bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing survival and impairment rates at 18–24 months in outborn very low‐birth‐weight infants: 1984–1987 versus 1980–1983
Authors: Wojtulewicz Julian , Alam Awatif , Brasher Penny , Whyte Hilary , Long David , Newman Chris , Perlman Max
Published: April 2008

Outcomes at 18–24 months corrected age of very low‐birth‐weight infants admitted to our Neonatal Intensive Care Unit in 1984–1987 (period 2) were compared with the outcomes of infants admitted in 1980–1983 (period 1) (total 1357 infants). In the 500–750–g birth‐weight subgroup, the survival rate increased from 32 to 54% (p = 0.002). Rates of moderate and severe impairment at 18–24 months (neurosensory deficit, or Bayley corrected mental developmental index <68) in this subgroup decreased from 41 to 15% (p = 0.005), and in those without severe impairment, mean mental Bayley scores in periods 1 and 2 were 84 ± 18 and 90 ± 16, respectively (p = 0.20). Analysis after exclusion of small‐for‐gestational‐age infants gave similar results. In the small‐for‐gestational‐age infants of birth weight 500–750 g, the survival rate increased but the impairment rate was unchanged between periods. It is concluded that outcomes improved in 1984–1987 compared with 1980–1983 only for infants with birth weight of 500–750 g.
CRIB, CRIB‐II, birth weight or gestational age to assess mortality risk in very low birth weight infants?
Authors: Bührer Christoph , Metze Boris , Obladen Michael
Published: April 2008

Aim: The mortality risk of very low birth weight (VLBW) (<1500 g) infants has been estimated by the Clinical Risk Index for Babies (CRIB). Superior discriminatory power has been claimed for the revised CRIB‐II score based on birth weight, gestational age, sex, temperature and base excess (BE) at admission. This analysis compared the power of CRIB, CRIB‐II, birth weight and gestational age to predict death prior to discharge.

Methods: Of 1485 consecutive VLBW infants admitted between January 1, 1991 and December 31, 2006, who survived for ≥12 h, CRIB and CRIB‐II calculations were possible in 1358 infants (92%). Predictive power of variables was assessed by comparing areas under receiver operator characteristics curves (AUC).

Results: CRIB (AUC [95% confidence intervals] 0.82 [0.78–0.86]) performed significantly better than birth weight (0.74 [0.69–0.79]) or gestational age (0.71 [0.66–0.76]), while CRIB‐II (0.69 [0.64–0.74]) was rather inferior to CRIB and did not differ significantly from birth weight or gestational age. No substantial changes were seen when substituting worst BE during the first 12 h of life for BE at admission when calculating CRIB‐II.

Conclusions: CRIB‐II does not result in improved estimation of mortality risk in VLBW infants as compared to CRIB, birth weight or gestational age.
Pacifier use: What makes mothers change their mind?
Authors: Pansy Jasmin , Zotter Heinz , Sauseng Werner , Schneuber Susanne , Lang Uwe , Kerbl Reinhold
Published: April 2008

Aim: To find out the reasons for mothers to either use or not use a pacifier and to find out the mother's reasons for changing their mind.

Method: We analysed the data of 174 mother–infant pairs by means of a semistructured questionnaire performed shortly after birth, and at the age of 7 weeks and 5 months, respectively.

Results: The main reason for mothers primarily refusing a pacifier was their concern about malformation of the teeth or jaw. Until the end of the fifth month, 31% of the mothers changed their mind about pacifier use. Mothers primarily refusing a pacifier introduced a pacifier due to the need of soothing the infant. Mothers, who initially intended to use a pacifier, changed their mind due to rejection by the infant. The prevalence of pacifier use at the age of 5 months was 78%. The majority of mothers (69%) introduced the pacifier during the first week of life.

Conclusion: About one third of mothers had changed their mind about pacifier use, either because of rejection by the infant or the need of settling. Breastfeeding mothers require more and better information concerning the appropriate time of pacifier onset.
Dynamin‐like protein‐dependent formation of Woronin bodies in Saccharomyces cerevisiae upon heterologous expression of a single protein
Authors: Würtz Christian , Schliebs Wolfgang , Erdmann Ralf , Rottensteiner Hanspeter
Published: April 2008

Filamentous ascomycetes harbor Woronin bodies and glyoxysomes, two types of microbodies, within one cell at the same time. The dominant protein of the Neurospora crassa Woronin body, HEX1, forms a hexagonal core crystal via oligomerization and evidence has accumulated that Woronin bodies bud off from glyoxysomes. We analyzed whether HEX1 is sufficient to induce Woronin body formation upon heterologous expression in Saccharomyces cerevisiae, an organism devoid of this specialized organelle. In wild‐type strain BY4742, initial import of HEX1 into existing peroxisomes enabled the formation of organelles with a hexagonal crystal. The observed structures mimicked the shape of genuine Woronin bodies, but exhibited a lower density and were significantly larger. Double‐immunofluorescence analysis revealed that hexagonal HEX1 structures only occasionally co‐localized with peroxisomal marker proteins, indicating that the Woronin‐body‐like structures are well separated from peroxisomes. In cells lacking Vps1p and Dnm1p, dynamin‐like proteins required for the division of peroxisomes, the Woronin‐body‐like organelles remained attached to peroxisomes. The data indicate that Woronin bodies emerge after the formation of a HEX1 core crystal within peroxisomes followed by Vps1p‐ and Dnm1p‐mediated fission.
Simulation of Fluid, Heat Transport to Estimate Desert Stream Infiltration
Authors: Kulongoski Justin T. , Izbicki John A.
Published: April 2008

In semiarid regions, the contribution of infiltration from intermittent streamflow to ground water recharge may be quantified by comparing simulations of fluid and heat transport beneath stream channels to observed ground temperatures. In addition to quantifying natural recharge, streamflow infiltration estimates provide a means to characterize the physical properties of stream channel sediments and to identify suitable locations for artificial recharge sites. Rates of winter streamflow infiltration along stream channels are estimated based on the cooling effect of infiltrated water on streambed sediments, combined with the simulation of two‐dimensional fluid and heat transport using the computer program VS2DH. The cooling effect of ground water is determined by measuring ground temperatures at regular intervals beneath stream channels and nearby channel banks in order to calculate temperature‐depth profiles. Additional data inputs included the physical, hydraulic, and thermal properties of unsaturated alluvium, and monthly ground temperatures measurements over an annual cycle. Observed temperatures and simulation results can provide estimates of the minimum threshold for deep infiltration, the variability of infiltration along stream channels, and also the frequency of infiltration events.
Influence of Photosensitizer Solvent on the Mechanisms of Photoactivated Killing of Enterococcus faecalis
Authors: George Saji , Kishen Anil
Published: April 2008

This study evaluated the mechanisms involved and the influence of photosensitizer solvent in the killing of Enterococcus faecalis using photodynamic therapy (PDT). Enterococcus faecalis cells incubated with 100 μm methylene blue dissolved in water and in MIX (a mixture of glycerol:ethanol:water) were irradiated with 664 nm diode laser (63.69 J cm−2). The effect of PDT on the viability of bacteria, and the functional integrity of cell wall, chromosomal DNA and membrane proteins were analyzed. The bactericidal action of PDT was significantly higher when a MIX‐based photosensitizer solvent was used (P < 0.001). Fluorimetric and fluorescence microscopy‐based analysis showed the functional impairment of E. faecalis cell wall which was significantly higher when a MIX‐based photosensitizer solvent was used (P < 0.001). PDT with MIX‐based photosensitizer solvent showed extensive damage to chromosomal DNA. However, both PDT conditions showed similar trend in the degradation of membrane proteins, although cross‐linked proteins were evident only in PDT conducted with MIX‐based photosensitizer solvent. The findings from our study showed that PDT destroyed the functional integrity of cell wall, DNA and membrane proteins of E. faecalis. The degrees of damage on these targets were influenced by the photosensitizer solvent used during PDT.
Molecular Recognition in Partially Folded States of a Transporter Protein: Temperature‐dependent Specificity of Bovine Serum Albumin
Authors: Banerjee Debapriya , Pal Samir Kumar
Published: April 2008

The specificity of molecular recognition of a transporter protein bovine serum albumin (BSA) in its different partially folded states has been studied. In order to avoid complications due to chemical denaturation, we have prepared thermally induced partially folded states of the protein. The partially folded states have been structurally characterized by circular dichroism and differential thermal analysis techniques. The change in the globular structure of the protein as a consequence of thermal unfolding has also been characterized by dynamic light scattering. Steady state, picosecond‐resolved fluorescence and polarization gated spectroscopies on the ligands (DCM, LDS 750) in the protein reveal the dynamics of the binding sites and the specificity of ligand binding of BSA. Picosecond resolved Förster resonance energy transfer studies on the donor DCM and acceptor LDS 750 confirm that the specificity of ligand binding in the binding site is maintained up to 70°C. At 75°C, the protein loses its specificity of recognition at the aforesaid site.
Spectroscopy, Binding to Liposomes and Production of Singlet Oxygen by Porphyrazines with Modularly Variable Water Solubility
Authors: Sholto Alan , Lee Sangwan , Hoffman Brian M. , Barrett Anthony G. M. , Ehrenberg Benjamin
Published: April 2008

Three novel classes of porphyrazine‐like structures were synthesized to form modular structures in which lipophilicity and water solubility can be tuned. Subtle modification of solubility is an important criterion in selecting a compound for biological photosensitization. The general structure takes the form H2[pz(AnB4−n)], where the core is a porphyrazine (pz) group, A is a pyrrole ring with two sulfide linkages (SR moieties) and B is a pyrrole fused with a 4,7‐bis(isopropyloxy)benzo group, with n = 4, 3 and 2. These molecules possess their longest wavelength absorption band between 700 and 810 nm, hence laser beams of higher tissue penetration depth could be used to illuminate them in photodynamic therapy (PDT). Armed with absorption bands in the far‐red and near‐infrared (near‐IR), and a capability to tune the solubility, these molecules could make for better sensitizers because of optimized uptake by lipidic membranes and better optical properties. We tested several derivatives of the A4, A3B and A2B2 structures for their singlet oxygen quantum yields in methanol and in liposomes, using 9,10‐dimethyl anthracene (DMA) as a singlet oxygen target. Singlet oxygen quantum yields in liposomes ranged from 0.01 to 0.44, with the A2B2 group showing the most promise. In the binding assay to find the equilibrium binding constant, Kb, we detected fluorescence changes due to a change in environment. Peripheral long‐chain moieties (the R group in the SR moieties) dominate lipid binding. These moieties range in the hydrophobicity that they induce from C8H17 and benzene, which rendered the molecule totally insoluble in water, to polyethylene glycol (PEG) and carboxylate groups, which imparted water solubility. Each molecule had between 4 and 8 such identical chains. Chains bearing an ether or ester link resulted in measurable equilibrium constants, with a higher Kb for ether substituents. Results for Kb ranged from 0.23 to 26.52 (mg mL−1)−1. A delicate balance exists between water solubility and good partitioning to membranes. In general, a higher oxygen‐to‐carbon ratio in the chains improves binding. Fewer chains and a centrally coordinated zinc ion further improve binding and singlet oxygen production.
Immunophototherapy Using PDT Combined with Rapid Intratumoral Dendritic Cell Injection
Authors: Sur Brandon W. , Nguyen Phuong , Sun Chung‐Ho , Tromberg Bruce J. , Nelson Edward L.
Published: April 2008

The capacity of photodynamic therapy (PDT) to induce localized cell death and tissue damage suggests that when applied to tumors it could create a local depot of tumor‐associated antigens, which would be available for uptake and presentation to the immune system, potentially leading to improved tumor control. Dendritic cells (DCs) are the most potent cells for antigen uptake, presentation, and stimulation of the immune system. However, it is unclear whether DCs would retain their viability and functional capacity for the requisite trafficking to draining lymph nodes when adoptively transferred in close temporal and anatomic proximity to the site of PDT‐induced cytotoxicity. We conducted studies of combined PDT and adoptive DC therapy, “immunophototherapy,” in a female, Fisher 344 rat orthotopic mammary tumor model. Using 5‐aminolevulinic acid as a pro‐drug, we demonstrated kinetically favorable biologic conversion to the photosensitive protoporphyrin IX, appropriate trafficking of syngeneic bone marrow‐derived DCs injected into PDT‐treated tumors within 15 min of completion of therapy, and improved survival over either modality alone. These data indicate that DCs rapidly administered into the site of PDT retain their viability and functional status, supporting the further evaluation of immunophototherapy strategies.
Human Natures: Psychological Essentialism in Thinking about Differences between People
Authors: Haslam Nick , Whelan Jennifer
Published: April 2008

‘Psychological essentialism’ is the belief that members of a category share deep‐seated properties that determine their identity. In the case of social categories, such beliefs have a variety of important implications. We review recent research that shows a central role for essentialist thinking in stereotyping, prejudice, and discrimination. Special attention is paid to beliefs about race and ethnicity, gender, sexual orientation, mental disorder, and personality. Lingering questions about essentialist thinking are discussed, and several directions for future research are suggested.
Phenomenology and Critical Social Psychology: Directions and Debates in Theory and Research
Authors: Langdridge Darren
Published: April 2008

There has been significant growth in critical approaches to social psychology in recent years. Phenomenological, discursive and psychoanalytically informed perspectives, amongst others, have become increasingly popular alternatives to ‘mainstream’ cognitive social psychology. This paper describes the fundamental philosophy and methodology underpinning phenomenological psychology along with discussion of a number of key issues in qualitative research in social psychology. In particular, I discuss the role of interpretation, the turn to language and need for political engagement within critical social psychology. More recently, there has been a growth in phenomenologically informed narrative theories and methodologies and in this paper I introduce my own development of a critical narrative analysis. In the process I discuss some of the most pressing debates about research within the phenomenological tradition and provide rebuttals, solutions and possible future directions for phenomenological theory and research that may lead to yet greater recognition for this social psychological perspective.
Molecular mechanisms of portal vein tolerance
Authors: Watanabe Tomohiro , Kudo Masatoshi , Chiba Tsutomu , Wakatsuki Yoshio
Published: April 2008

The liver has been considered as a tolerogenic organ in the sense that favors the induction of peripheral tolerance. The administration of antigens (Ags) via the portal vein causes tolerance, which is termed portal vein tolerance and can explain the occurrence of tolerogenic responses in the liver. Here we discuss the fundamental mechanisms accounting for portal vein tolerance. Antigen‐presenting cells (APCs) in the liver, especially dendritic cells and sinusoidal endothelial cells, have limited the ability to produce pro‐inflammatory cytokines upon stimulation with endotoxin, an effect that could be due to the continuous exposure to bacterial Ags derived from intestinal microflora. Ag presentation by liver APCs results in T cell tolerance through clonal deletion and selection of regulatory T cells. Thus, APCs with immunosuppressive functions are associated with the achievement of portal vein tolerance via the induction of clonal deletion and generation of regulatory T cells.
Radial Distribution Function in the Hard Sphere Mixtures
Authors: Boublík Tomáš
Published: April 2008

Equilibrium structures of both homogeneous and heterogeneous systems are, within statistical thermodynamics, characterized by distribution functions. Using the approach proposed recently - based on the determination of the cavity functions for the pair of hard spheres (HS) and the combined body - we studied the effect of different choices of the probe HS (which determines the shape of the combined hard body - enlarged dumbbell) on the prediction of the distribution functions in binary mixtures of HS with the aspect ratio 0.9, ternary mixtures with diameter ratios 1, 0.6 and 0.3, and density profiles of HS mixture with the aspect ratio 2 near a hard wall. It was found that the method, that uses the average geometric functionals determined for the probe HS with individual diameters multiplied by the respective mole fractions yields better results than the approaches based on average probe diameters.
On Universality of the Wrapping Percolation Transition
Authors: Škvor Jiří , Nezbeda Ivo
Published: April 2008

The hypotheses of the scaling universality of the wrapping probability at the percolation threshold and of the critical exponent ν have been examined for the PM/TIP4P primitive model of water. The obtained results confirm the validity of the recently proposed method of determination of the percolation threshold in fluids and its characteristics, supporting further the hypothesis of universality, and efficiency and accuracy of the method.
Prognostic value of mitotic counts and Ki-67 immunoreactivity in adult-type granulosa cell tumour of the ovary
Authors: Leuverink E M , Brennan B A , Crook M L , Doherty D A , Hammond I G , Ruba S , Stewart C J R
Published: April 2008

Aims:

The identification of reliable prognostic factors in patients with ovarian stage 1 adult-type granulosa cell tumour (GCT) has proved problematic. Some reports have suggested that proliferation indices may be of value, but the data are conflicting and the methods of assessment often poorly defined. In this study the mitotic activity and Ki-67 immunohistochemistry was assessed in a series of GCT using carefully specified methodology, and the findings were correlated with clinicopathological findings.

Methods:

Tumour proliferation was assessed in 38 primary GCT by counting mitotic figures in 50 high-power fields (×500 magnification) with results expressed as a mean count per 2 mm2standardised area. The number of mitotic figures and Ki-67 immunoreactive cells per 10 000 tumour cells was also assessed using an ocular cell counting graticule. The results were correlated with tumour stage at presentation and with the development of tumour recurrence.

Results:

Twenty-nine patients were stage 1 at presentation, and nine patients had high-stage disease (extra-ovarian spread). Nine patients with initial stage 1 disease developed metastases, and 20 patients had no evidence of recurrence over a mean follow-up period of 11.1 years. There was no significant correlation between any of the proliferation indices or with clinical outcomes.

Conclusions:

These results suggest that proliferation assessment is of limited value in the pathological assessment of GCT. Future studies should carefully specify the methods of assessing cell proliferation to ensure a reliable comparison of results.
Llandovery (Early Silurian) orthide brachiopod associations from Anticosti Island, eastern CanadaThis article is one of a series of papers published in this Special Issue on the theme The dynamic reef and shelly communities of the Paleozoic. This Special is in honour of our colleague and friend Paul Copper.
Authors: Li Rong-Yu , Allen Trevor
Published: April 2008

Five Llandovery orthide brachiopod associations, through cluster analysis, are delineated on Anticosti Island. The Levenea – Dicoelosia Association (A), occurring in the Goéland and Richardson members of the lower Jupiter Formation, represents a deep-water setting around or below the maximum storm wave base. The Flabellitesia – Dalejina Association (B), appearing in the Cybèle, Ferrum, and Pavillon members of the upper Jupiter Formation, indicates water depth in between the maximum and normal storm wave bases. The Isorthis ( Ovalella ) Association (C1), present in the Fox Point Member of Becscie Formation, corresponds to the shallower water setting around the normal storm wave base. The Mendacella bleikeriensis Association (C2), occurring in the Innommée, Sandtop, and Macgilvray members of Gun River Formation, characterizes the water depth slightly below the normal storm wave base. The Mendacella udauberis Association (D), appearing in the Merrimack Formation, signifies a water depth around the maximum storm wave base. The water depth indication of these associations may bear potential as future reference for other regions, but attention should be paid to the species level as some congeneric species can belong to different associations of different depth. The cluster analysis on orthide collections based on binary data demonstrates that statistical methods, Jaccard coefficient and Ward’s method of clustering, are practical and effective to delineate large brachiopod collections on Anticosti Island.
Environmental control on temporal and spatial differentiation of Early Silurian pentameride brachiopod communities, Anticosti Island, eastern CanadaThis article is one of a selection of papers published in this Special Issue on the themeThe dynamic reef and shelly communities of the Paleozoic. This Special is in honour of our colleague and friend Paul Copper.
Authors: Jin Jisuo
Published: April 2008

The Early Silurian carbonate succession of Anticosti Island, eastern Canada, contains a rich and diverse pentameride brachiopod fauna. Multivariate analyses of 91 samples (total 17 230 specimens) confirm a high degree of temporal segregation but only moderate spatial differentiation of the Virgiana , Pentamerus , Stricklandia , Ehlersella , Microcardinalia , and Clorinda communities. Most pentameride communities show a wider range of water depth than previously believed. The V. barrandei Community occupied a substrate setting from lower BA2 to upper BA3, whereas the V. mayvillensis Community lived mainly in BA4. The P. oblongus Community preferred a BA3 setting, comparable to the classic Pentamerus Community, but the P. palaformis Community was predominantly BA4. The stricklandiid communities have a high β diversity, dominated by various species of Stricklandia, Ehlersella, Microcardinalia, and Kulumbella, and occurred most commonly in BA4, but could extend to BA3 environments. The Clorinda Community of Anticosti Island preferred deep and quiet water settings, comparable to its widely accepted BA5 assignment elsewhere. At the generic level, the Virgiana, Pentamerus, and the stricklandiid communities have a largely overlapping BA range, but a clear stratigraphical separation. Thus, their temporal alternations were not likely controlled by water depth, water turbulence, or substrate conditions, but by fluctuating ocean water temperature, as suggested by chemostratigraphical and paleobiogeographical evidence.
Failed predation in Late Ordovician gastropods (Mollusca) from Manitoulin Island, Ontario, CanadaThis article is one of a selection of papers published in this Special Issue on the themeThe dynamic reef and shelly communities of the Paleozoic. This Special is in honour of our colleague and friend Paul Copper.
Authors: Ebbestad Jan Ove R. , Stott Christopher A.
Published: April 2008

Shell repairs resulting from presumed failed predation are documented in gastropods from the Late Ordovician (Cincinnatian; Richmondian) mid-to-upper Kagawong Submember of the Georgian Bay Formation on Manitoulin Island, Ontario, Canada. The bryozoan–mollusc biota and associated sediments generally suggest nearshore, shallow (<10 m), low energy (lagoonal), and perhaps mesotrophic to eutrophic conditions. Two sample sets from this unit have been studied for shell repair. One of the more commonly applied estimates of shell repair frequencies involves division of the number of individuals with at least one scar by the total number of individuals in the sample (the Individuals with scars method). Using this calculation, 207 specimens of Lophospira trilineata Ulrich and Scofield yielded a shell repair frequency of 4.8%; in 28 specimens of Trochonemella sp. the shell repair frequency was 35.7%. Repairs in Trochonemella occur primarily in the larger size class, suggesting that a size refuge was achieved by this species. Low repair frequencies in L. trilineata suggest predation with a higher success rate or fewer encounters. This study demonstrates that the paradigm of a standardized low level of shell repair in Ordovician and Silurian gastropods is oversimplistic and a range of frequency rates can be expected.
Benthic island community on the back of a snail: Silurian, Anticosti Island, CanadaThis article is one of a series of papers published in this Special Issue on the themeThe dynamic reef and shelly communities of the Paleozoic. This Special is in honour of our colleague and friend Paul Copper.
Authors: Tapanila Leif , Ebbestad Jan Ove R.
Published: April 2008

A single specimen of the large Silurian gastropod Phanerotrema sp. from the Goéland Member on Anticosti Island preserves an outstanding microcosm of its surrounding community, including multiple trophic groups, strategies for niche partitioning, and innovative adaptations for survival in a mud-dominated marine ecosystem. At least seven associations are recorded in this fossil specimen, including the gastropod itself, healed breakage from an apparently failed attempt at durophagous predation, domichnial bioerosion, encrustation by a stromatoporoid, nestling behaviour and commensal embedment by a lingulid brachiopod, and epifaunal attachment by two cornulitids. As a benthic island, the gastropod conch provided a favourable isolated habitat for hard substrate colonizers. This unique specimen sheds light on the broader Paleozoic ecosystem, including the potential importance of benthic islands in the evolution of niche-partitioning strategies in space-limited communities.
Statistical analysis of mixed-motive shell borings in Ordovician, Silurian, and Devonian brachiopods from northern and eastern CanadaThis article is one of a selection of papers published in this Special Issue on the themeThe dynamic reef and shelly communities of the Paleozoic. This Special is in honour of our colleague and friend Paul Copper.
Authors: Daley Allison C.
Published: April 2008

Hundreds of shell borings of different origin and displaying variable patterns were found in strophomenide, pentameride, and orthide brachiopods of five Paleozoic localities in northern and eastern Canada. The borings were analyzed using simple statistics as well as cluster and nonmetric multidimensional scaling analyses. At the Ordovician Anticosti Island locality, all borings are parasitic or post-mortem in origin, while at the Wenlock–Ludlow Baillie-Hamilton Island, almost all borings are predatory. At the remaining three localities, borings represent a mix of predatory, parasitic, and post-mortem domichnial borings in all three brachiopod taxa, the proportions of which were controlled largely by brachiopod shell morphology and paleoecology. For the strophomenides, predatory borings can be segregated from parasitic and post-mortem domichnial using simple and multivariate statistical analyses. Sowerbyella-type strophomenides have a higher proportion of predatory borings at the Lochkovian localities than at the Ordovician localities, while the reverse is true for the Strophomena-type strophomenides. In pentamerides and orthides, very few predatory borings are identified; most borings were emplaced by parasitic or post-mortem domichnial borers. In pentamerides, this is due to the internal structure of the shells, which elevated the muscles of the organism above the shell floor, rendering them inaccessible to boring predators. In orthides, more deliberate defense mechanisms such as toxins or external ornamentation may have deterred predation. This study indicates that throughout the Paleozoic interactions between borers and brachiopods were complex but can be elucidated using a large sample size and statistical analyses.
Evidence of Decreasing Spatial Diversity in British Columbia Salmon Stocks
Authors: Walters Carl J. , Cahoon Peter
Published: April 2008

Escapement records indicate a severe decline since 1950 in the number of streams contributing significantly to salmon production in southern British Columbia. To account for 90% of the escapement for chinook (Oncorhynchus tshawytscha), coho (O. kisutch), pink (O. gorbuscha), and chum (O. keta), one need examine only about half as many streams now as in 1950. The deterioration has been most pronounced for coho; only 40 of 350 south coast streams now account for 80% of the recorded escapement. The apparent changes are due partly to reduced monitoring effort rather than actual stock declines, but deterioration in the monitoring system is itself a cause for major concern.
Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene
Authors: Mateus F.H. , Lepera J.S. , Marques M.P. , Boralli V.B. , Lanchote V.L.
Published: April 2008

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal–Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng·h·mL–1; p ≤ 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng·h·mL–1; p ≤ 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.
Potential cytoprotection: antioxidant defence by caffeic acid phenethyl ester against free radical-induced damage of lipids, DNA, and proteins
Authors: Wang Ting , Chen Lixiang , Wu Weimin , Long Yuan , Wang Rui
Published: April 2008

Oxidative stress is considered to be a major cause of cellular injuries in a variety of chronic health problems, such as carcinogenesis and neurodegenerative disorders. Caffeic acid phenethyl ester (CAPE), derived from the propolis of honeybee hives, possesses a variety of biological and pharmacological properties including antioxidant and anticancer activity. In the present study, we focused on the diverse antioxidative functionalities of CAPE and its related polyphenolic acid esters on cellular macromolecules in vitro. The effects on human erythrocyte membrane ghost lipid peroxidation, plasmid pBR322 DNA, and protein damage initiated by the water-soluble initiator 2,2′-azobis(2-amidinopropane) hydrochloride (AAPH) and hydrogen peroxide (H2O2) were monitored by formation of hydroperoxides and by DNA nicking assay, single-cell alkaline electrophoresis, and SDS-polyacrylamide gel electrophoresis. Our results showed that CAPE and its related polyphenolic acid esters elicited remarkable inhibitory effects on erythrocyte membrane lipid peroxidation, cellular DNA strand breakage, and protein fragmentation. The results suggest that CAPE is a potent exogenous cytoprotective and antigenotoxic agent against cell oxidative damage that could be used as a template for designing novel drugs to combat diseases induced by oxidative stress components, such as various types of cancer.
Modulation of radiosensitivity in Chinese hamster lung fibroblasts by cisplatin
Authors: Akudugu J.M. , Slabbert J.P.
Published: April 2008

The effects of cisplatin exposure time, concentration, and irradiation sequence on the sensitivity of Chinese hamster lung fibroblasts (V79) to γ-ray exposure were examined. Based on clonogenic cell survival, the cisplatin concentrations corresponding to 50% cell survival (EC50) for exposure times of 1 h to 7 days followed a 2-phase exponential decay and ranged from 28.26 ± 3.32 to 1.53 ± 0.24 μmol/L, respectively. When cells were treated at EC50 for exposures of less than 4 h and irradiated immediately, cisplatin inhibited the effect of radiation. Exposures of 4–6 h did not affect radiosensitivity. For exposures of 8–12 h, radiosensitization was observed, which disappeared at 14 h and reappeared for much longer cisplatin treatments. At the lowest achievable EC50 (1.53 μmol/L), radiosensitization was observed if irradiation was delayed for 1–8 h. This enhancement in radiosensitivity disappeared for irradiation delays of 10–12 h, but reappeared when irradiation was delayed for 14–18 h. These data demonstrate that the mode of interaction between cisplatin and γ-irradiation depends on the concentration and exposure time of cisplatin, as well as on the timing of irradiation after cisplatin administration. Consideration of changes in cell cycle kinetics may contribute to the improvement of treatment outcomes in adjuvant chemoradiotherapy involving cisplatin.
Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits
Authors: Kubota Takashi , Jibiki Itsuki , Ishikawa Akira , Kawamura Tomomi , Kurokawa Sonoko , Wang Man
Published: April 2008

We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine’s clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path–dentate gyrus pathway.
Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals
Authors: Min Rui , Li Ting , Du Ju , Zhang Yan , Guo Jia , Lu Wan-Liang
Published: April 2008

Gemcitabine, a nucleoside analogue for treating lung cancer, is clinically administered as an intravenous infusion. To achieve better patient compliance and more direct effect on the lung, we explored a new gemcitabine pulmonary delivery route and evaluated the pharmacokinetics and acute lung injury aspects in animals. Pharmacokinetics of gemcitabine were measured in Sprague–Dawley rats after intravenous (i.v.), intratracheal instillation by tracheotomy (i.t.t.), intratracheal instillation via orotrachea (i.t.o.), and intragastric (i.g.) administration of gemcitabine. Acute lung injury effects of the pulmonary delivery of gemcitabine were performed in Sprague–Dawley rats after i.t.o. and i.v. administration of gemcitabine and i.t.o. administration of lipopolysaccharide (LPS) as a positive control and physiological saline as a blank control. Indicators for acute lung injury that were evaluated included lung morphology, lung histopathology, lung coefficient, lung wet/dry weight ratio, total cell and classification counts in bronchoalveolar lavage cells (BALC), and total protein and TNF-α levels in bronchoalveolar lavage fluids (BALF). After i.t.t. or i.t.o. administration, gemcitabine was quickly absorbed, but i.g. administration led to an undetectable plasma gemcitabine concentration. Absolute bioavailability of gemcitabine after i.t.t. and i.t.o. administration was 91% and 65%, respectively. Gemcitabine given as i.t.o. administration did not cause any overt acute lung injury. All indicators for acute lung injury in the i.t.o. group were similar to those in the i.v. group or in the blank control, but significantly different from those in the positive control. In conclusion, the pharmacokinetics and acute lung injury studies suggest that pulmonary gemcitabine delivery would be a new and promising administration route.
Missed hits or near misses: determining how many samples are necessary to confidently detect nugget-borne mineralization
Authors: Stanley Clifford R.
Published: April 2008

The probability of collecting a sample containing at least one large nugget from an exploration prospect (and thus detecting the nugget-borne mineralization) can be calculated using Poisson statistics and an equant grain model that describes the sampling characteristics of mineralization containing a range of nugget sizes. This procedure requires an estimate of the mass-weighted, average (effective) nugget grain size in the mineralized material, and an estimate of the (expected) grade of mineralization. Using these parameters, the number of effective nuggets in an equivalent equant grain model that describes the sampling characteristics of mineralization can be determined and used to estimate the Poisson probability of collecting at least one large nugget in a real sample. With this information, the probability of collecting
m
large nugget-bearing samples from a set of
n
samples can be determined using binomial statistics, providing the explorationist with an estimate of how well a prospect containing nugget-borne mineralization will be assessed using those
n
samples. Software can be used to perform the associated calculations.
Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice
Authors: Jeoung Nam Ho , Harris Robert A.
Published: April 2008

The effect of pyruvate dehydrogenase kinase-4 (PDK4) deficiency on glucose homeostasis was studied in mice fed a high-fat diet. Expression of PDK4 was greatly increased in skeletal muscle and diaphragm but not liver and kidney of wild-type mice fed the high-fat diet. Wild-type and PDK4−/−mice consumed similar amounts of the diet and became equally obese. Insulin resistance developed in both groups. Nevertheless, fasting blood glucose levels were lower, glucose tolerance was slightly improved, and insulin sensitivity was slightly greater in the PDK4−/−mice compared with wild-type mice. When the mice were killed in the fed state, the actual activity of the pyruvate dehydrogenase complex (PDC) was higher in the skeletal muscle and diaphragm but not in the liver and kidney of PDK4−/−mice compared with wild-type mice. When the mice were killed after overnight fasting, the actual PDC activity was higher only in the kidney of PDK4−/−mice compared with wild-type mice. The concentrations of gluconeogenic substrates were lower in the blood of PDK4−/−mice compared with wild-type mice, consistent with reduced formation in peripheral tissues. Diaphragms isolated from PDK4−/−mice oxidized glucose faster and fatty acids slower than diaphragms from wild-type mice. Fatty acid oxidation inhibited glucose oxidation by diaphragms from wild-type but not PDK4−/−mice. NEFA, ketone bodies, and branched-chain amino acids were elevated more in PDK4−/−mice, consistent with slower rates of oxidation. These findings show that PDK4 deficiency lowers blood glucose and slightly improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity.
Hormonal and purinergic stimulation of bicarbonate secretion in oviducts of rhesus monkey
Authors: Rajagopal M. , Fischer H. , Widdicombe J. H.
Published: April 2008

Because an increase in the HCO3−concentration of oviductal liquid at midcycle is believed to markedly enhance fertility, we have studied active secretion of HCO3−across highly differentiated cultures of monkey oviductal epithelium. Cultured cell sheets were mounted in Ussing chambers and bathed in medium containing 25 mM HCO3−. Purinergic agents potently stimulated short-circuit current ( Isc) with an initial transient response declining within ∼2 min to a sustained response. The potency sequence of ATP ≈ UTP > ADP >> AMP suggested that the Iscresponse was mediated mainly by P2Y2receptors. Acetazolamide, an inhibitor of carbonic anhydrase, had little or no effect on baseline Iscor the transient response to ATP but abolished the sustained response to ATP. Similar results were obtained on sheets of native epithelium. In pH-stat experiments, the abluminal medium of cell cultures was bathed in HCO3−-CO2medium, and the pH of the unbuffered luminal medium was maintained at ∼7.4 by addition of strong acid or base. ATP stimulated base secretion, and this was inhibited by acetazolamide. Furthermore, these changes in secretion of base were in good quantitative agreement with the Iscresponses. When phenol red (an estrogen) was removed from the culture medium, ATP-dependent HCO3−secretion was markedly reduced but could be restored by treatment with estradiol. Estrogens also markedly increased ciliation of the cultures. These results suggest that the midcycle increase in the HCO3−concentration of oviductal liquid may be mediated by the effects of estradiol on purinergic pathways or on ATP secretion.
Sevoflurane protects against renal ischemia and reperfusion injury in mice via the transforming growth factor-β1 pathway
Authors: Lee H. Thomas , Chen Sean W. C. , Doetschman Thomas C. , Deng Chuxia , D'Agati Vivette D. , Kim Mihwa
Published: April 2008

We previously demonstrated that several clinically utilized volatile anesthetics including sevoflurane protected against renal ischemia-reperfusion (IR) injury by reducing necrosis and inflammation in vivo. We also demonstrated that volatile anesthetics produced direct anti-necrotic and anti-inflammatory effects in cultured renal tubules via mechanisms involving the externalization of phosphatidylserine and subsequent release of transforming growth factor (TGF)-β1. In this study, we tested the hypothesis that volatile anesthetic-mediated renal protection requires TGF-β1 and SMAD3 signaling in vivo. We subjected TGF-β1+/+, TGF-β1+/−, SMAD3+/+, or SMAD3−/− mice to renal IR under anesthesia with pentobarbital sodium or with sevoflurane. Although TGF-β1+/+ and SMAD3+/+ mice were significantly protected against renal IR injury under sevoflurane anesthesia with reduced necrosis and inflammation, TGF-β1+/− mice and SMAD3−/− mice were not protected against renal IR with sevoflurane. Furthermore, a neutralizing TGF-β1 antibody blocked renal protection with sevoflurane in TGF-β1+/+ mice. Sevoflurane caused nuclear translocation of SMAD3 and reduced the TNF-α-induced nuclear translocation of NF-κB in primary cultures of proximal tubules from TGF-β1+/+ but not in TGF-β1+/− mice. Finally, sevoflurane protected against necrosis induced with hydrogen peroxide in primary cultures of proximal tubules from TGF-β1+/+ mice or SMAD3+/+ mice but not in proximal tubules from TGF-β1+/− or SMAD3−/− mice. Therefore, we demonstrate in this study that sevoflurane-mediated renal protection in vivo requires the TGF-β1→SMAD3 signaling pathway.
Physiological and molecular evidence of heat acclimation memory: a lesson from thermal responses and ischemic cross-tolerance in the heart
Authors: Tetievsky Anna , Cohen Omer , Eli-Berchoer Luba , Gerstenblith Gary , Stern Michael D. , Wapinski Ilan , Friedman Nir , Horowitz Michal
Published: April 2008

Sporadic findings in humans suggest that reinduction of heat acclimation (AC) after its loss occurs markedly faster than that during the initial AC session. Animal studies substantiated that the underlying acclimatory processes are molecular. Here we test the hypothesis that faster reinduction of AC (ReAC) implicates “molecular memory.” In vivo measurements of colonic temperature profiles during heat stress and ex vivo assessment of cross-tolerance to ischemia-reperfusion or anoxia insults in the heart demonstrated that ReAC only needs 2 days vs. the 30 days required for the initial development of AC. Stress gene profiling in the experimental groups highlighted clusters of transcriptionally activated genes (37%), which included heat shock protein (HSP) genes, antiapoptotic genes, and chromatin remodeling genes. Despite a return of the physiological phenotype to its preacclimation state, after a 1 mo deacclimation (DeAC) period, the gene transcripts did not resume their preacclimation levels, suggesting a dichotomy between genotype and phenotype in this system. Individual detection of hsp70 and hsf1 transcripts agreed with these findings. HSP72, HSF1/P-HSF1, and Bcl-xL protein profiles followed the observed dichotomized genomic response. In contrast, HSP90, an essential cytoprotective component mismatched transcriptional activation upon DeAC. The uniform activation of the similarly responding gene clusters upon De-/ReAC implies that reacclimatory phenotypic plasticity is associated with upstream denominators. During AC, DeAC, and ReAC, the maintenance of elevated/phosphorylated HSF1 protein levels and transcriptionally active chromatin remodeling genes implies that chromatin remodeling plays a pivotal role in the transcriptome profile and in preconditioning to rapid cytoprotective acclimatory memory.