bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Variable Sodium Profiles and Adverse Effects During Hemodialysis: A Randomized Crossover Study
Authors: Meira Fernanda S , Figueiredo Ana E , Zemiarcki Juscelino , Pacheco Jaqueline , Poli‐de‐Figueiredo Carlos E , D'Avila Domingos O
Published: December 2009

Intradialytic symptomatic hypotension and muscle cramps are frequent and disturbing adverse effects involving hemodialysis patients. The use of sodium profiling has been a proposed approach to preclude such events. The aim of the study was to compare the frequency of intradialytic adverse effects and changes in anthropometric and physiological variables without profiling and with two distinct sodium profiles. A prospective study randomized 22 stable hemodialysis patients to receive either a step (11 patients) or a linear (11 patients) dialysate sodium profile for 12 consecutive sessions, following a 12‐session steady sodium control period. After a wash‐out period of 12 sessions, the groups were crossed over for another 12‐session period. Frequency of adverse effects, interdialytic weight gain, pre‐ and post‐dialysis blood pressure were computed. The frequency of intradialytic adverse effects was significantly different between the control and either the step or linear periods (48.5%, 33.7%, and 36.0%, respectively; P < 0.001). No significant differences in interdialytic weight gain or pre‐dialysis blood pressure were detected between treatment periods. The mean post‐dialysis systolic blood pressure was lower in the linear period (128 ± 21; 127 ± 20; 123 ± 22 mm Hg, for the control, step and linear periods, respectively; P = 0.014). Seven patients benefited from sodium profiling, yet two became more symptomatic. Overall, both sodium profiles were associated with fewer intradialytic adverse effects. Intradialytic symptomatic hypotension occurred less often with the step profile, while a tendency to fewer cramps was associated with the linear profile. However, sodium profiling may not benefit every dialysis patient and should be individually evaluated.
AP24163 Inhibits the Gatekeeper Mutant of BCR‐ABL and Suppresses In vitro Resistance
Authors: Azam Mohammad , Powers John T. , Einhorn William , Huang Wei‐Sheng , Shakespeare William C. , Zhu Xiaotian , Dalgarno David , Clackson Tim , Sawyer Tomi K. , Daley George Q.
Published: December 2009

Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukaemia. The second generation BCR/ABL inhibitors nilotinib and dasatinib effectively inhibit most imatinib resistance variants, but are ineffective against the gatekeeper mutant, T315I. Gatekeeper mutation activates the kinase by stabilizing the hydrophobic spine. Here, we describe that the rationally designed compound AP24163 can inhibit native and gatekeeper mutants of the BCR/ABL kinase. Structural modelling suggests that AP24163 affects the flexibility of the P‐loop and destabilizes the active conformation by disrupting the hydrophobic spine. In vitro screening for drug resistance identified clones with compound mutations involving both the P‐loop and T315I. Our studies provide structural insights for the design of inhibitors against the gatekeeper mutant and suggest that up‐front combination therapy may be required to prevent the emergence of compound‐resistant mutations.
Synthesis, Preferred Conformation, and Membrane Activity of Medium‐Length Peptaibiotics: Tylopeptin B
Authors: Gobbo Marina , Poloni Claudia , De Zotti Marta , Peggion Cristina , Biondi Barbara , Ballano Gema , Formaggio Fernando , Toniolo Claudio
Published: December 2009

The solid‐phase synthesis and full chemical characterization of the medium‐length (14‐amino acid residues) peptaibol with antibiotic properties of tylopeptin B, originally extracted from the fruiting body of the mushroom Tylopilus neofelleus, are described. These data are accompanied by the results on the solution‐phase synthesis via the segment condensation approach of a selected, side‐chain protected, analog. A solution conformational analysis, performed by the combined use of FTIR absorption, circular dichroism, and 2D‐NMR (the latter technique coupled to molecular dynamics calculations), favors the conclusion that the 3D‐structure of tylopeptin B is largely helical with a preference for the α‐ or the 310‐helix type depending upon the nature of the solvent. Helix topology and (partial) amphiphilic character are responsible for the observed membrane‐modifying properties of this peptaibiotic.
How Much Binding Affinity Can be Gained by Filling a Cavity?
Authors: Kawasaki Yuko , Chufan Eduardo E. , Lafont Virginie , Hidaka Koushi , Kiso Yoshiaki , Mario Amzel L. , Freire Ernesto
Published: December 2009

Binding affinity optimization is critical during drug development. Here, we evaluate the thermodynamic consequences of filling a binding cavity with functionalities of increasing van der Waals radii (–H, –F, –Cl, and CH3) that improve the geometric fit without participating in hydrogen bonding or other specific interactions. We observe a binding affinity increase of two orders of magnitude. There appears to be three phases in the process. The first phase is associated with the formation of stable van der Waals interactions. This phase is characterized by a gain in binding enthalpy and a loss in binding entropy, attributed to a loss of conformational degrees of freedom. For the specific case presented in this article, the enthalpy gain amounts to −1.5 kcal/mol while the entropic losses amount to +0.9 kcal/mol resulting in a net 3.5‐fold affinity gain. The second phase is characterized by simultaneous enthalpic and entropic gains. This phase improves the binding affinity 25‐fold. The third phase represents the collapse of the trend and is triggered by the introduction of chemical functionalities larger than the binding cavity itself [CH(CH3)2]. It is characterized by large enthalpy and affinity losses. The thermodynamic signatures associated with each phase provide guidelines for lead optimization.
High Throughput Receptor‐Based Virtual Screening Under ZINC Database, Synthesis, and Biological Evaluation of Ketol‐Acid Reductoisomerase Inhibitors
Authors: Liu Xing‐Hai , Chen Pei‐Quan , Wang Bao‐Lei , Dong Wei‐Li , Li Yong‐Hong , Xie Xing‐Qiao , Li Zheng‐Ming
Published: December 2009

Ketol‐acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched‐chain amino acid biosynthesis. This enzyme is an important target for drug design. Based on the crystal structure of ketol‐acid reductoisomerase/N‐hydroxy‐N‐isopropyloxamate (IpOHA) complex, we have carried out high throughput receptor‐based virtual screening of the ZINC/drug like database (2 000 000 compounds) to look for novel inhibitors of KARI for the first time. Some novel compounds were found to inhibit rice KARI in vitro among 15 procured compounds. This method can provide useful information for further design and discovery of KARI inhibitors.
3D‐QSAR studies of arylcarboxamides with inhibitory activity on InhA using pharmacophore‐based alignment
Authors: Lu Xiao‐Yun , Chen Ya‐Dong , You Qi‐Dong
Published: December 2009

Enoyl acyl carrier protein reductase (InhA) is a promising target for the development of antituberculosis drugs. The InhA‐bound conformation of an indole‐5‐amide inhibitor (Genz 10850) (PDB code: IP44) was used to build a pharmacophore model by LigandScout. This model was then successfully used to identify the bioactive conformation and align 40 structurally diverse arylcarboxamide derivatives. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on arylcarboxamides‐based InhA inhibitors based on pharmacophore alignment. The best prediction was obtained with CoMSIA model combining steric and electrostatic fields (, r2 = 0.972). The model was validated by an external test set, which gave a good predictive value (). Graphical interpretation of the results revealed important structural features of the zarylcarboxamides related to the active site of InhA. The results may be exploited for further design and virtual screening for some novel InhA inhibitors.
The Aromatic Amino Acid Residues of Tumor Necrosis Factor Receptor‐1‐Derived Peptide are Important for Promoting Differentiation of Neural Stem Cells
Authors: Kajiwara Kazumi , Ogata Shin‐ich , Tanihara Masao
Published: December 2009

Neural stem cells have the self‐renewal capacity and the ability to differentiate into all types of nerve cells. We previously reported that the tumor necrosis factor receptor‐1‐derived peptide promotes neural differentiation of fetal rat hippocampal neural stem cells. The tumor necrosis factor receptor‐1‐derived peptide contains six aromatic amino acid residues among its 14 amino acid residues. To clarify the role of these aromatic amino acid residues in the action of tumor necrosis factor receptor‐1‐derived peptide on neural stem cells, we synthesized mutant peptides, in which aromatic residues were substituted with alanine, and we assessed their effects. Substitution of the tyrosine residue at position 103 (Y103) or 106 (Y106), the tryptophan residue at position 107 (W107), or the phenylalanine residue at position 112 (F112) or 115 (F115), decreased the ability of the peptide to promote neurite outgrowth of neural stem cells depending on their concentration. These data suggest that although all five aromatic amino acid residues mediate the action of the tumor necrosis factor receptor‐1‐derived peptide, their order of importance in this activity is F115 > Y103 > W107 > Y106 and F112.
Reduction and Recombination of Fingerprints of Different Design Increase Compound Recall and the Structural Diversity of Hits
Authors: Nisius Britta , Bajorath Jürgen
Published: December 2009

We report an advanced ‘hybrid fingerprint’ design concept specifically for the purpose of scaffold hopping. The generation of hybrid fingerprints includes two major steps. In the ‘fingerprint reduction’ step, bit positions of different types of fingerprints (e.g. substructural and pharmacophore fingerprints) are ranked according to their statistical significance and ability to discriminate between specifically active compounds and database decoys. On the basis of bit ranking, subsets containing the most discriminatory bit positions are determined. In the subsequent ‘fingerprint recombination’ step, bit subsets from different fingerprints are combined to yield a new compound class‐directed fingerprint representation for similarity searching. Here, we generate hybrids from multiple fingerprints and analyze their search performance in comparison with parental fingerprints on compound activity classes that exclusively consist of molecules with unique core structures and that exhibit different levels of intra‐class structural diversity. Fingerprint reduction is found to be a critical component of hybrid design. The resulting compound class‐directed hybrid fingerprints further increase the similarity search performance and scaffold hopping potential of their parental fingerprints. Thus, fingerprint reduction and recombination improve compound recall and increase the structural diversity of hits.
Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at‐risk myocardium: an experimental study in the pig
Authors: Waldenström A. , Haney M. , Biber B. , Kavianipour M. , Moritz T. , Strandén P. , Wikström G. , Ronquist G.
Published: December 2009

Aim:  ‘Pre‐treatment’ with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation.

Methods:  A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with 14C‐ adenosine with two different specific activities. 14C‐lactate was identified and measured in the effluent.

Results:  14C‐adenosine was taken up by non‐preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of 14C‐lactate were recovered in preconditioned myocardium. 14C‐adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of 14C‐adenosine with low specific activity. Mass spectrography verified the identity of 14C‐lactate.

Conclusions:  Preconditioning up‐regulates a new metabolic pathway (starting with 5′‐nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up‐regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved.
Review of the OSHA Framework for Oversight of Occupational Environments
Authors: Choi Jae-Young , Ramachandran Gurumurthy
Published: December 2009

Nanotechnology is a collection of different technologies and approaches dealing with manipulating matter with dimensions on the nanometer scale. The growth of nanotechnology has been rapid in recent years and encompasses a range of industries including pharmaceuticals, chemicals, robotics, medicine, agriculture, electronics, national defense, fiber optics, and energy. Nanoparticles with shapes, morphologies, and chemical compositions engineered for specific functions and applications are now common. While estimates of the numbers of new types of nanoparticles being produced in academic and industrial labs that combine these different characteristics are uncertain, it is likely that they run into the hundreds.
Developing U.S. Oversight Strategies for Nanobiotechnology: Learning from Past Oversight Experiences
Authors: Paradise Jordan , Wolf Susan M. , Kuzma Jennifer , Kuzhabekova Aliya , Tisdale Alison W. , Kokkoli Efrosini , Ramachandran Gurumurthy
Published: December 2009

Devising appropriate oversight for nanotechnology is a challenge. The field spans many scientific disciplines and product areas, capitalizing on the unusual properties and capabilities of material at the atomic scale. The critical feature of nanotechnology is not only the size at which manufacture occurs (˜1-100 nanometers), but also the ability to control and manipulate the novel chemical, physical, and mechanical properties that emerge at this scale, including increased conductivity, optical properties, and reactivity. As nano-products enter the research and development (R&D) phase, hit the market, and enter consumer households, debate has emerged on oversight approaches. Regulators, manufacturers, and commentators are considering whether existing oversight systems are sufficient, those oversight systems need adjustment, or new oversight systems are needed.
Between Public Opinion and Public Policy: Human Embryonic Stem-Cell Research and Path-Dependency
Authors: Latham Stephen R.
Published: December 2009

My aim in this paper is simply to show that, in bioethics no less than in other areas of health care, policy in democracies is shaped not only by principles and values, but also — and to some extent independently — by the shape and history of particular political institutions and past policies. “Path dependency,” or what one scholar has called the “accidental logics” of already-existing institutions, condition and guide national policy choices. These institutional and historical pressures can even create substantial policy divergences between quite likeminded nations. I shall illustrate the point using some comparative data about national policies regarding research on human embryonic stem cells. The fact that gaps can develop between values and policies is readily visible to anyone who compares national stemcell research policies to the expressed attitudes of the citizens of various democratic countries regarding human embryonic stem-cell research. The role of path dependency and the accidental logics of institutional structure in creating those gaps can be illustrated by tracking down the details of the development of human embryonic stem cell policies in a few different countries.
Team Building: Electronic Management‐Clinical Translational Research (eM‐CTR) Systems
Authors: Cecchetti Alfred A. , Parmanto Bambang , Vecchio Marcella L. , Ahmad Sjarif , Buch Shama , Zgheib Nathalie K , Groark Jr. Stephen J. , Vemuganti Anupama , Romkes Marjorie , Sciurba Frank , Donahoe Michael P. , Branch Robert A.
Published: December 2009

Classical drug exposure: response studies in clinical pharmacology represent the quintessential prototype for Bench to Bedside‐Clinical Translational Research. A fundamental premise of this approach is for a multidisciplinary team of researchers to design and execute complex, in‐depth mechanistic studies conducted in relatively small groups of subjects. The infrastructure support for this genre of clinical research is not well‐handled by scaling down of infrastructure used for large Phase III clinical trials. We describe a novel, integrated strategy, whose focus is to support and manage a study using an Information Hub, Communication Hub, and Data Hub design. This design is illustrated by an application to a series of varied projects sponsored by Special Clinical Centers of Research in chronic obstructive pulmonary disease at the University of Pittsburgh. In contrast to classical informatics support, it is readily scalable to large studies. Our experience suggests the culture consequences of research group self‐empowerment is not only economically efficient but transformative to the research process.
Divergent Effects of Losartan and Metoprolol on Cardiac Remodeling, C‐kit+Cells, Proliferation and Apoptosis in the Left Ventricle after Myocardial Infarction
Authors: Serpi Raisa , Tolonen Anna‐Maria , Tenhunen Olli , Pieviläinen Oskari , Kubin Anna‐Maria , Vaskivuo Tommi , Soini Ylermi , Kerkelä Risto , Leskinen Hanna , Ruskoaho Heikki
Published: December 2009

There is strong evidence for the use of angiotensin converting enzyme inhibitors and beta‐blockers to reduce morbidity and mortality in patients with myocardial infarction (MI), whereas the effect of angiotensin receptor blockers is less clear. We evaluated the effects of an angiotensin receptor blocker losartan and a beta‐blocker metoprolol on left ventricular (LV) remodeling, c‐kit+cells, proliferation, fibrosis, apoptosis, and angiogenesis using a model of coronary ligation in rats. Metoprolol treatment for 2 weeks improved LV systolic function. In contrast, losartan triggered deleterious structural remodeling and functional deterioration of LV systolic function, ejection fraction being 41% and fractional shortening 47% lower in losartan group than in controls 2 weeks after MI. The number of c‐kit+cells as well as expression of Ki‐67 was increased by metoprolol. Losartan‐induced thinning of the anterior wall and ventricular dilation were associated with increased apoptosis and fibrosis, while losartan had no effect on the expression of c‐kit or Ki‐67. Metoprolol or losartan had no effect on microvessel density. These results demonstrate that beta‐blocker treatment attenuated adverse remodeling via c‐kit+cells and proliferation, whereas angiotensin receptor blocker‐induced worsening of LV systolic function was associated with increased apoptosis and fibrosis in the peri‐infarct region.
The Alliance Transformation and US–Japan–Korea Security Network: A Case for Trilateral Cooperation
Authors: Nam Chang‐hee
Published: December 2009

During the Cold War, the heavily armed US forces in Korea were deployed along the demilitarized zone, mainly to defend South Korea and maintain deterrence on the Peninsula. The US forces in Japan on the other hand were charged with broader missions and roles, namely, for regional security. In accordance with the goals of the alliance transformation, the US forces are undertaking historic changes for reconfiguring their units to be ready for the rapid employment of globally networked forces. Should the two US forces in Japan and Korea, respectively, be transformed into regionally mobile units in the years to come, the two alliances are likely to be pressured to assume increasingly similar roles and missions. This emerging requirement calls on the three allies to adopt a more integrated approach to best utilize their given resources. Among the many items of cooperation agreed upon between the USA and Japan are some areas to which Korea can make a meaningful contribution and benefit from its participation. Those items, however, vary in terms of feasibility, difficulty, sensitivity, and importance. They can be divided into three categories that identify preconditions for moving on to a higher phase. The two neighbors and the USA are faced with growing regional security challenges in the age of spreading terrorism and proliferation. The changing regional environment demands restructuring of the alliance relations of the three, meaning that the trilateral security cooperation should be taken seriously again.
Objective Confirmation of Subjective Measures of Human Well-Being: Evidence from the U.S.A.
Authors: Oswald Andrew J. , Wu Stephen
Published: December 2009

The Best Things in Life Are Free?

Does money buy happiness? Answers to this question differ, depending, in part, on whether one asks an economist or a psychologist. The former would point to correlations between higher incomes and greater self-reported well-being, whereas the latter would argue that happiness shows little correlation with absolute material goods and is instead dictated largely by an individual's so-called set-point. Another strand of research invokes a hedonic treadmill, whereby income matters until subsistence requirements are met, at which point comparisons with one's neighbors are what influence one's sense of life satisfaction.
Oswald and Wu
(p.
576
, published online 17 December; see the Perspective by

Layard

) establish that the subjective responses from 1 million adults, collected within health surveys conducted by the U.S. Centers for Disease Control and Prevention, do indeed correlate with objective measures of quality of life.
Manipulating Each MreB ofBdellovibrio bacteriovorusGives Diverse Morphological and Predatory Phenotypes
Authors: Fenton Andrew Karl , Lambert Carey , Wagstaff Peter Charles , Sockett Renee Elizabeth
Published: December 2009

We studied the twomreBgenes, encoding actinlike cytoskeletal elements, in the predatory bacteriumBdellovibrio bacteriovorus. This bacterium enters and replicates within other Gram-negative bacteria by attack-phaseBdellovibriosqueezing through prey outer membrane, residing and growing filamentously in the prey periplasm forming an infective “bdelloplast,” and septating after 4 h, once the prey contents are consumed. This lifestyle brings challenges to theBdellovibriocytoskeleton. BothmreBgenes were essential for viable predatory growth, but C-terminal green fluorescent protein tagging each separately with monomeric teal-fluorescent protein (mTFP) gave two strains with phenotypic changes at different stages in predatory growth and development. MreB1-mTFP cells arrested growth early in bdelloplast formation, despite successful degradation of prey nucleoid. A large population of stalled bdelloplasts formed in predatory cultures and predation proceeded very slowly. A small proportion of bdelloplasts lysed after several days, liberating MreB1-mTFP attack-phase cells of wild-type morphology; this process was aided by subinhibitory concentrations of an MreB-specific inhibitor, A22. MreB2-mTFP, in contrast, was predatory at an almost wild-type rate but yielded attack-phase cells with diverse morphologies, including spherical, elongated, and branched, the first time such phenotypes have been described. Wild-type predatory rates were seen for all but spherical morphotypes, and septation of elongated morphotypes was achieved by the addition of A22.
The effectiveness of different buffer widths for protecting water quality and macroinvertebrate and periphyton assemblages of headwater streams in Maine, USA
Authors: Wilkerson Ethel , Hagan John M. , Whitman Andrew A.
Published: December 2009

We evaluated the effect of timber harvesting on water quality and macroinvertebrate and periphyton assemblages in first-order streams in Maine, USA. Fifteen streams were assigned to one of five treatments: clearcutting without a stream buffer, clearcutting with 11 m buffers, clearcutting with 23 m buffers, partial harvesting with no designated buffer, and unharvested controls. Harvest blocks on both sides of the stream were 6 ha and partial harvesting within buffers was allowed. Specific conductivity, pH, dissolved oxygen, turbidity, and soluble reactive phosphorus did not change significantly for 3 years after harvesting in all treatments. Unbuffered streams had significantly elevated concentrations of chlorophyll a as well as increased abundance of algal feeding organisms (Diperta Cricotopus and Diptera Psectrocladius ). Streams with 11 m buffers had substantial (10-fold) but nonsignificant increases in chlorophyll a. No other significant changes were detected in other treatment groups. In all treatment groups, the dominant taxa (periphyton Achnanthes minutissimum and macroinvertebrate Chironomidae) are adapted to disturbed environments. We attribute the limited harvest-induced changes to lack of soil disturbance within 8 m of the stream, the small (≤40%) proportion of watersheds harvested, and the resilient nature of aquatic organisms. However, small-scale changes may not be detected due to the small sample size, an inherent limitation of field-based studies.
Effects of Bythotrephes on the trophic position of native macroinvertebrates
Authors: Foster Sophie E. , Sprules W. Gary
Published: December 2009

We measured the δ15N and δ13C stable isotopes of pelagic invertebrate predators in six central Ontario lakes, three invaded by Bythotrephes and three not invaded, to determine the effects of Bythotrephes invasion on diet overlap and trophic position of the predators. Seasonally averaged, lake-specific isotope signatures of bulk zooplankton were used as the isotopic baseline for determining nitrogen-based trophic position or carbon enrichment of the predators. Trophic positions of native Chaoborus , Leptodora , and Mysis in invaded lakes were not elevated compared with noninvaded lakes, suggesting that these predators do not feed directly on Bythotrephes. Nitrogen signatures of Mysis and Chaoborus were similar as were those of Leptodora and Bythotrephes, suggesting that invasion impacts will be greatest on Leptodora as has been observed. The trophic position of large Mysis was generally the highest and most variable of all predators, probably because it feeds on copepods that are more enriched in the heavier nitrogen isotope than bulk zooplankton and because Bythotrephes tends to decrease the ratio of cladocerans to copepods in invaded zooplankton communities.
Distribution and biological characteristics of escaped farmed salmon in a major subarctic wild salmon river: implications for monitoring
Authors: Erkinaro Jaakko , Niemelä Eero , Vähä Juha-Pekka , Primmer Craig R. , Brørs Sturla , Hassinen Esa
Published: December 2009

We report the occurrence, distribution, and biological characteristics of escaped farmed salmon in the River Teno in northernmost Europe, which supports one of the largest and most versatile wild Atlantic salmon ( Salmo salar ) populations in the world. Farmed salmon were caught during the fishing season (May–August) when their proportion in the catch varied between 0.0% and 0.7%. Occasional sampling after the fishing season revealed much higher proportions of escapees, up to 47%, indicating a potential for a more severe impact of farmed fish than the in-season monitoring is able to uncover. Peak migration of the wild salmon was in June or July, but that of escaped farmed fish was in August. Up to 88% of the escaped salmon caught in August showed gonad development, and scale analysis indicated that 4.5% of them were repeat spawners. Genetic analyses using microsatellite markers revealed highly significant genetic differentiation between wild salmon and escaped farmed fish (FST = 0.05) caught in the River Teno and a Norwegian farmed strain (FST = 0.10). The heterogeneity of escapees compared with the single farmed strain indicated that escapees apparently originate from multiple sources, which will complicate their genetic identification and the assessment of the level of hybridization with wild salmon.
Hierarchical analysis of multiple noisy abundance indices
Authors: Conn Paul B.
Published: December 2009

Fisheries analysts often rely on relative abundance indices for assessing stock status. However, trends in abundance can be difficult to discern when there are multiple indices or when correlation among indices is weak or negative. In this paper, I present a hierarchical framework for analyzing multiple, noisy indices with the goal of estimating a single time series of relative abundance. An implicit assumption is that each index is measuring the same quantity (relative abundance) but that each is subject to process error (attributable to variation in catchability, spatial distribution, etc.) in addition to an estimable level of within-survey variance (i.e., sampling error). I use simulation to explore estimator performance under a number of scenarios, including several that violate underlying assumptions. In general, the hierarchical approach produced estimators with reasonable properties. I illustrate the method with an analysis of seven fishery-dependent catch-per-unit-effort indices of Spanish mackerel ( Scomberomorus maculatus ) off the US Atlantic coast and provide several suggestions for how this approach can be used in practice.
Comment on “Gene flow increases temporal stability of Chinook salmon (Oncorhynchus tshawytscha) populations in the Upper Fraser River, British Columbia, Canada”Appears in Can. J. Fish. Aquat. Sci.66: 167–176.
Authors: Beacham Terry D. , Withler Ruth E.
Published: December 2009

Temporally stable genetic structure among salmonid populations has been reported in many studies, although the time span evaluated in most studies is limited to 10 years or less. This result has important implications in conservation and management of Pacific salmon ( Oncorhynchus spp.) and ramifications for the construction and application of genetic databases for stock identification of fish sampled from mixed-stock fisheries. Walter et al. (2009. Can. J. Fish. Aquat. Sci. 66: 167–176) failed to consider recent studies providing evidence that their conclusion “the overall magnitude of temporal within-population variation exceeding that of among-population variation” for the populations under study may be invalid for Fraser River Chinook salmon ( Oncorhynchus tshawytscha ) populations. Their estimation of rates and patterns of migration among Chinook salmon populations also provided results that are difficult to reconcile with published information. Evaluation of the experimental designed employed by Walter et al. (2009) indicates that their sample sizes were too small to estimate reliably genetic variation among or within populations. Extrapolation of their conclusions relating temporal instability of population structure to other Chinook salmon populations or indeed other salmonid species is unwarranted.
AGGLUTININ RESPONSE TO SHEEP ERYTHROCYTES IN MICE FOLLOWING INTRAPERITONEAL INJECTION OF ALLOGENEIC SPLEEN CELLS
Authors: Bain Gordon O.
Published: December 2009

C3H mice were injected with C57L spleen cells and 24 hours later with sheep erythrocytes. Recipients of spleen cells from C57L donors previously injected with C3H tissue developed lower antisheep hemagglutinin titers than control mice. Neither donor serum nor saline extracts of lyophilized donor spleen cells had significant cytotoxicity demonstrable in vitro. However, both heat-killed spleen cells and lyophilized spleen cells injected in vivo had a depressant effect on the anti-sheep hemagglutinin titer. The depressant effect is attributed to isoimmunization of the spleen cell donors since injection of spleen cells from donors not previously exposed to C3H antigens did not result in a lowered antisheep hemagglutinin titer.
ADJUSTMENTS TO CONSTANT LOW TEMPERATURES IN WHITE RATS LIVING IN GROUPS
Authors: Héroux O.
Published: December 2009

White rats, in groups of 10, were exposed for 3 months in the laboratory to constant temperatures of 19 °C or −10 °C. Grouping the animals did not alter the pattern of metabolic adaptation usually observed in individually cold-acclimated rats and recently observed in group-caged white rats exposed outdoors during the winter. This pattern of adaptation is characterized by an increased capacity for heat production, as shown by a longer survival time at −35 °C, a reduction of shivering, an increased sensitivity to noradrenaline, an increased ear vascularization, a reduction in protein and fat deposition, and an enlargement of heart, liver, and kidneys. Group-caging at constant low temperature (a) prevented the development of cold injuries and the enlargement of pituitary, thyroid, adrenals, which are usually observed in individually cold-exposed rats indoors, (b) resulted in an increased resting metabolism, normal adrenal cortex activity, and no increase in pelt insulation in contrast to that previously found in white rats grouped outdoors during the winter. These different adjustments to cold in white rats exposed to different sets of environmental conditions are compared with similar adjustments found in wild Norway rats.From these comparisons, one must conclude that many of the structural and endocrine adjustments observed in individually cold-acclimated rats in the laboratory are reactions peculiar to continuous cold stimulus, i.e. reactions to a specific set of experimental conditions rather than essential components of the fundamental mechanism for non-shivering thermogenesis.
LIPID EXTRACTION AND DISTRIBUTION STUDIES OF EGG YOLK LIPOPROTEINS
Authors: Martin W. G. , Tattrie N. H. , Cook W. H.
Published: December 2009

The three lipoproteins of egg yolk, α- and β-lipovitellin and the low-density fraction (LDF), have been isolated and their lipid compositions determined. α- and β-lipovitellin comprise 22 to 26% lipid, of which 61% is phospholipid, 35% is triglyceride, and 4% is cholesterol and its esters. LDF contains about 89% lipid having 27% phospholipid, 69% triglyceride, and 4% cholesterol and cholesterol esters. The phospholipids of the three lipoproteins are similar, i.e., 74% lecithins, 18% cephalins, and 8% minor phospholipids. The fatty acid compositions of the neutral lipids, lecithins, and cephalins of the α- and β-lipovitellins were also similar, with only minor differences.Gentle extraction of the LDF solutions with ethyl ether readily removes about 85% of the total lipid and 55% of the phospholipid, while subsequent changes are slow. The lipoprotein residue contains 52% lipid which is mostly phospholipid; when the residual ether is removed, five sedimenting components are observed in the ultracentrifuge.
IMPROVED PROCEDURES FOR PREPARATION AND CHARACTERIZATION OF MYROTHECIUM CELLULASE: PART 2. PURIFICATION PROCEDURES
Authors: Whitaker D. R. , Hanson K. R. , Datta P. K.
Published: December 2009

Two methods are described for purification of the cellulase of Myrothecium verrucaria from concentrated culture filtrates. The steps of method I are (1) fractionation with ammonium sulphate, (2) elution through Sephadex G25, (3) elution through Sephadex G75, (4) precipitation with polymethacrylic acid, and (5) elution through Amberlite CG50 with citrate buffer containing a gradient of urea concentration. The steps of method II are precipitation by saturated ammonium sulphate, (2) and (4) as above, elution through DEAE-cellulose with phosphate buffer containing 7 M urea, followed by (2) and (3) as above. The two methods gave final products with identical specific activities toward carboxymethyl cellulose; the increase in specific activity was approximately 12-fold. Starch-gel electrophoresis at pH 6.8 showed no major indications of heterogeneity. The purified enzyme was unstable but could be stored frozen in dilute salt solution.Enzyme passed through DEAE-cellulose without an inhibitor of cellulase activity was contaminated by DEAE-substituted oligoglucosides and subject to proteolysis. Urea could be replaced by cellobiose as an inhibitor but the latter gave enzyme contaminated by products of transfer reactions.Binding of urea by the resin is shown to influence significantly the resolution attainable in chromatographic fractionations on Amberlite CG-50 with buffers containing gradients of urea concentration.Procedures for dialysis and desalting of cellulases and a compact reaction vessel for pH stats are described.
BIMODAL STIMULATION OF THE RETICULOENDOTHELIAL SYSTEM BY MYCOBACTERIUM PHLEI
Authors: DiCarlo Frederick J. , Haynes Lloyd J. , Malament Sylvia G. , Phillips George E.
Published: December 2009

A variety of substances which stimulate the reticuloendothelial system (RES) in the mouse were rated in potency by employing active dry bakers' yeast as the reference stimulant. Mycobacterium phlei Halpern was found to be a particularly effective RES stimulant. A single intravenous injection of this microorganism elicited a bimodal stimulation of global phagocytic activity. The peak rates of phagocytosis occurred at 1 and 21 days post administration. M. phlei Halpern also caused pronounced hypertrophy of the liver and spleen. Six weeks elapsed before these organs returned to normal size.
THE METABOLISM OF PROPIONATE BY WHEAT STEM RUST UREDOSPORES
Authors: Reisener H. , Finlayson A. J. , McConnell W. B. , Ledingham G. A.
Published: December 2009

When uredospores of wheat stem rust were shaken for 3 hours with phosphate buffer (pH 6.2) containing propionate-1-C14, -2-C14, or -3-C14, about 55% of the carbon-14 was removed from the solution. With propionate-1-C14, most of the carbon-14 taken up was released as carbon dioxide-C14, whereas about 20% and 31% of propionate carbon 2 and carbon 3, respectively, was incorporated into the spores. The specific activity of a fraction consisting of the free amino acids of a hot-alcohol and hot-water extract of the spores increased markedly with increase in the position number of propionate in which the carbon-14 was located. A similar relation was observed for other fractions such as soluble carbohydrates, ether-soluble material, organic acids, and insoluble residue from spores. The most active amino acids isolated were glutamic acid, γ-aminobutyric acid, and alanine. Partial degradations showed that with propionate-2-C14the carboxyl groups of glutamic acid were especially radioactive, whereas with propionate-3-C14the internal carbons were most radioactive.It is concluded that propionate metabolism in the rust spores involved conversion of carbon 1 to carbon dioxide, and utilization of carbons 2 and 3 as acetate with carbon 2 behaving as the carboxyl carbon.
EFFECTS OF ALIPHATIC ALCOHOLS ON THE METABOLISM OF GLUCOSE AND FRUCTOSE IN RAT LIVER SLICES
Authors: Majchrowicz Edward , Quastel J. H.
Published: December 2009

Ethanol, at concentrations up to 3 mM, whilst having little inhibitory effect on the production of respiratory CO2of rat liver slices, has a marked suppressing action on the formation of labelled CO2from labelled glucose. The suppression of C14O2formation by ethanol from radioactive glucose is independent of the concentration of the latter and amounts to 57% with 3 mM ethanol after 1 hour's incubation. The results are consistent with the conclusion that ethanol gives rise more rapidly than glucose to acetyl CoA and that the large suppressing action of ethanol in rat liver slices is due to isotopic dilution of labelled acetyl CoA derived from the labelled sugars with the unlabelled acetyl CoA derived from ethanol. Ethanol exercises a larger inhibition of the rate of C14O2formation from glucose-6-C14than from glucose-1-C14. The difference between the effects of ethanol on C14O2formation from glucose-1-C14and glucose-6-C14is presumably due to operation of the hexosemonophosphate shunt.The higher aliphatic alcohols have about the same diminishing effect on C14O2formation from glucose-U-C14and fructose-U-C14as does ethanol. This observation may also be a consequence of dilution of labelled acetyl CoA derived from the sugars by unlabelled acetyl CoA coming from the added alcohol. Incorporation of radioactive carbon from the labelled sugars into liver proteins and lipids is inhibited by ethanol and higher aliphatic alcohols, and the inhibitions are similar in magnitude to those of C14O2formation. These may be accounted for by isotopic dilution. The amounts of C14incorporated into lipids and proteins from radioactive glucose and fructose are small, being about 1/10th of that appearing in the CO2.The higher aliphatic alcohols suppress total CO2formation during rat liver slice respiration much more than does ethanol at equivalent concentrations.
AN ISOPHENOXAZINE SYNTHASE FROM PYGNOPORUS COCCINEUS (FR.) BOND. AND SING.
Authors: Nair P. M. , Vining L. C.
Published: December 2009

Mycelium from cultures of the red polypore Pycnoporus coccineus (Fr.) Bond. and Sing, contains an enzyme which catalyzes the oxidative condensation of 2 molecules of 2-aminophenol to yield 2-amino-3H-isophenoxazin-3-one. Fractionation of the crude extract has given a preparation with an 893-fold increase in specific activity. The purified enzyme has a pH optimum in citrate-phosphate buffer of 5.0, and a temperature optimum of 55°. The Kmvalue is 4.35 × 10−4 M. FMN and Mn++ions were required for maximum activity. FAD also served as an electron acceptor. Of the metal ions tested only Mn++activated the reaction. Hg++and Fe++inhibited strongly. The course of the reaction when cofactors were added separately suggested that flavin mononucleotide is the initial electron acceptor and that Mn++ions are required for reoxidation of the flavin. The enzyme has narrow specificity, and does not catalyze the oxidation of 3-hydroxyanthranilic acid, 3-hydroxykynurenine, or pyrocatechol.
INTERACTION OF BOVINE AUTOPROTHROMBIN C WITH PHOSPHOLIPIDS AND DIVALENT CATIONS
Authors: Cole Edmond R. , Koppel J. L. , Olwin John H.
Published: December 2009

A thromboplastic enzyme, autoprothrombin C, can be complexed to different phospholipids and removed from solution in the form of such complexes. A technique for dissociating these complexes was developed, resulting in the recovery of the thromboplastic enzyme essentially free of phospholipid and in a higher degree of purity. Calcium ions are required for the formation of the complex, but strontium can replace calcium not only as the metal ion in the phospholipid-complexing system, but also as an autoprothrombin C cofactor in a prothrombin activation mixture. Magnesium was not effective in either system. The role of different phospholipids in the complexing phenomenon was studied and compared with the suitability of the same phospholipids as prothrombin-activating cofactors of autoprothrombin C. All phospholipid preparations studied complexed with autoprothrombin C to some degree, but the most efficient complexing agents were found to be asolectin and a commercial phosphatidyl ethanolamine preparation, both materials being among the ones which demonstrated the highest prothrombin conversion activity. Since thrombin was not complexed under the same conditions, autoprothrombin C could be isolated from commercial thrombin preparations also containing autoprothrombin C.
THE EFFECT OF INSULIN ON HUMAN ADIPOSE TISSUE
Authors: Kahlenberg A. , Kalant N.
Published: December 2009

The effects of insulin on glucose transport and dissimilation have been studied in the rat fat pad and in human omentum. Intracellular glucose could not be demonstrated in the non-diabetic rat fat pad, with or without insulin. Slices of omentum, obtained during surgery from diabetic and non-diabetic patients, were incubated in a bicarbonate medium with a glucose concentration of 5.6 mM. Omentum from non-diabetic patients had intracellular glucose while diabetic tissue had none. Diabetic tissue had a significantly lower glucose uptake. In both, insulin stimulated glucose uptake in inverse relation to the basal uptake; but for comparable basal uptakes, the response to insulin was decreased in diabetic tissue. Glucose phosphorylation in omental tissue from non-diabetic humans had an apparent Kmof 1.10 m M and a Vmaxof 1.44 mg/g hour.Insulin (0.1 units/ml), bovine or human serum albumin, or a combination of insulin and bovine albumin, each increased glucose utilization by slices of non-diabetic omentum without affecting the intracellular glucose content or the free fatty acid content. In omental homogenates (cell-free), insulin and bovine serum albumin each increased the glucose utilization. In the presence of albumin, insulin increased the utilization only after the addition of glucose-6-phosphate dehydrogenase and phosphohexose isomerase in amounts sufficient to establish that hexokinase was rate-limiting for glucose utilization.It is concluded that (A) in diabetic human omentum and in normal rat fat pad, transport is rate-limiting in glucose utilization; (B) insulin and albumin each stimulate both transport and phosphorylation in human omentum; (C) in human diabetes, the glucose transport process of omentum has a decreased basal rate and a decreased responsiveness to insulin.
INTERFERENCE OF AUTOLYTIC ACTIVITY WITH THE DETERMINATION OF CELL NUCLEUS COMPOSITION UNDER DIFFERENT CONDITIONS OF PROTEIN DEFICIENCY
Authors: Umaña Roberto
Published: December 2009

The changes produced by protein-deficient diets and starvation on the composition of rat liver nuclei have been studied. It was found that the histone fraction and the histone to DNA ratio remained remarkably constant during the different experimental conditions studied. The rest of the protein fractions showed variations which can probably be ascribed to an increase in the autolytic activity of the preparations. It appears that the degree of autolysis varies with the type of dietary insult applied to the animal.
THE ENZYMIC FORMATION OF 6-(METHYLMERCAPTO)PURINE RIBONUCLEOSIDE 5′-PHOSPHATE
Authors: Caldwell Ian C. , Henderson J. Frank , Paterson A. R. P.
Published: December 2009

6-(Methylmercapto)purine ribonucleoside (Me6MPR) is efficiently phosphorylated in mouse tissues and in Ehrlich ascites carcinoma cells in vivo; tumor cells in vitro and cell-free extracts of the tumor also phosphorylate this analogue ribonucleoside. The product of this reaction has been identified by chemical and enzymatic methods and by its chromatographic behaviour as Me6MPR 5′-phosphate. The evidence presented in this report indicates that no other major metabolites of Me6MPR are formed.The phosphorylation of Me6MPR by cell-free tumor extracts requires ATP and Mn2+(or Mg2+), and evidence is presented that the reaction is probably mediated by adenosine kinase.Me-14C-6MPR is rapidly taken up by most mouse tissues following its intraperitoneal injection. Forty minutes after injection of the labeled drug, the highest levels of radioactivity were found in intestine, liver, blood cells, lung, and spleen, in descending order; virtually no radioactivity was found in brain tissue or in blood plasma.
DISTRIBUTION OF THE NUCLEASES OF THE MICROSOMAL FRACTION OF RAT LIVER BETWEEN RIBOSOMES AND ENDOPLASMIC MEMBRANES
Authors: Lamirande Gaston de , Boileau Serge , Morais Réjean
Published: December 2009

The distribution of nucleases of the microsomal fraction of rat liver between ribosomes and endoplasmic membranes was studied. The results show that the ribosomes contained a ribonuclease (RNase) inhibited by Mg++ions but activated by ethylenediaminetetraacetic acid (EDTA). Furthermore the degradation products of this enzyme were found to possess a 3′-phosphomonoester end group. The endoplasmic membranes contained a 5′-RNase that could degrade the purine—purine linkage of polyadenylic acid, and a 5′-phosphodiesterase.