bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis
Authors: Korobova Farida , Svitkina Tatyana
Published: November 2009

Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as dendritic filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated filopodia-like protrusions. Dynamically, dendritic filopodia emerged from densities in the dendritic shaft, which by electron microscopy contained branched actin network associated with dendritic microtubules. We propose that dendritic spine morphogenesis begins from an actin patch elongating into a dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility.
Effect of simvastatin vs. rosuvastatin on adiponectin and haemoglobin A1c levels in patients with non‐ischaemic chronic heart failure
Authors: Tsutamoto Takayoshi , Yamaji Masayuki , Kawahara Chiho , Nishiyama Keizo , Fujii Masanori , Yamamoto Takashi , Horie Minoru
Published: November 2009

Aims

To compare the effects of lipophilic simvastatin and hydrophilic rosuvastatin on plasma adiponectin and glycated haemoglobin A1c (HbA1c) levels in patients with non‐ischaemic chronic heart failure (NICHF).

Methods and results

Seventy‐one stable outpatients with NICHF, who were already receiving standard therapy for CHF, were randomized to simvastatin (n = 35) or rosuvastatin (n = 36). Plasma levels of brain natriuretic peptide (BNP), total adiponectin, high‐sensitive C‐reactive protein, HbA1c, and oxidized low‐density lipoprotein (oxLDL), a marker of oxidative stress, were measured before and 4 months after treatment with simvastatin or rosuvastatin. There was no difference in the baseline characteristics including left ventricular ejection fraction (LVEF) and biochemical parameters between the two groups. In both groups, plasma BNP levels and LVEF did not change after 4 months. Plasma levels of adiponectin and oxLDL did not change and HbA1c level was slightly increased (6.0 ± 0.9 vs. 6.1 ± 0.9%, P = 0.053) in the simvastatin group. In contrast, plasma adiponectin level was significantly increased (12.3 ± 7.3 vs. 14.0 ± 8.2 µg/mL, P = 0.012) concomitant with a significant reduction in oxLDL and HbA1c (oxLDL: 8.8 ± 4.7 vs. 7.6 ± 4.7 U/mL, P = 0.0059; HbA1c: 6.0 ± 0.7 vs. 5.9 ± 0.7%, P = 0.002) in the rosuvastatin group.

Conclusion

These findings suggest that hydrophilic rosuvastatin but not lipophilic simvastatin increases adiponectin and decreases HbA1c levels in patients with NICHF.
Heart failure in patients hospitalized with acute coronary syndromes: observations from the Gulf Registry of Acute Coronary Events (Gulf RACE)
Authors: Alsheikh‐Ali Alawi A. , Al‐Mallah Mouaz H. , Al‐Mahmeed Wael , Albustani Nazar , Al Suwaidi Jassim , Sulaiman Kadhim , Zubaid Mohammad ,   for the Gulf RACE Investigators
Published: November 2009

Aims

We describe the prevalence and prognostic significance of heart failure (HF) complicating acute coronary syndromes (ACS) in patients enrolled in the Gulf Registry of Acute Coronary Events (Gulf RACE).

Methods and results

Gulf RACE is a prospective, multi‐national study of all patients hospitalized with ACS in 65 centres in six Arab countries. Data were analysed based on HF on presentation (Killip class II/III) or during hospital stay. The study endpoint was all‐cause in‐hospital mortality. Of 8000 patients with ACS, 2009 (25%) had HF on presentation or during the hospital stay. Patients with HF were older, more often with co‐morbid conditions, and less often treated with evidence‐based therapies. Heart failure was associated with higher in‐hospital mortality (7.9 vs. 0.9%, P < 0.001), which persisted after adjusting for age, gender, and presentation and treatment characteristics [adjusted odds ratio 4.1 (1.8–9.4)]. There was a significant interaction between age and the prognostic effect of HF on in‐hospitality mortality, such that younger patients had a significantly higher increase in mortality related to HF (P for interaction = 0.002).

Conclusion

Heart failure complicates a substantial proportion of ACS admissions in the Arab Middle East and is associated with higher in‐hospital death. Younger patients with ACS have a higher relative increase in mortality related to HF.
Cardiac mortality in β‐thalassemia major: resting but not dobutamine stress echocardiography predicts mortality among initially cardiac disease‐free patients in a prospective 12‐year study
Authors: Hahalis George , Kourakli Alexandra , Gerasimidou Ioanna , Kalogeropoulos Andreas P. , Sitafidis George , Papageorgiou Urania , Davlouros Periklis , Grapsas Nikos , Zoumbos Nicholas C. , Alexopoulos Dimitrios
Published: November 2009

Aims

Cardiac death remains the principal cause of mortality in β‐thalassemia major (β‐TM). Echocardiography may provide additional information, incremental to haematological profile, both for guiding chelation therapy and to assess prognosis.

Methods and results

Between 1993 and 1995, 36 patients with β‐TM and normal cardiac function and 25 normal volunteers underwent evaluation using resting and dobutamine stress echocardiography (DSE). Dobutamine stress echocardiography was performed at baseline and repeated after 2 years. The primary endpoint was cardiac mortality. During a 12‐year observation period, seven patients (19%) died from heart failure. All seven deaths occurred among the cohort of 12 patients with median ferritin concentrations ≥2800 ng/mg. In addition, a resting left ventricular ejection fraction (LVEF), 60% was also associated with increased late mortality. In multivariate analysis, increased serum ferritin levels and reduced LVEF but not DSE or other haematological variables were independent survival determinants.

Conclusion

Resting LVEF provides prognostic information that is additional to ferritin levels among patients with β‐TM.
Relative Contribution of Various Sources of Botrytis cinerea Inoculum in Strawberry Fields in Norway
Authors: Strømeng Gunn Mari , Hjeljord Linda Gordon , Stensvand Arne
Published: November 2009

To identify the most important sources of inoculum of Botrytis cinerea (causal agent of gray mold) in commercial strawberry (Fragaria × ananassa) fields in Norway, soil and overwintered plant material were collected from planting beds and alleys at five locations in 2000 to 2002 (13 samples altogether). Plant material was sorted by category (e.g., leaves, stems, mulch, and weeds). After subsamples of each material were incubated for 5 days at 20°C at high humidity, conidiophores of B. cinerea growing from mycelia and sclerotia were counted. Overwintered plant debris within planting beds yielded more than 96% of total conidiophores counted, the remainder originating from plant debris collected from alleys or soil. Overwintered strawberry plant debris produced 98% of the conidiophores within planting beds and 80% of the conidiophores in the alleys, while the remaining was produced by weeds. Senescing and dead leaf laminae produced 45% of the conidiophores while stem residues (i.e., petioles, stolons, inflorescences, and unidentifiable stem parts) produced 50% and mummified fruit produced 5% within planting beds. The contribution of sclerotia, compared with mycelia, to conidiophore production varied greatly between fields and years. Overall, 47% of the total number of conidiophores produced in plant material within planting beds originated from sclerotia. More than 90% of the conidiophores from sclerotia were found in dead stem residues.
First Report of Botrytis cinerea Causing Gray Mold of Pomegranate (Punica granatum) in Greece
Authors: Bardas G. A. , Tzelepis G. D. , Lotos L. , Karaoglanidis G. S.
Published: November 2009

Pomegranate is rapidly increasing in production in Greece. During August of 2008 in the region of Larisa (central Greece), preharvest fruit rot was observed on pomegranate (cv. Kapmaditika) that caused losses estimated at 10%. Symptoms first appeared as small spots on the fruits that later increased in size and developed into expanded, dark brown lesions. Internally, tissues were soft and brown with gray mycelia and conidiophores observed. Affected fruits decayed completely during 2 months of storage (5 to 6°C), causing yield losses of up to 20%. To isolate the casual agent, conidia and conidiophores were scraped aseptically from the internal tissues, suspended in sterile water, and streaked onto the surface of potato dextrose agar (PDA). Single hyphal tips were transferred to PDA, and the isolated fungus was identified as Botrytis cinerea Pers.:Fr. on the basis of morphological characteristics (2). B. cinerea was consistently isolated from symptomatic tissues. Colonies of B. cinerea on PDA were at first colorless and became gray to brown with the development of lemon-shaped conidia (average 7.5 × 9 μm). Sclerotia were black and varied in size (1.4 to 4.5 × 1.5 to 2.7 mm) and shape (2). Pathogenicity of the isolated fungus was tested by wound inoculating five mature pomegranate fruits (cv. Kampaditika) after surface sterilization with 5% sodium hypochlorite. Plugs of the fungus (5 mm in diameter) obtained from the colony margins were transferred onto a 3- × 3-mm wound on the surface of sterilized fruit. Sterile PDA plugs were used to inoculate five control pomegranate fruits. Fruit were incubated at 22°C and 80% relative humidity in the dark. Extensive decay, similar to that observed on diseased fruits in the field, was observed on inoculated fruits 7 days after inoculation, whereas control fruits showed no decay. The pathogen was reisolated from internal rotten tissues of inoculated fruit, but not from the noninoculated control fruits. Fruit rot of pomegranate caused by B. cinerea has been reported previously in the United States (1) and China (3). However, to our knowledge, this is the first report of B. cinerea causing gray mold of pomegranate in Greece.

References: (1) A. M. French. California Plant Disease Host Index. Calif. Dept. Food Agric., Sacramento, 1989. (2) W. B. Hewitt. Compendium of Grape Diseases. American Phytopathological Society, 1994. (3) Z. Zhang. Flora Fungorum Sinicorum 26:277, 2006.
First Report of Penicillium glabrum Causing Fruit Rot of Pomegranate (Punica granatum) in Greece
Authors: Bardas G. A. , Tzelepis G. D. , Lotos L. , Karaoglanidis G. S.
Published: November 2009

During September and October of 2008 in the region of Larisa (central Greece), postharvest fruit rot was observed on pomegranate (cv. Kapmaditika), which is rapidly increasing in production in Greece, causing losses of 10 to 20% after 2 months of cold storage (5 to 6°C). Infected fruits showed green conidiophores in the calyx area, while internal symptoms consisted of soft, brown tissue that became covered with green mycelium and conidiophores. To isolate the casual agent, conidia and conidiophores were scraped aseptically from the internal fruit rot, suspended in sterile water, and streaked onto potato dextrose agar (PDA). Single hyphal tips were then transferred to new PDA plates. A fungus consistently isolated from the infected tissues was identified as Penicillium glabrum (Wehmer) Westling on the basis of morphological criteria, with conidiophores smooth or finely roughened and conidia in compact columns, glubose to subglubose, approximately 3.0 μm, with walls somewhat echinulate (1). The identification was confirmed by sequencing the internal transcribed spacer (ITS) region spanning ITS1, 5.8S, and ITS2 of the ribosomal DNA (2). The nucleotide sequence was submitted to GenBank (Accession No. FN313540). The pathogenicity of the isolated fungus was tested on five mature pomegranate fruit (cv. Kampaditika) after being surface sterilized with 5% sodium hypochlorite. A plug (5 mm in diameter) obtained from the margins of a P. glabrum colony was transferred to wounds (3 × 3 mm) made with a scalpel in the surface of fruit. Fruit inoculated with sterile PDA plugs served as controls. Fruit were incubated at 22°C and 80% relative humidity in the dark. Extensive decay, similar to that observed on diseased fruit in the field, was observed on the inoculated fruit 7 days after inoculation, whereas control fruit showed no decay. The pathogen was reisolated from inoculated fruit but not from the noninoculated fruit. To our knowledge, this is the first report of P. glabrum causing postharvest fruit rot of pomegranates in Greece.

References: (1) C. Thom and K. B. Raper. Page 176 in: A Manual of the Penicillia. Williams and Wilkins, Baltimore, 1949. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.
First Report of Orange Rust of Sugarcane Caused by Puccinia kuehnii in Mexico, El Salvador, and Panama
Authors: Flores R. C. , Loyo J. R. , Ojeda R. A. , Rangel O. C. A. , Cerón F. A. , Márquez W. , Guerra-Moreno A. S. , Hernandez-Ibarra H. M. , González R. E. , Castlebury L. A. , Dixon L. J. , Glynn N. C. , Comstock J. C. , Flynn J. , Amador J.
Published: November 2009

Symptoms of sugarcane orange rust were observed on July 17, 2008 on sugarcane cvs. Mex 57-1285, Mex 61-230, and Co 301 (a clone received in Mexico in 1953) at the Centro de Investigación y Desarrollo de la Caña de Azúcar en Tuxtla Chico, Chiapas, Mexico. In El Salvador, from August 2008 through January 2009, rust symptoms were observed on cv. CP 72-2086 (previously resistant to brown rust caused by Puccinia melanocephala Syd. & P. Syd.) in 117 dispersed sugarcane-production fields in various localities of El Salvador. Likewise, rust symptoms were first observed on sugarcane cv. SP 74-8355 (more than 25% severity and considered resistant to brown rust) at Natá, Coclé Province in Panama from January to February 2008. Dried herbarium leaf samples of sugarcane rust-infected leaves collected in El Salvador and Mexico were sent to the ARS, USDA Systematic Mycology and Microbiology Laboratory in Beltsville MD for identification. Panamanian samples were collected similarly and analyzed at the CALESA Biotechnology Laboratory. Morphological features of uredinial lesions and urediniospores were distinct from those of P. melanocephala and consistent with P. kuehnii E. J. Butler observed previously on specimens from Florida, Guatemala, Costa Rica, and Nicaragua (1–3). Analysis of the ITS1, 5.8S, and ITS2 and 28S large subunit rDNA sequences of the rust on infected cvs. Mex 57-1285, Mex 61-230, and Co 301 (BPI 878930, 879139, and 879140; GenBank Accession Nos. GO283006, GO283004, and GO283005, respectively) from Mexico and cv. CP 72-2086 from three locations in El Salvador (BPI 879135, 879136, and 879137; GenBank Accession Nos. GO283009, GO283007, and GO283008, respectively) all confirmed the identification of P. kuehnii. Similar analysis of the ITS1, 5.8S, and ITS2 rDNA sequence for the rust infecting cv. SP 74-8355 (GenBank Accession No. GO281584) confirmed the identification of P. kuehnii in Panama. To our knowledge, this is the first report of P. kuehnii causing orange rust disease of sugarcane in El Salvador, Mexico, and Panama. These findings also confirm the wider distribution of orange rust in the Western Hemisphere.

References: (1) E. Chavarria et al. Plant Dis. 93:425, 2009. (2) J. C. Comstock et al. Plant Dis. 92:175, 2008. (3) W. Ovalle et al. Plant Dis. 92:973, 2008.
First Report of Crown and Root Rot Caused by Binucleate Rhizoctonia AG-A on Dodonaea viscosa in Italy
Authors: Polizzi G. , Aiello D. , Vitale A. , Kato M. , Hyakumachi M.
Published: November 2009

Florida hopbush (Dodonaea viscosa (L.) Jacq.) is an evergreen bush or small tree native to Australia and a member of the Sapindaceae. During September of 2008, a crown and root rot of D. viscosa was observed on 1-year-old potted plants in a commercial nursery in eastern Sicily, Italy. More than 15% of the plants showed disease symptoms. Infected plants were characterized by a lack of vigor. Roots and crowns were partially or completely destroyed, and as a consequence, infected plants were often wilted. Early in the disease development, roots and crowns showed brown lesions. Successively, mature crown lesions turned dark brown. Diseased tissues were surface disinfested for 1 min in 1% NaOCl, rinsed in sterile water, plated on potato dextrose agar (PDA) amended with 100 mg/liter of streptomycin sulfate, and then incubated at 25°C. A binucleate Rhizoctonia (BNR) species was consistently isolated from affected tissue of plants. Fungal colonies were white with floccose, aerial hyphae. Hyphal cells were determined to be binucleate when stained with 1% safranin O and 3% KOH solution (1) and examined at ×400. Anastomosis groups were determined by pairing isolates with five different tester isolates of BNR AG-A on 2% water agar in petri plates (3). Anastomosis was observed with all tester isolates. The rDNA-ITS of one isolate of BNR (DISTEF-DV2) was sequenced (GenBank Accession No. AB514569) (2). The sequence from this isolate exhibited 99% homology with BNR AG-A (GenBank Accession No. AY738628). Pathogenicity tests were conducted on potted, healthy, 8-month-old plants of D. viscosa. Twenty plants were inoculated by placing 1/cm2 plugs of PDA from 5-day-old mycelial cultures near the base of the stem. The same number of plants was treated with 1/cm2 PDA plugs as controls. Plants were kept at 25°C and 95% relative humidity on a 12-h fluorescent light/dark regimen. Root and crown rots, identical to those observed in the nursery, appeared 30 days after inoculation, and all the inoculated plants died within 2 months. Control plants remained healthy. Binucleate Rhizoctonia was reisolated from symptomatic tissues, completing Koch's postulates. To our knowledge, this is the first report in the world of BNR AG-A causing disease on Florida hopbush.

References: (1) R. J. Bandoni. Mycologia 71:873, 1979. (2) M. Hyakumachi et al. Phytopathology 95:784, 2005. (3) C. C. Tu and J. W. Kimbrough. Mycologia 65:941, 1973.
Ineffective crypsis in a crab spider: a prey community perspective
Authors: Brechbühl Rolf , Casas Jérôme , Bacher Sven
Published: November 2009

Cryptic coloration is assumed to be beneficial to predators because of an increased encounter rate with unwary prey. This hypothesis is, however, very rarely, if ever, studied in the field. The aim of this study was to quantify the encounter rate and capture success of an ambush predator, in the field, as a function of its level of colour-matching with the background. We used the crab spider
Misumena vatia
, which varies its body colour and can thereby match the colour of the flower it hunts upon. We carried out a manipulative field experiment using a complete factorial design resulting in six different colour combinations of crab spiders and flowers differing in their degree of colour-matching. A rich and diverse set of naturally occurring insects visited the flowers while we continuously video-recorded the spider's foraging activity. This enabled us to test the crypsis, the spider avoidance and the flower visitor attraction hypotheses, all three supported by previous studies. Flower visitors of different groups either avoided crab spiders independent of colour-matching, such as solitary bees and syrphid flies, or ignored them, such as bumble-bees and honeybees. Moreover, colour-matched spiders did not have a higher encounter rate and capture success compared to the visually apparent ones. Thus, our results support the spider avoidance hypothesis, reject the two other hypotheses and uncovered a fourth behaviour: indifference to predators. Because flower visitors reacted differently, a community approach is mandatory in order to understand the function of background colour-matching in generalist predators. We discuss our results in relation to the size and sociality of the prey and in relation to the functional significance of colour change in this predator.
Personality matters: individual variation in reactions of naive bird predators to aposematic prey
Authors: Exnerová Alice , Svádová Kateřina Hotová , Fučíková Eva , Drent Pieter , Štys Pavel
Published: November 2009

Variation in reactions to aposematic prey is common among conspecific individuals of bird predators. It may result from different individual experience but it also exists among naive birds. This variation may possibly be explained by the effect of personality—a complex of correlated, heritable behavioural traits consistent across contexts. In the great tit (
Parus major
), two extreme personality types have been defined. ‘Fast’ explorers are bold, aggressive and routine-forming; ‘slow’ explorers are shy, non-aggressive and innovative. Influence of personality type on unlearned reaction to aposematic prey, rate of avoidance learning and memory were tested in naive, hand-reared great tits from two opposite lines selected for exploration (slow against fast). The birds were subjected to a sequence of trials in which they were offered aposematic adult firebugs (
Pyrrhocoris apterus
). Slow birds showed a greater degree of unlearned wariness and learned to avoid the firebugs faster than fast birds. Although birds of both personality types remembered their experience, slow birds were more cautious in the memory test. We conclude that not only different species but also populations of predators that differ in proportions of personality types may have different impacts on survival of aposematic insects under natural conditions.
Differential Sodium and Potassium Transport Selectivities of the Rice OsHKT2;1 and OsHKT2;2 Transporters in Plant Cells
Authors: Yao Xuan , Horie Tomoaki , Xue Shaowu , Leung Ho-Yin , Katsuhara Maki , Brodsky Dennis E. , Wu Yan , Schroeder Julian I.
Published: November 2009

Na+ and K+ homeostasis are crucial for plant growth and development. Two HKT transporter/channel classes have been characterized that mediate either Na+ transport or Na+ and K+ transport when expressed in Xenopus laevis oocytes and yeast. However, the Na+/K+ selectivities of the K+-permeable HKT transporters have not yet been studied in plant cells. One study expressing 5′ untranslated region-modified HKT constructs in yeast has questioned the relevance of cation selectivities found in heterologous systems for selectivity predictions in plant cells. Therefore, here we analyze two highly homologous rice (Oryza sativa) HKT transporters in plant cells, OsHKT2;1 and OsHKT2;2, that show differential K+ permeabilities in heterologous systems. Upon stable expression in cultured tobacco (Nicotiana tabacum) Bright-Yellow 2 cells, OsHKT2;1 mediated Na+ uptake, but little Rb+ uptake, consistent with earlier studies and new findings presented here in oocytes. In contrast, OsHKT2;2 mediated Na+-K+ cotransport in plant cells such that extracellular K+ stimulated OsHKT2;2-mediated Na+ influx and vice versa. Furthermore, at millimolar Na+ concentrations, OsHKT2;2 mediated Na+ influx into plant cells without adding extracellular K+. This study shows that the Na+/K+ selectivities of these HKT transporters in plant cells coincide closely with the selectivities in oocytes and yeast. In addition, the presence of external K+ and Ca2+ down-regulated OsHKT2;1-mediated Na+ influx in two plant systems, Bright-Yellow 2 cells and intact rice roots, and also in Xenopus oocytes. Moreover, OsHKT transporter selectivities in plant cells are shown to depend on the imposed cationic conditions, supporting the model that HKT transporters are multi-ion pores.
Clinical trial: oral colon‐release parnaparin sodium tablets (CB‐01‐05 MMX®) for active left‐sided ulcerative colitis
Authors: CELASCO G. , PAPA A. , JONES R. , MORO L. , BOZZELLA R. , SURACE M. M. , NACCARI G. C. , GASBARRINI G.
Published: November 2009

Aliment Pharmacol Ther 31, 375‐386

Background  The administration of parnaparin sodium as oral colon‐release tablets (CB‐01‐05 MMX®) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).

Aim  To assess the efficacy and the tolerability of 8 weeks’ oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable‐doses of oral aminosalicylates.

Methods  This multicenter, randomized, double‐blind proof of concept trial compared the efficacy of CB‐01‐05 MMX® 210 mg tablets to placebo in 141 subjects with mild to moderately active left‐sided UC treated with stable‐doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).

Results  A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB‐01‐05 MMX® group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).

Conclusions  CB‐01‐05 MMX® was safe and significantly effective in treating subjects with mild‐to‐moderate left‐sided UC treated with stable‐doses of aminosalicylates.
Systematic review: molecular chemoprevention of colorectal malignancy by mesalazine
Authors: LYAKHOVICH A. , GASCHE C.
Published: November 2009

Background  Mesalazine (mesalamine) (5‐ASA) is considered an anti‐inflammatory drug for the treatment of inflammatory bowel disease. It is well tolerated by most patients and induces mucosal healing specifically in ulcerative colitis. Besides its anti‐inflammatory properties, 5‐ASA has been studied for cancer inhibitory activities as it seems to reduce colorectal cancer incidence in patients using this drug for long periods of time. However, detailed molecular mechanisms of drug action are vague.

Aims  To evaluate known molecular mechanisms of 5‐ASA on chemoprevention of colorectal malignancy.

Methods  Systematic review with search terms ‘5 aminosalicylic acid, mesalazine, 5‐ASA, mesalazine, molecular mechanisms, chemoprevention’ between 2006 and August 2009.

Results  A total of 48 studies were retrieved that link 5‐ASA chemopreventive properties to five distinct pathways. These include interference with cell cycle progression (12 references), scavenging of reactive oxygen‐ or nitrogen‐derived metabolites (16 references), TNF‐α/TGF‐ß signalling (11 references), WNT/β‐catenin signalling (5 references) and anti‐bacterial properties (4 references).

Conclusions  In the recent years, a large amount of molecular data has accumulated supporting the notion that 5‐ASA biological effects interfere with colorectal cancer development. These molecular pathways are of special interest in the search for 5‐ASA’s molecular target(s) and development of novel chemopreventive compounds.

Aliment Pharmacol Ther 31, 202–209
The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma
Authors: Petersen Astrid H. , Korsatko Stefan , Köhler Gerd , Wutte Andrea , Olschewski Horst , Sparre Thomas , Råstam Jacob , Wollmer Per , Pieber Thomas R.
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects.

• In people with moderate asthma, the administration of a bronchodilator before inhalation of insulin has been shown to lead to increased uptake of inhaled insulin compared with no prior administration of bronchodilator.

WHAT THIS STUDY ADDS

• This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin.

• This study illustrates that due to the effect of terbutaline on glucose metabolism, the effect of insulin on plasma glucose is complex when terbutaline is administered concomitantly.

AIM To investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids.

METHODS A single‐centre, randomized, open‐label, two‐period cross‐over trial was carried out in 41 nondiabetic subjects with asthma treated with inhaled steroids, with reversible bronchoconstriction (Rev+; n= 25) or without reversible bronchoconstriction (Rev−; n= 16). A dose of 0.10 U kg−1 inhaled human insulin was administered on each dosing day with or without prior administration of the bronchodilator terbutaline (in random order).

RESULTS Prior administration of terbutaline led to a 44% increase in absorption of insulin over 6 h for the Rev+ group compared with no prior administration of bronchodilator [ratio (95% confidence interval) 1.44 (1.13, 1.82), P= 0.004], whereas no effect was seen for the Rev− or the whole group. The maximum insulin concentration (Cmax) increased by 34% for the Rev+ group (P = 0.018) and 17% for the whole group (P= 0.046), whereas no significant effect of prior terbutaline administration was seen for Rev−. The time to Cmax was not significantly different for the Rev+ group, whereas it was approximately 30% longer after bronchodilator administration for the Rev− group (P= 0.044) and the whole group (P= 0.032).

CONCLUSIONS In people with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin led to increased absorption of insulin, whereas no effect on insulin absorption in subjects without significant reversibility could be detected.
Pravastatin administration does not induce detrimental effects on hemodynamics and collaterals of portal hypertensive rats
Authors: Chang Ching‐Chih , Wang Sun‐Sang , Huang Hui‐Chun , Lee Jing‐Yi , Lee Fa‐Yauh , Lin Han‐Chieh , Lee Shou‐Dong
Published: November 2009

Background and Aims:  The 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor can enhance endothelial nitric oxide synthase expression and induce vasodilatation. The vasodilatory effect may be detrimental to portal‐systemic collaterals due to aggravating the shunting degrees. The present study investigated the effects of pravastatin, a HMG‐CoA reductase inhibitor, on the collateral vascular responsiveness to endothelin‐1 (ET‐1) and portal‐systemic shunting in portal hypertensive rats.

Methods:  The partial portal vein‐ligated (PVL) rats received either pravastatin (25 mg/kg per day) or distilled water since 2 days prior to until 7 days after ligation. On the 8th day following hemodynamic measurements, the collateral vascular responsiveness to ET‐1 was evaluated by an in situ collateral perfusion model. The shunting degrees of collaterals were evaluated by constructing vascular flow‐pressure curves and color microsphere study, respectively. PVL rats underwent pre‐incubation with: (i) Krebs solution (control); or Krebs solution plus (ii) 2 × 10−5 M pravastatin; (iii) pravastatin + Nω‐nitro‐L‐arginine (10−4 M); and (iv) pravastatin + indomethacin (10−5 M), followed by ET‐1 (10−10–10−7 M) administration to evaluate the collateral vascular responsiveness.

Results:  In chronic study, pravastatin did not modify systemic and portal hemodynamics and collateral vascular responsiveness to ET‐1. The resistances of flow‐pressure curves and the microsphere study demonstrated similar shunting degrees between both groups. Furthermore, pravastatin pre‐incubation didn't reduce collateral perfusion pressure to ET‐1.

Conclusion:  Chronic pravastatin administration does not induce detrimental effects on hemodynamics and collaterals in PVL rats, nor does it influence the shunting degree. In addition, it does not modify the vasoconstrictive effect of ET‐1 on the collaterals of PVL rats.
Can acid (pH) refluxes predict multichannel intraluminal impedance refluxes? A correlation study
Authors: Misra Sudipta
Published: November 2009

Background and Aim:  The present study aims to explore if and when acid (pH) refluxes can predict refluxes detected by multichannel intraluminal impedance (MII) studies. This correlation may indicate whether pH probe‐only and MII‐pH studies are interchangeable.

Methods:  Prospective observational cross sectional study of symptomatic children (below 18 years) who had MII‐pH studies done for gastroesophageal reflux. Clinical data were extracted from patient records. Non‐parametric tests, Pearson's ρ and receiver operating characteristic (ROC) curves were used for data analysis.

Results:  A total of 153 children were included in the study and 62% were on acid suppression. Indices for acid and MII refluxes correlated with each other only in those without acid suppression. This correlation was lost in children on acid suppression. There was no statistically significant difference in acid or MII reflux indices in children with or without acid suppression. Like acid reflux, indices for MII refluxes had good correlation with each other irrespective of acid suppression. Liquid and mixed MII refluxes showed excellent correlation with respective types of proximally migrating refluxes. The values for MII reflux indices derived from our patient population were in broad agreement with available pediatric and adult data.

Conclusions:  A pH probe‐only study in patients without acid suppression may reflect both acid and volume (MII) reflux activities adequately and can substitute for MII‐pH study. The observed excellent correlation between acid and MII refluxes with proximal migration may justify using pH probe‐only studies for extra esophageal symptoms in patients without acid suppression.
LIMITS TO COMPETITION AND REGULATION IN PRIVATIZED ELECTRICITY MARKETS
Authors: Dagdeviren Hulya
Published: November 2009

ABSTRACT**:  Privatization of electricity has been extensive both in the developed and the developing world. Failures in various areas have led to the emergence of a new consensus which regards competitive pressures and regulation as crucial for utility privatizations to work. This review paper presents a critical evaluation of this newly found wisdom with reference to the developing economies. The experience in the developed world, especially in the USA and the UK, has been used to draw conclusions for the developing economies. Overall, the paper highlights the problems associated with the ‘competitive model’ both in the developed and developing world and points to the potential instability in private competitive power supply systems. It also examines the degree to which regulation can be a panacea for market failures and structural problems under private provision.
Effects of a 2‐year school‐based daily physical activity intervention on cardiorespiratory fitness: the Sogndal school‐intervention study
Authors: Resaland G. K. , Andersen L. B. , Mamen A. , Anderssen S. A.
Published: November 2009

The aim of this study was to describe changes in children's cardiorespiratory fitness (CRF) following a school‐based physical activity (PA) intervention. In total, 259 children (age 9.3±0.3 years) were invited to participate, of whom 256 participated. The children from the intervention school (63 boys, 62 girls) carried out 60‐min PA over 2 school years. The children from the control school (62 boys, 69 girls) had the regular curriculum‐defined amount of physical education in school, i.e. 45 min twice weekly. One hundred and eighty‐eight children (73.4%) successfully completed both the baseline and the post‐intervention peak oxygen uptake (VO2peak) test. VO2peak was measured directly during a continuous progressive treadmill protocol where the children ran until exhaustion. The children from the intervention school increased their mean VO2peak (95% confidence interval) 3.6 (2.5–4.6) mL/kg/min more than the children from the control school. This VO2peak value was adjusted for both sex and baseline VO2peak. Boys and girls demonstrated similar VO2peak responses. The intervention, primarily carried out at a moderate intensity, had the biggest impact in children with low initial CRF levels. In conclusion, a 2‐year school‐based 60‐min daily PA intervention significantly improved CRF in children.
Reducing Reactive Aggression by Lowering Coping Demands and Boosting Regulation: Five Key Staff Behaviors
Authors: Delaney Kathleen R.
Published: November 2009

TOPIC:  Lowering the incidence of reactive aggression on inpatient child/adolescent psychiatric units by creating a milieu that reduces coping demands and augments children's self‐ regulation capabilities.

PURPOSE:  This article elaborates on specific staff approaches that have the potential to reduce occurrences of reactive aggression and behavioral eruptions frequently displayed by children and adolescents during inpatient psychiatric treatment. Identified are key staff behaviors along with explanations on how they dampen the kindling of reactive aggression and create an enhanced milieu. Accompanying each staff behavior is an explanation of the neuroscience and theory that supports the intervention.

SOURCES:  Published literature and clinical examples.

CONCLUSIONS:  Children hospitalized on inpatient psychiatric units frequently have poor self‐regulation skills and diffuse the negative affects they experience via behaviors such as tantrums, venting, and aggression. Staff can reduce this reactive aggression by tempering the way they set expectations, by providing structure, and by decreasing threat via sensible rules that encourage choice. Staff must also create and maintain relationships with the patients that set a particular tone, thereby creating an enhanced milieu populated with adults who are positive and able to attune to a child's changing affect level.
Structural Analysis of DFG‐in and DFG‐out Dual Src‐Abl Inhibitors Sharing a Common Vinyl Purine Template
Authors: Zhou Tianjun , Commodore Lois , Huang Wei‐Sheng , Wang Yihan , Sawyer Tomi K. , Shakespeare William C. , Clackson Tim , Zhu Xiaotian , Dalgarno David C.
Published: November 2009

Bcr‐Abl is the oncogenic protein tyrosine kinase responsible for chronic myeloid leukemia (CML). Treatment of the disease with imatinib (Gleevec) often results in drug resistance via kinase mutations at the advanced phases of the disease, which has necessitated the development of new mutation‐resistant inhibitors, notably against the T315I gatekeeper mutation. As part of our efforts to discover such mutation resistant Abl inhibitors, we have focused on optimizing purine template kinase inhibitors, leading to the discovery of potent DFG‐in and DFG‐out series of Abl inhibitors that are also potent Src inhibitors. Here we present crystal structures of Abl bound by two such inhibitors, based on a common N9‐arenyl purine, and that represent both DFG‐in and ‐out binding modes. In each structure the purine template is bound deeply in the adenine pocket and the novel vinyl linker forms a non‐classical hydrogen bond to the gatekeeper residue, Thr315. Specific template substitutions promote either a DFG‐in or ‐out binding mode, with the kinase binding site adjusting to optimize molecular recognition. Bcr‐Abl T315I mutant kinase is resistant to all currently marketed Abl inhibitors, and is the focus of intense drug discovery efforts. Notably, our DFG‐out inhibitor, AP24163, exhibits modest activity against this mutant, illustrating that this kinase mutant can be inhibited by DFG‐out class inhibitors. Furthermore our DFG‐out inhibitor exhibits dual Src‐Abl activity, absent from the prototypical DFG‐out inhibitor, imatinib as well as its analog, nilotinib. The data presented here provides structural guidance for the further design of novel potent DFG‐out class inhibitors against Src, Abl and Abl T315I mutant kinases.
Substance P and CGRP expression in dental pulps with irreversible pulpitis
Authors: Sattari Mandana , Mozayeni Mohammad Ali , Matloob Arash , Mozayeni Maryam , Javaheri Homan H.
Published: November 2009

The purpose of this study was to compare substance P (SP) and calcitonin gene‐related peptide (CGRP) expression in pulp tissue with clinically diagnosed symptomatic and asymptomatic irreversible pulpitis. Healthy pulps acted as controls. Five normal pulps and 40 with irreversible pulpitis (20 symptomatic and 20 asymptomatic) were obtained from 45 different patients. SP and CGRP expression was determined by competition binding assays using enzyme immunoassay. anova and Mann–Whitney tests were used to ascertain if there were statistically significant differences between the groups. The results showed that neuropeptides were found in all pulp samples. The highest and the lowest expressions for SP and CGRP were found in symptomatic irreversible pulpitis and healthy pulps groups, respectively. The differences between healthy pulps and the groups of pulps having irreversible pulpitis were significant (P < 0.001). Although Mann–Whitney's post‐hoc tests showed statistically significant differences in CGRP expression between two pulpitis groups (P < 0.05), differences in SP expression between symptomatic and asymptomatic irreversible pulpitis groups were not significant. This study demonstrated that the expression of CGRP and SP is significantly higher in pulps with irreversible pulpitis compared with healthy pulps.
Prevalence of Electrocardiographic Abnormalities in a Systolic Heart Failure Disease Management Population by Race, Ethnicity, and Sex
Authors: Hebert Kathy , Lopez Barbara , Dias Andre , Steen Dylan L. , Colombo Rosario A. , Franco Emiliana , Neistein Sholom , Arcement Lee M.
Published: November 2009

Congest Heart Fail. 2010;16:21–26. ©2009 Wiley Periodicals, Inc.

The prevalence of electrocardiographic (ECG) abnormalities in systolic heart failure patients have predominantly been described in white patients, with relatively little known about their prevalence in black and Hispanic populations. The purpose of this study is to compare the prevalence of ECG abnormalities by race, ethnicity, and sex. The authors conducted an observational prospective study that included 926 patients from 2 hospital facilities. A systolic heart failure disease management program implemented in both sites enrolled patients with an ejection fraction 40% by echocardiography. Black patients had less evidence of myocardial infarction than whites and Hispanics. Black patients had more evidence of left ventricular hypertrophy than Hispanics and whites. Hispanics evidenced more ischemic changes than blacks and whites. Among black patients, left ventricular hypertrophy was more prevalent in women. ECG abnormalities vary across race, ethnicity, and sex. These variations may have implications for further diagnostic testing and potential treatment regimens.
Local economic impact of different forms of nature‐based tourism
Authors: Sandbrook Chris. G.
Published: November 2009

Tourism has been widely used as a component of conservation interventions which are intended to deliver benefits to local people, thereby contributing to development and creating incentives for conservation. However, a large proportion of total tourist revenue can be lost from the local area as leakage. Nature‐based tourism is diverse and little is known about how locally retained revenue varies across different forms of tourism; this is information of great importance to policy makers. This article uses data from tourist interviews and local enterprise surveys to measure the total and locally retained spending from different forms of tourism at Bwindi Impenetrable National Park, Uganda. Whilst total spending increased with higher cost forms of tourism and length of stay, retained spending was predicted only by length of stay. High‐cost tourism may therefore be no more effective than other forms of tourism as a tool for generating local benefits from conservation.
Study of low temperature growth of III-V alloys for transparent layers
Authors: Wu L. , Iyer S. , Li J. , Gibson K. , Reppert J. , Rao A. M. , Matney K. , Lewis J.
Published: November 2009

The authors report on the successful growth of wide band gap III-V alloy systems on glass substrates at low growth temperatures that may be suitably exploited for the realization of novel high performance and stable optoelectronic devices. A systematic investigation on the growth of GaAs, GaAlAs(N), and AlAs(N) at low temperatures (<300°C) on various substrates has been carried out to determine the effects of constituent elements of the alloy and the growth process parameters on the surface morphology and structural and optical properties of the materials. Optimized growth conditions were thus established for the successful growth of GaAlAsN polycrystalline layers with an average transmission of 80% in the visible region, with optical absorption energy >3.0eV. The surface exhibited meandering cracks, with root mean square roughness of about 1nm in the smooth areas between the cracks. Peaks observed in the x-ray diffraction and Raman spectra of these layers were relatively sharp in comparison to the other unoptimized quaternary layers, clearly attesting to the better quality of these layers. In addition, these layers exhibit preferential Al–N bond formation as evidenced in the corresponding Raman spectra.
Tetracyclines That Promote
SMN2
Exon 7 Splicing as Therapeutics for Spinal Muscular Atrophy
Authors: Hastings Michelle L. , Berniac Joel , Liu Ying Hsiu , Abato Paul , Jodelka Francine M. , Barthel Lea , Kumar Sujatha , Dudley Caroline , Nelson Mark , Larson Kelley , Edmonds Jason , Bowser Todd , Draper Michael , Higgins Paul , Krainer Adrian R.
Published: November 2009

Tetracycline derivatives increase exon 7 splicing during RNA processing of the spinal muscular atrophy–modifying gene
SMN2
, which may prove therapeutically useful.
Use of a Baculovirus-Expressed Structural Protein for the Detection of Antibodies to Foot-and-Mouth Disease Virus Type A by a Blocking Enzyme-Linked Immunosorbent Assay
Authors: Ko Young-Joon , Lee Hyang-Sim , Jeoung Hye-Young , Heo Eun-Jeong , Ko Hyo-Rim , Chang Byung-Sik , Joo Hoo-Don , Gerelmaa U. , Dashzeveg B. , Tserendorj S. , Sodnomdarjaa R. , Park Jong-Hyeon , Kweon Chang-Hee , Cho In-Soo , Paik Sang-Gi
Published: November 2009

A blocking enzyme-linked immunosorbent assay (ELISA) with a baculovirus-expressed structural protein was developed for the detection of antibodies to foot-and-mouth disease virus type A. It exhibited 99% specificity with a cutoff of 53% inhibition. Its sensitivity was comparable to the sensitivities of the virus neutralization test and the liquid-phase blocking ELISA, indicating its potential as an alternative assay.