bluuebunny/crossref_metadata_2025 huggingface dataset:
A season‐ and gap‐detection mechanism regulates seed germination of two temperate forest pioneers
Authors: Vranckx G. , Vandelook F.
Published: December 2011

The survival of seedlings in temperate climate habitats depends on both temporal and spatial factors. The interaction between an internal seed dormancy mechanism and the ruling environmental conditions allows accurate cueing of germination. We analysed how environmental signals interact in seeds of temperate forest pioneer species, increasing the seed’s chances of germinating in the right place at the right time. Digitalis purpurea and Scrophularia nodosa are two small‐seeded herbaceous species that typically grow in vegetation gaps in European temperate forests. Seeds of both species are partially dormant at the time of dispersal in summer. This primary dormancy is released in autumn and early winter, resulting in a minimal level of physiological dormancy by late winter and early spring. We observed that physiological dormancy was induced again in seeds exhumed in late spring and in summer. Experiments in laboratory conditions revealed that primary dormancy in seeds of S  nodosa was broken by cold stratification, whereas primary dormancy in D. purpurea seeds was broken by both a cold and a warm stratification. The two species differed in their response to the tested gap‐detection signals, as light was the most important factor stimulating germination of D. purpurea, and seeds of S. nodosa germinated best when subjected to daily fluctuating temperatures. This study clearly indicates that the ability to germinate in response to gap‐detection signals changes seasonally in temperate forest pioneers. Additionally, seeds of both species responded differently to these environmental signals, probably reflecting differences in the regeneration niche.
Cytogenetic and phylogenetic studies of diploid and polyploid members of Tribe Anemoninae (Ranunculaceae)
Authors: Mlinarec J. , Šatović Z. , Mihelj D. , Malenica N. , Besendorfer V.
Published: December 2011

The ancestry, phylogenetic differentiation and systematic classification of the worldwide‐distributed genus Anemone have been debated for many years. In this paper 11 Anemone, three Pulsatilla species and Hepatica nobilis were subjected to detailed karyotype analysis with the aim of obtaining new cytogenetic data that will contribute to karyotype evolutionary studies of the tribe Anemoninae. The results are interpreted in a phylogenetic context, established from the intergenic nontranscribed spacer (NTS) of 5S rDNA and internal transcribed spacer (ITS) of 35S rDNA. One to three 35S and one to three 5S rDNA loci are present in diploid and polyploid taxa. The 35S rDNA loci are located terminally on the short arm of acrocentric chromosomes, while for 5S rDNA there is no preferential chromosomal position as it exhibits terminal, subterminal, interstitial or pericentromeric positions, and is located either on acrocentric or metacentric chromosomes. The karyotype of hexaploid A. baldensis (2n = 6x = 48) is presented for the first time, and A. sylvestris is proposed as one of its putative parental species. Chromosome fusion/translocation is proposed as the key mechanism involved in reduction of the basic chromosome number from 8 in the Anemone subgenus to 7 in the Anemonidium subgenus. The cytogenetic data obtained are mainly supported by ITS and NTS phylogeny. Diversification of the genus Anemone was accompanied by a large reduction of heterochromatin, from the Mediterranean anemones that have large amounts of heterochromatin to the New World anemones without any detectable heterochromatic blocks.
Photosynthesis, water use efficiency and stable carbon isotope composition are associated with anatomical properties of leaf and xylem in six poplar species
Authors: Cao X. , Jia J. B. , Li H. , Li M. C. , Luo J. , Liang Z. S. , Liu T. X. , Liu W. G. , Peng C. H. , Luo Z. B.
Published: December 2011

Although fast‐growing Populus species consume a large amount of water for biomass production, there are considerable variations in water use efficiency (WUE) across different poplar species. To compare differences in growth, WUE and anatomical properties of leaf and xylem and to examine the relationship between photosynthesis/WUE and anatomical properties of leaf and xylem, cuttings of six poplar species were grown in a botanical garden. The growth performance, photosynthesis, intrinsic WUE (WUEi), stable carbon isotope composition (δ13C) and anatomical properties of leaf and xylem were analysed in these poplar plants. Significant differences were found in growth, photosynthesis, WUEi and anatomical properties among the examined species. Populus cathayana was the clone with the fastest growth and the lowest WUEi/δ13C, whereas P. × euramericana had a considerable growth increment and the highest WUEi/δ13C. Among the analysed poplar species, the highest total stomatal density in P. cathayana was correlated with its highest stomatal conductance (gs) and lowest WUEi/δ13C. Moreover, significant correlations were observed between WUEi and abaxial stomatal density and stem vessel lumen area. These data suggest that photosynthesis, WUEi and δ13C are associated with leaf and xylem anatomy and there are tradeoffs between growth and WUEi. It is anticipated that some poplar species, e.g. P. × euramericana, are better candidates for water‐limited regions and others, e.g. P. cathayana, may be better for water‐abundant areas.
Pathogenicity of Phytophthora multivora to Eucalyptus gomphocephala and Eucalyptus marginata
Authors: Scott P. M. , Jung T. , Shearer B. L. , Barber P. A. , Calver M. , Hardy G. E. St. J.
Published: December 2011

Phytophthora multivora is associated with the rhizosphere of declining Eucalyptus gomphocephala, Eucalyptus marginata and Agonis flexuosa. Two pathogenicity experiments were conducted. The first experiment examined the pathogenicity of five P. multivora isolates and one Phytophthora cinnamomi isolate on the root systems of E. gomphocephala and one P. multivora isolate on the root system of E. marginata. In the second experiment, the pathogenicity of P. multivora to E. gomphocephala and E. marginata saplings was measured using under‐bark stem inoculation. In Experiment 1, the P. cinnamomi isolate was more aggressive than all P. multivora isolates causing significant loss of fine roots and plant death. Two P. multivora isolates and the P. cinnamomi isolate caused significant losses of E. gomphocephala fine roots 0–2 mm in diameter and significantly reduced the surface area of roots 0–1 mm in diameter. One P. multivora and the P. cinnamomi isolate significantly reduced the surface area of roots 1–2 mm in diameter. Two of the P. multivora isolates significantly reduced the number of E. gomphocephala root tips. In E. marginata, the length and surface area of roots 0–1 mm in diameter and number of root tips were significantly reduced by P. multivora infestation. Rhizosphere infestation with the P. multivora isolates and P. cinnamomi isolate on E. gomphocephala, and one P. multivora isolate on E. marginata, did not significantly influence the foliar nutrient concentrations. In Experiment 2, under‐bark inoculation with P. multivora caused significant lesion extension in E. gomphocephala and E. marginata saplings, compared to the control. We propose that P. multivora is inciting E. gomphocephala and E. marginata decline by causing fine root loss and subsequently interfering with nutrient cycling throughout the plant. The impact of fine root loss on the physiology of plants in sites infested with P. multivora requires further research.
Effect of pre‐partum supplementation of vitamin E to Murrah buffaloes on immune functions and viability of calves
Authors: Singh A. K. , Pandita S. , Pampoori Z. A. , Huozha R. , Ashutosh M.
Published: December 2011

This study was undertaken in buffalo neonates born to vitamin E (dl‐alpha‐tocopherol acetate)‐supplemented and non‐supplemented Murrah buffaloes. Calves from vitamin E‐supplemented buffaloes (n = 10; vitamin E ‐supplemented calves [VeC]) and non‐supplemented buffaloes (n = 10; control calves [CC]) constituted the treatment and control groups respectively. Two colostrum samples were taken at the first post‐partum milking and again after 12 h from dams for IgG estimation. Sampling of blood was performed on days 0 (before colostrum feeding), 1, 3, 7, 14, 21, 28, 42, 56, 70, 84, 98, 112 and 126 post‐birth and analysed for apparent efficiency of absorption (%) of IgG and various immune parameters. Colostral IgG level was significantly higher (p < 0.05) in vitamin E‐supplemented buffaloes. The calves in both groups were born hypogammaglobulinemic with IgG level <5 g/l. However, first colostrum feeding resulted in significantly elevated IgG levels (>10 g/l) in calves of both groups at 24 h, which remained high afterwards. Apparent efficiency of absorption (%) of IgG at 24 h was significantly higher (p < 0.05) in VeC than in CC. Plasma Nitric Oxide (NO) levels were significantly elevated in the calves of either group at birth, which declined significantly (p < 0.01) afterwards. Vitamin E feeding to dams had no added effect on NO levels in experimental calves. Total leucocyte counts did not differ significantly between the two groups. However, lymphocyte and neutrophil counts changed significantly between groups (p < 0.01) and days (p < 0.01), with lymphocytes increasing and neutrophils declining with age. This study revealed that the calves were immunologically immature at birth. Ante‐partum supplementation of vitamin E did not influence plasma NO or IgG but had a significant effect on colostral IgG (p < 0.05). It also improved the apparent efficiency of absorption (%) of IgG at 24 h in VeC as compared to CC.
Relationship between non‐alcoholic fatty liver disease and pulmonary function
Authors: Jung D.‐H. , Shim J.‐Y. , Lee H.‐R. , Moon B.‐S. , Park B.‐J. , Lee Y.‐J.
Published: December 2011

Background:  It has been observed that non‐alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease and insulin resistance. Pulmonary function is also known to be related with cardiovascular disease and metabolic syndrome.

Aims:  The objective of this study was to investigate the association between NAFLD and pulmonary function.

Methods:  We performed a cross‐sectional study to examine the association of NAFLD based on abdominal sonographic findings and pulmonary function in 2119 Korean men between the ages of 30 and 75. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were compared according to the presence of NAFLD. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship of NAFLD with FVC and FEV1 as pulmonary function tests.

Results:  The subjects with NAFLD had lower FVC and FEV1 than their non‐steatotic counterparts, and FVC and FEV1 gradually decreased according to the grade of hepatic steatosis. After adjusting for age, body mass index, smoking status, blood pressure, fasting plasma glucose, total cholesterol, hypertension, diabetes, triglyceride and high‐density lipoprotein cholesterol, the FVC and FEV1 were found to be inversely associated with the presence of NAFLD.

Conclusion:  NAFLD was independently associated with reduced pulmonary function, and the severity of NAFLD was inversely correlated with pulmonary function.
Production, size, and germination of broad‐leaved dock seeds collected from mother plants grown under different nitrogen, phosphorus, and potassium supplies
Authors: HRDLIČKOVÁ JANA , HEJCMAN MICHAL , KŘIŠŤÁLOVÁ VERONIKA , PAVLŮ VILÉM
Published: December 2011

Rumex obtusifolius is believed to be a nitrophilous weedy species that spreads mainly by seed. However, the effects of nutrient availability on seed production never have been investigated. In this study, how the amount of seed production per plant, the chemical composition of the seeds, and their size and germination are affected by the supply of N, P, and K was investigated. A pot fertilizer experiment with 10 treatments (combinations of 0, 150 [N1], and 300 [N2] kg N ha−1, 0, 40 [P1], and 80 [P2] kg P ha−1, and 0 and 100 [K] kg K ha−1 applied twice per vegetation season) was carried out in Prague, Czech Republic, in 2008 and 2009. The seeds from plants that were cultivated since the spring were collected each August. The germination of the seeds was determined in long‐daylight conditions at a stable temperature of 20°C. The number of seeds per plant ranged from 0 in the P1 and P2 treatments and <200 in the control and K treatments to almost 9000 in the N2P2K treatment. The number of seeds per plant was positively correlated with the number of stems per plant and the number of seeds per stem. The relationship between the amount of seeds per plant and the individual seed weight was positive. The concentration of N, P, and K in the seeds was affected by the treatments. The weight of 1000 seeds ranged from 1.3 to 1.7 g. The seed length ranged from 2.11 to 2.34 mm and the seed width varied from 1.26 to 1.42 mm. With the exception of the control (with 94% germination), the amount of seed germination was >98% in all the other treatments in 2008. In 2009, the amount of seed germination was >95% in all the treatments, except N1 and N2, where 93% and 89% germination, respectively, was recorded. The germination rate was positively related to the P concentration in the seeds. The amount of time that was necessary for 50% seed germination ranged from 1.53 to 2.89 days and was not related to the N concentration in the seeds, but it was negatively related to the P and K concentrations. A balanced N, P, and K supply to the mother plant strongly affected the number of produced seeds and their chemical composition and germination ability.
Analysis of the seed dispersal patterns of wild soybean as a reference for vegetation management around genetically modified soybean fields
Authors: YOSHIMURA YASUYUKI , MIZUGUTI AKI , MATSUO KAZUHITO
Published: December 2011

There are concerns that genetically modified soybean might threaten the genetic diversity of the wild soybean populations that are distributed in East Asia because genetically modified soybean has no crossing barrier with wild soybean. A simple and effective method to prevent hybridization via pollen flow is spatial separation between the two species because their hybridization occurs only when they grow in close proximity. Therefore, the invasiveness of wild soybean needs to be known in order to secure the appropriate distances. As wild soybean seeds are dispersed mechanically by pod dehiscence, an experiment was conducted in which white sheets were placed on the ground, concentric circles were drawn around the parent plants, and the number of dispersed seeds within each 0.5 m‐wide zone were counted. About 40% of the produced seeds were dispersed and the number of dispersed seeds gradually declined as the distance from the parent plants increased. The model that explained the relationship between the number and distance of the dispersed seeds was produced by using a generalized linear model procedure. More than 95, 99, and 99.9% of the produced seeds stayed within 3.5, 5.0, and 6.5 m after natural pod dehiscence. Knowing these values is useful for evaluating the level of invasive risk by mechanical seed dispersal. The goal of the work is to efficiently and deliberately prevent hybridization by isolating genetically modified soybean fields and wild soybean populations by vegetation management, including weeding and setting up specific‐width buffer zones.
Graphic Symbols as “The Mind on Paper”: Links Between Children’s Interpretive Theory of Mind and Symbol Understanding
Authors: Myers Lauren J. , Liben Lynn S.
Published: December 2011

Children gradually develop interpretive theory of mind (iToM)—the understanding that different people may interpret identical events or stimuli differently. The present study tested whether more advanced iToM underlies children’s recognition that map symbols’ meanings must be communicated to others when symbols are iconic (resemble their referents). Children (6–9 years;N = 80) made maps using either iconic or abstract symbols. After accounting for age, intelligence, vocabulary, and memory, iToM predicted children’s success in communicating symbols’ meaning to a naïve map‐user when mapping tasks involved iconic (but not abstract) symbols. Findings suggest children’s growing appreciation of alternative representations and of the intentional assignment of meaning, and support the contention that ToM progresses beyond mastery of false belief.
Wittgenstein on Grammar, Theses and Dogmatism
Authors: Hacker Peter M. S.
Published: December 2011

It is sometimes argued that Wittgenstein's conception of grammar and the role he allocated to grammar (in his sense of the term) in philosophy changed between the Big Typescript and the Philosophical Investigations. It is also held that some of the grammatical propositions Wittgenstein asserted prior to his writing of the Philosophical Investigations are theses, doctrines, opinions or dogmatism, which he abandoned by 1936/37. The purpose of this paper is to show these claims to be misunderstandings and misinterpretations. On all important matters, his conception of grammar and of grammatical investigations, of grammatical statements or propositions and of grammatical clarification did not change between the Big Typescript and the Investigations. Grammatical propositions (e.g. the meaning of a word is its use; a sample in an ostensive definition belongs to the means of representation; belief is not a mental state) are no more theses, doctrines or opinions than is “a bachelor is an unmarried man.” Nor are they in any way dogmatic.
Building on Forest Governance Reforms through FLEGT: The Best Way of Controlling Forests' Contribution to Climate Change?
Authors: Dooley Kate , Ozinga Saskia
Published: December 2011

Illegal logging is a major problem in the forestry sector, and legislation to combat it has recently been introduced in both the United States and the European Union (EU) – two of the world's largest importers of timber. Non‐governmental organizations (NGOs) and the timber industry have urged governments to use trade incentives to control illegalities, and this has been instrumental in the development of these laws. The Lacey Act, an American conservation law revised in 2008 to include illegal timber, requires businesses to demonstrate that their purchasing policies and mechanisms effectively avoid sourcing timber from illegal sources. Because tackling the problem depends on cooperation between importing and exporting countries, the EU has been working since 2002 on a comprehensive plan to control illegal timber imports: the EU Action Plan for Forest Law Enforcement, Governance and Trade (FLEGT). This Action Plan has led to new legislation to control illegal timber imports and help timber‐producing countries to improve forest governance. It is hoped that in this way FLEGT will also contribute to keeping forests standing, thereby mitigating climate change. However, it is feared that World Bank and United Nations initiatives on Reduced Emissions from Deforestation and Forest Degradation (REDD) may undermine the FLEGT initiative if they do not recognize the need to begin with forest governance reforms.
Excluding Coexistence of GMOs? The Impact of the EU Commission's 2010 Recommendation on Coexistence
Authors: Dobbs Mary
Published: December 2011

In the midst of the European Union (EU) genetically modified organisms (GMOs) regime, coexistence of GM and non‐GM crops alongside each other remains technically within the competence of the Member States. Post EU authorization of a GM crop, Member States may legally take appropriate measures to limit or prevent the presence of GMOs within non‐GM crops. In July 2010, as part of a Cultivation Package, the Commission created a new Coexistence Recommendation that supports a flexible approach to more stringent coexistence measures by the States, while attempting to maintain control over the legitimate objectives justifying the measures. This article analyzes the impact of the 2010 Recommendation upon coexistence in the context of the existing practices and the previous 2003 Recommendation, taking into account its status as a soft law document and the ‘domino effect’. It is argued that the 2010 Recommendation may have greater practical and legal ramifications for coexistence than might first be thought. In attempting to create guidelines that allow a more flexible and inclusive approach towards national measures, the 2010 Recommendation may act as a catalyst to eventually exclude GM cultivation within Member States.
The International Regime for the Compensation of Oil‐pollution Damage: A Good Candidate to Have a Human Rights Law Approach?
Authors: Gouritin Armelle
Published: December 2011

Questions such as who is to be held liable for oil‐spill damage, under which conditions and for which type of damage are currently highly debated and discussed by legal scholars and before national, European and international courts. While European Commission (EC) regulators have questioned the international civil liability regime for oil spills, some victims of harm caused by spills have been willing to circumvent the international regime in order to have national general rules of criminal law or the transposition of EC waste legislation applied. Noting the growing academic work on international liability mechanisms, and particularly the critical appraisal of the international regime, this article takes a different approach. It analyzes the compatibility of the international liability regime with the requirements of the European Convention on Human Rights. Does the liability scheme set by the international regime fulfill the human rights requirements of the European Convention for the Protection of Human Rights and Fundamental Freedoms and the European Court of Human Rights' caselaw? This article finds that it may not.
Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild‐to‐moderate toenail onychomycosis: results from three randomized studies using double‐blind vehicle‐controlled and open‐label active‐controlled designs
Authors: Elewski B.E. , Ghannoum M.A. , Mayser P. , Gupta A.K. , Korting H.‐C. , Shouey R.J. , Baker D.R. , Rich P.A. , Ling M. , Hugot S. , Damaj B. , Nyirady J. , Thangavelu K. , Notter M. , Parneix‐Spake A. , Sigurgeirsson B.
Published: December 2011

Background  Terbinafine nail solution (TNS) was developed for the treatment of onychomycosis.

Objective  To assess the efficacy of TNS vs. vehicle and amorolfine 5% nail lacquer.

Methods  Subjects with mild‐to‐moderate toe onychomycosis (25% to ≤75% nail‐involvement, matrix uninvolved) were randomized to receive either TNS or vehicle in two double‐blind studies, and to TNS or amorolfine in an active‐controlled, open‐label study. Primary endpoint was complete cure (no residual clinical involvement and negative mycology) at week 52. Secondary endpoints were mycological cure (negative mycology defined as negative KOH microscopy and negative culture) and clinical effectiveness (≤10% residual‐involvement and negative mycology) at week 52.

Results  Complete cure was not different between TNS vs. vehicle and amorolfine. Mycological cure was higher with TNS vs. vehicle, as was clinical effectiveness with TNS vs. vehicle, and TNS and amorolfine were not different for secondary efficacy endpoints. Patients achieving mycological cure had a better clinical outcome, and efficacy was improved in subjects with milder disease. Post hoc analysis suggests that nail thickness is an important prognostic factor. Moreover, mycological cure may require 6 months of treatment regimen while complete cure and clinical effectiveness may be achievable only after 10 months. A simulation study suggests that longer treatment duration would have resulted in higher complete cure with TNS vs. vehicle. Study treatments were well‐tolerated.

Conclusion  Primary efficacy objectives were not met in the studies reported herein. Possible reasons for failure to achieve significant outcomes include insufficient length of treatment; stringency of primary endpoint and severity of nail involvement of study population.
Lack of association between filaggrin gene mutations and onset of psoriasis in childhood
Authors: Winge M.C.G. , Suneson J. , Lysell J. , Nikamo P. , Liedén A. , Nordenskjöld M. , Wahlgren C.F. , Bradley M. , Ståhle M.
Published: December 2011

Background  Atopic dermatitis (AD; OMIM#603165) and psoriasis (OMIM#177900) are two common inflammatory skin disorders. Both are genetically complex, multifactorial and do not follow a Mendelian pattern of inheritance. Both diseases share several genetic susceptibility loci such as the epidermal differentiation complex (EDC) on chromosome 1q21. Within the EDC, mutations in the filaggrin (FLG) gene are strongly associated with AD whereas no association has been replicated with psoriasis. However, reduced levels of filaggrin have been reported in psoriatic skin. Further, filaggrin deficiency was shown to be a modifying factor for the phenotype in another epidermal skin disorder, X‐linked recessive ichthyosis. Altogether, this raises the question if FLG mutations may modify the disease course in other epidermal skin diseases such as psoriasis. Psoriasis is a highly heterogeneous disease and so far genetic studies have not taken the distinct sub‐phenotype childhood onset into account.

Objective  To determine if FLG mutations modify the onset of psoriasis.

Materials and methods  A total of 241 children with onset of psoriasis below 15 years of age and 314 healthy controls were identified at the Dermatology clinic, Karolinska University Hospital and diagnosed by the same dermatologist (JL). Blood samples were taken and medical history was recorded. FLG was genotyped in all patients and controls using allelic discrimination (n = 555) and sequencing (n = 20).

Results and conclusions  No association between FLG mutations and early onset of psoriasis was demonstrated (P = 0.57) and no novel mutations were detected, indicating that FLG loss‐of‐function variants do not have a strong effect on the onset of psoriasis in childhood.
Oral etoposide as first‐line therapy in the treatment of patients with advanced classic Kaposi’s sarcoma (CKS): a single‐arm trial (oral etoposide in CKS)
Authors: Tas F. , Sen F. , Keskin S. , Kilic L.
Published: December 2011

Background  Classic Kaposi’s sarcoma (CKS) affects an elderly population; it is important to have effective treatment options with high activity and relatively low toxicity, and availability to be used for long periods.

Objective  We investigated the activity and safety of single‐agent etoposide with an oral administration schedule in patients with advanced CKS.

Methods  Histologically confirmed, CKS patients were eligible for study. All had a negative test for HIV and good performance status. All patients received oral etoposide 50 mg twice daily for 10 days every 3 weeks.

Results  Thirty patients (median age 66 and 22 males) were enrolled into the study. The majority of them had non‐metastatic, local advanced disease and symptoms in nearly half of patients. Complete and partial responses were observed in 10% and 77% of patients, respectively, giving an overall response rate of 87%. Stable disease occurred in the other 13% of patients. Treatment was well tolerated. Grade IV toxicity was not observed. Haematological toxicity was the principal dose‐limiting side effect. Severe leucopaenia and neutropaenia were observed in 7% and 10% of patients respectively. No patient was complicated by febrile neutropaenia. Mild‐moderate anaemia observed frequently, but only 3% of patients had severe anaemia and severe thrombocytopaenia was not observed. The 5‐year overall survival rate was 92%.

Conclusions  Single‐agent oral etoposide is an effective treatment option and is acceptably toxic and easily administered. Therefore, we recommend the single agent of oral etoposide as the first‐line chemotherapy for advanced CKS.
The major volatile organic compound emitted from Arabidopsis thaliana flowers, the sesquiterpene (E)‐β‐caryophyllene, is a defense against a bacterial pathogen
Authors: Huang Mengsu , Sanchez‐Moreiras Adela M. , Abel Christian , Sohrabi Reza , Lee Sungbeom , Gershenzon Jonathan , Tholl Dorothea
Published: December 2011

See also the Commentary by Stephenson
Lost in translation: preclinical studies on 3,4‐methylenedioxymethamphetamine provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans
Authors: Green AR , King MV , Shortall SE , Fone KCF
Published: December 2011

3,4‐Methylenedioxymethamphetamine (MDMA) induces both acute adverse effects and long‐term neurotoxic loss of brain 5‐HT neurones in laboratory animals. However, when choosing doses, most preclinical studies have paid little attention to the pharmacokinetics of the drug in humans or animals. The recreational use of MDMA and current clinical investigations of the drug for therapeutic purposes demand better translational pharmacology to allow accurate risk assessment of its ability to induce adverse events. Recent pharmacokinetic studies on MDMA in animals and humans are reviewed and indicate that the risks following MDMA ingestion should be re‐evaluated. Acute behavioural and body temperature changes result from rapid MDMA‐induced monoamine release, whereas long‐term neurotoxicity is primarily caused by metabolites of the drug. Therefore acute physiological changes in humans are fairly accurately mimicked in animals by appropriate dosing, although allometric dosing calculations have little value. Long‐term changes require MDMA to be metabolized in a similar manner in experimental animals and humans. However, the rate of metabolism of MDMA and its major metabolites is slower in humans than rats or monkeys, potentially allowing endogenous neuroprotective mechanisms to function in a species specific manner. Furthermore acute hyperthermia in humans probably limits the chance of recreational users ingesting sufficient MDMA to produce neurotoxicity, unlike in the rat. MDMA also inhibits the major enzyme responsible for its metabolism in humans thereby also assisting in preventing neurotoxicity. These observations question whether MDMA alone produces long‐term 5‐HT neurotoxicity in human brain, although when taken in combination with other recreational drugs it may induce neurotoxicity.

LINKED ARTICLES

This article is commented on by Parrott, pp. 1518–1520 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01941.x and to view the the rebuttal by the authors (Green et al., pp. 1521–1522 of this issue) visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01940.x
Concomitant facilitation of GABAA receptors and KV7 channels by the non‐opioid analgesic flupirtine
Authors: Klinger Felicia , Geier Petra , Dorostkar Mario M , Chandaka Giri K , Yousuf Arsalan , Salzer Isabella , Kubista Helmut , Boehm Stefan
Published: December 2011

BACKGROUND AND PURPOSE

Flupirtine is a non‐opioid analgesic that has been in clinical use for more than 20 years. It is characterized as a selective neuronal potassium channel opener (SNEPCO). Nevertheless, its mechanisms of action remain controversial and are the purpose of this study.

EXPERIMENTAL APPROACH

Effects of flupirtine on native and recombinant voltage‐ and ligand‐gated ion channels were explored in patch‐clamp experiments using the following experimental systems: recombinant KIR3 and KV7 channels and α3β4 nicotinic acetylcholine receptors expressed in tsA 201 cells; native voltage‐gated Na+, Ca2+, inward rectifier K+, KV7 K+, and TRPV1 channels, as well as GABAA, glycine, and ionotropic glutamate receptors expressed in rat dorsal root ganglion, dorsal horn and hippocampal neurons.

KEY RESULTS

Therapeutic flupirtine concentrations (≤10 µM) did not affect voltage‐gated Na+ or Ca2+ channels, inward rectifier K+ channels, nicotinic acetylcholine receptors, glycine or ionotropic glutamate receptors. Flupirtine shifted the gating of KV7 K+ channels to more negative potentials and the gating of GABAA receptors to lower GABA concentrations. These latter effects were more pronounced in dorsal root ganglion and dorsal horn neurons than in hippocampal neurons. In dorsal root ganglion and dorsal horn neurons, the facilitatory effect of therapeutic flupirtine concentrations on KV7 channels and GABAA receptors was comparable, whereas in hippocampal neurons the effects on KV7 channels were more pronounced.

CONCLUSIONS AND IMPLICATIONS

These results indicate that flupirtine exerts its analgesic action by acting on both GABAA receptors and KV7 channels.
A Web‐Based Personal Health Information System for Homeless Youth and Young Adults
Authors: Dang Michelle T. , Whitney Kimberley D. , Virata Maria Catrina D. , Binger Melissa M. , Miller Elizabeth
Published: December 2011

Runaway and homeless youth face multiple challenges to their health and experience inadequate access to health care services. This article describes a Web‐based Personal Health Information System (PHIS) called Healthshack that was specifically designed to improve health care access and health outcomes for runaway and homeless youth at a community‐based agency that served homeless youth and young adults up to age 24. The program was developed in partnership with homeless youth and piloted by public health nurses. Preliminary findings from the program indicate that a PHIS is acceptable to runaway and homeless youth and feasible to incorporate into the flow of a youth agency. Thus, a PHIS may be an innovative model of service delivery for other marginalized populations.
VARIABILITY IN THE PRIMARY SITE OF PHOTOSYNTHETIC DAMAGE IN SYMBIODINIUM SP. (DINOPHYCEAE) EXPOSED TO THERMAL STRESS1
Authors: Buxton Lucy , Takahashi Shunichi , Hill Ross , Ralph Peter J.
Published: December 2011

Exposure to elevated temperature is known to cause photosynthetic inhibition in the coral symbiont Symbiodinium sp. Through the use of the artificial electron acceptor, methyl viologen, this study identified how reduced photosynthetic capacity occurs as a result of inhibition up‐ and/or downstream of ferredoxin in Symbiodinium sp. in hospite and in culture. Heterogeneity between coral species and symbiont clades was identified in the thermal sensitivity of photosynthesis in the symbionts of the scleractinian corals Stylophora pistillata and Pocillopora damicornis, as well as among Symbiodinium cultures of clades A, B, and C. The in hospite symbionts of S. pistillata and the cultured clade C Symbiodinium both exhibited similar patterns in that their primary site of thermal inhibition occurred downstream of ferredoxin at 32°C. In contrast, the primary site of thermal inhibition occurred upstream of ferredoxin in clades A and B at 32°C, while at 34°C, all samples showed combined up‐ and downstream inhibition. Although clade C is common to both P. damicornis and S. pistillata, the manner of thermal inhibition was not consistent when observed in hospite. Results showed that there is heterogeneity in the primal site of thermal damage in Symbiodinium among coral species and symbiont clades.
Palpation and Dorsal Acetabular Rim Radiographic Projection for Early Detection of Canine Hip Dysplasia: A Prospective Study
Authors: Gatineau Matthieu , Dupuis Jacques , Beauregard Guy , Charette Benoît , Breton Luc , Beauchamp Guy , d'Anjou Marc‐André
Published: December 2011

Objective

To determine the value of 2 diagnostic methods: (1) the reduction angle (RA) using theOrtolani maneuver and (2) the dorsal acetabular slope (DAS) from the dorsal acetabular rim (DAR) radiographic projection, to predict osteoarthritis (OA) in dogs with hip dysplasia.

Study Design

Prospective study.

Sample Population

Dogs (n = 73).

Methods

Hip‐extended ventrodorsal (VD) radiographic projections,RA, andDASwere evaluated when dogs were 6, 12, and 24 months of age.VDprojections were qualitatively scored forOA.RAwas determined using theOrtolani maneuver in dorsal recumbency andDASusing theDARprojection. Distraction index (DI) measurements from the compression–distraction radiographic projections (PennHIPmethod) were also performed at 6 months of age. Statistical analyses were used to establish the range of values of normal and abnormalRAandDAS, to document the temporal variation inRAandDAS, to compare the ability of the different methods to predict coxofemoralOA, to determine the influence of pure passive laxity and of theDASon the occurrence of anOrtolani sign and on the magnitude of theRA, to establish the relationship between theDASand subsequent development of passive laxity and coxofemoralOA, and to evaluate the influence of theDASandRAon the occurrence of coxofemoralOAwith severe, moderate, and minimal coxofemoral passive joint laxity, respectively.

Results

VD,RA,DAS, andDImethods of coxofemoral joint evaluation correlated significantly with the status of the coxofemoral joints at 2 years of age. The risk of occurrence of coxofemoralOAincreased, as theRA,DAS, orDIincreased. There was a significant positive linear relationship betweenRAandDI(P= .015, r2= 0.32),RAandDAS(P= .0078, r2= 0.38), andDASandDI(P= .015, r2= 0.33). A negativeOrtolani sign was at all times significantly predictive of absence of coxofemoralOAat 2 years of age.DASbest predicted coxofemoralOAforDI≥ 0.7, whereasRAbest predicted coxofemoralOAfor 0.3 <DI< 0.7; however,RAproved to be the best overall predictor of coxofemoralOA.

Conclusion

RAmeasured at 6 months of age in dorsal recumbency was the best predictor of coxofemoralOAat 2 years of age.
Radiographic Evaluation of Early Periprosthetic Femoral Bone Contrast and Prosthetic Stem Alignment after Uncemented and Cemented Total Hip Replacement in Dogs
Authors: Mostafa Ayman A. , Drüen Svenja , Nolte Ingo , Wefstaedt Patrick
Published: December 2011

Objective

To radiographically evaluate periprosthetic femoral bone contrast and assess alignment of the prosthetic stem after uncemented and cemented total hip replacement (THR).

Study Design

Prospective clinical study.

Animals

Dogs (n = 15).

Methods

Dogs were classified into uncemented (n = 8) and cemented (n = 7)THRgroups. Radiographs were analyzed using image processing software to evaluate femoral bone contrast (gray scale value,GV) for each and combined modifiedGruen zone(s) immediately and 4 months afterTHR. ModifiedGruen zones were classified into 5 zones to analyze retrospectively the regional radiographicGVof the femur around uncemented and cemented prosthetic stem. Alignment of prosthetic stem was assessed immediately and 4 months postoperatively. Variables were compared by use of 2‐tailed t‐test, withP< .05 considered significant.

Results

Zone 1 showed significant decrease in the mean boneGV4 months after uncementedTHR. No differences in zones 1–5 after 4 months of cementedTHR. Combined zones showed significant decrease in overall mean boneGV4 months after uncementedTHR. No changes were observed 4 months after cementedTHR. Number of limbs with varus‐aligned femoral stem markedly increased after 4 months of uncementedTHR.

Conclusions

Regional bone contrast and prosthetic stem alignment vary with the design ofTHR.
Pelvic Limb Kinematics and Surface Electromyography of the Vastus Lateralis, Biceps Femoris, and Gluteus Medius Muscle in Dogs with Hip Osteoarthritis
Authors: Bockstahler Barbara , Kräutler Cordula , Holler Peter , Kotschwar Alexander , Vobornik Angela , Peham Christian
Published: December 2011

Objective

To measure the activity patterns of the vastus lateralis (VL), biceps femoris, and gluteus medius (GM) muscle at a walk in sound dogs and dogs with hip osteoarthritis (OA).

Animals

Dogs (n = 10) with hipOAand 7 clinically sound dogs.

Methods

Self‐reflective markers and a high‐speed camera system were used for kinematic measurements and surface electrodes were used for the electromyography (EMG). All measurements were performed on walking dogs. Maximal, minimal, and mean values of the joint angles were evaluated, together with the surfaceEMGdata.

Results

In all muscles investigated, mean activity was significantly decreased during the early swing phase in dogs with hipOA. TheVLandGMmuscle of the clinically worse pelvic limb had significantly higher activity than the contralateral pelvic limb during early stance.

Conclusion

The muscles investigated were significantly affected by hipOA. This finding suggests that there is a more distinct resting phase of the muscles during swing and a higher activity during early stance.
Risk Factors and Clinical Relevance of Positive Intraoperative Bacterial Cultures in Dogs with Total Hip Replacement
Authors: Ireifej Shadi , Marino Dominic J. , Loughin Catherine A. , Lesser Martin L. , Akerman Meredith
Published: December 2011

Objective

To report incidence and relevance of positive intraoperative total hip replacement (THR) bacterial cultures taken at the time of surgical closure in dogs having unilateralTHR.

Study design

Retrospective case series.

Animals

Dogs (n = 100) with cemented (CFX), cementless (BFX), or hybridTHR.

Methods

Medical records (January 2007–March 2010) of dogs that hadTHRwere reviewed. Signalment, type and side ofTHR, concurrent surgery, operative and anesthetic times, intraoperative coxofemoral closing (CC) bacterial culture results, organism cultured, duration of postoperative antibiotic administration, physical examination findings at 3 weeks, 3 months, and at 6 months to 1 year after surgery, radiographic findings at 3 months and between 6 months and 1 year after surgery, and incidence of complications were retrieved.

Results

There was a significant difference in duration of surgery betweenCCculture negative andCCculture positive groups (103.27 minutes versus 122.50 minutes, respectively,P< .038) and in total anesthetic time betweenCCculture negative and culture positive groups (165.20 minutes versus 189.50 minutes, respectively,P< .038). There was no significant difference betweenCCculture negative and culture positive groups for median age (30 months versus 39 months, respectively,P< .75), median weight (36.91 kg versus 35.68 kg, respectively,P< .61), median clinical signs (4 months versus 3.5 months, respectively,P< .65), sex (males 44.32% versus females 25.00%, respectively,P< .20), laterality (left 55.68% versus right 50.00%, respectively,P< .71), concurrent surgery (extracapsular lateral imbrication/medial patella luxation/lateral patella luxation [ECLI/MPL/LPL] 22.73% versus none 25.00%, respectively,P< 1.00), andTHRtype (hybrid 17.05% versus 25.00% respectively;CFX60.23% versus 75.0%;BFX22.73% versus 0.0%;Fisher's exact testP< .17).

Conclusions

Surgical and anesthetic duration were significantly associated with positiveCCculture results. PositiveCCculture results were not associated with adverse results at 3 months and at 6‐month to 1‐year follow‐up evaluation.
Two Different Days of Transcranial Doppler Examinations Should Be Performed for Detection of Right‐to‐Left Shunt in Acute Stroke Patients
Authors: Aoki Junya , Kimura Kazumi , Iguchi Yasuyuki , Sakai Kenichiro , Sakamoto Yuki , Terasawa Yuka , Shibazaki Kensaku , Kobayashi Kazuto
Published: December 2011

BACKGROUND

We investigated how many contrast‐transcranial Doppler (c‐TCD) examinations should be performed on different days in patients with acute stroke.

METHODS

Consecutive acute stroke patients within 24 hours of onset were enrolled. Presence of RLS was examined using c‐TCD examinations on days 1, 7, and 14. Each c‐TCD examination used one test without Valsalva maneuver (VM) and three tests with VM. Patients were diagnosed with RLS when TCD detected ≥1 microembolic signal on ≥1 c‐TCD examination on any of the days 1, 7, or 14.

RESULTS

One hundred seventy patients (105 men [62%]; median age, 74 [IQR, 66–81] years) were enrolled. RLS was diagnosed in 45 patients (26%). RLS was identified on day 1 in 30 patients (18%), on day 7 in 28 patients (16%), and on day 14 in 23 patients (14%; P= .143). Detection rate of RLS by combining day 1 and 7 examinations was significantly higher than that of day 1 alone (25% vs 18%, P < .001). However, the rate did not increase when results of day 14 were added (25% vs 26%, P= .250).

CONCLUSIONS

c‐TCD examinations should be performed on at least two different days to assess the prevalence of RLS.
Lentiviral vectors for cutaneous RNA managing
Authors: Primo Maria Nascimento , Bak Rasmus O. , Mikkelsen Jacob Giehm
Published: December 2011

Abstract:  Post‐transcriptional managing of RNA plays a key role in the intricate network of cellular pathways that regulate our genes. Numerous small RNA species have emerged as crucial regulators of RNA processing and translation. Among these, microRNAs (miRNAs) regulate protein synthesis through specific interactions with target RNAs and are believed to play a role in almost any cellular process and tissue. Skin is no exception, and miRNAs are intensively studied for their role in skin homoeostasis and as potential triggers of disease. For use in skin and many other tissues, therapeutic RNA managing by small RNA technologies is now widely explored. Despite the easy accessibility of skin, the natural barrier properties of skin have challenged genetic intervention studies, and unique tools for studying gene expression and the regulatory role of small RNAs, including miRNAs, in human skin are urgently needed. Human immunodeficiency virus (HIV)‐derived lentiviral vectors (LVs) have been established as prominent carriers of foreign genetic cargo. In this review, we describe the use of HIV‐derived LVs for efficient gene transfer to skin and establishment of long‐term transgene expression in xenotransplanted skin. We outline the status of engineered LVs for delivery of small RNAs and their in vivo applicability for expression of genes and small RNA effectors including small hairpin RNAs, miRNAs and miRNA inhibitors. Current findings suggest that LVs may become key tools in experimental dermatology with particular significance for cutaneous RNA managing and in vivo genetic intervention.
8‐Methoxypsoralen plus UVA treatment increases the proportion of CLA+ CD25+ CD4+ T cells in lymph nodes of K5.hTGFβ1 transgenic mice
Authors: Singh Tej Pratap , Schön Michael P. , Wallbrecht Katrin , Wolf Peter
Published: December 2011

Abstract:  8‐Methoxypsoralen plus UVA (PUVA) photochemotherapy is an effective treatment for many skin diseases including psoriasis. However, its exact mechanism of therapeutic action is incompletely understood. Previously, in K5.hTGFβ1 transgenic psoriatic mice, we found that PUVA induces Foxp3+ CD25+ CD4+ regulatory T cells in both lymph node and spleen. Now, in the same model, we investigated whether cutaneous lymphocyte‐associated antigen (CLA) mediates PUVA’s effect on homing of CD25+ CD4+  T cells to the lymph nodes of K5.hTGFβ1 transgenic mice. We found that a low dose of topical PUVA maximally increased the proportion of CLA + CD25+ CD4 + T cells in the lymph nodes by up to 8‐fold. We also observed an increased number of Foxp3+ CD25+  T cells in the skin of the mice after PUVA treatment. Together, these findings suggest that PUVA affects the homing of regulatory T cells.