bluuebunny/crossref_metadata_2025 huggingface dataset:
Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome
Authors: Hethorn Whitney R. , Ciarlone Stephanie L. , Filonova Irina , Rogers Justin T. , Aguirre Daniela , Ramirez Raquel A. , Grieco Joseph C. , Peters Melinda M. , Gulick Danielle , Anderson Anne E. , L. Banko Jessica , Lussier April L. , Weeber Edwin J.
Published: April 2015

The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus‐dependent learning and memory. A single direct in vivo application of Reelin enhances long‐term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long‐term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus‐dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post‐mortem human brain.
Insect life history and the evolution of bacterial mutualism
Authors: Henry Lee M. , Maiden Martin C. J. , Ferrari Julia , Godfray H. Charles J.
Published: April 2015

Bacterial symbiosis has played a fundamental role in the evolution of eukaryotes. However, we still know little about how cooperative relationships with bacteria originate, and why they form in some host species but not others. Facultative symbionts that are beneficial, but not essential, provide unique insights into these processes. We use data from over a hundred aphid species to test if host life history is associated with the presence of facultative symbionts. We find that aphid species that have mutualistic associations with ants that protect them from natural enemies are less likely to carry symbionts that provide similar benefits. We also find one symbiont species occurs more frequently in unrelated aphid species that specialise on certain plant genera. In addition, aphid species that attack multiple plants often carry different symbiont complements. Our findings provide evidence of the ecological conditions that facilitate stable, mutually beneficial relationships between microbes and eukaryotic hosts.
How far to go? Determinants of migration distance in land mammals
Authors: Teitelbaum Claire S. , Fagan William F. , Fleming Chris H. , Dressler Gunnar , Calabrese Justin M. , Leimgruber Peter , Mueller Thomas
Published: April 2015

Animal migration is a global phenomenon, but few studies have examined the substantial within‐ and between‐species variation in migration distances. We built a global database of 94 land migrations of large mammalian herbivore populations ranging from 10 to 1638 km. We examined how resource availability, spatial scale of resource variability and body size affect migration distance among populations. Resource availability measured as normalised difference vegetation index had a strong negative effect, predicting a tenfold difference in migration distances between low‐ and high‐resource areas and explaining 23% of the variation in migration distances. We found a weak, positive effect of the spatial scale of resource variability but no effect of body size. Resource‐poor environments are known to increase the size of mammalian home ranges and territories. Here, we demonstrate that for migratory populations as well, animals living in resource‐poor environments travel farther to fulfil their resource needs.
Mixed effects of effluents from a wastewater treatment plant on river ecosystem metabolism: subsidy or stress?
Authors: Aristi Ibon , von Schiller Daniel , Arroita Maite , Barceló Damià , Ponsatí Lídia , García‐Galán María J. , Sabater Sergi , Elosegi Arturo , Acuña Vicenç
Published: April 2015

The effluents of wastewater treatment plants (WWTPs) include a complex mixture of nutrients and pollutants. Nutrients can subsidise autotrophic and heterotrophic organisms, while toxic pollutants can act as stressors, depending, for instance, on their concentration and interactions in the environment. Hence, it is difficult to predict the overall effect of WWTP effluents on river ecosystem functioning.

We assessed the effects of WWTP effluents on river biofilms and ecosystem metabolism in one river segment upstream from a WWTP and three segments downstream from the WWTP and following a pollution gradient.

The photosynthetic capacity and enzymatic activity of biofilms showed no change, with the exception of leucine aminopeptidase, which followed the pollution gradient most likely driven by changes in organic matter availability. The effluent produced mixed effects on ecosystem‐scale metabolism. It promoted respiration (subsidy effect), probably as a consequence of enhanced availability of organic matter. On the other hand, and despite enhanced nutrient concentrations, photosynthesis–irradiance relationships showed that the effluent partly decoupled primary production from light availability, thus suggesting a stress effect.

Overall, WWTP effluents can alter the balance between autotrophic and heterotrophic processes and produce spatial discontinuities in ecosystem functioning along rivers as a consequence of the mixed contribution of stressors and subsidisers.
Effects of extreme floods on trout populations and fish communities in a Catskill Mountain river
Authors: George S. D. , Baldigo B. P. , Smith A. J. , Robinson G. R.
Published: April 2015

Extreme hydrologic events are becoming more common with changing climate. Although the impacts of winter and spring floods on lotic ecosystems have been well studied, the effects of summer floods are less well known.

The Upper Esopus Creek Basin in the Catskill Mountains, NY, experienced severe flooding from Tropical Storm Irene on 28 August 2011, and peak discharges exceeded the 0.01 annual exceedance probability (>100 year flood) in some reaches. Three years of fish community data from pre‐flood surveys at nine sites were compared to data from 2 years of post‐flood surveys to evaluate changes in fish communities and populations of brown trout (Salmo trutta) and rainbow trout (Oncorhynchus mykiss).

Basinwide, fish assemblages were not strongly impacted and appeared highly resilient to the effects of the flood. Total density and biomass of fish communities were greater at most sites 10–11 months after the flood than 1 month prior to the flood while richness and diversity were generally unchanged. Community composition did not differ significantly between years or between the pre‐ and post‐flood periods.

Although the density of mature brown trout was low at most sites (mean density = 146 fish ha−1), young‐of‐the‐year brown trout reached their highest density (mean = 2312 fish ha−1) during 2012. In contrast, rainbow trout densities declined substantially during the 5‐year study and the 2012 year class was small (mean density = 222 fish ha−1).

Late summer floods may be less damaging to stream fish communities than winter or spring floods as spawning activity is negligible and early life stages of many species are generally larger and less susceptible to displacement and mortality. Additionally, post‐flood conditions may be advantageous for brown trout recruitment.
Growth of modern branched columnar stromatolites in Lake Joyce, Antarctica
Authors: Mackey T. J. , Sumner D. Y. , Hawes I. , Jungblut A. D. , Andersen D. T.
Published: April 2015

Modern decimeter‐scale columnar stromatolites from Lake Joyce, Antarctica, show a change in branching pattern during a period of lake level rise. Branching patterns correspond to a change in cyanobacterial community composition as preserved in authigenic calcite crystals. The transition in stromatolite morphology is preserved by mineralized layers that contain microfossils and cylindrical molds of cyanobacterial filaments. The molds are composed of two populations with different diameters. Large diameter molds (>2.8 μm) are abundant in calcite forming the oldest stromatolite layers, but are absent from younger layers. In contrast, <2.3 μm diameter molds are common in all stromatolites layers. Loss of large diameter molds corresponds to the transition from smooth‐sided stromatolitic columns to branched and irregular columns. Mold diameters are similar to trichome diameters of the four most abundant living cyanobacteria morphotypes in Lake Joyce: Phormidium autumnale morphotypes have trichome diameters >3.5 μm, whereas Leptolyngbya antarctica, L. fragilis, and Pseudanabaena frigida morphotypes have diameters <2.3 μm. P. autumnale morphotypes were only common in mats at <12 m depth. Mats containing abundant P. autumnale morphotypes were smooth, whereas mats with few P. autumnale morphotypes contained small peaks and protruding bundles of filaments, suggesting that the absence of P. autumnale morphotypes allowed small‐scale topography to develop on mats. Comparisons of living filaments and mold diameters suggest that P. autumnale morphotypes were present early in stromatolite growth, but disappeared from the community through time. We hypothesize that the mat‐smoothing behavior of P. autumnale morphotypes inhibited nucleation of stromatolite branches. When P. autumnale morphotypes were excluded from the community, potentially reflecting a rise in lake level, short‐wavelength roughness provided nuclei for stromatolite branches. This growth history provides a conceptual model for initiation of branched stromatolite growth resulting from a change in microbial community composition.
Helicobacter pylori Infection in Early Childhood and Growth at School Age
Authors: Muhsen Khitam , Goren Sophy , Cohen Dani
Published: April 2015

Background

There are conflicting results regarding the role of H. pylori in children's growth. We examined differences in growth indices at school age according to H. pylori infection acquisition in preschool age.

Materials and Methods

A prospective study was undertaken between 2004 and 2009, in which of healthy children (N = 139, ages 3–5 years at baseline) were tested for the presence of H. pylori antigen in their stool using enzyme‐linked immunoassay and followed‐up till age 6–9 years (median follow‐up time 45 months). Height, weight, and hemoglobin levels were measured, and socioeconomic data were obtained. Z scores of height for age, weight for age, and body mass index for age at baseline and follow‐up were calculated using the 2000 Center for Disease Control and Prevention growth reference curves. Growth velocity (cm/month) between preschool and school age was compared between H. pylori‐infected and uninfected children using mixed models.

Results

Fifty‐three percent of the children were H. pylori positive at baseline, and all except one child tested positive at follow‐up. The adjusted mean Z score of height for age at follow‐up was significantly lower among H. pylori‐infected children than uninfected ones: 0.15 (95% confidence intervals (CIs) 0.02, 0.29) and 0.45 (95% CI 0.29, 0.60), respectively (p = .002). Growth velocity was slower in the former group −0.0264 cm/month (95% CI −0.047, −0.005) (p = .014), after adjusting for baseline height and age. H. pylori infection was not associated with body weight.

Conclusions

Helicobacter pylori infection acquired in early childhood may have long‐term adverse influence on linear growth at school age.
Effect of maintaining apical patency on endodontic pain in posterior teeth with pulp necrosis and apical periodontitis: a randomized controlled trial
Authors: Arora M. , Sangwan P. , Tewari S. , Duhan J.
Published: April 2015

Aim

To evaluate the association between apical patency and post‐operative pain in posterior teeth with pulp necrosis and apical periodontitis.

Methodology

Sixty‐eight patients requiring primary root canal treatment in mandibular first molars with necrotic pulps and apical periodontitis were included. The patients were randomly allocated to one of two groups: patency (n = 34) and nonpatency (n = 34). After administering local anaesthesia, root canal preparation was completed using ProTaper rotary instruments. A size 10 K‐file was used as a patency file and carried 1 mm beyond the working length (WL) between each instrument change in the patency group, while it was carried up to WL in the nonpatency group. Patients were asked to record their pain experience on a pain chart daily for 7 days. Three patients (two in the patency group, one in the nonpatency group) did not return with completed pain charts on the subsequent visit, resulting in a total of 65 patients for the final analysis (patency, n = 32; nonpatency, n = 33). Data was analysed using Chi Square test, t‐test, Mann–Whitney test and Wilcoxon Signed Ranks test.

Results

Overall, 43% of the patients experienced post‐operative pain. The patency group had less incidence of pain (34%) as compared to the nonpatency group (52%), but the difference was not significant (P = 0.163).

Conclusion

Maintenance of apical patency during chemomechanical preparation had no significant influence on post‐operative pain in posterior teeth with necrotic pulps and apical periodontitis.
Locus of control and individual learning: the moderating role of interactional justice
Authors: Cappetta Rossella , Magni Massimo
Published: April 2015

Organizations are increasingly investing in training programs for building managerial skills, with a special focus on employees considered ‘talents’ who must be prepared to cover strategic roles within the organization. One of the main goals of such programs is to develop participants' learning in order to tap their potential in a short time frame, ultimately to gain competitive advantage. However, participant learning is a complex process that can be hindered by different elements related to the characteristics of individuals and the context in which they act. In our research, we conducted a field study to analyze how the individual trait of locus of control (LOC) may negatively affect learning. Moreover, our study indicates that the contextual characteristic of interactional justice mitigates the negative effect of LOC on individual learning. We provide theoretical contributions and suggestions for managers in the light of our results.
HES6 promotes prostate cancer aggressiveness independently of Notch signalling
Authors: Carvalho Filipe L. F. , Marchionni Luigi , Gupta Anuj , Kummangal Basheer A. , Schaeffer Edward M. , Ross Ashley E. , Berman David M.
Published: April 2015

Notch signalling is implicated in the pathogenesis of a variety of cancers, but its role in prostate cancer is poorly understood. However, selected Notch pathway members are overrepresented in high‐grade prostate cancers. We comprehensively profiled Notch pathway components in prostate cells and found prostate cancer‐specific up‐regulation ofNOTCH3andHES6. Their expression was particularly high in androgen responsive lines. Up‐ and down‐regulating Notch in these cells modulated expression of canonical Notch targets,HES1 andHEY1, which could also be induced by androgen. Surprisingly, androgen treatment also suppressed Notch receptor expression, suggesting that androgens can activate Notch target genes in a receptor‐independent manner. Using a Notch‐sensitiveRecombination signal binding protein for immunoglobulin kappa J region (RBPJ)reporter assay, we found that basal levels of Notch signalling were significantly lower in prostate cancer cells compared to benign cells. Accordingly pharmacological Notch pathway blockade did not inhibit cancer cell growth or viability. In contrast to canonical Notch targets,HES6, aHESfamily member known to antagonize Notch signalling, was not regulated by Notch signalling, but relied instead on androgen levels, both in cultured cells and in human cancer tissues. When engineered into prostate cancer cells, reduced levels ofHES6 resulted in reduced cancer cell invasion and clonogenic growth. By molecular profiling, we identified potential roles forHES6 in regulating hedgehog signalling, apoptosis and cell migration. Our results did not reveal any cell‐autonomous roles for canonical Notch signalling in prostate cancer. However, the results do implicateHES6 as a promoter of prostate cancer progression.
Money Makes theEUGo Round: The Objective Foundations of Conflict in theCouncil ofMinisters
Authors: Bailer Stefanie , Mattila Mikko , Schneider Gerald
Published: April 2015

Many examinations of the dimensions of conflict in theEuropeanUnionCouncil ofMinisters focus on the ideological roots of contestation in theEU. This article examines the extent to which structural attributes of theMember States explain the conflict within theCouncil ofMinisters in general as well as in selected policy domains (agriculture, fisheries, environment, economic affairs). Drawing on the political economy literature of legislative decision‐making, a multilevel analysis shows that country‐level redistributive interests shape the interactions considerably and in some of the policy domains that are examined in more detail. The impact of ideological variables like the left‐right positioning of theMember State governments remains inconsistent and marginal in this analysis.
Revisiting Fisher: range size drives the correlation between variability and abundance of British bird eggs
Authors: Lapiedra O. , Price T. D.
Published: April 2015

We evaluate the correlation between intraspecific variation in egg size and population size in breeding British birds. Using information on abundance, range occupancy, migration status and phylogenetic relationships among species, we show that a wider geographical distribution rather than larger population size per se best predicts egg size variability. A similar result applies to wing length variability. Results from a phylogenetic path analysis suggest that geographical variation is the most parsimonious causal explanation for high intraspecific variation in common species.
Expression of hepatic cytochrome P450 in a mouse model of ulcerative colitis changes with pathological conditions
Authors: Kusunoki Yoshiki , Ikarashi Nobutomo , Matsuda Shogo , Matsukawa Yoshimi , Kitaoka Satoshi , Kon Risako , Tajima Masataka , Wakui Nobuyuki , Ochiai Wataru , Machida Yoshiaki , Sugiyama Kiyoshi
Published: April 2015

Background and Aim

The expression levels of cytochrome P450 (CYP) in the liver were analyzed over time in dextran sulfate sodium (DSS)‐induced ulcerative colitis mouse model, from the initial active stage to the remission stage, to investigate the relationship between the changes in pathological conditions and CYP expression levels.

Methods

DSS solution was given to mice for 10 days, after which water without DSS was provided for 40 days. Pathological conditions and CYP expression levels were examined over time. The mechanism for variation in CYP expression was also analyzed.

Results

The mRNA expression levels of CYP (CYP3A11, CYP1A2, CYP2C29, CYP2D9, and CYP2E1) decreased as pathological conditions worsened and reached their lowest levels on day 10 of DSS treatment. Pathological conditions improved following the discontinuation of DSS, and CYP expression levels normalized by day 50. Blood lipopolysaccharide levels, the hepatic expression of inflammatory cytokines, and the nuclear translocation of pregnane X receptor and constitutive androstane receptor in the liver exhibited patterns similar to the observed variations in CYP expression levels.

Conclusion

The capacity for metabolizing drugs that are substrates of CYP decreases during the active stage of ulcerative colitis but subsequently improves during the remission stage. This decrease in CYP expression was likely caused by the observed reduction in the levels of nuclearly localized pregnane X receptor and constitutive androstane receptor, and the increase in the production of inflammatory cytokines triggered by lipopolysaccharides.
Clinical outcomes of cryptogenic compared with non‐cryptogenic cirrhosis: A retrospective cohort study
Authors: Mohammed Omar Kadhim , Mahadeva Sanjiv
Published: April 2015

Background and Aim

The consequences of the association between the metabolic syndrome and cryptogenic cirrhosis are uncertain. We aimed to compare the differences in clinical outcomes between cryptogenic and non‐cryptogenic cirrhosis.

Methods

A retrospective cohort study was conducted in a large, single academic center, over a 5‐year duration.

Results

Complete data were available in 301 patients with cirrhosis (cryptogenic n = 94, non‐cryptogenic n = 207). Compared with non‐cryptogenic cirrhosis, patients with cryptogenic cirrhosis were older (mean age 66.4 ± 12.5 vs 60.7 ± 11.3 years, P < 0.0001), had more females (43.6% vs 26.6%, P = 0.003), had less disease severity (Child–Pugh C 8.5% vs 15.9%, P = 0.042), and had a higher prevalence of the metabolic syndrome (83% vs 51.2%, P < 0.0001). During the 5‐year period, adults with cryptogenic Child–Pugh A cirrhosis had a longer total hospital admission duration compared with non‐cryptogenic cirrhosis (median 7.0 vs 3.0 days, P = 0.035), but this was less evident in patients with more advanced disease. This difference was due to a longer duration of hospitalization for non‐liver‐related morbidity (median 14.0 days vs 8.0 days, P = 0.04), rather than liver‐related morbidity (median 10.5 days vs 8.0 days, P = 0.34), in patients with cryptogenic compared with non‐cryptogenic cirrhosis. Kaplan–Meier survival analysis showed no significant differences in survival between both types of cirrhosis for all grades of severity.

Conclusions

Cryptogenic cirrhosis is associated with a longer duration of hospitalization compared with non‐cryptogenic cirrhosis at an early stage of the disease. This difference is due to a greater burden of non‐liver‐related complications in the former.
Concomitant and hybrid therapy for Helicobacter pylori infection: A randomized clinical trial
Authors: Heo Jun , Jeon Seong Woo , Jung Jin Tae , Kwon Joong Goo , Lee Dong Wook , Kim Hyun Soo , Yang Chang Hun , Park Jeong Bae , Park Kyung Sik , Cho Kwang Bum , Lee Si Hyung , Jang Byung Ik ,   Daegu‐Gyeongbuk Gastrointestinal Study Group
Published: April 2015

Background and Aims

This study aimed to validate the equivalence of first‐line concomitant and hybrid regimens for Helicobacter pylori infection in an era of increasing antibiotic resistance. The study also aimed to assess regimen compliance.

Methods

H. pylori‐infected patients from six hospitals in Korea were randomly assigned to either concomitant or hybrid regimens. The concomitant regimen consisted of 20 mg of esomeprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg metronidazole, twice daily for 10 days. The hybrid regimen consisted of a 5‐day dual therapy (20 mg of esomeprazole and 1 g of amoxicillin, twice daily) followed by a 5‐day quadruple therapy (20 mg of esomeprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily).

Results

Eradication rates for concomitant and hybrid therapy were 78.6% (187/238) and 78.8% (190/241) in the intention‐to‐treat analysis, and 89.8% (176/196) and 89.6% (181/202) in the per protocol analysis. For both analyses, 95% confidence intervals fell within the ± 8% equivalence margin. Adherence was better in the hybrid group (95.0%) than in the concomitant group (90.1%), a difference that was borderline significant (P = 0.051). Adverse event rates were higher in the concomitant group than in the hybrid group for nausea (15.8% vs 8.8%; P = 0.028) and regurgitation (17.6% vs 10.7%; P = 0.040).

Conclusion

As compared with concomitant therapy, hybrid therapy offered similar efficacy, better compliance, and fewer adverse events. Hybrid therapy could be a reasonable first‐line treatment option for H. pylori in areas with high antibiotics resistance.
Sequential or concomitant therapy for eradication of Helicobacter pylori infection: A systematic review and meta‐analysis
Authors: Kim Joon Sung , Park Sung Min , Kim Byung‐Wook
Published: April 2015

Background and Aim

Eradication of Helicobacter pylori (H. pylori) infection with triple therapy (TT) has declined in many countries prompting the search for alternative regimens. Sequential therapy (ST) and concomitant therapy (CT) have been suggested as first‐line regimens in areas of high clarithromycin resistance. We performed a meta‐analysis to compare the eradication rates of CT with ST for H. pylori.

Methods

A comprehensive literature search for studies comparing the efficacy of CT with ST was performed. Dichotomous data were pooled to obtain the odds ratio (OR) of the eradication rate with 95% confidence intervals (CIs). The eradication rates were considered both on an intention‐to‐treat (ITT) and on a per‐protocol (PP) bases.

Results

A total of 7 studies provided data on 2412 adult patients. Pooled estimates of the studies revealed no significant differences between CT and ST. The pooled OR was 1.116 (95% CI: 0.795–1.567, P = 0.526) for ITT analysis and 1.153 (95% CI: 0.793–1.677, P = 0.455) for PP analysis. There was no difference in the rate of adverse events (OR: 1.229, 95% CI: 0.971–1.556, P = 0.086) and compliance (OR: 0.945, 95% CI: 0.722–1.237, P = 0.681) between the two regimens. Subgroup analysis was performed to compare CT of 10 days and 5 days with ST of 10 days. The pooled OR was 1.518 for CT of 10days and 0.636 for CT of 5 days.

Conclusions

CT regimens did not achieve higher eradication rates compared with the ST regimen. The adverse events and adherence to medications were not different between the two regimens.
Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury
Authors: Gao Yang , Xu Siyi , Cui Zhenwen , Zhang Mingkun , Lin Yingying , Cai Lei , Wang Zhugang , Luo Xingguang , Zheng Yan , Wang Yong , Luo Qizhong , Jiang Jiyao , Neale Joseph H. , Zhong Chunlong
Published: April 2015

Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia‐bound GCPII mediates the hydrolysis of the neurotransmitter N‐acetylaspartylglutamate (NAAG) into glutamate and N‐acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3–5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild‐type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI‐induced deficits in long‐term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long‐term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors.

image

The peptide neurotransmitter N‐acetylaspartylglutamate (NAAG) suppresses glutamate transmission through selective activation of pre‐synaptic Group II metabotropic glutamate receptor subtype 3 (mGluR3) after traumatic brain injury (TBI). However, synaptically released NAAG is hydrolyzed to form N‐acetylaspartate and glutamate mainly by Glutamate carboxypeptidase II (GCPII), losing neuroprotective effect. In this study, we found that knock out of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long‐term behavioral outcomes after TBI.
Pro‐Opiomelanocortin (POMC) Neurones, POMC‐Derived Peptides, Melanocortin Receptors and Obesity: How Understanding of this System has Changed Over the Last Decade
Authors: Mountjoy K. G.
Published: April 2015

Following the cloning of the melanocortin receptor and agouti protein genes, a model was developed for the central melanocortin system with respect to the regulation of energy and glucose homeostasis. This model comprised leptin regulation of melanocortin peptides and agouti‐related peptide (AgRP) produced from central pro‐opiomelanocortin (POMC) and AgRP neurones, respectively, as well as AgRP competitive antagonism of melanocortin peptides activating melanocortin 4 receptor (MC4R) to Gαs and the cAMP signalling pathway. In the last decade, there have been paradigm shifts in our understanding of the central melanocortin system as a result of the application of advanced new technologies, including Cre‐LoxP transgenic mouse technology, pharmacogenetics and optogenetics. During this period, our understanding of G protein coupled receptor signal transduction has also dramatically changed, such that these receptors are now known to exist in the plasma membrane oscillating between various inactive and active conformational states, and the active states signal through G protein‐dependent and G protein‐independent pathways. The present review focuses on evidence obtained over the past decade that has changed our understanding of POMC gene expression and regulation in the central nervous system, POMC and AgRP neuronal circuitry, neuroanatomical functions of melanocortin receptors, melanocortin 3 receptor (MC3R) and MC4R, and signal transduction through MC3R and MC4R.
Hypophosphatemia is Associated with the Serial Administration of Triple‐Dose Gadolinium to Patients for Brain MRI
Authors: Wolansky Leo J. , Cadavid Diego , Punia Vineet , Kim Soyeon , Cheriyan Jojy , Haghighi Mershad , Cook Stuart D.
Published: April 2015

BACKGROUND AND PURPOSE

The purpose of this study is to report a metabolic abnormality associated with frequent, triple‐dose Gadolinium (TdGd) use in MS patients during BECOME trial.

METHODS

Potential clinical adverse events and lab abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for pairwise comparisons across visits and generalized estimating equations (GEE) to fit models over time.

RESULTS

Eight hundred seventy seven phosphate values were analyzed from the first 12 months. Compared with 4% of subjects at screening, an average of 15.1% (95% confidence interval (CI): 11.4%‐19.7%) of patients had hypophosphatemia at visits from months 1 to 12, during which subjects received serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia at least once. We also found a significant increasing trend in hypophosphatemia by visit when treatment groups were evaluated together or separately (p < .001). There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6‐19.8%) by month 24 (p = .005) coinciding with a period of less frequent gadolinium administration.

CONCLUSIONS

Serial TdGd in MS patients, unrelated to immunomodulatory treatment, was associated with increased frequency of hypophosphatemia that progressed with cumulative triple‐dose and markedly decreased in second year, with less frequent triple‐dose administration.
ShenKang injection suppresses kidney fibrosis and oxidative stress via transforming growth factor-β/Smad3 signalling pathway in vivo and in vitro
Authors: Wu Xiaoxiao , Guan Yue , Yan Jiajia , Liu Meiyou , Yin Ying , Duan Jialin , Wei Guo , Hu Tianxin , Weng Yan , Xi Miaomiao , Wen Aidong
Published: April 2015

Objectives

The purpose of this study is to investigate the antifibrosis and antioxidation of ShenKang injection (SKI) in vivo and in vitro and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD).

Methods

In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathological tests were performed by H&E and Masson trichrome stained. The protein expressions of fibronectin (FN), collagen Ι, α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) and phosphorylation of Smad3 were measured in 5/6Nx rats. In Human kidney proximal tubular cell line (HK-2) cells, the effects of TGF-β/Smad3 signalling pathway on renal fibrosis and oxidative injury were examined.

Key findings

5/6Nx induced severe renal damages. Treatment of rats with SKI markedly reduced levels of Scr and BUN, alleviated expression of fibrosis-associated signalling molecules and reduced expression of TGF-β and phosphorylated Smad3. Meanwhile, in HK-2 cells, after exposure to TGF-β and H2O2, the protein expression of renal fibrosis was significantly increased. The generation of oxidative stress was also elevated. The severity of fibrosis and oxidative damage appears to be reduced after treatment with SKI.

Conclusion

SKI inhibits renal fibrosis and oxidative stress through downregulation of TGF-β/Smad3 signalling pathway.
Effect of dietary fish oil on the expression of genes involved in lipid metabolism in liver and skeletal muscle of lactating sows
Authors: Gessner D. K. , Gröne B. , Rosenbaum S. , Most E. , Hillen S. , Becker S. , Erhardt G. , Reiner G. , Eder K.
Published: April 2015

This study investigated the hypothesis that dietary supplementation of fish oil as a source of n‐3 polyunsaturated fatty acids (PUFA) influences the expression of target genes of sterol regulatory element‐binding proteins (SREBP)‐1 and (SREBP)‐2 involved in triacylglycerol (TAG) synthesis and fatty acid and cholesterol metabolism in the liver, and moreover activates the expression of target genes of peroxisome proliferation‐activated receptor (PPAR)‐α involved in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating sows were fed a control diet or a fish oil diet with either 50 g of a mixture of palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish oil group contained 19.1 g of n‐3 PUFA (mainly 20:5 n‐3 and 22:6 n‐3) per 100 g of total fatty acids, while the diet of the control group contained 2.4 g of n‐3 PUFA (mainly 18:3 n‐3) per 100 g of total fatty acids. The fish oil group had reduced relative mRNA concentrations of various target genes of SREBP‐1 involved in fatty acid and TAG synthesis in comparison with the control group (p < 0.05). Relative mRNA concentrations of target genes of PPARα involved in fatty acid catabolism in both liver and muscle, and mRNA concentrations of target genes of SREBP‐2 involved in cholesterol synthesis and uptake were not influenced by fish oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content of milk and weight gains of litters during the suckling period were not different between the two groups of sows. In conclusion, this study suggests that fish oil has only minor effects on hepatic lipid metabolism, which are non‐critical with respect to milk production in sows.
Procoagulant Microparticles in Dogs with Immune‐Mediated Hemolytic Anemia
Authors: Kidd L. , Geddings J. , Hisada Y. , Sueda M. , Concannon T. , Nichols T. , Merricks E. , Mackman N.
Published: April 2015

Background

Studies of some human prothrombotic diseases suggest that phosphatidylserine‐positive (PS+) and tissue factor‐positive (TF+) microparticles (MPs) might play a role in the pathogenesis of thrombosis or serve as biomarkers of thrombotic risk.

Hypothesis/Objectives

To determine if circulating levels of PS+MP and procoagulant activity (PCA) associated with PS+MPs and TF+ MPs are increased in dogs with IMHA.

Animals

Fifteen dogs with primary or secondary IMHA and 17 clinically healthy dogs.

Methods

Prospective case‐controlled observational study. Circulating PS+MPs were measured by flow cytometry. PCA associated with PS+MPs and TF+MPs was measured by thrombin and Factor Xa generating assays, respectively.

Results

Circulating numbers of PS+MPs were not significantly higher in dogs with IMHA [control median 251,000/μL (36,992–1,141,250/μL); IMHA median 361,990/μL (21,766–47,650,600/μL) P = .30]. However, PS+MP PCA [control median 2.2 (0.0–16.8) nM PS eq; IMHA median 8.596, (0–49.33 nM PS eq) P = .01] and TF+MP PCA [control median 0.0, (0.0–0.0 pg/mL); IMHA median 0.0; (0–22.34 pg/mL], P = .04) were increased. Intravascular hemolysis, which we showed might increase PS+ and TF+MP PCA, was evident in 3 of 5 dogs with PS+MP PCA and 2 of 4 dogs with TF+MP PCA higher than controls. Underlying disease in addition to IMHA was detected in 1 of 5 dogs with PS+PCA and 3 of 4 dogs with TF+MP PCA higher than controls.

Conclusions and Clinical Importance

TF+ and PS+MP PCA is increased in some dogs with IMHA. Further studies that determine if measuring TF+ and PS+ MP PCA can help identify dogs at risk for thrombosis are warranted.
Gallium Maltolate as an Alternative to Macrolides for Treatment of Presumed Rhodococcus equi Pneumonia in Foals
Authors: Cohen Noah D. , Slovis Nathan M. , Giguère Steeve , Baker Samantha , Chaffin M. Keith , Bernstein Lawrence R.
Published: April 2015

Background

Macrolide‐resistant isolates of Rhodococcus equi are emerging, prompting the search for clinically effective alternative antimicrobials.

Hypothesis

The proportion of foals with ultrasonographic evidence of pneumonia presumed to be caused by R. equi that had a successful outcome when administered gallium maltolate (GaM) PO would not be more than 10% inferior (ie, lower) than that of foals receiving standard treatment.

Animals

Fifty‐four foals with subclinical pulmonary abscesses among 509 foals at 6 breeding farms in Kentucky.

Methods

Controlled, randomized, prospective noninferiority study. Foals with ultrasonographic lesions >1 cm in diameter (n = 54) were randomly allocated to receive per os either clarithromycin combined with rifampin (CLR+R) or GaM, and followed up for 28 days by daily physical inspections and weekly (n = 1 farm) or biweekly (n = 4 farms) thoracic ultrasound examinations by individuals unaware of treatment‐group assignments. Treatment success was defined as resolution of ultrasonographically identified pulmonary abscesses within 28 days of initiating treatment. Noninferiority was defined as a 90% confidence interval for the observed difference in CLR+R minus GaM that was ≤10%.

Results

The proportion of GaM‐treated foals that resolved (70%; 14/20) was similar to that of foals treated with CLR+R (74%; 25/34), but we failed to demonstrate noninferiority for GaM relative to CLR+R; however, GaM was noninferior to CLR+R treatment when results from a noncompliant farm were excluded.

Conclusions and Clinical Importance

Gallium maltolate is not inferior to macrolides for treating foals with subclinical pneumonia. Use of GaM might reduce pressure for macrolide‐resistance in R. equi.
Disturbance and stress gradients result in distinct taxonomic, functional and phylogenetic diversity patterns in a subtropical riparian tree community
Authors: Giehl Eduardo L. H. , Jarenkow João André
Published: April 2015

Questions

What are the key environmental variables that influence the structure of riparian forests? Do disturbance (flooding) and stress (soil fertility) gradients result in functionally and phylogenetically different riparian forests? Do patterns of functional and phylogenetic diversity follow patterns of taxonomic diversity?

Location

Subtropical riparian tree community, Turvo State Park, Rio Grande do Sul state, southern Brazil.

Methods

We collected data on nine functional traits and assembled a phylogeny for all tree species found in a sample with 100 plots. We then modelled species richness and evenness, and functional and phylogenetic richness, evenness and divergence as functions of flooding frequency and soil fertility. Next, we used a three‐table ordination method to look for associations between environmental conditions, the spatial locations of sampling sites and the distributions of species, trait values and lineages. We conducted these analyses for the entire area and separately for three habitats with different flooding frequencies. Finally, we tested for phylogenetic signal in functional traits.

Results

Species richness and evenness were highest under intermediate flooding frequency. In contrast, functional richness was negatively correlated with soil fertility, while phylogenetic richness increased with both flooding frequency and soil fertility (with phylogenetic evenness following a similar trend). Functional evenness was lowest under intermediate flooding frequency, and functional and phylogenetic divergence correlated in a complex quadratic way with both flooding and soil fertility. Functional traits were generally conserved in the phylogeny, although pioneer establishment strategy and resprouting capacity were convergent and strongly associated with frequent flooding. In contrast, the distribution of lineages was not associated with either environmental variables or site location.

Conclusions

There was a mismatch between taxonomic, functional and phylogenetic diversity patterns along disturbance and stress gradients. This mismatch likely occurs because functional traits involved in species sorting were either convergent or conserved in the phylogeny and because disturbance and stress gradients seem to differently affect each of the assessed diversity components. Even though disturbance seems to be the key driver of the structure of riparian tree communities, stress gradients (soil fertility) are the key predictors of important diversity components, especially functional richness. Thus, disturbance and stress gradients result in functionally and phylogenetically different riparian tree communities, leading to differences that cannot be predicted from differences in species richness and composition alone.
Let the concept of indicator species be functional!
Authors: Ricotta Carlo , Carboni Marta , Acosta Alicia T.R.
Published: April 2015

Aims

The identification of diagnostic or indicator species with high fidelity to a given group of sites is an important step for the ecological characterization of habitats or community types. The determination of the degree of fidelity to a target group is traditionally performed by analysing the concentration of species occurrences or abundances in different groups of sites. Surprisingly, although one of the main purposes of indicator species analysis is to give ecological meaning to groups of sites, none of the methods proposed to date take into account the functional ecology of diagnostic species. Therefore, the question we address here is: can we use functional traits of species to improve the diagnostic value of indicator species?

Location

Sand dune communities in central Italy.

Methods

In this paper we propose a two‐step procedure for incorporating the functional traits of a given species in the evaluation of its diagnostic value. For a given set of plots that are classified into different groups, first the indicator species that best characterize each group of plots are identified with the usual statistical tools based on species occurrences. Next, the functional association between the indicator species and the target groups of plots is tested by measuring the functional distance between the indicator species and the centroids of all plots in the target group. A species is positively associated with a group if its mean functional distance from all plot centroids in the group is significantly lower than expected.

Results

In this example, we show that the functional association of the indicator species with a given habitat type is represented by less species than the association highlighted solely through species occurrences and/or abundances. This subset of species appears to better characterize the functional ecology of coastal dune plant assemblages and shows a higher diagnostic value in comparison with those obtained through the traditional indicator analysis.

Conclusions

As functional traits are the main ecological attributes by which different species influence ecosystem processes, we believe that the methodology proposed here provides a relevant tool for ecological applications as distinct as vegetation science, conservation biology or landscape management.
Exploring origins, invasion history and genetic diversity ofImperata cylindrica(L.) P. Beauv. (Cogongrass) in the United States using genotyping by sequencing
Authors: Burrell A. Millie , Pepper Alan E. , Hodnett George , Goolsby John A. , Overholt William A. , Racelis Alexis E. , Diaz Rodrigo , Klein Patricia E.
Published: April 2015

Imperata cylindrica(Cogongrass, Speargrass) is a diploid C4 grass that is a noxious weed in 73 countries and constitutes a significant threat to global biodiversity and sustainable agriculture. We used a cost‐effective genotyping‐by‐sequencing (GBS) approach to identify the reproductive system, genetic diversity and geographic origins of invasions in the south‐eastern United States. In this work, we demonstrated the advantage of employing the closely related, fully sequenced crop speciesSorghum bicolor(L.) Moench as a proxy reference genome to identify a set of 2320 informative single nucleotide and insertion–deletion polymorphisms. Genetic analyses identified four clonal lineages of cogongrass and one clonal lineage ofImperata brasiliensisTrin. in the United States. Each lineage was highly homogeneous, and we found no evidence of hybridization among the different lineages, despite geographical overlap. We found evidence that at least three of these lineages showed clonal reproduction prior to introduction to the United States. These results indicate that cogongrass has limited evolutionary potential to adapt to novel environments and further suggest that upon arrival to its invaded range, this species did not require local adaptation through hybridization/introgression or selection of favourable alleles from a broad genetic base. Thus, cogongrass presents a clear case of broad invasive success, across a diversity of environments, in a clonal organism with limited genetic diversity.
More than one genotype: how common is intracolonial genetic variability in scleractinian corals?
Authors: Schweinsberg Maximilian , Weiss Linda C. , Striewski Sebastian , Tollrian Ralph , Lampert Kathrin P.
Published: April 2015

In recent years, a few colonial marine invertebrates have shown intracolonial genetic variability, a previously unreported phenomenon. Intracolonial genetic variability describes the occurrence of more than a single genotype within an individual colony. This variability can be traced back to two underlying processes: chimerism and mosaicism. Chimerism is the fusion of two or more individuals, whereas mosaicism mostly derives from somatic cell mutations. Until now, it remained unclear to what degree the ecologically important group of hermatypic (reef building) corals might be affected. We investigate the occurrence of intracolonial genetic variability in five scleractinian corals: Acropora florida, Acropora hyacinthus, Acropora sarmentosa, Pocillopora species complex and Porites australiensis. The main focus was to test different genera for the phenomenon via microsatellite markers and to distinguish which underlying process caused the genetic heterogeneity. Our results show that intracolonial genetic variability was common (between 46.6% for A. sarmentosa and 23.8% for P. species complex) in all tested corals. The main process was mosaicism (69 cases of 222 tested colonies), but at least one chimera existed in every species. This suggests that intracolonial genetic variability is widespread in scleractinian corals and could challenge the view of a coral colony as an individual and therefore a unit of selection. However, it might also hold potential for colony survival under rapidly changing environmental conditions.