bluuebunny/crossref_metadata_2025 huggingface dataset:
Dinantian conodont biostratigraphy of the Northumberland Trough
Authors: Armstrong H. A. , Purnell M. A.
Published: July 2010

Abstract. Conodont faunas from Dinantian strata of the Northumberland Trough and Tweed Basin are described. Five zones are recognised. These zones are correlated with the standard British Stages and where possible with European and American sections. Chadian and Arundian faunas are dominated by Taphrognathus, Cloghergnathus and Cavusgnathus which typically occur in shallow intertidal and shallow subtidal environments. Holkerian and Asbian strata are barren of conodonts. In the Brigantian deeper-water genera including Gnathodus are represented. The shallow water nature of the lower faunas causes difficulty in correlation with goniatite-bearing sequences in the Craven Basin but reasonable correlations can be made to Ravenstonedale and the Avon Gorge.
Wondersella athersuchi Banner & Strank: a corrective note on its systematic position
Authors: Banner F. T. , Strank A. R. E.
Published: July 2010

Abstract. The wall of Wondersella athersuchi is shown to be microperforate as well as smooth, so that this taxon is to be referred to the Praehedbergellidae rather than to the Hedbergellidae. This agrees with its proposed phylogenetic origin and its known biostratigraphical position.
Early Cretaceous striate tricolpate pollen from the Borehole Mersa Matruh 1, North West Desert, Egypt
Authors: Penny James H. J.
Published: July 2010

Abstract. Striate tricolpate pollen has been recovered from Early Cretaceous samples of the borehole Mersa Matruh 1 in the N.W. Desert of Egypt. Scanning Electron Microscope (SEM) study has revealed fine details of their exine scupture, on the basis of which four new taxa, STRIOTRI-OVAL, STRIOTRI-SMOOTHMUR, STRIOTRI-SEGMUR and STRIORET-SMOOTH, are distinguished. The stratigraphic ranges of these are discussed and they are compared with other published species. They are among the oldest striate tricolpate pollen yet described, appearing in sediments of Early Aptian age, slightly predating the first reliable records of reticulate tricolpates in the sequence studied. The lack of earlier reticulate grains is attributed to possible sample failure. There is evidence that the true first appearance of tricoplate pollen in Egypt may be late Barrenian.
Muellerisphaerids from the Llandovery of western mid-Wales
Authors: Loydell David K. , Mcmillan Ian , Barron Hugh F.
Published: July 2010

Abstract. Muellerisphaerids are described and illustrated from Britain for the first time. The mechanical processing method used in their extraction is described. They are preserved as pyrite internal moulds and thus lack the necessary morphological detail (i.e. spines) to be identified to family level. Other microfossils occurring in the samples are also recorded.
Samples taken off Jamestown, Saint Helena Island (South Atlantic Ocean)
Authors: Kouyoumontzakis Georges
Published: July 2010

Abstract. Three dredgings samples taken off the coast of Saint Helena, reveal two micropalaeontological associations. One is an infralittoral association, characterized by Miliolina (essentially Quinqueloculina), and by Rotaliina with various species of Amphistegina. The other is a circalittoral association, in which the following changes in family distribution may be observed: a decrease in Miliolina and others littoral species, and an increase in Discorbidae, Eponididae, Cibicididae, and Anomalinidae which indicate an increase in sea depth. The presence of relict Amphisteginidae might point to a Holocene stillstand of the transgressive sea.
Three new miospore genera from the Lower Carboniferous (Viséan) rocks of east Fife, Scotland
Authors: Neville Richard S. W.
Published: July 2010

Abstract. Three new miospore genera. Dillspora, Oswaldispora and Robandispora are described from the Lower Carboniferous (Viséan) rocks of east Fife. One new species. Robandispora claytonii is erected. Two new combinations. Dillspora disjuncta and Oswaldispora xenika, are proposed and the diagnosis of the latter is emended.
New data on the ostracod genus Aratrocypris Whatley et al. 1985, with descriptions of species from the Upper Cretaceous of Europe and the Cainozoic of the North Atlantic
Authors: Whatley Robin , Witte Leendert , Coles Graham
Published: July 2010

Abstract. Paradoxostoma ? cretacea Bonnema (1941), is shown to belong to the deep sea cyprid genus Aratrocypris Whatley et al (1985). The implications of the discovery of this genus, hitherto known only from the Palaeocene to Recent, in the Upper Cretaceous of the Netherlands are discussed with respect to the palaeodepth of the Dutch Chalk Sea and to the origin and palaeozoogeographical history of Aratrocypris. The new species Aratrocypris gigantea, from the Recent and Aratrocypris maddocksae from the Cainozoic, are described from the North Atlantic and other, nomina nuda species are described or discussed from the same area.
Micropalaeontology of the Permian Marls of Merbah el Oussif (Jebel Tebaga, Tunisia) with special emphasis on the Ostracods
Authors: Lethiers F. , Razgallah S. , Colin J. P. , Vachard D.
Published: July 2010

Abstract. The Marls of Merbah el Oussif are part of the Permian series of the Jebel Tebaga of Médénine in Tunisia. They belong to the uppermost Murghabian, a stage intermediate between the Wordian and the Capitanian. These green marls were deposited in lows at the base of sponge bioherms. The sedimentation rate was high and the environment well oxygenated. The marls contain a relatively rich assemblage of isolated sponges, gastropods, smaller foraminifera, fusulinids, dasycladacean algae and ostracods. Amongst those, for the first time reported from the Permian of Tunisia, 14 species have been identified and one new species described, Bairdiacypris postrectiformis sp. nov. The geographic and stratigraphic distribution of several species are discussed. This ostracod fauna indicates a shallow nearshore environment and suggests a western, not eastern connection between the Tethys and the Texas Sea.
Palaeoclimatic control of Upper Pliocene Discoaster assemblages in the North Atlantic
Authors: Chepstow-Lusty Alex , Backman Jan , Shackleton Nicholas J.
Published: July 2010

Abstract. Abundance variations of six Pliocene species of the nannofossil genus Discoaster were analyzed over the time interval 1.89–2.95 Ma at five sites in the North Atlantic; DSDP 552 (56°N), DSDP 607 (41°N), ODP 659 (18°N), ODP 658 (20°N) and ODP 662 (1°S). Individual species are compared between the five sites as a percentage of the total Discoaster assemblage, using age models based mainly on Discoaster datums (3 control points used at each site). The sampling interval is approximately 3 kyrs.Discoaster brouweri, the only species covering the complete time interval became a less significant component of the assemblages with increasing latitude during the interval prior to 2.3 Ma. Discoaster triradiatus shows a distinct abundance acme at all sites between 1.89–2.7 Ma. Discoaster surculus increased in relative abundance with higher latitudes and upwelling conditions (ODP Site 658).Discoaster pentaradiatus is an important component of the assemblages at all sites, but displays an inverse abundance relationship with D. surculus as a function of increasing latitude and upwelling conditions. Discoaster tamalis and Discoaster asymmetricus are reduced at low latitudes and in upwelling conditions and increase relative to D. brouweri at higher latitudes, where there is strong evidence for taxonomic affinity.
The search for a reliable mounting medium for Recent ‘live’ foraminifera
Authors: Maybury C. , Morrison L. , Stewart V.
Published: July 2010

Abstract. There is no suitable mounting medium for the longterm storage of Recent, ‘live’ foraminifera. Glycerol has been used for this purpose since the last century, but its properties do not meet our requirements (see below). We therefore began a series of trials in order to find the ‘perfect’ mountant. The inception of this ‘Micropalaeontological Notebook’ provides a timely opportunity to highlight the results of our experiments and to elicit a response from the readership to facilitate our search.In choosing mounting media for experiment it was first necessary to detail our requirements. The latter are as follows: the medium must be clear and possess a refractive index (nD:) close or equal to that of glass. The nD of the mounted specimens should differ from that of the mountant or they will be invisible. It should function as a permanent mount, fixing specimens in a position suitable for light microscopical examination. It should not form aggregations or induce overlap of specimens and should permit easy relocation of small organisms (i.e., fixing them so that their co-ordinates can be read with an England Finder) It should neither be messy nor aspirate air and should not contract, thereby crushing delicate specimens. The mountant must be treated to inhibit bacterial and fungal growths. It must be relatively inexpensive and quick to prepare and must not solidify too rapidly, leaving insufficient time to position specimens. Since the specimens are ‘live’ it is important that the protoplasmic contents of the cell and the mountant are isotonic. Similarly, . . .
Permocalculus iagifuensis sp. nov.: A new Miocene gymnocodiacean alga from Papua New Guinea
Authors: Simmons M. D. , Johnston M. J.
Published: July 2010

Abstract. Permocalculus iagifuensis, a new species of gymnocodiacean alga is described from the Miocene of the Darai Limestone Formation of Papua New Guinea. The discovery of this species greatly extends the range of gymnocodiacean algae, which previously had only been confidently recorded from the Permian and Cretaceous. It also suggests an evolutionary link to the Recent genus Galaxaura (order Nemalionales; family Chaetangiaceae), which is the only extant alga bearing a similarity to the Gymnocodiaceae. Alternatively, a closer relationship to the green udoteacean algae (e.g. Halimeda) is considered. The microfauna and other microflora associated with this new species are briefly described.
Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia
Authors: Masyuk Anatoliy I. , Huang Bing Q. , Ward Christopher J. , Gradilone Sergio A. , Banales Jesus M. , Masyuk Tatyana V. , Radtke Brynn , Splinter Patrick L. , LaRusso Nicholas F.
Published: July 2010

Exosomes are small extracellular vesicles that are thought to participate in intercellular communication. Recent work from our laboratory suggests that, in normal and cystic liver, exosome-like vesicles accumulate in the lumen of intrahepatic bile ducts, presumably interacting with cholangiocyte cilia. However, direct evidence for exosome-ciliary interaction is limited and the physiological relevance of such interaction remains unknown. Thus, in this study, we tested the hypothesis that biliary exosomes are involved in intercellular communication by interacting with cholangiocyte cilia and inducing intracellular signaling and functional responses. Exosomes were isolated from rat bile by differential ultracentrifugation and characterized by scanning, transmission, and immunoelectron microscopy. The exosome-ciliary interaction and its effects on ERK1/2 signaling, expression of the microRNA, miR-15A, and cholangiocyte proliferation were studied on ciliated and deciliated cultured normal rat cholangiocytes. Our results show that bile contains vesicles identified as exosomes by their size, characteristic “saucer-shaped” morphology, and specific markers, CD63 and Tsg101. When NRCs were exposed to isolated biliary exosomes, the exosomes attached to cilia, inducing a decrease of the phosphorylated-to-total ERK1/2 ratio, an increase of miR-15A expression, and a decrease of cholangiocyte proliferation. All these effects of biliary exosomes were abolished by the pharmacological removal of cholangiocyte cilia. Our findings suggest that bile contains exosomes functioning as signaling nanovesicles and influencing intracellular regulatory mechanisms and cholangiocyte proliferation through interaction with primary cilia.
Methodological assessment of skin and limb blood flows in the human forearm during thermal and baroreceptor provocations
Authors: Brothers R. Matthew , Wingo Jonathan E. , Hubing Kimberly A. , Crandall Craig G.
Published: July 2010

Skin blood flow responses in the human forearm, assessed by three commonly used technologies—single-point laser-Doppler flowmetry, integrated laser-Doppler flowmetry, and laser-Doppler imaging—were compared in eight subjects during normothermic baseline, acute skin-surface cooling, and whole body heat stress (Δ internal temperature = 1.0 ± 0.2°C; P < 0.001). In addition, while normothermic and heat stressed, subjects were exposed to 30-mmHg lower-body negative pressure (LBNP). Skin blood flow was normalized to the maximum value obtained at each site during local heating to 42°C for at least 30 min. Furthermore, comparisons of forearm blood flow (FBF) measures obtained using venous occlusion plethysmography and Doppler ultrasound were made during the aforementioned perturbations. Relative to normothermic baseline, skin blood flow decreased during normothermia + LBNP ( P < 0.05) and skin-surface cooling ( P < 0.01) and increased during whole body heating ( P < 0.001). Subsequent LBNP during whole body heating significantly decreased skin blood flow relative to control heat stress ( P < 0.05). Importantly, for each of the aforementioned conditions, skin blood flow was similar between the three measurement devices (main effect of device: P > 0.05 for all conditions). Similarly, no differences were identified across all perturbations between FBF measures using plethysmography and Doppler ultrasound ( P > 0.05 for all perturbations). These data indicate that when normalized to maximum, assessment of skin blood flow in response to vasoconstrictor and dilator perturbations are similar regardless of methodology. Likewise, FBF responses to these perturbations are similar between two commonly used methodologies of limb blood flow assessment.
Usefulness of Serum Insulin-Like Growth Factor I Assessment in the Diagnosis of Childhood-Onset Growth Hormone Deficiency
Authors: Federico Giovanni , Cianfarani Stefano
Published: July 2010

The diagnosis of childhood-onset growth hormone (GH) deficiency (GHD) is not straightforward, requiring a comprehensive clinical, anthropometric, biochemical, endocrine, and neuroradiological assessment. Although pharmacological GH stimulation tests are still considered the gold standard for GHD diagnosis, they are burdened by both poor specificity and side effects. The measurement of insulin-like growth factor I (IGF-I), due to its close GH dependency, was proposed for diagnosing GHD. However, a number of factors may affect the measurements. Herein, we propose an algorithm based on both IGF-I determination and anthropometry, aimed at simplifying the diagnosis of GHD in prepubertal children.
ApoA-1 Mimetic Peptide Reverses Uremia-Induced Upregulation of Pro-Atherogenic Pathways in the Aorta
Authors: Vaziri Nosratola D. , Bai Yongli , Yuan Jun , Said Hannah L. , Sigala Whitney , Ni Zhemin
Published: July 2010

Background: Chronic kidney disease (CKD) results in accelerated atherosclerosis and cardiovascular disease. This is primarily mediated by oxidative stress, inflammation and dyslipidemia. By mediating reverse cholesterol transport and exerting antioxidant/anti-inflammatory actions, high-density lipoprotein (HDL) and ApoA-1 protect against atherosclerosis. Plasma Apo-1, HDL cholesterol and HDL antioxidant/anti-inflammatory activities are reduced in CKD. ApoA-1 mimetic peptides associate with and enhance antioxidant/anti-inflammatory properties of HDL. We hypothesized that long-term administration of ApoA-1 mimetic peptide, L4F, may ameliorate inflammation and oxidative stress in the conduit arteries in experimental CKD. Methods: After 5/6 nephrectomy, rats were randomized to L4F (5 mg/kg s.c. 3 times weekly for 4 weeks) and placebo-treated groups. Sham-operated rats served as controls. Results: The untreated CKD group exhibited marked lipid accumulation and upregulations of NAD(P)H oxidase subunits (gp91phox, p22phox, and p47phox), COX-2, 12-lipoxygenase, MCP-1, PAI-1, myeloperoxidase and iNOS, NFĸB activation and nitrotyrosine accumulation in the thoracic aorta. L4F administration reversed or attenuated these abnormalities without altering renal function or plasma lipids. Conclusions: CKD leads to lipid accumulation and upregulation of pro-atherogenic pathways in the artery wall. These abnormalities are attenuated by ApoA-1 mimetic peptide, pointing to its protective effect in CKD. Future studies are needed to explore the effect of these peptides in CKD patients.
L-Carnitine Treatment in Patients with Mild Diastolic Heart Failure Is Associated with Improvement in Diastolic Function and Symptoms
Authors: Serati Ali Reza , Motamedi Mohammad Reza , Emami Sepideh , Varedi Peyman , Movahed Mohammad Reza
Published: July 2010

Objectives:L-Carnitine is a crucial component of activated fatty acid transport. The aim of this study was to evaluate the effect of L-carnitine on patients with a history of mild heart failure and diastolic dysfunction. Methods: Twenty-nine patients with a history of NYHA functional class II symptoms and ejection fraction >45% with documented grade 1 diastolic dysfunction on echocardiogram were randomized in blinded fashion to receive 1,500 mg of L-carnitine daily for 3 months in comparison to a no treatment group (31 patients). Baseline echocardiographic and follow-up measurements of diastolic parameters were assessed after 3 months. Results: Important parameters of diastolic function improved in the L-carnitine group only: left atrial size (3.6 ± 0.4 cm before treatment vs. 3.4 ± 0.5 cm after treatment, p = 0.01); isovolemic relaxation time (127 ± 26 ms before vs. 113 ± 24 ms after treatment, p = 0.007); septal mitral E′ velocity (0.064 ± 0.01 m/s before vs. 0.074 ± 0.01 m/s after treatment, p = 0.01), and lateral mitral E velocity (0.082 ± 0.01 m/s before vs. 0.091 ± 0.02 m/s after treatment, p = 0.006). Dyspnea also significantly improved in L-carnitine-treated patients. Conclusion: In patients with a history of diastolic heart failure, important indices of diastolic function and symptoms appear to improve with L-carnitine treatment.
p122 Protein Enhances Intracellular Calcium Increase to Acetylcholine
Authors: Murakami Reiichi , Osanai Tomohiro , Tomita Hirofumi , Sasaki Satoko , Maruyama Atsushi , Itoh Ken , Homma Yoshimi , Okumura Ken
Published: July 2010

Objective—

Phospholipase C-δ1 activity is enhanced in patients with coronary artery spasm, and a p122 protein was recently cloned to potentiate phospholipase C-δ1 activity. To investigate the role of p122 in enhanced vasomotility, we examined p122 expression in the cultured skin fibroblasts obtained from patients with and without coronary spasm, intracellular Ca
2+
concentration ([Ca
2+
]
i
) at baseline and after stimulation with acetylcholine in the cells transfected with p122, and promoter in genomic DNA.

Methods and Results—

p122 protein and gene expression levels in patients with coronary spasm (n=11) were enhanced compared with levels in control subjects (n=9) (
P
<0.01 for both). [Ca
2+
]
i
at baseline and the peak increase in [Ca
2+
]
i
in response to acetylcholine were both 2 times higher in cells transfected with p122 than in those without p122. Conversely, knockdown of p122 resulted in diminished [Ca
2+
]
i
response. In the p122 promoter analysis, the −228G/A and −1466C/T variants revealed the increase in luciferase activity. Although the −1466C/T variant was similar between 144 patients with coronary spasm and 148 controls, the −228G/A variant was more frequent in male patients than in male controls (
P
<0.05).

Conclusion—

The p122 protein is upregulated in patients with coronary spasm, causing increased [Ca
2+
]
i
to acetylcholine, and thereby seems to be related to enhanced coronary vasomotility.
Role of Cardiac Myocyte CXCR4 Expression in Development and Left Ventricular Remodeling After Acute Myocardial Infarction
Authors: Agarwal Udit , Ghalayini Wael , Dong Feng , Weber Kristal , Zou Yong-Rui , Rabbany Sina Y. , Rafii Shahin , Penn Marc S.
Published: July 2010

Rationale:

Stromal cell–derived factor (SDF)-1/CXCR4 axis has an instrumental role during cardiac development and has been shown to be a potential therapeutic target for optimizing ventricular remodeling after acute myocardial infarction (AMI) and in ischemic cardiomyopathy. Although a therapeutic target, the specific role of cardiac myocyte CXCR4 (CM-CXCR4) expression following cardiogenesis and survival of cardiac myocyte and left ventricular remodeling after AMI is unknown.

Objective:

We hypothesized that cardiac myocyte derived CXCR4 is critical for cardiac development, but it may have no role in adulthood secondary to the short transient expression of SDF-1 and the delayed expression of CM-CXCR4 following AMI. To address this issue, we developed congenital and conditional CM-CXCR4
−/−
mouse models.

Methods and Results:

Two strains of CM-CXCR4
flox/flox
mice were generated by crossing CXCR4
flox/flox
mice with MCM-Cre
+/−
mouse and MLC2v-Cre
+/−
mouse on the C57BL/6J background, yielding CXCR4
flox/flox
MCM-Cre
+/−
and CXCR4
flox/flox
MLC2v-Cre
+/−
mice. Studies demonstrated recombination in both models congenitally in the MLC2v-Cre
+/−
mice and following tamoxifen administration in the MCM-Cre
+/−
mice. Surprisingly the CXCR4
flox/flox
MLC2v-Cre
+/−
are viable, had normal cardiac function, and had no evidence of ventricular septal defect. CXCR4
flox/flox
MCM
+/−
treated with tamoxifen 2 weeks before AMI demonstrated 90% decrease in cardiac CXCR4 expression 48 hours after AMI. Twenty-one days post AMI, echocardiography revealed no statistically significant difference in the wall thickness, left ventricular dimensions or ejection fraction (40.9±7.5 versus 34.4±2.6%) in CXCR4
flox/flox
mice versus CM-CXCR4
−/−
mice regardless of strategy of Cre expression. No differences in vascular density (2369±131 versus 2471±126 vessels/mm
2
; CXCR4
flox/flox
versus CM-CXCR4
−/−
mouse), infarct size, collagen content, or noninfarct zone cardiac myocyte size were observed 21 days after AMI.

Conclusions:

We conclude that cardiac myocyte–derived CXCR4 is not essential for cardiac development and, potentially because of the mismatch in timings of peaks of SDF-1 and CXCR4, has no major role in ventricular remodeling after AMI.
Visual Anecdote
Authors: Offenhuber Dietmar
Published: July 2010

The discourse on information visualization often remains limited to the exploratory function — its potential for discovering patterns in the data. However, visual representations also have a rhetorical function: they demonstrate, persuade, and facilitate communication.

In observing how visualization is used in presentations and discussions, I often notice the use of what could be called “visual anecdotes.” Small narratives are tied to individual data points in the visualization, giving human context to the data and rooting the abstract representation in personal experience. This paper argues that these narratives are more than just illustrations of the dataset; they constitute a central epistemological element of the visualization. By considering these narrative elements as parts of the visualization, its design and knowledge organization appear in a different light.

This paper investigates how the “story” of data representation is delivered. By means of ethnographic interviews and observations, the author highlights the different aspects of the visual anecdote, a specific point where the exploratory and the rhetorical functions of visualization meet.
Review Section
Authors: Porter Pete
Published: July 2010

The live-action comedies Hotel for Dogs and Marley and Me illustrate the prominent American stereotypes of canines as surrogate children and models of human behavior. Both adopt a human perspective on nonhuman animals, particularly dogs. An ethic of caring goes awry, to become pampering and permissiveness, and precludes empathetic training that would help dogs to prosper as canines in a human world.
Cost-effectiveness of two monitoring strategies for the great crested newt (Triturus cristatus)
Authors: Pellet Jérôme , Kröpfli Madeleine , Heer Patrick
Published: July 2010

Designing cost-effective monitoring protocols is a fundamental prerequisite for amphibian conservation. Here, we report a comparison of flashlight survey and trapping (with and without light sticks as trap baits) in order to determine flashlight detectability and trap detectability of great crested newts (Triturus cristatus). Twelve ponds were surveyed in Switzerland where T. cristatus had been known to occur. We measured covariates affecting both flashlight detectability and trap detectability. Newt flashlight detectability using 20 min long flashlight surveys was on average ± SE = 39% ± 10%). Flashlight detectability was mostly influenced by surface and submerged vegetation density, as well as by water temperature. Newt trap detectability during one night using six funnel traps per pond was on average±SE = 41%±10%. Trap detectability was mainly affected by trap position in the pond, with traps lying on the pond floor being more likely to attract newts. The use of light sticks did not enhance the trap detectability. Estimates of flashlight detectability and trap detectability were used to define how many times the sites have to be visited to be 95% certain of not missing T. cristatus in ponds where they are present. In both cases multiple visits (7 flashlight surveys or 6 trapping sessions) have to be performed. Flashlight surveys are the most easily applied and most cost-effective method to use in large scale programs.
Genetic diversity and phylogenetic relationships of Mabuya spp. (Squamata: Scincidae) from western Indian Ocean islands
Authors: Rocha Sara , Harris D. James , Carretero Miguel
Published: July 2010

Western Indian Ocean islands (excluding Madagascar) are inhabited by at least five species of the lizard genus Mabuya, for which diversity and inter-island phylogenetic relationships are still unclear, particularly concerning island populations of M. maculilabris, M. comorensis and M. striata. With a comprehensive sampling across the Comoros archipelago and the islands of Zanzibar and Pemba (Tanzania) we use molecular data and previously published sequences of these species to describe genetic variation across their insular range and explore the possible distinction of insular populations of the different species, contributing to the clarification of their status and knowledge of their colonization patterns. We describe patterns of cryptic diversity within M. comorensis, revealing a West to East colonization of the Comoros archipelago and clarify the status of Malagasy populations of this species. Cryptic variation is also observed within M. maculilabris and M. striata, and the status of several continental and island populations discussed. M. sechellensis is shown to be paraphyletic relative to M. wrightii. Available data for all Afro-Malagasy Mabuya reveals additional possible instances of paraphyly within some species but does not allow for further resolution of basal relationships within this group, pointing to rapid and simultaneous divergences within this group and the need for multiple independent markers to recover the history of this group.
Diplomacy, Ethics and the National Interest: What Are Diplomats For?
Authors: Barder Brian
Published: July 2010

Drawing on the writer’s experience as a former British diplomat who served in Cold War Poland and elsewhere, this article explores rival concepts of the diplomat’s functions: the traditional UK Foreign Office emphasis on competitively and exclusively promoting the national interest; versus alternatively concentrating on the internationalist, ethical obligations that should govern diplomatic (and other) behaviour. Interference in the host country’s internal affairs is formally prohibited, but the question of whether diplomats’ contacts with, and implied moral support for, democratic dissident movements that are opposed to their undemocratic governments amount to unacceptable intervention raises difficult practical, political and ethical questions. An example of differing possible responses to a development aid proposal illustrates the dilemma. Differing views of diplomatic priorities and objectives, embedded in contrasting cultures at the UK Foreign Office and Department for International Development respectively, need to be sensitively resolved, mainly in the latter’s favour.
Israel and the Holy See Negotiate: A Case Study in Diplomacy across Religions
Authors: Cohen Raymond
Published: July 2010

For many years the Holy See recognized Israel de facto, but declined to open formal diplomatic relations. Historical and theological issues burdened mutual perceptions. Wishing to normalize the relationship, the Holy See and Israel concluded a Fundamental Agreement in 1993 and exchanged ambassadors. Under the terms of the accord, the parties were to negotiate further treaties on key issues of church and state. A Legal Personality Agreement was signed in 1997 but was never implemented; and another fiscal and property treaty is still being negotiated. The relationship itself, which is supposed to fulfil the promise of reconciliation between Catholics and Jews, has been ambivalent, and marked by recurrent controversy. This article surveys the issues currently under negotiation. It argues that the reasons for the reserve are structural and subjective, pointing to political, conceptual and institutional dissonances. However, the article also notes the steady progress recently made and expresses the hope that solutions can be found to contested matters.
Reducing the Gap between International Water Law and Human Rights Law: The UNECE Protocol on Water and Health
Authors: Attila Tanzi
Published: July 2010

This article addresses the different approaches to access to water and sanitation by two separate bodies of international law, i.e. water law and human rights law. It shows the slow evolution of the former from a purely inter-State economic dimension, dealing with competing sovereign claims over transboundary watercourses, to one concerned also the needs of peoples and individuals. In light of these developments at the customary level, it illustrates the significant progress in the field at the conventional and Pan-European level represented by the 1999 UN/ECE London Protocol on Water and Health. An analysis of the latter is carried out against the background of the authoritative interpretation of Articles 11 and 12 of the 1966 UN Covenant on Economic, Social and Cultural Rights contained in the 2002 General Comment 15 by the Committee of the Covenant. This comparative analysis shows the full complementarity and, in many respects, even the coincidence between those instruments. From a normative structural point of view, the common denominator between them appears to lie in the due diligence nature of their main obligations enhancing the state legal accountability for water services.
Waterborne Disease Surveillance: The Case for a Closer Interaction between the UNECE Protocol on Water and Health and the International Health Regulations (2005)
Authors: Negri Stefania
Published: July 2010

The UNECE Protocol on Water and Health prioritises prevention and control of waterborne diseases in the European Region. In order to protect public health from water-related outbreaks, the Protocol mandates the Parties to establish, improve and maintain comprehensive national and local surveillance as well as early warning systems. It also promotes international cooperation among Member States and fosters the development of joint and coordinated action aimed to complement or strengthen national capacities of response. Coordination and liaison with competent international agencies and organisations acting in the field of public health and disease surveillance is instead almost completely neglected. Despite the gap in the agreement, the relevance to the Protocol of existing surveillance networks has increasingly been acknowledged. Following this trend, the Protocol Bodies are exploring the opportunities for a closer interaction with regional and global alert and response systems. This effort is commendable, but much more can be done to reach a more intense cooperation and achieve a globally integrated system of disease surveillance. Harmonisation of legal frameworks (in this case, the UNECE Protocol, the EU legislation and the IHR 2005) and a better synergy among relevant networks will enhance protection of global health security, avoid useless duplications of efforts, and ensure coherence of the whole body of international law on public health.
The Emerging Human Right to Land
Authors: De Schutter Olivier
Published: July 2010

This article identifies the emergence of the right to land in international human rights law, and which measures of implementation are called for to ensure the full realization of this right. In certain contexts, the right to land may be seen as a self-standing right, whether it is protected as an element of the right to property, whether it is grounded on the special relationship of indigenous peoples to their lands, territories and resources, or whether it is a component of the right to food. In other cases, the right to land may be said to be instrumental to the right to food: it is protected as an indispensable means through which people can produce food, for their own consumption or as a source of income allowing them, in turn, to purchase food. In making the case for the explicit recognition of the right to land in international human rights law, this article recalls the current pressures on land; it examines the protection of landusers in their existing access to natural resources; and it discusses whether agrarian reform may be seen as a component of the progressive realization of the emerging human right to land.
Humanitarian Limits to Sovereignty: Common Concern and Common Heritage Approaches to Natural Resources and Environment
Authors: Stec Stephen
Published: July 2010

The Peace of Westphalia released forces leading to the Industrial Revolution, ultimately freeing sovereign states to develop competing systems of economic development that had in common the uncontrolled exploitation of the environment. Over time, a law of humanity developed in response to the failings of a law of sovereign states in two main spheres: that of the dignity of the individual and that of matters of “common concern” that require a global, humanitarian response. Environmental issues have moved to the forefront of the latter, as can be demonstrated by an examination of terms used in international law to describe environmental matters, and have given rise to new forms of international and transnational cooperation. By being reminded that humanitarian issues of common concern were at the root of the Westphalian shift itself, we see that it is the radical form of sovereignty that developed in the 19th and 20th centuries that in fact proved inadequate. The key questions, therefore, are what the global environmental challenge teaches us about the potential for sovereignty to be “reclaimed” for humanity, and how and whence authoritative norms to modulate sovereignty will arise.
ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling
Authors: Graham Daniel B. , Akilesh Holly M. , Gmyrek Grzegorz B. , Piccio Laura , Gilfillan Susan , Sim Julia , Belizaire Roger , Carrero Javier A. , Wang Yinan , Blaufuss Gregory S. , Sandoval Gabriel , Fujikawa Keiko , Cross Anne H. , Russell John H. , Cella Marina , Swat Wojciech
Published: July 2010

Immature dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of intracellular major histocompatibility complex class II (MHCII) that continuously recycles from peptide loading compartments to the plasma membrane and back again. This process facilitates sampling of environmental antigens for presentation to T helper cells. Here, we show that a signaling pathway mediated by the DC immunoreceptor tyrosine-based activation motif (ITAM)–containing adaptors (DAP12 and FcRγ) and Vav family guanine nucleotide exchange factors controls the half-life of surface peptide-MHCII (pMHCII) complexes and is critical for CD4 T-cell triggering in vitro. Strikingly, mice with disrupted DC ITAMs show defective T helper cell priming in vivo and are protected from experimental autoimmune encephalitis. Mechanistically, we show that deficiency in ITAM signaling results in increased pMHCII internalization, impaired recycling, and an accumulation of ubiquitinated MHCII species that are prematurely degraded in lysosomes. We propose a novel mechanism for control of T helper cell priming.
The poor response to imatinib observed in CML patients with low OCT-1 activity is not attributable to lower uptake of imatinib into their CD34+ cells
Authors: Engler Jane R. , Frede Amity , Saunders Verity , Zannettino Andrew , White Deborah L. , Hughes Timothy P.
Published: July 2010

The functional activity of the organic cation transporter 1 (OCT-1) protein in chronic myeloid leukemia (CML) mononuclear cells (MNCs) is highly predictive of molecular response in imatinib treated patients. Here we investigate whether the MNC OCT-1 activity (OA) provides a surrogate indicator of effective targeting of the more immature CD34+ cells. While confirming our previous findings that high MNC OA is significantly associated with the achievement of major molecular response (MMR; P = .017), the present studies found no relationship between high CD34+ OA and the achievement of MMR. Furthermore, no correlation was found between the MNC OA and the CD34+ OA in matched CML samples. These results suggest that the predictive value of the MNC OA may primarily reflect the effective targeting and subsequent reduction of mature CML cells. Therefore kinase inhibition in these mature cells, and not the CD34+ cells, may be the key determinant of response in CML.
Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule
Authors: Mishra Nitish K , Agarwal Sandhya , Raghava Gajendra PS
Published: July 2010

Background

Different isoforms of Cytochrome P450 (CYP) metabolized different types of substrates (or drugs molecule) and make them soluble during biotransformation. Therefore, fate of any drug molecule depends on how they are treated or metabolized by CYP isoform. There is a need to develop models for predicting substrate specificity of major isoforms of P450, in order to understand whether a given drug will be metabolized or not. This paper describes an in-silico method for predicting the metabolizing capability of major isoforms (e.g. CYP 3A4, 2D6, 1A2, 2C9 and 2C19).

Results

All models were trained and tested on 226 approved drug molecules. Firstly, 2392 molecular descriptors for each drug molecule were calculated using various softwares. Secondly, best 41 descriptors were selected using general and genetic algorithm. Thirdly, Support Vector Machine (SVM) based QSAR models were developed using 41 best descriptors and achieved an average accuracy of 86.02%, evaluated using fivefold cross-validation. We have also evaluated the performance of our model on an independent dataset of 146 drug molecules and achieved average accuracy 70.55%. In addition, SVM based models were developed using 26 Chemistry Development Kit (CDK) molecular descriptors and achieved an average accuracy of 86.60%.

Conclusions

This study demonstrates that SVM based QSAR model can predict substrate specificity of major CYP isoforms with high accuracy. These models can be used to predict isoform responsible for metabolizing a drug molecule. Thus these models can used to understand whether a molecule will be metabolized or not. This is possible to develop highly accurate models for predicting substrate specificity of major isoforms using CDK descriptors. A web server MetaPred has been developed for predicting metabolizing isoform of a drug molecule http://crdd.osdd.net/raghava/metapred/.
SMAD4 - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRASproto-oncogene
Authors: Sameer A Syed , Chowdri Nissar A , Syeed Nidda , Banday Mujeeb Z , Shah Zaffar A , Siddiqi Mushtaq A
Published: July 2010

Background

The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype.

Methods

We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing.

Results

The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P =< 0.05).

Conclusion

Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.
The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins
Authors: Guerfal Mouna , Ryckaert Stefan , Jacobs Pieter P , Ameloot Paul , Van Craenenbroeck Kathleen , Derycke Riet , Callewaert Nico
Published: July 2010

Background

The unfolded protein response (UPR) in eukaryotes upregulates factors that restore ER homeostasis upon protein folding stress and in yeast is activated by a non-conventional splicing of the HAC1 mRNA. The spliced HAC1 mRNA encodes an active transcription factor that binds to UPR-responsive elements in the promoter of UPR target genes. Overexpression of the HAC1 gene of S. cerevisiae can reportedly lead to increased production of heterologous proteins. To further such studies in the biotechnology favored yeast Pichia pastoris, we cloned and characterized the P. pastoris HAC1 gene and the splice event.

Results

We identified the HAC1 homologue of P. pastoris and its splice sites. Surprisingly, we could not find evidence for the non-spliced HAC1 mRNA when P. pastoris was cultivated in a standard growth medium without any endoplasmic reticulum stress inducers, indicating that the UPR is constitutively active to some extent in this organism. After identification of the sequence encoding active Hac1p we evaluated the effect of its overexpression in Pichia. The KAR2 UPR-responsive gene was strongly upregulated. Electron microscopy revealed an expansion of the intracellular membranes in Hac1p-overexpressing strains. We then evaluated the effect of inducible and constitutive UPR induction on the production of secreted, surface displayed and membrane proteins. Wherever Hac1p overexpression affected heterologous protein expression levels, this effect was always stronger when Hac1p expression was inducible rather than constitutive. Depending on the heterologous protein, co-expression of Hac1p increased, decreased or had no effect on expression level. Moreover, α-mating factor prepro signal processing of a G-protein coupled receptor was more efficient with Hac1p overexpression; resulting in a significantly improved homogeneity.

Conclusions

Overexpression of P. pastoris Hac1p can be used to increase the production of heterologous proteins but needs to be evaluated on a case by case basis. Inducible Hac1p expression is more effective than constitutive expression. Correct processing and thus homogeneity of proteins that are difficult to express, such as GPCRs, can be increased by co-expression with Hac1p.
Evaluation of medication adherence methods in the treatment of malaria in Rwandan infants
Authors: Twagirumukiza Marc , Kayumba Pierre Claver , Kips Jan G , Vrijens Bernard , Stichele Robert Vander , Vervaet Chris , Remon Jean Paul , Van Bortel M Luc
Published: July 2010

Objectives

To compare three methods for evaluating treatment adherence in a 7-day controlled treatment period for malaria in children in Rwanda.

Methods

Fifty-six children (< 5 years) with malaria were recruited at the University Hospital of Butare, Rwanda. Patients were treated with quinine sulfate, taste-masked, pellets during seven days: three days in hospital (in-patient) followed by a four-day out-patient period. Three methods to evaluate medication adherence among patients were compared: manual pill count of returned tablets, patient self-report and electronic pill-box monitoring. These pill-boxes were equipped with a microchip registering date and time of every opening. Medication adherence was defined as the proportion of prescribed doses taken. The inter-dose intervals were analysed as well.

Results

Medication adherence data were available for 54 of the 56 patients. Manual pill count and patient self-report yielded a medication adherence of 100% for the in- and out-patient treatment periods. Based on electronic pill-box monitoring, medication adherence during the seven-day treatment period was 90.5 ± 8.3%. Based on electronic pill-box monitoring inpatient medication adherence (99.3 ± 2.7%) was markedly higher (p < 0.03) than out-patient adherence (82.7 ± 14.7%), showing a clear difference between health workers' and consumers' medication adherence.

Conclusion

Health workers' medication adherence was good. However, a significant lower medication adherence was observed for consumers' adherence in the outpatient setting. This was only detected by electronic pill-box monitoring. Therefore, this latter method is more accurate than the two other methods used in this study.
Capecitabine and Temozolomide: Design, Implementation, and Preliminary Outcomes From a Pilot Project to Ensure Safe Prescribing of Oral Chemotherapy
Authors: Jatoi Aminah , Smith Emily L. , Gunderson Heidi D. , Hartgers Mindy L. , Looker Sherry A. , Santana-Davila Rafael , McWilliams Robert R.
Published: July 2010

Without adequate safety measures, oral chemotherapy can lead to undetected dosing errors. The Mayo Clinic launched a project to ensure that all capecitabine and temozolomide prescriptions receive an independent double check.
Practice and Productivity of Physician Assistants and Nurse Practitioners in Outpatient Oncology Clinics at National Comprehensive Cancer Network Institutions
Authors: Hinkel Jennifer M. , Vandergrift Jonathan L. , Perkel Sara J. , Waldinger Marcy B. , Levy William , Stewart F. Marc
Published: July 2010

Given the increasing complexity of oncologic care and population of patients and survivors requiring care, PAs/NPs have the potential to fill important roles in outpatient and inpatient care settings.
ASCO Provisional Clinical Opinion: Chronic Hepatitis B Virus Infection in Patients Receiving Cytotoxic Chemotherapy for Treatment of Malignant Diseases
Authors: Zon Robin T. , Neuss Michael N.
Published: July 2010

What does the ASCO provisional clinical opinion on hepatitis B virus mean for practices?
How to Negotiate With Health Care Plans
Authors: Gesme Dean H. , Wiseman Marian
Published: July 2010

With practice expenses increasing, boosting reimbursement from private payers is one way to stay in business. But successful negotiation is easier said than done.