecular markers highlight the rapidity of Polynesian human (plus commensal) migrations and the importance of admixture from other populations during the period of prehistoric human voyages. However, recent increase in traffic has brought many new, invasive species to the region, with the future of the indigenous biota uncertain.
Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity
Authors: Arita Minetaro , Wakita Takaji , Shimizu Hiroyuki
Published: September 2008

Poliovirus (PV) and enterovirus 71 (EV71) cause severe neurological symptoms in their infections of the central nervous system. To identify compounds with anti-PV and anti-EV71 activities that would not allow the emergence of resistant mutants, we performed drug screening by utilizing a pharmacologically active compound library targeting cellular factors with PV and EV71 pseudoviruses that encapsidated luciferase-encoding replicons. We have found that metrifudil (N-[2-methylphenyl]methyl)-adenosine) (an A2 adenosine receptor agonist), N
6-benzyladenosine (an A1 adenosine receptor agonist) and NF449 (4,4′,4″,4″′-[carbonylbis[imino-5,1,3-benzenetriyl bis(carbonyl-imino)]] tetrakis (benzene-1,3-disulfonic acid) octasodium salt) (a Gs-α inhibitor) have anti-EV71 activity, and that GW5074 (3-(3, 5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)) (a Raf-1 inhibitor) has both anti-PV and anti-EV71 activities. EV71 mutants resistant to metrifudil, N
6-benzyladenosine and NF449 were isolated after passages in the presence of these compounds, but mutants resistant to GW5074 were not isolated for both PV and EV71. The inhibitory effect of GW5074 was not observed in Sendai virus infection and the treatment did not induce the expression of OAS1 and STAT1 mRNA. Small interfering RNA treatment against putative cellular targets of GW5074, including Raf-1, B-Raf, Pim-1, -2, and -3, HIPK2, GAK, MST2 and ATF-3, did not consistently suppress PV replication. Moreover, downregulation of Raf-1 and B-Raf did not affect the sensitivity of RD cells to the inhibitory effect of GW5074. These results suggest that GW5074 has strong and selective inhibitory effect against the replication of PV and EV71 by inhibiting conserved targets in the infection independently of the interferon response.
Characterization of the Drosophila melanogaster retinin gene encoding a cornea‐specific protein
Authors: Kim E. , Choi Y. , Lee S. , Seo Y. , Yoon J. , Baek K.
Published: September 2008

Two‐dimensional analysis of head extracts from Drosophila melanogaster identified the four eye‐specific protein spots corresponding to the retinin protein. The retinin protein spots were specifically stained with phosphoprotein‐specific dye, suggesting that the retinin protein undergoes post‐translational modification by phosphorylation. Northern blot analysis showed that the retinin gene begins to be expressed during the late stage of puparium formation during development. Analysis of the N‐terminal sequence and expression of the retinin gene in S2 suggest that retinin is a secretory protein. Transgenic flies with knockdown expression of the retinin gene by RNA interference (RNAi) were established. However, no significant phenotypic changes in eye structure or phototransduction were observed in the transgenic flies. Western blot analysis and immunohistochemical studies of D. melanogaster eyes suggest that retinin is a cornea‐specific protein.
Land cover and tsetse fly distributions in sub‐Saharan Africa
Authors: CECCHI G. , MATTIOLI R. C. , SLINGENBERGH J. , DE LA ROCQUE S.
Published: September 2008

Abstract This study aims to provide trypanosomiasis‐affected countries with standardized datasets and methodologies for mapping the habitat of the tsetse fly (Glossina spp., the disease vector) by customizing and integrating state‐of‐the‐art land cover maps on different spatial scales. Using a combination of inductive and deductive approaches, land cover and fly distribution maps are analysed in a geographic information system (GIS) to estimate the suitability of different land cover units for the three groups (subgenera) of Glossina. All land cover datasets used for and produced by the study comply with the Land Cover Classification System (LCCS). At the continental scale, a strong correlation between land cover and tsetse habitat is found for both the fusca and palpalis groups, whereas a weaker correlation found for the morsitans group may be indicative of less restrictive ecological requirements. At the regional and national levels, thematic aggregation of the multi‐purpose Africover datasets yielded high‐resolution, standardized land cover maps tailored for tsetse habitat for eight East African countries. The national maps provide remarkable spatial resolution, thematic detail and geographical coverage. They may be applied in subsequent phases of tsetse and trypanosomiasis control projects, including the planning of entomological surveys, actual tsetse control operations and planning for land use in reclaimed areas. The methodology and datasets discussed in the paper may have applications beyond the tsetse and trypanosomiasis issue and may be used with reference to other arthropod vectors, vector‐borne and parasitic diseases.
Rice Resistance to Brown Spot Mediated by Silicon and its Interaction with Manganese
Authors: Zanão Júnior Luiz Antônio , Rodrigues Fabrício Ávila , Fontes Renildes Lucio Ferreira , Korndörfer Gaspar Henrique , Neves Júlio César Lima
Published: September 2008

Brown spot is one of the most devasting and prevalent disease of rice and its control is mainly dependent on fungicide application. Therefore, this study aimed to examine the effects of Si and Mn on the development of brown spot on rice plants grown in hydroponic culture. Rice plants (cv. ‘Metica‐1’) were grown in plastic pots containing 0 or 2 mm Si (−Si and +Si treatments, respectively) with three Mn rates (0.5, 2.5 and 10 μm). Plants were inoculated with B. oryzae 39 days after emergence. The following components of resistance were evaluated: incubation period (IP), number of lesions (NL) per cm2 of leaf area, real disease severity (RDS) and area under brown spot progress curve (AUBSPC). The content of Si and Mn in the plant tissues was also determined. Si content was significantly higher in rice tissue of plants of the +Si treatment than of the −Si treatment regardless of the Mn rates used. The Mn rates did not affect the Si content of the rice plants. The Mn content of the rice tissues was significantly higher in the −Si treatment than on +Si treatment, regardless of the Mn rate used. The Mn content was significantly lower at 0.5 μm Mn in comparison to the other rates for both −Si and +Si treatments. The IP of brown spot on rice leaves significantly increased in the +Si treatment; but the Mn rates in the presence of Si had no effect on IP. In the −Si treatment, the IP was significantly higher only at the rate of 2.5 μm. The NL, RDS and AUBSPC were significantly reduced in the +Si treatment regardless of the Mn rates. The Mn rates in the presence of Si had no effect on these components of resistance. Overall, Si dramatically impacted the development of brown spot regardless of the presence of Mn at either low or high rates. This may be useful in regions where the soil has either toxic or deficient levels of Mn and cultivars with brown spot resistance are not commercially available.
Fourier analysis of digital retinal images in estimation of cataract severity
Authors: Abdul‐Rahman Anmar M , Molteno Tim , Molteno Anthony CB
Published: September 2008

Abstract

Purpose:  To evaluate the efficacy of Fourier analysis of digital retinal images in grading cataract severity.

Methods:  A total of 330 eyes from 165 patients were divided into 287 phakic and 43 pseudophakic eyes. All patients underwent clinical examination, colour fundus photography and photoscreening. Phakic eyes were classified into 232 cataractous and 55 control eyes using the Lens Opacity Classification System (LOCS III). Assessment was repeated at 6 weeks postoperatively for 157 eyes in the cataractous group and in 24 pseudophakic eyes. The predictive value in assessing cataract severity using discrete Fourier transforms in fundus image analysis was compared with LogMAR visual acuity and LOCS III grading.

Results:  The mean age of the population was 71.7 years ± 13.4 (range 19–92) there were 70 (42.4%) males and 95 (57.6%) females. The mean LogMAR visual acuity was 0.44 ± 0.41 (range −0.2 to 1.4). In the cataract group there were 232 eyes (80.8%), the mean age was 75.5 years ± 9.3 (range 21–92). Fourier analysis of retinal images showed a moderate correlation with LOCS III (R2 = 0.59) in grading cataract severity and demonstrated a comparable correlation with visual acuity (R2 = 0.39) as LOCS III (R2 = 0.44). As with LOCS III score the Fourier value had a poor correlation with visual acuity in clear (R2 = 0.05) and pseudophakic lenses (R2 = 0.07).

Conclusion:  Fourier analysis is a useful automated method in grading of cataract severity for both pure and mixed types of cataract; however, similar to many objective systems it cannot determine the anatomic type of cataract.
Nucleus extraction in sutureless surgery: getting hooked!
Authors: Murray Neil L , Murray Tania NT
Published: September 2008

Abstract

Simple modifications to a readily available disposable 25 gauge cannula facilitate nucleus extraction in sutureless extracapsular cataract surgery. A case series using the modified cannula, and a temporal incision approach, are presented. Outcomes and complications attributable to the use of the cannula are discussed.
Reducing psychotropic medications in elderly rehabilitation inpatients with a fall‐related admission: How often is it happening?
Authors: Clements Richard M
Published: September 2008

Aim:  To assess the frequency of psychotropic medication withdrawal in an inpatient geriatric rehabilitation population with a fall‐related admission diagnosis.

Methods:  A retrospective medical record audit. The medical records department randomly selected 100 patients admitted between October 2006 and April 2007 to the geriatric rehabilitation ward of Casey Hospital with a fall‐related admission diagnosis.

Results:  The population was predominantly female (71%) and elderly (average age, 80 years) with the vast majority of patients living at home (88%) prior to admission. Twenty‐six of 49 (53%) of patients admitted on psychotropic medication were on a reduced regime by discharge (reduced dose or number of psychotropic medications). Just 7 of 100 patients had an increased psychotropic medication regime by discharge. Benzodiazepines were far more likely to be reduced (20/24, 83%) than other psychotropic medications.

Conclusion:  This audit does suggest an acceptable awareness in this geriatric rehabilitation setting of the fall risk posed by psychotropic medication. It needs to be further explored why benzodiazepines are so much more likely to be reduced in this population than other psychotropic medications, despite those other types also posing a significant fall risk.
Daily blood glucose profiles of glibenclamide and gliclazide taken once or twice daily in elderly type 2 diabetic patients
Authors: Kigawa Yoshiaki , Oba Kenzo , Futami‐Suda Shoko , Norose Jun , Yasuoka Hiroko , Suzuki Kazunari , Ouchi Motoshi , Watanabe Kentaro , Suzuki Tatsuya , Nakano Hiroshi
Published: September 2008

Aim:  The aim of this study was to evaluate the difference in daily blood glucose profiles between once‐ and twice‐daily regimens of a moderate daily dose of glibenclamide or gliclazide in elderly patients with type 2 diabetes.

Methods:  Daily blood glucose profile data were evaluated in 18 elderly type 2 diabetic patients treated with 80 mg/day gliclazide or 5 mg/day glibenclamide as monotherapy. The first daily blood glucose profile of the twice‐daily regimen was performed approximately 1 week before hospital discharge, and the second was performed after taking a once‐daily regimen for 4–7 days. Plasma glucose and plasma immunoreactive insulin (IRI) concentrations were measured daily at 12 time points: 08.00 (before breakfast); 10.00; 12.00 (before lunch); 14.00; 18.00 (before dinner); 20.00; 0.00; 02.00; 03.00; 04.00; 06.00; and 08.00 hours the next morning.

Results:  Daily blood glucose profiles and plasma IRI profiles did not differ between the once‐ and twice‐daily regimen groups in either the gliclazide group or the glibenclamide group. Plasma glucose values between midnight and early morning tended to be lower than the 08.00 hours plasma glucose value in the glibenclamide group, but not in the gliclazide group.

Conclusion:  These results suggest that the blood glucose‐lowering effects of a once‐ and twice‐daily moderate daily dose of glibenclamide or gliclazide do not differ in elderly type 2 diabetic patients. However, glibenclamide, regardless of the dosage schedule, tends to lower the plasma glucose values between midnight and early morning.
In‐depth descriptive analysis of trends in prevalence of long‐term care in Japan
Authors: Fukuda Yoshiharu , Nakao Hiroyuki , Yahata Yuichiro , Imai Hirohisa
Published: September 2008

Background:  Long‐term care (LTC) insurance was introduced in Japan in 2000. Herein, we describe the trends in demand for LTC, using age‐standardized and level‐specific rates of entitlement and utilization of LTC at national and prefectural levels.

Methods:  We analyzed LTC data from 2002–2005 to examine: (i) the influence of population aging, calculating crude and age‐standardized entitlement and utilization rates; (ii) the relation between baseline entitlement rate and increase in the rate over this 3‐year period; and (iii) differences in increases in entitlement rate between low and high care levels.

Results:  The entitlement and utilization rates increased even after adjustment for age; approximately two‐thirds of the increase was not due to population aging. Variations in the entitlement rates among prefectures did not decrease (coefficient of variance was 0.12 in 2002 and 0.11 in 2005), and there was no significant correlation between baseline entitlement rates and the later increases among prefectures (r = −0.20, P = 0.19). The increase in entitlement rate was larger for low than for high care levels (31% vs 6%), and those for low and high care levels were weakly correlated.

Conclusion:  This study suggested that a large part of the increase in LTC demand could not be explained by population aging, and the increase did not result from equalization of LTC services across the country. In addition, it seems that the demands of low and high care levels depend on different factors. The increase in LTC demand should be monitored carefully to identify underlying factors and to ensure sustainability of the system.