bluuebunny/crossref_metadata_2025 huggingface dataset:
Guarding the Green: Pathways to Stomatal Immunity
Authors: Sawinski Katja , Mersmann Sophia , Robatzek Silke , Böhmer Maik
Published: February 2013

Guard cells regulate plant gas exchange and transpiration by modulation of stomatal aperture upon integrating external cues like photosynthetic effective illumination, CO2 levels and water availability and internal signals like abscisic acid (ABA). Being pores, stomata constitute a natural entry site for potentially harmful microbes. To prevent microbial invasion, stomata close upon perception of microbe-associated molecular patterns (MAMPs), and this represents an important layer of active immunity at the preinvasive level. The signaling pathways leading to stomatal closure triggered by biotic and abiotic stresses employ several common components, such as reactive oxygen species, calcium, kinases, and hormones, suggesting considerable intersection between MAMP- and ABA-induced stomatal closures, which we will discuss in this review.
First Report of Crown Rot of Strawberry Caused by Macrophomina phaseolina in Chile
Authors: Sánchez S. , Gambardella M. , Henríquez J. L. , Díaz I.
Published: February 2013

In recent years, an increase of collapsed and dead strawberry plants has been observed in several fields in central Chile, specifically in San Pedro, Melipilla, an important area for strawberry cultivation in the country. To determine the causal agent of the disease and the extent of the problem, 25 sample sites of 1 ha each, distributed in different San Pedro zones, were surveyed at the end of the 2011 season (from December 2010 to February 2011). Cross sections of the crowns of symptomatic strawberry plants showed necrotic tissue and brown-red to dark brown areas on the vascular ring. Samples of the affected crowns were superficially disinfested and plated on potato dextrose agar with 200 μg/ml of streptomycin sulfate. Dark gray colonies were observed after 7 days of incubation at 24°C. Pure cultures of the pathogen showed aerial mycelium and abundant dark oblong sclerotia. Fifty sclerotia were measured, averaging 120 × 74 μm. Twenty-one isolates were identified molecularly utilizing the species specific primers MpKFI and MpKRI (2) that yielded a 350-bp fragment. The amplified DNA fragments were sequenced and BLAST analysis showed a 99% nucleotide sequence identity with Macrophomina phaseolina (GeneBank Accession No JX535007.1). Both morphological and molecular analyses confirmed that the isolated species corresponded to M. phaseolina, causal agent of crown and root rot in strawberry. Four representative isolates were selected to conduct pathogenicity tests. Inoculum was prepared by incubating the pathogen for 28 days at 20°C in sterilized oat seeds. Pots of 1.5 liters were filled with a mixed substrate of peat and perlite (2:1), amended with inoculated oats at 9 g per liter of substrate. ‘Camarosa’ strawberry plants were planted and grown in a glasshouse for 1 month. Six replicated plants per isolate and six plants growing on non-inoculated substrate were left as controls. Ninety-five percent of the inoculated plants showed wilt and collapse symptoms 22 days after transplant, whereas no symptoms were observed in the control plants. M. phaseolina was reisolated from the crowns of symptomatic plants, fulfilling Koch's postulates. The pathogen was isolated from symptomatic strawberry plants in 14 of the 25 sampled sites. Although M. phaseolina was described previously on other crops in Chile, to our knowledge, this is the first report of M. phaseolina causing crown rot of strawberry. The disease has been recently reported in Spain, the United States, and Argentina (1,3,4).

References: (1) M. Avilés et al. Plant Pathol. 57:382, 2008. (2) B. Babu et al. Mycologia 99:797, 2007. (3) O. Baino et al. Plant Dis. 95:1477, 2011. (4) S. Koike. Plant Dis. 92:1253, 2008.
Imaging the serotonin 1A receptor using [
11
C]WAY100635 in healthy controls and major depression
Authors: Hesselgrave Natalie , Parsey Ramin V.
Published: February 2013

As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the 1A receptor (5-HT
1A
) has been implicated in depression and suicide. Using the [carbonyl-
11
C]WAY100635 ([
11
C]WAY) ligand and positron emission tomography, we have studied the 5-HT
1A
receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT
1A
binding potential (BP
F
) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP
F
in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BP
F
in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT
1A
BP
F
may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT
1A
imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [
11
C]CUMI-101 agonist tracer.
Using the high-risk family design to identify biomarkers for major depression
Authors: Talati Ardesheer , Weissman Myrna M. , Hamilton Steven P.
Published: February 2013

The familial nature of major depressive disorder (MDD) is now well recognized. We followed children and grandchildren of probands with and without MDD to examine transmission of depression over generations, and to identify early vulnerability markers prior to the onset of disease. The study now includes three generations and five completed assessment waves spanning 25 years, with a sixth wave underway. Beginning with the fourth wave, we collected measures of brain structure (magnetic resonance imaging, MRI) and physiology (electroencephalography, EEG) and DNA in order to examine at a biological level why the offspring of depressed parents were at higher risk. In this paper, we provide an overview of the study design, the main findings, including new data, and the role of the high-risk design in translational research. We demonstrate that offspring of depressed parents (‘high-risk’), when compared with those of non-depressed parents (‘low-risk’), were at increased risk for depressive and anxiety disorders, with anxiety appearing earlier and being a predisposing factor for MDD. Offspring with two generations previously affected were at greatest risk. Thinning of the cortical mantle (MRI) and reduced resting-state activity (EEG) within the right parieto-temporal hemisphere differentiated high- from low-risk offspring, regardless of whether the offspring had MDD, suggesting that these measures might serve as familial trait markers for depression and related syndromes. The high- and low-risk offspring also differed by serotonin transporter promoter length polymorphism genotypes, even though the same genotypes were not associated with the presence of MDD. The high-risk epidemiological design appears to be a particularly valuable asset in translational research as it allows targeting of biological processes that emerge prior to the onset of disease, and identifies individuals at high risk for the disorder who may carry the trait or marker but not yet be affected.
Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity
Authors: Murphy Dennis L. , Moya Pablo R. , Fox Meredith A. , Rubenstein Liza M. , Wendland Jens R. , Timpano Kiara R.
Published: February 2013

Individuals with obsessive–compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene (
SLC6A4
), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders.
Efficient neocentromere formation is suppressed by gene conversion to maintain centromere function at native physical chromosomal loci in Candida albicans
Authors: Thakur Jitendra , Sanyal Kaustuv
Published: February 2013

CENPA/Cse4 assembles centromeric chromatin on diverse DNA. CENPA chromatin is epigenetically propagated on unique and different centromere DNA sequences in a pathogenic yeast Candida albicans. Formation of neocentromeres on DNA, nonhomologous to native centromeres, indicates a role of non-DNA sequence determinants in CENPA deposition. Neocentromeres have been shown to form at multiple loci in C. albicans when a native centromere was deleted. However, the process of site selection for CENPA deposition on native or neocentromeres in the absence of defined DNA sequences remains elusive. By systematic deletion of CENPA chromatin-containing regions of variable length of different chromosomes, followed by mapping of neocentromere loci in C. albicans and its related species Candida dubliniensis, which share similar centromere properties, we demonstrate that the chromosomal location is an evolutionarily conserved primary determinant of CENPA deposition. Neocentromeres on the altered chromosome are always formed close to the site which was once occupied by the native centromere. Interestingly, repositioning of CENPA chromatin from the neocentromere to the native centromere occurs by gene conversion in C. albicans.
Sympathetic skin responses from the scalp evoked by electrical stimulation in seborrheic dermatitis
Authors: Altunrende Burcu , Yildiz Serpil , Kandi Basak , Yildiz Nebil
Published: February 2013

Although the role of autonomic nervous system in seborrheic dermatitis (SD) is still unclear, seborrhea is sometimes accepted as a sign of autonomic dysfunction in several nervous system diseases. Therefore, we aimed to investigate the sympathetic nervous system (SNS) activity in SD by recording sympathetic skin responses (SSR) from the scalp (S‐SSR). Thirty‐one control subjects and 22 SD patients were studied by evoking right and left S‐SSR with electrical stimulation of the right median nerve at the wrist. Mean latencies and maximum amplitudes were calculated for both sides in each group. In seven out of 31 control subjects and in 13 out of 22 patients, the S‐SSR could not be elicited on either side. There were four subjects with unilateral response in the patient group. There were significantly more non‐responders among the patients with SD (P < 0.000). This study suggests that in SD, the autonomic nervous system may be involved. The S‐SSR is a new site for recording SSR. The responses are relatively symmetrical and can be evoked easily by electrical stimulation, and may be used to evaluate the SNS function in SD patients and also in healthy subjects.
How Enlightened Can a Monk Be? The Efforts of Eighteenth‐Century German Benedictines to Reform Monastery and Church
Authors: Lehner Ulrich L.
Published: February 2013

This article investigates how German Benedictines in the eighteenth century tried to reform monastic life and Catholic theology by adopting various aspects of Enlightenment lifestyle and thought. It demonstrates the intellectual diversity that existed in this religious order and the order's intensive dialogue with contemporary culture.
Commentary on Politics of Urbanism: Seeing Like a City by Warren Magnusson
Authors: Brunet‐Jailly Emmanuel , Kataoka Serena , Keil Roger , Sancton Andrew , Taylor Zack
Published: February 2013

Politics of Urbanism: Seeing Like a City is Warren Magnusson's most recent book. It will find a permanent place as a key contribution in the annals of urban studies, urban politics, political and state theory and international relations, marking a turning point in the way scholars, activists and policymakers see the world. In particular, Magnusson fundamentally questions how we understand and analyse our world from the perspective of the state (the illusion of the sovereign), suggesting we shift instead to the perspective of the city (with its multiplicity of authorities). ‘How welcome should this be?’ is the question that I put to three Canadian colleagues — Roger Keil, Andrew Sancton and Zack Taylor — at the 2011 meeting of the Canadian Political Science Association in Waterloo, ON, Canada. Their answers follow a summary of this rather concise and very readable book that Serena Kataoka and I prepared to introduce those commentaries.
Seeing Like a Theorist
Authors: King Loren
Published: February 2013

Warren Magnusson sees a problem endemic to political thought and practice: we see the world in ways that presume and reaffirm the necessity of a sovereign territorial state, on pain of violent disorder in its absence. The solution is to ‘see like a city’, shaking off the dualism of sovereignty versus anarchy and finding a richer space of political possibilities. I admire and applaud Magnusson's critical efforts to challenge dominant categories and illuminate possibilities, but these aims rest uneasily with his polemical contrast between sovereignty and cities.
Crisis, Resources and the State: Executive Politics in the Age of the Depleted State
Authors: Lodge Martin
Published: February 2013

Questions regarding the problem-solving capacity of the state have been long-standing. The financial crisis as well as future demographic and environmental challenges have raised the spectre of the depleted state, a state that lacks legitimacy and resources to steer social, economic and political developments. This article considers how a perspective that centres on executive politics can illuminate key debates surrounding the depleted state. It does so in three steps. First, it considers whether the earlier literature on the ‘crisis of the state’ of the 1970s contributes to contemporary debates. Second, it questions whether the age of ‘governance’ has come to the rescue, and not just of the challenges outlined by the earlier literature. Third, it discusses the contribution of executive politics to the study of the contemporary state's problem-solving capacity and draws wider implications of the age of the depleted state for executive politics.
Species delimitation in Cladonia (Ascomycota): a challenge to the DNA barcoding philosophy
Authors: Pino‐Bodas Raquel , Martín María P. , Burgaz Ana R. , Lumbsch H. Thorsten
Published: February 2013

The lichen‐forming fungal genus Cladonia is species‐rich with approximately 500 described species. The accepted barcode for fungi (ITS rDNA) often fails in identifying Cladonia spp. In order to find other markers that, in combination with the ITS rDNA region can be used for species identification in Cladonia, we studied the loci IGS rDNA, ef1α, rpb2 and cox1. A total of 782 sequences from 36 species have been analyzed. PCR amplification success rate, intraspecific and interspecific genetic distance variation, calculated using the K2P model, and the correct identification percentage (PCI) were taken into account to assess possible barcode regions. The marker showing the least intraspecific genetic distance range was cox1, followed by ITS rDNA and ef1α. Of the five studied markers only cox1 showed a barcoding gap. The rpb2 locus showed the highest PCI values, but it was the most difficult to amplify. The highest correct identification rates using blast method were obtained with rpb2.
Cytomegalovirus infection is associated with increased mortality in the older population
Authors: Savva George M. , Pachnio Annette , Kaul Baksho , Morgan Kevin , Huppert Felicia A. , Brayne Carol , Moss Paul A. H.
Published: February 2013

Cytomegalovirus (CMV) is a common herpesvirus infection and stimulates the expansion of very large numbers of CMV‐specific T cells that reduce the CD4/CD8 ratio and suppress the number of naïve T cells. CMV infection has been associated with frailty and impaired survival. We investigated the correlates of CMV and the impact of the CMV infection on mortality within a cohort of 511 individuals aged at least 65 years who were followed up for 18 years. The mean age of the participants was 74 years of which 70% were CMV‐seropositive. CMV was strongly linked to socio‐economic status, and CMV infection increased the annual mortality rate by 42% (Hazard ratio = 1.42, 95% CI: 1.11–1.76 after adjusting for age, sex and baseline socio‐economic and health variables) corresponding to 3.7 years lower life expectancy from age 65. Infection was associated with a near doubling of cardiovascular deaths, whereas there was no increase in mortality from other causes. These results show that CMV infection markedly increases the mortality rate in healthy older individuals due to an excess of vascular deaths. These findings may have significant implications for the study of immune senescence and if confirmed more generally could have important implications for measures to optimize the health of the elderly.
Targeting macrophages rescues age‐related immune deficiencies in C57BL/6J geriatric mice
Authors: Jackaman Connie , Radley‐Crabb Hannah G. , Soffe Zoe , Shavlakadze Tea , Grounds Miranda D. , Nelson Delia J.
Published: February 2013

Changes to innate cells, such as macrophages and myeloid‐derived suppressor cells (MDSCs), during aging in healthy or tumor‐bearing hosts are not well understood. We compared macrophage subpopulations and MDSCs from healthy young (6–8 weeks) C57BL/6J mice to those from healthy geriatric (24–28 months) mice. Spleens, lymph nodes, and bone marrow of geriatric hosts contained significantly more M2 macrophages and MDSCs than their younger counterparts. Peritoneal macrophages from geriatric, but not young, mice co‐expressed CD40 and CX3CR1 that are usually mutually exclusively expressed by M1 or M2 macrophages. Nonetheless, macrophages from geriatric mice responded to M1 or M2 stimuli similarly to macrophages from young mice, although they secreted higher levels of TGF‐β in response to IL‐4. We mimicked conditions that may occur within tumors by exposing macrophages from young vs. geriatric mice to mesothelioma or lung carcinoma tumor cell–derived supernatants. While both supernatants skewed macrophages toward the M2‐phenotype regardless of age, only geriatric‐derived macrophages produced IL‐4, suggesting a more immunosuppressive tumor microenvironment will be established in the elderly. Both geriatric‐ and young‐derived macrophages induced allogeneic T‐cell proliferation, regardless of the stimuli used, including tumor supernatant. However, only macrophages from young mice induced T‐cell IFN‐γ production. We examined the potential of an IL‐2/agonist anti‐CD40 antibody immunotherapy that eradicates large tumors in young hosts to activate macrophages from geriatric mice. IL‐2‐/CD40‐activated macrophages rescued T‐cell production of IFN‐γ in geriatric mice. Therefore, targeting macrophages with IL‐2/anti‐CD40 antibody may improve innate and T‐cell immunity in aging hosts.
Absence of the Articular Disc in the Tasmanian Devil Temporomandibular Joint
Authors: Hayashi K. , Sugisaki M. , Kino K. , Ishikawa T. , Sugisaki M. , Abe S.
Published: February 2013

The articular disc of the temporomandibular joint is a constant structure in mammals. According to Parsons' report in 1900, however, it is absent in four animals: the armadillo, two kinds of monotremes and the Tasmanian devil. Thereafter, no research was performed to confirm this observation. The aim of this study was to determine by anatomical and histological examination whether the Tasmanian devil has an articular disc in its temporomandibular joint. Six fresh frozen corpses and one dry skull of Tasmanian devils were obtained from the School of Zoology, University of Tasmania. The corpses were dissected and the morphology of the temporomandibular joint was carefully observed by gross anatomical and histological examination. The structure of the temporomandibular joint of the dry skull was examined macroscopically and by micro‐computed tomography. In all cases, absence of the articular disc in the Tasmanian devil temporomandibular joint was morphologically confirmed. The surface layer of both the condyle and the glenoid fossa comprised a thick fibrous tissue. Micro‐computed tomography revealed dense and fine trabecular bone in the condyle. The thick fibrous tissue covering the condyle and high‐density trabecular bone in the condyle might play a role in absorption against powerful mastication and heavy loading of the Tasmanian devil temporomandibular joint.
Placental weight relative to birthweight in pregnancies with maternal diabetes mellitus
Authors: Strøm‐Roum Ellen M. , Haavaldsen Camilla , Tanbo Tom G. , Eskild Anne
Published: February 2013

Objectives

To study the association of maternal diabetes mellitus with placental weight, birthweight and placental weight‐to‐birthweight ratio.

Design

Population‐based study.

Setting

Medical Birth Registry of Norway.

Population

All singleton births in Norway during 1999–2008 (n = 536 997).

Methods

We compared the distribution of placental weight z‐scores and placental weight‐to‐birthweight ratio between pregnancies with and without diabetes. The associations of diabetes with placental weight z‐scores were also estimated as odds ratios with and without adjustment for birthweight, maternal age, parity, preeclampsia, smoking and cesarean delivery.

Main outcome measures

Placental weight, birthweight and placental weight‐to‐birthweight ratio.

Results

Mean placental weight was 736.6 g in diabetic pregnancies and 672.1 g in non‐diabetic pregnancies. The corresponding birthweights were 3682.1 g and 3557.0 g. In diabetic pregnancies, 26.2% of the placentas were in the highest decile of placental weight z‐score, as compared with 9.7% in non‐diabetic pregnancies (p < 0.001). The corresponding figures for being in the highest decile of placental weight‐to‐birthweight ratio were 18.2 and 9.9% (p < 0.001). The crude odds ratio for having a placenta in the highest decile of placental weight z‐score was 3.29 (95% confidence interval 3.14–3.45) in diabetic pregnancies with non‐diabetic pregnancies as the reference. After adjustment for birthweight and other variables, the odds ratio was 2.42 (95% confidence interval 2.29–2.56).

Conclusions

In diabetic pregnancies, placental weight as well as placental weight relative to birthweight were higher than in non‐diabetic pregnancies.
Alarelin active immunization influences expression levels of GnRHR, FSHR and LHR proteins in the ovary and enhances follicular development in ewes
Authors: Wei Suocheng , Chen Shien , Gong Zhuandi , Ouyang Xiahui , An Lifeng , Xie Kun , Dong Jiangling , Wei Min
Published: February 2013

We investigated the effects of gonadotropin releasing hormone (GnRH) agonist on expressions of GnRH receptor (GnRHR), follicle‐stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) proteins in the ovaries and follicular development in the ewes. Forty‐two pre‐pubertal ewes were assigned to experimental groups 1 to 5 (EG‐I to EG‐V) and control group (CG). Ewes in EG‐I, EG‐II and EG‐III were subcutaneously injected with 200, 300 or 400 μg alarelin antigens twice (on days 0 and 14), respectively. Ewes in EG‐IV and EG‐V were subcutaneously injected with 200 μg and 300 μg alarelin antigen four times (on days 0, 7, 14 and 21). Ewes in CG were subcutaneously injected with a solvent twice (on days 0 and 14). Serum concentrations of GnRH antibody in the EGs increased and were higher than (P < 0.05) that of CG from day 14 to day 60. GnRH antibody concentrations in EG‐IV and EG‐V were higher than that in EG‐I, EG‐II and EG‐III from days 35 to 45. Expressions of GnRHR protein in EG‐IV and EG‐V were lower than that in CG (P < 0. 01). Expressions of FSHR and LHR proteins in EGs increased. Levels of FSHR and LHR proteins in EG‐IV and EG‐V (P < 0.05) were higher than CG. Ovarian weights in EGs increased. Values of follicle vertical diameter, follicle transverse diameter, follicle wall thickness, follicle externatheca thickness and follicle internatheca thickness in EG‐III and EG‐V were greater than other groups. Primordial follicles and primary follicles developed quickly in alarelin‐immunized animals. Secondary follicles and mature follicles became more abundant. Mitochondria, mitochondrial cristaes and cortical granules increased. Serum FSH concentrations of EGs remained higher than that in CG from days 28 to 70 (P < 0.05). Alarelin immunization stimulated GnRH antibody production, suppressed expression of GnRHR protein, enhanced expressions of FSHR and LHR proteins in ovaries, promoted FSH secretion and thereby accelerated the development of ovaries and follicles in ewes.
Lower initial dose desoxycorticosterone pivalate for treatment of canine primary hypoadrenocorticism
Authors: Bates JA , Shott S , Schall WD
Published: February 2013

Objective

To evaluate the efficacy of initial doses of desoxycorticosterone pivalate (DOCP) that are lower and less expensive than the presently recommended initial dose of 2.2 mg/kg for treating dogs with primary hypoadrenocorticism.

Methods

A retrospective study was performed on 49 dogs with primary hypoadrenocorticism, including 36 with initialDOCPdoses less than 2.2 mg/kg. Medical records were reviewed for clinical data. All study dogs were followed up with telephone calls to owners or veterinarians to determine the date of death or last follow‐up. Data were analysed to investigate relationships between initialDOCPdose and survival and serumNa,Kand their ratio.

Results

Regardless of their initialDOCPdose, none of the dogs developed uncontrolled hypoadrenocorticism or severe electrolyte abnormalities or clinical problems that would have made an increase in theDOCPdose necessary. Over time, most dogs had a decrease in theirDOCPdose in mg/kg, because of weight gain during treatment. No statistically significant relationships were found between initialDOCPdose and survival or post‐treatment serumNa,KorNa : K, with the exception of one statistically significant result that suggested lower efficacy for higher doses.

Conclusion

InitialDOCPdoses less than 2.2 mg/kg may be effective in controlling serum electrolyte concentrations in dogs with primary hypoadrenocorticism without adversely affecting survival. If confirmed by additional research, these findings would enable practitioners to reduce the cost ofDOCPtreatment by using lower initial doses, potentially saving the lives of dogs that would otherwise be euthanased because of treatment expense.
Bioavailability of twoL‐thyroxine formulations after oral administration to healthy dogs
Authors: Simpson C , Devi JL , Whittem T
Published: February 2013

Objective

To describe the pharmacokinetics of two veterinary formulations ofL‐thyroxine available inAustralia.

Methods

A two‐phase randomised, crossover, open‐label trial followed by a third‐phase parallel‐dosing trial was conducted in 11 healthy dogs with an investigative oralL‐thyroxine liquid formulation and a reference tablet formulation. Blood sampling was done at defined intervals and serum totalL‐thyroxine concentrations were measured by radioimmunoassay. The post‐dose concentrations were plotted as a function of time for each period and the relative bioavailability of the two formulations were compared using a general linear model with factors for dog, phase, sequence and formulation.

Results

Following oral administration of the reference tablet at the dose of 100 μg/kg, a maximum plasma concentration of approximately 96.2 nmol/L (baseline endogenous corrected) was reached within 3.77 h. For the investigative liquid preparation at a dose of 50 μg/kg, the maximum plasma concentration was 60.1 nmol/L (baseline endogenous corrected), which was reached within 3.59 h.

Conclusion

The geometric mean of the relative bioavailability for the liquid/tablet product was 1.1, which suggests that the relative bioavailability of thyroxine following administration of tablet or liquid formulation is similar.
Role of genetically engineered animals in future food production
Authors: McColl KA , Clarke B , Doran TJ
Published: February 2013

Genetically engineered (GE) animals are likely to have an important role in the future in meeting the food demand of a burgeoning global population. There have already been many notable achievements using this technology in livestock, poultry and aquatic species. In particular, the use of RNA interference (RNAi) to produce virus‐resistant animals is a rapidly‐developing area of research. However, despite the promise of this technology, very few GE animals have been commercialised. This review aims to provide information so that veterinarians and animal health scientists are better able to participate in the debate on GE animals.
Suicide in prisoners with bipolar disorder and other psychiatric disorders: a systematic review
Authors: Fazel Seena , Wolf Achim , Geddes John R
Published: February 2013

Objectives

To examine the risk of suicide and suicide attempts in prisoners with bipolar disorder and other psychiatric disorders compared with prisoners without psychiatric disorders.

Methods

We conducted a systematic review and meta‐analysis of observational studies comparing suicide outcomes in prisoners with bipolar disorder and other psychiatric disorders to other prisoners.

Results

Five studies reported the risk of suicidal outcomes in prisoners with bipolar disorder compared with other prisoners, with a random effects pooled odds ratio of 2.4 (95% confidence interval: 1.6–3.7; I2 = 0%). This appeared to be lower than the risk of suicidal outcomes for all psychiatric disorders and for depression, specifically, and, in meta‐regression, significantly lower (p = 0.03) than for schizophrenia‐spectrum disorders.

Conclusions

Although bipolar disorder is associated with suicide and non‐fatal suicidal behavior in prisoners, further research is necessary to confirm any associations and mediating mechanisms.
Sexual distractors boost younger and older adults' visual search RSVP performance
Authors: Didierjean André , Maquestiaux François , Vieillard Sandrine , Ruthruff Eric , Hartley Alan
Published: February 2013

Do sexual words have high attentional priority? How does the ability to ignore sexual distractors evolve with age? To answer these questions, two experiments using Rapid Serial Visual Presentation (RSVP) were conducted. Experiment 1 showed that both younger and older participants were better at identifying a target (the name of a colour) when it was preceded by 336 ms by a sexual word rather than by a musical word. Strikingly, the sexual‐word advantage was more pronounced for older adults than for younger adults. Experiment 2 showed that introducing a variable delay between the distractor and the target eliminated the sexual‐word advantage. This finding suggests that the sexual‐word advantage found in Experiment 1 was due to learning to utilize the sexual word as a temporal cue with a fixed duration between the distractor and the target. Contrary to previous research [Arnell et al., 2007, Emotion, 7, 465), neither experiment showed that sexual words produce an attentional blink.
Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy
Authors: Zhou Q , Gil-Krzewska A , Peruzzi G , Borrego F
Published: February 2013

Activation of human natural killer (NK) cells is associated with the cleavage of CD16 from the cell surface, a process mediated by matrix metalloproteinases (MMPs). In this report, we examined whether inhibition of MMPs would lead to improved NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) function. Using an in-vitro ADCC assay, we tested the anti-tumour function of NK cells with three different therapeutic monoclonal antibodies (mAbs) in the presence of MMPs inhibitor GM6001 or its control. Loss of CD16 was observed when NK cells were co-cultured with tumour targets in the presence of specific anti-tumour antibodies, and was found particularly on the majority of degranulating NK responding cells. Treatment with MMPs inhibitors not only prevented CD16 down-regulation, but improved the quality of the responding cells significantly, as shown by an increase in the percentage of polyfunctional NK cells that are capable of both producing cytokines and degranulation. Furthermore, MMPs inhibition resulted in augmented and sustained CD16-mediated signalling, as shown by increased tyrosine phosphorylation of CD3ζ and other downstream signalling intermediates, which may account for the improved NK cell function. Collectively, our results provide a foundation for combining MMPs inhibitors and therapeutic mAbs in new clinical trials for cancer treatment.
Unilesional self‐limited Langerhans cell histiocytosis: a case report and review of the literature
Authors: Wheller Laura , Carman Nicholas , Butler Greg
Published: February 2013

Self‐limited Langerhans cell histiocytosis (LCH) represents a rare, congenital, cutaneous form of LCH associated with a good prognosis. Only 35 cases of solitary lesion self‐limited LCH have been reported. Herein, we present an additional case in a 3‐month‐old boy who presented with an isolated pigmented nodule on his left posterior shoulder, which had been present since birth. Punch biopsy showed histopathologic features of LCH with positive CD1a and CD68 stains. Further examination and investigation showed no features of systemic involvement. The lesion spontaneously resolved within 2 months, and there has been no evidence of recurrence on follow up. As several cases of recurrence and complications have been reported in self‐limited LCH, we emphasize the need for long‐term, and perhaps indefinite, follow up for symptoms and signs associated with LCH in these patients.
Phosphohistone‐H3 and Ki‐67 immunostaining in cutaneous pilar leiomyoma and leiomyosarcoma (atypical intradermal smooth muscle neoplasm)
Authors: Idriss Munir H , Kazlouskaya Viktoryia , Malhotra Saurabh , Andres Christian , Elston Dirk M.
Published: February 2013

Background

The mitotic index is important in the assessment of tumors such as leiomyoma (LM) and leiomyosarcoma (LMS), which may exhibit a range of cytological atypia. The mitotic marker phosphohistone‐H3 (PHH3) was shown to improve interobserver and intraobserver variability in many tumors.

Materials and methods

We evaluated the mitotic index in 20 pilar LM and cutaneous LMS using PHH3 and hematoxylin and eosin (H&E)‐stained sections. Ki‐67 staining characteristics of the tumors were also assessed.

Results

Mitotic figures were more easily identified within PHH3 sections. The mitotic index per 10 high power fields (HPF) on the PHH3 stain was slightly higher than H&E both in the LM (mean 0.1, range 0–1 vs. mean 0) and LMS groups (mean 8.6 vs. 8.0 with range of 1–24 for both stains). The difference in mitotic index between the two stains was not statistically significant in either group (p = 0.7). The Ki‐67 proliferative index showed a statistically significant correlation with a diagnosis of LMS.

Conclusion

PHH3 immunostain can simplify counting of mitotic figures in cutaneous smooth muscle neoplasms, especially those with many pyknotic nuclei, and may help to reduce interobserver variability. Ki‐67 staining may also be of help in establishing a diagnosis of LMS.
Practicability of combined treatment with calcipotriol/betamethasone gel (Daivobet® Gel) and improvement of quality of life in patients with psoriasis
Authors: Sticherling Michael , Eicke Christoph , Anger Tobias
Published: February 2013

Background

The successful treatment of psoriasis depends not only on the efficacy of the medication but also on patientsí acceptance and adherence to the prescribed regimen.

Patients and Methods

In this non‐interventional, prospective trial 579 patients with psoriasis were treated once daily with the fixed combination of calcipotriol 50 μg/g plus betamethasone 0.5 mg/g (Daivobet® Gel) for 4 weeks. Comparing the new medication to their previous treatment, patients assessed their quality of life by means of the Dermatology Life Quality Index (DLQI), reported their therapy‐ associated burden in daily life by the Psoriasis Disability Index (PDI) and assessed how easy the new medication was to employ. Disease severity was rated at the start and end of the study by physicians and patients using a Global Assessment (PGA from 0–5 points) and the Body Surface Area (BSA) assessed by the physicians.

Results

Quality of life improved from 8.7 to 3.2 points (p < 0.0001) parallel to a significant decrease of PGA by 39.6% (p < 0.0001) and BSA (72.5% of patients with BSA > 4% before vs. 37.3% after therapy). The application of the study medication was 30% less time‐consuming and handling associated with significantly higher patient satisfaction. Efficacy and tolerability of Daivobet® Gel versus prior treatment were judged “very good” in 85.7% vs. 27.6% of patients.

Conclusions

The study substantiates a significant improvement of the quality of life during therapy with the fixed combination. Patients benefit from the convenience and time‐saving as compared to their prior treatment. Thus, Daivobet® Gel can be recommended as an effective and well‐tolerated treatment which may easily be integrated into daily life of patients with psoriasis.
Intensive dysarthria therapy for younger children with cerebral palsy
Authors: Pennington Lindsay , Roelant Ella , Thompson Vicki , Robson Sheila , Steen Nick , Miller Nick
Published: February 2013

Aim

The aim of this study was to investigate if intervention targeting breath support, phonation, and speech rate increases speech intelligibility and participation in the conversational interactions of younger children with dysarthria and cerebral palsy (CP).

Method

Fifteen children with dysarthria andCP(nine males, six females; age range 5–11y, mean age 8y,SD2y;CPtype: eight spastic, four dyskinetic, one ataxia, twoWorsterDrought syndrome;GrossMotorFunctionClassificationSystem levelsII–IV, median levelII) participated in this study. Children received three sessions of individual therapy per week for 6 weeks. Intelligibility of single words and connected speech was compared across five points: 1 and 6 weeks before therapy and 1, 6, and 12 weeks after therapy. Three familiar listeners and three unfamiliar listeners scored each recording. Participation in communicative interactions was measured using theFocus on theOutcomes ofCommunicationUnderSix (FOCUS) tool. Analyses of variance and pairedt‐tests were used to investigate change.

Results

Mean speech intelligibility increased after therapy to familiar listeners (single words 10.8%, 95% confidence interval [CI] 7.2–14.4; connected speech 9.4%, 95%CI4.8–14.1) and unfamiliar listeners (single words 9.3%, 95%CI6.8–11.8; connected speech 10.5%, 95%CI7.3–13.8).FOCUSscores increased following therapy for parents (mean increase 30.3, 95%CI10.2–50.4) and for teachers (28.25, 95%CI14.4–42.1), but changes did not correlate with intelligibility. A wide variation was seen in individual responses to therapy.

Interpretation

Brief intensive therapy is associated with gains in intelligibility and communicative interactions for some younger children with dysarthria.
Prognostic value of neonatal brain imaging for very low birthweight preterm infants
Authors: Mirmiran Majid
Published: February 2013

This commentary is on the original article by de Bruïne et al on pages 427–433 of this issue.
Fragmented Legislatures and the Budget: Analyzing Presidential Democracies
Authors: Hankla Charles R.
Published: February 2013

What impact does party fragmentation have on the likelihood of democracies to run a fiscal deficit? Past research is almost unanimous in finding that as the number of parties in a country's legislature or government grows, so does its probability of overspending. However, this finding is based largely on parliamentary systems, and there is no reason to believe that it should hold when executives are independent. In this article, I develop a theory for the impact of legislative fragmentation on budgetary politics in presidential democracies. I argue that unified presidential systems should tend most toward fiscal solvency but that increasing fragmentation should actually facilitate budget balancing when government is divided. The logic is that presidents, who are likely to prefer balanced budgets due to their broad constituencies, will be better able to craft acceptable governing coalitions from divided legislatures than from ones controlled by a single opposing party. They will also be better able to circumvent such fragmented legislatures should a coalition prove impossible. I test these propositions quantitatively in all presidential democracies from 1976 to 2007. The results provide support for the theory and highlight the contrasting impact of legislative fragmentation on public policy in presidential vs. parliamentary systems.
Implications of hypoxia tolerance for wetland refugia use in Lake Nabugabo, Uganda
Authors: Reid Andrea J. , Farrell Maxwell J. , Luke Max N. , Chapman Lauren J.
Published: February 2013

Aquatic hypoxia can affect predator‐prey interactions by altering the success rate of the predator and/or the vulnerability of prey. For example, in the Lake Victoria basin of East Africa, native prey exploit hypoxic wetlands as refugia from predation by introduced Nile perch (Lates niloticus). Here, it is predicted that species exploitation of wetlands depends on their hypoxia tolerance relative to the heterogeneity of wetland hypoxia. In this study, we compared the hypoxia tolerance of four fish taxa that differ in their use of hypoxic wetlands in Lake Nabugabo, Uganda: the cichlid Pseudocrenilabrus multicolor victoriae that inhabits the dense swamp interior; and three taxa that inhabit wetland ecotones including Nile tilapia (Oreochromis niloticus), L. niloticus and juvenile endemic haplochromine cichlids. We characterised hypoxia tolerance by exposing fish to progressive hypoxia and quantifying variation in aquatic surface respiration (ASR). The effect of body size on tolerance was explored in L. niloticus by quantifying ASR behaviour across a range of size classes. ASR behaviour was also compared between O. niloticus groups from wetland versus open‐water habitats to detect habitat‐associated intraspecific variation. The most tolerant taxon was the swamp specialist P. multicolor, indicated by its low ASR thresholds and small percentage of fish using ASR during the final sample interval. The other three taxa did not differ in ASR behaviour, and no differences were detected between O. niloticus groups. Body size effects were present for L. niloticus suggesting a lower tolerance to hypoxia in larger‐bodied individuals, thus limiting their ability to penetrate wetlands.
Predicting ecosystem stability from community composition and biodiversity
Authors: de Mazancourt Claire , Isbell Forest , Larocque Allen , Berendse Frank , De Luca Enrica , Grace James B. , Haegeman Bart , Wayne Polley H. , Roscher Christiane , Schmid Bernhard , Tilman David , van Ruijven Jasper , Weigelt Alexandra , Wilsey Brian J. , Loreau Michel
Published: February 2013

As biodiversity is declining at an unprecedented rate, an important current scientific challenge is to understand and predict the consequences of biodiversity loss. Here, we develop a theory that predicts the temporal variability of community biomass from the properties of individual component species in monoculture. Our theory shows that biodiversity stabilises ecosystems through three main mechanisms: (1) asynchrony in species’ responses to environmental fluctuations, (2) reduced demographic stochasticity due to overyielding in species mixtures and (3) reduced observation error (including spatial and sampling variability). Parameterised with empirical data from four long‐term grassland biodiversity experiments, our prediction explained 22–75% of the observed variability, and captured much of the effect of species richness. Richness stabilised communities mainly by increasing community biomass and reducing the strength of demographic stochasticity. Our approach calls for a re‐evaluation of the mechanisms explaining the effects of biodiversity on ecosystem stability.
Highly‐enhanced larval growth during the cold season mediated by the basking behavior of the butterfly Parnassius citrinarius (Lepidoptera: Papilionidae)
Authors: Akiyama Koji , Nishida Takayoshi
Published: February 2013

Some insect species are thought to grow quickly, even in low temperatures under natural conditions, presumably by conducting basking behaviors to use sunlight. However, whether basking behavior in fact enhances developmental speed and shortens the larval period in the field has not been determined. Moreover, few studies have examined whether basking is behavioral thermoregulation or simply the result of highly‐heterogeneous heat environments in the field. To examine these issues, we conducted field observations and laboratory experiments using larvae of Parnassius citrinarius Motschulsky, which mature within a short period after the thaw in early spring. First, body temperatures of larvae were measured under sunny and cloudy conditions. Second, larval preference for warmer locations was examined. Finally, we compared the developmental speed of larvae when they basked under field conditions and when did not bask in laboratory conditions under different air temperature regimes. Under sunny conditions, larval body temperature was substantially higher than either the temperature of the host plant or the air temperature, and was equivalent to the temperature of dead leaves, which the larvae used as basking sites. In contrast, no such tendency was observed under cloudy conditions. Larvae exhibited an exclusive preference for warmer locations. Moreover, in the field, despite the low ambient temperature, larvae grew much faster than those reared in the laboratory. These results imply that the basking behavior of P. citrinarius larvae is active thermoregulation to maintain high body temperatures in the cold season.
Transport of endocannabinoids across the plasma membrane and within the cell
Authors: Fowler Christopher J.
Published: February 2013

Endocannabinoids are readily accumulated from the extracellular space by cells. Although their uptake properties have the appearance of a process of facilitated diffusion, it is by no means clear as to whether there is a plasma membrane transporter dedicated to this task. Intracellular carrier proteins that shuttle the endocannabinoid anandamide from the plasma membrane to its intracellular targets such as the metabolic enzyme, fatty acid amide hydrolase, have been identified. These include proteins with other primary functions, such as fatty‐acid‐binding proteins and heat shock protein 70, and possibly a fatty acid amide hydrolase‐like anandamide transporter protein. Thus, anandamide uptake can be adequately described as a diffusion process across the plasma membrane followed by intracellular carrier‐mediated transport to effector molecules, catabolic enzymes and sequestration sites, although it is recognized that different cells are likely to utilize different mechanisms of endocannabinoid transport depending upon the utility of the endocannabinoid for the cell in question.